Sample records for cell values global

  1. The Impact of Different Sources of Fluctuations on Mutual Information in Biochemical Networks

    PubMed Central

    Chevalier, Michael; Venturelli, Ophelia; El-Samad, Hana

    2015-01-01

    Stochastic fluctuations in signaling and gene expression limit the ability of cells to sense the state of their environment, transfer this information along cellular pathways, and respond to it with high precision. Mutual information is now often used to quantify the fidelity with which information is transmitted along a cellular pathway. Mutual information calculations from experimental data have mostly generated low values, suggesting that cells might have relatively low signal transmission fidelity. In this work, we demonstrate that mutual information calculations might be artificially lowered by cell-to-cell variability in both initial conditions and slowly fluctuating global factors across the population. We carry out our analysis computationally using a simple signaling pathway and demonstrate that in the presence of slow global fluctuations, every cell might have its own high information transmission capacity but that population averaging underestimates this value. We also construct a simple synthetic transcriptional network and demonstrate using experimental measurements coupled to computational modeling that its operation is dominated by slow global variability, and hence that its mutual information is underestimated by a population averaged calculation. PMID:26484538

  2. Dynamic Modeling of Cell-Free Biochemical Networks Using Effective Kinetic Models

    DTIC Science & Technology

    2015-03-16

    sensitivity value was the maximum uncertainty in that value estimated by the Sobol method. 2.4. Global Sensitivity Analysis of the Reduced Order Coagulation...sensitivity analysis, using the variance-based method of Sobol , to estimate which parameters controlled the performance of the reduced order model [69]. We...Environment. Comput. Sci. Eng. 2007, 9, 90–95. 69. Sobol , I. Global sensitivity indices for nonlinear mathematical models and their Monte Carlo estimates

  3. Downscaling global land-use/land-cover projections for use in region-level state-and-transition simulation modeling

    USGS Publications Warehouse

    Sherba, Jason T.; Sleeter, Benjamin M.; Davis, Adam W.; Parker, Owen P.

    2015-01-01

    Global land-use/land-cover (LULC) change projections and historical datasets are typically available at coarse grid resolutions and are often incompatible with modeling applications at local to regional scales. The difficulty of downscaling and reapportioning global gridded LULC change projections to regional boundaries is a barrier to the use of these datasets in a state-and-transition simulation model (STSM) framework. Here we compare three downscaling techniques to transform gridded LULC transitions into spatial scales and thematic LULC classes appropriate for use in a regional STSM. For each downscaling approach, Intergovernmental Panel on Climate Change (IPCC) Representative Concentration Pathway (RCP) LULC projections, at the 0.5 × 0.5 cell resolution, were downscaled to seven Level III ecoregions in the Pacific Northwest, United States. RCP transition values at each cell were downscaled based on the proportional distribution between ecoregions of (1) cell area, (2) land-cover composition derived from remotely-sensed imagery, and (3) historic LULC transition values from a LULC history database. Resulting downscaled LULC transition values were aggregated according to their bounding ecoregion and “cross-walked” to relevant LULC classes. Ecoregion-level LULC transition values were applied in a STSM projecting LULC change between 2005 and 2100. While each downscaling methods had advantages and disadvantages, downscaling using the historical land-use history dataset consistently apportioned RCP LULC transitions in agreement with historical observations. Regardless of the downscaling method, some LULC projections remain improbable and require further investigation.

  4. Developing Character and Values for Global Citizens: Analysis of pre-service science teachers' moral reasoning on socioscientific issues

    NASA Astrophysics Data System (ADS)

    Lee, Hyunju; Chang, Hyunsook; Choi, Kyunghee; Kim, Sung-Won; Zeidler, Dana L.

    2012-04-01

    Character and values are the essential driving forces that serve as general guides or points of reference for individuals to support decision-making and to act responsibly about global socioscientific issues (SSIs). Based on this assumption, we investigated to what extent pre-service science teachers (PSTs) of South Korea possess character and values as global citizens; these values include ecological worldview, socioscientific accountability, and social and moral compassion. Eighteen PSTs participated in the SSI programs focusing on developing character and values through dialogical and reflective processes. SSIs were centered on the use of nuclear power generation, climate change, and embryonic stem cell research. The results indicated that PSTs showed three key elements of character and values, but failed to apply consistent moral principles on the issues and demonstrated limited global perspectives. While they tended to approach the issues with emotion and sympathy, they nonetheless failed to perceive themselves as major moral agents who are able to actively resolve large-scale societal issues. This study also suggests that the SSI programs can facilitate socioscientific reasoning to include abilities such as recognition of the complexity of SSIs, examine issues from multiple perspectives, and exhibit skepticism about information.

  5. Linking field-based ecological data with remotely sensed data using a geographic information system in two malaria endemic urban areas of Kenya.

    PubMed

    Eisele, Thomas P; Keating, Joseph; Swalm, Chris; Mbogo, Charles M; Githeko, Andrew K; Regens, James L; Githure, John I; Andrews, Linda; Beier, John C

    2003-12-10

    BACKGROUND: Remote sensing technology provides detailed spectral and thermal images of the earth's surface from which surrogate ecological indicators of complex processes can be measured. METHODS: Remote sensing data were overlaid onto georeferenced entomological and human ecological data randomly sampled during April and May 2001 in the cities of Kisumu (population asymptotically equal to 320,000) and Malindi (population asymptotically equal to 81,000), Kenya. Grid cells of 270 meters x 270 meters were used to generate spatial sampling units for each city for the collection of entomological and human ecological field-based data. Multispectral Thermal Imager (MTI) satellite data in the visible spectrum at five meter resolution were acquired for Kisumu and Malindi during February and March 2001, respectively. The MTI data were fit and aggregated to the 270 meter x 270 meter grid cells used in field-based sampling using a geographic information system. The normalized difference vegetation index (NDVI) was calculated and scaled from MTI data for selected grid cells. Regression analysis was used to assess associations between NDVI values and entomological and human ecological variables at the grid cell level. RESULTS: Multivariate linear regression showed that as household density increased, mean grid cell NDVI decreased (global F-test = 9.81, df 3,72, P-value = <0.01; adjusted R2 = 0.26). Given household density, the number of potential anopheline larval habitats per grid cell also increased with increasing values of mean grid cell NDVI (global F-test = 14.29, df 3,36, P-value = <0.01; adjusted R2 = 0.51). CONCLUSIONS: NDVI values obtained from MTI data were successfully overlaid onto georeferenced entomological and human ecological data spatially sampled at a scale of 270 meters x 270 meters. Results demonstrate that NDVI at such a scale was sufficient to describe variations in entomological and human ecological parameters across both cities.

  6. A Discrete Global Grid System Programming Language Using MapReduce

    NASA Astrophysics Data System (ADS)

    Peterson, P.; Shatz, I.

    2016-12-01

    A discrete global grid system (DGGS) is a powerful mechanism for storing and integrating geospatial information. As a "pixelization" of the Earth, many image processing techniques lend themselves to the transformation of data values referenced to the DGGS cells. It has been shown that image algebra, as an example, and advanced algebra, like Fast Fourier Transformation, can be used on the DGGS tiling structure for geoprocessing and spatial analysis. MapReduce has been shown to provide advantages for processing and generating large data sets within distributed and parallel computing. The DGGS structure is ideally suited for big distributed Earth data. We proposed that basic expressions could be created to form the atoms of a generalized DGGS language using the MapReduce programming model. We created three very efficient expressions: Selectors (aka filter) - A selection function that generate a set of cells, cell collections, or geometries; Calculators (aka map) - A computational function (including quantization of raw measurements and data sources) that generate values in a DGGS cell; and Aggregators (aka reduce) - A function that generate spatial statistics from cell values within a cell. We found that these three basic MapReduce operations along with a forth function, the Iterator, for horizontal and vertical traversing of any DGGS structure, provided simple building block resulting in very efficient operations and processes that could be used with any DGGS. We provide examples and a demonstration of their effectiveness using the ISEA3H DGGS on the PYXIS Studio.

  7. Stem Cell Banking: A Global View.

    PubMed

    Stacey, Glyn

    2017-01-01

    Stem cell banking has been a topic of discussion and debate for more than a decade since the first public services to supply human embryonic stem cells (hESCs) were established in the USA and the UK. This topic has received a recent revival with numerous ambitious programmes announced to deliver large collections of human induced pluripotency cell (hiPSC) lines. This chapter will provide a brief overview charting the development of stem cell banks, their value, and their likely role in the future.

  8. Missing Value Monitoring Enhances the Robustness in Proteomics Quantitation.

    PubMed

    Matafora, Vittoria; Corno, Andrea; Ciliberto, Andrea; Bachi, Angela

    2017-04-07

    In global proteomic analysis, it is estimated that proteins span from millions to less than 100 copies per cell. The challenge of protein quantitation by classic shotgun proteomic techniques relies on the presence of missing values in peptides belonging to low-abundance proteins that lowers intraruns reproducibility affecting postdata statistical analysis. Here, we present a new analytical workflow MvM (missing value monitoring) able to recover quantitation of missing values generated by shotgun analysis. In particular, we used confident data-dependent acquisition (DDA) quantitation only for proteins measured in all the runs, while we filled the missing values with data-independent acquisition analysis using the library previously generated in DDA. We analyzed cell cycle regulated proteins, as they are low abundance proteins with highly dynamic expression levels. Indeed, we found that cell cycle related proteins are the major components of the missing values-rich proteome. Using the MvM workflow, we doubled the number of robustly quantified cell cycle related proteins, and we reduced the number of missing values achieving robust quantitation for proteins over ∼50 molecules per cell. MvM allows lower quantification variance among replicates for low abundance proteins with respect to DDA analysis, which demonstrates the potential of this novel workflow to measure low abundance, dynamically regulated proteins.

  9. Hegemony in the marketplace of biomedical innovation: consumer demand and stem cell science.

    PubMed

    Salter, Brian; Zhou, Yinhua; Datta, Saheli

    2015-04-01

    The global political economy of stem cell therapies is characterised by an established biomedical hegemony of expertise, governance and values in collision with an increasingly informed health consumer demand able to define and pursue its own interest. How does the hegemony then deal with the challenge from the consumer market and what does this tell us about its modus operandi? In developing a theoretical framework to answer these questions, the paper begins with an analysis of the nature of the hegemony of biomedical innovation in general, its close relationship with the research funding market, the current political modes of consumer incorporation, and the ideological role performed by bioethics as legitimating agency. Secondly, taking the case of stem cell innovation, it explores the hegemonic challenge posed by consumer demand working through the global practice based market of medical innovation, the response of the national and international institutions of science and their reassertion of the values of the orthodox model, and the supporting contribution of bioethics. Finally, the paper addresses the tensions within the hegemonic model of stem cell innovation between the key roles and values of scientist and clinician, the exacerbation of these tensions by the increasingly visible demands of health consumers, and the emergence of political compromise. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Global microRNA expression profiling of microdissected tissues identifies miR-135b as a novel biomarker for pancreatic ductal adenocarcinoma.

    PubMed

    Munding, Johanna B; Adai, Alex T; Maghnouj, Abdelouahid; Urbanik, Aleksandra; Zöllner, Hannah; Liffers, Sven T; Chromik, Ansgar M; Uhl, Waldemar; Szafranska-Schwarzbach, Anna E; Tannapfel, Andrea; Hahn, Stephan A

    2012-07-15

    Pancreatic ductal adenocarcinoma (PDAC) is known for its poor prognosis resulting from being diagnosed at an advanced stage. Accurate early diagnosis and new therapeutic modalities are therefore urgently needed. MicroRNAs (miRNAs), considered a new class of biomarkers and therapeutic targets, may be able to fulfill those needs. Combining tissue microdissection with global miRNA array analyses, cell type-specific miRNA expression profiles were generated for normal pancreatic ductal cells, acinar cells, PDAC cells derived from xenografts and also from macrodissected chronic pancreatitis (CP) tissues. We identified 78 miRNAs differentially expressed between ND and PDAC cells providing new insights into the miRNA-driven pathophysiological mechanisms involved in PDAC development. Having filtered miRNAs which are upregulated in the three pairwise comparisons of PDAC vs. ND, PDAC vs. AZ and PDAC vs. CP, we identified 15 miRNA biomarker candidates including miR-135b. Using relative qRT-PCR to measure miR-135b normalized to miR-24 in 75 FFPE specimens (42 PDAC and 33 CP) covering a broad range of tumor content, we discriminated CP from PDAC with a sensitivity and specificity of 92.9% [95% CI=(80.5, 98.5)] and 93.4% [95% CI=(79.8, 99.3)], respectively. Furthermore, the area under the curve (AUC) value reached of 0.97 was accompanied by positive and negative predictive values of 95% and 91%, respectively. In conclusion, we report pancreatic cell-specific global miRNA profiles, which offer new candidate miRNAs to be exploited for functional studies in PDAC. Furthermore, we provide evidence that miRNAs are well-suited analytes for development of sensitive and specific aid-in-diagnosis tests for PDAC. Copyright © 2011 UICC.

  11. Role of spatial averaging in multicellular gradient sensing.

    PubMed

    Smith, Tyler; Fancher, Sean; Levchenko, Andre; Nemenman, Ilya; Mugler, Andrew

    2016-05-20

    Gradient sensing underlies important biological processes including morphogenesis, polarization, and cell migration. The precision of gradient sensing increases with the length of a detector (a cell or group of cells) in the gradient direction, since a longer detector spans a larger range of concentration values. Intuition from studies of concentration sensing suggests that precision should also increase with detector length in the direction transverse to the gradient, since then spatial averaging should reduce the noise. However, here we show that, unlike for concentration sensing, the precision of gradient sensing decreases with transverse length for the simplest gradient sensing model, local excitation-global inhibition. The reason is that gradient sensing ultimately relies on a subtraction of measured concentration values. While spatial averaging indeed reduces the noise in these measurements, which increases precision, it also reduces the covariance between the measurements, which results in the net decrease in precision. We demonstrate how a recently introduced gradient sensing mechanism, regional excitation-global inhibition (REGI), overcomes this effect and recovers the benefit of transverse averaging. Using a REGI-based model, we compute the optimal two- and three-dimensional detector shapes, and argue that they are consistent with the shapes of naturally occurring gradient-sensing cell populations.

  12. Role of spatial averaging in multicellular gradient sensing

    NASA Astrophysics Data System (ADS)

    Smith, Tyler; Fancher, Sean; Levchenko, Andre; Nemenman, Ilya; Mugler, Andrew

    2016-06-01

    Gradient sensing underlies important biological processes including morphogenesis, polarization, and cell migration. The precision of gradient sensing increases with the length of a detector (a cell or group of cells) in the gradient direction, since a longer detector spans a larger range of concentration values. Intuition from studies of concentration sensing suggests that precision should also increase with detector length in the direction transverse to the gradient, since then spatial averaging should reduce the noise. However, here we show that, unlike for concentration sensing, the precision of gradient sensing decreases with transverse length for the simplest gradient sensing model, local excitation-global inhibition. The reason is that gradient sensing ultimately relies on a subtraction of measured concentration values. While spatial averaging indeed reduces the noise in these measurements, which increases precision, it also reduces the covariance between the measurements, which results in the net decrease in precision. We demonstrate how a recently introduced gradient sensing mechanism, regional excitation-global inhibition (REGI), overcomes this effect and recovers the benefit of transverse averaging. Using a REGI-based model, we compute the optimal two- and three-dimensional detector shapes, and argue that they are consistent with the shapes of naturally occurring gradient-sensing cell populations.

  13. Asymptotic behaviors of a cell-to-cell HIV-1 infection model perturbed by white noise

    NASA Astrophysics Data System (ADS)

    Liu, Qun

    2017-02-01

    In this paper, we analyze a mathematical model of cell-to-cell HIV-1 infection to CD4+ T cells perturbed by stochastic perturbations. First of all, we investigate that there exists a unique global positive solution of the system for any positive initial value. Then by using Lyapunov analysis methods, we study the asymptotic property of this solution. Moreover, we discuss whether there is a stationary distribution for this system and if it owns the ergodic property. Numerical simulations are presented to illustrate the theoretical results.

  14. Curcumin modulates DNA methylation in colorectal cancer cells.

    PubMed

    Link, Alexander; Balaguer, Francesc; Shen, Yan; Lozano, Juan Jose; Leung, Hon-Chiu E; Boland, C Richard; Goel, Ajay

    2013-01-01

    Recent evidence suggests that several dietary polyphenols may exert their chemopreventive effect through epigenetic modifications. Curcumin is one of the most widely studied dietary chemopreventive agents for colon cancer prevention, however, its effects on epigenetic alterations, particularly DNA methylation, remain unclear. Using systematic genome-wide approaches, we aimed to elucidate the effect of curcumin on DNA methylation alterations in colorectal cancer cells. To evaluate the effect of curcumin on DNA methylation, three CRC cell lines, HCT116, HT29 and RKO, were treated with curcumin. 5-aza-2'-deoxycytidine (5-aza-CdR) and trichostatin A treated cells were used as positive and negative controls for DNA methylation changes, respectively. Methylation status of LINE-1 repeat elements, DNA promoter methylation microarrays and gene expression arrays were used to assess global methylation and gene expression changes. Validation was performed using independent microarrays, quantitative bisulfite pyrosequencing, and qPCR. As expected, genome-wide methylation microarrays revealed significant DNA hypomethylation in 5-aza-CdR-treated cells (mean β-values of 0.12), however, non-significant changes in mean β-values were observed in curcumin-treated cells. In comparison to mock-treated cells, curcumin-induced DNA methylation alterations occurred in a time-dependent manner. In contrast to the generalized, non-specific global hypomethylation observed with 5-aza-CdR, curcumin treatment resulted in methylation changes at selected, partially-methylated loci, instead of fully-methylated CpG sites. DNA methylation alterations were supported by corresponding changes in gene expression at both up- and down-regulated genes in various CRC cell lines. Our data provide previously unrecognized evidence for curcumin-mediated DNA methylation alterations as a potential mechanism of colon cancer chemoprevention. In contrast to non-specific global hypomethylation induced by 5-aza-CdR, curcumin-induced methylation changes occurred only in a subset of partially-methylated genes, which provides additional mechanistic insights into the potent chemopreventive effect of this dietary nutraceutical.

  15. Curcumin Modulates DNA Methylation in Colorectal Cancer Cells

    PubMed Central

    Link, Alexander; Balaguer, Francesc; Shen, Yan; Lozano, Juan Jose; Leung, Hon-Chiu E.; Boland, C. Richard; Goel, Ajay

    2013-01-01

    Aim Recent evidence suggests that several dietary polyphenols may exert their chemopreventive effect through epigenetic modifications. Curcumin is one of the most widely studied dietary chemopreventive agents for colon cancer prevention, however, its effects on epigenetic alterations, particularly DNA methylation, remain unclear. Using systematic genome-wide approaches, we aimed to elucidate the effect of curcumin on DNA methylation alterations in colorectal cancer cells. Materials and Methods To evaluate the effect of curcumin on DNA methylation, three CRC cell lines, HCT116, HT29 and RKO, were treated with curcumin. 5-aza-2′-deoxycytidine (5-aza-CdR) and trichostatin A treated cells were used as positive and negative controls for DNA methylation changes, respectively. Methylation status of LINE-1 repeat elements, DNA promoter methylation microarrays and gene expression arrays were used to assess global methylation and gene expression changes. Validation was performed using independent microarrays, quantitative bisulfite pyrosequencing, and qPCR. Results As expected, genome-wide methylation microarrays revealed significant DNA hypomethylation in 5-aza-CdR-treated cells (mean β-values of 0.12), however, non-significant changes in mean β-values were observed in curcumin-treated cells. In comparison to mock-treated cells, curcumin-induced DNA methylation alterations occurred in a time-dependent manner. In contrast to the generalized, non-specific global hypomethylation observed with 5-aza-CdR, curcumin treatment resulted in methylation changes at selected, partially-methylated loci, instead of fully-methylated CpG sites. DNA methylation alterations were supported by corresponding changes in gene expression at both up- and down-regulated genes in various CRC cell lines. Conclusions Our data provide previously unrecognized evidence for curcumin-mediated DNA methylation alterations as a potential mechanism of colon cancer chemoprevention. In contrast to non-specific global hypomethylation induced by 5-aza-CdR, curcumin-induced methylation changes occurred only in a subset of partially-methylated genes, which provides additional mechanistic insights into the potent chemopreventive effect of this dietary nutraceutical. PMID:23460897

  16. Mapping local and global variability in plant trait distributions

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Butler, Ethan E.; Datta, Abhirup; Flores-Moreno, Habacuc

    2017-12-01

    Our ability to understand and predict the response of ecosystems to a changing environment depends on quantifying vegetation functional diversity. However, representing this diversity at the global scale is challenging. Typically, in Earth system models, characterization of plant diversity has been limited to grouping related species into plant functional types (PFTs), with all trait variation in a PFT collapsed into a single mean value that is applied globally. Using the largest global plant trait database and state of the art Bayesian modeling, we created fine-grained global maps of plant trait distributions that can be applied to Earth system models. Focusingmore » on a set of plant traits closely coupled to photosynthesis and foliar respiration—specific leaf area (SLA) and dry mass-based concentrations of leaf nitrogen (N m) and phosphorus (P m), we characterize how traits vary within and among over 50,000 ~50×50-km cells across the entire vegetated land surface. We do this in several ways—without defining the PFT of each grid cell and using 4 or 14 PFTs; each model’s predictions are evaluated against out-of-sample data. This endeavor advances prior trait mapping by generating global maps that preserve variability across scales by using modern Bayesian spatial statistical modeling in combination with a database over three times larger than that in previous analyses. Our maps further reveal that the most diverse grid cells possess trait variability close to the range of global PFT means.« less

  17. Mapping local and global variability in plant trait distributions.

    PubMed

    Butler, Ethan E; Datta, Abhirup; Flores-Moreno, Habacuc; Chen, Ming; Wythers, Kirk R; Fazayeli, Farideh; Banerjee, Arindam; Atkin, Owen K; Kattge, Jens; Amiaud, Bernard; Blonder, Benjamin; Boenisch, Gerhard; Bond-Lamberty, Ben; Brown, Kerry A; Byun, Chaeho; Campetella, Giandiego; Cerabolini, Bruno E L; Cornelissen, Johannes H C; Craine, Joseph M; Craven, Dylan; de Vries, Franciska T; Díaz, Sandra; Domingues, Tomas F; Forey, Estelle; González-Melo, Andrés; Gross, Nicolas; Han, Wenxuan; Hattingh, Wesley N; Hickler, Thomas; Jansen, Steven; Kramer, Koen; Kraft, Nathan J B; Kurokawa, Hiroko; Laughlin, Daniel C; Meir, Patrick; Minden, Vanessa; Niinemets, Ülo; Onoda, Yusuke; Peñuelas, Josep; Read, Quentin; Sack, Lawren; Schamp, Brandon; Soudzilovskaia, Nadejda A; Spasojevic, Marko J; Sosinski, Enio; Thornton, Peter E; Valladares, Fernando; van Bodegom, Peter M; Williams, Mathew; Wirth, Christian; Reich, Peter B

    2017-12-19

    Our ability to understand and predict the response of ecosystems to a changing environment depends on quantifying vegetation functional diversity. However, representing this diversity at the global scale is challenging. Typically, in Earth system models, characterization of plant diversity has been limited to grouping related species into plant functional types (PFTs), with all trait variation in a PFT collapsed into a single mean value that is applied globally. Using the largest global plant trait database and state of the art Bayesian modeling, we created fine-grained global maps of plant trait distributions that can be applied to Earth system models. Focusing on a set of plant traits closely coupled to photosynthesis and foliar respiration-specific leaf area (SLA) and dry mass-based concentrations of leaf nitrogen ([Formula: see text]) and phosphorus ([Formula: see text]), we characterize how traits vary within and among over 50,000 [Formula: see text]-km cells across the entire vegetated land surface. We do this in several ways-without defining the PFT of each grid cell and using 4 or 14 PFTs; each model's predictions are evaluated against out-of-sample data. This endeavor advances prior trait mapping by generating global maps that preserve variability across scales by using modern Bayesian spatial statistical modeling in combination with a database over three times larger than that in previous analyses. Our maps reveal that the most diverse grid cells possess trait variability close to the range of global PFT means.

  18. Global Population Distribution (1990),Terrestrial Area and Country Name Information on a One by One Degree Grid Cell Basis

    DOE Data Explorer

    Li, Yi-Fan [Canadian Global Emissions Inventory Centre, Downsview, Ontario (Canada); Brenkert, A. L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    1996-01-01

    This data base contains gridded (one degree by one degree) information on the world-wide distribution of the population for 1990 and country-specific information on the percentage of the country's population present in each grid cell (Li, 1996a). Secondly, the data base contains the percentage of a country's total area in a grid cell and the country's percentage of the grid cell that is terrestrial (Li, 1996b). Li (1996b) also developed an indicator signifying how many countries are represented in a grid cell and if a grid cell is part of the sea; this indicator is only relevant for the land, countries, and sea-partitioning information of the grid cell. Thirdly, the data base includes the latitude and longitude coordinates of each grid cell; a grid code number, which is a translation of the latitude/longitude value and is used in the Global Emission Inventory Activity (GEIA) data bases; the country or region's name; and the United Nations three-digit country code that represents that name.

  19. Navigating the network: signaling cross-talk in hematopoietic cells

    PubMed Central

    Fraser, Iain D C; Germain, Ronald N

    2009-01-01

    Recent studies in hematopoietic cells have led to a growing appreciation of the diverse modes of molecular and functional cross-talk between canonical signaling pathways. However, these intersections represent only the tip of the iceberg. Emerging global analytical methods are providing an even richer and more complete picture of the many components that measurably interact in a network manner to produce cellular responses. Here we highlight the pieces in this Focus, emphasize the limitations of the present canonical pathway paradigm, and discuss the value of a systems biology approach using more global, quantitative experimental design and data analysis strategies. Lastly, we urge caution about overly facile interpretation of genome- and proteome-level studies. PMID:19295628

  20. The informational architecture of the cell.

    PubMed

    Walker, Sara Imari; Kim, Hyunju; Davies, Paul C W

    2016-03-13

    We compare the informational architecture of biological and random networks to identify informational features that may distinguish biological networks from random. The study presented here focuses on the Boolean network model for regulation of the cell cycle of the fission yeast Schizosaccharomyces pombe. We compare calculated values of local and global information measures for the fission yeast cell cycle to the same measures as applied to two different classes of random networks: Erdös-Rényi and scale-free. We report patterns in local information processing and storage that do indeed distinguish biological from random, associated with control nodes that regulate the function of the fission yeast cell-cycle network. Conversely, we find that integrated information, which serves as a global measure of 'emergent' information processing, does not differ from random for the case presented. We discuss implications for our understanding of the informational architecture of the fission yeast cell-cycle network in particular, and more generally for illuminating any distinctive physics that may be operative in life. © 2016 The Author(s).

  1. Methods to achieve accurate projection of regional and global raster databases

    USGS Publications Warehouse

    Usery, E. Lynn; Seong, Jeong Chang; Steinwand, Dan

    2002-01-01

    Modeling regional and global activities of climatic and human-induced change requires accurate geographic data from which we can develop mathematical and statistical tabulations of attributes and properties of the environment. Many of these models depend on data formatted as raster cells or matrices of pixel values. Recently, it has been demonstrated that regional and global raster datasets are subject to significant error from mathematical projection and that these errors are of such magnitude that model results may be jeopardized (Steinwand, et al., 1995; Yang, et al., 1996; Usery and Seong, 2001; Seong and Usery, 2001). There is a need to develop methods of projection that maintain the accuracy of these datasets to support regional and global analyses and modeling

  2. Exploratory spatial data analysis of global MODIS active fire data

    NASA Astrophysics Data System (ADS)

    Oom, D.; Pereira, J. M. C.

    2013-04-01

    We performed an exploratory spatial data analysis (ESDA) of autocorrelation patterns in the NASA MODIS MCD14ML Collection 5 active fire dataset, for the period 2001-2009, at the global scale. The dataset was screened, resulting in an annual rate of false alarms and non-vegetation fires ranging from a minimum of 3.1% in 2003 to a maximum of 4.4% in 2001. Hot bare soils and gas flares were the major sources of false alarms and non-vegetation fires. The data were aggregated at 0.5° resolution for the global and local spatial autocorrelation Fire counts were found to be positively correlated up to distances of around 200 km, and negatively for larger distances. A value of 0.80 (p = 0.001, α = 0.05) for Moran's I indicates strong spatial autocorrelation between fires at global scale, with 60% of all cells displaying significant positive or negative spatial correlation. Different types of spatial autocorrelation were mapped and regression diagnostics allowed for the identification of spatial outlier cells, with fire counts much higher or lower than expected, considering their spatial context.

  3. Microanalytical study of discontinuous precipitation and dissolution in Ni-4 at. % Sn: Local and global characterization of the reactions

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zieba, P.; Gust, W.

    1999-07-09

    The morphology and kinetics of the discontinuous precipitation (DP) and discontinuous dissolution (DD) reactions have been studied in a Ni-4 at.% Sn alloy. High spatial resolution energy-dispersive X-ray microanalysis has been used to determine the Sn concentration profiles left behind the moving reaction front for the individual cells of the Sn-depleted [alpha] lamellae and Ni[sub 3]Sn compound. These data, combined with the local values of the reaction front velocity and the thickness of the [alpha]lamellae, have been used to evaluate the local s[delta]D[sub b] values (D[sub b] is the grain-boundary chemical diffusion coefficient, [delta] is the grain-boundary thickness and smore » is the segregation factor). The obtained results have been compared with those calculated by the global approach to the DP and DD reactions, which is relevant for the whole population of the cells. It has been shown that the application of the local characterization of the DP and DD reactions removes essentially the differences between the s[delta]D[sub b] values calculated by the Petermann-Hornbogen equation and the equations of Cahn and Zieba-Pawlowski. Moreover, both sets of data do not show any substantial differences from the s[delta]D[sub b] values obtained from measurements of the tracer diffusion of tin along stationary grain boundaries in nickel.« less

  4. Reconnection in the Martian Magnetotail: Hall-MHD With Embedded Particle-in-Cell Simulations

    NASA Astrophysics Data System (ADS)

    Ma, Yingjuan; Russell, Christopher T.; Toth, Gabor; Chen, Yuxi; Nagy, Andrew F.; Harada, Yuki; McFadden, James; Halekas, Jasper S.; Lillis, Rob; Connerney, John E. P.; Espley, Jared; DiBraccio, Gina A.; Markidis, Stefano; Peng, Ivy Bo; Fang, Xiaohua; Jakosky, Bruce M.

    2018-05-01

    Mars Atmosphere and Volatile EvolutioN (MAVEN) mission observations show clear evidence of the occurrence of the magnetic reconnection process in the Martian plasma tail. In this study, we use sophisticated numerical models to help us understand the effects of magnetic reconnection in the plasma tail. The numerical models used in this study are (a) a multispecies global Hall-magnetohydrodynamic (HMHD) model and (b) a global HMHD model two-way coupled to an embedded fully kinetic particle-in-cell code. Comparison with MAVEN observations clearly shows that the general interaction pattern is well reproduced by the global HMHD model. The coupled model takes advantage of both the efficiency of the MHD model and the ability to incorporate kinetic processes of the particle-in-cell model, making it feasible to conduct kinetic simulations for Mars under realistic solar wind conditions for the first time. Results from the coupled model show that the Martian magnetotail is highly dynamic due to magnetic reconnection, and the resulting Mars-ward plasma flow velocities are significantly higher for the lighter ion fluid, which are quantitatively consistent with MAVEN observations. The HMHD with Embedded Particle-in-Cell model predicts that the ion loss rates are more variable but with similar mean values as compared with HMHD model results.

  5. TNK2 Tyrosine Kinase as a Novel Therapeutic Target in Triple-Negative Breast Cancer

    DTIC Science & Technology

    2017-10-01

    performed global phosphotyrosine profiling for a panel of 25 TNBC cell lines. When we correlated protein phosphorylation levels with cellular oncogenic...levels and activation correlate with clinical and pathological features of TNBC? Aim 2: What is the value of TNK2 as a therapeutic target in vitro and

  6. Dynamics of total electron content distribution during strong geomagnetic storms

    NASA Astrophysics Data System (ADS)

    Astafyeva, E. I.; Afraimovich, E. L.; Kosogorov, E. A.

    We worked out a new method of mapping of total electron content TEC equal lines displacement velocity The method is based on the technique of global absolute vertical TEC value mapping Global Ionospheric Maps technique GIM GIM with 2-hours time resolution are available from Internet underline ftp cddisa gsfc nasa gov in standard IONEX-files format We determine the displacement velocity absolute value as well as its wave vector orientation from increments of TEC x y derivatives and TEC time derivative for each standard GIM cell 5 in longitude to 2 5 in latitude Thus we observe global traveling of TEC equal lines but we also can estimate the velocity of these line traveling Using the new method we observed anomalous rapid accumulation of the ionosphere plasma at some confined area due to the depletion of the ionization at the other spacious territories During the main phase of the geomagnetic storm on 29-30 October 2003 very large TEC enhancements appeared in the southwest of North America TEC value in that area reached up to 200 TECU 1 TECU 10 16 m -2 It was found that maximal velocity of TEC equal lines motion exceeded 1500 m s and the mean value of the velocity was about 400 m s Azimuth of wave vectors of TEC equal lines were orientated toward the center of region with anomaly high values of TEC the southwest of North America It should be noted that maximal TEC values during geomagnetically quiet conditions is about 60-80 TECU the value of TEC equal lines

  7. Global Analysis of Empirical Relationships Between Annual Climate and Seasonality of NDVI

    NASA Technical Reports Server (NTRS)

    Potter, C. S.

    1997-01-01

    This study describes the use of satellite data to calibrate a new climate-vegetation greenness function for global change studies. We examined statistical relationships between annual climate indexes (temperature, precipitation, and surface radiation) and seasonal attributes of the AVHRR Normalized Difference Vegetation Index (NDVI) time series for the mid-1980s in order to refine our empirical understanding of intraannual patterns and global abiotic controls on natural vegetation dynamics. Multiple linear regression results using global l(sup o) gridded data sets suggest that three climate indexes: growing degree days, annual precipitation total, and an annual moisture index together can account to 70-80 percent of the variation in the NDVI seasonal extremes (maximum and minimum values) for the calibration year 1984. Inclusion of the same climate index values from the previous year explained no significant additional portion of the global scale variation in NDVI seasonal extremes. The monthly timing of NDVI extremes was closely associated with seasonal patterns in maximum and minimum temperature and rainfall, with lag times of 1 to 2 months. We separated well-drained areas from l(sup o) grid cells mapped as greater than 25 percent inundated coverage for estimation of both the magnitude and timing of seasonal NDVI maximum values. Predicted monthly NDVI, derived from our climate-based regression equations and Fourier smoothing algorithms, shows good agreement with observed NDVI at a series of ecosystem test locations from around the globe. Regions in which NDVI seasonal extremes were not accurately predicted are mainly high latitude ecosystems and other remote locations where climate station data are sparse.

  8. Modelling of Fiber/Matrix Debonding of Composites Under Cyclic Loading

    NASA Technical Reports Server (NTRS)

    Naghipour, Paria; Pineda, Evan J.; Bednarcyk, Brett A.; Arnold, Steven M.

    2013-01-01

    The micromechanics theory, generalized method of cells (GMC), was employed to simulate the debonding of fiber/matrix interfaces, within a repeating unit cell subjected to global, cyclic loading, utilizing a cyclic crack growth law. Cycle dependent, interfacial debonding was implemented as a new module to the available GMC formulation. The degradation of interfacial stresses, with applied load cycles, was achieved via progressive evolution of the interfacial compliance. A periodic repeating unit cell, representing the fiber/matrix architecture of a composite, was subjected to combined normal and shear loadings, and degradation of the global transverse stress in successive cycles was monitored. The obtained results were compared to values from a corresponding finite element model. Reasonable agreement was achieved for combined normal and shear loading conditions, with minimal variation for pure loading cases. The local effects of interfacial debonding, and fatigue damage will later be combined as sub-models to predict the experimentally obtained fatigue life of Ti-15-3/Sic composites at the laminate level.

  9. Acid-base properties of the N3 ruthenium(II) solar cell sensitizer: a combined experimental and computational analysis.

    PubMed

    Pizzoli, Giuliano; Lobello, Maria Grazia; Carlotti, Benedetta; Elisei, Fausto; Nazeeruddin, Mohammad K; Vitillaro, Giuseppe; De Angelis, Filippo

    2012-10-14

    We report a combined spectro-photometric and computational investigation of the acid-base equilibria of the N3 solar cell sensitizer [Ru(dcbpyH(2))(2)(NCS)(2)] (dcbpyH(2) = 4,4'-dicarboxyl-2,2' bipyridine) in aqueous/ethanol solutions. The absorption spectra of N3 recorded at various pH values were analyzed by Single Value Decomposition techniques, followed by Global Fitting procedures, allowing us to identify four separate acid-base equilibria and their corresponding ground state pK(a) values. DFT/TDDFT calculations were performed for the N3 dye in solution, investigating the possible relevant species obtained by sequential deprotonation of the four dye carboxylic groups. TDDFT excited state calculations provided UV-vis absorption spectra which nicely agree with the experimental spectral shapes at various pH values. The calculated pK(a) values are also in good agreement with experimental data, within <1 pK(a) unit. Based on the calculated energy differences a tentative assignment of the N3 deprotonation pathway is reported.

  10. The added value of dynamical downscaling in a climate change scenario simulation:A case study for European Alps and East Asia

    NASA Astrophysics Data System (ADS)

    Im, Eun-Soon; Coppola, Erika; Giorgi, Filippo

    2010-05-01

    Since anthropogenic climate change is a rather important factor for the future human life all over the planet and its effects are not globally uniform, climate information at regional or local scales become more and more important for an accurate assessment of the potential impact of climate change on societies and ecosystems. High resolution information with suitably fine-scale for resolving complex geographical features could be a critical factor for successful linkage between climate models and impact assessment studies. However, scale mismatch between them still remains major problem. One method for overcoming the resolution limitations of global climate models and for adding regional details to coarse-grid global projections is to use dynamical downscaling by means of a regional climate model. In this study, the ECHAM5/MPI-OM (1.875 degree) A1B scenario simulation has been dynamically downscaled by using two different approaches within the framework of RegCM3 modeling system. First, a mosaic-type parameterization of subgrid-scale topography and land use (Sub-BATS) is applied over the European Alpine region. The Sub-BATS system is composed of 15 km coarse-grid cell and 3 km sub-grid cell. Second, we developed the RegCM3 one-way double-nested system, with the mother domain encompassing the eastern regions of Asia at 60 km grid spacing and the nested domain covering the Korean Peninsula at 20 km grid spacing. By comparing the regional climate model output and the driving global model ECHAM5/MPI-OM output, it is possible to estimate the added value of physically-based dynamical downscaling when for example impact studies at hydrological scale are performed.

  11. Cell-specific prediction and application of drug-induced gene expression profiles.

    PubMed

    Hodos, Rachel; Zhang, Ping; Lee, Hao-Chih; Duan, Qiaonan; Wang, Zichen; Clark, Neil R; Ma'ayan, Avi; Wang, Fei; Kidd, Brian; Hu, Jianying; Sontag, David; Dudley, Joel

    2018-01-01

    Gene expression profiling of in vitro drug perturbations is useful for many biomedical discovery applications including drug repurposing and elucidation of drug mechanisms. However, limited data availability across cell types has hindered our capacity to leverage or explore the cell-specificity of these perturbations. While recent efforts have generated a large number of drug perturbation profiles across a variety of human cell types, many gaps remain in this combinatorial drug-cell space. Hence, we asked whether it is possible to fill these gaps by predicting cell-specific drug perturbation profiles using available expression data from related conditions--i.e. from other drugs and cell types. We developed a computational framework that first arranges existing profiles into a three-dimensional array (or tensor) indexed by drugs, genes, and cell types, and then uses either local (nearest-neighbors) or global (tensor completion) information to predict unmeasured profiles. We evaluate prediction accuracy using a variety of metrics, and find that the two methods have complementary performance, each superior in different regions in the drug-cell space. Predictions achieve correlations of 0.68 with true values, and maintain accurate differentially expressed genes (AUC 0.81). Finally, we demonstrate that the predicted profiles add value for making downstream associations with drug targets and therapeutic classes.

  12. Cell-specific prediction and application of drug-induced gene expression profiles

    PubMed Central

    Hodos, Rachel; Zhang, Ping; Lee, Hao-Chih; Duan, Qiaonan; Wang, Zichen; Clark, Neil R.; Ma'ayan, Avi; Wang, Fei; Kidd, Brian; Hu, Jianying; Sontag, David

    2017-01-01

    Gene expression profiling of in vitro drug perturbations is useful for many biomedical discovery applications including drug repurposing and elucidation of drug mechanisms. However, limited data availability across cell types has hindered our capacity to leverage or explore the cell-specificity of these perturbations. While recent efforts have generated a large number of drug perturbation profiles across a variety of human cell types, many gaps remain in this combinatorial drug-cell space. Hence, we asked whether it is possible to fill these gaps by predicting cell-specific drug perturbation profiles using available expression data from related conditions--i.e. from other drugs and cell types. We developed a computational framework that first arranges existing profiles into a three-dimensional array (or tensor) indexed by drugs, genes, and cell types, and then uses either local (nearest-neighbors) or global (tensor completion) information to predict unmeasured profiles. We evaluate prediction accuracy using a variety of metrics, and find that the two methods have complementary performance, each superior in different regions in the drug-cell space. Predictions achieve correlations of 0.68 with true values, and maintain accurate differentially expressed genes (AUC 0.81). Finally, we demonstrate that the predicted profiles add value for making downstream associations with drug targets and therapeutic classes. PMID:29218867

  13. Leveraging cell type specific regulatory regions to detect SNPs associated with tissue factor pathway inhibitor plasma levels.

    PubMed

    Dennis, Jessica; Medina-Rivera, Alejandra; Truong, Vinh; Antounians, Lina; Zwingerman, Nora; Carrasco, Giovana; Strug, Lisa; Wells, Phil; Trégouët, David-Alexandre; Morange, Pierre-Emmanuel; Wilson, Michael D; Gagnon, France

    2017-07-01

    Tissue factor pathway inhibitor (TFPI) regulates the formation of intravascular blood clots, which manifest clinically as ischemic heart disease, ischemic stroke, and venous thromboembolism (VTE). TFPI plasma levels are heritable, but the genetics underlying TFPI plasma level variability are poorly understood. Herein we report the first genome-wide association scan (GWAS) of TFPI plasma levels, conducted in 251 individuals from five extended French-Canadian Families ascertained on VTE. To improve discovery, we also applied a hypothesis-driven (HD) GWAS approach that prioritized single nucleotide polymorphisms (SNPs) in (1) hemostasis pathway genes, and (2) vascular endothelial cell (EC) regulatory regions, which are among the highest expressers of TFPI. Our GWAS identified 131 SNPs with suggestive evidence of association (P-value < 5 × 10 -8 ), but no SNPs reached the genome-wide threshold for statistical significance. Hemostasis pathway genes were not enriched for TFPI plasma level associated SNPs (global hypothesis test P-value = 0.147), but EC regulatory regions contained more TFPI plasma level associated SNPs than expected by chance (global hypothesis test P-value = 0.046). We therefore stratified our genome-wide SNPs, prioritizing those in EC regulatory regions via stratified false discovery rate (sFDR) control, and reranked the SNPs by q-value. The minimum q-value was 0.27, and the top-ranked SNPs did not show association evidence in the MARTHA replication sample of 1,033 unrelated VTE cases. Although this study did not result in new loci for TFPI, our work lays out a strategy to utilize epigenomic data in prioritization schemes for future GWAS studies. © 2017 WILEY PERIODICALS, INC.

  14. Global-scale analysis of satellite-derived time series of naturally inundated areas as a basis for floodplain modeling

    NASA Astrophysics Data System (ADS)

    Adam, L.; Döll, P.; Prigent, C.; Papa, F.

    2010-08-01

    Floodplains play an important role in the terrestrial water cycle and are very important for biodiversity. Therefore, an improved representation of the dynamics of floodplain water flows and storage in global hydrological and land surface models is required. To support model validation, we combined monthly time series of satellite-derived inundation areas (Papa et al., 2010) with data on irrigated rice areas (Portmann et al., 2010). In this way, we obtained global-scale time series of naturally inundated areas (NIA), with monthly values of inundation extent during 1993-2004 and a spatial resolution of 0.5°. For most grid cells (0.5°×0.5°), the mean annual maximum of NIA agrees well with the static open water extent of the Global Lakes and Wetlands database (GLWD) (Lehner and Döll, 2004), but in 16% of the cells NIA is larger than GLWD. In some regions, like Northwestern Europe, NIA clearly overestimates inundated areas, probably because of confounding very wet soils with inundated areas. In other areas, such as South Asia, it is likely that NIA can help to enhance GLWD. NIA data will be very useful for developing and validating a floodplain modeling algorithm for the global hydrological model WGHM. For example, we found that monthly NIAs correlate with observed river discharges.

  15. Carbonic anhydrase IX as a potential biomarker of efficacy in metastatic clear-cell renal cell carcinoma patients receiving sorafenib or placebo: analysis from the treatment approaches in renal cancer global evaluation trial (TARGET).

    PubMed

    Choueiri, Toni K; Cheng, Suchun; Qu, Angela Q; Pastorek, Jaromir; Atkins, Michael B; Signoretti, Sabina

    2013-11-01

    Retrospective data analyses have suggested that carbonic anhydrase IX (CAIX) may have a predictive role in patients with metastatic clear cell renal cell carcinoma (ccRCC) receiving high dose interleukin-2 or sorafenib. We examined the predictive value of CAIX in estimating treatment outcome in patients receiving sorafenib vs. placebo as part of the Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET) study. Paraffin embedded tumor tissues were collected from 133 patients from the TARGET study (n = 903). The percentage of CAIX-positive cells was assessed by a single pathologist. The impact of CAIX expression on progression-free survival (PFS, primary endpoint) and tumor shrinkage (TS, secondary endpoint) was analyzed. Clinical characteristics were similarly distributed between patients with low vs. high CAIX staining, as well as patients with available CAIX data vs. not. Median PFS for patients with high CAIX vs. low CAIX expression was 5.5 and 5.4 months, respectively, on the sorafenib arm (P = 0.97), and 1.5 and 1.7 months on the placebo arm (P = 0.76). Median TS for patients with high CAIX status was -14.9% vs. -12.6% in patients with low CAIX status (P = 0.63) on the sorafenib arm, and +1.3% (high CAIX) vs. +4.8% (low CAIX) in patients on the placebo arm (P = 0.60). Despite suggestive retrospective evidence, data from the TARGET study did not find CAIX expression status to be either predictive of clinical benefit for treatment with sorafenib or of prognostic value in patients with metastatic ccRCC following cytokine therapy. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Global Analysis of Empirical Relationships Between Annual Climate and Seasonality of NDVI

    NASA Technical Reports Server (NTRS)

    Potter, C. S.; Brooks, V.

    1997-01-01

    This paper describes the use of satellite data to calibrate a new climate-vegetation greenness relationship for global change studies. We examined statistical relationships between annual climate indexes (temperature, precipitation, and surface radiation) and seasonal attributes If the AVHRR Normalized Difference Vegetation Index (NDVI) time series for the mid-1980's in order to refine our understanding of intra-annual patterns and global abiotic controls on natural vegetation dynamics. Multiple linear regression results using global 1o gridded data sets suggest that three climate indexes: degree days (growing/chilling), annual precipitation total, and an annual moisture index together can account to 70-80 percent of the geographic variation in the NDVI seasonal extremes (maximum and minimum values) for the calibration year 1984. Inclusion of the same annual climate index values from the previous year explains no substantial additional portion of the global scale variation in NDVI seasonal extremes. The monthly timing of NDVI extremes is closely associated with seasonal patterns in maximum and minimum temperature and rainfall, with lag times of 1 to 2 months. We separated well-drained areas from lo grid cells mapped as greater than 25 percent inundated coverage for estimation of both the magnitude and timing of seasonal NDVI maximum values. Predicted monthly NDVI, derived from our climate-based regression equations and Fourier smoothing algorithms, shows good agreement with observed NDVI for several different years at a series of ecosystem test locations from around the globe. Regions in which NDVI seasonal extremes are not accurately predicted are mainly high latitude zones, mixed and disturbed vegetation types, and other remote locations where climate station data are sparse.

  17. Effects of BPA on global DNA methylation and global histone 3 lysine modifications in SH-SY5Y cells: An epigenetic mechanism linking the regulation of chromatin modifiying genes.

    PubMed

    Senyildiz, Mine; Karaman, Ecem Fatma; Bas, Serap Sancar; Pirincci, Pelin Arda; Ozden, Sibel

    2017-10-01

    Bisphenol A (BPA), an estrogenic endocrine disruptor, is widely used in the production of polycarbonate plastic and epoxy resins, resulting in high risk on human health. In present study we aimed to investigate the effects of BPA on global and gene specific DNA methylation, global histone modifications and regulation of chromatin modifiying enzymes in human neuroblastoma cells (SH-SY5Y). Cells were treated with BPA at 0.1, 1 and 10μM concentrations for 48 and 96h. IC 50 value of BPA was determined as 183 and 129μM in SH-SY5Y cells after 24h by MTT and NRU tests, respectively. We observed significant alterations on the 5-mC% levels (1.3 fold) and 5-hmC% levels (1.67 fold) after 10μM of BPA for 96h. Significant decrease was identified in H3K9me3 and H3K9ac after 10μM of BPA for 96h while decrease was observed in H3K4me3 at 10μM of BPA for 48h. Alterations were observed in chromatin modifiying genes including G9a, EZH2, SETD8, SETD1A, HAT1, SIRT1, DNMT1, RIZ1 and Suv39h1 after 96h of BPA exposure. Taken together, this study suggests that BPA might modulate the epigenetic regulators which would be key molecular events in the toxicity of endocrine disrupting chemicals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. A global sensitivity analysis of crop virtual water content

    NASA Astrophysics Data System (ADS)

    Tamea, S.; Tuninetti, M.; D'Odorico, P.; Laio, F.; Ridolfi, L.

    2015-12-01

    The concepts of virtual water and water footprint are becoming widely used in the scientific literature and they are proving their usefulness in a number of multidisciplinary contexts. With such growing interest a measure of data reliability (and uncertainty) is becoming pressing but, as of today, assessments of data sensitivity to model parameters, performed at the global scale, are not known. This contribution aims at filling this gap. Starting point of this study is the evaluation of the green and blue virtual water content (VWC) of four staple crops (i.e. wheat, rice, maize, and soybean) at a global high resolution scale. In each grid cell, the crop VWC is given by the ratio between the total crop evapotranspiration over the growing season and the crop actual yield, where evapotranspiration is determined with a detailed daily soil water balance and actual yield is estimated using country-based data, adjusted to account for spatial variability. The model provides estimates of the VWC at a 5x5 arc minutes and it improves on previous works by using the newest available data and including multi-cropping practices in the evaluation. The model is then used as the basis for a sensitivity analysis, in order to evaluate the role of model parameters in affecting the VWC and to understand how uncertainties in input data propagate and impact the VWC accounting. In each cell, small changes are exerted to one parameter at a time, and a sensitivity index is determined as the ratio between the relative change of VWC and the relative change of the input parameter with respect to its reference value. At the global scale, VWC is found to be most sensitive to the planting date, with a positive (direct) or negative (inverse) sensitivity index depending on the typical season of crop planting date. VWC is also markedly dependent on the length of the growing period, with an increase in length always producing an increase of VWC, but with higher spatial variability for rice than for other crops. The sensitivity to the reference evapotranspiration is highly variable with the considered crop and ranges from positive values (for soybean), to negative values (for rice and maize) and near-zero values for wheat. This variability reflects the different yield response factors of crops, which expresses their tolerance to water stress.

  19. Mapping suitability areas for concentrated solar power plants using remote sensing data

    DOE PAGES

    Omitaomu, Olufemi A.; Singh, Nagendra; Bhaduri, Budhendra L.

    2015-05-14

    The political push to increase power generation from renewable sources such as solar energy requires knowing the best places to site new solar power plants with respect to the applicable regulatory, operational, engineering, environmental, and socioeconomic criteria. Therefore, in this paper, we present applications of remote sensing data for mapping suitability areas for concentrated solar power plants. Our approach uses digital elevation model derived from NASA s Shuttle Radar Topographic Mission (SRTM) at a resolution of 3 arc second (approx. 90m resolution) for estimating global solar radiation for the study area. Then, we develop a computational model built on amore » Geographic Information System (GIS) platform that divides the study area into a grid of cells and estimates site suitability value for each cell by computing a list of metrics based on applicable siting requirements using GIS data. The computed metrics include population density, solar energy potential, federal lands, and hazardous facilities. Overall, some 30 GIS data are used to compute eight metrics. The site suitability value for each cell is computed as an algebraic sum of all metrics for the cell with the assumption that all metrics have equal weight. Finally, we color each cell according to its suitability value. Furthermore, we present results for concentrated solar power that drives a stream turbine and parabolic mirror connected to a Stirling Engine.« less

  20. Mathematical model for the analysis of structure and optimal operational parameters of a solid oxide fuel cell generator

    NASA Astrophysics Data System (ADS)

    Coralli, Alberto; Villela de Miranda, Hugo; Espiúca Monteiro, Carlos Felipe; Resende da Silva, José Francisco; Valadão de Miranda, Paulo Emílio

    2014-12-01

    Solid oxide fuel cells are globally recognized as a very promising technology in the area of highly efficient electricity generation with a low environmental impact. This technology can be advantageously implemented in many situations in Brazil and it is well suited to the use of ethanol as a primary energy source, an important feature given the highly developed Brazilian ethanol industry. In this perspective, a simplified mathematical model is developed for a fuel cell and its balance of plant, in order to identify the optimal system structure and the most convenient values for the operational parameters, with the aim of maximizing the global electric efficiency. In this way it is discovered the best operational configuration for the desired application, which is the distributed generation in the concession area of the electricity distribution company Elektro. The data regarding this configuration are required for the continuation of the research project, i.e. the development of a prototype, a cost analysis of the developed system and a detailed perspective of the market opportunities in Brazil.

  1. Galleria mellonella larvae allow the discrimination of toxic and non-toxic chemicals.

    PubMed

    Allegra, Enrico; Titball, Richard W; Carter, John; Champion, Olivia L

    2018-05-01

    The acute toxicities of 19 chemicals were assessed using G. mellonella larvae. The results obtained were compared against LD50 values derived from in vitro cytotoxicity tests and against in vivo acute oral LD50 values. In general, cell culture systems overestimated the toxicity of chemicals, especially low toxicity chemicals. In contrast, toxicity testing in G. mellonella larvae was found to be a reliable predictor for low toxicity chemicals. For the 9 chemicals tested which were assigned to Globally Harmonised System (GHS) category 5, the toxicity measured in G. mellonella larvae was consistent with their GHS categorisation but cytotoxicity measured in 3T3 or NHK cells predicted 4 out of 9 chemicals as having low toxicity. A more robust assessment of the likely toxicity of chemicals in mammals could be made by taking into account their toxicities in both cell cultures and in G. mellonella larvae. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Global asymptotic stability for HIV-1 dynamics with two distributed delays.

    PubMed

    Wang, Jinliang; Huang, Gang; Takeuchi, Yasuhiro

    2012-09-01

    Based on the drugs treatment to control HIV-1 infection and viral replication, we express the intracellular eclipse phase of virions in host cell as distributed delays because of pharmacological actions. In present paper, we investigate a class of HIV-1 infection dynamical model with two distributed delays. One of them describes the period between the time that HIV virion enters (infects) target cell and the time that the infected cell starts to produce new viral particles. The other describes the time for the virion maturation process. They are both allowed to tend to be infinite because of drugs resistent strains. By the Lyapunov direct method of and utilizing the technology of constructing Lyapunov functionals, we identify the basic reproduction number R(0) as a threshold quantity for the stability of equilibria. More precisely, if R(0) ≤ 1, the infection-free equilibrium is globally asymptotically stable; on the contrary, if R(0) > 1, then an infected equilibrium appears which is globally asymptotically stable. The dynamical results indicate that time delays have effect on the global stability of two equilibria through threshold value R(0), which is a decreasing function of delays. The biological meanings imply that any drugs that can prolong the time of viral reproduction through slowing down the reverse transcription of HIV in host and virus maturation process may also help control the HIV-1 infection and virus loads. Another way to increase the efficacy of the protease inhibitor and the reverse transcriptase inhibitor (i.e. increasing n(p) and n(rt)) is also desirable treatment strategies.

  3. Cartograms Facilitate Communication of Climate Change Risks and Responsibilities

    NASA Astrophysics Data System (ADS)

    Döll, Petra

    2017-12-01

    Communication of climate change (CC) risks is challenging, in particular if global-scale spatially resolved quantitative information is to be conveyed. Typically, visualization of CC risks, which arise from the combination of hazard, exposure and vulnerability, is confined to showing only the hazards in the form of global thematic maps. This paper explores the potential of contiguous value-by-area cartograms, that is, distorted density-equalizing maps, for improving communication of CC risks and the countries' differentiated responsibilities for CC. Two global-scale cartogram sets visualize, as an example, groundwater-related CC risks in 0.5° grid cells, another one the correlation of (cumulative) fossil-fuel carbon dioxide emissions with the countries' population and gross domestic product. Viewers of the latter set visually recognize the lack of global equity and that the countries' wealth has been built on harmful emissions. I recommend that CC risks are communicated by bivariate gridded cartograms showing the hazard in color and population, or a combination of population and a vulnerability indicator, by distortion of grid cells. Gridded cartograms are also appropriate for visualizing the availability of natural resources to humans. For communicating complex information, sets of cartograms should be carefully designed instead of presenting single cartograms. Inclusion of a conventionally distorted map enhances the viewers' capability to take up the information represented by distortion. Empirical studies about the capability of global cartograms to convey complex information and to trigger moral emotions should be conducted, with a special focus on risk communication.

  4. A Program for Solving the Brain Ischemia Problem

    PubMed Central

    DeGracia, Donald J.

    2013-01-01

    Our recently described nonlinear dynamical model of cell injury is here applied to the problems of brain ischemia and neuroprotection. We discuss measurement of global brain ischemia injury dynamics by time course analysis. Solutions to proposed experiments are simulated using hypothetical values for the model parameters. The solutions solve the global brain ischemia problem in terms of “master bifurcation diagrams” that show all possible outcomes for arbitrary durations of all lethal cerebral blood flow (CBF) decrements. The global ischemia master bifurcation diagrams: (1) can map to a single focal ischemia insult, and (2) reveal all CBF decrements susceptible to neuroprotection. We simulate measuring a neuroprotectant by time course analysis, which revealed emergent nonlinear effects that set dynamical limits on neuroprotection. Using over-simplified stroke geometry, we calculate a theoretical maximum protection of approximately 50% recovery. We also calculate what is likely to be obtained in practice and obtain 38% recovery; a number close to that often reported in the literature. The hypothetical examples studied here illustrate the use of the nonlinear cell injury model as a fresh avenue of approach that has the potential, not only to solve the brain ischemia problem, but also to advance the technology of neuroprotection. PMID:24961411

  5. DNA methylation analysis in rat kidney epithelial cells exposed to 3-MCPD and glycidol.

    PubMed

    Senyildiz, Mine; Alpertunga, Buket; Ozden, Sibel

    2017-10-01

    3-Monochloropropane-1,2-diol (3-MCPD) is a well-known food processing contaminant that has been regarded as a rat carcinogen, which is known to induce Leydig-cell and mammary gland tumors in males, as well as kidney tumors in both genders. 3-MCPD is highly suspected to be a non-genotoxic carcinogen. 2,3-Epoxy-1-propanol (glycidol) can be formed via dehalogenation from 3-MCPD. We aimed to investigate the cytotoxic effects of 3-MCPD and glycidol, then to demonstrate the possible epigenetic mechanisms with global and gene-specific DNA methylation in rat kidney epithelial cells (NRK-52E). IC 50 value of 3-MCPD was determined as 48 mM and 41.39 mM, whereas IC 50 value of glycidol was 1.67 mM and 1.13 mM by MTT and NRU test, respectively. Decreased global DNA methylation at the concentrations of 100 μM and 1000 μM for 3-MCPD and 100 μM and 500 μM for glycidol were observed after 48 h exposure by using 5-methylcytosine (5-mC) ELISA kit. Methylation changes were detected in promoter regions of c-myc and Rassf1a in 3-MCPD and glycidol treated NRK-52E cells by using methylation-specific PCR (MSP), whereas changes on gene expression of c-myc and Rassf1a were observed by using real-time PCR. However, e-cadherin, p16, VHL and p15 genes were unmethylated in their CpG promoter regions in response to treatment with 3-MCPD and glycidol. Alterations in DNA methylation might be key events in the toxicity of 3-MCPD and glycidol.

  6. A model of global citizenship: antecedents and outcomes.

    PubMed

    Reysen, Stephen; Katzarska-Miller, Iva

    2013-01-01

    As the world becomes increasingly interconnected, exposure to global cultures affords individuals opportunities to develop global identities. In two studies, we examine the antecedents and outcomes of identifying with a superordinate identity--global citizen. Global citizenship is defined as awareness, caring, and embracing cultural diversity while promoting social justice and sustainability, coupled with a sense of responsibility to act. Prior theory and research suggest that being aware of one's connection with others in the world (global awareness) and embedded in settings that value global citizenship (normative environment) lead to greater identification with global citizens. Furthermore, theory and research suggest that when global citizen identity is salient, greater identification is related to adherence to the group's content (i.e., prosocial values and behaviors). Results of the present set of studies showed that global awareness (knowledge and interconnectedness with others) and one's normative environment (friends and family support global citizenship) predicted identification with global citizens, and global citizenship predicted prosocial values of intergroup empathy, valuing diversity, social justice, environmental sustainability, intergroup helping, and a felt responsibility to act for the betterment of the world. The relationship between antecedents (normative environment and global awareness) and outcomes (prosocial values) was mediated by identification with global citizens. We discuss the relationship between the present results and other research findings in psychology, the implications of global citizenship for other academic domains, and future avenues of research. Global citizenship highlights the unique effect of taking a global perspective on a multitude of topics relevant to the psychology of everyday actions, environments, and identity.

  7. Microbial production of value-added nutraceuticals.

    PubMed

    Wang, Jian; Guleria, Sanjay; Koffas, Mattheos Ag; Yan, Yajun

    2016-02-01

    Nutraceuticals are important natural bioactive compounds that confer health-promoting and medical benefits to humans. Globally growing demands for value-added nutraceuticals for prevention and treatment of human diseases have rendered nutraceuticals a multi-billion dollar market. However, supply limitations and extraction difficulties from natural sources such as plants, animals or fungi, restrict the large-scale use of nutraceuticals. Metabolic engineering via microbial production platforms has been advanced as an eco-friendly alternative approach for production of value-added nutraceuticals from simple carbon sources. Microbial platforms like the most widely used Escherichia coli and Saccharomyces cerevisiae have been engineered as versatile cell factories for production of diverse and complex value-added chemicals such as phytochemicals, prebiotics, polysaccaharides and poly amino acids. This review highlights the recent progresses in biological production of value-added nutraceuticals via metabolic engineering approaches. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Identifying Priority Areas for Conservation: A Global Assessment for Forest-Dependent Birds

    PubMed Central

    Buchanan, Graeme M.; Donald, Paul F.; Butchart, Stuart H. M.

    2011-01-01

    Limited resources are available to address the world's growing environmental problems, requiring conservationists to identify priority sites for action. Using new distribution maps for all of the world's forest-dependent birds (60.6% of all bird species), we quantify the contribution of remaining forest to conserving global avian biodiversity. For each of the world's partly or wholly forested 5-km cells, we estimated an impact score of its contribution to the distribution of all the forest bird species estimated to occur within it, and so is proportional to the impact on the conservation status of the world's forest-dependent birds were the forest it contains lost. The distribution of scores was highly skewed, a very small proportion of cells having scores several orders of magnitude above the global mean. Ecoregions containing the highest values of this score included relatively species-poor islands such as Hawaii and Palau, the relatively species-rich islands of Indonesia and the Philippines, and the megadiverse Atlantic Forests and northern Andes of South America. Ecoregions with high impact scores and high deforestation rates (2000–2005) included montane forests in Cameroon and the Eastern Arc of Tanzania, although deforestation data were not available for all ecoregions. Ecoregions with high impact scores, high rates of recent deforestation and low coverage by the protected area network included Indonesia's Seram rain forests and the moist forests of Trinidad and Tobago. Key sites in these ecoregions represent some of the most urgent priorities for expansion of the global protected areas network to meet Convention on Biological Diversity targets to increase the proportion of land formally protected to 17% by 2020. Areas with high impact scores, rapid deforestation, low protection and high carbon storage values may represent significant opportunities for both biodiversity conservation and climate change mitigation, for example through Reducing Emissions from Deforestation and Forest Degradation (REDD+) initiatives. PMID:22205998

  9. Noise in gene expression is coupled to growth rate.

    PubMed

    Keren, Leeat; van Dijk, David; Weingarten-Gabbay, Shira; Davidi, Dan; Jona, Ghil; Weinberger, Adina; Milo, Ron; Segal, Eran

    2015-12-01

    Genetically identical cells exposed to the same environment display variability in gene expression (noise), with important consequences for the fidelity of cellular regulation and biological function. Although population average gene expression is tightly coupled to growth rate, the effects of changes in environmental conditions on expression variability are not known. Here, we measure the single-cell expression distributions of approximately 900 Saccharomyces cerevisiae promoters across four environmental conditions using flow cytometry, and find that gene expression noise is tightly coupled to the environment and is generally higher at lower growth rates. Nutrient-poor conditions, which support lower growth rates, display elevated levels of noise for most promoters, regardless of their specific expression values. We present a simple model of noise in expression that results from having an asynchronous population, with cells at different cell-cycle stages, and with different partitioning of the cells between the stages at different growth rates. This model predicts non-monotonic global changes in noise at different growth rates as well as overall higher variability in expression for cell-cycle-regulated genes in all conditions. The consistency between this model and our data, as well as with noise measurements of cells growing in a chemostat at well-defined growth rates, suggests that cell-cycle heterogeneity is a major contributor to gene expression noise. Finally, we identify gene and promoter features that play a role in gene expression noise across conditions. Our results show the existence of growth-related global changes in gene expression noise and suggest their potential phenotypic implications. © 2015 Keren et al.; Published by Cold Spring Harbor Laboratory Press.

  10. Noise in gene expression is coupled to growth rate

    PubMed Central

    Keren, Leeat; van Dijk, David; Weingarten-Gabbay, Shira; Davidi, Dan; Jona, Ghil; Weinberger, Adina; Milo, Ron; Segal, Eran

    2015-01-01

    Genetically identical cells exposed to the same environment display variability in gene expression (noise), with important consequences for the fidelity of cellular regulation and biological function. Although population average gene expression is tightly coupled to growth rate, the effects of changes in environmental conditions on expression variability are not known. Here, we measure the single-cell expression distributions of approximately 900 Saccharomyces cerevisiae promoters across four environmental conditions using flow cytometry, and find that gene expression noise is tightly coupled to the environment and is generally higher at lower growth rates. Nutrient-poor conditions, which support lower growth rates, display elevated levels of noise for most promoters, regardless of their specific expression values. We present a simple model of noise in expression that results from having an asynchronous population, with cells at different cell-cycle stages, and with different partitioning of the cells between the stages at different growth rates. This model predicts non-monotonic global changes in noise at different growth rates as well as overall higher variability in expression for cell-cycle–regulated genes in all conditions. The consistency between this model and our data, as well as with noise measurements of cells growing in a chemostat at well-defined growth rates, suggests that cell-cycle heterogeneity is a major contributor to gene expression noise. Finally, we identify gene and promoter features that play a role in gene expression noise across conditions. Our results show the existence of growth-related global changes in gene expression noise and suggest their potential phenotypic implications. PMID:26355006

  11. Incremental triangulation by way of edge swapping and local optimization

    NASA Technical Reports Server (NTRS)

    Wiltberger, N. Lyn

    1994-01-01

    This document is intended to serve as an installation, usage, and basic theory guide for the two dimensional triangulation software 'HARLEY' written for the Silicon Graphics IRIS workstation. This code consists of an incremental triangulation algorithm based on point insertion and local edge swapping. Using this basic strategy, several types of triangulations can be produced depending on user selected options. For example, local edge swapping criteria can be chosen which minimizes the maximum interior angle (a MinMax triangulation) or which maximizes the minimum interior angle (a MaxMin or Delaunay triangulation). It should be noted that the MinMax triangulation is generally only locally optical (not globally optimal) in this measure. The MaxMin triangulation, however, is both locally and globally optical. In addition, Steiner triangulations can be constructed by inserting new sites at triangle circumcenters followed by edge swapping based on the MaxMin criteria. Incremental insertion of sites also provides flexibility in choosing cell refinement criteria. A dynamic heap structure has been implemented in the code so that once a refinement measure is specified (i.e., maximum aspect ratio or some measure of a solution gradient for the solution adaptive grid generation) the cell with the largest value of this measure is continually removed from the top of the heap and refined. The heap refinement strategy allows the user to specify either the number of cells desired or refine the mesh until all cell refinement measures satisfy a user specified tolerance level. Since the dynamic heap structure is constantly updated, the algorithm always refines the particular cell in the mesh with the largest refinement criteria value. The code allows the user to: triangulate a cloud of prespecified points (sites), triangulate a set of prespecified interior points constrained by prespecified boundary curve(s), Steiner triangulate the interior/exterior of prespecified boundary curve(s), refine existing triangulations based on solution error measures, and partition meshes based on the Cuthill-McKee, spectral, and coordinate bisection strategies.

  12. Gene Expression ‏‏‏‏Profiles of BAD and Bcl-xL in the CA1 Region of the Hippocampus Following Global Ischemic/Reperfusion and FK-506 Administration.

    PubMed

    Badr, Ramak; Hashemi, Mehrdad; Javadi, Gholamreza; Movafagh, Abolfazl; Mahdian, Reza

    2015-12-01

    The hippocampus is a tiny nub in the mammalian brain that is involved in forming, organizing, and storing memories. Global cerebral ischemia (GCI) and reperfusion induced apoptosis lead to cell injury and death. FK-506 is a strong immunosuppressant drug that has neuroprotective effects on the hypoxic-ischemic effects of brain damage. BAD and Bcl-xL are pro-apoptotic and anti-apoptotic genes, respectively. These genes belong to The B-cell lymphoma-2 (Bcl-2) family. In this study, we assessed the neurotrophic properties of FK-506 on expression of the BAD and Bcl-xL genes in the hippocampus following global ischemia and reperfusion. In the present experimental study, adult male Wistar rats were obtained and housed under standard conditions in the Tehran University of Medical Science in Iran. Rats were equally distributed in groups of three among the following groups: normal control, treated-1 (ischemia/reperfusion), and treated-2 (ischemia/reperfusion followed by FK-506). Global ischemia was induced for animals in the treated-1 and treated-2 groups. In treated-2, two doses of FK-506 were injected: one dose as an IV injection immediately after reperfusion and another as an intra-peritoneal (IP) injection after 48 hours. Then, the hippocampus tissue was removed after anaesthetizing the rats. RNA was isolated, cDNA was synthesized, and real-time PCR was performed. Finally, the obtained data were analyzed statistically (P value ˂ 0.05). The quantitative results of real-time PCR show that the mRNA expression ratio of Bcl-xL down-regulated was 0.75 ± 0.06 in the ischemia/reperfusion group versus 1.57 ± 0.09 in the control group (P value < 0.001), whereas Bcl-xL gene expression was greater in the ischemia/reperfusion +FK506 group (1.93 ± 0.15) than in the ischemia/reperfusion group. Moreover, the mRNA expression ratio of BAD up-regulated in the ischemia/reperfusion + FK506 group was 3.65 ± 0.49 compared to Normal control (1.39 ± 0.09) and Ischemia/reperfusion + FK506 was 1.09 ± 0.20 (P value < 0.001). The analysis of the pro-apoptotic gene to anti-apoptotic gene expression ratio (BAD /Bcl-xL) confirmed that expression of the pro-apoptotic gene significantly decreased (P value ˂ 0.001) under the ischemia/reperfusion condition. In contrast, the expression of the anti-apoptotic gene increased after administration of FK-506 (P value ˂ 0.001).

  13. Adaptive Multilinear Tensor Product Wavelets

    DOE PAGES

    Weiss, Kenneth; Lindstrom, Peter

    2015-08-12

    Many foundational visualization techniques including isosurfacing, direct volume rendering and texture mapping rely on piecewise multilinear interpolation over the cells of a mesh. However, there has not been much focus within the visualization community on techniques that efficiently generate and encode globally continuous functions defined by the union of multilinear cells. Wavelets provide a rich context for analyzing and processing complicated datasets. In this paper, we exploit adaptive regular refinement as a means of representing and evaluating functions described by a subset of their nonzero wavelet coefficients. We analyze the dependencies involved in the wavelet transform and describe how tomore » generate and represent the coarsest adaptive mesh with nodal function values such that the inverse wavelet transform is exactly reproduced via simple interpolation (subdivision) over the mesh elements. This allows for an adaptive, sparse representation of the function with on-demand evaluation at any point in the domain. In conclusion, we focus on the popular wavelets formed by tensor products of linear B-splines, resulting in an adaptive, nonconforming but crack-free quadtree (2D) or octree (3D) mesh that allows reproducing globally continuous functions via multilinear interpolation over its cells.« less

  14. 77 FR 36599 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-19

    ... Change Relating to the Accuvest Global Long Short ETF (Formerly the Mars Hill Global Relative Value ETF...) applicable to, the Accuvest Global Long Short ETF (``Fund'') (formerly known as the Mars Hill Global Relative... the Exchange of shares (``Shares'') of the Mars Hill Global Relative Value ETF, a series of Advisor...

  15. Theoretical analysis of three methods for calculating thermal insulation of clothing from thermal manikin.

    PubMed

    Huang, Jianhua

    2012-07-01

    There are three methods for calculating thermal insulation of clothing measured with a thermal manikin, i.e. the global method, the serial method, and the parallel method. Under the condition of homogeneous clothing insulation, these three methods yield the same insulation values. If the local heat flux is uniform over the manikin body, the global and serial methods provide the same insulation value. In most cases, the serial method gives a higher insulation value than the global method. There is a possibility that the insulation value from the serial method is lower than the value from the global method. The serial method always gives higher insulation value than the parallel method. The insulation value from the parallel method is higher or lower than the value from the global method, depending on the relationship between the heat loss distribution and the surface temperatures. Under the circumstance of uniform surface temperature distribution over the manikin body, the global and parallel methods give the same insulation value. If the constant surface temperature mode is used in the manikin test, the parallel method can be used to calculate the thermal insulation of clothing. If the constant heat flux mode is used in the manikin test, the serial method can be used to calculate the thermal insulation of clothing. The global method should be used for calculating thermal insulation of clothing for all manikin control modes, especially for thermal comfort regulation mode. The global method should be chosen by clothing manufacturers for labelling their products. The serial and parallel methods provide more information with respect to the different parts of clothing.

  16. Interactive influence of the Atlantic and Pacific climates and their contribution to the multidecadal variations of global temperature and precipitation.

    NASA Astrophysics Data System (ADS)

    Barcikowska, M. J.; Knutson, T. R.; Zhang, R.

    2016-12-01

    This study investigates mechanisms and global-scale climate impacts of multidecadal climate variability. Here we show, using observations and CSIRO-Mk3.6.0 model control run, that multidecadal variability of the Atlantic Meridional Overturning Circulation (AMOC) may have a profound impact on the thermal- and hydro-climatic changes over the Pacific region. In our model-based analysis we propose a mechanism, which comprises a coupled ocean-atmosphere teleconnection, established through the atmospheric overturning circulation cell between the tropical North Atlantic and tropical Pacific. For example, warming SSTs over the tropical North Atlantic intensify local convection and reinforce subsidence, low-level divergence in the eastern tropical Pacific. This is also accompanied with an intensification of trade winds, cooling and drying anomalies in the tropical central-east Pacific. The derived multidecadal changes, associated with the AMOC, contribute remarkably to the global temperature and precipitation variations. This highlights its potential predictive value. Shown here results suggest a possibility that: 1) recently observed slowdown in global warming may partly originate from internal variability, 2) climate system may be undergoing a transition to a cold AMO phase which could prolong the global slowdown.

  17. Recommended GIS Analysis Methods for Global Gridded Population Data

    NASA Astrophysics Data System (ADS)

    Frye, C. E.; Sorichetta, A.; Rose, A.

    2017-12-01

    When using geographic information systems (GIS) to analyze gridded, i.e., raster, population data, analysts need a detailed understanding of several factors that affect raster data processing, and thus, the accuracy of the results. Global raster data is most often provided in an unprojected state, usually in the WGS 1984 geographic coordinate system. Most GIS functions and tools evaluate data based on overlay relationships (area) or proximity (distance). Area and distance for global raster data can be either calculated directly using the various earth ellipsoids or after transforming the data to equal-area/equidistant projected coordinate systems to analyze all locations equally. However, unlike when projecting vector data, not all projected coordinate systems can support such analyses equally, and the process of transforming raster data from one coordinate space to another often results unmanaged loss of data through a process called resampling. Resampling determines which values to use in the result dataset given an imperfect locational match in the input dataset(s). Cell size or resolution, registration, resampling method, statistical type, and whether the raster represents continuous or discreet information potentially influence the quality of the result. Gridded population data represent estimates of population in each raster cell, and this presentation will provide guidelines for accurately transforming population rasters for analysis in GIS. Resampling impacts the display of high resolution global gridded population data, and we will discuss how to properly handle pyramid creation using the Aggregate tool with the sum option to create overviews for mosaic datasets.

  18. Power Generation Potential and Cost of a Roof Top Solar PV System in Kathmandu, Nepal

    NASA Astrophysics Data System (ADS)

    Sanjel, N.; Zhand, A.

    2017-12-01

    The paper presents a comparative study of the 3 most used solar PV module technologies in Nepal, which are Si-mono-crystalline, Si-poly-crystalline and Si-amorphous. The aim of the paper is to present and discuss the recorded Global Solar Radiation, received in the Kathmandu valley by three different, Si-mono-crystalline, Si-poly-crystalline and Si-amorphous calibrated solar cell pyranometers and to propose the best-suited solar PV module technology for roof top solar PV systems inside the Kathmandu valley. Data recorded over the course of seven months, thus covering most of the seasonal meteorological conditions determining Kathmandu valley's global solar radiation reception are presented. The results indicate that the Si-amorphous pyranometer captured 1.56% more global solar radiation than the Si-mono-crystalline and 18.4% more than Si-poly-crystalline pyranometer over the course of seven months. Among the three pyranometer technologies the maximum and minimum cell temperature was measured by the Si-mono-crystalline pyranometer. Following the technical data and discussion, an economical analysis, using the versatile software tool PVSYST V5.01is used to calculate the life cycle costs of a 1kW roof top solar PV RAPS system, with battery storage, and a 1kW roof top solar PV grid connected system with no energy storage facility, through simulations, using average recorded global solar radiation data for the KTM valley and investigated market values for each solar PV module and peripheral equipment costs.

  19. Materials towards carbon-free, emission-free and oil-free mobility: hydrogen fuel-cell vehicles--now and in the future.

    PubMed

    Hirose, Katsuhiko

    2010-07-28

    In the past, material innovation has changed society through new material-induced technologies, adding a new value to society. In the present world, engineers and scientists are expected to invent new materials to solve the global problem of climate change. For the transport sector, the challenge for material engineers is to change the oil-based world into a sustainable world. After witnessing the recent high oil price and its adverse impact on the global economy, it is time to accelerate our efforts towards this change. Industries are tackling global energy issues such as oil and CO2, as well as local environmental problems, such as NO(x) and particulate matter. Hydrogen is the most promising candidate to provide carbon-free, emission-free and oil-free mobility. As such, engineers are working very hard to bring this technology into the real society. This paper describes recent progress of vehicle technologies, as well as hydrogen-storage technologies to extend the cruise range and ensure the easiness of refuelling and requesting material scientists to collaborate with industry to fight against global warming.

  20. Stress Modulus of Cancer Cells

    NASA Astrophysics Data System (ADS)

    Bonin, Keith; Guthold, Martin; Guo, Xinyi; Sigley, Justin

    2012-02-01

    Our main goal is to study the different physical and mechanical properties of cells as they advance through different stages of neoplastic transformation from normal to the metastatic state. Since recent reports indicate there is significant ambiguity about how these properties change for different cancer cells, we plan to measure these properties for a single line of cells, and to determine whether the changes vary for different cellular components: i.e. whether the change in physical properties is due to a change in the cytoskeleton, the cell membrane, the cytoplasm, or a combination of these elements. Here we expect to present data on the stress modulus of cancer cells at different stages: normal, mortal cancerous, immortal cancerous, and tumorigenic. The cells are Weinberg cell line Human Mammary Epithelial (HME) cells. Atomic force microscope (AFM) probes with different diameters are used to push on the cell membrane to measure the local, regional and global cell stress modulus. Preliminary results on normal HME cells suggests a stress modulus of 1.5 ± 0.8 kPa when pushing with 7 μm spherical probes. We anticipate reporting an improved value for the modulus as well as results for some of the Weinberg cancer cells.

  1. Engineering Ethics Education Having Reflected Various Values and a Global Code of Ethics

    NASA Astrophysics Data System (ADS)

    Kanemitsu, Hidekazu

    At the present day, a movement trying to establish a global code of ethics for science and engineering is in activity. The author overviews the context of this movement, and examines the possibility of engineering ethics education which uses global code of ethics. In this paper, the engineering ethics education which uses code of ethics in general will be considered, and an expected function of global code of ethics will be also. Engineering ethics education in the new century should be aimed to share the values among different countries and cultures. To use global code of ethics as a tool for such education, the code should include various values, especially Asian values which engineering ethics has paid little attention to.

  2. The Global Regulatory Architecture of Transcription during the Caulobacter Cell Cycle

    PubMed Central

    Zhou, Bo; Schrader, Jared M.; Kalogeraki, Virginia S.; Abeliuk, Eduardo; Dinh, Cong B.; Pham, James Q.; Cui, Zhongying Z.; Dill, David L.; McAdams, Harley H.; Shapiro, Lucy

    2015-01-01

    Each Caulobacter cell cycle involves differentiation and an asymmetric cell division driven by a cyclical regulatory circuit comprised of four transcription factors (TFs) and a DNA methyltransferase. Using a modified global 5′ RACE protocol, we globally mapped transcription start sites (TSSs) at base-pair resolution, measured their transcription levels at multiple times in the cell cycle, and identified their transcription factor binding sites. Out of 2726 TSSs, 586 were shown to be cell cycle-regulated and we identified 529 binding sites for the cell cycle master regulators. Twenty-three percent of the cell cycle-regulated promoters were found to be under the combinatorial control of two or more of the global regulators. Previously unknown features of the core cell cycle circuit were identified, including 107 antisense TSSs which exhibit cell cycle-control, and 241 genes with multiple TSSs whose transcription levels often exhibited different cell cycle timing. Cumulatively, this study uncovered novel new layers of transcriptional regulation mediating the bacterial cell cycle. PMID:25569173

  3. The global regulatory architecture of transcription during the Caulobacter cell cycle.

    PubMed

    Zhou, Bo; Schrader, Jared M; Kalogeraki, Virginia S; Abeliuk, Eduardo; Dinh, Cong B; Pham, James Q; Cui, Zhongying Z; Dill, David L; McAdams, Harley H; Shapiro, Lucy

    2015-01-01

    Each Caulobacter cell cycle involves differentiation and an asymmetric cell division driven by a cyclical regulatory circuit comprised of four transcription factors (TFs) and a DNA methyltransferase. Using a modified global 5' RACE protocol, we globally mapped transcription start sites (TSSs) at base-pair resolution, measured their transcription levels at multiple times in the cell cycle, and identified their transcription factor binding sites. Out of 2726 TSSs, 586 were shown to be cell cycle-regulated and we identified 529 binding sites for the cell cycle master regulators. Twenty-three percent of the cell cycle-regulated promoters were found to be under the combinatorial control of two or more of the global regulators. Previously unknown features of the core cell cycle circuit were identified, including 107 antisense TSSs which exhibit cell cycle-control, and 241 genes with multiple TSSs whose transcription levels often exhibited different cell cycle timing. Cumulatively, this study uncovered novel new layers of transcriptional regulation mediating the bacterial cell cycle.

  4. Phosphatidylserine is a global immunosuppressive signal in efferocytosis, infectious disease, and cancer

    PubMed Central

    Birge, R B; Boeltz, S; Kumar, S; Carlson, J; Wanderley, J; Calianese, D; Barcinski, M; Brekken, R A; Huang, X; Hutchins, J T; Freimark, B; Empig, C; Mercer, J; Schroit, A J; Schett, G; Herrmann, M

    2016-01-01

    Apoptosis is an evolutionarily conserved and tightly regulated cell death modality. It serves important roles in physiology by sculpting complex tissues during embryogenesis and by removing effete cells that have reached advanced age or whose genomes have been irreparably damaged. Apoptosis culminates in the rapid and decisive removal of cell corpses by efferocytosis, a term used to distinguish the engulfment of apoptotic cells from other phagocytic processes. Over the past decades, the molecular and cell biological events associated with efferocytosis have been rigorously studied, and many eat-me signals and receptors have been identified. The externalization of phosphatidylserine (PS) is arguably the most emblematic eat-me signal that is in turn bound by a large number of serum proteins and opsonins that facilitate efferocytosis. Under physiological conditions, externalized PS functions as a dominant and evolutionarily conserved immunosuppressive signal that promotes tolerance and prevents local and systemic immune activation. Pathologically, the innate immunosuppressive effect of externalized PS has been hijacked by numerous viruses, microorganisms, and parasites to facilitate infection, and in many cases, establish infection latency. PS is also profoundly dysregulated in the tumor microenvironment and antagonizes the development of tumor immunity. In this review, we discuss the biology of PS with respect to its role as a global immunosuppressive signal and how PS is exploited to drive diverse pathological processes such as infection and cancer. Finally, we outline the rationale that agents targeting PS could have significant value in cancer and infectious disease therapeutics. PMID:26915293

  5. Phosphatidylserine is a global immunosuppressive signal in efferocytosis, infectious disease, and cancer.

    PubMed

    Birge, R B; Boeltz, S; Kumar, S; Carlson, J; Wanderley, J; Calianese, D; Barcinski, M; Brekken, R A; Huang, X; Hutchins, J T; Freimark, B; Empig, C; Mercer, J; Schroit, A J; Schett, G; Herrmann, M

    2016-06-01

    Apoptosis is an evolutionarily conserved and tightly regulated cell death modality. It serves important roles in physiology by sculpting complex tissues during embryogenesis and by removing effete cells that have reached advanced age or whose genomes have been irreparably damaged. Apoptosis culminates in the rapid and decisive removal of cell corpses by efferocytosis, a term used to distinguish the engulfment of apoptotic cells from other phagocytic processes. Over the past decades, the molecular and cell biological events associated with efferocytosis have been rigorously studied, and many eat-me signals and receptors have been identified. The externalization of phosphatidylserine (PS) is arguably the most emblematic eat-me signal that is in turn bound by a large number of serum proteins and opsonins that facilitate efferocytosis. Under physiological conditions, externalized PS functions as a dominant and evolutionarily conserved immunosuppressive signal that promotes tolerance and prevents local and systemic immune activation. Pathologically, the innate immunosuppressive effect of externalized PS has been hijacked by numerous viruses, microorganisms, and parasites to facilitate infection, and in many cases, establish infection latency. PS is also profoundly dysregulated in the tumor microenvironment and antagonizes the development of tumor immunity. In this review, we discuss the biology of PS with respect to its role as a global immunosuppressive signal and how PS is exploited to drive diverse pathological processes such as infection and cancer. Finally, we outline the rationale that agents targeting PS could have significant value in cancer and infectious disease therapeutics.

  6. Stack Number Influence on the Accuracy of Aster Gdem (V2)

    NASA Astrophysics Data System (ADS)

    Mirzadeh, S. M. J.; Alizadeh Naeini, A.; Fatemi, S. B.

    2017-09-01

    In this research, the influence of stack number (STKN) on the accuracy of Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) Global DEM (GDEM) has been investigated. For this purpose, two data sets of ASTER and Reference DEMs from two study areas with various topography (Bomehen and Tazehabad) were used. The Results show that in both study areas, STKN of 19 results in minimum error so that this minimum error has small difference with other STKN. The analysis of slope, STKN, and error values shows that there is no strong correlation between these parameters in both study areas. For example, the value of mean absolute error increase by changing the topography and the increase of slope values and height on cells but, the changes in STKN has no important effect on error values. Furthermore, according to high values of STKN, effect of slope on elevation accuracy has practically decreased. Also, there is no great correlation between the residual and STKN in ASTER GDEM.

  7. From a declaration of values to the creation of value in global health: a report from Harvard University's Global Health Delivery Project.

    PubMed

    Kim, J Y; Rhatigan, J; Jain, S H; Weintraub, R; Porter, M E

    2010-01-01

    To make best use of the new dollars available for the treatment of disease in resource-poor settings, global health practice requires a strategic approach that emphasises value for patients. Practitioners and global health academics should seek to identify and elaborate the set of factors that drives value for patients through the detailed study of actual care delivery organisations in multiple settings. Several frameworks can facilitate this study, including the care delivery value chain. We report on our efforts to catalyse the study of health care delivery in resource-limited settings in the hope that this inquiry will lead to insights that can improve the health of the neediest worldwide.

  8. Forest biomass mapping from fusion of GEDI Lidar data and TanDEM-X InSAR data

    NASA Astrophysics Data System (ADS)

    Qi, W.; Hancock, S.; Armston, J.; Marselis, S.; Dubayah, R.

    2017-12-01

    Mapping forest above-ground biomass (hereafter biomass) can significantly improve our ability to assess the role of forest in terrestrial carbon budget and to analyze the ecosystem productivity. Global Ecosystem Dynamic Investigation (GEDI) mission will provide the most complete lidar observations of forest vertical structure and has the potential to provide global-scale forest biomass data at 1-km resolution. However, GEDI is intrinsically a sampling mission and will have a between-track spacing of 600 m. An increase in adjacent-swath distance and the presence of cloud cover may also lead to larger gaps between GEDI tracks. In order to provide wall-to-wall forest biomass maps, fusion algorithms of GEDI lidar data and TanDEM-X InSAR data were explored in this study. Relationship between biomass and lidar RH metrics was firstly developed and used to derive biomass values over GEDI tracks which were simulated using airborne lidar data. These GEDI biomass values were then averaged in each 1-km cell to represent the biomass density within that cell. Whereas for cells without any GEDI observations, regression models developed between GEDI-derived biomass and TDX InSAR variables were applied to predict biomass over those places. Based on these procedures, contiguous biomass maps were finally generated at 1-km resolution over three representative forest types. Uncertainties for these biomass maps were also estimated at 1 km following methods developed in Saarela et al. (2016). Our results indicated great potential of GEDI/TDX fusion for large-scale biomass mapping. Saarela, S., Holm, S., Grafstrom, A., Schnell, S., Naesset, E., Gregoire, T.G., Nelson, R.F., & Stahl, G. (2016). Hierarchical model-based inference for forest inventory utilizing three sources of information. Annals of Forest Science, 73, 895-910

  9. Global methylation silencing of clustered proto-cadherin genes in cervical cancer: serving as diagnostic markers comparable to HPV

    PubMed Central

    Wang, Kai-Hung; Lin, Cuei-Jyuan; Liu, Chou-Jen; Liu, Dai-Wei; Huang, Rui-Lan; Ding, Dah-Ching; Weng, Ching-Feng; Chu, Tang-Yuan

    2015-01-01

    Epigenetic remodeling of cell adhesion genes is a common phenomenon in cancer invasion. This study aims to investigate global methylation of cell adhesion genes in cervical carcinogenesis and to apply them in early detection of cancer from cervical scraping. Genome-wide methylation array was performed on an investigation cohort, including 16 cervical intraepithelial neoplasia 3 (CIN3) and 20 cervical cancers (CA) versus 12 each of normal, inflammation and CIN1 as controls. Twelve members of clustered proto-cadherin (PCDH) genes were collectively methylated and silenced, which were validated in cancer cells of the cervix, endometrium, liver, head and neck, breast, and lung. In an independent cohort including 107 controls, 66 CIN1, 85 CIN2/3, and 38 CA, methylated PCDHA4 and PCDHA13 were detected in 2.8%, 24.2%, 52.9%, and 84.2% (P < 10−25), and 2.8%, 24.2%, 50.6%, and 94.7% (P < 10−29), respectively. In diagnosis of CIN2 or more severe lesion of the cervix, a combination test of methylated PCDHA4 or PCDHA13 from cervical scraping had a sensitivity, specificity, positive predictive value, and negative predictive value of 74.8%, 80.3%, 73%, and 81.8%, respectively. Testing of this combination from cervical scraping is equally sensitive but more specific than human papillomavirus (HPV) test in diagnosis of CIN2 or more severe lesions. The study disclosed a collective methylation of PCDH genes in cancer of cervix and other sites. At least two of them can be promising diagnostic markers for cervical cancer noninferior to HPV. PMID:25418975

  10. Global methylation silencing of clustered proto-cadherin genes in cervical cancer: serving as diagnostic markers comparable to HPV.

    PubMed

    Wang, Kai-Hung; Lin, Cuei-Jyuan; Liu, Chou-Jen; Liu, Dai-Wei; Huang, Rui-Lan; Ding, Dah-Ching; Weng, Ching-Feng; Chu, Tang-Yuan

    2015-01-01

    Epigenetic remodeling of cell adhesion genes is a common phenomenon in cancer invasion. This study aims to investigate global methylation of cell adhesion genes in cervical carcinogenesis and to apply them in early detection of cancer from cervical scraping. Genome-wide methylation array was performed on an investigation cohort, including 16 cervical intraepithelial neoplasia 3 (CIN3) and 20 cervical cancers (CA) versus 12 each of normal, inflammation and CIN1 as controls. Twelve members of clustered proto-cadherin (PCDH) genes were collectively methylated and silenced, which were validated in cancer cells of the cervix, endometrium, liver, head and neck, breast, and lung. In an independent cohort including 107 controls, 66 CIN1, 85 CIN2/3, and 38 CA, methylated PCDHA4 and PCDHA13 were detected in 2.8%, 24.2%, 52.9%, and 84.2% (P < 10(-25) ), and 2.8%, 24.2%, 50.6%, and 94.7% (P < 10(-29) ), respectively. In diagnosis of CIN2 or more severe lesion of the cervix, a combination test of methylated PCDHA4 or PCDHA13 from cervical scraping had a sensitivity, specificity, positive predictive value, and negative predictive value of 74.8%, 80.3%, 73%, and 81.8%, respectively. Testing of this combination from cervical scraping is equally sensitive but more specific than human papillomavirus (HPV) test in diagnosis of CIN2 or more severe lesions. The study disclosed a collective methylation of PCDH genes in cancer of cervix and other sites. At least two of them can be promising diagnostic markers for cervical cancer noninferior to HPV. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  11. Landsat 8 Data Modeled as DGGS Data Cubes

    NASA Astrophysics Data System (ADS)

    Sherlock, M. J.; Tripathi, G.; Samavati, F.

    2016-12-01

    In the context of tracking recent global changes in the Earth's landscape, Landsat 8 provides high-resolution multi-wavelength data with a temporal resolution of sixteen days. Such a live dataset can benefit novel applications in environmental monitoring. However, a temporal analysis of this dataset in its native format is a challenging task mostly due to the huge volume of geospatial images and imperfect overlay of different day Landsat 8 images. We propose the creation of data cubes derived from Landsat 8 data, through the use of a Discrete Global Grid System (DGGS). DGGS referencing of Landsat 8 data provides a cell-based representation of the pixel values for a fixed area on earth, indexed by keys. Having the calibrated cell-based Landsat 8 images can speed up temporal analysis and facilitate parallel processing using distributed systems. In our method, the Landsat 8 dataset hosted on Amazon Web Services (AWS) is downloaded using a web crawler and stored on a filesystem. We apply the cell-based DGGS referencing (using Pyxis SDK) to Landsat 8 images which provide a rhombus based tessellation of equal area cells for our use-case. After this step, the cell-images which overlay perfectly on different days, are stacked in the temporal dimension and stored into data cube units. The depth of the cube represents the number of temporal images of the same cell and can be updated when new images are received each day. Harnessing the regular spatio-temporal structure of data cubes, we want to compress, query, transmit and visualize big Landsat 8 data in an efficient way for temporal analysis.

  12. Compound Capillary Flows in Complex Containers: Drop Tower Test Results

    NASA Astrophysics Data System (ADS)

    Bolleddula, Daniel A.; Chen, Yongkang; Semerjian, Ben; Tavan, Noël; Weislogel, Mark M.

    2010-10-01

    Drop towers continue to provide unique capabilities to investigate capillary flow phenomena relevant to terrestrial and space-based capillary fluidics applications. In this study certain `capillary rise' flows and the value of drop tower experimental investigations are briefly reviewed. A new analytic solution for flows along planar interior edges is presented. A selection of test cell geometries are then discussed where compound capillary flows occur spontaneously and simultaneously over local and global length scales. Sample experimental results are provided. Tertiary experiments on a family of asymmetric geometries that isolate the global component of such flows are then presented along with a qualitative analysis that may be used to either avoid or exploit such flows. The latter may also serve as a design tool with which to assess the impact of inadvertent container asymmetry.

  13. Study of the L-mode tokamak plasma “shortfall” with local and global nonlinear gyrokinetic δf particle-in-cell simulation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chowdhury, J.; Wan, Weigang; Chen, Yang

    2014-11-15

    The δ f particle-in-cell code GEM is used to study the transport “shortfall” problem of gyrokinetic simulations. In local simulations, the GEM results confirm the previously reported simulation results of DIII-D [Holland et al., Phys. Plasmas 16, 052301 (2009)] and Alcator C-Mod [Howard et al., Nucl. Fusion 53, 123011 (2013)] tokamaks with the continuum code GYRO. Namely, for DIII-D the simulations closely predict the ion heat flux at the core, while substantially underpredict transport towards the edge; while for Alcator C-Mod, the simulations show agreement with the experimental values of ion heat flux, at least within the range of experimental error.more » Global simulations are carried out for DIII-D L-mode plasmas to study the effect of edge turbulence on the outer core ion heat transport. The edge turbulence enhances the outer core ion heat transport through turbulence spreading. However, this edge turbulence spreading effect is not enough to explain the transport underprediction.« less

  14. Proteomic Signatures of Acquired Letrozole Resistance in Breast Cancer: Suppressed Estrogen Signaling and Increased Cell Motility and Invasiveness*

    PubMed Central

    Tilghman, Syreeta L.; Townley, Ian; Zhong, Qiu; Carriere, Patrick P.; Zou, Jin; Llopis, Shawn D.; Preyan, Lynez C.; Williams, Christopher C.; Skripnikova, Elena; Bratton, Melyssa R.; Zhang, Qiang; Wang, Guangdi

    2013-01-01

    Aromatase inhibitors, such as letrozole, have become the first-line treatment for postmenopausal women with estrogen-dependent breast cancer. However, acquired resistance remains a major clinical obstacle. Previous studies demonstrated constitutive activation of the MAPK signaling, overexpression of HER2, and down-regulation of aromatase and ERα in letrozole-resistant breast cancer cells. Given the complex signaling network involved in letrozole-refractory breast cancer and the lack of effective treatment for hormone resistance, further investigation of aromatase inhibitor resistance by a novel systems biology approach may reveal previously unconsidered molecular changes that could be utilized as therapeutic targets. This study was undertaken to characterize for the first time global proteomic alterations occurring in a letrozole-resistant cell line. A quantitative proteomic analysis of the whole cell lysates of LTLT-Ca (resistant) versus AC-1 cells (sensitive) was performed to identify significant protein expression changes. A total of 1743 proteins were identified and quantified, of which 411 were significantly up-regulated and 452 significantly down-regulated (p < 0.05, fold change > 1.20). Bioinformatics analysis revealed that acquired letrozole resistance is associated with a hormone-independent, more aggressive phenotype. LTLT-Ca cells exhibited 84% and 138% increase in migration and invasion compared with the control cells. The ROCK inhibitor partially abrogated the enhanced migration and invasion of the letrozole-resistant cells. Flow cytometric analyses also demonstrated an increase in vimentin and twist expression in letrozole-resistance cells, suggesting an onset of epithelial to mesenchymal transition (EMT). Moreover, targeted gene expression arrays confirmed a 28-fold and sixfold up-regulation of EGFR and HER2, respectively, whereas ERα and pS2 were dramatically reduced by 28-fold and 1100-fold, respectively. Taken together, our study revealed global proteomic signatures of a letrozole-resistant cell line associated with hormone independence, enhanced cell motility, EMT and the potential values of several altered proteins as novel prognostic markers or therapeutic targets for letrozole resistant breast cancer. PMID:23704778

  15. Prognostic and Added Value of Two-Dimensional Global Longitudinal Strain for Prediction of Survival in Patients with Light Chain Amyloidosis Undergoing Autologous Hematopoietic Cell Transplantation.

    PubMed

    Pun, Shawn C; Landau, Heather J; Riedel, Elyn R; Jordan, Jonathan; Yu, Anthony F; Hassoun, Hani; Chen, Carol L; Steingart, Richard M; Liu, Jennifer E

    2018-01-01

    Autologous hematopoietic cell transplantation (HCT) is a first-line therapy for prolonging survival in patients with light-chain (AL) amyloidosis. Cardiac involvement is the most important determinant of survival. However, patients with advanced cardiac involvement have often been excluded from HCT because of high risk for transplantation-related mortality and poor overall survival. Whether baseline left ventricular global longitudinal strain (GLS) can provide additional risk stratification and predict survival after HCT in this high-risk population remains unclear. The aim of this study was to evaluate the prognostic implication of baseline GLS and the added value of GLS beyond circulating cardiac biomarkers for risk stratification in patients with AL amyloidosis undergoing HCT. Eighty-two patients with newly diagnosed AL amyloidosis who underwent upfront HCT between January 2007 and April 2014 were included in the study. Clinical, echocardiographic, and serum cardiac biomarker data were collected at baseline and 12 months following HCT. GLS measurements were performed using a vendor-independent offline system. The median follow-up time for survivors was 58 months. Sixty-four percent of patients were in biomarker-based Mayo stage II or III. GLS, brain natriuretic peptide, troponin, and mitral E/A ratio were identified as the strongest predictors of survival (P < .0001). Other predictors included sex, creatinine, free AL, wall thickness, and ejection fraction. Mayo stage was significantly associated with outcome, with 5-year survival of 93%, 72% and 31% in stage I, II, and III patients, respectively. GLS of 17% was identified as the value that best discriminated survivors from nonsurvivors, and the application of this cutoff value provided further mortality risk stratification within each Mayo stage. GLS is a strong predictor of survival in patients with AL amyloidosis undergoing HCT, potentially providing incremental value over serum cardiac biomarkers for risk stratification. GLS should be considered as a standard parameter along with serum cardiac biomarkers when evaluating eligibility for HCT or other investigational therapies. Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

  16. Interactions between nutrition and immunity in anorexia nervosa: a 1-y follow-up study.

    PubMed

    Marcos, A; Varela, P; Toro, O; López-Vidriero, I; Nova, E; Madruga, D; Casas, J; Morandé, G

    1997-08-01

    Nutritional status and immunocompetence were evaluated in 15 patients suffering from anorexia nervosa in comparison with a control group (n = 15). After 1 y, data from six phases of the study were evaluated: immediately after admittance to the hospital (AN1), after 1 mo (AN2), after 2 mo (AN3), after 3 mo (AN4), after 6 mo (AN5), and after 1 y, (AN6). Patients recovered weight from AN4 until AN6 although, according to body mass index values, all patients had low weights during the 1-y follow-up. Likewise, leukocyte and lymphocyte values were borderline and lower in patients in all phases tested than in control subjects. All lymphocyte subpopulations were lower in AN1 and AN2 patients (inpatients) than in control subjects, except for CD19 cells, which remained unmodified. There seemed to be a recovery of lymphocyte subsets after hospitalization in AN3 and AN4 patients (outpatients), except for CD57, which remained below control values. However, there was a global decrease of the lymphocyte subsets in AN5 and AN6. Ratios of CD4 to CD8 cells were not altered but the ratio of CD2 to CD19 cells was lower in all phases except AN6. Moreover, cell-mediated immune function was impaired and none of the patients showed normal responses. Thus, despite the slight weight increase found in AN4, AN5, and AN6 and the apparent cell subset recovery after hospitalization, these results suggest a greatly depleted nutritional status that remained during the whole year in all patients.

  17. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Parkin, E. R.; Bicknell, G. V., E-mail: parkin@mso.anu.edu.au

    Global three-dimensional magnetohydrodynamic (MHD) simulations of turbulent accretion disks are presented which start from fully equilibrium initial conditions in which the magnetic forces are accounted for and the induction equation is satisfied. The local linear theory of the magnetorotational instability (MRI) is used as a predictor of the growth of magnetic field perturbations in the global simulations. The linear growth estimates and global simulations diverge when nonlinear motions-perhaps triggered by the onset of turbulence-upset the velocity perturbations used to excite the MRI. The saturated state is found to be independent of the initially excited MRI mode, showing that once themore » disk has expelled the initially net flux field and settled into quasi-periodic oscillations in the toroidal magnetic flux, the dynamo cycle regulates the global saturation stress level. Furthermore, time-averaged measures of converged turbulence, such as the ratio of magnetic energies, are found to be in agreement with previous works. In particular, the globally averaged stress normalized to the gas pressure <{alpha}{sub P}>bar = 0.034, with notably higher values achieved for simulations with higher azimuthal resolution. Supplementary tests are performed using different numerical algorithms and resolutions. Convergence with resolution during the initial linear MRI growth phase is found for 23-35 cells per scale height (in the vertical direction).« less

  18. A new map of global ecological land units—An ecophysiographic stratification approach

    USGS Publications Warehouse

    Sayre, Roger; Dangermond, Jack; Frye, Charlie; Vaughan, Randy; Aniello, Peter; Breyer, Sean P.; Cribbs, Douglas; Hopkins, Dabney; Nauman, Richard; Derrenbacher, William; Wright, Dawn J.; Brown, Clint; Convis, Charles; Smith, Jonathan H.; Benson, Laurence; Van Sistine, Darren; Warner, Harumi; Cress, Jill Janene; Danielson, Jeffrey J.; Hamann, Sharon L.; Cecere, Thomas; Reddy, Ashwan D.; Burton, Devon; Grosse, Andrea; True, Diane; Metzger, Marc; Hartmann, Jens; Moosdorf, Nils; Durr, Hans; Paganini, Marc; Defourny, Pierre; Arino, Olivier; Maynard, Simone; Anderson, Mark; Comer, Patrick

    2014-01-01

    In response to the need and an intergovernmental commission for a high resolution and data-derived global ecosystem map, land surface elements of global ecological pattern were characterized in an ecophysiographic stratification of the planet. The stratification produced 3,923 terrestrial ecological land units (ELUs) at a base resolution of 250 meters. The ELUs were derived from data on land surface features in a three step approach. The first step involved acquiring or developing four global raster datalayers representing the primary components of ecosystem structure: bioclimate, landform, lithology, and land cover. These datasets generally represent the most accurate, current, globally comprehensive, and finest spatial and thematic resolution data available for each of the four inputs. The second step involved a spatial combination of the four inputs into a single, new integrated raster dataset where every cell represents a combination of values from the bioclimate, landforms, lithology, and land cover datalayers. This foundational global raster datalayer, called ecological facets (EFs), contains 47,650 unique combinations of the four inputs. The third step involved an aggregation of the EFs into the 3,923 ELUs. This subdivision of the Earth’s surface into relatively fine, ecological land areas is designed to be useful for various types of ecosystem research and management applications, including assessments of climate change impacts to ecosystems, economic and non-economic valuation of ecosystem services, and conservation planning.

  19. Pantropic retroviruses as a transduction tool for sea urchin embryos

    PubMed Central

    Core, Amanda B.; Reyna, Arlene E.; Conaway, Evan A.; Bradham, Cynthia A.

    2012-01-01

    Sea urchins are an important model for experiments at the intersection of development and systems biology, and technical innovations that enhance the utility of this model are of great value. This study explores pantropic retroviruses as a transduction tool for sea urchin embryos, and demonstrates that pantropic retroviruses infect sea urchin embryos with high efficiency and genomically integrate at a copy number of one per cell. We successfully used a self-inactivation strategy to both insert a sea urchin-specific enhancer and disrupt the endogenous viral enhancer. The resulting self-inactivating viruses drive global and persistent gene expression, consistent with genomic integration during the first cell cycle. Together, these data provide substantial proof of principle for transduction technology in sea urchin embryos. PMID:22431628

  20. The protective effect of autophagy on mouse spermatocyte derived cells exposure to 1800MHz radiofrequency electromagnetic radiation.

    PubMed

    Liu, Kaijun; Zhang, Guowei; Wang, Zhi; Liu, Yong; Dong, Jianyun; Dong, Xiaomei; Liu, Jinyi; Cao, Jia; Ao, Lin; Zhang, Shaoxiang

    2014-08-04

    The increasing exposure to radiofrequency (RF) radiation emitted from mobile phone use has raised public concern regarding the biological effects of RF exposure on the male reproductive system. Autophagy contributes to maintaining intracellular homeostasis under environmental stress. To clarify whether RF exposure could induce autophagy in the spermatocyte, mouse spermatocyte-derived cells (GC-2) were exposed to 1800MHz Global System for Mobile Communication (GSM) signals in GSM-Talk mode at specific absorption rate (SAR) values of 1w/kg, 2w/kg or 4w/kg for 24h, respectively. The results indicated that the expression of LC3-II increased in a dose- and time-dependent manner with RF exposure, and showed a significant change at the SAR value of 4w/kg. The autophagosome formation and the occurrence of autophagy were further confirmed by GFP-LC3 transient transfection assay and transmission electron microscopy (TEM) analysis. Furthermore, the conversion of LC3-I to LC3-II was enhanced by co-treatment with Chloroquine (CQ), indicating autophagic flux could be enhanced by RF exposure. Intracellular ROS levels significantly increased in a dose- and time-dependent manner after cells were exposed to RF. Pretreatment with anti-oxidative NAC obviously decreased the conversion of LC3-I to LC3-II and attenuated the degradation of p62 induced by RF exposure. Meanwhile, phosphorylated extracellular-signal-regulated kinase (ERK) significantly increased after RF exposure at the SAR value of 2w/kg and 4w/kg. Moreover, we observed that RF exposure did not increase the percentage of apoptotic cells, but inhibition of autophagy could increase the percentage of apoptotic cells. These findings suggested that autophagy flux could be enhanced by 1800MHz GSM exposure (4w/kg), which is mediated by ROS generation. Autophagy may play an important role in preventing cells from apoptotic cell death under RF exposure stress. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. Global gene expression and systems biology analysis of bovine monocyte-derived macrophages in response to in vitro challenge with Mycobacterium bovis.

    PubMed

    Magee, David A; Taraktsoglou, Maria; Killick, Kate E; Nalpas, Nicolas C; Browne, John A; Park, Stephen D E; Conlon, Kevin M; Lynn, David J; Hokamp, Karsten; Gordon, Stephen V; Gormley, Eamonn; MacHugh, David E

    2012-01-01

    Mycobacterium bovis, the causative agent of bovine tuberculosis, is a major cause of mortality in global cattle populations. Macrophages are among the first cell types to encounter M. bovis following exposure and the response elicited by these cells is pivotal in determining the outcome of infection. Here, a functional genomics approach was undertaken to investigate global gene expression profiles in bovine monocyte-derived macrophages (MDM) purified from seven age-matched non-related females, in response to in vitro challenge with M. bovis (multiplicity of infection 2:1). Total cellular RNA was extracted from non-challenged control and M. bovis-challenged MDM for all animals at intervals of 2 hours, 6 hours and 24 hours post-challenge and prepared for global gene expression analysis using the Affymetrix® GeneChip® Bovine Genome Array. Comparison of M. bovis-challenged MDM gene expression profiles with those from the non-challenged MDM controls at each time point identified 3,064 differentially expressed genes 2 hours post-challenge, with 4,451 and 5,267 differentially expressed genes detected at the 6 hour and 24 hour time points, respectively (adjusted P-value threshold ≤ 0.05). Notably, the number of downregulated genes exceeded the number of upregulated genes in the M. bovis-challenged MDM across all time points; however, the fold-change in expression for the upregulated genes was markedly higher than that for the downregulated genes. Systems analysis revealed enrichment for genes involved in: (1) the inflammatory response; (2) cell signalling pathways, including Toll-like receptors and intracellular pathogen recognition receptors; and (3) apoptosis. The increased number of downregulated genes is consistent with previous studies showing that M. bovis infection is associated with the repression of host gene expression. The results also support roles for MyD88-independent signalling and intracellular PRRs in mediating the host response to M. bovis.

  2. Measures of International Manufacturing and Trade of Clean Energy Technologies

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Engel-Cox, Jill; Sandor, Debbie; Keyser, David

    The technologies that produce clean energy, such as solar photovoltaic panels and lithium ion batteries for electric vehicles, are globally manufactured and traded. As demand and deployment of these technologies grows exponentially, the innovation to reach significant economies of scale and drive down energy production costs becomes less in the technology and more in the manufacturing of the technology. Manufacturing innovations and other manufacturing decisions can reduce costs of labor, materials, equipment, operating costs, and transportation, across all the links in the supply chain. To better understand the manufacturing aspect of the clean energy economy, we have developed key metricsmore » for systematically measuring and benchmarking international manufacturing of clean energy technologies. The metrics are: trade, market size, manufacturing value-added, and manufacturing capacity and production. These metrics were applied to twelve global economies and four representative technologies: wind turbine components, crystalline silicon solar photovoltaic modules, vehicle lithium ion battery cells, and light emitting diode packages for efficient lighting and other consumer products. The results indicated that clean energy technologies are being developed via complex, dynamic, and global supply chains, with individual economies benefiting from different technologies and links in the supply chain, through both domestic manufacturing and global trade.« less

  3. Global Citizenship in Pakistan

    ERIC Educational Resources Information Center

    Pasha, Aamna

    2015-01-01

    This paper attempts to understand the value of the ideology of global citizenship in Pakistan by looking at students' values and attitudes. In particular, it explores students' understanding of the term "global citizen" and their attitude towards the concept. Using a case study approach, interviews were conducted with six students in a…

  4. CalQuo: automated, simultaneous single-cell and population-level quantification of global intracellular Ca2+ responses.

    PubMed

    Fritzsche, Marco; Fernandes, Ricardo A; Colin-York, Huw; Santos, Ana M; Lee, Steven F; Lagerholm, B Christoffer; Davis, Simon J; Eggeling, Christian

    2015-11-13

    Detecting intracellular calcium signaling with fluorescent calcium indicator dyes is often coupled with microscopy techniques to follow the activation state of non-excitable cells, including lymphocytes. However, the analysis of global intracellular calcium responses both at the single-cell level and in large ensembles simultaneously has yet to be automated. Here, we present a new software package, CalQuo (Calcium Quantification), which allows the automated analysis and simultaneous monitoring of global fluorescent calcium reporter-based signaling responses in up to 1000 single cells per experiment, at temporal resolutions of sub-seconds to seconds. CalQuo quantifies the number and fraction of responding cells, the temporal dependence of calcium signaling and provides global and individual calcium-reporter fluorescence intensity profiles. We demonstrate the utility of the new method by comparing the calcium-based signaling responses of genetically manipulated human lymphocytic cell lines.

  5. A crisis in the marketplace: how food marketing contributes to childhood obesity and what can be done.

    PubMed

    Harris, Jennifer L; Pomeranz, Jennifer L; Lobstein, Tim; Brownell, Kelly D

    2009-01-01

    Reducing food marketing to children has been proposed as one means for addressing the global crisis of childhood obesity, but significant social, legal, financial, and public perception barriers stand in the way. The scientific literature documents that food marketing to children is (a) massive; (b) expanding in number of venues (product placements, video games, the Internet, cell phones, etc.); (c) composed almost entirely of messages for nutrient-poor, calorie-dense foods; (d) having harmful effects; and (e) increasingly global and hence difficult to regulate by individual countries. The food industry, governmental bodies, and advocacy groups have proposed a variety of plans for altering the marketing landscape. This article reviews existing knowledge of the impact of marketing and addresses the value of various legal, legislative, regulatory, and industry-based approaches to change.

  6. The analysis of tensegrity structures for the design of a morphing wing

    NASA Astrophysics Data System (ADS)

    Moored, Keith W., III; Bart-Smith, Hilary

    2005-05-01

    Tensegrity structures have become of engineering interest in recent years, but very few have found practical use. This lack of integration is attributed to the lack of a well formulated design procedure. In this paper, a preliminary procedure is presented for developing morphing tensegrity structures that include actuating elements. To do this, the virtual work method has been modified to allow for individual actuation of struts and cables. A generalized connectivity matrix for a cantilever beam constructed from either a single 4-strut cell or multiple 4-strut cells has been developed. Global deflections resulting from actuation of specific elements have been calculated. Furthermore, the force density method is expanded to include a necessary upper bound condition such that a physically feasible structure can be designed. Finally, the importance of relative force density values on the overall shape of a structure comprising of multiple unit cells is discussed.

  7. Global Value Trees

    PubMed Central

    Zhu, Zhen; Puliga, Michelangelo; Cerina, Federica; Chessa, Alessandro; Riccaboni, Massimo

    2015-01-01

    The fragmentation of production across countries has become an important feature of the globalization in recent decades and is often conceptualized by the term “global value chains” (GVCs). When empirically investigating the GVCs, previous studies are mainly interested in knowing how global the GVCs are rather than how the GVCs look like. From a complex networks perspective, we use the World Input-Output Database (WIOD) to study the evolution of the global production system. We find that the industry-level GVCs are indeed not chain-like but are better characterized by the tree topology. Hence, we compute the global value trees (GVTs) for all the industries available in the WIOD. Moreover, we compute an industry importance measure based on the GVTs and compare it with other network centrality measures. Finally, we discuss some future applications of the GVTs. PMID:25978067

  8. Analysis of trichloroethylene-induced global DNA hypomethylation in hepatic L-02 cells by liquid chromatography-electrospray ionization tandem mass spectrometry.

    PubMed

    Zhang, Hang; Hong, Wen-Xu; Ye, Jinbo; Yang, Xifei; Ren, Xiaohu; Huang, Aibo; Yang, Linqing; Zhou, Li; Huang, Haiyan; Wu, Desheng; Huang, Xinfeng; Zhuang, Zhixiong; Liu, Jianjun

    2014-04-04

    Trichloroethylene (TCE), a major occupational and environmental pollutant, has been recently associated with aberrant epigenetic changes in experimental animals and cultured cells. TCE is known to cause severe hepatotoxicity; however, the association between epigenetic alterations and TCE-induced hepatotoxicity are not yet well explored. DNA methylation, catalyzed by enzymes known as DNA methyltransferases (DNMT), is a major epigenetic modification that plays a critical role in regulating many cellular processes. In this study, we analyzed the TCE-induced effect on global DNA methylation and DNMT enzymatic activity in human hepatic L-02 cells. A sensitive and quantitative method combined with liquid chromatography and electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) was validated and utilized for assessing the altered DNA methylation in TCE-induced L-02 cells. Quantification was accomplished in multiple reaction monitoring (MRM) mode by monitoring a transition pair of m/z 242.1 (molecular ion)/126.3 (fragment ion) for 5-mdC and m/z 268.1/152.3 for dG. The correlation coefficient of calibration curves between 5-mdC and dG was higher than 0.9990. The intra-day and inter-day relative standard derivation values (RSD) were on the range of 0.53-7.09% and 0.40-2.83%, respectively. We found that TCE exposure was able to significantly decrease the DNA methylation and inhibit DNMT activity in L-02 cells. Our results not only reveal the association between TCE exposure and epigenetic alterations, but also provide an alternative mass spectrometry-based method for rapid and accurate assessment of chemical-induced altered DNA methylation in mammal cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Rapid and sensitive MRM-based mass spectrometry approach for systematically exploring ganglioside-protein interactions.

    PubMed

    Tian, Ruijun; Jin, Jing; Taylor, Lorne; Larsen, Brett; Quaggin, Susan E; Pawson, Tony

    2013-04-01

    Gangliosides are ubiquitous components of cell membranes. Their interactions with bacterial toxins and membrane-associated proteins (e.g. receptor tyrosine kinases) have important roles in the regulation of multiple cellular functions. Currently, an effective approach for measuring ganglioside-protein interactions especially in a large-scale fashion is largely missing. To this end, we report a facile MS-based approach to explore gangliosides extracted from cells and measure their interactions with protein of interest globally. We optimized a two-step protocol for extracting total gangliosides from cells within 2 h. Easy-to-use magnetic beads conjugated with a protein of interest were used to capture interacting gangliosides. To measure ganglioside-protein interaction on a global scale, we applied a high-sensitive LC-MS system, containing hydrophilic interaction LC separation and multiple reaction monitoring-based MS for ganglioside detection. Sensitivity for ganglioside GM1 is below 100 pg, and the whole analysis can be done in 20 min with isocratic elution. To measure ganglioside interactions with soluble vascular endothelial growth factor receptor 1 (sFlt1), we extracted and readily detected 36 species of gangliosides from perivascular retinal pigment epithelium cells across eight different classes. Twenty-three ganglioside species have significant interactions with sFlt1 as compared with IgG control based on p value cutoff <0.05. These results show that the described method provides a rapid and high-sensitive approach for systematically measuring ganglioside-protein interactions. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Prediction of B-cell linear epitopes with a combination of support vector machine classification and amino acid propensity identification.

    PubMed

    Wang, Hsin-Wei; Lin, Ya-Chi; Pai, Tun-Wen; Chang, Hao-Teng

    2011-01-01

    Epitopes are antigenic determinants that are useful because they induce B-cell antibody production and stimulate T-cell activation. Bioinformatics can enable rapid, efficient prediction of potential epitopes. Here, we designed a novel B-cell linear epitope prediction system called LEPS, Linear Epitope Prediction by Propensities and Support Vector Machine, that combined physico-chemical propensity identification and support vector machine (SVM) classification. We tested the LEPS on four datasets: AntiJen, HIV, a newly generated PC, and AHP, a combination of these three datasets. Peptides with globally or locally high physicochemical propensities were first identified as primitive linear epitope (LE) candidates. Then, candidates were classified with the SVM based on the unique features of amino acid segments. This reduced the number of predicted epitopes and enhanced the positive prediction value (PPV). Compared to four other well-known LE prediction systems, the LEPS achieved the highest accuracy (72.52%), specificity (84.22%), PPV (32.07%), and Matthews' correlation coefficient (10.36%).

  11. The identification of complete domains within protein sequences using accurate E-values for semi-global alignment

    PubMed Central

    Kann, Maricel G.; Sheetlin, Sergey L.; Park, Yonil; Bryant, Stephen H.; Spouge, John L.

    2007-01-01

    The sequencing of complete genomes has created a pressing need for automated annotation of gene function. Because domains are the basic units of protein function and evolution, a gene can be annotated from a domain database by aligning domains to the corresponding protein sequence. Ideally, complete domains are aligned to protein subsequences, in a ‘semi-global alignment’. Local alignment, which aligns pieces of domains to subsequences, is common in high-throughput annotation applications, however. It is a mature technique, with the heuristics and accurate E-values required for screening large databases and evaluating the screening results. Hidden Markov models (HMMs) provide an alternative theoretical framework for semi-global alignment, but their use is limited because they lack heuristic acceleration and accurate E-values. Our new tool, GLOBAL, overcomes some limitations of previous semi-global HMMs: it has accurate E-values and the possibility of the heuristic acceleration required for high-throughput applications. Moreover, according to a standard of truth based on protein structure, two semi-global HMM alignment tools (GLOBAL and HMMer) had comparable performance in identifying complete domains, but distinctly outperformed two tools based on local alignment. When searching for complete protein domains, therefore, GLOBAL avoids disadvantages commonly associated with HMMs, yet maintains their superior retrieval performance. PMID:17596268

  12. Phase angle assessment by bioelectrical impedance analysis and its predictive value for malnutrition risk in hospitalized geriatric patients.

    PubMed

    Varan, Hacer Dogan; Bolayir, Basak; Kara, Ozgur; Arik, Gunes; Kizilarslanoglu, Muhammet Cemal; Kilic, Mustafa Kemal; Sumer, Fatih; Kuyumcu, Mehmet Emin; Yesil, Yusuf; Yavuz, Burcu Balam; Halil, Meltem; Cankurtaran, Mustafa

    2016-12-01

    Phase angle (PhA) value determined by bioelectrical impedance analysis (BIA) is an indicator of cell membrane damage and body cell mass. Recent studies have shown that low PhA value is associated with increased nutritional risk in various group of patients. However, there have been only a few studies performed globally assessing the relationship between nutritional risk and PhA in hospitalized geriatric patients. The aim of the study is to evaluate the predictive value of the PhA for malnutrition risk in hospitalized geriatric patients. One hundred and twenty-two hospitalized geriatric patients were included in this cross-sectional study. Comprehensive geriatric assessment tests and BIA measurements were performed within the first 48 h after admission. Nutritional risk state of the patients was determined with NRS-2002. Phase angle values of the patients with malnutrition risk were compared with the patients that did not have the same risk. The independent variables for predicting malnutrition risk were determined. SPSS version 15 was utilized for the statistical analyzes. The patients with malnutrition risk had significantly lower phase angle values than the patients without malnutrition risk (p = 0.003). ROC curve analysis suggested that the optimum PhA cut-off point for malnutrition risk was 4.7° with 79.6 % sensitivity, 64.6 % specificity, 73.9 % positive predictive value, and 73.9 % negative predictive value. BMI, prealbumin, PhA, and Mini Mental State Examination Test scores were the independent variables for predicting malnutrition risk. PhA can be a useful, independent indicator for predicting malnutrition risk in hospitalized geriatric patients.

  13. An approach for characterising cellular polymeric foam structures using computed tomography

    NASA Astrophysics Data System (ADS)

    Chen, Youming; Das, Raj; Battley, Mark

    2018-02-01

    Global properties of foams depend on foam base materials and microstructures. Characterisation of foam microstructures is important for developing numerical foam models. In this study, the microstructures of four polymeric structural foams were imaged using a micro-CT scanner. Image processing and analysis methods were proposed to quantify the relative density, cell wall thickness and cell size of these foams from the captured CT images. Overall, the cells in these foams are fairly isotropic, and cell walls are rather straight. The measured average relative densities are in good agreement with the actual values. Relative density, cell size and cell wall thickness in these foams are found to vary along the thickness of foam panel direction. Cell walls in two of these foams are found to be filled with secondary pores. In addition, it is found that the average cell wall thickness measured from 2D images is around 1.4 times of that measured from 3D images, and the average cell size measured from 3D images is 1.16 times of that measured from 2D images. The distributions of cell wall thickness and cell size measured from 2D images exhibit lager dispersion in comparison to those measured from 3D images.

  14. Antileukemic Activity of Tillandsia recurvata and Some of its Cycloartanes

    PubMed Central

    LOWE, HENRY I.C.; TOYANG, NGEH J.; WATSON, CHARAH T.; AYEAH, KENNETH N.N.; BRYANT, JOSEPH

    2015-01-01

    Background Approximately 250,000 deaths were caused by leukemia globally in 2012 and about 40%-50% of all leukemia diagnoses end-up in death. Medicinal plants are a rich source for the discovery of new drugs against leukemia and other types of cancers. To this end, we subjected the Jamaican ball moss (Tillandsia recurvata) and its cycloartanes, as well as some analogs, to in vitro screening against a number of leukemia cell lines. The WST-1 anti-proliferation assay was used to determine the anticancer activity of ball moss and two cycloartanes isolated from ball moss and four of their analogs against four leukemia cell lines (HL-60, K562, MOLM-14, monoMac6). Ball moss crude methanolic extract showed activity with a 50% inhibition concentration (IC50) value of 3.028 μg/ml against the Molm-14 cell line but was ineffective against HL-60 cells. The six cycloartanes tested demonstrated varying activity against the four leukemia cancer cell lines with IC50 values ranging from 1.83 μM to 18.3 μM. Five out of the six cycloartanes demonstrated activity, while one was inactive against all four cell lines. The preliminary activity demonstrated by the Jamaican ball moss and its cycloartanes against selected leukemia cell lines continues to throw light on the broad anticancer activity of ball moss. Further studies to evaluate the efficacy of these molecules in other leukemia cell lines are required in order to validate the activity of these molecules, as well as to determine their mechanisms of action and ascertain the activity in vivo in order to establish efficacy and safety profiles. PMID:24982361

  15. Antileukemic activity of Tillandsia recurvata and some of its cycloartanes.

    PubMed

    Lowe, Henry I C; Toyang, Ngeh J; Watson, Charah T; Ayeah, Kenneth N N; Bryant, Joseph

    2014-07-01

    Approximately 250,000 deaths were caused by leukemia globally in 2012 and about 40%-50% of all leukemia diagnoses end-up in death. Medicinal plants are a rich source for the discovery of new drugs against leukemia and other types of cancers. To this end, we subjected the Jamaican ball moss (Tillandsia recurvata) and its cycloartanes, as well as some analogs, to in vitro screening against a number of leukemia cell lines. The WST-1 anti-proliferation assay was used to determine the anticancer activity of ball moss and two cycloartanes isolated from ball moss and four of their analogs against four leukemia cell lines (HL-60, K562, MOLM-14, monoMac6). Ball moss crude methanolic extract showed activity with a 50% inhibition concentration (IC50) value of 3.028 μg/ml against the Molm-14 cell line but was ineffective against HL-60 cells. The six cycloartanes tested demonstrated varying activity against the four leukemia cancer cell lines with IC50 values ranging from 1.83 μM to 18.3 μM. Five out of the six cycloartanes demonstrated activity, while one was inactive against all four cell lines. The preliminary activity demonstrated by the Jamaican ball moss and its cycloartanes against selected leukemia cell lines continues to throw light on the broad anticancer activity of ball moss. Further studies to evaluate the efficacy of these molecules in other leukemia cell lines are required in order to validate the activity of these molecules, as well as to determine their mechanisms of action and ascertain the activity in vivo in order to establish efficacy and safety profiles. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  16. Helping Adults Learn To Deliver Value in a Global Society.

    ERIC Educational Resources Information Center

    Montgomery, Joel R.

    Andersen Consulting is a global management and technology consulting organization whose mission is to boost clients' success by teaching them to link strategy, people, processes, and technology. Andersen's professional development program for its own 41,000-person global work force is designed to help adults learn to deliver value to global…

  17. Immune Centroids Over-Sampling Method for Multi-Class Classification

    DTIC Science & Technology

    2015-05-22

    recognize to specific antigens . The response of a receptor to an antigen can activate its hosting B-cell. Activated B-cell then proliferates and...modifying N.K. Jerne’s theory. The theory states that in a pre-existing group of lympho- cytes ( specifically B cells), a specific antigen only...the clusters of each small class, which have high data density, called global immune centroids over-sampling (denoted as Global-IC). Specifically

  18. Conceptualising global health: theoretical issues and their relevance for teaching

    PubMed Central

    2012-01-01

    Background There has long been debate around the definition of the field of education, research and practice known as global health. In this article we step back from attempts at definition and instead ask what current definitions tell us about the evolution of the field, identifying gaps and points of debate and using these to inform discussions of how global health might be taught. Discussion What we now know as global health has its roots in the late 19th century, in the largely colonial, biomedical pursuit of ‘international health’. The twentieth century saw a change in emphasis of the field towards a much broader conceptualisation of global health, encompassing broader social determinants of health and a truly global focus. The disciplinary focus has broadened greatly to include economics, anthropology and political science, among others. There have been a number of attempts to define the new field of global health. We suggest there are three central areas of contention: what the object of knowledge of global health is, the types of knowledge to be used and around the purpose of knowledge in the field of global health. We draw a number of conclusions from this discussion. First, that definitions should pay attention to differences as well as commonalities in different parts of the world, and that the definitions of global health themselves depend to some extent on the position of the definer. Second, global health’s core strength lies in its interdisciplinary character, in particular the incorporation of approaches from outside biomedicine. This approach recognises that political, social and economic factors are central causes of ill health. Last, we argue that definition should avoid inclusion of values. In particular we argue that equity, a key element of many definitions of global health, is a value-laden concept and carries with it significant ideological baggage. As such, its widespread inclusion in the definitions of global health is inappropriate as it suggests that only people sharing these values may be seen as ‘doing’ global health. Nevertheless, discussion of values should be a key part of global health education. Summary Our discussions lead us to emphasise the importance of an approach to teaching global health that is flexible, interdisciplinary and acknowledges the different interpretations and values of those practising and teaching the field. PMID:23148788

  19. A global portrait of the manganese industry-A socioeconomic perspective.

    PubMed

    Clarke, Carl; Upson, Sophie

    2017-01-01

    In 2013/14, Risk & Policy Analysts Ltd undertook the first global study on the socio-economic value of Manganese (Mn). Based on a top-down analysis of the key supply chains for Mn, it outlined the economic importance of Mn ore and alloys in terms of their direct and indirect economic value, as well as their effects on employment (jobs and wages). In 2013, global production of Mn ore was worth an estimated US$ 10.2-11.1 billion. Taking into account multiplier effects in the supply chain, the total economic value of Mn ore production globally in 2013 is estimated at US$ 21-23 billion. Direct employment related to Mn ore production is estimated at 44,000-78,000 people worldwide (with total wages estimated at US$ 2.7-4.6 billion per year), plus 33,000-59,000 jobs are created through indirect and induced employment effects. Meanwhile, the production of Mn alloy contributes around US$ 23 billion per year to the global economy (based on global production of around 19 million mt and 2013 market prices). In total, the value of Mn alloy production worldwide, taking into account downstream multiplier effects in the supply chain, is estimated at around US$ 146 billion per year. Direct employment related to Mn alloy production is estimated at 67,000-86,000 jobs worldwide (with total wages estimated at US$ 613-796 million per year), plus 217,000-278,000 jobs created through indirect & induced employment effects. In addition, numerous industries/sectors, products and/or applications are heavily dependent on Mn production and use. Mn is a critical raw material input and alloying element for the steel industry, for which there are no known alternatives. It can be argued that without Mn the entire steel industry (based on the current physico-chemical properties of steel) would not exist and, as a result, the value of the steel industry - an estimated US$ 964 billion to US$ 1446 billion in 2013 - is reliant on the continued supply and use of Mn. Besides its use in steel, Mn is also a critical element in the manufacture of dry cell and other batteries (notably, those used in electric vehicles) and the production of aluminium alloys (e.g. for beverage cans). Mn is also a micronutrient needed for plant growth and plays a vital role in agricultural production. It is also essential for maintaining the health and well-being of the human body and is used in food supplements and medicines. Furthermore, its use in developing applications (such as advanced steel products in automotive applications and batteries for electric vehicles) has the potential to provide socio-economic and environmental benefits in the future through enhancing vehicle safety and reducing fuel use/emissions. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Terahertz Spectroscopy and Global Analysis of the Rotational Spectrum of Doubly Deuterated Amidogen Radical ND2

    NASA Astrophysics Data System (ADS)

    Melosso, Mattia; Degli Esposti, Claudio; Dore, Luca

    2017-11-01

    The deuteration mechanism of molecules in the interstellar medium is still being debated. Observations of deuterium-bearing species in several astronomical sources represent a powerful tool to improve our understanding of the interstellar chemistry. The doubly deuterated form of the astrophysically interesting amidogen radical could be a target of detection in space. In this work, the rotational spectrum of the ND2 radical in its ground vibrational and electronic {X}2{B}1 state has been investigated between 588 and 1131 GHz using a frequency modulation millimeter/submillimeter-wave spectrometer. The ND2 molecule has been produced in a free-space glass absorption cell by discharging a mixture of ND3 and Ar. Sixty-four new transition frequencies involving J values from 2 to 5 and K a values from 0 to 4 have been measured. A global analysis including all the previous field-free pure rotational data has been performed, allowing for a more precise determination of a very large number of spectroscopic parameters. Accurate predictions of rotational transition frequencies of ND2 are now available from a few gigahertz up to several terahertz.

  1. Forest Values of national park neighbors in Costa Rica

    Treesearch

    John Schelhas; Max J. Pfeffer

    2005-01-01

    Global environmental concern and action have increased markedly over the past few decades. Rather than resulting in uniform environmental values across the globe, we argue that distinct environmentalisms are socially constructed in different places through the complex interactions between the global environmental values and locally unique historical, political, and...

  2. Health consumers and stem cell therapy innovation: markets, models and regulation.

    PubMed

    Salter, Brian; Zhou, Yinhua; Datta, Saheli

    2014-05-01

    Global health consumer demand for stem cell therapies is vibrant, but the supply of treatments from the conventional science-based model of innovation is small and unlikely to increase in the near future. At the same time, several models of medical innovation have emerged that can respond to the demand, often employing a transnational value chain to deliver the product. Much of the commentary has approached the issue from a supply side perspective, demonstrating the extent to which national and transnational regulation fails to impose what are regarded as appropriate standards on the 'illicit' supply of stem cell therapies characterized by little data and poor outcomes. By contrast, this article presents a political economic analysis with a strong demand side perspective, arguing that the problem of what is termed 'stem cell tourism' is embedded in the demand-supply relationship of the health consumer market and its engagement with different types of stem cell therapy innovation. To be meaningful, discussions of regulation must recognize that analysis or risk being sidelined by a market, which ignores their often wishful thinking.

  3. Computational deconvolution of genome wide expression data from Parkinson's and Huntington's disease brain tissues using population-specific expression analysis

    PubMed Central

    Capurro, Alberto; Bodea, Liviu-Gabriel; Schaefer, Patrick; Luthi-Carter, Ruth; Perreau, Victoria M.

    2015-01-01

    The characterization of molecular changes in diseased tissues gives insight into pathophysiological mechanisms and is important for therapeutic development. Genome-wide gene expression analysis has proven valuable for identifying biological processes in neurodegenerative diseases using post mortem human brain tissue and numerous datasets are publically available. However, many studies utilize heterogeneous tissue samples consisting of multiple cell types, all of which contribute to global gene expression values, confounding biological interpretation of the data. In particular, changes in numbers of neuronal and glial cells occurring in neurodegeneration confound transcriptomic analyses, particularly in human brain tissues where sample availability and controls are limited. To identify cell specific gene expression changes in neurodegenerative disease, we have applied our recently published computational deconvolution method, population specific expression analysis (PSEA). PSEA estimates cell-type-specific expression values using reference expression measures, which in the case of brain tissue comprises mRNAs with cell-type-specific expression in neurons, astrocytes, oligodendrocytes and microglia. As an exercise in PSEA implementation and hypothesis development regarding neurodegenerative diseases, we applied PSEA to Parkinson's and Huntington's disease (PD, HD) datasets. Genes identified as differentially expressed in substantia nigra pars compacta neurons by PSEA were validated using external laser capture microdissection data. Network analysis and Annotation Clustering (DAVID) identified molecular processes implicated by differential gene expression in specific cell types. The results of these analyses provided new insights into the implementation of PSEA in brain tissues and additional refinement of molecular signatures in human HD and PD. PMID:25620908

  4. Distributions of phytoplankton carbohydrate, protein and lipid in the world oceans from satellite ocean colour.

    PubMed

    Roy, Shovonlal

    2018-06-01

    Energy value of phytoplankton regulates the growth of higher trophic species, affecting the tropic balance and sustainability of marine food webs. Therefore, developing our capability to estimate and monitor, on a global scale, the concentrations of macromolecules that determine phytoplankton energy value, would be invaluable. Reported here are the first estimates of carbohydrate, protein, lipid, and overall energy value of phytoplankton in the world oceans, using ocean-colour data from satellites. The estimates are based on a novel bio-optical method that utilises satellite-derived bio-optical fingerprints of living phytoplankton combined with allometric relationships between phytoplankton cells and cellular macromolecular contents. The annually averaged phytoplankton energy value, per cubic metre of sub-surface ocean, varied from less than 0.1 kJ in subtropical gyres, to 0.5-1.0 kJ in parts of the equatorial, northern and southern latitudes, and rising to >10 kJ in certain coastal and optically complex waters. The annually averaged global stocks of carbohydrate, protein and lipid were 0.044, 0.17 and 0.108 gigatonnes, respectively, with monthly stocks highest in September and lowest in June, over 1997-2013. The fractional contributions of phytoplankton size classes e.g., picoplankton, nanoplankton and microplankton to surface concentrations and global stocks of macromolecules varied considerably across marine biomes classified as Longhurst provinces. Among these provinces, the highest annually averaged surface concentrations of carbohydrate, protein, and lipid were in North-East Atlantic Coastal Shelves, whereas, the lowest concentration of carbohydrate or lipid were in North Atlantic Tropical Gyral, and that of protein was in North Pacific Subtropical Gyre West. The regional accuracy of the estimates and their sensitivity to satellite inputs are quantified from the bio-optical model, which show promise for possible operational monitoring of phytoplankton energy value from satellite ocean colour. Adequate in situ measurements of macromolecules and improved retrievals of inherent optical properties from high-resolution satellite images, would be required to validate these estimates at local sites, and to further improve their accuracy in the world oceans.

  5. Improved method to fully compensate the spatial phase nonuniformity of LCoS devices with a Fizeau interferometer.

    PubMed

    Lu, Qiang; Sheng, Lei; Zeng, Fei; Gao, Shijie; Qiao, Yanfeng

    2016-10-01

    Liquid crystal on silicon (LCoS) devices usually show spatial phase nonuniformity (SPNU) in applications of phase modulation, which comprises the phase retardance nonuniformity (PRNU) as a function of the applied voltage and inherent wavefront distortion (WFD) introduced by the device itself. We propose a multipoint calibration method utilizing a Fizeau interferometer to compensate SPNU of the device. Calibration of PRNU is realized by defining a grid of 3×6 cells onto the aperture and then calculating phase retardance of each cell versus a gradient gray pattern. With designing an adjusted gray pattern calculated by the calibrated multipoint phase retardance function, compensation of inherent WFD is achieved. The peak-to-valley (PV) value of the residual WFD compensated by the multipoint calibration method is significantly reduced from 2.5λ to 0.140λ, while the PV value of the residual WFD after global calibration is reduced to 0.364λ. Experimental results of the generated finite-energy 2D Airy beams in Fourier space demonstrate the effectiveness of this multipoint calibration method.

  6. A segmentation approach for a delineation of terrestrial ecoregions

    NASA Astrophysics Data System (ADS)

    Nowosad, J.; Stepinski, T.

    2017-12-01

    Terrestrial ecoregions are the result of regionalization of land into homogeneous units of similar ecological and physiographic features. Terrestrial Ecoregions of the World (TEW) is a commonly used global ecoregionalization based on expert knowledge and in situ observations. Ecological Land Units (ELUs) is a global classification of 250 meters-sized cells into 4000 types on the basis of the categorical values of four environmental variables. ELUs are automatically calculated and reproducible but they are not a regionalization which makes them impractical for GIS-based spatial analysis and for comparison with TEW. We have regionalized terrestrial ecosystems on the basis of patterns of the same variables (land cover, soils, landform, and bioclimate) previously used in ELUs. Considering patterns of categorical variables makes segmentation and thus regionalization possible. Original raster datasets of the four variables are first transformed into regular grids of square-sized blocks of their cells called eco-sites. Eco-sites are elementary land units containing local patterns of physiographic characteristics and thus assumed to contain a single ecosystem. Next, eco-sites are locally aggregated using a procedure analogous to image segmentation. The procedure optimizes pattern homogeneity of all four environmental variables within each segment. The result is a regionalization of the landmass into land units characterized by uniform pattern of land cover, soils, landforms, climate, and, by inference, by uniform ecosystem. Because several disjoined segments may have very similar characteristics, we cluster the segments to obtain a smaller set of segment types which we identify with ecoregions. Our approach is automatic, reproducible, updatable, and customizable. It yields the first automatic delineation of ecoregions on the global scale. In the resulting vector database each ecoregion/segment is described by numerous attributes which make it a valuable GIS resource for global ecological and conservation studies.

  7. An Example of Creative Drama Implementation in Values Education: Mevlana's Global Messages "Love-Respect-Tolerance"

    ERIC Educational Resources Information Center

    Akhan, Nadire Emel; Altikulaç, Ali

    2014-01-01

    This study aims to discover how social studies teachers' personal and professional values can be improved by having a basis in Mevlana's global messages "love-respect-tolerance" in terms of "Personal and Professional Values-Professional Development", which is the first component of general efficacies of teaching profession. The…

  8. Mapping global vulnerability index in mining sectors: A case study Moulares-Redayef aquifer system, southwestern Tunisia

    NASA Astrophysics Data System (ADS)

    Khelif, Nadia; Jmal, Ikram; Bouri, Salem

    2016-09-01

    Contrary to the DRASTIC model grouping together the saturated and unsaturated zones to compute a global intrinsic vulnerability index, the global vulnerability index method incorporates both hydrogeological and hydrochemical data for a comprehensive index mapping for the saturated zones. This concept depends on the behavior and the uses of the groundwater. The main aim of this study is to propose a scientific basis for sustainable land use planning and groundwater management of the Moulares-Reayef aquifer, located in Southwestern Tunisia. The overexploitation of this aquifer causes the threat of groundwater quality by various sources of pollution. The global vulnerability index was applied in the Moulares-Reayef aquifer. The results show that the most favorable zones to pollutant percolation are situated along the wadis (Tabaddit, Zallaz, Berka, …) which are drained by continuous discharges. The global vulnerability values were correlated with nitrates values for validation. It revealed a significant correlation showing that high values of nitrates occurred in highly vulnerable zones with a value of 0.69 for the Pearson coefficient. The global vulnerability evaluation shows that the aquifer is characterized by high vertical vulnerability and high susceptibility.

  9. Focal Low and Global High Permeability Predict the Possibility, Risk, and Location of Hemorrhagic Transformation following Intra-Arterial Thrombolysis Therapy in Acute Stroke.

    PubMed

    Li, Y; Xia, Y; Chen, H; Liu, N; Jackson, A; Wintermark, M; Zhang, Y; Hu, J; Wu, B; Zhang, W; Tu, J; Su, Z; Zhu, G

    2017-09-01

    The contrast volume transfer coefficient ( K trans ), which reflects blood-brain barrier permeability, is influenced by circulation and measurement conditions. We hypothesized that focal low BBB permeability values can predict the spatial distribution of hemorrhagic transformation and global high BBB permeability values can predict the likelihood of hemorrhagic transformation. We retrospectively enrolled 106 patients with hemispheric stroke who received intra-arterial thrombolytic treatment. K trans maps were obtained with first-pass perfusion CT data. The K trans values at the region level, obtained with the Alberta Stroke Program Early CT Score system, were compared to determine the differences between the hemorrhagic transformation and nonhemorrhagic transformation regions. The K trans values of the whole ischemic region based on baseline perfusion CT were obtained as a variable to hemorrhagic transformation possibility at the global level. Forty-eight (45.3%) patients had hemorrhagic transformation, and 21 (19.8%) had symptomatic intracranial hemorrhage. At the region level, there were 82 ROIs with hemorrhagic transformation and parenchymal hemorrhage with a mean K trans , 0.5 ± 0.5/min, which was significantly lower than that in the nonhemorrhagic transformation regions ( P < .01). The mean K trans value of 615 nonhemorrhagic transformation ROIs was 0.7 ± 0.6/min. At the global level, there was a significant difference ( P = .01) between the mean K trans values of patients with symptomatic intracranial hemorrhage (1.3 ± 0.9) and those without symptomatic intracranial hemorrhage (0.8 ± 0.4). Only a high K trans value at the global level could predict the occurrence of symptomatic intracranial hemorrhage ( P < .01; OR = 5.04; 95% CI, 2.01-12.65). Global high K trans values can predict the likelihood of hemorrhagic transformation or symptomatic intracranial hemorrhage at the patient level, whereas focal low K trans values can predict the spatial distributions of hemorrhagic transformation at the region level. © 2017 by American Journal of Neuroradiology.

  10. Refining our estimate of atmospheric CO2 across the Eocene-Oligocene climatic transition

    NASA Astrophysics Data System (ADS)

    Heureux, Ana M. C.; Rickaby, Rosalind E. M.

    2015-01-01

    The Eocene-Oligocene transition (EOT) followed by Oligocene isotope event 1 (Oi-1) is a dramatic global switch in climate characterized by deep-sea cooling and the first formation of permanent Antarctic ice. Models and proxy evidence suggest that declining partial pressure of atmospheric carbon dioxide (CO2atm) below a threshold may explain the onset of global cooling and associated ice formation at Oi-1. However, significant uncertainty remains in the estimated values and salient features of reconstructed CO2atm across this interval. In this study, we present novel carbon isotope records from size separated diatom associated organic matter (δ13Cdiatom) preserved in silica frustules. Physical preservation of this material allows concurrent investigation of isotopic and cell size information, providing two input parameters for biogeochemical models and the reconstruction of CO2atm. We estimate CO2atm in two ways; first we use size and reaction-diffusion kinetics of a cell to calculate a CO2atm threshold. Second we use the calibrated relationship between ɛp(diatom) and carbon dioxide from culture and field studies to create a record of CO2atm prior to and across the transition. Our study, from site 1090 in the Atlantic sector of the Southern Ocean, shows CO2atm values fluctuating between 900 and 1700 ± 100 p.p.m.v. across the EOT followed by a drop to values in the order of 700 to 800 ± 100 p.p.m.v. just prior to the onset of Oi-1. Our values and magnitude of CO2atm change differ from previous estimates, but confirm the overall trends inferred from boron isotopes and alkenones, including a marked rebound following Oi-1. Due to the intricate nature of the climate system and complexities in constraining paleo-proxies, this work emphasizes the importance of a multi-proxy approach to estimating of CO2atm in order to elucidate its role in the emplacement of Antarctic ice-sheets at the EOT.

  11. Data Provenance as a Tool for Debugging Hydrological Models based on Python

    NASA Astrophysics Data System (ADS)

    Wombacher, A.; Huq, M.; Wada, Y.; Van Beek, R.

    2012-12-01

    There is an increase in data volume used in hydrological modeling. The increasing data volume requires additional efforts in debugging models since a single output value is influenced by a multitude of input values. Thus, it is difficult to keep an overview among the data dependencies. Further, knowing these dependencies, it is a tedious job to infer all the relevant data values. The aforementioned data dependencies are also known as data provenance, i.e. the determination of how a particular value has been created and processed. The proposed tool infers the data provenance automatically from a python script and visualizes the dependencies as a graph without executing the script. To debug the model the user specifies the value of interest in space and time. The tool infers all related data values and displays them in the graph. The tool has been evaluated by hydrologists developing a model for estimating the global water demand [1]. The model uses multiple different data sources. The script we analysed has 120 lines of codes and used more than 3000 individual files, each of them representing a raster map of 360*720 cells. After importing the data of the files into a SQLite database, the data consumes around 40 GB of memory. Using the proposed tool a modeler is able to select individual values and infer which values have been used to calculate the value. Especially in cases of outliers or missing values it is a beneficial tool to provide the modeler with efficient information to investigate the unexpected behavior of the model. The proposed tool can be applied to many python scripts and has been tested with other scripts in different contexts. In case a python code contains an unknown function or class the tool requests additional information about the used function or class to enable the inference. This information has to be entered only once and can be shared with colleagues or in the community. Reference [1] Y. Wada, L. P. H. van Beek, D. Viviroli, H. H. Drr, R. Weingartner, and M. F. P. Bierkens, "Global monthly water stress: II. water demand and severity of water," Water Resources Research, vol. 47, 2011.

  12. The error and bias of supplementing a short, arid climate, rainfall record with regional vs. global frequency analysis

    NASA Astrophysics Data System (ADS)

    Endreny, Theodore A.; Pashiardis, Stelios

    2007-02-01

    SummaryRobust and accurate estimates of rainfall frequencies are difficult to make with short, and arid-climate, rainfall records, however new regional and global methods were used to supplement such a constrained 15-34 yr record in Cyprus. The impact of supplementing rainfall frequency analysis with the regional and global approaches was measured with relative bias and root mean square error (RMSE) values. Analysis considered 42 stations with 8 time intervals (5-360 min) in four regions delineated by proximity to sea and elevation. Regional statistical algorithms found the sites passed discordancy tests of coefficient of variation, skewness and kurtosis, while heterogeneity tests revealed the regions were homogeneous to mildly heterogeneous. Rainfall depths were simulated in the regional analysis method 500 times, and then goodness of fit tests identified the best candidate distribution as the general extreme value (GEV) Type II. In the regional analysis, the method of L-moments was used to estimate location, shape, and scale parameters. In the global based analysis, the distribution was a priori prescribed as GEV Type II, a shape parameter was a priori set to 0.15, and a time interval term was constructed to use one set of parameters for all time intervals. Relative RMSE values were approximately equal at 10% for the regional and global method when regions were compared, but when time intervals were compared the global method RMSE had a parabolic-shaped time interval trend. Relative bias values were also approximately equal for both methods when regions were compared, but again a parabolic-shaped time interval trend was found for the global method. The global method relative RMSE and bias trended with time interval, which may be caused by fitting a single scale value for all time intervals.

  13. Simulation of lithium ion battery replacement in a battery pack for application in electric vehicles

    NASA Astrophysics Data System (ADS)

    Mathew, M.; Kong, Q. H.; McGrory, J.; Fowler, M.

    2017-05-01

    The design and optimization of the battery pack in an electric vehicle (EV) is essential for continued integration of EVs into the global market. Reconfigurable battery packs are of significant interest lately as they allow for damaged cells to be removed from the circuit, limiting their impact on the entire pack. This paper provides a simulation framework that models a battery pack and examines the effect of replacing damaged cells with new ones. The cells within the battery pack vary stochastically and the performance of the entire pack is evaluated under different conditions. The results show that by changing out cells in the battery pack, the state of health of the pack can be consistently maintained above a certain threshold value selected by the user. In situations where the cells are checked for replacement at discrete intervals, referred to as maintenance event intervals, it is found that the length of the interval is dependent on the mean time to failure of the individual cells. The simulation framework as well as the results from this paper can be utilized to better optimize lithium ion battery pack design in EVs and make long term deployment of EVs more economically feasible.

  14. Progressive Chromatin Condensation and H3K9 Methylation Regulate the Differentiation of Embryonic and Hematopoietic Stem Cells

    DOE PAGES

    Ugarte, Fernando; Sousae, Rebekah; Cinquin, Bertrand; ...

    2015-10-17

    Epigenetic regulation serves as the basis for stem cell differentiation into distinct cell types, but it is unclear how global epigenetic changes are regulated during this process. Here, we tested the hypothesis that global chromatin organization affects the lineage potential of stem cells and that manipulation of chromatin dynamics influences stem cell function. Using nuclease sensitivity assays, we found a progressive decrease in chromatin digestion among pluripotent embryonic stem cells (ESCs), multipotent hematopoietic stem cells (HSCs), and mature hematopoietic cells. Quantitative high-resolution microscopy revealed that ESCs contain significantly more euchromatin than HSCs, with a further reduction in mature cells. Increasedmore » cellular maturation also led to heterochromatin localization to the nuclear periphery. Functionally, prevention of heterochromatin formation by inhibition of the histone methyltransferase G9A resulted in delayed HSC differentiation. Lastly, our results demonstrate global chromatin rearrangements during stem cell differentiation and that heterochromatin formation by H3K9 methylation regulates HSC differentiation.« less

  15. Progressive Chromatin Condensation and H3K9 Methylation Regulate the Differentiation of Embryonic and Hematopoietic Stem Cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ugarte, Fernando; Sousae, Rebekah; Cinquin, Bertrand

    Epigenetic regulation serves as the basis for stem cell differentiation into distinct cell types, but it is unclear how global epigenetic changes are regulated during this process. Here, we tested the hypothesis that global chromatin organization affects the lineage potential of stem cells and that manipulation of chromatin dynamics influences stem cell function. Using nuclease sensitivity assays, we found a progressive decrease in chromatin digestion among pluripotent embryonic stem cells (ESCs), multipotent hematopoietic stem cells (HSCs), and mature hematopoietic cells. Quantitative high-resolution microscopy revealed that ESCs contain significantly more euchromatin than HSCs, with a further reduction in mature cells. Increasedmore » cellular maturation also led to heterochromatin localization to the nuclear periphery. Functionally, prevention of heterochromatin formation by inhibition of the histone methyltransferase G9A resulted in delayed HSC differentiation. Lastly, our results demonstrate global chromatin rearrangements during stem cell differentiation and that heterochromatin formation by H3K9 methylation regulates HSC differentiation.« less

  16. Global increase in replication fork speed during a p57KIP2-regulated erythroid cell fate switch

    PubMed Central

    Hwang, Yung; Futran, Melinda; Hidalgo, Daniel; Pop, Ramona; Iyer, Divya Ramalingam; Scully, Ralph; Rhind, Nicholas; Socolovsky, Merav

    2017-01-01

    Cell cycle regulators are increasingly implicated in cell fate decisions, such as the acquisition or loss of pluripotency and self-renewal potential. The cell cycle mechanisms that regulate these cell fate decisions are largely unknown. We studied an S phase–dependent cell fate switch, in which murine early erythroid progenitors transition in vivo from a self-renewal state into a phase of active erythroid gene transcription and concurrent maturational cell divisions. We found that progenitors are dependent on p57KIP2-mediated slowing of replication forks for self-renewal, a novel function for cyclin-dependent kinase inhibitors. The switch to differentiation entails rapid down-regulation of p57KIP2 with a consequent global increase in replication fork speed and an abruptly shorter S phase. Our work suggests that cell cycles with specialized global DNA replication dynamics are integral to the maintenance of specific cell states and to cell fate decisions. PMID:28560351

  17. Global Mapping of Provisioning Ecosystem Services

    NASA Astrophysics Data System (ADS)

    Bingham, Lisa; Straatsma, Menno; Karssenberg, Derek

    2016-04-01

    Attributing monetary value to ecosystem services for decision-making has become more relevant as a basis for decision-making. There are a number of problematic aspects of the calculations, including consistency of economy represented (e.g., purchasing price, production price) and determining which ecosystem subservices to include in a valuation. While several authors have proposed methods for calculating ecosystem services and calculations are presented for global and regional studies, the calculations are mostly broken down into biomes and regions without showing spatially explicit results. The key to decision-making for governments is to be able to make spatial-based decisions because a large spatial variation may exist within a biome or region. Our objective was to compute the spatial distribution of global ecosystem services based on 89 subservices. Initially, only the provisioning ecosystem service category is presented. The provisioning ecosystem service category was calculated using 6 ecosystem services (food, water, raw materials, genetic resources, medical resources, and ornaments) divided into 41 subservices. Global data sets were obtained from a variety of governmental and research agencies for the year 2005 because this is the most data complete and recent year available. All data originated either in tabular or grid formats and were disaggregated to 10 km cell length grids. A lookup table with production values by subservice by country were disaggregated over the economic zone (either marine, land, or combination) based on the spatial existence of the subservice (e.g. forest cover, crop land, non-arable land). Values express the production price in international dollars per hectare. The ecosystem services and the ecosystem service category(ies) maps may be used to show spatial variation of a service within and between countries as well as to specifically show the values within specific regions (e.g. countries, continents), biomes (e.g. coastal, forest), or hazardous regions (e.g. landslides, flood plains, war zones). A preliminary example of the provisioning ecosystem service category illustrates the valuation of deltaic regions and a second example illustrates the valuation of the subservice category of food production prices in flood zones. Future work of this research will spatially represent the calculations of the remaining three ecosystem service categories (regulating, habitat, cultural) and investigate the propagation of uncertainty of the input data to ecosystem service maps.

  18. Regional climates in the GISS general circulation model: Surface air temperature

    NASA Technical Reports Server (NTRS)

    Hewitson, Bruce

    1994-01-01

    One of the more viable research techniques into global climate change for the purpose of understanding the consequent environmental impacts is based on the use of general circulation models (GCMs). However, GCMs are currently unable to reliably predict the regional climate change resulting from global warming, and it is at the regional scale that predictions are required for understanding human and environmental responses. Regional climates in the extratropics are in large part governed by the synoptic-scale circulation and the feasibility of using this interscale relationship is explored to provide a way of moving to grid cell and sub-grid cell scales in the model. The relationships between the daily circulation systems and surface air temperature for points across the continental United States are first developed in a quantitative form using a multivariate index based on principal components analysis (PCA) of the surface circulation. These relationships are then validated by predicting daily temperature using observed circulation and comparing the predicted values with the observed temperatures. The relationships predict surface temperature accurately over the major portion of the country in winter, and for half the country in summer. These relationships are then applied to the surface synoptic circulation of the Goddard Institute for Space Studies (GISS) GCM control run, and a set of surface grid cell temperatures are generated. These temperatures, based on the larger-scale validated circulation, may now be used with greater confidence at the regional scale. The generated temperatures are compared to those of the model and show that the model has regional errors of up to 10 C in individual grid cells.

  19. Global Precipitation: Means, Variations and Trends During the Satellite Era (1979-2014)

    NASA Astrophysics Data System (ADS)

    Adler, Robert F.; Gu, Guojun; Sapiano, Matthew; Wang, Jian-Jian; Huffman, George J.

    2017-07-01

    Global precipitation variations over the satellite era are reviewed using the Global Precipitation Climatology Project (GPCP) monthly, globally complete analyses, which integrate satellite and surface gauge information. Mean planetary values are examined and compared, over ocean, with information from recent satellite programs and related estimates, with generally positive agreements, but with some indication of small underestimates for GPCP over the global ocean. Variations during the satellite era in global precipitation are tied to ENSO events, with small increases during El Ninos, and very noticeable decreases after major volcanic eruptions. No overall significant trend is noted in the global precipitation mean value, unlike that for surface temperature and atmospheric water vapor. However, there is a pattern of positive and negative trends across the planet with increases over tropical oceans and decreases over some middle latitude regions. These observed patterns are a result of a combination of inter-decadal variations and the effect of the global warming during the period. The results reviewed here indicate the value of such analyses as GPCP and the possible improvement in the information as the record lengthens and as new, more sophisticated and more accurate observations are included.

  20. Exosomes Secreted by Apoptosis-Resistant Acute Myeloid Leukemia (AML) Blasts Harbor Regulatory Network Proteins Potentially Involved in Antagonism of Apoptosis*

    PubMed Central

    Wojtuszkiewicz, Anna; Schuurhuis, Gerrit J.; Kessler, Floortje L.; Piersma, Sander R.; Knol, Jaco C.; Pham, Thang V.; Jansen, Gerrit; Musters, René J. P.; van Meerloo, Johan; Assaraf, Yehuda G.; Kaspers, Gertjan J. L.; Zweegman, Sonja; Cloos, Jacqueline; Jimenez, Connie R.

    2016-01-01

    Expression of apoptosis-regulating proteins (B-cell CLL/lymphoma 2 - BCL-2, Myeloid Cell Leukemia 1 - MCL-1, BCL-2 like 1 - BCL-X and BCL-2-associated X protein - BAX) in acute myeloid leukemia (AML) blasts at diagnosis is associated with disease-free survival. We previously found that the initially high apoptosis-resistance of AML cells decreased after therapy, while regaining high levels at relapse. Herein, we further explored this aspect of dynamic apoptosis regulation in AML. First, we showed that the intraindividual ex vivo apoptosis-related profiles of normal lymphocytes and AML blasts within the bone marrow of AML patients were highly correlated. The expression values of apoptosis-regulating proteins were far beyond healthy control lymphocytes, which implicates the influence of microenvironmental factors. Second, we demonstrated that apoptosis-resistant primary AML blasts, as opposed to apoptosis-sensitive cells, were able to up-regulate BCL-2 expression in sensitive AML blasts in contact cultures (p = 0.0067 and p = 1.0, respectively). Using secretome proteomics, we identified novel proteins possibly engaged in apoptosis regulation. Intriguingly, this analysis revealed that major functional protein clusters engaged in global gene regulation, including mRNA splicing, protein translation, and chromatin remodeling, were more abundant (p = 4.01E-06) in secretomes of apoptosis-resistant AML. These findings were confirmed by subsequent extracellular vesicle proteomics. Finally, confocal-microscopy-based colocalization studies show that splicing factors-containing vesicles secreted by high AAI cells are taken up by low AAI cells. The current results constitute the first comprehensive analysis of proteins released by apoptosis-resistant and sensitive primary AML cells. Together, the data point to vesicle-mediated release of global gene regulatory protein clusters as a plausible novel mechanism of induction of apoptosis resistance. Deciphering the modes of communication between apoptosis-resistant blasts may in perspective lead to the discovery of prognostic tools and development of novel therapeutic interventions, aimed at limiting or overcoming therapy resistance. PMID:26801919

  1. Globalization, Values Education, and School Music Education in China

    ERIC Educational Resources Information Center

    Law, Wing-Wah; Ho, Wai-Chung

    2009-01-01

    This paper examines music education's legitimation of values as a means of preparing students for entry into the new "knowledge society" of the People's Republic of China in a global age. It explores the ways in which values education relates to the teaching of both musical and non-musical meanings in the dual context of nationalism and…

  2. Samoa's Education Policy: Negotiating a Hybrid Space for Values

    ERIC Educational Resources Information Center

    Tuia, Tagataese Tupu; Iyer, Radha

    2015-01-01

    This paper analyses the education policy of Samoa to examine the values that are presented within as relevant to the education system. Drawing on the theory of postcolonialism and globalization, we illustrate how the global and local interact within the education policy to create a hybrid, heterogeneous mix of values and, while the policy…

  3. Examining Cross-Cultural Affective Components of Global Competence from a Value Perspective

    ERIC Educational Resources Information Center

    Awaida-Nachabe, Nadia

    2017-01-01

    The purpose of this study was to explore perceived importance of cultural values and affective components in the Middle East and North Africa (MENA) region and their relationships. This study identified which of the nine affective components of global competence and four higher order cultural values were perceived to be important in the MENA…

  4. A simple, physically-based method for evaluating the economic costs of geo-engineering schemes

    NASA Astrophysics Data System (ADS)

    Garrett, T. J.

    2009-04-01

    The consumption of primary energy (e.g coal, oil, uranium) by the global economy is done in expectation of a return on investment. For geo-engineering schemes, however, the relationship between the primary energy consumption required and the economic return is, at first glance, quite different. The energy costs of a given scheme represent a removal of economically productive available energy to do work in the normal global economy. What are the economic implications of the energy consumption associated with geo-engineering techniques? I will present a simple thermodynamic argument that, in general, real (inflation-adjusted) economic value has a fixed relationship to the rate of global primary energy consumption. This hypothesis will be shown to be supported by 36 years of available energy statistics and a two millennia period of statistics for global economic production. What is found from this analysis is that the value in any given inflation-adjusted 1990 dollar is sustained by a constant 9.7 +/- 0.3 milliwatts of global primary energy consumption. Thus, insofar as geo-engineering is concerned, any scheme that requires some nominal fraction of continuous global primary energy output necessitates a corresponding inflationary loss of real global economic value. For example, if 1% of global energy output is required, at today's consumption rates of 15 TW this corresponds to an inflationary loss of 15 trillion 1990 dollars of real value. The loss will be less, however, if the geo-engineering scheme also enables a demonstrable enhancement to global economic production capacity through climate modification.

  5. AUI&GIV: Recommendation with Asymmetric User Influence and Global Importance Value.

    PubMed

    Zhao, Zhi-Lin; Wang, Chang-Dong; Lai, Jian-Huang

    2016-01-01

    The user-based collaborative filtering (CF) algorithm is one of the most popular approaches for making recommendation. Despite its success, the traditional user-based CF algorithm suffers one serious problem that it only measures the influence between two users based on their symmetric similarities calculated by their consumption histories. It means that, for a pair of users, the influences on each other are the same, which however may not be true. Intuitively, an expert may have an impact on a novice user but a novice user may not affect an expert at all. Besides, each user may possess a global importance factor that affects his/her influence to the remaining users. To this end, in this paper, we propose an asymmetric user influence model to measure the directed influence between two users and adopt the PageRank algorithm to calculate the global importance value of each user. And then the directed influence values and the global importance values are integrated to deduce the final influence values between two users. Finally, we use the final influence values to improve the performance of the traditional user-based CF algorithm. Extensive experiments have been conducted, the results of which have confirmed that both the asymmetric user influence model and global importance value play key roles in improving recommendation accuracy, and hence the proposed method significantly outperforms the existing recommendation algorithms, in particular the user-based CF algorithm on the datasets of high rating density.

  6. AUI&GIV: Recommendation with Asymmetric User Influence and Global Importance Value

    PubMed Central

    Zhao, Zhi-Lin; Wang, Chang-Dong; Lai, Jian-Huang

    2016-01-01

    The user-based collaborative filtering (CF) algorithm is one of the most popular approaches for making recommendation. Despite its success, the traditional user-based CF algorithm suffers one serious problem that it only measures the influence between two users based on their symmetric similarities calculated by their consumption histories. It means that, for a pair of users, the influences on each other are the same, which however may not be true. Intuitively, an expert may have an impact on a novice user but a novice user may not affect an expert at all. Besides, each user may possess a global importance factor that affects his/her influence to the remaining users. To this end, in this paper, we propose an asymmetric user influence model to measure the directed influence between two users and adopt the PageRank algorithm to calculate the global importance value of each user. And then the directed influence values and the global importance values are integrated to deduce the final influence values between two users. Finally, we use the final influence values to improve the performance of the traditional user-based CF algorithm. Extensive experiments have been conducted, the results of which have confirmed that both the asymmetric user influence model and global importance value play key roles in improving recommendation accuracy, and hence the proposed method significantly outperforms the existing recommendation algorithms, in particular the user-based CF algorithm on the datasets of high rating density. PMID:26828803

  7. Structure based alignment and clustering of proteins (STRALCP)

    DOEpatents

    Zemla, Adam T.; Zhou, Carol E.; Smith, Jason R.; Lam, Marisa W.

    2013-06-18

    Disclosed are computational methods of clustering a set of protein structures based on local and pair-wise global similarity values. Pair-wise local and global similarity values are generated based on pair-wise structural alignments for each protein in the set of protein structures. Initially, the protein structures are clustered based on pair-wise local similarity values. The protein structures are then clustered based on pair-wise global similarity values. For each given cluster both a representative structure and spans of conserved residues are identified. The representative protein structure is used to assign newly-solved protein structures to a group. The spans are used to characterize conservation and assign a "structural footprint" to the cluster.

  8. U.S. Clean Energy Hydrogen and Fuel Cell Technologies: A Competitiveness Analysis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fullenkamp, Patrick; Holody, Diane; James, Brian

    The objectives of this project are a 1) Global Competitiveness Analysis of hydrogen and fuel cell systems and components manufactured including 700 bar compressed hydrogen storage system in the U.S., Europe, Asia, and other key areas to be identified to determine the global cost leaders, the best current manufacturing processes, the key factors determining competitiveness, and the potential means of cost reductions; and an 2) Analysis to assess the status of global hydrogen and fuel cell markets. The analysis of units, megawatts by country and by application will focus on polymer electrolyte membrane (PEM) fuel cell systems (automotive and stationary).

  9. Global Manufacturing of CAR T Cell Therapy.

    PubMed

    Levine, Bruce L; Miskin, James; Wonnacott, Keith; Keir, Christopher

    2017-03-17

    Immunotherapy using chimeric antigen receptor-modified T cells has demonstrated high response rates in patients with B cell malignancies, and chimeric antigen receptor T cell therapy is now being investigated in several hematologic and solid tumor types. Chimeric antigen receptor T cells are generated by removing T cells from a patient's blood and engineering the cells to express the chimeric antigen receptor, which reprograms the T cells to target tumor cells. As chimeric antigen receptor T cell therapy moves into later-phase clinical trials and becomes an option for more patients, compliance of the chimeric antigen receptor T cell manufacturing process with global regulatory requirements becomes a topic for extensive discussion. Additionally, the challenges of taking a chimeric antigen receptor T cell manufacturing process from a single institution to a large-scale multi-site manufacturing center must be addressed. We have anticipated such concerns in our experience with the CD19 chimeric antigen receptor T cell therapy CTL019. In this review, we discuss steps involved in the cell processing of the technology, including the use of an optimal vector for consistent cell processing, along with addressing the challenges of expanding chimeric antigen receptor T cell therapy to a global patient population.

  10. The Role of Discrete Global Grid Systems in the Global Statistical Geospatial Framework

    NASA Astrophysics Data System (ADS)

    Purss, M. B. J.; Peterson, P.; Minchin, S. A.; Bermudez, L. E.

    2016-12-01

    The United Nations Committee of Experts on Global Geospatial Information Management (UN-GGIM) has proposed the development of a Global Statistical Geospatial Framework (GSGF) as a mechanism for the establishment of common analytical systems that enable the integration of statistical and geospatial information. Conventional coordinate reference systems address the globe with a continuous field of points suitable for repeatable navigation and analytical geometry. While this continuous field is represented on a computer in a digitized and discrete fashion by tuples of fixed-precision floating point values, it is a non-trivial exercise to relate point observations spatially referenced in this way to areal coverages on the surface of the Earth. The GSGF states the need to move to gridded data delivery and the importance of using common geographies and geocoding. The challenges associated with meeting these goals are not new and there has been a significant effort within the geospatial community to develop nested gridding standards to tackle these issues over many years. These efforts have recently culminated in the development of a Discrete Global Grid Systems (DGGS) standard which has been developed under the auspices of Open Geospatial Consortium (OGC). DGGS provide a fixed areal based geospatial reference frame for the persistent location of measured Earth observations, feature interpretations, and modelled predictions. DGGS address the entire planet by partitioning it into a discrete hierarchical tessellation of progressively finer resolution cells, which are referenced by a unique index that facilitates rapid computation, query and analysis. The geometry and location of the cell is the principle aspect of a DGGS. Data integration, decomposition, and aggregation is optimised in the DGGS hierarchical structure and can be exploited for efficient multi-source data processing, storage, discovery, transmission, visualization, computation, analysis, and modelling. During the 6th Session of the UN-GGIM in August 2016 the role of DGGS in the context of the GSGF was formally acknowledged. This paper proposes to highlight the synergies and role of DGGS in the Global Statistical Geospatial Framework and to show examples of the use of DGGS to combine geospatial statistics with traditional geoscientific data.

  11. Plastic and Reconstructive Surgery in Global Health: Let’s Reconstruct Global Surgery

    PubMed Central

    2017-01-01

    Summary: Since the inception of the Lancet Commission in 2013 and consequent prioritization of Global Surgery at the World Health Assembly, international surgical outreach efforts have increased and become more synergistic. Plastic surgeons have been involved in international outreach for decades, and there is now a demand to collaborate and address local need in an innovative way. The aim of this article was to summarize new developments in plastic and reconstructive surgery in global health, to unify our approach to international outreach. Specifically, 5 topics are explored: current models in international outreach, benefits and concerns, the value of research, the value of international surgical outreach education, and the value of technology. A “Let’s Reconstruct Global Surgery” network has been formed using Facebook as a platform to unite plastic and reconstructive surgeons worldwide who are interested in international outreach. The article concludes with actionable recommendations from each topic. PMID:28507847

  12. Global architecture of the F-actin cytoskeleton regulates cell shape-dependent endothelial mechanotransduction.

    PubMed

    Shao, Yue; Mann, Jennifer M; Chen, Weiqiang; Fu, Jianping

    2014-03-01

    Uniaxial stretch is an important biophysical regulator of cell morphology (or shape) and functions of vascular endothelial cells (ECs). However, it is unclear whether and how cell shape can independently regulate EC mechanotransductive properties under uniaxial stretch. Herein, utilizing a novel uniaxial cell-stretching device integrated with micropost force sensors, we reported the first experimental evidence showing cell shape-dependent EC mechanotransduction via cytoskeleton (CSK) contractile forces in response to uniaxial stretch. Combining experiments and theoretical modeling from first principles, we showed that it was the global architecture of the F-actin CSK that instructed the cell shape-dependent EC mechanotransductive process. Furthermore, a cell shape-dependent nature was relayed in EC mechanotransduction via dynamic focal adhesion (FA) assembly. Our results suggested a novel mechanotransductive process in ECs wherein the global architecture of the F-actin CSK, governed by cell shape, controls mechanotransduction via CSK contractile forces and force-dependent FA assembly under uniaxial stretch.

  13. Comparison of professional values of Taiwanese and United States nursing students.

    PubMed

    Alfred, Danita; Yarbrough, Susan; Martin, Pam; Mink, Janice; Lin, Yu-Hua; Wang, Liching S

    2013-12-01

    Globalization is a part of modern life. Sharing a common set of professional nursing values is critical in this global environment. The purpose of this research was to examine the professional values of nursing students from two distinct cultural perspectives. Nurse educators in Taiwan partnered with nurse educators in the United States to compare professional values of their respective graduating nursing students. The American Nurses Association Code of Ethics served as the philosophical framework for this examination. The convenience sample comprised 94 Taiwanese students and 168 US students. Both groups reported high scores on an overall measure of values. They did differ substantially on the relative importance of individual items related to advocacy, competence, education, self-evaluation, professional advancement, and professional associations. Global implications for the collaborative practice of nurses from different cultures working together can be improved by first recognizing and then attending to these differences in value priorities.

  14. Global characterization of in vivo enzyme catalytic rates and their correspondence to in vitro kcat measurements

    PubMed Central

    Davidi, Dan; Noor, Elad; Liebermeister, Wolfram; Bar-Even, Arren; Flamholz, Avi; Tummler, Katja; Barenholz, Uri; Goldenfeld, Miki; Shlomi, Tomer; Milo, Ron

    2016-01-01

    Turnover numbers, also known as kcat values, are fundamental properties of enzymes. However, kcat data are scarce and measured in vitro, thus may not faithfully represent the in vivo situation. A basic question that awaits elucidation is: how representative are kcat values for the maximal catalytic rates of enzymes in vivo? Here, we harness omics data to calculate kmaxvivo, the observed maximal catalytic rate of an enzyme inside cells. Comparison with kcat values from Escherichia coli, yields a correlation of r2= 0.62 in log scale (p < 10−10), with a root mean square difference of 0.54 (3.5-fold in linear scale), indicating that in vivo and in vitro maximal rates generally concur. By accounting for the degree of saturation of enzymes and the backward flux dictated by thermodynamics, we further refine the correspondence between kmaxvivo and kcat values. The approach we present here characterizes the quantitative relationship between enzymatic catalysis in vitro and in vivo and offers a high-throughput method for extracting enzyme kinetic constants from omics data. PMID:26951675

  15. Global gene expression analyses of hematopoietic stem cell-like cell lines with inducible Lhx2 expression

    PubMed Central

    Richter, Karin; Wirta, Valtteri; Dahl, Lina; Bruce, Sara; Lundeberg, Joakim; Carlsson, Leif; Williams, Cecilia

    2006-01-01

    Background Expression of the LIM-homeobox gene Lhx2 in murine hematopoietic cells allows for the generation of hematopoietic stem cell (HSC)-like cell lines. To address the molecular basis of Lhx2 function, we generated HSC-like cell lines where Lhx2 expression is regulated by a tet-on system and hence dependent on the presence of doxycyclin (dox). These cell lines efficiently down-regulate Lhx2 expression upon dox withdrawal leading to a rapid differentiation into various myeloid cell types. Results Global gene expression of these cell lines cultured in dox was compared to different time points after dox withdrawal using microarray technology. We identified 267 differentially expressed genes. The majority of the genes overlapping with HSC-specific databases were those down-regulated after turning off Lhx2 expression and a majority of the genes overlapping with those defined as late progenitor-specific genes were the up-regulated genes, suggesting that these cell lines represent a relevant model system for normal HSCs also at the level of global gene expression. Moreover, in situ hybridisations of several genes down-regulated after dox withdrawal showed overlapping expression patterns with Lhx2 in various tissues during embryonic development. Conclusion Global gene expression analysis of HSC-like cell lines with inducible Lhx2 expression has identified genes putatively linked to self-renewal / differentiation of HSCs, and function of Lhx2 in organ development and stem / progenitor cells of non-hematopoietic origin. PMID:16600034

  16. An assessment on convective and radiative heat transfer modelling in tubular solid oxide fuel cells

    NASA Astrophysics Data System (ADS)

    Sánchez, D.; Muñoz, A.; Sánchez, T.

    Four models of convective and radiative heat transfer inside tubular solid oxide fuel cells are presented in this paper, all of them applicable to multidimensional simulations. The work is aimed at assessing if it is necessary to use a very detailed and complicated model to simulate heat transfer inside this kind of device and, for those cases when simple models can be used, the errors are estimated and compared to those of the more complex models. For the convective heat transfer, two models are presented. One of them accounts for the variation of film coefficient as a function of local temperature and composition. This model gives a local value for the heat transfer coefficients and establishes the thermal entry length. The second model employs an average value of the transfer coefficient, which is applied to the whole length of the duct being studied. It is concluded that, unless there is a need to calculate local temperatures, a simple model can be used to evaluate the global performance of the cell with satisfactory accuracy. For the radiation heat transfer, two models are presented again. One of them considers radial radiation exclusively and, thus, radiative exchange between adjacent cells is neglected. On the other hand, the second model accounts for radiation in all directions but increases substantially the complexity of the problem. For this case, it is concluded that deviations between both models are higher than for convection. Actually, using a simple model can lead to a not negligible underestimation of the temperature of the cell.

  17. Stem cell science in India: emerging economies and the politics of globalization.

    PubMed

    Salter, Brian; Cooper, Melinda; Dickins, Amanda; Cardo, Valentina

    2007-01-01

    The globalization of stem cell science is increasingly being shaped by the emerging economies of the Asia/Pacific region. Undaunted and unhampered by the more established views of the commercialization of science, countries such as India are constructing models of innovation, policies and patterns of investment that challenge such orthodoxies. This report examines the position of India within the globalization of stem cell science, its adjustments to the developing knowledge market in this field and its particular contribution to the likely future of this promising bioeconomy.

  18. Single-Frame Terrain Mapping Software for Robotic Vehicles

    NASA Technical Reports Server (NTRS)

    Rankin, Arturo L.

    2011-01-01

    This software is a component in an unmanned ground vehicle (UGV) perception system that builds compact, single-frame terrain maps for distribution to other systems, such as a world model or an operator control unit, over a local area network (LAN). Each cell in the map encodes an elevation value, terrain classification, object classification, terrain traversability, terrain roughness, and a confidence value into four bytes of memory. The input to this software component is a range image (from a lidar or stereo vision system), and optionally a terrain classification image and an object classification image, both registered to the range image. The single-frame terrain map generates estimates of the support surface elevation, ground cover elevation, and minimum canopy elevation; generates terrain traversability cost; detects low overhangs and high-density obstacles; and can perform geometry-based terrain classification (ground, ground cover, unknown). A new origin is automatically selected for each single-frame terrain map in global coordinates such that it coincides with the corner of a world map cell. That way, single-frame terrain maps correctly line up with the world map, facilitating the merging of map data into the world map. Instead of using 32 bits to store the floating-point elevation for a map cell, the vehicle elevation is assigned to the map origin elevation and reports the change in elevation (from the origin elevation) in terms of the number of discrete steps. The single-frame terrain map elevation resolution is 2 cm. At that resolution, terrain elevation from 20.5 to 20.5 m (with respect to the vehicle's elevation) is encoded into 11 bits. For each four-byte map cell, bits are assigned to encode elevation, terrain roughness, terrain classification, object classification, terrain traversability cost, and a confidence value. The vehicle s current position and orientation, the map origin, and the map cell resolution are all included in a header for each map. The map is compressed into a vector prior to delivery to another system.

  19. COAL USE REPORT

    EPA Science Inventory

    The world's coal reserves have been estimated to be about one exagram accessible with current extraction technology. The energy content has been valued at 290 zettajourles. Using a value of 15 terawatt as the current global energy consumption, the coal supply could global needs f...

  20. Should Social Value Obligations be Local or Global?

    PubMed

    Nayak, Rahul; Shah, Seema K

    2017-02-01

    According to prominent bioethics scholars and international guidelines, researchers and sponsors have obligations to ensure that the products of their research are reasonably available to research participants and their communities. In other words, the claim is that research is unethical unless it has local social value. In this article, we argue that the existing conception of reasonable availability should be replaced with a social value obligation that extends to the global poor (and not just research participants and host communities). To the extent the social value requirement has been understood as geographically constrained to the communities that host research and the countries that can afford the products of research, it has neglected to include the global poor as members of the relevant society. We argue that a new conception of social value obligations is needed for two reasons. First, duties of global beneficence give reason for researchers, sponsors, and institutions to take steps to make their products more widely accessible. Second, public commitments made by many institutions acknowledge and engender responsibilities to make the products of research more accessible to the global poor. Future research is needed to help researchers and sponsors discharge these obligations in ways that unlock their full potential. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  1. Impairment of DNA Methylation Maintenance Is the Main Cause of Global Demethylation in Naive Embryonic Stem Cells.

    PubMed

    von Meyenn, Ferdinand; Iurlaro, Mario; Habibi, Ehsan; Liu, Ning Qing; Salehzadeh-Yazdi, Ali; Santos, Fátima; Petrini, Edoardo; Milagre, Inês; Yu, Miao; Xie, Zhenqing; Kroeze, Leonie I; Nesterova, Tatyana B; Jansen, Joop H; Xie, Hehuang; He, Chuan; Reik, Wolf; Stunnenberg, Hendrik G

    2016-06-16

    Global demethylation is part of a conserved program of epigenetic reprogramming to naive pluripotency. The transition from primed hypermethylated embryonic stem cells (ESCs) to naive hypomethylated ones (serum-to-2i) is a valuable model system for epigenetic reprogramming. We present a mathematical model, which accurately predicts global DNA demethylation kinetics. Experimentally, we show that the main drivers of global demethylation are neither active mechanisms (Aicda, Tdg, and Tet1-3) nor the reduction of de novo methylation. UHRF1 protein, the essential targeting factor for DNMT1, is reduced upon transition to 2i, and so is recruitment of the maintenance methylation machinery to replication foci. Concurrently, there is global loss of H3K9me2, which is needed for chromatin binding of UHRF1. These mechanisms synergistically enforce global DNA hypomethylation in a replication-coupled fashion. Our observations establish the molecular mechanism for global demethylation in naive ESCs, which has key parallels with those operating in primordial germ cells and early embryos. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  2. Evaluation of Pistacia lentiscus seed oil and phenolic compounds for in vitro antiproliferative effects against BHK21 cells.

    PubMed

    Mezni, Faten; Shili, Sarra; Ben Ali, Nejia; Larbi Khouja, Mohamed; Khaldi, Abdelhamid; Maaroufi, Abderrazak

    2016-01-01

    Within the global context of increasing cancer diseases, natural products are important in devising new drugs and providing unique ideas in cancer therapy. In Tunisian folk medicine, Pistacia lentiscus L. (Anacardiaceae) fixed oil is used for cancer treatment. This investigation studied, for the first time, the antiproliferative effect of Pistacia lentiscus fixed oil and its phenolic extract on BHK21 cancer cells. Oil was extracted from fruits harvested in northwest Tunisia and the phenolic fraction was obtained by mixing with methanol. The anti-proliferative activity of the two tested substances on BHK 21 cells were investigated in vitro using trypan blue assays. Cells were treated with different concentrations of P. lentiscus oil (0.009, 0.018, 0.036, and 0.09 g/mL) and the phenolic extract (0.007, 0.014, 0.03, and 0.07 g/mL) for 24, 48, and 72 h. The inhibitory effect of Pistacia lentiscus fixed oil increases with the increase in dose. The IC50 value was estimated at 0.029 g/mL. The percentage of cell viability was 42.46 ± 3.4% at a dose of 0.09 g/mL and was significantly lower than that of the untreated control (96.24 ± 2.5%, p<0.01). The phenolic extract demonstrated a dose- and time-dependent inhibitory effect on BHK21 cell growth. After 48 h of incubation, the IC50 value was estimated at 0.15 g/mL. The results demonstrated the potential of Pistacia lentiscus fixed oil in treating cancer, as it is used in traditional medicine.

  3. Developing global regression models for metabolite concentration prediction regardless of cell line.

    PubMed

    André, Silvère; Lagresle, Sylvain; Da Sliva, Anthony; Heimendinger, Pierre; Hannas, Zahia; Calvosa, Éric; Duponchel, Ludovic

    2017-11-01

    Following the Process Analytical Technology (PAT) of the Food and Drug Administration (FDA), drug manufacturers are encouraged to develop innovative techniques in order to monitor and understand their processes in a better way. Within this framework, it has been demonstrated that Raman spectroscopy coupled with chemometric tools allow to predict critical parameters of mammalian cell cultures in-line and in real time. However, the development of robust and predictive regression models clearly requires many batches in order to take into account inter-batch variability and enhance models accuracy. Nevertheless, this heavy procedure has to be repeated for every new line of cell culture involving many resources. This is why we propose in this paper to develop global regression models taking into account different cell lines. Such models are finally transferred to any culture of the cells involved. This article first demonstrates the feasibility of developing regression models, not only for mammalian cell lines (CHO and HeLa cell cultures), but also for insect cell lines (Sf9 cell cultures). Then global regression models are generated, based on CHO cells, HeLa cells, and Sf9 cells. Finally, these models are evaluated considering a fourth cell line(HEK cells). In addition to suitable predictions of glucose and lactate concentration of HEK cell cultures, we expose that by adding a single HEK-cell culture to the calibration set, the predictive ability of the regression models are substantially increased. In this way, we demonstrate that using global models, it is not necessary to consider many cultures of a new cell line in order to obtain accurate models. Biotechnol. Bioeng. 2017;114: 2550-2559. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  4. Dual Targeting of Intracellular Pathogenic Bacteria with a Cleavable Conjugate of Kanamycin and an Antibacterial Cell-Penetrating Peptide.

    PubMed

    Brezden, Anna; Mohamed, Mohamed F; Nepal, Manish; Harwood, John S; Kuriakose, Jerrin; Seleem, Mohamed N; Chmielewski, Jean

    2016-08-31

    Bacterial infection caused by intracellular pathogens, such as Mycobacterium, Salmonella, and Brucella, is a burgeoning global health epidemic that necessitates urgent action. However, the therapeutic value of a number of antibiotics, including aminoglycosides, against intracellular pathogenic bacteria is compromised due to their inability to traverse eukaryotic membranes. For this significant problem to be addressed, a cleavable conjugate of the antibiotic kanamycin and a nonmembrane lytic, broad-spectrum antimicrobial peptide with efficient mammalian cell penetration, P14LRR, was prepared. This approach allows kanamycin to enter mammalian cells as a conjugate linked via a tether that breaks down in the reducing environment within cells. Potent antimicrobial activity of the P14KanS conjugate was demonstrated in vitro, and this reducible conjugate effectively cleared intracellular pathogenic bacteria within macrophages more potently than that of a conjugate lacking the disulfide moiety. Notably, successful clearance of Mycobacterium tuberculosis within macrophages was observed with the dual antibiotic conjugate, and Salmonella levels were significantly reduced in an in vivo Caenorhabditis elegans model.

  5. Rivers, runoff, and reefs

    USGS Publications Warehouse

    McLaughlin, C.J.; Smith, C.A.; Buddemeier, R.W.; Bartley, J.D.; Maxwell, B.A.

    2003-01-01

    The role of terrigenous sediment in controlling the occurrence of coral reef ecosystems is qualitatively understood and has been studied at local scales, but has not been systematically evaluated on a global-to-regional scale. Current concerns about degradation of reef environments and alteration of the hydrologic and sediment cycles place the issue at a focal point of multiple environmental concerns. We use a geospatial clustering of a coastal zone database of river and local runoff identified with 0.5?? grid cells to identify areas of high potential runoff effects, and combine this with a database of reported coral reef locations. Coastal cells with high runoff values are much less likely to contain reefs than low runoff cells and GIS buffer analysis demonstrates that this inhibition extends to offshore ocean cells as well. This analysis does not uniquely define the effects of sediment, since salinity, nutrients, and contaminants are potentially confounding variables also associated with runoff. However, sediment effects are likely to be a major factor and a basis is provided for extending the study to higher resolution with more specific variables. ?? 2003 Elsevier B.V. All rights reserved.

  6. How Philip Morris built Marlboro into a global brand for young adults: implications for international tobacco control.

    PubMed

    Hafez, N; Ling, P M

    2005-08-01

    To describe Philip Morris' global market research and international promotional strategies targeting young adults. Analysis of previously secret tobacco industry documents. Philip Morris pursued standardised market research and strategic marketing plans in different regions throughout the world using research on young adults with three principle foci: lifestyle/psychographic research, brand studies, and advertising/communication effectiveness. Philip Morris identified core similarities in the lifestyles and needs of young consumers worldwide, such as independence, hedonism, freedom, and comfort. In the early 1990s Philip Morris adopted standardised global marketing efforts, creating a central advertising production bank and guidelines for brand images and promotions, but allowing regional managers to create regionally appropriate individual advertisements. Values and lifestyles play a central role in the global marketing of tobacco to young adults. Worldwide counter marketing initiatives, coupled with strong, coherent global marketing policies such as the Framework Convention on Tobacco Control, are needed to break associations between young adult values and tobacco brands. As globalisation promotes the homogenisation of values and lifestyles, tobacco control messages that resonate with young adults in one part of the world may appeal to young adults in other countries. Successful tobacco control messages that appeal to young people, such as industry denormalisation, may be expanded globally with appropriate tailoring to appeal to regional values.

  7. Self-Orientation Modulates the Neural Correlates of Global and Local Processing

    PubMed Central

    Liddell, Belinda J.; Das, Pritha; Battaglini, Eva; Malhi, Gin S.; Felmingham, Kim L.; Whitford, Thomas J.; Bryant, Richard A.

    2015-01-01

    Differences in self-orientation (or “self-construal”) may affect how the visual environment is attended, but the neural and cultural mechanisms that drive this remain unclear. Behavioral studies have demonstrated that people from Western backgrounds with predominant individualistic values are perceptually biased towards local-level information; whereas people from non-Western backgrounds that support collectivist values are preferentially focused on contextual and global-level information. In this study, we compared two groups differing in predominant individualistic (N = 15) vs collectivistic (N = 15) self-orientation. Participants completed a global/local perceptual conflict task whilst undergoing functional Magnetic Resonance Imaging (fMRI) scanning. When participants high in individualistic values attended to the global level (ignoring the local level), greater activity was observed in the frontoparietal and cingulo-opercular networks that underpin attentional control, compared to the match (congruent) baseline. Participants high in collectivistic values activated similar attentional control networks o only when directly compared with global processing. This suggests that global interference was stronger than local interference in the conflict task in the collectivistic group. Both groups showed increased activity in dorsolateral prefrontal regions involved in resolving perceptual conflict during heightened distractor interference. The findings suggest that self-orientation may play an important role in driving attention networks to facilitate interaction with the visual environment. PMID:26270820

  8. Self-Orientation Modulates the Neural Correlates of Global and Local Processing.

    PubMed

    Liddell, Belinda J; Das, Pritha; Battaglini, Eva; Malhi, Gin S; Felmingham, Kim L; Whitford, Thomas J; Bryant, Richard A

    2015-01-01

    Differences in self-orientation (or "self-construal") may affect how the visual environment is attended, but the neural and cultural mechanisms that drive this remain unclear. Behavioral studies have demonstrated that people from Western backgrounds with predominant individualistic values are perceptually biased towards local-level information; whereas people from non-Western backgrounds that support collectivist values are preferentially focused on contextual and global-level information. In this study, we compared two groups differing in predominant individualistic (N = 15) vs collectivistic (N = 15) self-orientation. Participants completed a global/local perceptual conflict task whilst undergoing functional Magnetic Resonance Imaging (fMRI) scanning. When participants high in individualistic values attended to the global level (ignoring the local level), greater activity was observed in the frontoparietal and cingulo-opercular networks that underpin attentional control, compared to the match (congruent) baseline. Participants high in collectivistic values activated similar attentional control networks o only when directly compared with global processing. This suggests that global interference was stronger than local interference in the conflict task in the collectivistic group. Both groups showed increased activity in dorsolateral prefrontal regions involved in resolving perceptual conflict during heightened distractor interference. The findings suggest that self-orientation may play an important role in driving attention networks to facilitate interaction with the visual environment.

  9. Introducing difference recurrence relations for faster semi-global alignment of long sequences.

    PubMed

    Suzuki, Hajime; Kasahara, Masahiro

    2018-02-19

    The read length of single-molecule DNA sequencers is reaching 1 Mb. Popular alignment software tools widely used for analyzing such long reads often take advantage of single-instruction multiple-data (SIMD) operations to accelerate calculation of dynamic programming (DP) matrices in the Smith-Waterman-Gotoh (SWG) algorithm with a fixed alignment start position at the origin. Nonetheless, 16-bit or 32-bit integers are necessary for storing the values in a DP matrix when sequences to be aligned are long; this situation hampers the use of the full SIMD width of modern processors. We proposed a faster semi-global alignment algorithm, "difference recurrence relations," that runs more rapidly than the state-of-the-art algorithm by a factor of 2.1. Instead of calculating and storing all the values in a DP matrix directly, our algorithm computes and stores mainly the differences between the values of adjacent cells in the matrix. Although the SWG algorithm and our algorithm can output exactly the same result, our algorithm mainly involves 8-bit integer operations, enabling us to exploit the full width of SIMD operations (e.g., 32) on modern processors. We also developed a library, libgaba, so that developers can easily integrate our algorithm into alignment programs. Our novel algorithm and optimized library implementation will facilitate accelerating nucleotide long-read analysis algorithms that use pairwise alignment stages. The library is implemented in the C programming language and available at https://github.com/ocxtal/libgaba .

  10. Analysis of the solar radiation data for Beer Sheva, Israel, and its environs

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kudish, A.I.; Ianetz, A.

    The solar radiation climate of Beer Sheva, Israel, is reported upon in detail. The database utilized in this analysis consisted of global radiation on a horizontal surface, normal incidence beam radiation, and global radiation on a south-facing surface tilted at 40{degree}. Monthly-average hourly and daily values are reported for each of these three types of measured radiations, together with the calculated monthly-average daily values for the components of the global radiation, viz. the horizontal beam and diffuse radiations. The monthly-average hourly and daily clearness index values have also been calculated and analyzed. Monthly-average daily frequency distributions of the clearness indexmore » values are reported for each month. The solar radiation climate of Beer Sheva has also been compared to those reported for a number of countries in this region. The annual-average daily global radiation incident on a horizontal surface is 18.91 MG/m{sup 2} and that for normal incidence beam radiation is 21.17 MG/m{sup 2}. The annual-average daily fraction of the horizontal global radiation that is beam is 0.72. The annual-average daily value for the clearness index is 0.587 and the average frequency of clear days annually is 58.6%. The authors conclude, based upon the above analysis, that Beer Sheva and its environs are characterized by relatively high, average-daily irradiation rates, both global and beam, and a relatively high frequency of clear days.« less

  11. Sliding mode observer for proton exchange membrane fuel cell: automotive application

    NASA Astrophysics Data System (ADS)

    Piffard, Maxime; Gerard, Mathias; Fonseca, Ramon Da; Massioni, Paolo; Bideaux, Eric

    2018-06-01

    This work proposes a state observer as a tool to manage cost and durability issues for PEMFC (Proton Exchange Membrane Fuel Cell) in automotive applications. Based on a dead-end anode architecture, the observer estimates the nitrogen build-up in the anode side, as well as relative humidities in the channels. These estimated parameters can then be used at fuel cell management level to enhance the durability of the stack. This observer is based on transport equations through the membrane and it reconstructs the behavior of the water and nitrogen inside the channels without the need of additional humidity sensors to correct the estimate. The convergence of the output variables is proved with Lyapunov theory for dynamic operating conditions. The validation is made with a high-fidelity model running a WLTC (Worldwide harmonized Light vehicles Test Cycle). This observer provides the average values of nitrogen and relative humidities with sufficient precision to be used in a global real-time control scheme.

  12. Measuring the impact of final demand on global production system based on Markov process

    NASA Astrophysics Data System (ADS)

    Xing, Lizhi; Guan, Jun; Wu, Shan

    2018-07-01

    Input-output table is a comprehensive and detailed in describing the national economic systems, consisting of supply and demand information among various industrial sectors. The complex network, a theory and method for measuring the structure of complex system, can depict the structural properties of social and economic systems, and reveal the complicated relationships between the inner hierarchies and the external macroeconomic functions. This paper tried to measure the globalization degree of industrial sectors on the global value chain. Firstly, it constructed inter-country input-output network models to reproduce the topological structure of global economic system. Secondly, it regarded the propagation of intermediate goods on the global value chain as Markov process and introduced counting first passage betweenness to quantify the added processing amount when globally final demand stimulates this production system. Thirdly, it analyzed the features of globalization at both global and country-sector level

  13. Cryopreservation of Fish Spermatogonial Cells: The Future of Natural History Collections.

    PubMed

    Hagedorn, Mary M; Daly, Jonathan P; Carter, Virginia L; Cole, Kathleen S; Jaafar, Zeehan; Lager, Claire V A; Parenti, Lynne R

    2018-04-18

    As global biodiversity declines, the value of biological collections increases. Cryopreserved diploid spermatogonial cells meet two goals: to yield high-quality molecular sequence data; and to regenerate new individuals, hence potentially countering species extinction. Cryopreserved spermatogonial cells that allow for such mitigative measures are not currently in natural history museum collections because there are no standard protocols to collect them. Vertebrate specimens, especially fishes, are traditionally formalin-fixed and alcohol-preserved which makes them ideal for morphological studies and as museum vouchers, but inadequate for molecular sequence data. Molecular studies of fishes routinely use tissues preserved in ethanol; yet tissues preserved in this way may yield degraded sequences over time. As an alternative to tissue fixation methods, we assessed and compared previously published cryopreservation methods by gating and counting fish testicular cells with flow cytometry to identify presumptive spermatogonia A-type cells. Here we describe a protocol to cryopreserve tissues that yields a high percentage of viable spermatogonial cells from the testes of Asterropteryx semipunctata, a marine goby. Material cryopreserved using this protocol represents the first frozen and post-thaw viable spermatogonial cells of fishes archived in a natural history museum to provide better quality material for re-derivation of species and DNA preservation and analysis.

  14. Using a medium-throughput comet assay to evaluate the global DNA methylation status of single cells

    PubMed Central

    Lewies, Angélique; Van Dyk, Etresia; Wentzel, Johannes F.; Pretorius, Pieter J.

    2014-01-01

    The comet assay is a simple and cost effective technique, commonly used to analyze and quantify DNA damage in individual cells. The versatility of the comet assay allows introduction of various modifications to the basic technique. The difference in the methylation sensitivity of the isoschizomeric restriction enzymes HpaII and MspI are used to demonstrate the ability of the comet assay to measure the global DNA methylation level of individual cells when using cell cultures. In the experiments described here, a medium-throughput comet assay and methylation sensitive comet assay are combined to produce a methylation sensitive medium-throughput comet assay to measure changes in the global DNA methylation pattern in individual cells under various growth conditions. PMID:25071840

  15. Development of AM 1.5 global measurement procedures and international cell measurement round robin

    NASA Technical Reports Server (NTRS)

    Mueller, R.

    1985-01-01

    The development of the capability for measurement under global irradiance spectral distribution is reported. The airmass 1.5 global measurement procedure is given. Also given is the procedure and justification for using the large area pulsed solar simulator (LAPSS). The status of the international round robin of reference cell measurements managed by the Commission of European Communities (CEC) is described.

  16. Nonalcoholic Fatty Liver Is Associated With Further Left Ventricular Abnormalities in Patients With Type 2 Diabetes Mellitus: A 3-Dimensional Speckle-Tracking Study.

    PubMed

    Wang, Qingqing; Ma, Wenyan; Xia, Jizhu

    2018-01-24

    The aim of this study was to detect left ventricular (LV) structure and function abnormalities in patients with type 2 diabetes mellitus with or without nonalcoholic fatty liver (NAFL) using 3-dimensional speckle-tracking echocardiography. Eighty patients with type 2 diabetes and a normal LV ejection fraction (≥55%), including 40 with coexistent NAFL, and 40 age- and sex-matched control participants were recruited. Conventional echocardiography and 3-dimensional speckle-tracking echocardiography were performed, and global longitudinal strain, global circumferential strain, global area strain, and global radial strain values were measured. Significant differences in 2-dimensional LV functional patterns were found among the 3 groups (P = .031), and LV hypertrophy was the most prevalent in patients with diabetes and NAFL. The patients with diabetes only had significantly lower global longitudinal strain, global circumferential strain, and global radial strain than the controls (all P < .05). The patients with diabetes and NAFL had severely lower global longitudinal strain, global circumferential strain, global area strain, and global radial strain than the controls (all P < .001), and they also had severely lower global longitudinal strain, global area strain, and global radial strain than the patients with diabetes only (all P < 0.001). The hemoglobin A 1c level and NAFL were independently associated with strain values in all patients with diabetes. The strain values in multiple directions (≥2 of global longitudinal, global circumferential, global area, and global radial strain) decreased significantly in the patients with diabetes and moderate and severe NAFL compared to those with mild NAFL (all P < .05). Nonalcoholic fatty liver could aggravate LV hypertrophy and dysfunction in patients with type 2 diabetes. The combined application of conventional and 3-dimensional speckle-tracking echocardiography could detect these asymptomatic preclinical abnormalities. © 2018 by the American Institute of Ultrasound in Medicine.

  17. Joint Geophysical Inversion With Multi-Objective Global Optimization Methods

    NASA Astrophysics Data System (ADS)

    Lelievre, P. G.; Bijani, R.; Farquharson, C. G.

    2015-12-01

    Pareto multi-objective global optimization (PMOGO) methods generate a suite of solutions that minimize multiple objectives (e.g. data misfits and regularization terms) in a Pareto-optimal sense. Providing a suite of models, as opposed to a single model that minimizes a weighted sum of objectives, allows a more complete assessment of the possibilities and avoids the often difficult choice of how to weight each objective. We are applying PMOGO methods to three classes of inverse problems. The first class are standard mesh-based problems where the physical property values in each cell are treated as continuous variables. The second class of problems are also mesh-based but cells can only take discrete physical property values corresponding to known or assumed rock units. In the third class we consider a fundamentally different type of inversion in which a model comprises wireframe surfaces representing contacts between rock units; the physical properties of each rock unit remain fixed while the inversion controls the position of the contact surfaces via control nodes. This third class of problem is essentially a geometry inversion, which can be used to recover the unknown geometry of a target body or to investigate the viability of a proposed Earth model. Joint inversion is greatly simplified for the latter two problem classes because no additional mathematical coupling measure is required in the objective function. PMOGO methods can solve numerically complicated problems that could not be solved with standard descent-based local minimization methods. This includes the latter two classes of problems mentioned above. There are significant increases in the computational requirements when PMOGO methods are used but these can be ameliorated using parallelization and problem dimension reduction strategies.

  18. Global rates of marine sulfate reduction and implications for sub-sea-floor metabolic activities

    NASA Astrophysics Data System (ADS)

    Bowles, Marshall W.; Mogollón, José M.; Kasten, Sabine; Zabel, Matthias; Hinrichs, Kai-Uwe

    2014-05-01

    Sulfate reduction is a globally important redox process in marine sediments, yet global rates are poorly quantified. We developed an artificial neural network trained with 199 sulfate profiles, constrained with geomorphological and geochemical maps to estimate global sulfate-reduction rate distributions. Globally, 11.3 teramoles of sulfate are reduced yearly (~15% of previous estimates), accounting for the oxidation of 12 to 29% of the organic carbon flux to the sea floor. Combined with global cell distributions in marine sediments, these results indicate a strong contrast in sub-sea-floor prokaryote habitats: In continental margins, global cell numbers in sulfate-depleted sediment exceed those in the overlying sulfate-bearing sediment by one order of magnitude, whereas in the abyss, most life occurs in oxic and/or sulfate-reducing sediments.

  19. Decoupling global biases and local interactions between cell biological variables

    PubMed Central

    Zaritsky, Assaf; Obolski, Uri; Gan, Zhuo; Reis, Carlos R; Kadlecova, Zuzana; Du, Yi; Schmid, Sandra L; Danuser, Gaudenz

    2017-01-01

    Analysis of coupled variables is a core concept of cell biological inference, with co-localization of two molecules as a proxy for protein interaction being a ubiquitous example. However, external effectors may influence the observed co-localization independently from the local interaction of two proteins. Such global bias, although biologically meaningful, is often neglected when interpreting co-localization. Here, we describe DeBias, a computational method to quantify and decouple global bias from local interactions between variables by modeling the observed co-localization as the cumulative contribution of a global and a local component. We showcase four applications of DeBias in different areas of cell biology, and demonstrate that the global bias encapsulates fundamental mechanistic insight into cellular behavior. The DeBias software package is freely accessible online via a web-server at https://debias.biohpc.swmed.edu. DOI: http://dx.doi.org/10.7554/eLife.22323.001 PMID:28287393

  20. Regulatory Insight into the European Human Pluripotent Stem Cell Registry

    PubMed Central

    Kurtz, Andreas; Stacey, Glyn; Kidane, Luam; Seriola, Anna; Stachelscheid, Harald; Veiga, Anna

    2014-01-01

    Abstract The European pluripotent stem cell registry aims at listing qualified pluripotent stem cell (PSC) lines that are available globally together with relevant information for each cell line. Specific emphasis is being put on documenting ethical procurement of the cells and providing evidence of pluripotency. The report discusses the tasks and challenges for a global PSC registry as an instrument to develop collaboration, to access cells from diverse resources and banks, and to implement standards, and as a means to follow up usage of cells and support adherence to regulatory and scientific standards and transparency for stakeholders. PMID:25457963

  1. Regulatory insight into the European human pluripotent stem cell registry.

    PubMed

    Kurtz, Andreas; Stacey, Glyn; Kidane, Luam; Seriola, Anna; Stachelscheid, Harald; Veiga, Anna

    2014-12-01

    The European pluripotent stem cell registry aims at listing qualified pluripotent stem cell (PSC) lines that are available globally together with relevant information for each cell line. Specific emphasis is being put on documenting ethical procurement of the cells and providing evidence of pluripotency. The report discusses the tasks and challenges for a global PSC registry as an instrument to develop collaboration, to access cells from diverse resources and banks, and to implement standards, and as a means to follow up usage of cells and support adherence to regulatory and scientific standards and transparency for stakeholders.

  2. The impact of global signal regression on resting state correlations: Are anti-correlated networks introduced?

    PubMed Central

    Murphy, Kevin; Birn, Rasmus M.; Handwerker, Daniel A.; Jones, Tyler B.; Bandettini, Peter A.

    2009-01-01

    Low-frequency fluctuations in fMRI signal have been used to map several consistent resting state networks in the brain. Using the posterior cingulate cortex as a seed region, functional connectivity analyses have found not only positive correlations in the default mode network but negative correlations in another resting state network related to attentional processes. The interpretation is that the human brain is intrinsically organized into dynamic, anti-correlated functional networks. Global variations of the BOLD signal are often considered nuisance effects and are commonly removed using a general linear model (GLM) technique. This global signal regression method has been shown to introduce negative activation measures in standard fMRI analyses. The topic of this paper is whether such a correction technique could be the cause of anti-correlated resting state networks in functional connectivity analyses. Here we show that, after global signal regression, correlation values to a seed voxel must sum to a negative value. Simulations also show that small phase differences between regions can lead to spurious negative correlation values. A combination breath holding and visual task demonstrates that the relative phase of global and local signals can affect connectivity measures and that, experimentally, global signal regression leads to bell-shaped correlation value distributions, centred on zero. Finally, analyses of negatively correlated networks in resting state data show that global signal regression is most likely the cause of anti-correlations. These results call into question the interpretation of negatively correlated regions in the brain when using global signal regression as an initial processing step. PMID:18976716

  3. The impact of global signal regression on resting state correlations: are anti-correlated networks introduced?

    PubMed

    Murphy, Kevin; Birn, Rasmus M; Handwerker, Daniel A; Jones, Tyler B; Bandettini, Peter A

    2009-02-01

    Low-frequency fluctuations in fMRI signal have been used to map several consistent resting state networks in the brain. Using the posterior cingulate cortex as a seed region, functional connectivity analyses have found not only positive correlations in the default mode network but negative correlations in another resting state network related to attentional processes. The interpretation is that the human brain is intrinsically organized into dynamic, anti-correlated functional networks. Global variations of the BOLD signal are often considered nuisance effects and are commonly removed using a general linear model (GLM) technique. This global signal regression method has been shown to introduce negative activation measures in standard fMRI analyses. The topic of this paper is whether such a correction technique could be the cause of anti-correlated resting state networks in functional connectivity analyses. Here we show that, after global signal regression, correlation values to a seed voxel must sum to a negative value. Simulations also show that small phase differences between regions can lead to spurious negative correlation values. A combination breath holding and visual task demonstrates that the relative phase of global and local signals can affect connectivity measures and that, experimentally, global signal regression leads to bell-shaped correlation value distributions, centred on zero. Finally, analyses of negatively correlated networks in resting state data show that global signal regression is most likely the cause of anti-correlations. These results call into question the interpretation of negatively correlated regions in the brain when using global signal regression as an initial processing step.

  4. Variations and determinants of carbon content in plants: a global synthesis

    NASA Astrophysics Data System (ADS)

    Ma, Suhui; He, Feng; Tian, Di; Zou, Dongting; Yan, Zhengbing; Yang, Yulong; Zhou, Tiancheng; Huang, Kaiyue; Shen, Haihua; Fang, Jingyun

    2018-02-01

    Plant carbon (C) content is one of the most important plant traits and is critical to the assessment of global C cycle and ecological stoichiometry; however, the global variations in plant C content remain poorly understood. In this study, we conducted a global analysis of the plant C content by synthesizing data from 4318 species to document specific values and their variation of the C content across plant organs and life forms. Plant organ C contents ranged from 45.0 % in reproductive organs to 47.9 % in stems at global scales, which were significantly lower than the widely employed canonical value of 50 %. Plant C content in leaves (global mean of 46.9 %) was higher than that in roots (45.6 %). Across life forms, woody plants exhibited higher C content than herbaceous plants. Conifers, relative to broad-leaved woody species, had higher C content in roots, leaves, and stems. Plant C content tended to show a decrease with increasing latitude. The life form explained more variation of the C content than climate. Our findings suggest that specific C content values of different organs and life forms developed in our study should be incorporated into the estimations of regional and global vegetation biomass C stocks.

  5. Opening our eyes to Global Health; a philosophy of universal values.

    PubMed

    Wass, Val

    2015-12-01

    Globalization is advancing at a pace. As we strive to introduce 'Global Health' into clinical curricula we risk fundamental misunderstandings unless we clearly define what we aim to achieve. Clinicians must be prepared for a life time of uncertainty, change and challenge. The fluctuating world arena will undoubtedly impact on their future work in ways we cannot predict. Population migration, climate change and shifts in cultural dominance are already at play. Global health risks being translated through the eyes of Western ideology as disease-based curricula focused paternalistically on 'helping' the developing world. We must not lack humility to open eyes to learning within the context of increasingly diverse environments and patient populations. Global health is as 'local' as it is 'international'. It should be viewed, I argue, as a philosophy based on the values and expectations found within ourselves and our communities. Responding to globalization lies not only in knowledge but embraces human rights, justice and, most importantly, self-awareness. Knowledge is more easily translated into curriculum objectives. We risk letting future clinicians and their patients down if we ignore the other universal values.

  6. Dynamic Modeling of the Human Coagulation Cascade Using Reduced Order Effective Kinetic Models (Open Access)

    DTIC Science & Technology

    2015-03-16

    shaded region around each total sensitivity value was the maximum uncertainty in that value estimated by the Sobol method. 2.4. Global Sensitivity...Performance We conducted a global sensitivity analysis, using the variance-based method of Sobol , to estimate which parameters controlled the...Hunter, J.D. Matplotlib: A 2D Graphics Environment. Comput. Sci. Eng. 2007, 9, 90–95. 69. Sobol , I. Global sensitivity indices for nonlinear

  7. The distribution of blood eosinophil levels in a Japanese COPD clinical trial database and in the rest of the world.

    PubMed

    Barnes, Neil; Ishii, Takeo; Hizawa, Nobuyuki; Midwinter, Dawn; James, Mark; Hilton, Emma; Jones, Paul W

    2018-01-01

    Blood eosinophil measurements may help to guide physicians on the use of inhaled corticosteroids (ICS) for patients with chronic obstructive pulmonary disease (COPD). Emerging data suggest that COPD patients with higher blood eosinophil counts may be at higher risk of exacerbations and more likely to benefit from combined ICS/long-acting beta 2 -agonist (LABA) treatment than therapy with a LABA alone. This analysis describes the distribution of blood eosinophil count at baseline in Japanese COPD patients in comparison with non-Japanese COPD patients. A post hoc analysis of eosinophil distribution by percentage and absolute cell count was performed across 12 Phase II-IV COPD clinical studies (seven Japanese studies [N=848 available absolute eosinophil counts] and five global studies [N=5,397 available eosinophil counts] that included 246 Japanese patients resident in Japan with available counts). Blood eosinophil distributions were assessed at baseline, before blinded treatment assignment. Among Japanese patients, the median (interquartile range) absolute eosinophil count was 170 cells/mm 3 (100-280 cells/mm 3 ). Overall, 612/1,094 Japanese patients (56%) had an absolute eosinophil count ≥150 cells/mm 3 and 902/1,304 Japanese patients (69%) had a percentage eosinophil ≥2%. Among non-Japanese patients, these values were 160 (100-250) cells/mm 3 , 2,842/5,151 patients (55%), and 2,937/5,155 patients (57%), respectively. The eosinophil distribution among Japanese patients was similar to that among non-Japanese patients. Within multi-country studies with similar inclusion criteria, the eosinophil count was numerically lower in Japanese compared with non-Japanese patients (median 120 vs 160 cells/mm 3 ). The eosinophil distribution in Japanese patients seems comparable to that of non-Japanese patients; although within multi-country studies, there was a slightly lower median eosinophil count for Japanese patients compared with non-Japanese patients. These findings suggest that blood eosinophil data from global studies are of relevance in Japan.

  8. Determining the longitudinal validity and meaningful differences in HRQL of the PedsQL™ Sickle Cell Disease Module.

    PubMed

    Panepinto, Julie A; Paul Scott, J; Badaki-Makun, Oluwakemi; Darbari, Deepika S; Chumpitazi, Corrie E; Airewele, Gladstone E; Ellison, Angela M; Smith-Whitley, Kim; Mahajan, Prashant; Sarnaik, Sharada A; Charles Casper, T; Cook, Larry J; Leonard, Julie; Hulbert, Monica L; Powell, Elizabeth C; Liem, Robert I; Hickey, Robert; Krishnamurti, Lakshmanan; Hillery, Cheryl A; Brousseau, David C

    2017-06-12

    Detecting change in health status over time and ascertaining meaningful changes are critical elements when using health-related quality of life (HRQL) instruments to measure patient-centered outcomes. The PedsQL™ Sickle Cell Disease module, a disease specific HRQL instrument, has previously been shown to be valid and reliable. Our objectives were to determine the longitudinal validity of the PedsQL™ Sickle Cell Disease module and the change in HRQL that is meaningful to patients. An ancillary study was conducted utilizing a multi-center prospective trial design. Children ages 4-21 years with sickle cell disease admitted to the hospital for an acute painful vaso-oclusive crisis were eligible. Children completed HRQL assessments at three time points (in the Emergency Department, one week post-discharge, and at return to baseline (One to three months post-discharge). The primary outcome was change in HRQL score. Both distribution (effect size, standard error of measurement (SEM)) and anchor (global change assessment) based methods were used to determine the longitudinal validity and meaningful change in HRQL. Changes in HRQL meaningful to patients were identified by anchoring the change scores to the patient's perception of global improvement in pain. Moderate effect sizes (0.20-0.80) were determined for all domains except the Communication I and Cognitive Fatigue domains. The value of 1 SEM varied from 3.8-14.6 across all domains. Over 50% of patients improved by at least 1 SEM in Total HRQL score. A HRQL change score of 7-10 in the pain domains represented minimal perceived improvement in HRQL and a HRQL change score of 18 or greater represented moderate to large improvement. The PedsQL™ Sickle Cell Disease Module is responsive to changes in HRQL in patients experiencing acute painful vaso-occlusive crises. The study data establish longitudinal validity and meaningful change parameters for the PedsQL™ Sickle Cell Disease Module. ClinicalTrials.gov (study identifier: NCT01197417 ). Date of registration: 08/30/2010.

  9. Functional neuroimaging in multiple sclerosis with radiolabelled glia markers: preliminary comparative PET studies with [11C]vinpocetine and [11C]PK11195 in patients.

    PubMed

    Vas, Adám; Shchukin, Yevgeni; Karrenbauer, Virginija D; Cselényi, Zsolt; Kostulas, Kosta; Hillert, Jan; Savic, Ivanka; Takano, Akihiro; Halldin, Christer; Gulyás, Balázs

    2008-01-15

    With the purpose of demonstrating the use of positron emission tomography (PET) and radiolabelled glia markers to indicate regional cerebral damage, we measured with PET in four young multiplex sclerosis (MS) patients in two consecutive measurements the global and regional brain uptake as well as regional distribution and binding potential (BP) of [(11)C]vinpocetine and [(11)C]PK11195. Both ligands showed increased uptake and BP in the regions of local brain damage. However, regional BP values for [(11)C]vinpocetine were markedly higher than those for [(11)C]PK11195. This feature of the former radioligand may be related to its high brain uptake and marked affinity to the peripheral benzodiazepine receptor binding sites (PBBS), characteristic for glia cells. As local brain traumas entail reactive glia accumulation in and around the site of the damage, the present findings may indicate that [(11)C]vinpocetine marks the place or boundaries of local brain damage by binding to the PBBS present in glia cells, which, in turn, accumulate in the region of the damage. The present findings (i) confirm earlier observations with [(11)C]PK11195 as a potential glia marker in PET studies and (ii) support the working hypothesis that [(11)C]vinpocetine is a potentially useful PET marker of regional and global brain damage resulting in glia accumulation locally or globally in the human brain. The comparative analysis of the two ligands indicate that [(11)C]vinpocetine shows a number of characteristics favourable in comparison with [(11)C]PK11195.

  10. Targeted Deletion and Lipidomic Analysis Identify Epithelial Cell COX-2 as a Major Driver of Chemically-induced Skin Cancer

    PubMed Central

    Jiao, Jing; Ishikawa, Tomo-o; Dumlao, Darren S.; Norris, Paul C.; Magyar, Clara E.; Mikulec, Carol; Catapang, Art; Dennis, Edward A.; Fischer, Susan M.; Herschman, Harvey R.

    2014-01-01

    Pharmacologic and global gene deletion studies demonstrate that cyclooxygenase-2 (PTGS2/COX2) plays a critical role in DMBA/TPA-induced skin tumor induction. While many cell types in the tumor microenvironment express COX-2, the cell types in which COX-2 expression is required for tumor promotion are not clearly established. Here, cell-type specific Cox-2 gene deletion reveals a vital role for skin epithelial cell COX-2 expression in DMBA/TPA tumor induction. In contrast, myeloid Cox-2 gene deletion has no effect on DMBA/TPA tumorigenesis. The infrequent, small tumors that develop on mice with an epithelial cell-specific Cox-2 gene deletion have decreased proliferation and increased cell differentiation properties. Blood vessel density is reduced in tumors with an epithelial cell-specific Cox-2 gene deletion, compared to littermate control tumors, suggesting a reciprocal relationship in tumor progression between COX-2 expressing tumor epithelial cells and microenvironment endothelial cells. Lipidomics analysis of skin and tumors from DMBA/TPA-treated mice suggests that the prostaglandins PGE2 and PGF2α are likely candidates for the epithelial cell COX-2-dependent eicosanoids that mediate tumor progression. This study both illustrates the value of cell-type specific gene deletions in understanding the cellular roles of signal-generating pathways in complex microenvironments and emphasizes the benefit of a systems-based lipidomic analysis approach to identify candidate lipid mediators of biological responses. PMID:25063587

  11. Field significance of performance measures in the context of regional climate model evaluation. Part 2: precipitation

    NASA Astrophysics Data System (ADS)

    Ivanov, Martin; Warrach-Sagi, Kirsten; Wulfmeyer, Volker

    2018-04-01

    A new approach for rigorous spatial analysis of the downscaling performance of regional climate model (RCM) simulations is introduced. It is based on a multiple comparison of the local tests at the grid cells and is also known as `field' or `global' significance. The block length for the local resampling tests is precisely determined to adequately account for the time series structure. New performance measures for estimating the added value of downscaled data relative to the large-scale forcing fields are developed. The methodology is exemplarily applied to a standard EURO-CORDEX hindcast simulation with the Weather Research and Forecasting (WRF) model coupled with the land surface model NOAH at 0.11 ∘ grid resolution. Daily precipitation climatology for the 1990-2009 period is analysed for Germany for winter and summer in comparison with high-resolution gridded observations from the German Weather Service. The field significance test controls the proportion of falsely rejected local tests in a meaningful way and is robust to spatial dependence. Hence, the spatial patterns of the statistically significant local tests are also meaningful. We interpret them from a process-oriented perspective. While the downscaled precipitation distributions are statistically indistinguishable from the observed ones in most regions in summer, the biases of some distribution characteristics are significant over large areas in winter. WRF-NOAH generates appropriate stationary fine-scale climate features in the daily precipitation field over regions of complex topography in both seasons and appropriate transient fine-scale features almost everywhere in summer. As the added value of global climate model (GCM)-driven simulations cannot be smaller than this perfect-boundary estimate, this work demonstrates in a rigorous manner the clear additional value of dynamical downscaling over global climate simulations. The evaluation methodology has a broad spectrum of applicability as it is distribution-free, robust to spatial dependence, and accounts for time series structure.

  12. On the global "two-sided" characteristic Cauchy problem for linear wave equations on manifolds

    NASA Astrophysics Data System (ADS)

    Lupo, Umberto

    2018-04-01

    The global characteristic Cauchy problem for linear wave equations on globally hyperbolic Lorentzian manifolds is examined, for a class of smooth initial value hypersurfaces satisfying favourable global properties. First it is shown that, if geometrically well-motivated restrictions are placed on the supports of the (smooth) initial datum and of the (smooth) inhomogeneous term, then there exists a continuous global solution which is smooth "on each side" of the initial value hypersurface. A uniqueness result in Sobolev regularity H^{1/2+ɛ }_{loc} is proved among solutions supported in the union of the causal past and future of the initial value hypersurface, and whose product with the indicator function of the causal future (resp. past) of the hypersurface is past compact (resp. future compact). An explicit representation formula for solutions is obtained, which prominently features an invariantly defined, densitised version of the null expansion of the hypersurface. Finally, applications to quantum field theory on curved spacetimes are briefly discussed.

  13. Contract Research Organizations (CROs) in China: integrating Chinese research and development capabilities for global drug innovation.

    PubMed

    Shi, Yun-Zhen; Hu, Hao; Wang, Chunming

    2014-11-19

    The significance of R&D capabilities of China has become increasingly important as an emerging force in the context of globalization of pharmaceutical research and development (R&D). While China has prospered in its R&D capability in the past decade, how to integrate the rising pharmaceutical R&D capability of China into the global development chain for innovative drugs remains challenging. For many multinational corporations and research organizations overseas, their attempt to integrate China's pharmaceutical R&D capabilities into their own is always hindered by policy constraints and reluctance of local universities and pharmaceutical firms. In light of the situation, contract research organizations (CROs) in China have made great innovation in value proposition, value chain and value networking to be at a unique position to facilitate global and local R&D integration. Chinese CROs are now being considered as the essentially important and highly versatile integrator of local R&D capability for global drug discovery and innovation.

  14. Benefits of rebuilding global marine fisheries outweigh costs.

    PubMed

    Sumaila, Ussif Rashid; Cheung, William; Dyck, Andrew; Gueye, Kamal; Huang, Ling; Lam, Vicky; Pauly, Daniel; Srinivasan, Thara; Swartz, Wilf; Watson, Reginald; Zeller, Dirk

    2012-01-01

    Global marine fisheries are currently underperforming, largely due to overfishing. An analysis of global databases finds that resource rent net of subsidies from rebuilt world fisheries could increase from the current negative US$13 billion to positive US$54 billion per year, resulting in a net gain of US$600 to US$1,400 billion in present value over fifty years after rebuilding. To realize this gain, governments need to implement a rebuilding program at a cost of about US$203 (US$130-US$292) billion in present value. We estimate that it would take just 12 years after rebuilding begins for the benefits to surpass the cost. Even without accounting for the potential boost to recreational fisheries, and ignoring ancillary and non-market values that would likely increase, the potential benefits of rebuilding global fisheries far outweigh the costs.

  15. Benefits of Rebuilding Global Marine Fisheries Outweigh Costs

    PubMed Central

    Sumaila, Ussif Rashid; Cheung, William; Dyck, Andrew; Gueye, Kamal; Huang, Ling; Lam, Vicky; Pauly, Daniel; Srinivasan, Thara; Swartz, Wilf; Watson, Reginald; Zeller, Dirk

    2012-01-01

    Global marine fisheries are currently underperforming, largely due to overfishing. An analysis of global databases finds that resource rent net of subsidies from rebuilt world fisheries could increase from the current negative US$13 billion to positive US$54 billion per year, resulting in a net gain of US$600 to US$1,400 billion in present value over fifty years after rebuilding. To realize this gain, governments need to implement a rebuilding program at a cost of about US$203 (US$130–US$292) billion in present value. We estimate that it would take just 12 years after rebuilding begins for the benefits to surpass the cost. Even without accounting for the potential boost to recreational fisheries, and ignoring ancillary and non-market values that would likely increase, the potential benefits of rebuilding global fisheries far outweigh the costs. PMID:22808187

  16. Valuing a Global Environmental Good: U.S. Residents' Willingness to Pay to Protect Tropical Rain Forests

    Treesearch

    Randall A. Kramer; D. Evan Mercer

    1997-01-01

    (CV) is the most common technique for valuing nonmarket environmental resources, rarely has it been applied to global environmental goods. This study uses CV in a national survey to assess the value U.S. residents place on tropical rain forest protection. On average, respondents were willing to make a one-time payment of approximately $21-31 per household to protect an...

  17. Testing the Efficacy of Global Biodiversity Hotspots for Insect Conservation: The Case of South African Katydids.

    PubMed

    Bazelet, Corinna S; Thompson, Aileen C; Naskrecki, Piotr

    2016-01-01

    The use of endemism and vascular plants only for biodiversity hotspot delineation has long been contested. Few studies have focused on the efficacy of global biodiversity hotspots for the conservation of insects, an important, abundant, and often ignored component of biodiversity. We aimed to test five alternative diversity measures for hotspot delineation and examine the efficacy of biodiversity hotspots for conserving a non-typical target organism, South African katydids. Using a 1° fishnet grid, we delineated katydid hotspots in two ways: (1) count-based: grid cells in the top 10% of total, endemic, threatened and/or sensitive species richness; vs. (2) score-based: grid cells with a mean value in the top 10% on a scoring system which scored each species on the basis of its IUCN Red List threat status, distribution, mobility and trophic level. We then compared katydid hotspots with each other and with recognized biodiversity hotspots. Grid cells within biodiversity hotspots had significantly higher count-based and score-based diversity than non-hotspot grid cells. There was a significant association between the three types of hotspots. Of the count-based measures, endemic species richness was the best surrogate for the others. However, the score-based measure out-performed all count-based diversity measures. Species richness was the least successful surrogate of all. The strong performance of the score-based method for hotspot prediction emphasizes the importance of including species' natural history information for conservation decision-making, and is easily adaptable to other organisms. Furthermore, these results add empirical support for the efficacy of biodiversity hotspots in conserving non-target organisms.

  18. Gene expression, signal transduction pathways and functional networks associated with growth of sporadic vestibular schwannomas.

    PubMed

    Sass, Hjalte C R; Borup, Rehannah; Alanin, Mikkel; Nielsen, Finn Cilius; Cayé-Thomasen, Per

    2017-01-01

    The objective of this study was to determine global gene expression in relation to Vestibular schwannomas (VS) growth rate and to identify signal transduction pathways and functional molecular networks associated with growth. Repeated magnetic resonance imaging (MRI) prior to surgery determined tumor growth rate. Following tissue sampling during surgery, mRNA was extracted from 16 sporadic VS. Double stranded cDNA was synthesized from the mRNA and used as template for in vitro transcription reaction to synthesize biotin-labeled antisense cRNA, which was hybridized to Affymetrix HG-U133A arrays and analyzed by dChip software. Differential gene expression was defined as a 1.5-fold difference between fast and slow growing tumors (><0.5 ccm/year), employing a p-value <0.01. Deregulated transcripts were matched against established gene ontology. Ingenuity Pathway Analysis was used for identification of signal transduction pathways and functional molecular networks associated with tumor growth. In total 109 genes were deregulated in relation to tumor growth rate. Genes associated with apoptosis, growth and cell proliferation were deregulated. Gene ontology included regulation of the cell cycle, cell differentiation and proliferation, among other functions. Fourteen pathways were associated with tumor growth. Five functional molecular networks were generated. This first study on global gene expression in relation to vestibular schwannoma growth rate identified several genes, signal transduction pathways and functional networks associated with tumor progression. Specific genes involved in apoptosis, cell growth and proliferation were deregulated in fast growing tumors. Fourteen pathways were associated with tumor growth. Generated functional networks underlined the importance of the PI3K family, among others.

  19. Testing the Efficacy of Global Biodiversity Hotspots for Insect Conservation: The Case of South African Katydids

    PubMed Central

    Bazelet, Corinna S.; Thompson, Aileen C.; Naskrecki, Piotr

    2016-01-01

    The use of endemism and vascular plants only for biodiversity hotspot delineation has long been contested. Few studies have focused on the efficacy of global biodiversity hotspots for the conservation of insects, an important, abundant, and often ignored component of biodiversity. We aimed to test five alternative diversity measures for hotspot delineation and examine the efficacy of biodiversity hotspots for conserving a non-typical target organism, South African katydids. Using a 1° fishnet grid, we delineated katydid hotspots in two ways: (1) count-based: grid cells in the top 10% of total, endemic, threatened and/or sensitive species richness; vs. (2) score-based: grid cells with a mean value in the top 10% on a scoring system which scored each species on the basis of its IUCN Red List threat status, distribution, mobility and trophic level. We then compared katydid hotspots with each other and with recognized biodiversity hotspots. Grid cells within biodiversity hotspots had significantly higher count-based and score-based diversity than non-hotspot grid cells. There was a significant association between the three types of hotspots. Of the count-based measures, endemic species richness was the best surrogate for the others. However, the score-based measure out-performed all count-based diversity measures. Species richness was the least successful surrogate of all. The strong performance of the score-based method for hotspot prediction emphasizes the importance of including species’ natural history information for conservation decision-making, and is easily adaptable to other organisms. Furthermore, these results add empirical support for the efficacy of biodiversity hotspots in conserving non-target organisms. PMID:27631131

  20. How Philip Morris built Marlboro into a global brand for young adults: implications for international tobacco control

    PubMed Central

    Hafez, N; Ling, P

    2005-01-01

    Objective: To describe Philip Morris' global market research and international promotional strategies targeting young adults. Methods: : Analysis of previously secret tobacco industry documents. Results: Philip Morris pursued standardised market research and strategic marketing plans in different regions throughout the world using research on young adults with three principle foci: lifestyle/psychographic research, brand studies, and advertising/communication effectiveness. Philip Morris identified core similarities in the lifestyles and needs of young consumers worldwide, such as independence, hedonism, freedom, and comfort. In the early 1990s Philip Morris adopted standardised global marketing efforts, creating a central advertising production bank and guidelines for brand images and promotions, but allowing regional managers to create regionally appropriate individual advertisements. Conclusions: Values and lifestyles play a central role in the global marketing of tobacco to young adults. Worldwide counter marketing initiatives, coupled with strong, coherent global marketing policies such as the Framework Convention on Tobacco Control, are needed to break associations between young adult values and tobacco brands. As globalisation promotes the homogenisation of values and lifestyles, tobacco control messages that resonate with young adults in one part of the world may appeal to young adults in other countries. Successful tobacco control messages that appeal to young people, such as industry denormalisation, may be expanded globally with appropriate tailoring to appeal to regional values. PMID:16046690

  1. An easy-to-parameterise physics-informed battery model and its application towards lithium-ion battery cell design, diagnosis, and degradation

    NASA Astrophysics Data System (ADS)

    Merla, Yu; Wu, Billy; Yufit, Vladimir; Martinez-Botas, Ricardo F.; Offer, Gregory J.

    2018-04-01

    Accurate diagnosis of lithium ion battery state-of-health (SOH) is of significant value for many applications, to improve performance, extend life and increase safety. However, in-situ or in-operando diagnosis of SOH often requires robust models. There are many models available however these often require expensive-to-measure ex-situ parameters and/or contain unmeasurable parameters that were fitted/assumed. In this work, we have developed a new empirically parameterised physics-informed equivalent circuit model. Its modular construction and low-cost parametrisation requirements allow end users to parameterise cells quickly and easily. The model is accurate to 19.6 mV for dynamic loads without any global fitting/optimisation, only that of the individual elements. The consequences of various degradation mechanisms are simulated, and the impact of a degraded cell on pack performance is explored, validated by comparison with experiment. Results show that an aged cell in a parallel pack does not have a noticeable effect on the available capacity of other cells in the pack. The model shows that cells perform better when electrodes are more porous towards the separator and have a uniform particle size distribution, validated by comparison with published data. The model is provided with this publication for readers to use.

  2. Swimming Motility Reduces Deposition to Silica Surfaces

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lu, Nanxi; Massoudieh, Arash; Liang, Xiaomeng

    The role of swimming motility on bacterial transport and fate in porous media was evaluated. We present microscopic evidence showing that strong swimming motility reduces attachment of Azotobacter vinelandii cells to silica surfaces. Applying global and cluster statistical analyses to microscopic videos taken under non-flow conditions, wild type, flagellated A. vinelandii strain DJ showed strong swimming ability with an average speed of 13.1 μm/s, DJ77 showed impaired swimming averaged at 8.7 μm/s, and both the non-flagellated JZ52 and chemically treated DJ cells were non-motile. Quantitative analyses of trajectories observed at different distances above the collector of a radial stagnation pointmore » flow cell (RSPF) revealed that both swimming and non-swimming cells moved with the flow when at a distance of at least 20 μm from the collector surface. Near the surface, DJ cells showed both horizontal and vertical movement diverging them from reaching surfaces, while chemically treated DJ cells moved with the flow to reach surfaces, suggesting that strong swimming reduced attachment. In agreement with the RSPF results, the deposition rates obtained for two-dimensional multiple-collector micromodels were also lowest for DJ, while DJ77 and JZ52 showed similar values. Strong swimming specifically reduced deposition on the upstream surfaces of the micromodel collectors.« less

  3. Assessing the sensitivity of coral reef condition indicators to local and global stressors with Bayesian networks

    EPA Science Inventory

    Coral reefs are highly valued ecosystems that are currently imperiled. Although the value of coral reefs to human societies is only just being investigated and better understood, for many local and global economies coral reefs are important providers of ecosystem services that su...

  4. Collaboration, Innovation, and Value Creation in a Global Telecom

    ERIC Educational Resources Information Center

    Allee, Verna; Taug, Jan

    2006-01-01

    Purpose: The purpose of this paper is to review a systemic organizational change initiative for improving collaboration, innovation and value creation at a global telecom. Design/methodology/approach: Based on a comprehensive internal assessment Telenor identified core issues and challenges in supporting collaboration after several years of…

  5. Tired telomeres: Poor global sleep quality, perceived stress, and telomere length in immune cell subsets in obese men and women.

    PubMed

    Prather, Aric A; Gurfein, Blake; Moran, Patricia; Daubenmier, Jennifer; Acree, Michael; Bacchetti, Peter; Sinclair, Elizabeth; Lin, Jue; Blackburn, Elizabeth; Hecht, Frederick M; Epel, Elissa S

    2015-07-01

    Poor sleep quality and short sleep duration are associated with increased incidence and progression of a number of chronic health conditions observed at greater frequency among the obese and those experiencing high levels of stress. Accelerated cellular aging, as indexed by telomere attrition in immune cells, is a plausible pathway linking sleep and disease risk. Prior studies linking sleep and telomere length are mixed. One factor may be reliance on leukocytes, which are composed of varied immune cell types, as the sole measure of telomere length. To better clarify these associations, we investigated the relationships of global sleep quality, measured by the Pittsburgh Sleep Quality Index (PSQI), and diary-reported sleep duration with telomere length in different immune cell subsets, including granulocytes, peripheral blood mononuclear cells (PBMCs), CD8+ and CD4+ T lymphocytes, and B lymphocytes in a sample of 87 obese men and women (BMI mean=35.4, SD=3.6; 81.6% women; 62.8% Caucasian). Multiple linear regression analyses were performed adjusting for age, gender, race, education, BMI, sleep apnea risk, and perceived stress. Poorer PSQI global sleep quality was associated with statistically significantly shorter telomere length in lymphocytes but not granulocytes and in particular CD8+ T cells (b=-56.8 base pairs per one point increase in PSQI, SE=20.4, p=0.007) and CD4+ T cells (b=-37.2, SE=15.9, p=0.022). Among separate aspects of global sleep quality, low perceived sleep quality and decrements in daytime function were most related to shorter telomeres. In addition, perceived stress moderated the sleep-CD8+ telomere association. Poorer global sleep quality predicted shorter telomere length in CD8+ T cells among those with high perceived stress but not in low stress participants. These findings provide preliminary evidence that poorer global sleep quality is related to telomere length in several immune cell types, which may serve as a pathway linking sleep and disease risk in obese individuals. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Designing Training for Global Environments: Knowing What Questions To Ask.

    ERIC Educational Resources Information Center

    Gayeski, Diane M.; Sanchirico, Christine; Anderson, Janet

    2002-01-01

    Presents a framework for identifying important issues for instructional design and delivery in global settings. Highlights include cultural factors in global training; an instructional design model; corporate globalization strategy; communication and training norms; language barriers; implicit value differences; and technical and legal…

  7. Global Health in the Anthropocene: Moving Beyond Resilience and Capitalism

    PubMed Central

    van de Pas, Remco

    2017-01-01

    There has been much reflection on the need for a new understanding of global health and the urgency of a paradigm shift to address global health issues. A crucial question is whether this is still possible in current modes of global governance based on capitalist values. Four reflections are provided. (1) Ecological –centered values must become central in any future global health framework. (2) The objectives of ‘sustainability’ and ‘economic growth’ present a profound contradiction. (3) The resilience discourse maintains a gridlock in the functioning of the global health system. (4) The legitimacy of multi-stakeholder governance arrangements in global health requires urgent attention. A dual track approach is suggested. It must be aimed to transform capitalism into something better for global health while in parallel there is an urgent need to imagine a future and pathways to a different world order rooted in the principles of social justice, protecting the commons and a central role for the preservation of ecology. PMID:28812849

  8. Global Identification of Disease Associated Genes in Fragile X Cells

    DTIC Science & Technology

    2016-08-01

    for this study listed as follows: 1) Validate the co-localized R-loop formation and chromosome fragility in Fragile X cells, particularly at the brain ...retardation protein February 2016, NGS Data Analysis & Informatics Conference, San Diego, California (Poster presentation) Title: Global detection

  9. Expression profiling of the mouse early embryo: Reflections and Perspectives

    PubMed Central

    Ko, Minoru S. H.

    2008-01-01

    Laboratory mouse plays important role in our understanding of early mammalian development and provides invaluable model for human early embryos, which are difficult to study for ethical and technical reasons. Comprehensive collection of cDNA clones, their sequences, and complete genome sequence information, which have been accumulated over last two decades, have provided even more advantages to mouse models. Here the progress in global gene expression profiling in early mouse embryos and, to some extent, stem cells are reviewed and the future directions and challenges are discussed. The discussions include the restatement of global gene expression profiles as snapshot of cellular status, and subsequent distinction between the differentiation state and physiological state of the cells. The discussions then extend to the biological problems that can be addressed only through global expression profiling, which include: bird’s-eye view of global gene expression changes, molecular index for developmental potency, cell lineage trajectory, microarray-guided cell manipulation, and the possibility of delineating gene regulatory cascades and networks. PMID:16739220

  10. Global Representations of Goal-Directed Behavior in Distinct Cell Types of Mouse Neocortex

    PubMed Central

    Allen, William E.; Kauvar, Isaac V.; Chen, Michael Z.; Richman, Ethan B.; Yang, Samuel J.; Chan, Ken; Gradinaru, Viviana; Deverman, Benjamin E.; Luo, Liqun; Deisseroth, Karl

    2017-01-01

    SUMMARY The successful planning and execution of adaptive behaviors in mammals may require long-range coordination of neural networks throughout cerebral cortex. The neuronal implementation of signals that could orchestrate cortex-wide activity remains unclear. Here, we develop and apply methods for cortex-wide Ca2+ imaging in mice performing decision-making behavior and identify a global cortical representation of task engagement encoded in the activity dynamics of both single cells and superficial neuropil distributed across the majority of dorsal cortex. The activity of multiple molecularly defined cell types was found to reflect this representation with type-specific dynamics. Focal optogenetic inhibition tiled across cortex revealed a crucial role for frontal cortex in triggering this cortex-wide phenomenon; local inhibition of this region blocked both the cortex-wide response to task-initiating cues and the voluntary behavior. These findings reveal cell-type-specific processes in cortex for globally representing goal-directed behavior and identify a major cortical node that gates the global broadcast of task-related information. PMID:28521139

  11. The dependence of the oceans MOC on mesoscale eddy diffusivities: A model study

    NASA Technical Reports Server (NTRS)

    Marshall, John; Scott, Jeffery R.; Romanou, Anastasia; Kelley, Maxwell; Leboissetier, Anthony

    2017-01-01

    The dependence of the depth and strength of the ocean's global meridional overturning cells (MOC) on the specification of mesoscale eddy diffusivity (K) is explored in two ocean models. The GISS and MIT ocean models are driven by the same prescribed forcing fields, configured in similar ways, spun up to equilibrium for a range of K 's and the resulting MOCs mapped and documented. Scaling laws implicit in modern theories of the MOC are used to rationalize the results. In all calculations the K used in the computation of eddy-induced circulation and that used in the representation of eddy stirring along neutral surfaces, is set to the same value but is changed across experiments. We are able to connect changes in the strength and depth of the Atlantic MOC, the southern ocean upwelling MOC, and the deep cell emanating from Antarctica, to changes in K.

  12. Attitude towards technology, social media usage and grade-point average as predictors of global citizenship identification in Filipino University Students.

    PubMed

    Lee, Romeo B; Baring, Rito; Maria, Madelene Sta; Reysen, Stephen

    2017-06-01

    We examine the influence of a positive attitude towards technology, number of social media network memberships and grade-point average (GPA) on global citizenship identification antecedents and outcomes. Students (N = 3628) at a university in the Philippines completed a survey assessing the above constructs. The results showed that attitude towards technology, number of social network site memberships and GPA-predicted global citizenship identification, and subsequent prosocial outcomes (e.g. intergroup helping, responsibility to act for the betterment of the world), through the perception that valued others prescribe a global citizen identity (normative environment) and perceived knowledge of the world and felt interconnectedness with others (global awareness). The results highlight the associations between technology and academic performance with a global identity and associated values. © 2015 International Union of Psychological Science.

  13. Early In Vitro Differentiation of Mouse Definitive Endoderm Is Not Correlated with Progressive Maturation of Nuclear DNA Methylation Patterns

    PubMed Central

    Tajbakhsh, Jian; Gertych, Arkadiusz; Fagg, W. Samuel; Hatada, Seigo; Fair, Jeffrey H.

    2011-01-01

    The genome organization in pluripotent cells undergoing the first steps of differentiation is highly relevant to the reprogramming process in differentiation. Considering this fact, chromatin texture patterns that identify cells at the very early stage of lineage commitment could serve as valuable tools in the selection of optimal cell phenotypes for regenerative medicine applications. Here we report on the first-time use of high-resolution three-dimensional fluorescence imaging and comprehensive topological cell-by-cell analyses with a novel image-cytometrical approach towards the identification of in situ global nuclear DNA methylation patterns in early endodermal differentiation of mouse ES cells (up to day 6), and the correlations of these patterns with a set of putative markers for pluripotency and endodermal commitment, and the epithelial and mesenchymal character of cells. Utilizing this in vitro cell system as a model for assessing the relationship between differentiation and nuclear DNA methylation patterns, we found that differentiating cell populations display an increasing number of cells with a gain in DNA methylation load: first within their euchromatin, then extending into heterochromatic areas of the nucleus, which also results in significant changes of methylcytosine/global DNA codistribution patterns. We were also able to co-visualize and quantify the concomitant stochastic marker expression on a per-cell basis, for which we did not measure any correlation to methylcytosine loads or distribution patterns. We observe that the progression of global DNA methylation is not correlated with the standard transcription factors associated with endodermal development. Further studies are needed to determine whether the progression of global methylation could represent a useful signature of cellular differentiation. This concept of tracking epigenetic progression may prove useful in the selection of cell phenotypes for future regenerative medicine applications. PMID:21779341

  14. A database of global marine commercial, small-scale, illegal and unreported fisheries catch 1950-2014

    NASA Astrophysics Data System (ADS)

    Watson, Reg A.

    2017-04-01

    Global fisheries landings data from a range of public sources was harmonised and mapped to 30-min spatial cells based on the distribution of the reported taxa and the fishing fleets involved. This data was extended to include the associated fishing gear used, as well as estimates of illegal, unregulated and unreported catch (IUU) and discards at sea. Expressed as catch rates, these results also separated small-scale fisheries from other fishing operations. The dataset covers 1950 to 2014 inclusive. Mapped catch allows study of the impacts of fisheries on habitats and fauna, on overlap with the diets of marine birds and mammals, and on the related use of fuels and release of greenhouse gases. The fine-scale spatial data can be aggregated to the exclusive economic zone claims of countries and will allow study of the value of landed marine products to their economies and food security, and to those of their trading partners.

  15. A database of global marine commercial, small-scale, illegal and unreported fisheries catch 1950-2014.

    PubMed

    Watson, Reg A

    2017-04-11

    Global fisheries landings data from a range of public sources was harmonised and mapped to 30-min spatial cells based on the distribution of the reported taxa and the fishing fleets involved. This data was extended to include the associated fishing gear used, as well as estimates of illegal, unregulated and unreported catch (IUU) and discards at sea. Expressed as catch rates, these results also separated small-scale fisheries from other fishing operations. The dataset covers 1950 to 2014 inclusive. Mapped catch allows study of the impacts of fisheries on habitats and fauna, on overlap with the diets of marine birds and mammals, and on the related use of fuels and release of greenhouse gases. The fine-scale spatial data can be aggregated to the exclusive economic zone claims of countries and will allow study of the value of landed marine products to their economies and food security, and to those of their trading partners.

  16. Analysis of spatial patterns underlying the linkage between solar irradiance and near-surface air temperatures

    NASA Astrophysics Data System (ADS)

    Balling, Robert C.; Roy, Shouraseni Sen

    2005-06-01

    Many scientists have noted that global temperature anomalies were highly correlated with solar irradiance values until sometime in the 1970s, but since that time, the pronounced warming in the near-surface temperature record is not explained by variations or trends in solar receipt. In this investigation, spatial dimensions are explored in the relationship between irradiance and near-surface air temperatures. At the scale of individual 5° by 5° grid cells, the solar control on annual temperature variations is not statistically significant. When the temperature data are aggregated by 5° latitudinal bands, the solar - temperature connect is generally significant, and in every band, there is substantial evidence that a non-solar control has become dominant in recent decades. The buildup of greenhouse gases and/or some other global-scale feedback, such as widespread changes in atmospheric water vapor, emerge as potential explanations for the recent residual warming found in all latitudinal bands.

  17. A database of global marine commercial, small-scale, illegal and unreported fisheries catch 1950–2014

    PubMed Central

    Watson, Reg A.

    2017-01-01

    Global fisheries landings data from a range of public sources was harmonised and mapped to 30-min spatial cells based on the distribution of the reported taxa and the fishing fleets involved. This data was extended to include the associated fishing gear used, as well as estimates of illegal, unregulated and unreported catch (IUU) and discards at sea. Expressed as catch rates, these results also separated small-scale fisheries from other fishing operations. The dataset covers 1950 to 2014 inclusive. Mapped catch allows study of the impacts of fisheries on habitats and fauna, on overlap with the diets of marine birds and mammals, and on the related use of fuels and release of greenhouse gases. The fine-scale spatial data can be aggregated to the exclusive economic zone claims of countries and will allow study of the value of landed marine products to their economies and food security, and to those of their trading partners. PMID:28398351

  18. Global warming and neurodegenerative disorders: speculations on their linkage.

    PubMed

    Habibi, Laleh; Perry, George; Mahmoudi, Morteza

    2014-01-01

    Climate change is having considerable impact on biological systems. Eras of ice ages and warming shaped the contemporary earth and origin of creatures including humans. Warming forces stress conditions on cells. Therefore, cells evolved elaborate defense mechanisms, such as creation of heat shock proteins, to combat heat stress. Global warming is becoming a crisis and this process would yield an undefined increasing rate of neurodegenerative disorders in future decades. Since heat stress is known to have a degenerative effects on neurons and, conversely, cold conditions have protective effect on these cells, we hypothesize that persistent heat stress forced by global warming might play a crucial role in increasing neurodegenerative disorders.

  19. Value Assessment at the Point of Care: Incorporating Patient Values throughout Care Delivery and a Draft Taxonomy of Patient Values.

    PubMed

    Armstrong, Melissa J; Mullins, C Daniel

    2017-02-01

    Incorporation of patient values is a key element of patient-centered care, but consistent incorporation of patient values at the point of care is lacking. Shared decision making encourages incorporation of patient values in decision making, but associated tools often lack guidance on value assessment. In addition, focusing on patient values relating only to specific decisions misses an opportunity for a more holistic approach to value assessment that could impact other aspects of clinical encounters, including health care planning, communication, and stakeholder involvement. In this commentary, we propose a taxonomy of values underlying patient decision making and provide examples of how these impact provision of health care. The taxonomy describes four categories of patient values: global, decisional, situational, and external. Global values are personal values impacting decision making at a universal level and can include value traits and life priorities. Decisional values are the values traditionally conceptualized in decision making, including considerations such as efficacy, toxicity, quality of life, convenience, and cost. Situational values are values tied to a specific moment in time that modify patients' existing global and decisional values. Finally, discussion of external values acknowledges that many patients consider values other than their own when making decisions. Recognizing the breadth of values impacting patient decision making has implications for both overall health care delivery and shared decision making because value assessments focusing only on decisional values may miss important patient considerations. This draft taxonomy highlights different values impacting decision making and facilitates a more complete value assessment at the point of care. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  20. Fermionic vacuum polarization in a higher-dimensional global monopole spacetime

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bezerra de Mello, E. R.

    2007-12-15

    In this paper we analyze the vacuum polarization effects associated with a massless fermionic field in a higher-dimensional global monopole spacetime in the 'braneworld' scenario. In this context we admit that our Universe, the bulk, is represented by a flat (n-1)-dimensional brane having a global monopole in an extra transverse three-dimensional submanifold. We explicitly calculate the renormalized vacuum average of the energy-momentum tensor, {sub Ren}, admitting the global monopole as being a pointlike object. We observe that this quantity depends crucially on the value of n, and provide explicit expressions to it for specific values attributed to n.

  1. Value-based formulas for purchasing. PEHP's designated service provider program: value-based purchasing through global fees.

    PubMed

    Emery, D W

    1997-01-01

    In many circles, managed care and capitation have become synonymous; unfortunately, the assumptions informing capitation are based on a flawed unidimensional model of risk. PEHP of Utah has rejected the unidimensional model and has therefore embraced a multidimensional model of risk that suggests that global fees are the optimal purchasing modality. A globally priced episode of care forms a natural unit of analysis that enhances purchasing clarity, allows providers to more efficiently focus on the Marginal Rate of Technical Substitution, and conforms to the multidimensional reality of risk. Most importantly, global fees simultaneously maximize patient choice and provider cost consciousness.

  2. Temporal Fourier analysis applied to equilibrium radionuclide cineangiography. Importance in the study of global and regional left ventricular wall motion.

    PubMed

    Cardot, J C; Berthout, P; Verdenet, J; Bidet, A; Faivre, R; Bassand, J P; Bidet, R; Maurat, J P

    1982-01-01

    Regional and global left ventricular wall motion was assessed in 120 patients using radionuclide cineangiography (RCA) and contrast angiography. Functional imaging procedures based on a temporal Fourier analysis of dynamic image sequences were applied to the study of cardiac contractility. Two images were constructed by taking the phase and amplitude values of the first harmonic in the Fourier transform for each pixel. These two images aided in determining the perimeter of the left ventricle to calculate the global ejection fraction. Regional left ventricular wall motion was studied by analyzing the phase value and by examining the distribution histogram of these values. The accuracy of global ejection fraction calculation was improved by the Fourier technique. This technique increased the sensitivity of RCA for determining segmental abnormalities especially in the left anterior oblique view (LAO).

  3. Comparison of Water Vapor Measurements from Ground-based and Space-based GPS Atmospheric Remote Sensing Techniques

    NASA Astrophysics Data System (ADS)

    Colon-Pagan, Ian; Kuo, Ying-Hwa

    2008-10-01

    In this study, we compare precipitable water vapor (PWV) values from ground-based GPS water vapor sensing and COSMIC radio occultation (RO) measurements over the Caribbean Sea, Gulf of Mexico, and United States regions as well as global analyses from NCEP and ECMWF models. The results show good overall agreement; however, the PWV values estimated by ground-based GPS receivers tend to have a slight dry bias for low PWV values and a slight wet bias for higher PWV values, when compared with GPS RO measurements and global analyses. An application of a student T-test indicates that there is a significant difference between both ground- and space-based GPS measured datasets. The dry bias associated with space-based GPS is attributed to the missing low altitude data, where the concentration of water vapor is large. The close agreements between space-based and global analyses are due to the fact that these global analyses assimilate space-based GPS RO data from COSMIC, and the retrieval of water vapor profiles from space-based technique requires the use of global analyses as the first guess. This work is supported by UCAR SOARS and a grant from the National Oceanic and Atmospheric Administration, Educational Partnership Program under the cooperative agreement NA06OAR4810187.

  4. Global estimate of net annual carbon flow to phenylpropanoid metabolism

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Walton, A.B.; Norman, E.G.; Turpin, D.H.

    1993-05-01

    The steady increase in the concentration of CO[sub 2] in the atmosphere is the focus of renewed interest in the global carbon cycle. Current research is centered upon modeling the effects of the increasing CO[sub 2] concentrations, and thus global warning, on global plant homeostasis. It has been estimated that the annual net primary production (NPP) values for terrestrial and oceanic biomes are 59.9 and 35 Pg C-yr[sup [minus]1], respectively (Melillo et al., 1990). Based on these NPP values, we have estimated the annual C flow to phenlpropanoid metabolism. In our calculation, lignin was used as a surrogate for phenylpropanoidmore » compounds, as lignin is the second most abundant plant polymer. This approach means that our estimate defines the lower limit of C flow to phenylpropanoid metabolism. Each biome was considered separately to determine the percent of the NPP which was directed to the biosynthesis of leaves, stems/branches, and roots. From published values of the lignin content of these organs, the total amount of C directed to the biosynthesis of lignin in each biome was determined. This was used to obtain a global value. Implications of these estimates will be discussed with reference to plant carbon and nitrogen metabolism.« less

  5. Introduction--Improving Skills Development for Employability in an Ever-Changing World

    ERIC Educational Resources Information Center

    Maclean, Rupert; Jagannathan, Shanti

    2014-01-01

    The article provides an overview of the global economic landscape in which the contemporary skills development discourse is located. Effective skills development oriented to market needs and to competitiveness in high-value global value chains will help developing economies to avoid the middle income trap. It outlines major issues and challenges…

  6. OECD Skills Outlook 2017: Skills and Global Value Chains

    ERIC Educational Resources Information Center

    OECD Publishing, 2017

    2017-01-01

    Since the 1990s, the world has entered a new phase of globalisation. Information and communication technology, trade liberalisation and lower transport costs have enabled firms and countries to fragment the production process into global value chains (GVCs). Many products are now designed in one country and assembled in another country from parts…

  7. Hierarchicality of trade flow networks reveals complexity of products.

    PubMed

    Shi, Peiteng; Zhang, Jiang; Yang, Bo; Luo, Jingfei

    2014-01-01

    With globalization, countries are more connected than before by trading flows, which amounts to at least 36 trillion dollars today. Interestingly, around 30-60 percents of exports consist of intermediate products in global. Therefore, the trade flow network of particular product with high added values can be regarded as value chains. The problem is weather we can discriminate between these products from their unique flow network structure? This paper applies the flow analysis method developed in ecology to 638 trading flow networks of different products. We claim that the allometric scaling exponent η can be used to characterize the degree of hierarchicality of a flow network, i.e., whether the trading products flow on long hierarchical chains. Then, it is pointed out that the flow networks of products with higher added values and complexity like machinary, transport equipment etc. have larger exponents, meaning that their trade flow networks are more hierarchical. As a result, without the extra data like global input-output table, we can identify the product categories with higher complexity, and the relative importance of a country in the global value chain by the trading network solely.

  8. Hierarchicality of Trade Flow Networks Reveals Complexity of Products

    PubMed Central

    Shi, Peiteng; Zhang, Jiang; Yang, Bo; Luo, Jingfei

    2014-01-01

    With globalization, countries are more connected than before by trading flows, which amounts to at least trillion dollars today. Interestingly, around percents of exports consist of intermediate products in global. Therefore, the trade flow network of particular product with high added values can be regarded as value chains. The problem is weather we can discriminate between these products from their unique flow network structure? This paper applies the flow analysis method developed in ecology to 638 trading flow networks of different products. We claim that the allometric scaling exponent can be used to characterize the degree of hierarchicality of a flow network, i.e., whether the trading products flow on long hierarchical chains. Then, it is pointed out that the flow networks of products with higher added values and complexity like machinary, transport equipment etc. have larger exponents, meaning that their trade flow networks are more hierarchical. As a result, without the extra data like global input-output table, we can identify the product categories with higher complexity, and the relative importance of a country in the global value chain by the trading network solely. PMID:24905753

  9. 77 FR 42516 - The Dreyfus Corporation, et al.; Notice of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-19

    ... Funds, Inc., on behalf of its series Dreyfus Global Absolute Return Fund, Dreyfus Global Dynamic Bond Fund, Dreyfus Global Real Return Fund, Dreyfus International Value Fund, Dreyfus Opportunistic Midcap... Markets Fund, Dreyfus Total Return Advantage Fund and Global Alpha Fund; BNY Mellon Funds Trust, on behalf...

  10. 78 FR 20632 - Mandatory Reporting of Greenhouse Gases: Notice of Data Availability Regarding Global Warming...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-05

    ... Greenhouse Gases: Notice of Data Availability Regarding Global Warming Potential Values for Certain... the availability of estimated global warming potentials, as well as data and analysis submitted in... global warming potentials and the data and analysis supporting them. We are also requesting comment on...

  11. The Ecology of Global English

    ERIC Educational Resources Information Center

    Canagarajah, A. Suresh

    2007-01-01

    Global English is under contestation. Although some consider lingua franca English (LFE) as a neutral medium or code that does not belong to any specific culture or nationality, others see the deceptive nature of this linguistic globalization. Along with Spring (2007/this issue), they see global English as embodying partisan interests and values.…

  12. Self-Organizing Global Gene Expression Regulated through Criticality: Mechanism of the Cell-Fate Change

    PubMed Central

    Tsuchiya, Masa; Giuliani, Alessandro; Hashimoto, Midori; Erenpreisa, Jekaterina; Yoshikawa, Kenichi

    2016-01-01

    Background A fundamental issue in bioscience is to understand the mechanism that underlies the dynamic control of genome-wide expression through the complex temporal-spatial self-organization of the genome to regulate the change in cell fate. We address this issue by elucidating a physically motivated mechanism of self-organization. Principal Findings Building upon transcriptome experimental data for seven distinct cell fates, including early embryonic development, we demonstrate that self-organized criticality (SOC) plays an essential role in the dynamic control of global gene expression regulation at both the population and single-cell levels. The novel findings are as follows: i) Mechanism of cell-fate changes: A sandpile-type critical transition self-organizes overall expression into a few transcription response domains (critical states). A cell-fate change occurs by means of a dissipative pulse-like global perturbation in self-organization through the erasure of initial-state critical behaviors (criticality). Most notably, the reprogramming of early embryo cells destroys the zygote SOC control to initiate self-organization in the new embryonal genome, which passes through a stochastic overall expression pattern. ii) Mechanism of perturbation of SOC controls: Global perturbations in self-organization involve the temporal regulation of critical states. Quantitative evaluation of this perturbation in terminal cell fates reveals that dynamic interactions between critical states determine the critical-state coherent regulation. The occurrence of a temporal change in criticality perturbs this between-states interaction, which directly affects the entire genomic system. Surprisingly, a sub-critical state, corresponding to an ensemble of genes that shows only marginal changes in expression and consequently are considered to be devoid of any interest, plays an essential role in generating a global perturbation in self-organization directed toward the cell-fate change. Conclusion and Significance ‘Whole-genome’ regulation of gene expression through self-regulatory SOC control complements gene-by-gene fine tuning and represents a still largely unexplored non-equilibrium statistical mechanism that is responsible for the massive reprogramming of genome expression. PMID:27997556

  13. Differences in Multitask Resource Reallocation After Change in Task Values.

    PubMed

    Matton, Nadine; Paubel, Pierre; Cegarra, Julien; Raufaste, Eric

    2016-12-01

    The objective was to characterize multitask resource reallocation strategies when managing subtasks with various assigned values. When solving a resource conflict in multitasking, Salvucci and Taatgen predict a globally rational strategy will be followed that favors the most urgent subtask and optimizes global performance. However, Katidioti and Taatgen identified a locally rational strategy that optimizes only a subcomponent of the whole task, leading to detrimental consequences on global performance. Moreover, the question remains open whether expertise would have an impact on the choice of the strategy. We adopted a multitask environment used for pilot selection with a change in emphasis on two out of four subtasks while all subtasks had to be maintained over a minimum performance. A laboratory eye-tracking study contrasted 20 recently selected pilot students considered as experienced with this task and 15 university students considered as novices. When two subtasks were emphasized, novices focused their resources particularly on one high-value subtask and failed to prevent both low-value subtasks falling below minimum performance. On the contrary, experienced people delayed the processing of one low-value subtask but managed to optimize global performance. In a multitasking environment where some subtasks are emphasized, novices follow a locally rational strategy whereas experienced participants follow a globally rational strategy. During complex training, trainees are only able to adjust their resource allocation strategy to subtask emphasis changes once they are familiar with the multitasking environment. © 2016, Human Factors and Ergonomics Society.

  14. Global motion perception in children with amblyopia as a function of spatial and temporal stimulus parameters.

    PubMed

    Meier, Kimberly; Sum, Brian; Giaschi, Deborah

    2016-10-01

    Global motion sensitivity in typically developing children depends on the spatial (Δx) and temporal (Δt) displacement parameters of the motion stimulus. Specifically, sensitivity for small Δx values matures at a later age, suggesting it may be the most vulnerable to damage by amblyopia. To explore this possibility, we compared motion coherence thresholds of children with amblyopia (7-14years old) to age-matched controls. Three Δx values were used with two Δt values, yielding six conditions covering a range of speeds (0.3-30deg/s). We predicted children with amblyopia would show normal coherence thresholds for the same parameters on which 5-year-olds previously demonstrated mature performance, and elevated coherence thresholds for parameters on which 5-year-olds demonstrated immaturities. Consistent with this, we found that children with amblyopia showed deficits with amblyopic eye viewing compared to controls for small and medium Δx values, regardless of Δt value. The fellow eye showed similar results at the smaller Δt. These results confirm that global motion perception in children with amblyopia is particularly deficient at the finer spatial scales that typically mature later in development. An additional implication is that carefully designed stimuli that are adequately sensitive must be used to assess global motion function in developmental disorders. Stimulus parameters for which performance matures early in life may not reveal global motion perception deficits. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Global DNA hypomethylation in peripheral blood mononuclear cells as a biomarker of cancer risk

    USDA-ARS?s Scientific Manuscript database

    Global DNA hypomethylation is an early molecular event in carcinogenesis. Whether methylation measured in peripheral blood mononuclear cells (PBMCs) DNA is a clinically reliable biomarker for early detection or cancer risk assessment is to be established. From an original sample-set of 753 male and...

  16. Finite Element Analysis of Single Cell Stiffness Measurements Using PZT-Integrated Buckling Nanoneedles.

    PubMed

    Rad, Maryam Alsadat; Tijjani, Auwal Shehu; Ahmad, Mohd Ridzuan; Auwal, Shehu Muhammad

    2016-12-23

    This paper proposes a new technique for real-time single cell stiffness measurement using lead zirconate titanate (PZT)-integrated buckling nanoneedles. The PZT and the buckling part of the nanoneedle have been modelled and validated using the ABAQUS software. The two parts are integrated together to function as a single unit. After calibration, the stiffness, Young's modulus, Poisson's ratio and sensitivity of the PZT-integrated buckling nanoneedle have been determined to be 0.7100 N·m -1 , 123.4700 GPa, 0.3000 and 0.0693 V·m·N -1 , respectively. Three Saccharomyces cerevisiae cells have been modelled and validated based on compression tests. The average global stiffness and Young's modulus of the cells are determined to be 10.8867 ± 0.0094 N·m -1 and 110.7033 ± 0.0081 MPa, respectively. The nanoneedle and the cell have been assembled to measure the local stiffness of the single Saccharomyces cerevisiae cells The local stiffness, Young's modulus and PZT output voltage of the three different size Saccharomyces cerevisiae have been determined at different environmental conditions. We investigated that, at low temperature the stiffness value is low to adapt to the change in the environmental condition. As a result, Saccharomyces cerevisiae becomes vulnerable to viral and bacterial attacks. Therefore, the proposed technique will serve as a quick and accurate process to diagnose diseases at early stage in a cell for effective treatment.

  17. Prognostic Value of Strain by Tissue Tracking Cardiac Magnetic Resonance After ST-Segment Elevation Myocardial Infarction.

    PubMed

    Gavara, Jose; Rodriguez-Palomares, Jose F; Valente, Filipa; Monmeneu, Jose V; Lopez-Lereu, Maria P; Bonanad, Clara; Ferreira-Gonzalez, Ignacio; Garcia Del Blanco, Bruno; Rodriguez-Garcia, Julian; Mutuberria, Maria; de Dios, Elena; Rios-Navarro, Cesar; Perez-Sole, Nerea; Racugno, Paolo; Paya, Ana; Minana, Gema; Canoves, Joaquim; Pellicer, Mauricio; Lopez-Fornas, Francisco J; Barrabes, Jose; Evangelista, Arturo; Nunez, Julio; Chorro, Francisco J; Garcia-Dorado, David; Bodi, Vicente

    2017-12-08

    The aim of this study was to evaluate the prognostic value of strain as assessed by tissue tracking (TT) cardiac magnetic resonance (CMR) soon after ST-segment elevation myocardial infarction (STEMI). The prognostic value of myocardial strain as assessed post-STEMI by TT-CMR is unknown. The authors studied the prognostic value of TT-CMR in 323 patients who underwent CMR 1 week post-STEMI. Global (average of peak segmental values [%]) and segmental (number of altered segments) longitudinal (LS), circumferential, and radial strain were assessed using TT-CMR. Global and segmental strain cutoff values were derived from 32 control patients. CMR-derived left ventricular ejection fraction, microvascular obstruction, and infarct size were determined. Results were validated in an external cohort of 190 STEMI patients. During a median follow-up of 1,085 days, 54 first major adverse cardiac events (MACE), which included 10 cardiac deaths, 25 readmissions for heart failure, and 19 readmissions for reinfarction were documented. MACE was associated with more severe abnormalities in all strain indexes (p < 0.001), although only global LS was an independent predictor (p < 0.001). The MACE rate was higher in patients with a global LS of ≥-11% (22% vs. 9%; p = 0.001). After adjustment for baseline and CMR variables, global LS (hazard ratio [HR]: 1.21; 95% confidence interval [CI]: 1.11 to 1.32; p < 0.001) was associated with MACE. In the external validation cohort, a global LS ≥-11% was seen in a higher proportion of patients with MACE (34% vs. 9%; p < 0.001). Global LS predicted MACE after adjustment for baseline and CMR variables (HR: 1.18; 95% CI: 1.04 to 1.33; p = 0.008). The addition of global LS to the multivariate models, including baseline and CMR variables, did not significantly improve the categorical net reclassification improvement index in either the study group (-0.015; p = 0.7) or in the external validation cohort (-0.019; p = 0.9). TT-CMR provided prognostic information soon after STEMI. However, it did not substantially improve risk reclassification beyond traditional CMR indexes. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  18. Knowledge and Adherence to Medications among Palestinian Geriatrics Living with Chronic Diseases in the West Bank and East Jerusalem

    PubMed Central

    Najjar, Anas; Amro, Yazan; Kitaneh, Islam; Abu-Sharar, Salam; Sawalha, Maryam; Jamous, Abrar; Qiq, Muhannad; Makharzeh, Enas; Subb Laban, Bayan; Amro, Wafa; Amro, Ahmad

    2015-01-01

    Background Adequate patient knowledge about medications is essential for appropriate drug taking behavior and patient adherence. This study aims to assess and quantify the level of knowledge and adherence to medications among Palestinian geriatrics living with chronic diseases and to investigate possible associated socio-demographic characteristics. Methods and Findings We conducted a cross-sectional study during June 2013 and January 2014 among Palestinian geriatrics ≥60 years old living with chronic disease in the West Bank and East Jerusalem. A stratified random sample was selected and a questionnaire-assisted interview was applied for data collection. T-test was applied for bivariate analyzing and one-way ANOVA test was applied for multivariate analyses. Results A total of 1192 Palestinian geriatrics were studied. The average age was 70.3 (SD=8.58) years and ranged from 60-110 years. The sample comprised 659 (55.3%) females and 533 (44.7%) males. The global knowledge and global adherence scores were (67.57%) and (89.29%), respectively. Adequate levels of knowledge were 71.4%, and of adherence 75%, which were recorded for 705 (59.1%) and 1088 (91.3%) participants, respectively. Significant higher levels of global knowledge and global adherence were recorded for males, and for participants who hold a Bachelor’s degree, those who live on their own, and did physical activity for more than 40 hours/week (p-value <0.05). Furthermore, workers, participants with a higher monthly income, and non-smokers have a higher knowledge level with (p-value <0.05). We found positive correlation between participants’ global adherence and global knowledge (r=0.487 and p-value <0.001). Negative correlation was found between participants’ global knowledge and adherence with age (r= -0.236, p-value <0.001 and r= -0.211 and p-value <0.001, respectively. Negative correlation between global knowledge and the number of drugs taken (r= -0.130, p-value <0.001) was predicted. Conclusion We concluded that patients with a higher level of knowledge are more adherent to their medications and that better understanding of socio-demographic factors has a clear influence on the level of knowledge and adherence to medications and thus contributes to the development of guidelines for treatment and may consequently lead to favourable clinical outcomes and savings of health care costs. PMID:26046771

  19. Stem Cells News Update: A Personal Perspective

    PubMed Central

    Wong, SC

    2013-01-01

    This article is a follow-up to a previous Commentary published in 2011. It updates some of the events mentioned in that Commentary and continues with more interesting and exciting news on stem cell research and the emerging field of Regenerative Medicine. Some of the news includes: 1) the 2012 Nobel Prize for Medicine awarded to John B. Gurdon and Shinya Yamanaka; 2) the cloning of human embryonic stem cells; 3) the continued search for truly pluripotent adult stem cells via in vitro and in vivo protocols; 4) the breakthrough in organ replacements; 5) the global stem cell race; 6) the global stem cell cryo-preservation business; 7) the worldwide stem cell donor registries, and 8) the issue of government regulation on stem cell therapy. PMID:24778557

  20. Stem cells news update: a personal perspective.

    PubMed

    Wong, Sc

    2013-12-01

    This article is a follow-up to a previous Commentary published in 2011. It updates some of the events mentioned in that Commentary and continues with more interesting and exciting news on stem cell research and the emerging field of Regenerative Medicine. Some of the news includes: 1) the 2012 Nobel Prize for Medicine awarded to John B. Gurdon and Shinya Yamanaka; 2) the cloning of human embryonic stem cells; 3) the continued search for truly pluripotent adult stem cells via in vitro and in vivo protocols; 4) the breakthrough in organ replacements; 5) the global stem cell race; 6) the global stem cell cryo-preservation business; 7) the worldwide stem cell donor registries, and 8) the issue of government regulation on stem cell therapy.

  1. Deep sequencing reveals transcriptome re-programming of Taxus × media cells to the elicitation with methyl jasmonate.

    PubMed

    Sun, Guiling; Yang, Yanfang; Xie, Fuliang; Wen, Jian-Fan; Wu, Jianqiang; Wilson, Iain W; Tang, Qi; Liu, Hongwei; Qiu, Deyou

    2013-01-01

    Plant cell culture represents an alternative source for producing high-value secondary metabolites including paclitaxel (Taxol®), which is mainly produced in Taxus and has been widely used in cancer chemotherapy. The phytohormone methyl jasmonate (MeJA) can significantly increase the production of paclitaxel, which is induced in plants as a secondary metabolite possibly in defense against herbivores and pathogens. In cell culture, MeJA also elicits the accumulation of paclitaxel; however, the mechanism is still largely unknown. To obtain insight into the global regulation mechanism of MeJA in the steady state of paclitaxel production (7 days after MeJA addition), especially on paclitaxel biosynthesis, we sequenced the transcriptomes of MeJA-treated and untreated Taxus × media cells and obtained ∼ 32.5 M high quality reads, from which 40,348 unique sequences were obtained by de novo assembly. Expression level analysis indicated that a large number of genes were associated with transcriptional regulation, DNA and histone modification, and MeJA signaling network. All the 29 known genes involved in the biosynthesis of terpenoid backbone and paclitaxel were found with 18 genes showing increased transcript abundance following elicitation of MeJA. The significantly up-regulated changes of 9 genes in paclitaxel biosynthesis were validated by qRT-PCR assays. According to the expression changes and the previously proposed enzyme functions, multiple candidates for the unknown steps in paclitaxel biosynthesis were identified. We also found some genes putatively involved in the transport and degradation of paclitaxel. Potential target prediction of miRNAs indicated that miRNAs may play an important role in the gene expression regulation following the elicitation of MeJA. Our results shed new light on the global regulation mechanism by which MeJA regulates the physiology of Taxus cells and is helpful to understand how MeJA elicits other plant species besides Taxus.

  2. Methane Emissions from Landfill: Isotopic Evidence for Low Percentage of Oxidation from Gas Wells, Active and Closed Cells

    NASA Astrophysics Data System (ADS)

    Lowry, David; Fisher, Rebecca; Zazzeri, Giulia; al-Shalaan, Aalia; France, James; Lanoisellé, Mathias; Nisbet, Euan

    2017-04-01

    Large landfill sites remain a significant source of methane emissions in developed and developing countries, with a global estimated flux of 29 Tg / yr in the EDGAR 2008 database. This is significantly lower than 20 years ago due to the introduction of gas extraction systems, but active cells still emit significant amounts of methane before the gas is ready for extraction. Historically the methane was either passively oxidized through topsoil layers or flared. Oxidation is still the primary method of methane removal in many countries, and covered, remediated cells across the world continue to emit small quantities of methane. The isotopic signatures of methane from landfill gas wells, and that emitted from active and closed cells have been characterized for more than 20 UK landfills since 2011, with more recent work in Kuwait and Hong Kong. Since 2013 the emission plumes have been identified by a mobile measurement system (Zazzeri et al., 2015). Emissions in all 3 countries have a characteristic δ13C signature of -58 ± 3 ‰ dominated by emissions from the active cells, despite the hot, dry conditions of Kuwait and the hot, humid conditions of Hong Kong. Gas well samples define a similar range. Surface emissions from closed cells and closed landfills are mostly in the range -56 to -52 ‰Ṫhese are much more depleted values than those observed in the 1990s (up to -35 ) when soil oxidation was the dominant mechanism of methane removal. Calculations using isotopic signatures of the amount of methane oxidised in these closed areas before emission to atmosphere range from 5 to 15%, but average less than 10%, and are too small to calculate from the high-emitting active cells. Compared to other major methane sources, landfills have the most consistent isotopic signature globally, and are distinct from the more 13C-enriched natural gas, combustion and biomass burning sources. Zazzeri, G. et al. (2015) Plume mapping and isotopic characterization of anthropogenic methane sources, Atmospheric Environment, 110, 151-162, doi.org/10.1016/j.atmosenv.2015.03.029.

  3. Migratory potential of transplanted glial progenitors as critical factor for successful translation of glia replacement therapy: The gap between mice and men.

    PubMed

    Srivastava, Rohit K; Bulte, Jeff W M; Walczak, Piotr; Janowski, Miroslaw

    2018-05-01

    Neurological disorders are a major threat to public health. Stem cell-based regenerative medicine is now a promising experimental paradigm for its treatment, as shown in pre-clinical animal studies. Initial attempts have been on the replacement of neuronal cells only, but glial progenitors (GPs) are now becoming strong alternative cellular therapeutic candidates to replace oligodendrocytes and astrocytes as knowledge accumulates about their important emerging role in various disease processes. There are many examples of successful therapeutic outcomes for transplanted GPs in small animal models, but clinical translation has proved to be challenging due to the 1,000-fold larger volume of the human brain compared to mice. Human GPs transplanted into the mouse brain migrate extensively and can induce global cell replacement, but a similar extent of migration in the human brain would only allow for local rather than global cell replacement. We review here the mechanisms that govern cell migration, which could potentially be exploited to enhance the migratory properties of GPs through cell engineering pre-transplantation. We furthermore discuss the (dis)advantages of the various cell delivery routes that are available, with particular emphasis on intra-arterial injection as the most suitable route for achieving global cell distribution in the larger brain. Now that therapeutic success has proven to be feasible in small animal models, future efforts will need to be directed to enhance global cell delivery and migration to make bench-to-bedside translation a reality. © 2017 Wiley Periodicals, Inc.

  4. Concentrator photovoltaic module architectures with capabilities for capture and conversion of full global solar radiation

    PubMed Central

    Lee, Kyu-Tae; Yao, Yuan; He, Junwen; Fisher, Brent; Sheng, Xing; Lumb, Matthew; Xu, Lu; Anderson, Mikayla A.; Scheiman, David; Han, Seungyong; Kang, Yongseon; Gumus, Abdurrahman; Bahabry, Rabab R.; Lee, Jung Woo; Paik, Ungyu; Bronstein, Noah D.; Alivisatos, A. Paul; Meitl, Matthew; Burroughs, Scott; Hussain, Muhammad Mustafa; Lee, Jeong Chul; Nuzzo, Ralph G.; Rogers, John A.

    2016-01-01

    Emerging classes of concentrator photovoltaic (CPV) modules reach efficiencies that are far greater than those of even the highest performance flat-plate PV technologies, with architectures that have the potential to provide the lowest cost of energy in locations with high direct normal irradiance (DNI). A disadvantage is their inability to effectively use diffuse sunlight, thereby constraining widespread geographic deployment and limiting performance even under the most favorable DNI conditions. This study introduces a module design that integrates capabilities in flat-plate PV directly with the most sophisticated CPV technologies, for capture of both direct and diffuse sunlight, thereby achieving efficiency in PV conversion of the global solar radiation. Specific examples of this scheme exploit commodity silicon (Si) cells integrated with two different CPV module designs, where they capture light that is not efficiently directed by the concentrator optics onto large-scale arrays of miniature multijunction (MJ) solar cells that use advanced III–V semiconductor technologies. In this CPV+ scheme (“+” denotes the addition of diffuse collector), the Si and MJ cells operate independently on indirect and direct solar radiation, respectively. On-sun experimental studies of CPV+ modules at latitudes of 35.9886° N (Durham, NC), 40.1125° N (Bondville, IL), and 38.9072° N (Washington, DC) show improvements in absolute module efficiencies of between 1.02% and 8.45% over values obtained using otherwise similar CPV modules, depending on weather conditions. These concepts have the potential to expand the geographic reach and improve the cost-effectiveness of the highest efficiency forms of PV power generation. PMID:27930331

  5. Concentrator photovoltaic module architectures with capabilities for capture and conversion of full global solar radiation

    DOE PAGES

    Lee, Kyu-Tae; Yao, Yuan; He, Junwen; ...

    2016-12-05

    Emerging classes ofconcentrator photovoltaic (CPV) modules reach efficiencies that are far greater than those of even the highest performance flat-plate PV technologies, with architectures that have the potential to provide the lowest cost of energy in locations with high direct normal irradiance (DNI). A disadvantage is their inability to effectively use diffuse sunlight, thereby constraining widespread geographic deployment and limiting performance even under the most favorable DNI conditions. This study introduces a module design that integrates capabilities in flat-plate PV directly with the most sophisticated CPV technologies, for capture of both direct and diffuse sunlight, thereby achieving efficiency in PVmore » conversion of the global solar radiation. Specific examples of this scheme exploit commodity silicon (Si) cells integrated with two different CPV module designs, where they capture light that is not efficiently directed by the concentrator optics onto large-scale arrays of miniature multijunction (MJ) solar cells that use advanced III-V semiconductor technologies. In this CPV + scheme ("+" denotes the addition of diffuse collector), the Si and MJ cells operate independently on indirect and direct solar radiation, respectively. On-sun experimental studies of CPV + modules at latitudes of 35.9886° N (Durham, NC), 40.1125° N (Bondville, IL), and 38.9072° N (Washington, DC) show improvements in absolute module efficiencies of between 1.02% and 8.45% over values obtained using otherwise similar CPV modules, depending on weather conditions. These concepts have the potential to expand the geographic reach and improve the cost-effectiveness of the highest efficiency forms of PV power generation.« less

  6. Concentrator photovoltaic module architectures with capabilities for capture and conversion of full global solar radiation

    NASA Astrophysics Data System (ADS)

    Lee, Kyu-Tae; Yao, Yuan; He, Junwen; Fisher, Brent; Sheng, Xing; Lumb, Matthew; Xu, Lu; Anderson, Mikayla A.; Scheiman, David; Han, Seungyong; Kang, Yongseon; Gumus, Abdurrahman; Bahabry, Rabab R.; Lee, Jung Woo; Paik, Ungyu; Bronstein, Noah D.; Alivisatos, A. Paul; Meitl, Matthew; Burroughs, Scott; Mustafa Hussain, Muhammad; Lee, Jeong Chul; Nuzzo, Ralph G.; Rogers, John A.

    2016-12-01

    Emerging classes of concentrator photovoltaic (CPV) modules reach efficiencies that are far greater than those of even the highest performance flat-plate PV technologies, with architectures that have the potential to provide the lowest cost of energy in locations with high direct normal irradiance (DNI). A disadvantage is their inability to effectively use diffuse sunlight, thereby constraining widespread geographic deployment and limiting performance even under the most favorable DNI conditions. This study introduces a module design that integrates capabilities in flat-plate PV directly with the most sophisticated CPV technologies, for capture of both direct and diffuse sunlight, thereby achieving efficiency in PV conversion of the global solar radiation. Specific examples of this scheme exploit commodity silicon (Si) cells integrated with two different CPV module designs, where they capture light that is not efficiently directed by the concentrator optics onto large-scale arrays of miniature multijunction (MJ) solar cells that use advanced III-V semiconductor technologies. In this CPV+ scheme (“+” denotes the addition of diffuse collector), the Si and MJ cells operate independently on indirect and direct solar radiation, respectively. On-sun experimental studies of CPV+ modules at latitudes of 35.9886° N (Durham, NC), 40.1125° N (Bondville, IL), and 38.9072° N (Washington, DC) show improvements in absolute module efficiencies of between 1.02% and 8.45% over values obtained using otherwise similar CPV modules, depending on weather conditions. These concepts have the potential to expand the geographic reach and improve the cost-effectiveness of the highest efficiency forms of PV power generation.

  7. Climate Simulations based on a different-grid nested and coupled model

    NASA Astrophysics Data System (ADS)

    Li, Dan; Ji, Jinjun; Li, Yinpeng

    2002-05-01

    An atmosphere-vegetation interaction model (A VIM) has been coupled with a nine-layer General Cir-culation Model (GCM) of Institute of Atmospheic Physics/State Key Laboratory of Numerical Modeling for Atmospheric Sciences and Geophysical Fluid Dynamics (IAP/LASG), which is rhomboidally truncated at zonal wave number 15, to simulate global climatic mean states. A VIM is a model having inter-feedback between land surface processes and eco-physiological processes on land. As the first step to couple land with atmosphere completely, the physiological processes are fixed and only the physical part (generally named the SVAT (soil-vegetation-atmosphere-transfer scheme) model) of AVIM is nested into IAP/LASG L9R15 GCM. The ocean part of GCM is prescribed and its monthly sea surface temperature (SST) is the climatic mean value. With respect to the low resolution of GCM, i.e., each grid cell having lon-gitude 7.5° and latitude 4.5°, the vegetation is given a high resolution of 1.5° by 1.5° to nest and couple the fine grid cells of land with the coarse grid cells of atmosphere. The coupling model has been integrated for 15 years and its last ten-year mean of outputs was chosen for analysis. Compared with observed data and NCEP reanalysis, the coupled model simulates the main characteris-tics of global atmospheric circulation and the fields of temperature and moisture. In particular, the simu-lated precipitation and surface air temperature have sound results. The work creates a solid base on coupling climate models with the biosphere.

  8. Concentrator photovoltaic module architectures with capabilities for capture and conversion of full global solar radiation.

    PubMed

    Lee, Kyu-Tae; Yao, Yuan; He, Junwen; Fisher, Brent; Sheng, Xing; Lumb, Matthew; Xu, Lu; Anderson, Mikayla A; Scheiman, David; Han, Seungyong; Kang, Yongseon; Gumus, Abdurrahman; Bahabry, Rabab R; Lee, Jung Woo; Paik, Ungyu; Bronstein, Noah D; Alivisatos, A Paul; Meitl, Matthew; Burroughs, Scott; Hussain, Muhammad Mustafa; Lee, Jeong Chul; Nuzzo, Ralph G; Rogers, John A

    2016-12-20

    Emerging classes of concentrator photovoltaic (CPV) modules reach efficiencies that are far greater than those of even the highest performance flat-plate PV technologies, with architectures that have the potential to provide the lowest cost of energy in locations with high direct normal irradiance (DNI). A disadvantage is their inability to effectively use diffuse sunlight, thereby constraining widespread geographic deployment and limiting performance even under the most favorable DNI conditions. This study introduces a module design that integrates capabilities in flat-plate PV directly with the most sophisticated CPV technologies, for capture of both direct and diffuse sunlight, thereby achieving efficiency in PV conversion of the global solar radiation. Specific examples of this scheme exploit commodity silicon (Si) cells integrated with two different CPV module designs, where they capture light that is not efficiently directed by the concentrator optics onto large-scale arrays of miniature multijunction (MJ) solar cells that use advanced III-V semiconductor technologies. In this CPV + scheme ("+" denotes the addition of diffuse collector), the Si and MJ cells operate independently on indirect and direct solar radiation, respectively. On-sun experimental studies of CPV + modules at latitudes of 35.9886° N (Durham, NC), 40.1125° N (Bondville, IL), and 38.9072° N (Washington, DC) show improvements in absolute module efficiencies of between 1.02% and 8.45% over values obtained using otherwise similar CPV modules, depending on weather conditions. These concepts have the potential to expand the geographic reach and improve the cost-effectiveness of the highest efficiency forms of PV power generation.

  9. Deep sequencing reveals distinct patterns of DNA methylation in prostate cancer.

    PubMed

    Kim, Jung H; Dhanasekaran, Saravana M; Prensner, John R; Cao, Xuhong; Robinson, Daniel; Kalyana-Sundaram, Shanker; Huang, Christina; Shankar, Sunita; Jing, Xiaojun; Iyer, Matthew; Hu, Ming; Sam, Lee; Grasso, Catherine; Maher, Christopher A; Palanisamy, Nallasivam; Mehra, Rohit; Kominsky, Hal D; Siddiqui, Javed; Yu, Jindan; Qin, Zhaohui S; Chinnaiyan, Arul M

    2011-07-01

    Beginning with precursor lesions, aberrant DNA methylation marks the entire spectrum of prostate cancer progression. We mapped the global DNA methylation patterns in select prostate tissues and cell lines using MethylPlex-next-generation sequencing (M-NGS). Hidden Markov model-based next-generation sequence analysis identified ∼68,000 methylated regions per sample. While global CpG island (CGI) methylation was not differential between benign adjacent and cancer samples, overall promoter CGI methylation significantly increased from ~12.6% in benign samples to 19.3% and 21.8% in localized and metastatic cancer tissues, respectively (P-value < 2 × 10(-16)). We found distinct patterns of promoter methylation around transcription start sites, where methylation occurred not only on the CGIs, but also on flanking regions and CGI sparse promoters. Among the 6691 methylated promoters in prostate tissues, 2481 differentially methylated regions (DMRs) are cancer-specific, including numerous novel DMRs. A novel cancer-specific DMR in the WFDC2 promoter showed frequent methylation in cancer (17/22 tissues, 6/6 cell lines), but not in the benign tissues (0/10) and normal PrEC cells. Integration of LNCaP DNA methylation and H3K4me3 data suggested an epigenetic mechanism for alternate transcription start site utilization, and these modifications segregated into distinct regions when present on the same promoter. Finally, we observed differences in repeat element methylation, particularly LINE-1, between ERG gene fusion-positive and -negative cancers, and we confirmed this observation using pyrosequencing on a tissue panel. This comprehensive methylome map will further our understanding of epigenetic regulation in prostate cancer progression.

  10. Physiological and transcriptional responses and cross protection of Lactobacillus plantarum ZDY2013 under acid stress.

    PubMed

    Huang, Renhui; Pan, Mingfang; Wan, Cuixiang; Shah, Nagendra P; Tao, Xueying; Wei, Hua

    2016-02-01

    Acid tolerance responses (ATR) in Lactobacillus plantarum ZDY2013 were investigated at physiological and molecular levels. A comparison of composition of cell membrane fatty acids (CMFA) between acid-challenged and unchallenged cells showed that acid adaptation evoked a significantly higher percentage of saturated fatty acids and cyclopropane fatty acids in acid-challenged than in unchallenged cells. In addition, reverse transcription-quantitative PCR analysis in acid-adapted cells at different pH values (ranging from 3.0 to 4.0) indicated that several genes were differently regulated, including those related to proton pumps, amino acid metabolism, sugar metabolism, and class I and class III stress response pathways. Expression of genes involved in fatty acid synthesis and production of alkali was significantly upregulated. Upon exposure to pH 4.5 for 2 h, a higher survival rate (higher viable cell count) of Lactobacillus plantarum ZDY2013 was achieved following an additional challenge to 40 mM hydrogen peroxide for 60 min, but no difference in survival rate of cells was found with further challenge to heat, ethanol, or salt. Therefore, we concluded that the physiological and metabolic changes of acid-treated cells of Lactobacillus plantarum ZDY2013 help the cells resist damage caused by acid, and further initiated global response signals to bring the whole cell into a state of defense to other stress factors, especially hydrogen peroxide. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  11. Role of platinum DNA damage-induced transcriptional inhibition in chemotherapy-induced neuronal atrophy and peripheral neurotoxicity.

    PubMed

    Yan, Fang; Liu, Johnson J; Ip, Virginia; Jamieson, Stephen M F; McKeage, Mark J

    2015-12-01

    Platinum-based anticancer drugs cause peripheral neurotoxicity by damaging sensory neurons within the dorsal root ganglia (DRG), but the mechanisms are incompletely understood. The roles of platinum DNA binding, transcription inhibition and altered cell size were investigated in primary cultures of rat DRG cells. Click chemistry quantitative fluorescence imaging of RNA-incorporated 5-ethynyluridine showed high, but wide ranging, global levels of transcription in individual neurons that correlated with their cell body size. Treatment with platinum drugs reduced neuronal transcription and cell body size to an extent that corresponded to the amount of preceding platinum DNA binding, but without any loss of neuronal cells. The effects of platinum drugs on neuronal transcription and cell body size were inhibited by blocking platinum DNA binding with sodium thiosulfate, and mimicked by treatment with a model transcriptional inhibitor, actinomycin D. In vivo oxaliplatin treatment depleted the total RNA content of DRG tissue concurrently with altering DRG neuronal size. These findings point to a mechanism of chemotherapy-induced peripheral neurotoxicity, whereby platinum DNA damage induces global transcriptional arrest leading in turn to neuronal atrophy. DRG neurons may be particularly vulnerable to this mechanism of toxicity because of their requirements for high basal levels of global transcriptional activity. Findings point to a new stepwise mechanism of chemotherapy-induced peripheral neurotoxicity, whereby platinum DNA damage induces global transcriptional arrest leading in turn to neuronal atrophy. Dorsal root ganglion neurons may be particularly vulnerable to this neurotoxicity because of their high global transcriptional outputs, demonstrated in this study by click chemistry quantitative fluorescence imaging. © 2015 International Society for Neurochemistry.

  12. Identification of significant features by the Global Mean Rank test.

    PubMed

    Klammer, Martin; Dybowski, J Nikolaj; Hoffmann, Daniel; Schaab, Christoph

    2014-01-01

    With the introduction of omics-technologies such as transcriptomics and proteomics, numerous methods for the reliable identification of significantly regulated features (genes, proteins, etc.) have been developed. Experimental practice requires these tests to successfully deal with conditions such as small numbers of replicates, missing values, non-normally distributed expression levels, and non-identical distributions of features. With the MeanRank test we aimed at developing a test that performs robustly under these conditions, while favorably scaling with the number of replicates. The test proposed here is a global one-sample location test, which is based on the mean ranks across replicates, and internally estimates and controls the false discovery rate. Furthermore, missing data is accounted for without the need of imputation. In extensive simulations comparing MeanRank to other frequently used methods, we found that it performs well with small and large numbers of replicates, feature dependent variance between replicates, and variable regulation across features on simulation data and a recent two-color microarray spike-in dataset. The tests were then used to identify significant changes in the phosphoproteomes of cancer cells induced by the kinase inhibitors erlotinib and 3-MB-PP1 in two independently published mass spectrometry-based studies. MeanRank outperformed the other global rank-based methods applied in this study. Compared to the popular Significance Analysis of Microarrays and Linear Models for Microarray methods, MeanRank performed similar or better. Furthermore, MeanRank exhibits more consistent behavior regarding the degree of regulation and is robust against the choice of preprocessing methods. MeanRank does not require any imputation of missing values, is easy to understand, and yields results that are easy to interpret. The software implementing the algorithm is freely available for academic and commercial use.

  13. Diversity in spatial scope of contrast adaptation among mouse retinal ganglion cells.

    PubMed

    Khani, Mohammad Hossein; Gollisch, Tim

    2017-12-01

    Retinal ganglion cells adapt to changes in visual contrast by adjusting their response kinetics and sensitivity. While much work has focused on the time scales of these adaptation processes, less is known about the spatial scale of contrast adaptation. For example, do small, localized contrast changes affect a cell's signal processing across its entire receptive field? Previous investigations have provided conflicting evidence, suggesting that contrast adaptation occurs either locally within subregions of a ganglion cell's receptive field or globally over the receptive field in its entirety. Here, we investigated the spatial extent of contrast adaptation in ganglion cells of the isolated mouse retina through multielectrode-array recordings. We applied visual stimuli so that ganglion cell receptive fields contained regions where the average contrast level changed periodically as well as regions with constant average contrast level. This allowed us to analyze temporal stimulus integration and sensitivity separately for stimulus regions with and without contrast changes. We found that the spatial scope of contrast adaptation depends strongly on cell identity, with some ganglion cells displaying clear local adaptation, whereas others, in particular large transient ganglion cells, adapted globally to contrast changes. Thus, the spatial scope of contrast adaptation in mouse retinal ganglion cells appears to be cell-type specific. This could reflect differences in mechanisms of contrast adaptation and may contribute to the functional diversity of different ganglion cell types. NEW & NOTEWORTHY Understanding whether adaptation of a neuron in a sensory system can occur locally inside the receptive field or whether it always globally affects the entire receptive field is important for understanding how the neuron processes complex sensory stimuli. For mouse retinal ganglion cells, we here show that both local and global contrast adaptation exist and that this diversity in spatial scope can contribute to the functional diversity of retinal ganglion cell types. Copyright © 2017 the American Physiological Society.

  14. Determination of incoming solar radiation in major tree species in Turkey.

    PubMed

    Yilmaz, Osman Yalcin; Sevgi, Orhan; Koc, Ayhan

    2012-07-01

    Light requirements and spatial distribution of major forest tree species in Turkey hasn't been analyzed yet. Continuous surface solar radiation data, especially at mountainous-forested areas, are needed to put forward this relationship between forest tree species and solar radiation. To achieve this, GIS-based modeling of solar radiation is one of the methods used in rangelands to estimate continuous surface solar radiation. Therefore, mean monthly and annual total global solar radiation maps of whole Turkey were computed spatially using GRASS GIS software "r.sun" model under clear-sky (cloudless) conditions. 147498 pure forest stand point-based data were used in the study for calculating mean global solar radiation values of all the major forest tree species of Turkey. Beech had the lowest annual mean total global solar radiation value of 1654.87 kWh m(-2), whereas juniper had the highest value of 1928.89 kWh m(-2). The rank order of tree species according to the mean monthly and annual total global solar radiation values, using a confidence level of p < 0.05, was as follows: Beech < Spruce < Fir species < Oak species < Scotch pine < Red pine < Cedar < Juniper. The monthly and annual solar radiation values of sites and light requirements of forest trees ranked similarly.

  15. Changing values of farm animal genomic resources. from historical breeds to the Nagoya Protocol.

    PubMed

    Tamminen, Sakari

    2015-01-01

    The paper reviews the history of Animal genetic resources (AnGRs) and claims that over the course of history they have been conceptually transformed from economic, ecologic and scientific life forms into political objects, reflecting in the way in which any valuation of AnGRs is today inherently imbued with national politics and its values enacted by legally binding global conventions. Historically, the first calls to conservation were based on the economic, ecological and scientific values of the AnGR. While the historical arguments are valid and still commonly proposed values for conservation, the AnGR have become highly politicized since the adoption of the Convention of Biological Diversity (CBD), the subsequent Interlaken Declaration, the Global Plan for Action (GPA) and the Nagoya Protocol. The scientific and political definitions of the AnGRs were creatively reshuffled within these documents and the key criteria by which they are now identified and valued today were essentially redefined. The criteria of "in situ condition" has become the necessary starting point for all valuation efforts of AnGRs, effectively transforming their previous nature as natural property and global genetic commons into objects of national concern pertaining to territorially discrete national genetic landscapes, regulated by the sovereign powers of the parties to the global conventions.

  16. Making stem cells count for global health.

    PubMed

    McMahon, Dominique S; Thorsteinsdóttir, Halla

    2011-11-01

    Developing countries such as China, India and Brazil are making large investments in the stem cell field. Here we argue that hands-on involvement in the field by these countries is essential if the products developed are going to be locally relevant, affordable and appropriate. However, stem cells are a high-risk investment and any global health impacts are still likely to be far off. Even if they are eventually successful, better clinical oversight and measures to ensure access are required for stem cells to have a substantial and equitable impact.

  17. Global Three-dimensional Simulation of the Solar Wind-Magnetosphere Interaction Using a Two-way Coupled Magnetohydrodynamics with Embedded Particle-in-Cell Model

    NASA Astrophysics Data System (ADS)

    Chen, Y.; Toth, G.; Cassak, P.; Jia, X.; Gombosi, T. I.; Slavin, J. A.; Welling, D. T.; Markidis, S.; Peng, I. B.; Jordanova, V. K.; Henderson, M. G.

    2017-12-01

    We perform a three-dimensional (3D) global simulation of Earth's magnetosphere with kinetic reconnection physics to study the interaction between the solar wind and Earth's magnetosphere. In this global simulation with magnetohydrodynamics with embedded particle-in-cell model (MHD-EPIC), both the dayside magnetopause reconnection region and the magnetotail reconnection region are covered with a kinetic particle-in-cell code iPIC3D, which is two-way coupled with the global MHD model BATS-R-US. We will describe the dayside reconnection related phenomena, such as the lower hybrid drift instability (LHDI) and the evolution of the flux transfer events (FTEs) along the magnetopause, and compare the simulation results with observations. We will also discuss the response of the magnetotail to the southward IMF. The onset of the tail reconnection and the properties of the magnetotail flux ropes will be discussed.

  18. Reinforcement learning of targeted movement in a spiking neuronal model of motor cortex.

    PubMed

    Chadderdon, George L; Neymotin, Samuel A; Kerr, Cliff C; Lytton, William W

    2012-01-01

    Sensorimotor control has traditionally been considered from a control theory perspective, without relation to neurobiology. In contrast, here we utilized a spiking-neuron model of motor cortex and trained it to perform a simple movement task, which consisted of rotating a single-joint "forearm" to a target. Learning was based on a reinforcement mechanism analogous to that of the dopamine system. This provided a global reward or punishment signal in response to decreasing or increasing distance from hand to target, respectively. Output was partially driven by Poisson motor babbling, creating stochastic movements that could then be shaped by learning. The virtual forearm consisted of a single segment rotated around an elbow joint, controlled by flexor and extensor muscles. The model consisted of 144 excitatory and 64 inhibitory event-based neurons, each with AMPA, NMDA, and GABA synapses. Proprioceptive cell input to this model encoded the 2 muscle lengths. Plasticity was only enabled in feedforward connections between input and output excitatory units, using spike-timing-dependent eligibility traces for synaptic credit or blame assignment. Learning resulted from a global 3-valued signal: reward (+1), no learning (0), or punishment (-1), corresponding to phasic increases, lack of change, or phasic decreases of dopaminergic cell firing, respectively. Successful learning only occurred when both reward and punishment were enabled. In this case, 5 target angles were learned successfully within 180 s of simulation time, with a median error of 8 degrees. Motor babbling allowed exploratory learning, but decreased the stability of the learned behavior, since the hand continued moving after reaching the target. Our model demonstrated that a global reinforcement signal, coupled with eligibility traces for synaptic plasticity, can train a spiking sensorimotor network to perform goal-directed motor behavior.

  19. Public Constructs of Energy Values and Behaviors in Implementing Taiwan's "Energy-Conservation/Carbon-Reduction" Declarations

    ERIC Educational Resources Information Center

    Chiu, Mei-Shiu; Yeh, Huei-Ming; Spangler, Jonathan

    2016-01-01

    The emergent crisis of global warming calls for energy education for people of all ages and social groups. The Taiwanese government has publicized 10 declarations on energy conservation and carbon reduction as public behavior guidelines to mitigate global warming. This study uses interviews with quantitative assessment to explore the values and…

  20. MODELING THE DYNAMICS OF THE INTEGRATED EARTH SYSTEM AND THE VALUE OF GLOBAL ECOSYSTEM SERVICES USING THE GUMBO MODEL. (R827169)

    EPA Science Inventory

    A global unified metamodel of the biosphere (GUMBO) was developed to simulate the integrated earth system and assess the dynamics and values of ecosystem services. It is a `metamodel' in that it represents a synthesis and a simplification of several existing dynamic gl...

  1. Ten Sins Challenging Education in the Contemporary Global Era: A Philosophical Essay

    ERIC Educational Resources Information Center

    Sinagatullin, Ilghiz M.

    2004-01-01

    According to this author, the modern epoch is characterized by a decrease of vital spirituality and an increase of materialistic values and virtues. This article discusses what the author views as the ten sins challenging education in the contemporary global era. These are: (1) the shrinking of spiritual values; (2) corruption; (3) sexual…

  2. A Conceptual Framework for Exploring the Role of Studies Abroad in Nurturing Global Citizenship

    ERIC Educational Resources Information Center

    Tarrant, Michael Andrew

    2010-01-01

    A conceptual framework, adapted from the Value-Belief-Norm theory, is proposed for understanding the role of studying abroad in nurturing global citizenship. The framework is oriented in concepts of justice, the environment, and civic obligations as key issues in the predictive validity of values, beliefs, and norms. The VBN approach is then…

  3. 76 FR 51449 - Self-Regulatory Organizations; New York Stock Exchange LLC; Order Granting Approval of Proposed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-18

    ... listed issuers, on total global market value based on a public offering price. \\7\\ See e-mail from..., media visibility, corporate governance, and advocacy initiatives.\\9\\ Additionally, the NYSE Market... includes issuers with a global market value of $400 million or more based on the public offering price...

  4. The Role of Policy in Constructing the Peripheral Scientist in the Era of Globalization

    ERIC Educational Resources Information Center

    Englander, Karen; Uzuner-Smith, Sedef

    2013-01-01

    This study explores how the logic and values of globalization are manifested in international discourses of higher education in relation to scientific knowledge production and how those values are appropriated in national and institutional policies. This study also explores how this confluence of discourses and policies construct scientists in two…

  5. Global health and justice: re-examining our values.

    PubMed

    Benatar, Solomon R

    2013-07-01

    Widening disparities in health within and between nations reflect a trajectory of 'progress' that has 'run its course' and needs to be significantly modified if progress is to be sustainable. Values and a value system that have enabled progress are now being distorted to the point where they undermine the future of global health by generating multiple crises that perpetuate injustice. Reliance on philanthropy for rectification, while necessary in the short and medium terms, is insufficient to address the challenge of economic and other systems spinning out of control. Innovative approaches are required and it is suggested that these could best emerge from in-depth multidisciplinary research supported by endeavours to promote a 'global mind-set.' © 2013 John Wiley & Sons Ltd.

  6. Citizenship, Identity and Education: Examining the Public Purposes of Schools in an Age of Globalization

    ERIC Educational Resources Information Center

    Reimers, Fernando

    2006-01-01

    One of the purposes of educational institutions is to develop citizenship. In the 21st century, citizenship includes global citizenship. Addressing the challenges of globalization will require making citizenship education and the development of global values an explicit objective of efforts to improve quality throughout the world, critically…

  7. Global Learning as General Education for the Twenty-First Century

    ERIC Educational Resources Information Center

    Reich, Jacqueline C.

    2012-01-01

    Global awareness has emerged as a valued learning outcome in higher education. Students need repeated and on-going learning opportunities to develop the global competencies and habits of mind that are necessary to navigate our increasingly interconnected and complex world. This paper argues that situating an introductory global studies course into…

  8. An Improved Incremental Learning Approach for KPI Prognosis of Dynamic Fuel Cell System.

    PubMed

    Yin, Shen; Xie, Xiaochen; Lam, James; Cheung, Kie Chung; Gao, Huijun

    2016-12-01

    The key performance indicator (KPI) has an important practical value with respect to the product quality and economic benefits for modern industry. To cope with the KPI prognosis issue under nonlinear conditions, this paper presents an improved incremental learning approach based on available process measurements. The proposed approach takes advantage of the algorithm overlapping of locally weighted projection regression (LWPR) and partial least squares (PLS), implementing the PLS-based prognosis in each locally linear model produced by the incremental learning process of LWPR. The global prognosis results including KPI prediction and process monitoring are obtained from the corresponding normalized weighted means of all the local models. The statistical indicators for prognosis are enhanced as well by the design of novel KPI-related and KPI-unrelated statistics with suitable control limits for non-Gaussian data. For application-oriented purpose, the process measurements from real datasets of a proton exchange membrane fuel cell system are employed to demonstrate the effectiveness of KPI prognosis. The proposed approach is finally extended to a long-term voltage prediction for potential reference of further fuel cell applications.

  9. Scotblood 2007: Tackling local and global issues in transfusion medicine - donor recruitment, effective use of blood, stem cell plasticity, and vCJD.

    PubMed

    Bessos, Hagop; Fraser, Robin; Seghatchian, Jerard

    2008-02-01

    This commentary briefly highlights some of the local and the global contemporary issues affecting transfusion medicine worldwide. The main areas of focus addressed this year were: donor recruitment, stem cell plasticity, the effective use of blood, and vCJD.

  10. Assessment of global DNA methylation in peripheral blood cell subpopulations of early rheumatoid arthritis before and after methotrexate.

    PubMed

    de Andres, María C; Perez-Pampin, Eva; Calaza, Manuel; Santaclara, Francisco J; Ortea, Ignacio; Gomez-Reino, Juan J; Gonzalez, Antonio

    2015-08-29

    DNA methylation is an epigenetic mechanism regulating gene expression that has been insufficiently studied in the blood of rheumatoid arthritis (RA) patients, as only T cells and total peripheral blood mononuclear cells (PBMCs) from patients with established RA have been studied and with conflicting results. Five major blood cell subpopulations: T, B and NK cells, monocytes, and polymorphonuclear leukocytes, were isolated from 19 early RA patients and 17 healthy controls. Patient samples were taken before and 1 month after the start of treatment with methotrexate (MTX). Analysis included DNA methylation with high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry-selected reaction monitoring (HPLC-ESI-MS/MS-SRM) and expression levels of seven methylation-specific enzymes by quantitative polymerase chain reaction (qPCR). Disease-modifying anti-rheumatic drug (DMARD)-naïve early RA patients showed global DNA hypomethylation in T cells and monocytes, together with a lower expression of DNA methyltrasnferase 1 (DNMT1), the maintenance DNA methyltransferase, which was also decreased in B cells. Furthermore, significantly increased expression of ten-eleven translocation1 (TET1), TET2 and TET3, enzymes involved in demethylation, was found in monocytes and of TET2 in T cells. There was also modest decreased expression of DNMT3A in B cells and of growth arrest and DNA-damage-inducible protein 45A (GADD45A) in T and B cells. Treatment with MTX reverted hypomethylation in T cells and monocytes, which were no longer different from controls, and increased global methylation in B cells. In addition, DNMT1 and DNMT3A showed a trend to reversion of their decreased expression. Our results confirm global DNA hypomethylation in patients with RA with specificity for some blood cell subpopulations and their reversal with methotrexate treatment. These changes are accompanied by parallel changes in the levels of enzymes involved in methylation, suggesting the possibility of regulation at this level.

  11. Global Three-Dimensional Simulation of Earth's Dayside Reconnection Using a Two-Way Coupled Magnetohydrodynamics With Embedded Particle-in-Cell Model: Initial Results

    NASA Astrophysics Data System (ADS)

    Chen, Yuxi; Tóth, Gábor; Cassak, Paul; Jia, Xianzhe; Gombosi, Tamas I.; Slavin, James A.; Markidis, Stefano; Peng, Ivy Bo; Jordanova, Vania K.; Henderson, Michael G.

    2017-10-01

    We perform a three-dimensional (3-D) global simulation of Earth's magnetosphere with kinetic reconnection physics to study the flux transfer events (FTEs) and dayside magnetic reconnection with the recently developed magnetohydrodynamics with embedded particle-in-cell model. During the 1 h long simulation, the FTEs are generated quasi-periodically near the subsolar point and move toward the poles. We find that the magnetic field signature of FTEs at their early formation stage is similar to a "crater FTE," which is characterized by a magnetic field strength dip at the FTE center. After the FTE core field grows to a significant value, it becomes an FTE with typical flux rope structure. When an FTE moves across the cusp, reconnection between the FTE field lines and the cusp field lines can dissipate the FTE. The kinetic features are also captured by our model. A crescent electron phase space distribution is found near the reconnection site. A similar distribution is found for ions at the location where the Larmor electric field appears. The lower hybrid drift instability (LHDI) along the current sheet direction also arises at the interface of magnetosheath and magnetosphere plasma. The LHDI electric field is about 8 mV/m, and its dominant wavelength relative to the electron gyroradius agrees reasonably with Magnetospheric Multiscale (MMS) observations.

  12. Climatic irregular staircases: generalized acceleration of global warming

    PubMed Central

    De Saedeleer, Bernard

    2016-01-01

    Global warming rates mentioned in the literature are often restricted to a couple of arbitrary periods of time, or of isolated values of the starting year, lacking a global view. In this study, we perform on the contrary an exhaustive parametric analysis of the NASA GISS LOTI data, and also of the HadCRUT4 data. The starting year systematically varies between 1880 and 2002, and the averaging period from 5 to 30 yr — not only decades; the ending year also varies . In this way, we uncover a whole unexplored space of values for the global warming rate, and access the full picture. Additionally, stairstep averaging and linear least squares fitting to determine climatic trends have been sofar exclusive. We propose here an original hybrid method which combines both approaches in order to derive a new type of climatic trend. We find that there is an overall acceleration of the global warming whatever the value of the averaging period, and that 99.9% of the 3029 Earth’s climatic irregular staircases are rising. Graphical evidence is also given that choosing an El Niño year as starting year gives lower global warming rates — except if there is a volcanic cooling in parallel. Our rates agree and generalize several results mentioned in the literature. PMID:26813867

  13. Climatic irregular staircases: generalized acceleration of global warming.

    PubMed

    De Saedeleer, Bernard

    2016-01-27

    Global warming rates mentioned in the literature are often restricted to a couple of arbitrary periods of time, or of isolated values of the starting year, lacking a global view. In this study, we perform on the contrary an exhaustive parametric analysis of the NASA GISS LOTI data, and also of the HadCRUT4 data. The starting year systematically varies between 1880 and 2002, and the averaging period from 5 to 30 yr - not only decades; the ending year also varies . In this way, we uncover a whole unexplored space of values for the global warming rate, and access the full picture. Additionally, stairstep averaging and linear least squares fitting to determine climatic trends have been sofar exclusive. We propose here an original hybrid method which combines both approaches in order to derive a new type of climatic trend. We find that there is an overall acceleration of the global warming whatever the value of the averaging period, and that 99.9% of the 3029 Earth's climatic irregular staircases are rising. Graphical evidence is also given that choosing an El Niño year as starting year gives lower global warming rates - except if there is a volcanic cooling in parallel. Our rates agree and generalize several results mentioned in the literature.

  14. TORC1 signaling inhibition by rapamycin and caffeine affect lifespan, global gene expression, and cell proliferation of fission yeast.

    PubMed

    Rallis, Charalampos; Codlin, Sandra; Bähler, Jürg

    2013-08-01

    Target of rapamycin complex 1 (TORC1) is implicated in growth control and aging from yeast to humans. Fission yeast is emerging as a popular model organism to study TOR signaling, although rapamycin has been thought to not affect cell growth in this organism. Here, we analyzed the effects of rapamycin and caffeine, singly and combined, on multiple cellular processes in fission yeast. The two drugs led to diverse and specific phenotypes that depended on TORC1 inhibition, including prolonged chronological lifespan, inhibition of global translation, inhibition of cell growth and division, and reprograming of global gene expression mimicking nitrogen starvation. Rapamycin and caffeine differentially affected these various TORC1-dependent processes. Combined drug treatment augmented most phenotypes and effectively blocked cell growth. Rapamycin showed a much more subtle effect on global translation than did caffeine, while both drugs were effective in prolonging chronological lifespan. Rapamycin and caffeine did not affect the lifespan via the pH of the growth media. Rapamycin prolonged the lifespan of nongrowing cells only when applied during the growth phase but not when applied after cells had stopped proliferation. The doses of rapamycin and caffeine strongly correlated with growth inhibition and with lifespan extension. This comprehensive analysis will inform future studies into TORC1 function and cellular aging in fission yeast and beyond. © 2013 The Authors. Aging Cell published by John Wiley & Sons Ltd and the Anatomical Society.

  15. Relativistic Thomas-Fermi treatment of compressed atoms and compressed nuclear matter cores of stellar dimensions

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rotondo, M.; Rueda, Jorge A.; Xue, S.-S.

    The Feynman-Metropolis-Teller treatment of compressed atoms is extended to the relativistic regimes. Each atomic configuration is confined by a Wigner-Seitz cell and is characterized by a positive electron Fermi energy. The nonrelativistic treatment assumes a pointlike nucleus and infinite values of the electron Fermi energy can be attained. In the relativistic treatment there exists a limiting configuration, reached when the Wigner-Seitz cell radius equals the radius of the nucleus, with a maximum value of the electron Fermi energy (E{sub e}{sup F}){sub max}, here expressed analytically in the ultrarelativistic approximation. The corrections given by the relativistic Thomas-Fermi-Dirac exchange term are alsomore » evaluated and shown to be generally small and negligible in the relativistic high-density regime. The dependence of the relativistic electron Fermi energies by compression for selected nuclei are compared and contrasted to the nonrelativistic ones and to the ones obtained in the uniform approximation. The relativistic Feynman-Metropolis-Teller approach here presented overcomes some difficulties in the Salpeter approximation generally adopted for compressed matter in physics and astrophysics. The treatment is then extrapolated to compressed nuclear matter cores of stellar dimensions with A{approx_equal}(m{sub Planck}/m{sub n}){sup 3}{approx}10{sup 57} or M{sub core}{approx}M{sub {circle_dot}}. A new family of equilibrium configurations exists for selected values of the electron Fermi energy varying in the range 0

  16. Identifying Functional Neighborhoods within the Cell Nucleus: Proximity Analysis of Early S-Phase Replicating Chromatin Domains to Sites of Transcription, RNA Polymerase II, HP1γ, Matrin 3 and SAF-A

    PubMed Central

    Malyavantham, Kishore S; Bhattacharya, Sambit; Barbeitos, Marcos; Mukherjee, Lopamudra; Xu, Jinhui; Fackelmayer, Frank O; Berezney, Ronald

    2009-01-01

    Higher order chromatin organization in concert with epigenetic regulation is a key process that determines gene expression at the global level. The organization of dynamic chromatin domains and their associated protein factors is intertwined with nuclear function to create higher levels of functional zones within the cell nucleus. As a step towards elucidating the organization and dynamics of these functional zones, we have investigated the spatial proximities among a constellation of functionally related sites that are found within euchromatic regions of the cell nucleus including: HP1γ, nascent transcript sites (TS), active DNA replicating sites in early S phase (PCNA) and RNA polymerase II sites. We report close associations among these different sites with proximity values specific for each combination. Analysis of matrin 3 and SAF-A sites demonstrates that these nuclear matrix proteins are highly proximal with the functionally related sites as well as to each other and display closely aligned and overlapping regions following application of the minimal spanning tree (MST) algorithm to visualize higher order network-like patterns. Our findings suggest that multiple factors within the nuclear microenvironment collectively form higher order combinatorial arrays of function. We propose a model for the organization of these functional neighborhoods which takes into account the proximity values of the individual sites and their spatial organization within the nuclear architecture. PMID:18618731

  17. Variation of solar cell sensitivity and solar radiation on tilted surfaces

    NASA Technical Reports Server (NTRS)

    Klucher, T. M.

    1978-01-01

    The validity is studied that one of various insolation models used to compute solar radiation incident on tilted surfaces from global data measured on horizontal surfaces. The variation of solar cell sensitivity to solar radiation is determined over a wide range of atmospheric condition. A new model was formulated that reduced the deviations between measured and predicted insolation to less than 3 percent. Evaluation of solar cell sensitivity data indicates small change (2-3 percent) in sensitivity from winter to summer for tilted cells. The feasibility of using such global data as a means for calibrating terrestrial solar cells is discussed.

  18. Heart-Derived Stem Cells in Miniature Swine with Coronary Microembolization: Novel Ischemic Cardiomyopathy Model to Assess the Efficacy of Cell-Based Therapy

    PubMed Central

    Young, Rebeccah F.; Leiker, Merced M.; Suzuki, Takayuki

    2016-01-01

    A major problem in translating stem cell therapeutics is the difficulty of producing stable, long-term severe left ventricular (LV) dysfunction in a large animal model. For that purpose, extensive infarction was created in sinclair miniswine by injecting microspheres (1.5 × 106 microspheres, 45 μm diameter) in LAD. At 2 months after embolization, animals (n = 11) were randomized to receive allogeneic cardiosphere-derived cells derived from atrium (CDCs: 20 × 106, n = 5) or saline (untreated, n = 6). Four weeks after therapy myocardial function, myocyte proliferation (Ki67), mitosis (phosphor-Histone H3; pHH3), apoptosis, infarct size (TTC), myocyte nuclear density, and cell size were evaluated. CDCs injected into infarcted and remodeled remote myocardium (global infusion) increased regional function and global function contrasting no change in untreated animals. CDCs reduced infarct volume and stimulated Ki67 and pHH3 positive myocytes in infarct and remote regions. As a result, myocyte number (nuclear density) increased and myocyte cell diameter decreased in both infarct and remote regions. Coronary microembolization produces stable long-term ischemic cardiomyopathy. Global infusion of CDCs stimulates myocyte regeneration and improves left ventricular ejection fraction. Thus, global infusion of CDCs could become a new therapy to reverse LV dysfunction in patients with asymptomatic heart failure. PMID:27738436

  19. Non-biased and efficient global amplification of a single-cell cDNA library

    PubMed Central

    Huang, Huan; Goto, Mari; Tsunoda, Hiroyuki; Sun, Lizhou; Taniguchi, Kiyomi; Matsunaga, Hiroko; Kambara, Hideki

    2014-01-01

    Analysis of single-cell gene expression promises a more precise understanding of molecular mechanisms of a living system. Most techniques only allow studies of the expressions for limited numbers of gene species. When amplification of cDNA was carried out for analysing more genes, amplification biases were frequently reported. A non-biased and efficient global-amplification method, which uses a single-cell cDNA library immobilized on beads, was developed for analysing entire gene expressions for single cells. Every step in this analysis from reverse transcription to cDNA amplification was optimized. By removing degrading excess primers, the bias due to the digestion of cDNA was prevented. Since the residual reagents, which affect the efficiency of each subsequent reaction, could be removed by washing beads, the conditions for uniform and maximized amplification of cDNAs were achieved. The differences in the amplification rates for randomly selected eight genes were within 1.5-folds, which could be negligible for most of the applications of single-cell analysis. The global amplification gives a large amount of amplified cDNA (>100 μg) from a single cell (2-pg mRNA), and that amount is enough for downstream analysis. The proposed global-amplification method was used to analyse transcript ratios of multiple cDNA targets (from several copies to several thousand copies) quantitatively. PMID:24141095

  20. Patterns of globalized reproduction: Egg cells regulation in Israel and Austria

    PubMed Central

    2012-01-01

    Since the successful introduction of in vitro fertilization in 1978, medically assisted reproduction (MAR) has proliferated in multiple clinical innovations. Consequently, egg cells have become an object of demand for both infertility treatment and stem cell research, and this raises complex legal, ethical, social and economic issues. In this paper we compare how the procurement and use of human egg cells is regulated in two countries: Israel and Austria. Israel is known for its scientific leadership, generous public funding, high utilization and liberal regulation of assisted reproductive technology (ART). Austria lies at the other extreme of the regulatory spectrum in terms of restrictions on reproductive interventions. In both countries, however, there is a constant increase in the use of the technology, and recent legal developments make egg cells more accessible. Also, in both countries the scarcity of egg cells in concert with the rising demand for donations has led to the emergence of cross-border markets and global 'reproductive tourism' practices. In Israel, in particular, a scandal known as the 'eggs affair' was followed by regulation that allowed egg cell donations from outside the country under certain conditions. Cross-border markets are developed by medical entrepreneurs, driven by global economic gaps, made possible by trans-national regulatory lacunae and find expression as consumer demand. The transnational practice of egg cell donations indicates the emergence of a global public health issue, but there is a general lack of medical and epidemiological data on its efficacy and safety. We conclude that there is need for harmonisation of domestic laws and formulation of new instruments for international governance. PMID:22913734

  1. Patterns of globalized reproduction: Egg cells regulation in Israel and Austria.

    PubMed

    Shalev, Carmel; Werner-Felmayer, Gabriele

    2012-04-18

    Since the successful introduction of in vitro fertilization in 1978, medically assisted reproduction (MAR) has proliferated in multiple clinical innovations. Consequently, egg cells have become an object of demand for both infertility treatment and stem cell research, and this raises complex legal, ethical, social and economic issues.In this paper we compare how the procurement and use of human egg cells is regulated in two countries: Israel and Austria. Israel is known for its scientific leadership, generous public funding, high utilization and liberal regulation of assisted reproductive technology (ART). Austria lies at the other extreme of the regulatory spectrum in terms of restrictions on reproductive interventions.In both countries, however, there is a constant increase in the use of the technology, and recent legal developments make egg cells more accessible. Also, in both countries the scarcity of egg cells in concert with the rising demand for donations has led to the emergence of cross-border markets and global 'reproductive tourism' practices. In Israel, in particular, a scandal known as the 'eggs affair' was followed by regulation that allowed egg cell donations from outside the country under certain conditions.Cross-border markets are developed by medical entrepreneurs, driven by global economic gaps, made possible by trans-national regulatory lacunae and find expression as consumer demand. The transnational practice of egg cell donations indicates the emergence of a global public health issue, but there is a general lack of medical and epidemiological data on its efficacy and safety. We conclude that there is need for harmonisation of domestic laws and formulation of new instruments for international governance.

  2. Forecasting Plant Productivity and Health Using Diffuse-to-Global Irradiance Ratios Extracted from the OMI Aerosol Product

    NASA Technical Reports Server (NTRS)

    Knowlton, Kelly; Andrews, Jane C.; Ryan, Robert E.

    2007-01-01

    Atmospheric aerosols are a major contributor to diffuse irradiance. This Candidate Solution suggests using the OMI (Ozone Monitoring Instrument) aerosol product as input into a radiative transfer model, which would calculate the ratio of diffuse to global irradiance at the Earth s surface. This ratio can significantly influence the rate of photosynthesis in plants; increasing the ratio of diffuse to global irradiance can accelerate photosynthesis, resulting in greater plant productivity. Accurate values of this ratio could be useful in predicting crop productivity, thereby improving forecasts of regional food resources. However, disagreements exist between diffuse-to-global irradiance values measured by different satellites and ground sensors. OMI, with its unique combination of spectral bands, high resolution, and daily global coverage, may be able to provide more accurate aerosol measurements than other comparable sensors.

  3. Global Effects of DDX3 Inhibition on Cell Cycle Regulation Identified by a Combined Phosphoproteomics and Single Cell Tracking Approach.

    PubMed

    Heerma van Voss, Marise R; Kammers, Kai; Vesuna, Farhad; Brilliant, Justin; Bergman, Yehudit; Tantravedi, Saritha; Wu, Xinyan; Cole, Robert N; Holland, Andrew; van Diest, Paul J; Raman, Venu

    2018-06-01

    DDX3 is an RNA helicase with oncogenic properties. The small molecule inhibitor RK-33 is designed to fit into the ATP binding cleft of DDX3 and hereby block its activity. RK-33 has shown potent activity in preclinical cancer models. However, the mechanism behind the antineoplastic activity of RK-33 remains largely unknown. In this study we used a dual phosphoproteomic and single cell tracking approach to evaluate the effect of RK-33 on cancer cells. MDA-MB-435 cells were treated for 24 hours with RK-33 or vehicle control. Changes in phosphopeptide abundance were analyzed with quantitative mass spectrometry using isobaric mass tags (Tandem Mass Tags). At the proteome level we mainly observed changes in mitochondrial translation, cell division pathways and proteins related to cell cycle progression. Analysis of the phosphoproteome indicated decreased CDK1 activity after RK-33 treatment. To further evaluate the effect of DDX3 inhibition on cell cycle progression over time, we performed timelapse microscopy of Fluorescent Ubiquitin Cell Cycle Indicators labeled cells after RK-33 or siDDX3 exposure. Single cell tracking indicated that DDX3 inhibition resulted in a global delay in cell cycle progression in interphase and mitosis. In addition, we observed an increase in endoreduplication. Overall, we conclude that DDX3 inhibition affects cells in all phases and causes a global cell cycle progression delay. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Forecasting Electric Power Generation of Photovoltaic Power System for Energy Network

    NASA Astrophysics Data System (ADS)

    Kudo, Mitsuru; Takeuchi, Akira; Nozaki, Yousuke; Endo, Hisahito; Sumita, Jiro

    Recently, there has been an increase in concern about the global environment. Interest is growing in developing an energy network by which new energy systems such as photovoltaic and fuel cells generate power locally and electric power and heat are controlled with a communications network. We developed the power generation forecast method for photovoltaic power systems in an energy network. The method makes use of weather information and regression analysis. We carried out forecasting power output of the photovoltaic power system installed in Expo 2005, Aichi Japan. As a result of comparing measurements with a prediction values, the average prediction error per day was about 26% of the measured power.

  5. The Impact of Different Absolute Solar Irradiance Values on Current Climate Model Simulations

    NASA Technical Reports Server (NTRS)

    Rind, David H.; Lean, Judith L.; Jonas, Jeffrey

    2014-01-01

    Simulations of the preindustrial and doubled CO2 climates are made with the GISS Global Climate Middle Atmosphere Model 3 using two different estimates of the absolute solar irradiance value: a higher value measured by solar radiometers in the 1990s and a lower value measured recently by the Solar Radiation and Climate Experiment. Each of the model simulations is adjusted to achieve global energy balance; without this adjustment the difference in irradiance produces a global temperature change of 0.48C, comparable to the cooling estimated for the Maunder Minimum. The results indicate that by altering cloud cover the model properly compensates for the different absolute solar irradiance values on a global level when simulating both preindustrial and doubled CO2 climates. On a regional level, the preindustrial climate simulations and the patterns of change with doubled CO2 concentrations are again remarkably similar, but there are some differences. Using a higher absolute solar irradiance value and the requisite cloud cover affects the model's depictions of high-latitude surface air temperature, sea level pressure, and stratospheric ozone, as well as tropical precipitation. In the climate change experiments it leads to an underestimation of North Atlantic warming, reduced precipitation in the tropical western Pacific, and smaller total ozone growth at high northern latitudes. Although significant, these differences are typically modest compared with the magnitude of the regional changes expected for doubled greenhouse gas concentrations. Nevertheless, the model simulations demonstrate that achieving the highest possible fidelity when simulating regional climate change requires that climate models use as input the most accurate (lower) solar irradiance value.

  6. Micromechanics Fatigue Damage Analysis Modeling for Fabric Reinforced Ceramic Matrix Composites

    NASA Technical Reports Server (NTRS)

    Min, J. B.; Xue, D.; Shi, Y.

    2013-01-01

    A micromechanics analysis modeling method was developed to analyze the damage progression and fatigue failure of fabric reinforced composite structures, especially for the brittle ceramic matrix material composites. A repeating unit cell concept of fabric reinforced composites was used to represent the global composite structure. The thermal and mechanical properties of the repeating unit cell were considered as the same as those of the global composite structure. The three-phase micromechanics, the shear-lag, and the continuum fracture mechanics models were integrated with a statistical model in the repeating unit cell to predict the progressive damages and fatigue life of the composite structures. The global structure failure was defined as the loss of loading capability of the repeating unit cell, which depends on the stiffness reduction due to material slice failures and nonlinear material properties in the repeating unit cell. The present methodology is demonstrated with the analysis results evaluated through the experimental test performed with carbon fiber reinforced silicon carbide matrix plain weave composite specimens.

  7. Diagnostic Capability of Peripapillary Three-dimensional Retinal Nerve Fiber Layer Volume for Glaucoma Using Optical Coherence Tomography Volume Scans.

    PubMed

    Khoueir, Ziad; Jassim, Firas; Poon, Linda Yi-Chieh; Tsikata, Edem; Ben-David, Geulah S; Liu, Yingna; Shieh, Eric; Lee, Ramon; Guo, Rong; Papadogeorgou, Georgia; Braaf, Boy; Simavli, Huseyin; Que, Christian; Vakoc, Benjamin J; Bouma, Brett E; de Boer, Johannes F; Chen, Teresa C

    2017-10-01

    To determine the diagnostic capability of peripapillary 3-dimensional (3D) retinal nerve fiber layer (RNFL) volume measurements from spectral-domain optical coherence tomography (OCT) volume scans for open-angle glaucoma (OAG). Assessment of diagnostic accuracy. Setting: Academic clinical setting. Total of 180 patients (113 OAG and 67 normal subjects). One eye per subject was included. Peripapillary 3D RNFL volumes were calculated for global, quadrant, and sector regions, using 4 different-size annuli. Peripapillary 2D RNFL thickness circle scans were also obtained. Area under the receiver operating characteristic curve (AUROC) values, sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios. Among all 2D and 3D RNFL parameters, best diagnostic capability was associated with inferior quadrant 3D RNFL volume of the smallest annulus (AUROC value 0.977). Otherwise, global 3D RNFL volume AUROC values were comparable to global 2D RNFL thickness AUROC values for all 4 annulus sizes (P values: .0593 to .6866). When comparing the 4 annulus sizes for global RNFL volume, the smallest annulus had the best AUROC values (P values: .0317 to .0380). The smallest-size annulus may have the best diagnostic potential, partly owing to having no areas excluded for being larger than the 6 × 6 mm 2 scanned region. Peripapillary 3D RNFL volume showed excellent diagnostic performance for detecting glaucoma. Peripapillary 3D RNFL volume parameters have the same or better diagnostic capability compared to peripapillary 2D RNFL thickness measurements, although differences were not statistically significant. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Exploration of DGVM Parameter Solution Space Using Simulated Annealing: Implications for Forecast Uncertainties

    NASA Astrophysics Data System (ADS)

    Wells, J. R.; Kim, J. B.

    2011-12-01

    Parameters in dynamic global vegetation models (DGVMs) are thought to be weakly constrained and can be a significant source of errors and uncertainties. DGVMs use between 5 and 26 plant functional types (PFTs) to represent the average plant life form in each simulated plot, and each PFT typically has a dozen or more parameters that define the way it uses resource and responds to the simulated growing environment. Sensitivity analysis explores how varying parameters affects the output, but does not do a full exploration of the parameter solution space. The solution space for DGVM parameter values are thought to be complex and non-linear; and multiple sets of acceptable parameters may exist. In published studies, PFT parameters are estimated from published literature, and often a parameter value is estimated from a single published value. Further, the parameters are "tuned" using somewhat arbitrary, "trial-and-error" methods. BIOMAP is a new DGVM created by fusing MAPSS biogeography model with Biome-BGC. It represents the vegetation of North America using 26 PFTs. We are using simulated annealing, a global search method, to systematically and objectively explore the solution space for the BIOMAP PFTs and system parameters important for plant water use. We defined the boundaries of the solution space by obtaining maximum and minimum values from published literature, and where those were not available, using +/-20% of current values. We used stratified random sampling to select a set of grid cells representing the vegetation of the conterminous USA. Simulated annealing algorithm is applied to the parameters for spin-up and a transient run during the historical period 1961-1990. A set of parameter values is considered acceptable if the associated simulation run produces a modern potential vegetation distribution map that is as accurate as one produced by trial-and-error calibration. We expect to confirm that the solution space is non-linear and complex, and that multiple acceptable parameter sets exist. Further we expect to demonstrate that the multiple parameter sets produce significantly divergent future forecasts in NEP, C storage, and ET and runoff; and thereby identify a highly important source of DGVM uncertainty

  9. Whole-genome transcriptional analysis of Escherichia coli during heat inactivation processes related to industrial cooking.

    PubMed

    Guernec, A; Robichaud-Rincon, P; Saucier, L

    2013-08-01

    Escherichia coli K-12 was grown to the stationary phase, for maximum physiological resistance, in brain heart infusion (BHI) broth at 37°C. Cells were then heated at 58°C or 60°C to reach a process lethality value \\[\\mathbf{\\left(}{{\\mathit{F}}^{\\mathit{o}}}_{\\mathbf{70}}^{\\mathbf{10}}\\mathbf{\\right)} \\] of 2 or 3 or to a core temperature of 71°C (control industrial cooking temperature). Growth recovery and cell membrane integrity were evaluated immediately after heating, and a global transcription analysis was performed using gene expression microarrays. Only cells heated at 58°C with F(o) = 2 were still able to grow on liquid or solid BHI broth after heat treatment. However, their transcriptome did not differ from that of bacteria heated at 58°C with F(o) = 3 (P value for the false discovery rate [P-FDR] > 0.01), where no growth recovery was observed posttreatment. Genome-wide transcriptomic data obtained at 71°C were distinct from those of the other treatments without growth recovery. Quantification of heat shock gene expression by real-time PCR revealed that dnaK and groEL mRNA levels decreased significantly above 60°C to reach levels similar to those of control cells at 37°C (P < 0.0001). Furthermore, despite similar levels of cell inactivation measured by growth on BHI media after heating, 132 and 8 genes were differentially expressed at 71°C compared to 58°C and 60°C at F(o) = 3, respectively (P-FDR < 0.01). Among them, genes such as aroA, citE, glyS, oppB, and asd, whose expression was upregulated at 71°C, may be worth investigating as good biomarkers for accurately determining the efficiency of heat treatments, especially when cells are too injured to be enumerated using growth media.

  10. Developing Character and Values for Global Citizens: Analysis of Pre-Service Science Teachers' Moral Reasoning on Socioscientific Issues

    ERIC Educational Resources Information Center

    Lee, Hyunju; Chang, Hyunsook; Choi, Kyunghee; Kim, Sung-Won; Zeidler, Dana L.

    2012-01-01

    Character and values are the essential driving forces that serve as general guides or points of reference for individuals to support decision-making and to act responsibly about global socioscientific issues (SSIs). Based on this assumption, we investigated to what extent pre-service science teachers (PSTs) of South Korea possess character and…

  11. Diversity in spatial scope of contrast adaptation among mouse retinal ganglion cells

    PubMed Central

    Khani, Mohammad Hossein

    2017-01-01

    Retinal ganglion cells adapt to changes in visual contrast by adjusting their response kinetics and sensitivity. While much work has focused on the time scales of these adaptation processes, less is known about the spatial scale of contrast adaptation. For example, do small, localized contrast changes affect a cell’s signal processing across its entire receptive field? Previous investigations have provided conflicting evidence, suggesting that contrast adaptation occurs either locally within subregions of a ganglion cell’s receptive field or globally over the receptive field in its entirety. Here, we investigated the spatial extent of contrast adaptation in ganglion cells of the isolated mouse retina through multielectrode-array recordings. We applied visual stimuli so that ganglion cell receptive fields contained regions where the average contrast level changed periodically as well as regions with constant average contrast level. This allowed us to analyze temporal stimulus integration and sensitivity separately for stimulus regions with and without contrast changes. We found that the spatial scope of contrast adaptation depends strongly on cell identity, with some ganglion cells displaying clear local adaptation, whereas others, in particular large transient ganglion cells, adapted globally to contrast changes. Thus, the spatial scope of contrast adaptation in mouse retinal ganglion cells appears to be cell-type specific. This could reflect differences in mechanisms of contrast adaptation and may contribute to the functional diversity of different ganglion cell types. NEW & NOTEWORTHY Understanding whether adaptation of a neuron in a sensory system can occur locally inside the receptive field or whether it always globally affects the entire receptive field is important for understanding how the neuron processes complex sensory stimuli. For mouse retinal ganglion cells, we here show that both local and global contrast adaptation exist and that this diversity in spatial scope can contribute to the functional diversity of retinal ganglion cell types. PMID:28904106

  12. 40 CFR 52.223 - Approval status.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from paragraph (b)(4)(ii)(A) of... associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming...

  13. 40 CFR 52.1634 - Significant deterioration of air quality.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... gases in the pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from paragraph (b)(4... associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming...

  14. 40 CFR 52.223 - Approval status.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from paragraph (b)(4)(ii)(A) of... associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming...

  15. 40 CFR 52.223 - Approval status.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from paragraph (b)(4)(ii)(A) of... associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming...

  16. 40 CFR 52.223 - Approval status.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from paragraph (b)(4)(ii)(A) of... associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming...

  17. Global preamplification simplifies targeted mRNA quantification

    PubMed Central

    Kroneis, Thomas; Jonasson, Emma; Andersson, Daniel; Dolatabadi, Soheila; Ståhlberg, Anders

    2017-01-01

    The need to perform gene expression profiling using next generation sequencing and quantitative real-time PCR (qPCR) on small sample sizes and single cells is rapidly expanding. However, to analyse few molecules, preamplification is required. Here, we studied global and target-specific preamplification using 96 optimised qPCR assays. To evaluate the preamplification strategies, we monitored the reactions in real-time using SYBR Green I detection chemistry followed by melting curve analysis. Next, we compared yield and reproducibility of global preamplification to that of target-specific preamplification by qPCR using the same amount of total RNA. Global preamplification generated 9.3-fold lower yield and 1.6-fold lower reproducibility than target-specific preamplification. However, the performance of global preamplification is sufficient for most downstream applications and offers several advantages over target-specific preamplification. To demonstrate the potential of global preamplification we analysed the expression of 15 genes in 60 single cells. In conclusion, we show that global preamplification simplifies targeted gene expression profiling of small sample sizes by a flexible workflow. We outline the pros and cons for global preamplification compared to target-specific preamplification. PMID:28332609

  18. Epigenetic regulation of open chromatin in pluripotent stem cells

    PubMed Central

    Kobayashi, Hiroshi; Kikyo, Nobuaki

    2014-01-01

    The recent progress in pluripotent stem cell research has opened new avenues of disease modeling, drug screening, and transplantation of patient-specific tissues that had been unimaginable until a decade ago. The central mechanism underlying pluripotency is epigenetic gene regulation; the majority of cell signaling pathways, both extracellular and cytoplasmic, eventually alter the epigenetic status of their target genes during the process of activating or suppressing the genes to acquire or maintain pluripotency. It has long been thought that the chromatin of pluripotent stem cells is globally open to enable the timely activation of essentially all genes in the genome during differentiation into multiple lineages. The current article reviews descriptive observations and the epigenetic machinery relevant to what is supposed to be globally open chromatin in pluripotent stem cells. This includes microscopic appearance, permissive gene transcription, chromatin remodeling complexes, histone modifications, DNA methylation, noncoding RNAs, dynamic movement of chromatin proteins, nucleosome accessibility and positioning, and long-range chromosomal interactions. Detailed analyses of each element, however, have revealed that the globally open chromatin hypothesis is not necessarily supported by some of the critical experimental evidence, such as genome-wide nucleosome accessibility and nucleosome positioning. Further understanding of the epigenetic gene regulation is expected to determine the true nature of the so-called globally open chromatin in pluripotent stem. PMID:24695097

  19. Computer Modelling and Simulation of Solar PV Array Characteristics

    NASA Astrophysics Data System (ADS)

    Gautam, Nalin Kumar

    2003-02-01

    The main objective of my PhD research work was to study the behaviour of inter-connected solar photovoltaic (PV) arrays. The approach involved the construction of mathematical models to investigate different types of research problems related to the energy yield, fault tolerance, efficiency and optimal sizing of inter-connected solar PV array systems. My research work can be divided into four different types of research problems: 1. Modeling of inter-connected solar PV array systems to investigate their electrical behavior, 2. Modeling of different inter-connected solar PV array networks to predict their expected operational lifetimes, 3. Modeling solar radiation estimation and its variability, and 4. Modeling of a coupled system to estimate the size of PV array and battery-bank in the stand-alone inter-connected solar PV system where the solar PV system depends on a system providing solar radiant energy. The successful application of mathematics to the above-m entioned problems entailed three phases: 1. The formulation of the problem in a mathematical form using numerical, optimization, probabilistic and statistical methods / techniques, 2. The translation of mathematical models using C++ to simulate them on a computer, and 3. The interpretation of the results to see how closely they correlated with the real data. Array is the most cost-intensive component of the solar PV system. Since the electrical performances as well as life properties of an array are highly sensitive to field conditions, different characteristics of the arrays, such as energy yield, operational lifetime, collector orientation, and optimal sizing were investigated in order to improve their efficiency, fault-tolerance and reliability. Three solar cell interconnection configurations in the array - series-parallel, total-cross-tied, and bridge-linked, were considered. The electrical characteristics of these configurations were investigated to find out one that is comparatively less susceptible to the mismatches due to manufacturer's tolerances in cell characteristics, shadowing, soiling and aging of solar cells. The current-voltage curves and the values of energy yield characterized by maximum-power points and fill factors for these arrays were also obtained. Two different mathematical models, one for smaller size arrays and the other for the larger size arrays, were developed. The first model takes account of the partial differential equations with boundary value conditions, whereas the second one involves the simple linear programming concept. Based on the initial information on the values of short-circuit current and open-circuit voltage of thirty-six single-crystalline silicon solar cells provided by a manufacturer, the values of these parameters for up to 14,400 solar cells were generated randomly. Thus, the investigations were done for three different cases of array sizes, i.e., (6 x 6), (36 x 8) and (720 x 20), for each configuration. The operational lifetimes of different interconnected solar PV arrays and the improvement in their life properties through different interconnection and modularized configurations were investigated using a reliability-index model. Under normal conditions, the efficiency of a solar cell degrades in an exponential manner, and its operational life above a lowest admissible efficiency may be considered as the upper bound of its lifetime. Under field conditions, the solar cell may fail any time due to environmental stresses, or it may function up to the end of its expected lifetime. In view of this, the lifetime of a solar cell in an array was represented by an exponentially distributed random variable. At any instant of time t, this random variable was considered to have two states: (i) the cell functioned till time t, or (ii) the cell failed within time t. It was considered that the functioning of the solar cell included its operation at an efficiency decaying with time under normal conditions. It was assumed that the lifetime of a solar cell had lack of memory or aging property, which meant that no matter how long (say, t) the cell had been operational, the probability that it would last an additional time ?t was independent of t. The operational life of the solar cell above a lowest admissible efficiency was considered as the upper bound of its expected lifetime. The value of the upper bound on the expected life of solar cell was evaluated using the information provided by the manufacturers of the single-crystalline silicon solar cells. Then on the basis of these lifetimes, the expected operational lifetimes of the array systems were obtained. Since the investigations of the effects of collector orientation on the performance of an array require the continuous values of global solar radiation on a surface, a method to estimate the global solar radiation on a surface (horizontal or tilted) was also proposed. The cloudiness index was defined as the fraction of extraterrestrial radiation that reached the earth's surface when the sky above the location of interest was obscured by the cloud cover. The cloud cover at the location of interest during any time interval of a day was assumed to follow the fuzzy random phenomenon. The cloudiness index, therefore, was considered as a fuzzy random variable that accounted for the cloud cover at the location of interest during any time interval of a day. This variable was assumed to depend on four other fuzzy random variables that, respectively, accounted for the cloud cover corresponding to the 1) type of cloud group, 2) climatic region, 3) season with most of the precipitation, and 4) type of precipitation at the location of interest during any time interval. All possible types of cloud covers were categorized into five types of cloud groups. Each cloud group was considered to be a fuzzy subset. In this model, the cloud cover at the location of interest during a time interval was considered to be the clouds that obscure the sky above the location. The cloud covers, with all possible types of clouds having transmissivities corresponding to values in the membership range of a fuzzy subset (i.e., a type of cloud group), were considered to be the membership elements of that fuzzy subset. The transmissivities of different types of cloud covers in a cloud group corresponded to the values in the membership range of that cloud group. Predicate logic (i.e., if---then---, else---, conditions) was used to set the relationship between all the fuzzy random variables. The values of the above-mentioned fuzzy random variables were evaluated to provide the value of cloudiness index for each time interval at the location of interest. For each case of the fuzzy random variable, heuristic approach was used to identify subjectively the range ([a, b], where a and b were real numbers with in [0, 1] such that a

  20. Beyond offshoring: assess your company's global potential.

    PubMed

    Farrell, Diana

    2004-12-01

    In the past few years, companies have become aware that they can slash costs by offshoring: moving jobs to lower-wage locations. But this practice is just the tip of the iceberg in terms of how globalization can transform industries, according to research by the McKinsey Global Institute (MGI). The institute's yearlong study suggests that by streamlining their production processes and supply chains globally, rather than just nationally or regionally, companies can lower their costs-as we've seen in the consumer-electronics and PC industries. Companies can save as much as 70% of their total costs through globalization--50% from offshoring, 5% from training and business-task redesign, and 15% from process improvements. But they don't have to stop there. The cost reductions make it possible to lower prices and expand into new markets, attracting whole new classes of customers. To date, however, few businesses have recognized the full scope of performance improvements that globalization makes possible, much less developed sound strategies for capturing those opportunities. In this article, Diana Farrell, director of MGI, offers a step-by-step approach to doing both things. Among her suggestions: Assess where your industry falls along the globalization spectrum, because not all sectors of the economy face the same challenges and opportunities at the same time. Also, pay attention to production, regulatory, and organizational barriers to globalization. If any of these can be changed, size up the cost-saving (and revenue-generating) opportunities that will emerge for your company as a result of those changes. Farrell also defines the five stages of globalization-market entry, product specialization, value chain disaggregation, value chain reengineering, and the creation of new markets-and notes the different levers for cutting costs and creating value that companies can use in each phase.

  1. The global distribution of pteropods and their contribution to carbonate and carbon biomass in the modern ocean

    NASA Astrophysics Data System (ADS)

    Bednaršek, N.; Možina, J.; Vogt, M.; O'Brien, C.; Tarling, G. A.

    2012-12-01

    Pteropods are a group of holoplanktonic gastropods for which global biomass distribution patterns remain poorly described. The aim of this study was to collect and synthesise existing pteropod (Gymnosomata, Thecosomata and Pseudothecosomata) abundance and biomass data, in order to evaluate the global distribution of pteropod carbon biomass, with a particular emphasis on temporal and spatial patterns. We collected 25 939 data points from several online databases and 41 scientific articles. These data points corresponded to observations from 15 134 stations, where 93% of observations were of shelled pteropods (Thecosomata) and 7% of non-shelled pteropods (Gymnosomata). The biomass data has been gridded onto a 360 × 180° grid, with a vertical resolution of 33 depth levels. Both the raw data file and the gridded data in NetCDF format can be downloaded from PANGAEA, doi:10.1594/PANGAEA.777387. Data were collected between 1950-2010, with sampling depths ranging from 0-2000 m. Pteropod biomass data was either extracted directly or derived through converting abundance to biomass with pteropod-specific length to carbon biomass conversion algorithms. In the Northern Hemisphere (NH), the data were distributed quite evenly throughout the year, whereas sampling in the Southern Hemisphere (SH) was biased towards winter and summer values. 86% of all biomass values were located in the NH, most (37%) within the latitudinal band of 30-60° N. The range of global biomass values spanned over four orders of magnitude, with mean and median (non-zero) biomass values of 4.6 mg C m-3 (SD = 62.5) and 0.015 mg C m-3, respectively. The highest mean biomass was located in the SH within the 70-80° S latitudinal band (39.71 mg C m-3, SD = 93.00), while the highest median biomass was in the NH, between 40-50° S (0.06 mg C m-3, SD = 79.94). Shelled pteropods constituted a mean global carbonate biomass of 23.17 mg CaCO3 m-3 (based on non-zero records). Total biomass values were lowest in the equatorial regions and equally high at both poles. Pteropods were found at least to depths of 1000 m, with the highest biomass values located in the surface layer (0-10 m) and gradually decreasing with depth, with values in excess of 100 mg C m-3 only found above 200 m depth. Tropical species tended to concentrate at greater depths than temperate or high-latitude species. Global biomass levels in the NH were relatively invariant over the seasonal cycle, but more seasonally variable in the SH. The collected database provides a valuable tool for modellers for the study of marine ecosystem processes and global biogeochemical cycles. By extrapolating regional biomass to a global scale, we established global pteropod biomass to add up to 500 Tg C.

  2. Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis

    PubMed Central

    Rajasingham, Radha; Smith, Rachel M; Park, Benjamin J; Jarvis, Joseph N; Govender, Nelesh P; Chiller, Tom M; Denning, David W; Loyse, Angela; Boulware, David R

    2018-01-01

    Summary Background Cryptococcus is the most common cause of meningitis in adults living with HIV in sub-Saharan Africa. Global burden estimates are crucial to guide prevention strategies and to determine treatment needs, and we aimed to provide an updated estimate of global incidence of HIV-associated cryptococcal disease. Methods We used 2014 Joint UN Programme on HIV and AIDS estimates of adults (aged >15 years) with HIV and antiretroviral therapy (ART) coverage. Estimates of CD4 less than 100 cells per µL, virological failure incidence, and loss to follow-up were from published multinational cohorts in low-income and middle-income countries. We calculated those at risk for cryptococcal infection, specifically those with CD4 less than 100 cells/µL not on ART, and those with CD4 less than 100 cells per µL on ART but lost to follow-up or with virological failure. Cryptococcal antigenaemia prevalence by country was derived from 46 studies globally. Based on cryptococcal antigenaemia prevalence in each country and region, we estimated the annual numbers of people who are developing and dying from cryptococcal meningitis. Findings We estimated an average global cryptococcal antigenaemia prevalence of 6·0% (95% CI 5·8–6·2) among people with a CD4 cell count of less than 100 cells per µL, with 278 000 (95% CI 195 500–340 600) people positive for cryptococcal antigen globally and 223 100 (95% CI 150 600–282 400) incident cases of cryptococcal meningitis globally in 2014. Sub-Saharan Africa accounted for 73% of the estimated cryptococcal meningitis cases in 2014 (162 500 cases [95% CI 113 600–193 900]). Annual global deaths from cryptococcal meningitis were estimated at 181 100 (95% CI 119 400–234 300), with 135 900 (75%; [95% CI 93 900–163 900]) deaths in sub-Saharan Africa. Globally, cryptococcal meningitis was responsible for 15% of AIDS-related deaths (95% CI 10–19). Interpretation Our analysis highlights the substantial ongoing burden of HIV-associated cryptococcal disease, primarily in sub-Saharan Africa. Cryptococcal meningitis is a metric of HIV treatment programme failure; timely HIV testing and rapid linkage to care remain an urgent priority. Funding None. PMID:28483415

  3. Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis.

    PubMed

    Rajasingham, Radha; Smith, Rachel M; Park, Benjamin J; Jarvis, Joseph N; Govender, Nelesh P; Chiller, Tom M; Denning, David W; Loyse, Angela; Boulware, David R

    2017-08-01

    Cryptococcus is the most common cause of meningitis in adults living with HIV in sub-Saharan Africa. Global burden estimates are crucial to guide prevention strategies and to determine treatment needs, and we aimed to provide an updated estimate of global incidence of HIV-associated cryptococcal disease. We used 2014 Joint UN Programme on HIV and AIDS estimates of adults (aged >15 years) with HIV and antiretroviral therapy (ART) coverage. Estimates of CD4 less than 100 cells per μL, virological failure incidence, and loss to follow-up were from published multinational cohorts in low-income and middle-income countries. We calculated those at risk for cryptococcal infection, specifically those with CD4 less than 100 cells/μL not on ART, and those with CD4 less than 100 cells per μL on ART but lost to follow-up or with virological failure. Cryptococcal antigenaemia prevalence by country was derived from 46 studies globally. Based on cryptococcal antigenaemia prevalence in each country and region, we estimated the annual numbers of people who are developing and dying from cryptococcal meningitis. We estimated an average global cryptococcal antigenaemia prevalence of 6·0% (95% CI 5·8-6·2) among people with a CD4 cell count of less than 100 cells per μL, with 278 000 (95% CI 195 500-340 600) people positive for cryptococcal antigen globally and 223 100 (95% CI 150 600-282 400) incident cases of cryptococcal meningitis globally in 2014. Sub-Saharan Africa accounted for 73% of the estimated cryptococcal meningitis cases in 2014 (162 500 cases [95% CI 113 600-193 900]). Annual global deaths from cryptococcal meningitis were estimated at 181 100 (95% CI 119 400-234 300), with 135 900 (75%; [95% CI 93 900-163 900]) deaths in sub-Saharan Africa. Globally, cryptococcal meningitis was responsible for 15% of AIDS-related deaths (95% CI 10-19). Our analysis highlights the substantial ongoing burden of HIV-associated cryptococcal disease, primarily in sub-Saharan Africa. Cryptococcal meningitis is a metric of HIV treatment programme failure; timely HIV testing and rapid linkage to care remain an urgent priority. None. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Soybean Trade: Balancing Environmental and Socio-Economic Impacts of an Intercontinental Market.

    PubMed

    Boerema, Annelies; Peeters, Alain; Swolfs, Sanne; Vandevenne, Floor; Jacobs, Sander; Staes, Jan; Meire, Patrick

    2016-01-01

    The trade in soybean, an important animal feed product, exemplifies the environmental and socio-economic impact of global markets and global agricultural policy. This paper analyses the impact of increasing production of soybean in the exporting countries (deforestation and grassland conversion) as well as in importing regions (decrease in permanent grassland by substitution of grass as feed). Ecosystem services monetary values were used to calculate the environmental and socio-economic impact of observed land use changes. This is balanced against the economic value of the global soybean trade. The results prove that consumption choices in one region have real effects on the supply of ecosystem services at a large spatial scale. Conclusively, solutions to make this global market more sustainable are discussed.

  5. Emerging correlations between measures of population well-being, suicide and homicide: a look at global and Australian data.

    PubMed

    Lee, Adrian Ys; Pridmore, Saxby

    2014-04-01

    Our aim was (1) to examine global and Australian data with a view to determining the presence of an inverse relationship between suicide and homicide rates, and (2) to examine global Human Development Index (HDI) values and suicide and homicide rates, with a view to determining any statistical relationship. Suicide and homicide rates and HDI values were available for 102 countries, and suicide and homicide rates were available for the states and territories of Australia. The three data sets had non-normal distributions, and the non-parametric Spearman's ρ was used for correlation statistics with α = 0.05. We found a weak, statistically significant inverse relationship between the suicide and homicide rates of 102 countries (ρ = -0.244, p = 0.014). No relationship was established for the Australian values, however. As anticipated, we found a significant negative correlation between homicide and HDI values. We unexpectedly demonstrated a positive correlation between suicide rates and HDI values. The notion that suicide and homicide have an inverse relationship now has some scientific support; but additional research is warranted to characterise and explain this relationship. The unexpected finding of a positive correlation between suicide rates and HDI values requires further examination.

  6. The distribution of blood eosinophil levels in a Japanese COPD clinical trial database and in the rest of the world

    PubMed Central

    Ishii, Takeo; Hizawa, Nobuyuki; Midwinter, Dawn; James, Mark; Hilton, Emma; Jones, Paul W

    2018-01-01

    Background Blood eosinophil measurements may help to guide physicians on the use of inhaled corticosteroids (ICS) for patients with chronic obstructive pulmonary disease (COPD). Emerging data suggest that COPD patients with higher blood eosinophil counts may be at higher risk of exacerbations and more likely to benefit from combined ICS/long-acting beta2-agonist (LABA) treatment than therapy with a LABA alone. This analysis describes the distribution of blood eosinophil count at baseline in Japanese COPD patients in comparison with non-Japanese COPD patients. Methods A post hoc analysis of eosinophil distribution by percentage and absolute cell count was performed across 12 Phase II–IV COPD clinical studies (seven Japanese studies [N=848 available absolute eosinophil counts] and five global studies [N=5,397 available eosinophil counts] that included 246 Japanese patients resident in Japan with available counts). Blood eosinophil distributions were assessed at baseline, before blinded treatment assignment. Findings Among Japanese patients, the median (interquartile range) absolute eosinophil count was 170 cells/mm3 (100–280 cells/mm3). Overall, 612/1,094 Japanese patients (56%) had an absolute eosinophil count ≥150 cells/mm3 and 902/1,304 Japanese patients (69%) had a percentage eosinophil ≥2%. Among non-Japanese patients, these values were 160 (100–250) cells/mm3, 2,842/5,151 patients (55%), and 2,937/5,155 patients (57%), respectively. The eosinophil distribution among Japanese patients was similar to that among non-Japanese patients. Within multi-country studies with similar inclusion criteria, the eosinophil count was numerically lower in Japanese compared with non-Japanese patients (median 120 vs 160 cells/mm3). Interpretation The eosinophil distribution in Japanese patients seems comparable to that of non-Japanese patients; although within multi-country studies, there was a slightly lower median eosinophil count for Japanese patients compared with non-Japanese patients. These findings suggest that blood eosinophil data from global studies are of relevance in Japan. PMID:29440882

  7. Silver nanoparticles induce tight junction disruption and astrocyte neurotoxicity in a rat blood-brain barrier primary triple coculture model.

    PubMed

    Xu, Liming; Dan, Mo; Shao, Anliang; Cheng, Xiang; Zhang, Cuiping; Yokel, Robert A; Takemura, Taro; Hanagata, Nobutaka; Niwa, Masami; Watanabe, Daisuke

    2015-01-01

    Silver nanoparticles (Ag-NPs) can enter the brain and induce neurotoxicity. However, the toxicity of Ag-NPs on the blood-brain barrier (BBB) and the underlying mechanism(s) of action on the BBB and the brain are not well understood. To investigate Ag-NP suspension (Ag-NPS)-induced toxicity, a triple coculture BBB model of rat brain microvascular endothelial cells, pericytes, and astrocytes was established. The BBB permeability and tight junction protein expression in response to Ag-NPS, NP-released Ag ions, and polystyrene-NP exposure were investigated. Ultrastructural changes of the microvascular endothelial cells, pericytes, and astrocytes were observed using transmission electron microscopy (TEM). Global gene expression of astrocytes was measured using a DNA microarray. A triple coculture BBB model of primary rat brain microvascular endothelial cells, pericytes, and astrocytes was established, with the transendothelial electrical resistance values >200 Ω·cm(2). After Ag-NPS exposure for 24 hours, the BBB permeability was significantly increased and expression of the tight junction (TJ) protein ZO-1 was decreased. Discontinuous TJs were also observed between microvascular endothelial cells. After Ag-NPS exposure, severe mitochondrial shrinkage, vacuolations, endoplasmic reticulum expansion, and Ag-NPs were observed in astrocytes by TEM. Global gene expression analysis showed that three genes were upregulated and 20 genes were downregulated in astrocytes treated with Ag-NPS. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the 23 genes were associated with metabolic processes, biosynthetic processes, response to stimuli, cell death, the MAPK pathway, and so on. No GO term and KEGG pathways were changed in the released-ion or polystyrene-NP groups. Ag-NPS inhibited the antioxidant defense of the astrocytes by increasing thioredoxin interacting protein, which inhibits the Trx system, and decreasing Nr4a1 and Dusp1. Meanwhile, Ag-NPS induced inflammation and apoptosis through modulation of the MAPK pathway or B-cell lymphoma-2 expression or mTOR activity in astrocytes. These results draw our attention to the importance of Ag-NP-induced toxicity on the neurovascular unit and provide a better understanding of its toxicological mechanisms on astrocytes.

  8. Quantifying Cell Fate Decisions for Differentiation and Reprogramming of a Human Stem Cell Network: Landscape and Biological Paths

    PubMed Central

    Li, Chunhe; Wang, Jin

    2013-01-01

    Cellular reprogramming has been recently intensively studied experimentally. We developed a global potential landscape and kinetic path framework to explore a human stem cell developmental network composed of 52 genes. We uncovered the underlying landscape for the stem cell network with two basins of attractions representing stem and differentiated cell states, quantified and exhibited the high dimensional biological paths for the differentiation and reprogramming process, connecting the stem cell state and differentiated cell state. Both the landscape and non-equilibrium curl flux determine the dynamics of cell differentiation jointly. Flux leads the kinetic paths to be deviated from the steepest descent gradient path, and the corresponding differentiation and reprogramming paths are irreversible. Quantification of paths allows us to find out how the differentiation and reprogramming occur and which important states they go through. We show the developmental process proceeds as moving from the stem cell basin of attraction to the differentiation basin of attraction. The landscape topography characterized by the barrier heights and transition rates quantitatively determine the global stability and kinetic speed of cell fate decision process for development. Through the global sensitivity analysis, we provided some specific predictions for the effects of key genes and regulation connections on the cellular differentiation or reprogramming process. Key links from sensitivity analysis and biological paths can be used to guide the differentiation designs or reprogramming tactics. PMID:23935477

  9. An Improved Statistical Solution for Global Seismicity by the HIST-ETAS Approach

    NASA Astrophysics Data System (ADS)

    Chu, A.; Ogata, Y.; Katsura, K.

    2010-12-01

    For long-term global seismic model fitting, recent work by Chu et al. (2010) applied the spatial-temporal ETAS model (Ogata 1998) and analyzed global data partitioned into tectonic zones based on geophysical characteristics (Bird 2003), and it has shown tremendous improvements of model fitting compared with one overall global model. While the ordinary ETAS model assumes constant parameter values across the complete region analyzed, the hierarchical space-time ETAS model (HIST-ETAS, Ogata 2004) is a newly introduced approach by proposing regional distinctions of the parameters for more accurate seismic prediction. As the HIST-ETAS model has been fit to regional data of Japan (Ogata 2010), our work applies the model to describe global seismicity. Employing the Akaike's Bayesian Information Criterion (ABIC) as an assessment method, we compare the MLE results with zone divisions considered to results obtained by an overall global model. Location dependent parameters of the model and Gutenberg-Richter b-values are optimized, and seismological interpretations are discussed.

  10. Water T2 as an early, global and practical biomarker for metabolic syndrome: an observational cross-sectional study.

    PubMed

    Robinson, Michelle D; Mishra, Ina; Deodhar, Sneha; Patel, Vipulkumar; Gordon, Katrina V; Vintimilla, Raul; Brown, Kim; Johnson, Leigh; O'Bryant, Sid; Cistola, David P

    2017-12-19

    Metabolic syndrome (MetS) is a highly prevalent condition that identifies individuals at risk for type 2 diabetes mellitus and atherosclerotic cardiovascular disease. Prevention of these diseases relies on early detection and intervention in order to preserve pancreatic β-cells and arterial wall integrity. Yet, the clinical criteria for MetS are insensitive to the early-stage insulin resistance, inflammation, cholesterol and clotting factor abnormalities that characterize the progression toward type 2 diabetes and atherosclerosis. Here we report the discovery and initial characterization of an atypical new biomarker that detects these early conditions with just one measurement. Water T 2 , measured in a few minutes using benchtop nuclear magnetic resonance relaxometry, is exquisitely sensitive to metabolic shifts in the blood proteome. In an observational cross-sectional study of 72 non-diabetic human subjects, the association of plasma and serum water T 2 values with over 130 blood biomarkers was analyzed using bivariate, multivariate and logistic regression. Plasma and serum water T 2 exhibited strong bivariate correlations with markers of insulin, lipids, inflammation, coagulation and electrolyte balance. After correcting for confounders, low water T 2 values were independently and additively associated with fasting hyperinsulinemia, dyslipidemia and subclinical inflammation. Plasma water T 2 exhibited 100% sensitivity and 87% specificity for detecting early insulin resistance in normoglycemic subjects, as defined by the McAuley Index. Sixteen normoglycemic subjects with early metabolic abnormalities (22% of the study population) were identified by low water T 2 values. Thirteen of the 16 did not meet the harmonized clinical criteria for metabolic syndrome and would have been missed by conventional screening for diabetes risk. Low water T 2 values were associated with increases in the mean concentrations of 6 of the 16 most abundant acute phase proteins and lipoproteins in plasma. Water T 2 detects a constellation of early abnormalities associated with metabolic syndrome, providing a global view of an individual's metabolic health. It circumvents the pitfalls associated with fasting glucose and hemoglobin A1c and the limitations of the current clinical criteria for metabolic syndrome. Water T 2 shows promise as an early, global and practical screening tool for the identification of individuals at risk for diabetes and atherosclerosis.

  11. Ethics in practice: the state of the debate on promoting the social value of global health research in resource poor settings particularly Africa.

    PubMed

    Lairumbi, Geoffrey M; Michael, Parker; Fitzpatrick, Raymond; English, Michael C

    2011-11-15

    Promoting the social value of global health research undertaken in resource poor settings has become a key concern in global research ethics. The consideration for benefit sharing, which concerns the elucidation of what if anything, is owed to participants, their communities and host nations that take part in such research, and the obligations of researchers involved, is one of the main strategies used for promoting social value of research. In the last decade however, there has been intense debate within academic bioethics literature seeking to define the benefits, the beneficiaries, and the scope of obligations for providing these benefits. Although this debate may be indicative of willingness at the international level to engage with the responsibilities of researchers involved in global health research, it remains unclear which forms of benefits or beneficiaries should be considered. International and local research ethics guidelines are reviewed here to delineate the guidance they provide. We reviewed documents selected from the international compilation of research ethics guidelines by the Office for Human Research Protections under the US Department of Health and Human Services. Access to interventions being researched, the provision of unavailable health care, capacity building for individuals and institutions, support to health care systems and access to medical and public health interventions proven effective, are the commonly recommended forms of benefits. The beneficiaries are volunteers, disease or illness affected communities and the population in general. Interestingly however, there is a divide between "global opinion" and the views of particular countries within resource poor settings as made explicit by differences in emphasis regarding the potential benefits and the beneficiaries. Although in theory benefit sharing is widely accepted as one of the means for promoting the social value of international collaborative health research, there is less agreement amongst major guidelines on the specific responsibilities of researchers over what is ethical in promoting the social value of research. Lack of consensus might have practical implications for efforts aimed at enhancing the social value of global health research undertaken in resource poor settings. Further developments in global research ethics require more reflection, paying attention to the practical realities of implementing the ethical principles in real world context. © 2011 Lairumbi et al; licensee BioMed Central Ltd.

  12. Global value chains: Building blocks and network dynamics

    NASA Astrophysics Data System (ADS)

    Tsekeris, Theodore

    2017-12-01

    The paper employs measures and tools from complex network analysis to enhance the understanding and interpretation of structural characteristics pertaining to the Global Value Chains (GVCs) during the period 1995-2011. The analysis involves the country, sector and country-sector value chain networks to identify main drivers of structural change. The results indicate significant intertemporal changes, mirroring the increased globalization in terms of network size, strength and connectivity. They also demonstrate higher clustering and increased concentration of the most influential countries and country-sectors relative to all others in the GVC network, with the geographical dimension to prevail over the sectoral dimension in the formation of value chains. The regionalization and less hierarchical organization drive country-sector production sharing, while the sectoral value chain network has become more integrated and more competitive over time. The findings suggest that the impact of country-sector policies and/or shocks may vary with the own-group and network-wide influence of each country, take place in multiple geographical scales, as GVCs have a block structure, and involve time dynamics.

  13. Spatial Pattern of Standing Timber Value across the Brazilian Amazon

    PubMed Central

    Ahmed, Sadia E.; Ewers, Robert M.

    2012-01-01

    The Amazon is a globally important system, providing a host of ecosystem services from climate regulation to food sources. It is also home to a quarter of all global diversity. Large swathes of forest are removed each year, and many models have attempted to predict the spatial patterns of this forest loss. The spatial patterns of deforestation are determined largely by the patterns of roads that open access to frontier areas and expansion of the road network in the Amazon is largely determined by profit seeking logging activities. Here we present predictions for the spatial distribution of standing value of timber across the Amazon. We show that the patterns of timber value reflect large-scale ecological gradients, determining the spatial distribution of functional traits of trees which are, in turn, correlated with timber values. We expect that understanding the spatial patterns of timber value across the Amazon will aid predictions of logging movements and thus predictions of potential future road developments. These predictions in turn will be of great use in estimating the spatial patterns of deforestation in this globally important biome. PMID:22590520

  14. A global scale mechanistic model of photosynthetic capacity (LUNA V1.0)

    DOE PAGES

    Ali, Ashehad A.; Xu, Chonggang; Rogers, Alistair; ...

    2016-02-12

    Although plant photosynthetic capacity as determined by the maximum carboxylation rate (i.e., V c,max25) and the maximum electron transport rate (i.e., J max25) at a reference temperature (generally 25 °C) is known to vary considerably in space and time in response to environmental conditions, it is typically parameterized in Earth system models (ESMs) with tabulated values associated with plant functional types. In this study, we have developed a mechanistic model of leaf utilization of nitrogen for assimilation (LUNA) to predict photosynthetic capacity at the global scale under different environmental conditions. We adopt an optimality hypothesis to nitrogen allocation among lightmore » capture, electron transport, carboxylation and respiration. The LUNA model is able to reasonably capture the measured spatial and temporal patterns of photosynthetic capacity as it explains ~55 % of the global variation in observed values of V c,max25 and ~65 % of the variation in the observed values of J max25. Model simulations with LUNA under current and future climate conditions demonstrate that modeled values of V c,max25 are most affected in high-latitude regions under future climates. In conclusion, ESMs that relate the values of V c,max25 or J max25 to plant functional types only are likely to substantially overestimate future global photosynthesis.« less

  15. A Simple Model of Global Aerosol Indirect Effects

    NASA Technical Reports Server (NTRS)

    Ghan, Steven J.; Smith, Steven J.; Wang, Minghuai; Zhang, Kai; Pringle, Kirsty; Carslaw, Kenneth; Pierce, Jeffrey; Bauer, Susanne; Adams, Peter

    2013-01-01

    Most estimates of the global mean indirect effect of anthropogenic aerosol on the Earth's energy balance are from simulations by global models of the aerosol lifecycle coupled with global models of clouds and the hydrologic cycle. Extremely simple models have been developed for integrated assessment models, but lack the flexibility to distinguish between primary and secondary sources of aerosol. Here a simple but more physically based model expresses the aerosol indirect effect (AIE) using analytic representations of cloud and aerosol distributions and processes. Although the simple model is able to produce estimates of AIEs that are comparable to those from some global aerosol models using the same global mean aerosol properties, the estimates by the simple model are sensitive to preindustrial cloud condensation nuclei concentration, preindustrial accumulation mode radius, width of the accumulation mode, size of primary particles, cloud thickness, primary and secondary anthropogenic emissions, the fraction of the secondary anthropogenic emissions that accumulates on the coarse mode, the fraction of the secondary mass that forms new particles, and the sensitivity of liquid water path to droplet number concentration. Estimates of present-day AIEs as low as 5 W/sq m and as high as 0.3 W/sq m are obtained for plausible sets of parameter values. Estimates are surprisingly linear in emissions. The estimates depend on parameter values in ways that are consistent with results from detailed global aerosol-climate simulation models, which adds to understanding of the dependence on AIE uncertainty on uncertainty in parameter values.

  16. Compiling and Mapping Global Permeability of the Unconsolidated and Consolidated Earth: GLobal HYdrogeology MaPS 2.0 (GLHYMPS 2.0)

    NASA Astrophysics Data System (ADS)

    Huscroft, Jordan; Gleeson, Tom; Hartmann, Jens; Börker, Janine

    2018-02-01

    The spatial distribution of subsurface parameters such as permeability are increasingly relevant for regional to global climate, land surface, and hydrologic models that are integrating groundwater dynamics and interactions. Despite the large fraction of unconsolidated sediments on Earth's surface with a wide range of permeability values, current global, high-resolution permeability maps distinguish solely fine-grained and coarse-grained unconsolidated sediments. Representative permeability values are derived for a wide variety of unconsolidated sediments and applied to a new global map of unconsolidated sediments to produce the first geologically constrained, two-layer global map of shallower and deeper permeability. The new mean logarithmic permeability of the Earth's surface is -12.7 ± 1.7 m2 being 1 order of magnitude higher than that derived from previous maps, which is consistent with the dominance of the coarser sediments. The new data set will benefit a variety of scientific applications including the next generation of climate, land surface, and hydrology models at regional to global scales.

  17. Global/local methods for probabilistic structural analysis

    NASA Technical Reports Server (NTRS)

    Millwater, H. R.; Wu, Y.-T.

    1993-01-01

    A probabilistic global/local method is proposed to reduce the computational requirements of probabilistic structural analysis. A coarser global model is used for most of the computations with a local more refined model used only at key probabilistic conditions. The global model is used to establish the cumulative distribution function (cdf) and the Most Probable Point (MPP). The local model then uses the predicted MPP to adjust the cdf value. The global/local method is used within the advanced mean value probabilistic algorithm. The local model can be more refined with respect to the g1obal model in terms of finer mesh, smaller time step, tighter tolerances, etc. and can be used with linear or nonlinear models. The basis for this approach is described in terms of the correlation between the global and local models which can be estimated from the global and local MPPs. A numerical example is presented using the NESSUS probabilistic structural analysis program with the finite element method used for the structural modeling. The results clearly indicate a significant computer savings with minimal loss in accuracy.

  18. Global/local methods for probabilistic structural analysis

    NASA Astrophysics Data System (ADS)

    Millwater, H. R.; Wu, Y.-T.

    1993-04-01

    A probabilistic global/local method is proposed to reduce the computational requirements of probabilistic structural analysis. A coarser global model is used for most of the computations with a local more refined model used only at key probabilistic conditions. The global model is used to establish the cumulative distribution function (cdf) and the Most Probable Point (MPP). The local model then uses the predicted MPP to adjust the cdf value. The global/local method is used within the advanced mean value probabilistic algorithm. The local model can be more refined with respect to the g1obal model in terms of finer mesh, smaller time step, tighter tolerances, etc. and can be used with linear or nonlinear models. The basis for this approach is described in terms of the correlation between the global and local models which can be estimated from the global and local MPPs. A numerical example is presented using the NESSUS probabilistic structural analysis program with the finite element method used for the structural modeling. The results clearly indicate a significant computer savings with minimal loss in accuracy.

  19. Development of second generation peptides modulating cellular adiponectin receptor responses

    NASA Astrophysics Data System (ADS)

    Otvos, Laszlo; Knappe, Daniel; Hoffmann, Ralf; Kovalszky, Ilona; Olah, Julia; Hewitson, Tim; Stawikowska, Roma; Stawikowski, Maciej; Cudic, Predrag; Lin, Feng; Wade, John; Surmacz, Eva; Lovas, Sandor

    2014-10-01

    The adipose tissue participates in the regulation of energy homeostasis as an important endocrine organ that secretes a number of biologically active adipokines, including adiponectin. Recently we developed and characterized a first-in-class peptide-based adiponectin receptor agonist by using in vitro and in vivo models of glioblastoma and breast cancer (BC). In the current study, we further explored the effects of peptide ADP355 in additional cellular models and found that ADP355 inhibited chronic myeloid leukemia (CML) cell proliferation and renal myofibroblast differentiation with mid-nanomolar IC50 values. According to molecular modeling calculations, ADP355 was remarkably flexible in the global minimum with a turn present in the middle of the peptide. Considering these structural features of ADP355 and the fact that adiponectin normally circulates as multimeric complexes, we developed and tested the activity of a linear branched dimer (ADP399). The dimer exhibited approximately 20-fold improved cellular activity inhibiting K562 CML and MCF-7 cell growth with high pM - low nM relative IC50 values. Biodistribution studies suggested superior tissue dissemination of both peptides after subcutaneous administration relative to intraperitoneal inoculation. After screening of a 397-member adiponectin active site library, a novel octapeptide (ADP400) was designed that counteracted 10-1000 nM ADP355- and ADP399-mediated effects on CML and BC cell growth at nanomolar concentrations. ADP400 induced mitogenic effects in MCF-7 BC cells perhaps due to antagonizing endogenous adiponectin actions or acting as an inverse agonist. While the linear dimer agonist ADP399 meets pharmacological criteria of a contemporary peptide drug lead, the peptide showing antagonist activity (ADP400) at similar concentrations will be an important target validation tool to study adiponectin functions.

  20. Global priorities for research and the relative importance of different research outcomes: an international Delphi survey of malaria research experts.

    PubMed

    Mulligan, Jo-Ann; Conteh, Lesong

    2016-12-06

    As global research investment increases, attention inevitably turns to assessing and measuring the outcomes and impact from research programmes. Research can have many different outcomes such as producing advances in scientific knowledge, building research capacity and, ultimately, health and broader societal benefits. The aim of this study was to test the use of a Delphi methodology as a way of gathering views from malaria research experts on research priorities and eliciting relative valuations of the different types of health research impact. An international Delphi survey of 60 malaria research experts was used to understand views on research outcomes and priorities within malaria and across global health more widely. The study demonstrated the application of the Delphi technique to eliciting views on malaria specific research priorities, wider global health research priorities and the values assigned to different types of research impact. In terms of the most important past research successes, the development of new anti-malarial drugs and insecticide-treated bed nets were rated as the most important. When asked about research priorities for future funding, respondents ranked tackling emerging drug and insecticide resistance the highest. With respect to research impact, the panel valued research that focuses on health and health sector benefits and informing policy and product development. Contributions to scientific knowledge, although highly valued, came lower down the ranking, suggesting that efforts to move research discoveries to health products and services are valued more highly than pure advances in scientific knowledge. Although the Delphi technique has been used to elicit views on research questions in global health this was the first time it has been used to assess how a group of research experts value or rank different types of research impact. The results suggest it is feasible to inject the views of a key stakeholder group into the research prioritization process and the Delphi approach is a useful tool for eliciting views on the value or importance of research impact. Future work will explore other methods for assessing and valuing research impact and test the feasibility of developing a composite tool for measuring research outcomes weighted by the values of different stakeholders.

  1. Global DNA methylation in fetal human germ cells and germ cell tumours: association with differentiation and cisplatin resistance.

    PubMed

    Wermann, Hendrik; Stoop, Hans; Gillis, Ad J M; Honecker, Friedemann; van Gurp, Ruud J H L M; Ammerpohl, Ole; Richter, Julia; Oosterhuis, J Wolter; Bokemeyer, Carsten; Looijenga, Leendert H J

    2010-08-01

    Differences in the global methylation pattern, ie hyper- as well as hypo-methylation, are observed in cancers including germ cell tumours (GCTs). Related to their precursor cells, GCT methylation status differs according to histology. We investigated the methylation pattern of normal fetal, infantile, and adult germ cells (n = 103) and GCTs (n = 251) by immunohistochemical staining for 5-(m)cytidine. The global methylation pattern of male germ cells changes from hypomethylation to hypermethylation, whereas female germ cells remain unmethylated at all stages. Undifferentiated GCTs (seminomas, intratubular germ cell neoplasia unclassified, and gonadoblastomas) are hypomethylated, whereas more differentiated GCTs (teratomas, yolk sac tumours, and choriocarcinomas) show a higher degree of methylation. Embryonal carcinomas show an intermediate pattern. Resistance to cisplatin was assessed in the seminomatous cell line TCam-2 before and after demethylation using 5-azacytidine. Exposure to 5-azacytidine resulted in decreased resistance to cisplatin. Furthermore, after demethylation, the stem cell markers NANOG and POU5F1 (OCT3/4), as well as the germ cell-specific marker VASA, showed increased expression. Following treatment with 5-azacytidine, TCam-2 cells were analysed using a high-throughput methylation screen for changes in the methylation sites of 14,000 genes. Among the genes revealing changes, interesting targets were identified: ie demethylation of KLF11, a putative tumour suppressor gene, and hypermethylation of CFLAR, a gene previously described in treatment resistance in GCTs.

  2. The PHI/GHFP-II Employers' Study: The Hidden Barriers Between Domestic and Global Health Careers and Crucial Competencies for Success.

    PubMed

    Rudy, Sharon; Wanchek, Natasha; Godsted, David; Blackburn, Morgan; Mann, Elise

    An ongoing discussion in global health in the United States centers on the future of the US-trained global health workforce and how best to prepare professionals for this career path. The Public Health Institute, through its Global Health Fellows Program (I and II), has been in a unique position to identify the shifting employment dynamic in global health. The purpose of the survey was to gather information on global health employers' hiring practices and insights into the importance of nonclinical skills in contributing to successful professional work; preparedness of graduates with needed nonclinical skills; and the value of domestic work experience for global health careers. The focus was on individuals primarily raised in the United States who studied global health in either graduate or undergraduate settings. A web-based survey and telephone interviews were conducted in early 2015. Overall, 49 project directors from 32 organizations participated. Key findings included: CONCLUSIONS: The process of preparing professionals for global health work has fallen behind emerging realities, including globalization, ever-evolving technologies, and advances in health care. Universities must provide an increased curricular emphasis on nonclinical skills, both interpersonal and business related, as well as the international experience that is valued in the global health workplace. Copyright © 2016 Icahn School of Medicine at Mount Sinai. All rights reserved.

  3. Modeling global mangrove soil carbon stocks: filling the gaps in coastal environments

    NASA Astrophysics Data System (ADS)

    Rovai, A.; Twilley, R.

    2017-12-01

    We provide an overview of contemporaneous global mangrove soil organic carbon (SOC) estimates, focusing on a framework to explain disproportionate differences among observed data as a way to improve global estimates. This framework is based on a former conceptual model, the coastal environmental setting, in contrast to the more popular latitude-based hypotheses largely believed to explain hemispheric variation in mangrove ecosystem properties. To demonstrate how local and regional estimates of SOC linked to coastal environmental settings can render more realistic global mangrove SOC extrapolations we combined published and unpublished data, yielding a total of 106 studies, reporting on 552 sites from 43 countries. These sites were classified into distinct coastal environmental setting types according to two concurrent worldwide typology of nearshore coastal systems classifications. Mangrove SOC density varied substantially across coastal environmental settings, ranging from 14.9 ± 0.8 in river dominated (deltaic) soils to 53.9 ± 1.6 mg cm-3 (mean ± SE) in karstic coastlines. Our findings reveal striking differences between published values and contemporary global mangrove SOC extrapolation based on country-level mean reference values, particularly for karstic-dominated coastlines where mangrove SOC stocks have been underestimated by up to 50%. Correspondingly, climate-based global estimates predicted lower mangrove SOC density values (32-41 mg C cm-3) for mangroves in karstic environments, differing from published (21-126 mg C cm-3) and unpublished (47-58 mg C cm-3) values. Moreover, climate-based projections yielded higher SOC density values (27-70 mg C cm-3) for river-dominated mangroves compared to lower ranges reported in the literature (11-24 mg C cm-3). We argue that this inconsistent reporting of SOC stock estimates between river-dominated and karstic coastal environmental settings is likely due to the omission of geomorphological and geophysical environmental drivers, which control C storage in coastal wetlands. We encourage the science community more close utilize coastal environmental settings and new inventories of geomorphological typologies to build more robust estimates of local and regional estimates of SOC that can be extrapolated to global C estimates.

  4. Celebrating the work of Gavin Mooney: inclusiveness and involvement in global and public health issues.

    PubMed

    McIntyre, Diane

    2014-05-01

    This paper considers Gavin Mooney's contributions to the research literature on inclusiveness in global and public health issues. Much of his contribution in this area stems from engaging with Indigenous people, which cemented his conviction that it is important to recognise the heterogeneity of groups in society, especially in relation to cultural differences. He believed that in order to develop appropriate equitable and efficient health and related policies, the preferences of citizens should be elicited. While this could feed into very specific policy decisions, such as how to allocate available resources within a particular community, more generally, community preferences should determine the core values that underpin a health system. He proposed that these values be documented in a 'constitution' and serve as the basis on which policy-makers and health managers make decisions. Preference elicitation has value in itself, as procedural justice allows for self-determination and contributes to empowerment. Further, engagement by citizens in deliberative processes can overcome polarisation. Health systems themselves, if developed as social institutions, can influence the nature of society and contribute to greater unity. Mooney raised similar concerns about policies arising from mono-cultural global perspectives and argued that, whether at the national or global level, values for health systems should be based on community preferences. He particularly highlighted the unequal distribution of benefits of neoliberal globalisation as the cause of growing health and wealth inequalities globally. There is resonance between Mooney's views on these issues and some of the contributions to the post-2015 development agenda debates. While it is unlikely that we have reached a point where the stranglehold of neo-liberal governments on key global institutions will be broken, the current debates nevertheless present an important window of opportunity to struggle for shifts in the global political economy. Current debates about universal coverage also provide a critical opportunity to move towards health systems that are built on values determined by citizens and are social institutions that build solidarity, redress inequalities and unite fractured societies. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Daisaku Ikeda's Curriculum of Soka Education: Creating Value through Dialogue, Global Citizenship, and "Human Education" in the Mentor-Disciple Relationship

    ERIC Educational Resources Information Center

    Goulah, Jason; Ito, Takao

    2012-01-01

    This essay review focuses on Daisaku Ikeda (b. 1928) and his curriculum of Soka, or value-creating, education present in two works: "Choose Life: A Dialogue" (Toynbee & Ikeda, 1976) and "Thoughts on Education for Global Citizenship" (Ikeda, 1996b). In reviewing these works, the authors trace the biographical roots of Ikeda's educational philosophy…

  6. Global Mental Health: Five Areas for Value-Driven Training Innovation.

    PubMed

    Kohrt, Brandon A; Marienfeld, Carla B; Panter-Brick, Catherine; Tsai, Alexander C; Wainberg, Milton L

    2016-08-01

    In the field of global mental health, there is a need for identifying core values and competencies to guide training programs in professional practice as well as in academia. This paper presents the results of interdisciplinary discussions fostered during an annual meeting of the Society for the Study of Psychiatry and Culture to develop recommendations for value-driven innovation in global mental health training. Participants (n = 48), who registered for a dedicated workshop on global mental health training advertised in conference proceedings, included both established faculty and current students engaged in learning, practice, and research. They proffered recommendations in five areas of training curriculum: values, competencies, training experiences, resources, and evaluation. Priority values included humility, ethical awareness of power differentials, collaborative action, and "deep accountability" when working in low-resource settings in low- and middle-income countries and high-income countries. Competencies included flexibility and tolerating ambiguity when working across diverse settings, the ability to systematically evaluate personal biases, historical and linguistic proficiency, and evaluation skills across a range of stakeholders. Training experiences included didactics, language training, self-awareness, and supervision in immersive activities related to professional or academic work. Resources included connections with diverse faculty such as social scientists and mentors in addition to medical practitioners, institutional commitment through protected time and funding, and sustainable collaborations with partners in low resource settings. Finally, evaluation skills built upon community-based participatory methods, 360-degree feedback from partners in low-resource settings, and observed structured clinical evaluations (OSCEs) with people of different cultural backgrounds. Global mental health training, as envisioned in this workshop, exemplifies an ethos of working through power differentials across clinical, professional, and social contexts in order to form longstanding collaborations. If incorporated into the ACGME/ABPN Psychiatry Milestone Project, such recommendations will improve training gained through international experiences as well as the everyday training of mental health professionals, global health practitioners, and social scientists.

  7. Global Mental Health: Five Areas for Value-Driven Training Innovation

    PubMed Central

    Kohrt, Brandon A.; Marienfeld, Carla B.; Panter-Brick, Catherine; Tsai, Alexander C.; Wainberg, Milton L.

    2016-01-01

    OBJECTIVE In the field of global mental health, there is a need for identifying core values and competencies to guide training programs in professional practice as well as in academia. This paper presents the results of interdisciplinary discussions fostered during an annual meeting of the Society for the Study of Psychiatry and Culture to develop recommendations for value-driven innovation in global mental health training. METHODS Participants (n=48), who registered for a dedicated workshop on global mental health training advertised in conference proceedings, included both established faculty and current students engaged in learning, practice, and research. They proffered recommendations in five areas of training curriculum: values, competencies, training experiences, resources, and evaluation. RESULTS Priority values included humility, ethical awareness of power differentials, collaborative action, and “deep accountability” when working in low-resource settings in both low- and middle-income countries (LMIC) and high-income countries. Competencies included flexibility and tolerating ambiguity when working across diverse settings, the ability to systematically evaluate personal biases, historical and linguistic proficiency, and evaluation skills across a range of stakeholders. Training experiences included didactics, language, self-awareness, and supervision in immersive activities related to professional or academic work. Resources included connections with diverse faculty such as social scientists and mentors other than medical practitioners, institutional commitment through protected time and funding, and sustainable collaborations with partners in low resource settings. Finally, evaluation skills built upon community-based participatory methods, 360-degree feedback from partners in low-resource settings, and observed structured clinical evaluations (OSCEs) with people of different cultural backgrounds. CONCLUSIONS Global mental health training, as envisioned in this workshop, exemplifies an ethos of working through power differentials across clinical, professional, and social contexts in order to form longstanding collaborations. If incorporated into the ACGME/ABPN Psychiatry Milestone Project, such recommendations will improve training gained through international experiences as well as the everyday training of mental health professionals, global health practitioners, and social scientists. PMID:26983416

  8. Value and Performance in the IT Society.

    ERIC Educational Resources Information Center

    Bryson, Jo

    This paper discusses valuing information and its supporting technologies in the global environment. Different value propositions are explored from a financial, social, cultural, political, economic, corporate, and personal values perspective. Various means of measuring the relevancy of these value propositions to the individual, organization or…

  9. Increased intracellular adenosine triphosphate level as an index to predict acute rejection in kidney transplant recipients.

    PubMed

    Wang, Xu-Zhen; Jin, Zhan-Kui; Tian, Xiao-Hui; Xue, Wu-Jun; Tian, Pu-Xun; Ding, Xiao-Ming; Zheng, Jin; Li, Yang; Jing, Xin; Luo, Zi-Zhen

    2014-01-01

    Peripheral blood CD4+ T cell adenosine triphosphate (ATP) release has been reported to be an adjunct tool to evaluate global cellular immune response in solid-organ transplant recipients. However, the correlation between the ATP level and rejection was controversial. The aim of this prospective clinical study was to explore the association between the intracellular ATP level and the occurrence, progression, and treatment of acute rejection (AR) episodes, determine the predicting value of intracellular ATP level for AR in kidney transplant (KT) recipients. In the period of October 2011 to October 2012, 140 KT recipients were recruited and followed for six months after transplantation. Patients were categorized into stable group and AR group according to their clinical course. Whole blood samples were collected pretransplantation, and at 7, 14, 21, and 28days, and at 2, 3, 4, 5 and 6months post-transplantation. Additional blood samples were obtained from AR patients on the day AR occurred, on the day before and 3 and 7days after intravenous anti-rejection therapy started, and on the day when AR reversed. The intracellular ATP in CD4+ T cells was detected by ImmuKnow Immune Cell Function Assay according to the manufacturer's instruction. The absolute number of CD4+ T cells and the trough levels of tacrolimus and cyclosporine were also measured. The ATP level detected on the day AR occurred (627.07±149.85ng/ml) was obviously higher than that of the stable group (320.48±149.11ng/ml, P<0.05). ATP value decreased to 265.35±84.33ng/m at the end of anti-rejection therapy, which was obviously lower than that measured on the day before the anti-rejection therapy started (665.87±162.85ng/ml, P<0.05). ROC analysis revealed that increased intracellular adenosine triphosphate level showed better sensitivity and specificity than those obtained using single time point detection (89.5% vs 85.0%;95.0% vs 88.9%). The best cutoff value was 172.55ng/ml. A positive correlation between the intracellular ATP level and absolute CD4+ T cell number (r=0.656, P<0.001) was found in the patients with CD4+ T cell counts <200/μl. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. How well do terrestrial biosphere models simulate coarse-scale runoff in the contiguous United States?

    DOE PAGES

    Schwalm, C.; Huntzinger, Deborah N.; Cook, Robert B.; ...

    2015-03-11

    Significant changes in the water cycle are expected under current global environmental change. Robust assessment of present-day water cycle dynamics at continental to global scales is confounded by shortcomings in the observed record. Modeled assessments also yield conflicting results which are linked to differences in model structure and simulation protocol. Here we compare simulated gridded (1 spatial resolution) runoff from six terrestrial biosphere models (TBMs), seven reanalysis products, and one gridded surface station product in the contiguous United States (CONUS) from 2001 to 2005. We evaluate the consistency of these 14 estimates with stream gauge data, both as depleted flowmore » and corrected for net withdrawals (2005 only), at the CONUS and water resource region scale, as well as examining similarity across TBMs and reanalysis products at the grid cell scale. Mean runoff across all simulated products and regions varies widely (range: 71 to 356 mm yr(-1)) relative to observed continental-scale runoff (209 or 280 mm yr(-1) when corrected for net withdrawals). Across all 14 products 8 exhibit Nash-Sutcliffe efficiency values in excess of 0.8 and three are within 10% of the observed value. Region-level mismatch exhibits a weak pattern of overestimation in western and underestimation in eastern regions although two products are systematically biased across all regions and largely scales with water use. Although gridded composite TBM and reanalysis runoff show some regional similarities, individual product values are highly variable. At the coarse scales used here we find that progress in better constraining simulated runoff requires standardized forcing data and the explicit incorporation of human effects (e.g., water withdrawals by source, fire, and land use change). (C) 2015 Elsevier B.V. All rights reserved.« less

  11. Finite Element Analysis of Single Cell Stiffness Measurements Using PZT-Integrated Buckling Nanoneedles

    PubMed Central

    Rad, Maryam Alsadat; Tijjani, Auwal Shehu; Ahmad, Mohd Ridzuan; Auwal, Shehu Muhammad

    2016-01-01

    This paper proposes a new technique for real-time single cell stiffness measurement using lead zirconate titanate (PZT)-integrated buckling nanoneedles. The PZT and the buckling part of the nanoneedle have been modelled and validated using the ABAQUS software. The two parts are integrated together to function as a single unit. After calibration, the stiffness, Young’s modulus, Poisson’s ratio and sensitivity of the PZT-integrated buckling nanoneedle have been determined to be 0.7100 N·m−1, 123.4700 GPa, 0.3000 and 0.0693 V·m·N−1, respectively. Three Saccharomyces cerevisiae cells have been modelled and validated based on compression tests. The average global stiffness and Young’s modulus of the cells are determined to be 10.8867 ± 0.0094 N·m−1 and 110.7033 ± 0.0081 MPa, respectively. The nanoneedle and the cell have been assembled to measure the local stiffness of the single Saccharomyces cerevisiae cells The local stiffness, Young’s modulus and PZT output voltage of the three different size Saccharomyces cerevisiae have been determined at different environmental conditions. We investigated that, at low temperature the stiffness value is low to adapt to the change in the environmental condition. As a result, Saccharomyces cerevisiae becomes vulnerable to viral and bacterial attacks. Therefore, the proposed technique will serve as a quick and accurate process to diagnose diseases at early stage in a cell for effective treatment. PMID:28025571

  12. Relative Error Evaluation to Typical Open Global dem Datasets in Shanxi Plateau of China

    NASA Astrophysics Data System (ADS)

    Zhao, S.; Zhang, S.; Cheng, W.

    2018-04-01

    Produced by radar data or stereo remote sensing image pairs, global DEM datasets are one of the most important types for DEM data. Relative error relates to surface quality created by DEM data, so it relates to geomorphology and hydrologic applications using DEM data. Taking Shanxi Plateau of China as the study area, this research evaluated the relative error to typical open global DEM datasets including Shuttle Radar Terrain Mission (SRTM) data with 1 arc second resolution (SRTM1), SRTM data with 3 arc second resolution (SRTM3), ASTER global DEM data in the second version (GDEM-v2) and ALOS world 3D-30m (AW3D) data. Through process and selection, more than 300,000 ICESat/GLA14 points were used as the GCP data, and the vertical error was computed and compared among four typical global DEM datasets. Then, more than 2,600,000 ICESat/GLA14 point pairs were acquired using the distance threshold between 100 m and 500 m. Meanwhile, the horizontal distance between every point pair was computed, so the relative error was achieved using slope values based on vertical error difference and the horizontal distance of the point pairs. Finally, false slope ratio (FSR) index was computed through analyzing the difference between DEM and ICESat/GLA14 values for every point pair. Both relative error and FSR index were categorically compared for the four DEM datasets under different slope classes. Research results show: Overall, AW3D has the lowest relative error values in mean error, mean absolute error, root mean square error and standard deviation error; then the SRTM1 data, its values are a little higher than AW3D data; the SRTM3 and GDEM-v2 data have the highest relative error values, and the values for the two datasets are similar. Considering different slope conditions, all the four DEM data have better performance in flat areas but worse performance in sloping regions; AW3D has the best performance in all the slope classes, a litter better than SRTM1; with slope increasing, the relative error for the SRTM3 data increases faster than other DEM datasets; so SRTM3 is better than GDEM-v2 in flat regions but worse in sloping regions. As to FSR value, AW3D has the lowest value, 4.37 %; then SRTM1 data, 5.80 %, similar to AW3D data; SRTM3 has higher value, about 8.27 %; GDEM-v2 data has the highest FSR value, about 12.15 %. FSR can represent the performance of correctly creating the earth surface based on DEM data. Hence, AW3D has the best performance, which is approximate to but a little better than SRTM1. The performance of SRTM3 and GDEM-v2 is similar, which is much worse than AW3D and SRTM1, and the performance of GDEM-v2 is the worst of all. Originated from the DEM dataset with 5m resolution, AW3D is regarded as the most precise global DEM datasets up to now, so it may exerts more effect in topographic analysis and geographic research. Through analysis and comparison of the relative error for the four open global DEM datasets, this research will provide reference in open global DEM datasets selection and applications in geosciences and other relevant fields.

  13. Global Diversity and Leadership.

    ERIC Educational Resources Information Center

    Ruiz, Art

    2003-01-01

    Argues that global diversity has become a business imperative in today's business climate. Global diversity is of core importance even for companies that are considered domestic. Suggests community colleges need help in understanding their customer base and their shifting values in order to meet their needs and win customer loyalty. (NB)

  14. From global to local: exploring the relationship between parameters and behaviors in models of electrical excitability.

    PubMed

    Fletcher, Patrick; Bertram, Richard; Tabak, Joel

    2016-06-01

    Models of electrical activity in excitable cells involve nonlinear interactions between many ionic currents. Changing parameters in these models can produce a variety of activity patterns with sometimes unexpected effects. Further more, introducing new currents will have different effects depending on the initial parameter set. In this study we combined global sampling of parameter space and local analysis of representative parameter sets in a pituitary cell model to understand the effects of adding K (+) conductances, which mediate some effects of hormone action on these cells. Global sampling ensured that the effects of introducing K (+) conductances were captured across a wide variety of contexts of model parameters. For each type of K (+) conductance we determined the types of behavioral transition that it evoked. Some transitions were counterintuitive, and may have been missed without the use of global sampling. In general, the wide range of transitions that occurred when the same current was applied to the model cell at different locations in parameter space highlight the challenge of making accurate model predictions in light of cell-to-cell heterogeneity. Finally, we used bifurcation analysis and fast/slow analysis to investigate why specific transitions occur in representative individual models. This approach relies on the use of a graphics processing unit (GPU) to quickly map parameter space to model behavior and identify parameter sets for further analysis. Acceleration with modern low-cost GPUs is particularly well suited to exploring the moderate-sized (5-20) parameter spaces of excitable cell and signaling models.

  15. Targeted deletion and lipidomic analysis identify epithelial cell COX-2 as a major driver of chemically induced skin cancer.

    PubMed

    Jiao, Jing; Ishikawa, Tomo-O; Dumlao, Darren S; Norris, Paul C; Magyar, Clara E; Mikulec, Carol; Catapang, Art; Dennis, Edward A; Fischer, Susan M; Herschman, Harvey R

    2014-11-01

    Pharmacologic and global gene deletion studies demonstrate that cyclooxygenase-2 (PTGS2/COX-2) plays a critical role in DMBA/TPA-induced skin tumor induction. Although many cell types in the tumor microenvironment express COX-2, the cell types in which COX-2 expression is required for tumor promotion are not clearly established. Here, cell type-specific Cox-2 gene deletion reveals a vital role for skin epithelial cell COX-2 expression in DMBA/TPA tumor induction. In contrast, myeloid Cox-2 gene deletion has no effect on DMBA/TPA tumorigenesis. The infrequent, small tumors that develop on mice with an epithelial cell-specific Cox-2 gene deletion have decreased proliferation and increased cell differentiation properties. Blood vessel density is reduced in tumors with an epithelial cell-specific Cox-2 gene deletion, compared with littermate control tumors, suggesting a reciprocal relationship in tumor progression between COX-2-expressing tumor epithelial cells and microenvironment endothelial cells. Lipidomics analysis of skin and tumors from DMBA/TPA-treated mice suggests that the prostaglandins PGE2 and PGF2α are likely candidates for the epithelial cell COX-2-dependent eicosanoids that mediate tumor progression. This study both illustrates the value of cell type-specific gene deletions in understanding the cellular roles of signal-generating pathways in complex microenvironments and emphasizes the benefit of a systems-based lipidomic analysis approach to identify candidate lipid mediators of biologic responses. Cox-2 gene deletion demonstrates that intrinsic COX-2 expression in initiated keratinocytes is a principal driver of skin carcinogenesis; lipidomic analysis identifies likely prostanoid effectors. ©2014 American Association for Cancer Research.

  16. Global mammal distributions, biodiversity hotspots, and conservation.

    PubMed

    Ceballos, Gerardo; Ehrlich, Paul R

    2006-12-19

    Hotspots, which have played a central role in the selection of sites for reserves, require careful rethinking. We carried out a global examination of distributions of all nonmarine mammals to determine patterns of species richness, endemism, and endangerment, and to evaluate the degree of congruence among hotspots of these three measures of diversity in mammals. We then compare congruence of hotspots in two animal groups (mammals and birds) to assess the generality of these patterns. We defined hotspots as the richest 2.5% of cells in a global equal-area grid comparable to 1 degrees latitude x 1 degrees longitude. Hotspots of species richness, "endemism," and extinction threat were noncongruent. Only 1% of cells and 16% of species were common to the three types of mammalian hotspots. Congruence increased with increases in both the geographic scope of the analysis and the percentage of cells defined as being hotspots. The within-mammal hotspot noncongruence was similar to the pattern recently found for birds. Thus, assigning global conservation priorities based on hotspots is at best a limited strategy.

  17. Global industrial impact coefficient based on random walk process and inter-country input-output table

    NASA Astrophysics Data System (ADS)

    Xing, Lizhi; Dong, Xianlei; Guan, Jun

    2017-04-01

    Input-output table is very comprehensive and detailed in describing the national economic system with lots of economic relationships, which contains supply and demand information among industrial sectors. The complex network, a theory and method for measuring the structure of complex system, can describe the structural characteristics of the internal structure of the research object by measuring the structural indicators of the social and economic system, revealing the complex relationship between the inner hierarchy and the external economic function. This paper builds up GIVCN-WIOT models based on World Input-Output Database in order to depict the topological structure of Global Value Chain (GVC), and assumes the competitive advantage of nations is equal to the overall performance of its domestic sectors' impact on the GVC. Under the perspective of econophysics, Global Industrial Impact Coefficient (GIIC) is proposed to measure the national competitiveness in gaining information superiority and intermediate interests. Analysis of GIVCN-WIOT models yields several insights including the following: (1) sectors with higher Random Walk Centrality contribute more to transmitting value streams within the global economic system; (2) Half-Value Ratio can be used to measure robustness of open-economy macroeconomics in the process of globalization; (3) the positive correlation between GIIC and GDP indicates that one country's global industrial impact could reveal its international competitive advantage.

  18. Field significance of performance measures in the context of regional climate model evaluation. Part 1: temperature

    NASA Astrophysics Data System (ADS)

    Ivanov, Martin; Warrach-Sagi, Kirsten; Wulfmeyer, Volker

    2018-04-01

    A new approach for rigorous spatial analysis of the downscaling performance of regional climate model (RCM) simulations is introduced. It is based on a multiple comparison of the local tests at the grid cells and is also known as "field" or "global" significance. New performance measures for estimating the added value of downscaled data relative to the large-scale forcing fields are developed. The methodology is exemplarily applied to a standard EURO-CORDEX hindcast simulation with the Weather Research and Forecasting (WRF) model coupled with the land surface model NOAH at 0.11 ∘ grid resolution. Monthly temperature climatology for the 1990-2009 period is analysed for Germany for winter and summer in comparison with high-resolution gridded observations from the German Weather Service. The field significance test controls the proportion of falsely rejected local tests in a meaningful way and is robust to spatial dependence. Hence, the spatial patterns of the statistically significant local tests are also meaningful. We interpret them from a process-oriented perspective. In winter and in most regions in summer, the downscaled distributions are statistically indistinguishable from the observed ones. A systematic cold summer bias occurs in deep river valleys due to overestimated elevations, in coastal areas due probably to enhanced sea breeze circulation, and over large lakes due to the interpolation of water temperatures. Urban areas in concave topography forms have a warm summer bias due to the strong heat islands, not reflected in the observations. WRF-NOAH generates appropriate fine-scale features in the monthly temperature field over regions of complex topography, but over spatially homogeneous areas even small biases can lead to significant deteriorations relative to the driving reanalysis. As the added value of global climate model (GCM)-driven simulations cannot be smaller than this perfect-boundary estimate, this work demonstrates in a rigorous manner the clear additional value of dynamical downscaling over global climate simulations. The evaluation methodology has a broad spectrum of applicability as it is distribution-free, robust to spatial dependence, and accounts for time series structure.

  19. Comprehensive analysis of genome-wide DNA methylation across human polycystic ovary syndrome ovary granulosa cell.

    PubMed

    Xu, Jiawei; Bao, Xiao; Peng, Zhaofeng; Wang, Linlin; Du, Linqing; Niu, Wenbin; Sun, Yingpu

    2016-05-10

    Polycystic ovary syndrome (PCOS) affects approximately 7% of the reproductive-age women. A growing body of evidence indicated that epigenetic mechanisms contributed to the development of PCOS. The role of DNA modification in human PCOS ovary granulosa cell is still unknown in PCOS progression. Global DNA methylation and hydroxymethylation were detected between PCOS' and controls' granulosa cell. Genome-wide DNA methylation was profiled to investigate the putative function of DNA methylaiton. Selected genes expressions were analyzed between PCOS' and controls' granulosa cell. Our results showed that the granulosa cell global DNA methylation of PCOS patients was significant higher than the controls'. The global DNA hydroxymethylation showed low level and no statistical difference between PCOS and control. 6936 differentially methylated CpG sites were identified between control and PCOS-obesity. 12245 differential methylated CpG sites were detected between control and PCOS-nonobesity group. 5202 methylated CpG sites were significantly differential between PCOS-obesity and PCOS-nonobesity group. Our results showed that DNA methylation not hydroxymethylation altered genome-wide in PCOS granulosa cell. The different methylation genes were enriched in development protein, transcription factor activity, alternative splicing, sequence-specific DNA binding and embryonic morphogenesis. YWHAQ, NCF2, DHRS9 and SCNA were up-regulation in PCOS-obesity patients with no significance different between control and PCOS-nonobesity patients, which may be activated by lower DNA methylaiton. Global and genome-wide DNA methylation alteration may contribute to different genes expression and PCOS clinical pathology.

  20. Wall-motion tracking in fetal echocardiography-Influence of frame rate on longitudinal strain analysis assessed by two-dimensional speckle tracking.

    PubMed

    Enzensberger, Christian; Achterberg, Friederike; Graupner, Oliver; Wolter, Aline; Herrmann, Johannes; Axt-Fliedner, Roland

    2017-06-01

    Frame rates (FR) used for strain analysis assessed by speckle tracking in fetal echocardiography show a considerable variation. The aim of this study was to investigate the influence of the FR on strain analysis in 2D speckle tracking. Fetal echocardiography was performed prospectively on a Toshiba Aplio 500 system and a Toshiba Artida system, respectively. Based on an apical or basal four-chamber view of the fetal heart, cine loops were stored with a FR of 30 fps (Aplio 500) and 60 fps (Artida/Aplio 500). For both groups (30fps and 60fps), global and segmental longitudinal peak systolic strain (LPSS) values of both, left (LV) and right ventricle (RV), were assessed by 2D wall-motion tracking. A total of 101 fetuses, distributed to three study groups, were included. The mean gestational age was 25.2±5.0 weeks. Mean global LPSS values for RV in the 30 fps group and in the 60 fps group were -16.07% and -16.47%, respectively. Mean global LPSS values for LV in the 30 fps group and in the 60 fps group were -17.54% and -17.06%, respectively. Comparing global and segmental LPSS values of both, the RV and LV, did not show any statistically significant differences within the two groups. Performance of myocardial 2D strain analysis by wall-motion tracking was feasible with 30 and 60 fps. Obtained global and segmental LPSS values of both ventricles were relatively independent from acquisition rate. © 2017, Wiley Periodicals, Inc.

  1. Local small airway epithelial injury induces global smooth muscle contraction and airway constriction

    PubMed Central

    Zhou, Jian; Alvarez-Elizondo, Martha B.; Botvinick, Elliot

    2012-01-01

    Small airway epithelial cells form a continuous sheet lining the conducting airways, which serves many functions including a physical barrier to protect the underlying tissue. In asthma, injury to epithelial cells can occur during bronchoconstriction, which may exacerbate airway hyperreactivity. To investigate the role of epithelial cell rupture in airway constriction, laser ablation was used to precisely rupture individual airway epithelial cells of small airways (<300-μm diameter) in rat lung slices (∼250-μm thick). Laser ablation of single epithelial cells using a femtosecond laser reproducibly induced airway contraction to ∼70% of the original cross-sectional area within several seconds, and the contraction lasted for up to 40 s. The airway constriction could be mimicked by mechanical rupture of a single epithelial cell using a sharp glass micropipette but not with a blunt glass pipette. These results suggest that soluble mediators released from the wounded epithelial cell induce global airway contraction. To confirm this hypothesis, the lysate of primary human small airway epithelial cells stimulated a similar airway contraction. Laser ablation of single epithelial cells triggered a single instantaneous Ca2+ wave in the epithelium, and multiple Ca2+ waves in smooth muscle cells, which were delayed by several seconds. Removal of extracellular Ca2+ or decreasing intracellular Ca2+ both blocked laser-induced airway contraction. We conclude that local epithelial cell rupture induces rapid and global airway constriction through release of soluble mediators and subsequent Ca2+-dependent smooth muscle shortening. PMID:22114176

  2. Local small airway epithelial injury induces global smooth muscle contraction and airway constriction.

    PubMed

    Zhou, Jian; Alvarez-Elizondo, Martha B; Botvinick, Elliot; George, Steven C

    2012-02-01

    Small airway epithelial cells form a continuous sheet lining the conducting airways, which serves many functions including a physical barrier to protect the underlying tissue. In asthma, injury to epithelial cells can occur during bronchoconstriction, which may exacerbate airway hyperreactivity. To investigate the role of epithelial cell rupture in airway constriction, laser ablation was used to precisely rupture individual airway epithelial cells of small airways (<300-μm diameter) in rat lung slices (∼250-μm thick). Laser ablation of single epithelial cells using a femtosecond laser reproducibly induced airway contraction to ∼70% of the original cross-sectional area within several seconds, and the contraction lasted for up to 40 s. The airway constriction could be mimicked by mechanical rupture of a single epithelial cell using a sharp glass micropipette but not with a blunt glass pipette. These results suggest that soluble mediators released from the wounded epithelial cell induce global airway contraction. To confirm this hypothesis, the lysate of primary human small airway epithelial cells stimulated a similar airway contraction. Laser ablation of single epithelial cells triggered a single instantaneous Ca(2+) wave in the epithelium, and multiple Ca(2+) waves in smooth muscle cells, which were delayed by several seconds. Removal of extracellular Ca(2+) or decreasing intracellular Ca(2+) both blocked laser-induced airway contraction. We conclude that local epithelial cell rupture induces rapid and global airway constriction through release of soluble mediators and subsequent Ca(2+)-dependent smooth muscle shortening.

  3. Advanced subgrid-scale modeling for convection-dominated species transport at fluid interfaces with application to mass transfer from rising bubbles

    NASA Astrophysics Data System (ADS)

    Weiner, Andre; Bothe, Dieter

    2017-10-01

    This paper presents a novel subgrid scale (SGS) model for simulating convection-dominated species transport at deformable fluid interfaces. One possible application is the Direct Numerical Simulation (DNS) of mass transfer from rising bubbles. The transport of a dissolving gas along the bubble-liquid interface is determined by two transport phenomena: convection in streamwise direction and diffusion in interface normal direction. The convective transport for technical bubble sizes is several orders of magnitude higher, leading to a thin concentration boundary layer around the bubble. A true DNS, fully resolving hydrodynamic and mass transfer length scales results in infeasible computational costs. Our approach is therefore a DNS of the flow field combined with a SGS model to compute the mass transfer between bubble and liquid. An appropriate model-function is used to compute the numerical fluxes on all cell faces of an interface cell. This allows to predict the mass transfer correctly even if the concentration boundary layer is fully contained in a single cell layer around the interface. We show that the SGS-model reduces the resolution requirements at the interface by a factor of ten and more. The integral flux correction is also applicable to other thin boundary layer problems. Two flow regimes are investigated to validate the model. A semi-analytical solution for creeping flow is used to assess local and global mass transfer quantities. For higher Reynolds numbers ranging from Re = 100 to Re = 460 and Péclet numbers between Pe =104 and Pe = 4 ṡ106 we compare the global Sherwood number against correlations from literature. In terms of accuracy, the predicted mass transfer never deviates more than 4% from the reference values.

  4. Phenotypic Intratumoral Heterogeneity of Endometrial Carcinomas.

    PubMed

    Silva, Cátia; Pires-Luís, Ana S; Rocha, Eduardo; Bartosch, Carla; Lopes, José M

    2018-03-01

    Intratumoral heterogeneity has been shown to play an important role in diagnostic accuracy, development of treatment resistance, and prognosis of cancer patients. Recent studies have proposed quantitative measurement of phenotypic intratumoral heterogeneity, but no study is yet available in endometrial carcinomas. In our study we evaluated the phenotypic intratumoral heterogeneity of a consecutive series of 10 endometrial carcinomas using measures of dispersion and diversity. Morphometric architectural (%tumor cells, %solid tumor, %differentiated tumor, and %lumens) and nuclear [volume-weighted mean nuclear volume ((Equation is included in full-text article.))] parameters, as well as estrogen receptor, progesterone receptor, p53, vimentin, and beta-catenin immunoexpression (H-score) were digitally analyzed in 20 microscopic fields per carcinoma. Quantitative measures of intratumoral heterogeneity included coefficient of variation (CV) and relative quadratic entropy (rQE). In each endometrial carcinoma there was slight variation of architecture from field to field, resulting in globally low levels of heterogeneity measures (mean CV %tumor cells: 0.10, %solid tumor: 0.73, %differentiated tumor: 0.19, %lumens: 0.61 and mean rQE %tumor cells: 18.5, %solid tumor: 20.3, %differentiated tumor: 25.6, %lumens: 21.8). Nuclear intratumoral heterogeneity was also globally low (mean (Equation is included in full-text article.)CV: 0.23 and rQE: 27.3), but significantly higher than the heterogeneity of architectural parameters within most carcinomas. In general, there was low to moderate variability of immunoexpression markers within each carcinoma, but estrogen receptor (mean CV: 0.56 and rQE: 46.2) and progesterone receptor (mean CV: 0.60 and rQE: 39.3) displayed the highest values of heterogeneity measures. Intratumoral heterogeneity of immunoexpression was significantly higher than that observed for morphometric parameters. In conclusion, our study indicates that endometrial carcinomas present a variable but predominantly low degree of phenotypic intratumoral heterogeneity.

  5. Functional anatomy of an allosteric protein

    NASA Astrophysics Data System (ADS)

    Purohit, Prasad; Gupta, Shaweta; Jadey, Snehal; Auerbach, Anthony

    2013-12-01

    Synaptic receptors are allosteric proteins that switch on and off to regulate cell signalling. Here, we use single-channel electrophysiology to measure and map energy changes in the gating conformational change of a nicotinic acetylcholine receptor. Two separated regions in the α-subunits—the transmitter-binding sites and αM2-αM3 linkers in the membrane domain—have the highest ϕ-values (change conformation the earliest), followed by the extracellular domain, most of the membrane domain and the gate. Large gating-energy changes occur at the transmitter-binding sites, α-subunit interfaces, the αM1 helix and the gate. We hypothesize that rearrangements of the linkers trigger the global allosteric transition, and that the hydrophobic gate unlocks in three steps. The mostly local character of side-chain energy changes and the similarly high ϕ-values of separated domains, both with and without ligands, suggest that gating is not strictly a mechanical process initiated by the affinity change for the agonist.

  6. Neutron densities from a global analysis of medium-energy proton-nucleus elastic scattering

    NASA Astrophysics Data System (ADS)

    Clark, B. C.; Kerr, L. J.; Hama, S.

    2003-05-01

    A new method for extracting neutron densities from intermediate-energy elastic proton-nucleus scattering observables uses a global Dirac phenomenological approach based on the relativistic impulse approximation. Datasets for 40Ca, 48Ca, and 208Pb in the energy range from 500 MeV to 1040 MeV are considered. The global fits are successful in reproducing the data and in predicting datasets not included in the analysis. Using this global approach, energy-independent neutron densities are obtained. The vector point proton density distribution ρpv is determined from the empirical charge density after unfolding the proton form factor. The other densities, ρnv, ρps, ρns, are parametrized. This work provides energy-independent values for the rms neutron radius Rn and the neutron skin thickness Sn, in contrast to the energy-dependent values obtained by previous studies. In addition, the results presented in this paper show that the expected rms neutron radius and the skin thickness for 40Ca are accurately reproduced. The values of Rn and Sn obtained from the global fits that we consider to be the most reliable are given as follows: for 40Ca, 3.314>Rn>3.310 fm and -0.063>Sn >-0.067 fm; for 48Ca, 3.459>Rn>3.413 fm and 0.102>Sn>0.056 fm; and for 208Pb, 5.550>Rn>5.522 fm and 0.111>Sn>0.083 fm. These values are in reasonable agreement with nonrelativistic Skyrme-Hartree-Fock models and with relativistic Hartree-Bogoliubov models with density-dependent meson-nucleon couplings. The results from the global fits for 48Ca and 208Pb are generally not in agreement with the usual relativistic mean-field models.

  7. Dynamic Analysis of the Melanoma Model: From Cancer Persistence to Its Eradication

    NASA Astrophysics Data System (ADS)

    Starkov, Konstantin E.; Jimenez Beristain, Laura

    In this paper, we study the global dynamics of the five-dimensional melanoma model developed by Kronik et al. This model describes interactions of tumor cells with cytotoxic T cells and respective cytokines under cellular immunotherapy. We get the ultimate upper and lower bounds for variables of this model, provide formulas for equilibrium points and present local asymptotic stability/hyperbolic instability conditions. Next, we prove the existence of the attracting set. Based on these results we come to global asymptotic melanoma eradication conditions via global stability analysis. Finally, we provide bounds for a locus of the melanoma persistence equilibrium point, study the case of melanoma persistence and describe conditions under which we observe global attractivity to the unique melanoma persistence equilibrium point.

  8. Global health ethics: an introduction to prominent theories and relevant topics

    PubMed Central

    Stapleton, Greg; Schröder-Bäck, Peter; Laaser, Ulrich; Meershoek, Agnes; Popa, Daniela

    2014-01-01

    Global health ethics is a relatively new term that is used to conceptualize the process of applying moral value to health issues that are typically characterized by a global level effect or require action coordinated at a global level. It is important to acknowledge that this account of global health ethics takes a predominantly geographic approach and may infer that the subject relates primarily to macro-level health phenomena. However, global health ethics could alternatively be thought of as another branch of health ethics. It may then relate to specific topics in themselves, which might also include micro-level health phenomena. In its broadest sense, global health ethics is a normative project that is best characterized by the challenge of developing common values and universal norms for responding to global health threats. Consequently, many subjects fall within its scope. Whilst several accounts of global health ethics have been conceptualized in the literature, a concise demarcation of the paradigm is still needed. Through means of a literature review, this paper presents a two-part introduction to global health ethics. First, the framework of ‘borrowed’ ethics that currently form the core of global health ethics is discussed in relation to two essential ethical considerations: 1) what is the moral significance of health and 2) what is the moral significance of boundaries? Second, a selection of exemplar ethical topics is presented to illustrate the range of topics within global health ethics. PMID:24560262

  9. Global health ethics: an introduction to prominent theories and relevant topics.

    PubMed

    Stapleton, Greg; Schröder-Bäck, Peter; Laaser, Ulrich; Meershoek, Agnes; Popa, Daniela

    2014-01-01

    Global health ethics is a relatively new term that is used to conceptualize the process of applying moral value to health issues that are typically characterized by a global level effect or require action coordinated at a global level. It is important to acknowledge that this account of global health ethics takes a predominantly geographic approach and may infer that the subject relates primarily to macro-level health phenomena. However, global health ethics could alternatively be thought of as another branch of health ethics. It may then relate to specific topics in themselves, which might also include micro-level health phenomena. In its broadest sense, global health ethics is a normative project that is best characterized by the challenge of developing common values and universal norms for responding to global health threats. Consequently, many subjects fall within its scope. Whilst several accounts of global health ethics have been conceptualized in the literature, a concise demarcation of the paradigm is still needed. Through means of a literature review, this paper presents a two-part introduction to global health ethics. First, the framework of 'borrowed' ethics that currently form the core of global health ethics is discussed in relation to two essential ethical considerations: 1) what is the moral significance of health and 2) what is the moral significance of boundaries? Second, a selection of exemplar ethical topics is presented to illustrate the range of topics within global health ethics.

  10. Gyrokinetic global three-dimensional simulations of linear ion-temperature-gradient modes in Wendelstein 7-X

    NASA Astrophysics Data System (ADS)

    Kornilov, V.; Kleiber, R.; Hatzky, R.; Villard, L.; Jost, G.

    2004-06-01

    Using a global approach for solving an ion gyrokinetic model in three-dimensional geometry the linear stability and structure of ion-temperature-gradient (ITG) modes in the configuration of the stellarator Wendelstein 7-X (W7-X) [G. Grieger et al., in Plasma Physics and Controlled Nuclear Fusion Research 1990 (International Atomic Energy Agency, Vienna, 1991), Vol. 3, p. 525.] is studied. The time evolution of electrostatic perturbations is solved as an initial value problem with a particle-in-cell δf method. The vacuum magnetohydrodynamic equilibrium is calculated by the code VMEC [S. P. Hirshman and D. K. Lee, Comput. Phys. Commun. 39, 161 (1986)]. In this work the most unstable ITG mode in W7-X is presented. This mode has a pronounced ballooning-type structure; however, it is not tokamak-like. A driving mechanism analysis using the energy transfer shows that the contribution of curvature effects is non-negligible. The growth rate and the mixing-length estimate for transport are compared with those for ITG modes found in axisymmetric geometries.

  11. Universities and Globalization: Critical Perspectives.

    ERIC Educational Resources Information Center

    Currie, Jan, Ed.; Newson, Janice, Ed.

    The 14 papers in this collection examine how a globalizing political economy affects the way universities are governed, discussing practices such as managerialism, accountability, and privatization which represent a shift toward business values and a market agenda. Part 1 gives a theoretical overview of the globalization agenda. Part 2 gives three…

  12. Faith & Globalization:the Challenge for Higher Education

    ERIC Educational Resources Information Center

    Blair, Tony; Bardsley, Craig

    2013-01-01

    Globalization continues to transform how universities work: the students and subjects they teach, and the way they conduct and disseminate research. With tight budgets everywhere in the wake of the global economic downturn, universities are under increasing pressure to demonstrate value for money to the wider public from their research and…

  13. International Education: The International Baccalaureate, Montessori and Global Citizenship

    ERIC Educational Resources Information Center

    Brunold-Conesa, Cynthia

    2010-01-01

    The International Baccalaureate (IB) programs and Montessori education both claim to promote values associated with global citizenship in order to help prepare students for new challenges presented by an increasingly globalized world. While the IB's secondary programs are widespread in international schools, Montessori programs at that level are…

  14. Programming mRNA decay to modulate synthetic circuit resource allocation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Venturelli, Ophelia S.; Tei, Mika; Bauer, Stefan

    Synthetic circuits embedded in host cells compete with cellular processes for limited intracellular resources. Here we show how funnelling of cellular resources, after global transcriptome degradation by the sequence-dependent endoribonuclease MazF, to a synthetic circuit can increase production. Target genes are protected from MazF activity by recoding the gene sequence to eliminate recognition sites, while preserving the amino acid sequence. The expression of a protected fluorescent reporter and flux of a high-value metabolite are significantly enhanced using this genome-scale control strategy. Proteomics measurements discover a host factor in need of protection to improve resource redistribution activity. A computational model demonstratesmore » that the MazF mRNA-decay feedback loop enables proportional control of MazF in an optimal operating regime. Transcriptional profiling of MazF-induced cells elucidates the dynamic shifts in transcript abundance and discovers regulatory design elements. Altogether, our results suggest that manipulation of cellular resource allocation is a key control parameter for synthetic circuit design.« less

  15. Programming mRNA decay to modulate synthetic circuit resource allocation

    DOE PAGES

    Venturelli, Ophelia S.; Tei, Mika; Bauer, Stefan; ...

    2017-04-26

    Synthetic circuits embedded in host cells compete with cellular processes for limited intracellular resources. Here we show how funnelling of cellular resources, after global transcriptome degradation by the sequence-dependent endoribonuclease MazF, to a synthetic circuit can increase production. Target genes are protected from MazF activity by recoding the gene sequence to eliminate recognition sites, while preserving the amino acid sequence. The expression of a protected fluorescent reporter and flux of a high-value metabolite are significantly enhanced using this genome-scale control strategy. Proteomics measurements discover a host factor in need of protection to improve resource redistribution activity. A computational model demonstratesmore » that the MazF mRNA-decay feedback loop enables proportional control of MazF in an optimal operating regime. Transcriptional profiling of MazF-induced cells elucidates the dynamic shifts in transcript abundance and discovers regulatory design elements. Altogether, our results suggest that manipulation of cellular resource allocation is a key control parameter for synthetic circuit design.« less

  16. High pCO2-induced exopolysaccharide-rich ballasted aggregates of planktonic cyanobacteria could explain Paleoproterozoic carbon burial.

    PubMed

    Kamennaya, Nina A; Zemla, Marcin; Mahoney, Laura; Chen, Liang; Holman, Elizabeth; Holman, Hoi-Ying; Auer, Manfred; Ajo-Franklin, Caroline M; Jansson, Christer

    2018-05-29

    The contribution of planktonic cyanobacteria to burial of organic carbon in deep-sea sediments before the emergence of eukaryotic predators ~1.5 Ga has been considered negligible owing to the slow sinking speed of their small cells. However, global, highly positive excursion in carbon isotope values of inorganic carbonates ~2.22-2.06 Ga implies massive organic matter burial that had to be linked to oceanic cyanobacteria. Here to elucidate that link, we experiment with unicellular planktonic cyanobacteria acclimated to high partial CO 2 pressure (pCO 2 ) representative of the early Paleoproterozoic. We find that high pCO 2 boosts generation of acidic extracellular polysaccharides (EPS) that adsorb Ca and Mg cations, support mineralization, and aggregate cells to form ballasted particles. The down flux of such self-assembled cyanobacterial aggregates would decouple the oxygenic photosynthesis from oxidative respiration at the ocean scale, drive export of organic matter from surface to deep ocean and sustain oxygenation of the planetary surface.

  17. Next generation bone tissue engineering: non-viral miR-133a inhibition using collagen-nanohydroxyapatite scaffolds rapidly enhances osteogenesis

    NASA Astrophysics Data System (ADS)

    Mencía Castaño, Irene; Curtin, Caroline M.; Duffy, Garry P.; O'Brien, Fergal J.

    2016-06-01

    Bone grafts are the second most transplanted materials worldwide at a global cost to healthcare systems valued over $30 billion every year. The influence of microRNAs in the regenerative capacity of stem cells offers vast therapeutic potential towards bone grafting; however their efficient delivery to the target site remains a major challenge. This study describes how the functionalisation of porous collagen-nanohydroxyapatite (nHA) scaffolds with miR-133a inhibiting complexes, delivered using non-viral nHA particles, enhanced human mesenchymal stem cell-mediated osteogenesis through the novel focus on a key activator of osteogenesis, Runx2. This study showed enhanced Runx2 and osteocalcin expression, as well as increased alkaline phosphatase activity and calcium deposition, thus demonstrating a further enhanced therapeutic potential of a biomaterial previously optimised for bone repair applications. The promising features of this platform offer potential for a myriad of applications beyond bone repair and tissue engineering, thus presenting a new paradigm for microRNA-based therapeutics.

  18. [Globalization of acupuncture technology innovation: a quantitative analysis based on acupuncture patents in the U.S.A].

    PubMed

    Pan, Wei; Hu, Yuan-Jia; Wang, Yi-Tao

    2011-08-01

    The structure of international flow of acupuncture knowledge was explored in this article so as to promote the globalization of acupuncture technology innovation. Statistical methods were adopted to reveal geographical distribution of acupuncture patents in the U.S.A. and the influencing factors of cumulative advantage of acupuncture techniques as well as innovation value of application of acupuncture patents. Social network analysis was also utilized to establish a global innovation network of acupuncture technology. The result shows that the cumulative strength on acupuncture technology correlates with the patent retention period. The innovative value of acupuncture invention correlates with the frequency of patent citation. And the U. S. A. and Canada seize central positions in the global acupuncture information and technology delivery system.

  19. Soybean Trade: Balancing Environmental and Socio-Economic Impacts of an Intercontinental Market

    PubMed Central

    Boerema, Annelies; Peeters, Alain; Swolfs, Sanne; Vandevenne, Floor; Jacobs, Sander; Staes, Jan; Meire, Patrick

    2016-01-01

    The trade in soybean, an important animal feed product, exemplifies the environmental and socio-economic impact of global markets and global agricultural policy. This paper analyses the impact of increasing production of soybean in the exporting countries (deforestation and grassland conversion) as well as in importing regions (decrease in permanent grassland by substitution of grass as feed). Ecosystem services monetary values were used to calculate the environmental and socio-economic impact of observed land use changes. This is balanced against the economic value of the global soybean trade. The results prove that consumption choices in one region have real effects on the supply of ecosystem services at a large spatial scale. Conclusively, solutions to make this global market more sustainable are discussed. PMID:27244079

  20. Global asymptotic stability and hopf bifurcation for a blood cell production model.

    PubMed

    Crauste, Fabien

    2006-04-01

    We analyze the asymptotic stability of a nonlinear system of two differential equations with delay, describing the dynamics of blood cell produc- tion. This process takes place in the bone marrow, where stem cells differen- tiate throughout division in blood cells. Taking into account an explicit role of the total population of hematopoietic stem cells in the introduction of cells in cycle, we are led to study a characteristic equation with delay-dependent coefficients. We determine a necessary and sufficient condition for the global stability of the first steady state of our model, which describes the popula- tion's dying out, and we obtain the existence of a Hopf bifurcation for the only nontrivial positive steady state, leading to the existence of periodic solutions. These latter are related to dynamical diseases affecting blood cells known for their cyclic nature.

  1. Future battlegrounds for conservation under global change

    PubMed Central

    Lee, Tien Ming; Jetz, Walter

    2008-01-01

    Global biodiversity is under significant threat from the combined effects of human-induced climate and land-use change. Covering 12% of the Earth's terrestrial surface, protected areas are crucial for conserving biodiversity and supporting ecological processes beneficial to human well-being, but their selection and design are usually uninformed about future global change. Here, we quantify the exposure of the global reserve network to projected climate and land-use change according to the Millennium Ecosystem Assessment and set these threats in relation to the conservation value and capacity of biogeographic and geopolitical regions. We find that geographical patterns of past human impact on the land cover only poorly predict those of forecasted change, thus revealing the inadequacy of existing global conservation prioritization templates. Projected conservation risk, measured as regional levels of land-cover change in relation to area protected, is the greatest at high latitudes (due to climate change) and tropics/subtropics (due to land-use change). Only some high-latitude nations prone to high conservation risk are also of high conservation value, but their high relative wealth may facilitate additional conservation efforts. In contrast, most low-latitude nations tend to be of high conservation value, but they often have limited capacity for conservation which may exacerbate the global biodiversity extinction crisis. While our approach will clearly benefit from improved land-cover projections and a thorough understanding of how species range will shift under climate change, our results provide a first global quantitative demonstration of the urgent need to consider future environmental change in reserve-based conservation planning. They further highlight the pressing need for new reserves in target regions and support a much extended ‘north–south’ transfer of conservation resources that maximizes biodiversity conservation while mitigating global climate change. PMID:18302999

  2. The calculated influence of atmospheric conditions on solar cell ISC under direct and global solar irradiances

    NASA Technical Reports Server (NTRS)

    Mueller, Robert L.

    1987-01-01

    Calculations of the influence of atmospheric conditions on solar cell short-circuit current (Isc) are made using a recently developed computer model for solar spectral irradiance distribution. The results isolate the dependence of Isc on changes in the spectral irradiance distribution without the direct influence of the total irradiance level. The calculated direct normal irradiance and percent diffuse irradiance are given as a reference to indicate the expected irradiance levels. This method can be applied to the calibration of photovoltaic reference cells. Graphic examples are provided for amorphous silicon and monocrystalline silicon solar cells under direct normal and global normal solar irradiances.

  3. Enhancing the Biological Relevance of Secretome-Based Proteomics by Linking Tumor Cell Proliferation and Protein Secretion.

    PubMed

    Gregori, Josep; Méndez, Olga; Katsila, Theodora; Pujals, Mireia; Salvans, Cándida; Villarreal, Laura; Arribas, Joaquin; Tabernero, Josep; Sánchez, Alex; Villanueva, Josep

    2014-07-15

    Secretome profiling has become a methodology of choice for the identification of tumor biomarkers. We hypothesized that due to the dynamic nature of secretomes cellular perturbations could affect their composition but also change the global amount of protein secreted per cell. We confirmed our hypothesis by measuring the levels of secreted proteins taking into account the amount of proteome produced per cell. Then, we established a correlation between cell proliferation and protein secretion that explained the observed changes in global protein secretion. Next, we implemented a normalization correcting the statistical results of secretome studies by the global protein secretion of cells into a generalized linear model (GLM). The application of the normalization to two biological perturbations on tumor cells resulted in drastic changes in the list of statistically significant proteins. Furthermore, we found that known epithelial-to-mesenchymal transition (EMT) effectors were only statistically significant when the normalization was applied. Therefore, the normalization proposed here increases the sensitivity of statistical tests by increasing the number of true-positives. From an oncology perspective, the correlation between protein secretion and cellular proliferation suggests that slow-growing tumors could have high-protein secretion rates and consequently contribute strongly to tumor paracrine signaling.

  4. Physics of Cellular Movements

    NASA Astrophysics Data System (ADS)

    Sackmann, Erich; Keber, Felix; Heinrich, Doris

    2010-04-01

    The survival of cells depends on perpetual active motions, including (a) bending excitations of the soft cell envelopes, (b) the bidirectional transport of materials and organelles between the cell center and the periphery, and (c) the ongoing restructuring of the intracellular macromolecular scaffolds mediating global cell changes associated with cell adhesion locomotion and phagocytosis. Central questions addressed are the following: How can this bustling motion of extremely complex soft structures be characterized and measured? What are the major driving forces? Further topics include (a) the active dynamic control of global shape changes by the interactive coupling of the aster-like soft scaffold of microtubules and the network of actin filaments associated with the cell envelope (the actin cortex) and (b) the generation of propulsion forces by solitary actin gelation waves propagating within the actin cortex.

  5. Globally optimal trial design for local decision making.

    PubMed

    Eckermann, Simon; Willan, Andrew R

    2009-02-01

    Value of information methods allows decision makers to identify efficient trial design following a principle of maximizing the expected value to decision makers of information from potential trial designs relative to their expected cost. However, in health technology assessment (HTA) the restrictive assumption has been made that, prospectively, there is only expected value of sample information from research commissioned within jurisdiction. This paper extends the framework for optimal trial design and decision making within jurisdiction to allow for optimal trial design across jurisdictions. This is illustrated in identifying an optimal trial design for decision making across the US, the UK and Australia for early versus late external cephalic version for pregnant women presenting in the breech position. The expected net gain from locally optimal trial designs of US$0.72M is shown to increase to US$1.14M with a globally optimal trial design. In general, the proposed method of globally optimal trial design improves on optimal trial design within jurisdictions by: (i) reflecting the global value of non-rival information; (ii) allowing optimal allocation of trial sample across jurisdictions; (iii) avoiding market failure associated with free-rider effects, sub-optimal spreading of fixed costs and heterogeneity of trial information with multiple trials. Copyright (c) 2008 John Wiley & Sons, Ltd.

  6. In-phase oscillation of global regulons is orchestrated by a pole-specific organizer

    PubMed Central

    Janakiraman, Balaganesh; Mignolet, Johann; Narayanan, Sharath; Viollier, Patrick H.

    2016-01-01

    Cell fate determination in the asymmetric bacterium Caulobacter crescentus (Caulobacter) is triggered by the localization of the developmental regulator SpmX to the old (stalked) cell pole during the G1→S transition. Although SpmX is required to localize and activate the cell fate-determining kinase DivJ at the stalked pole in Caulobacter, in cousins such as Asticcacaulis, SpmX directs organelle (stalk) positioning and possibly other functions. We define the conserved σ54-dependent transcriptional activator TacA as a global regulator in Caulobacter whose activation by phosphorylation is indirectly down-regulated by SpmX. Using a combination of forward genetics and cytological screening, we uncover a previously uncharacterized and polarized component (SpmY) of the TacA phosphorylation control system, and we show that SpmY function and localization are conserved. Thus, SpmX organizes a site-specific, ancestral, and multifunctional regulatory hub integrating the in-phase oscillation of two global transcriptional regulators, CtrA (the master cell cycle transcriptional regulator A) and TacA, that perform important cell cycle functions. PMID:27791133

  7. Study of temperature, air dew point temperature and reactant flow effects on proton exchange membrane fuel cell performances using electrochemical spectroscopy and voltammetry techniques

    NASA Astrophysics Data System (ADS)

    Wasterlain, S.; Candusso, D.; Hissel, D.; Harel, F.; Bergman, P.; Menard, P.; Anwar, M.

    A single PEMFC has been operated by varying the assembly temperature, the air dew point temperature and the anode/cathode stoichiometry rates with the aim to identify the parameters and combinations of factors affecting the cell performance. Some of the experiments were conducted with low humidified reactants (relative humidity of 12%). The FC characterizations tests have been conducted using in situ electrochemical methods based on load current and cell voltage signal analysis, namely: polarization curves, EIS measurements, cyclic and linear sweep voltammetries (CV and LSV). The impacts of the parameters on the global FC performances were observed using the polarization curves whereas EIS, CV and LSV test results were used to discriminate the different voltage loss sources. The test results suggest that some parameter sets allow maximal output voltages but can also induce material degradation. For instance, higher FC temperature and air flow values can induce significant electrical efficiency benefits, notably by increasing the reversible potential and the reaction kinetics. However, raising the cell temperature can also gradually dry the FC and increase the risk of membrane failure. LSV has also shown that elevated FC temperature and relative humidity can also accelerate the electrolyte degradation (i.e. slightly higher fuel crossover rate) and reduce the lifetime consequently.

  8. Environmental and economic assessment of a cracked ammonia fuelled alkaline fuel cell for off-grid power applications

    NASA Astrophysics Data System (ADS)

    Cox, Brian; Treyer, Karin

    2015-02-01

    Global mobile telecommunication is possible due to millions of Base Transceiver Stations (BTS). Nearly 1 million of these are operating off-grid, typically powered by diesel generators and therefore leading to significant CO2 emissions and other environmental burdens. A novel type of Alkaline Fuel Cell (AFC) powered by cracked ammonia is being developed for replacement of these generators. This study compares the environmental and economic performance of the two systems by means of Life Cycle Assessment (LCA) and Levelised Cost of Electricity (LCOE), respectively. Results show that the production of ammonia dominates the LCA results, and that renewable ammonia production pathways greatly improve environmental performance. Sensitivity analyses reveal that the fuel cell parameters that most affect system cost and environmental burdens are cell power density and lifetime and system efficiency. Recycling of anode catalyst and electrode substrate materials is found to have large impacts on environmental performance, though without large cost incentives. For a set of target parameter values and fossil sourced ammonia, the AFC is calculated to produce electricity with life cycle CO2 eq emissions of 1.08 kg kWh-1, which is 23% lower than a diesel generator with electricity costs that are 14% higher in the same application.

  9. Global stability for an HIV-1 infection model with Beddington-DeAngelis incidence rate and CTL immune response

    NASA Astrophysics Data System (ADS)

    Lv, Cuifang; Huang, Lihong; Yuan, Zhaohui

    2014-01-01

    In this paper, an HIV-1 infection model with Beddington-DeAngelis incidence rate and CTL immune response is investigated. One main feature of this model is that an eclipse stage for the infected cells is included and a portion of these cells is reverted to uninfected cells. We derive the basic reproduction number R1 and the immune response reproduction number R2 for the HIV-1 infection model. By constructing Lyapunov functions, the global stabilities for the equilibria have been analyzed.

  10. Grid cells form a global representation of connected environments.

    PubMed

    Carpenter, Francis; Manson, Daniel; Jeffery, Kate; Burgess, Neil; Barry, Caswell

    2015-05-04

    The firing patterns of grid cells in medial entorhinal cortex (mEC) and associated brain areas form triangular arrays that tessellate the environment [1, 2] and maintain constant spatial offsets to each other between environments [3, 4]. These cells are thought to provide an efficient metric for navigation in large-scale space [5-8]. However, an accurate and universal metric requires grid cell firing patterns to uniformly cover the space to be navigated, in contrast to recent demonstrations that environmental features such as boundaries can distort [9-11] and fragment [12] grid patterns. To establish whether grid firing is determined by local environmental cues, or provides a coherent global representation, we recorded mEC grid cells in rats foraging in an environment containing two perceptually identical compartments connected via a corridor. During initial exposures to the multicompartment environment, grid firing patterns were dominated by local environmental cues, replicating between the two compartments. However, with prolonged experience, grid cell firing patterns formed a single, continuous representation that spanned both compartments. Thus, we provide the first evidence that in a complex environment, grid cell firing can form the coherent global pattern necessary for them to act as a metric capable of supporting large-scale spatial navigation. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Grid Cells Form a Global Representation of Connected Environments

    PubMed Central

    Carpenter, Francis; Manson, Daniel; Jeffery, Kate; Burgess, Neil; Barry, Caswell

    2015-01-01

    Summary The firing patterns of grid cells in medial entorhinal cortex (mEC) and associated brain areas form triangular arrays that tessellate the environment [1, 2] and maintain constant spatial offsets to each other between environments [3, 4]. These cells are thought to provide an efficient metric for navigation in large-scale space [5–8]. However, an accurate and universal metric requires grid cell firing patterns to uniformly cover the space to be navigated, in contrast to recent demonstrations that environmental features such as boundaries can distort [9–11] and fragment [12] grid patterns. To establish whether grid firing is determined by local environmental cues, or provides a coherent global representation, we recorded mEC grid cells in rats foraging in an environment containing two perceptually identical compartments connected via a corridor. During initial exposures to the multicompartment environment, grid firing patterns were dominated by local environmental cues, replicating between the two compartments. However, with prolonged experience, grid cell firing patterns formed a single, continuous representation that spanned both compartments. Thus, we provide the first evidence that in a complex environment, grid cell firing can form the coherent global pattern necessary for them to act as a metric capable of supporting large-scale spatial navigation. PMID:25913404

  12. Global Identification of Disease-Associated Genes in Fragile X Cells

    DTIC Science & Technology

    2017-03-01

    identify those specific gene substrates of FMRP, particularly those expressed in the brain , that are implicated in FXS progression. Moreover, we use...the co-localized R-loop formation and chromosome fragility in Fragile X cells, particularly at the brain -expressed genes, by ChIP-seq (detecting...X mental retardation protein February 2016, NGS Data Analysis & Informatics Conference, San Diego, California (Poster presentation) Title: Global

  13. Emergent global oscillations in heterogeneous excitable media: The example of pancreatic β cells

    NASA Astrophysics Data System (ADS)

    Cartwright, Julyan H. E.

    2000-07-01

    Using the standard van der Pol-FitzHugh-Nagumo excitable medium model, I demonstrate a generic mechanism, diversity, that provokes the emergence of global oscillations from individually quiescent elements in heterogeneous excitable media. This mechanism may be operating in the mammalian pancreas, where excitable β cells, quiescent when isolated, are found to oscillate when coupled, despite the absence of a pacemaker region.

  14. TCF21 hypermethylation in genetically quiescent clear cell sarcoma of the kidney | Office of Cancer Genomics

    Cancer.gov

    Clear Cell Sarcoma of the Kidney (CCSK) is a rare childhood tumor whose molecular pathogenesis remains poorly understood. We analyzed a discovery set of 13 CCSKs for changes in chromosome copy number, mutations, rearrangements, global gene expression and global DNA methylation. No recurrent segmental chromosomal copy number changes or somatic variants (single nucleotide or small insertion/deletion) were identified.

  15. Value-cell bar charts for visualizing large transaction data sets.

    PubMed

    Keim, Daniel A; Hao, Ming C; Dayal, Umeshwar; Lyons, Martha

    2007-01-01

    One of the common problems businesses need to solve is how to use large volumes of sales histories, Web transactions, and other data to understand the behavior of their customers and increase their revenues. Bar charts are widely used for daily analysis, but only show highly aggregated data. Users often need to visualize detailed multidimensional information reflecting the health of their businesses. In this paper, we propose an innovative visualization solution based on the use of value cells within bar charts to represent business metrics. The value of a transaction can be discretized into one or multiple cells: high-value transactions are mapped to multiple value cells, whereas many small-value transactions are combined into one cell. With value-cell bar charts, users can 1) visualize transaction value distributions and correlations, 2) identify high-value transactions and outliers at a glance, and 3) instantly display values at the transaction record level. Value-Cell Bar Charts have been applied with success to different sales and IT service usage applications, demonstrating the benefits of the technique over traditional charting techniques. A comparison with two variants of the well-known Treemap technique and our earlier work on Pixel Bar Charts is also included.

  16. Local behavioral rules sustain the cell allocation pattern in the combs of honey bee colonies (Apis mellifera).

    PubMed

    Montovan, Kathryn J; Karst, Nathaniel; Jones, Laura E; Seeley, Thomas D

    2013-11-07

    In the beeswax combs of honey bees, the cells of brood, pollen, and honey have a consistent spatial pattern that is sustained throughout the life of a colony. This spatial pattern is believed to emerge from simple behavioral rules that specify how the queen moves, where foragers deposit honey/pollen and how honey/pollen is consumed from cells. Prior work has shown that a set of such rules can explain the formation of the allocation pattern starting from an empty comb. We show that these rules cannot maintain the pattern once the brood start to vacate their cells, and we propose new, biologically realistic rules that better sustain the observed allocation pattern. We analyze the three resulting models by performing hundreds of simulation runs over many gestational periods and a wide range of parameter values. We develop new metrics for pattern assessment and employ them in analyzing pattern retention over each simulation run. Applied to our simulation results, these metrics show alteration of an accepted model for honey/pollen consumption based on local information can stabilize the cell allocation pattern over time. We also show that adding global information, by biasing the queen's movements towards the center of the comb, expands the parameter regime over which pattern retention occurs. © 2013 Published by Elsevier Ltd. All rights reserved.

  17. Micro-proteomics with iterative data analysis: Proteome analysis in C. elegans at the single worm level.

    PubMed

    Bensaddek, Dalila; Narayan, Vikram; Nicolas, Armel; Murillo, Alejandro Brenes; Gartner, Anton; Kenyon, Cynthia J; Lamond, Angus I

    2016-02-01

    Proteomics studies typically analyze proteins at a population level, using extracts prepared from tens of thousands to millions of cells. The resulting measurements correspond to average values across the cell population and can mask considerable variation in protein expression and function between individual cells or organisms. Here, we report the development of micro-proteomics for the analysis of Caenorhabditis elegans, a eukaryote composed of 959 somatic cells and ∼1500 germ cells, measuring the worm proteome at a single organism level to a depth of ∼3000 proteins. This includes detection of proteins across a wide dynamic range of expression levels (>6 orders of magnitude), including many chromatin-associated factors involved in chromosome structure and gene regulation. We apply the micro-proteomics workflow to measure the global proteome response to heat-shock in individual nematodes. This shows variation between individual animals in the magnitude of proteome response following heat-shock, including variable induction of heat-shock proteins. The micro-proteomics pipeline thus facilitates the investigation of stochastic variation in protein expression between individuals within an isogenic population of C. elegans. All data described in this study are available online via the Encyclopedia of Proteome Dynamics (http://www.peptracker.com/epd), an open access, searchable database resource. © 2015 The Authors. PROTEOMICS Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Engineering microbial cell factories for the production of plant natural products: from design principles to industrial-scale production.

    PubMed

    Liu, Xiaonan; Ding, Wentao; Jiang, Huifeng

    2017-07-19

    Plant natural products (PNPs) are widely used as pharmaceuticals, nutraceuticals, seasonings, pigments, etc., with a huge commercial value on the global market. However, most of these PNPs are still being extracted from plants. A resource-conserving and environment-friendly synthesis route for PNPs that utilizes microbial cell factories has attracted increasing attention since the 1940s. However, at the present only a handful of PNPs are being produced by microbial cell factories at an industrial scale, and there are still many challenges in their large-scale application. One of the challenges is that most biosynthetic pathways of PNPs are still unknown, which largely limits the number of candidate PNPs for heterologous microbial production. Another challenge is that the metabolic fluxes toward the target products in microbial hosts are often hindered by poor precursor supply, low catalytic activity of enzymes and obstructed product transport. Consequently, despite intensive studies on the metabolic engineering of microbial hosts, the fermentation costs of most heterologously produced PNPs are still too high for industrial-scale production. In this paper, we review several aspects of PNP production in microbial cell factories, including important design principles and recent progress in pathway mining and metabolic engineering. In addition, implemented cases of industrial-scale production of PNPs in microbial cell factories are also highlighted.

  19. Time-optimal trajectory planning for underactuated spacecraft using a hybrid particle swarm optimization algorithm

    NASA Astrophysics Data System (ADS)

    Zhuang, Yufei; Huang, Haibin

    2014-02-01

    A hybrid algorithm combining particle swarm optimization (PSO) algorithm with the Legendre pseudospectral method (LPM) is proposed for solving time-optimal trajectory planning problem of underactuated spacecrafts. At the beginning phase of the searching process, an initialization generator is constructed by the PSO algorithm due to its strong global searching ability and robustness to random initial values, however, PSO algorithm has a disadvantage that its convergence rate around the global optimum is slow. Then, when the change in fitness function is smaller than a predefined value, the searching algorithm is switched to the LPM to accelerate the searching process. Thus, with the obtained solutions by the PSO algorithm as a set of proper initial guesses, the hybrid algorithm can find a global optimum more quickly and accurately. 200 Monte Carlo simulations results demonstrate that the proposed hybrid PSO-LPM algorithm has greater advantages in terms of global searching capability and convergence rate than both single PSO algorithm and LPM algorithm. Moreover, the PSO-LPM algorithm is also robust to random initial values.

  20. Seasonal Variability in Global Eddy Diffusion and the Effect on Thermospheric Neutral Density

    NASA Astrophysics Data System (ADS)

    Pilinski, M.; Crowley, G.

    2014-12-01

    We describe a method for making single-satellite estimates of the seasonal variability in global-average eddy diffusion coefficients. Eddy diffusion values as a function of time between January 2004 and January 2008 were estimated from residuals of neutral density measurements made by the CHallenging Minisatellite Payload (CHAMP) and simulations made using the Thermosphere Ionosphere Mesosphere Electrodynamics - Global Circulation Model (TIME-GCM). The eddy diffusion coefficient results are quantitatively consistent with previous estimates based on satellite drag observations and are qualitatively consistent with other measurement methods such as sodium lidar observations and eddy-diffusivity models. The eddy diffusion coefficient values estimated between January 2004 and January 2008 were then used to generate new TIME-GCM results. Based on these results, the RMS difference between the TIME-GCM model and density data from a variety of satellites is reduced by an average of 5%. This result, indicates that global thermospheric density modeling can be improved by using data from a single satellite like CHAMP. This approach also demonstrates how eddy diffusion could be estimated in near real-time from satellite observations and used to drive a global circulation model like TIME-GCM. Although the use of global values improves modeled neutral densities, there are some limitations of this method, which are discussed, including that the latitude-dependence of the seasonal neutral-density signal is not completely captured by a global variation of eddy diffusion coefficients. This demonstrates the need for a latitude-dependent specification of eddy diffusion consistent with diffusion observations made by other techniques.

  1. Seasonal variability in global eddy diffusion and the effect on neutral density

    NASA Astrophysics Data System (ADS)

    Pilinski, M. D.; Crowley, G.

    2015-04-01

    We describe a method for making single-satellite estimates of the seasonal variability in global-average eddy diffusion coefficients. Eddy diffusion values as a function of time were estimated from residuals of neutral density measurements made by the Challenging Minisatellite Payload (CHAMP) and simulations made using the thermosphere-ionosphere-mesosphere electrodynamics global circulation model (TIME-GCM). The eddy diffusion coefficient results are quantitatively consistent with previous estimates based on satellite drag observations and are qualitatively consistent with other measurement methods such as sodium lidar observations and eddy diffusivity models. Eddy diffusion coefficient values estimated between January 2004 and January 2008 were then used to generate new TIME-GCM results. Based on these results, the root-mean-square sum for the TIME-GCM model is reduced by an average of 5% when compared to density data from a variety of satellites, indicating that the fidelity of global density modeling can be improved by using data from a single satellite like CHAMP. This approach also demonstrates that eddy diffusion could be estimated in near real-time from satellite observations and used to drive a global circulation model like TIME-GCM. Although the use of global values improves modeled neutral densities, there are limitations to this method, which are discussed, including that the latitude dependence of the seasonal neutral-density signal is not completely captured by a global variation of eddy diffusion coefficients. This demonstrates the need for a latitude-dependent specification of eddy diffusion which is also consistent with diffusion observations made by other techniques.

  2. Basal CD34+ Cell Count Predicts Peripheral Blood Stem Cell Mobilization in Healthy Donors after Administration of Granulocyte Colony-Stimulating Factor: A Longitudinal, Prospective, Observational, Single-Center, Cohort Study.

    PubMed

    Martino, Massimo; Gori, Mercedes; Pitino, Annalisa; Gentile, Massimo; Dattola, Antonia; Pontari, Antonella; Vigna, Ernesto; Moscato, Tiziana; Recchia, Anna Grazia; Barilla', Santina; Tripepi, Giovanni; Morabito, Fortunato

    2017-07-01

    A longitudinal, prospective, observational, single-center, cohort study on healthy donors (HDs) was designed to identify predictors of CD34 + cells on day 5 with emphasis on the predictive value of the basal CD34 + cell count. As potential predictors of mobilization, age, sex, body weight, height, blood volume as well as white blood cell count, peripheral blood (PB) mononuclear cells, platelet count, hematocrit, and hemoglobin levels were considered. Two different evaluations of CD34 + cell counts were determined for each donor: baseline (before granulocyte colony-stimulating factor [G-CSF] administration) and in PB after G-CSF administration on the morning of the fifth day (day 5). A total of 128 consecutive HDs (66 males) with a median age of 43 years were enrolled. CD34 + levels on day 5 displayed a non-normal distribution, with a median value of 75.5 cells/µL. To account for the non-normal distribution of the dependent variable, a quantile regression analysis to predict CD34 + on day 5 using the baseline value of CD34 + as the key predictor was performed. On crude analysis, a baseline value of CD34 + ranging from .5 cells/µL to 1 cells/µL predicts a median value of 50 cells/µL on day 5; a value of 2 cells/µL predicts a median value of 70.7 cells/µL; a value of 3 cells/µL to 4 cells/µL predicts a median value of 91.3 cells/µL, and a value ≥ 5 predicts a median value of 112 cells/µL. In conclusion, the baseline PB CD34 + cell count correlates with the effectiveness of allogeneic PB stem cell mobilization and could be useful to plan the collection. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  3. Perceived reciprocal value of health professionals' participation in global child health-related work.

    PubMed

    Carbone, Sarah; Wigle, Jannah; Akseer, Nadia; Barac, Raluca; Barwick, Melanie; Zlotkin, Stanley

    2017-05-22

    Leading children's hospitals in high-income settings have become heavily engaged in international child health research and educational activities. These programs aim to provide benefit to the institutions, children and families in the overseas locations where they are implemented. Few studies have measured the actual reciprocal value of this work for the home institutions and for individual staff who participate in these overseas activities. Our objective was to estimate the perceived reciprocal value of health professionals' participation in global child health-related work. Benefits were measured in the form of skills, knowledge and attitude strengthening as estimated by an adapted Global Health Competency Model. A survey questionnaire was developed following a comprehensive review of literature and key competency models. It was distributed to all health professionals at the Hospital for Sick Children with prior international work experience (n = 478). One hundred fifty six health professionals completed the survey (34%). A score of 0 represented negligible value gained and a score of 100 indicated significant capacity improvement. The mean respondent improvement score was 57 (95% CI 53-62) suggesting improved overall competency resulting from their international experiences. Mean scores were >50% in 8 of 10 domains. Overall scores suggest that international work brought value to the hospital and over half responded that their international experience would influence their decision to stay on at the hospital. The findings offer tangible examples of how global child health work conducted outside of one's home institution impacts staff and health systems locally.

  4. Marine Geoid Undulation Assessment Over South China Sea Using Global Geopotential Models and Airborne Gravity Data

    NASA Astrophysics Data System (ADS)

    Yazid, N. M.; Din, A. H. M.; Omar, K. M.; Som, Z. A. M.; Omar, A. H.; Yahaya, N. A. Z.; Tugi, A.

    2016-09-01

    Global geopotential models (GGMs) are vital in computing global geoid undulations heights. Based on the ellipsoidal height by Global Navigation Satellite System (GNSS) observations, the accurate orthometric height can be calculated by adding precise and accurate geoid undulations model information. However, GGMs also provide data from the satellite gravity missions such as GRACE, GOCE and CHAMP. Thus, this will assist to enhance the global geoid undulations data. A statistical assessment has been made between geoid undulations derived from 4 GGMs and the airborne gravity data provided by Department of Survey and Mapping Malaysia (DSMM). The goal of this study is the selection of the best possible GGM that best matches statistically with the geoid undulations of airborne gravity data under the Marine Geodetic Infrastructures in Malaysian Waters (MAGIC) Project over marine areas in Sabah. The correlation coefficients and the RMS value for the geoid undulations of GGM and airborne gravity data were computed. The correlation coefficients between EGM 2008 and airborne gravity data is 1 while RMS value is 0.1499.In this study, the RMS value of EGM 2008 is the lowest among the others. Regarding to the statistical analysis, it clearly represents that EGM 2008 is the best fit for marine geoid undulations throughout South China Sea.

  5. Joint spatiotemporal variability of global sea surface temperatures and global Palmer drought severity index values

    USGS Publications Warehouse

    Apipattanavis, S.; McCabe, G.J.; Rajagopalan, B.; Gangopadhyay, S.

    2009-01-01

    Dominant modes of individual and joint variability in global sea surface temperatures (SST) and global Palmer drought severity index (PDSI) values for the twentieth century are identified through a multivariate frequency domain singular value decomposition. This analysis indicates that a secular trend and variability related to the El Niño–Southern Oscillation (ENSO) are the dominant modes of variance shared among the global datasets. For the SST data the secular trend corresponds to a positive trend in Indian Ocean and South Atlantic SSTs, and a negative trend in North Pacific and North Atlantic SSTs. The ENSO reconstruction shows a strong signal in the tropical Pacific, North Pacific, and Indian Ocean regions. For the PDSI data, the secular trend reconstruction shows high amplitudes over central Africa including the Sahel, whereas the regions with strong ENSO amplitudes in PDSI are the southwestern and northwestern United States, South Africa, northeastern Brazil, central Africa, the Indian subcontinent, and Australia. An additional significant frequency, multidecadal variability, is identified for the Northern Hemisphere. This multidecadal frequency appears to be related to the Atlantic multidecadal oscillation (AMO). The multidecadal frequency is statistically significant in the Northern Hemisphere SST data, but is statistically nonsignificant in the PDSI data.

  6. A non-cytotoxic N-dehydroabietylamine derivative with potent antimalarial activity.

    PubMed

    Sadashiva, Maralinganadoddi P; Gowda, Raghavendra; Wu, Xianzhu; Inamdar, Gajanan S; Kuzu, Omer F; Rangappa, Kanchugarakoppal S; Robertson, Gavin P; Gowda, D Channe

    2015-08-01

    Malaria caused by the Plasmodium parasites continues to be an enormous global health problem owing to wide spread drug resistance of parasites to many of the available antimalarial drugs. Therefore, development of new classes of antimalarial agents is essential to effectively treat malaria. In this study, the efficacy of naturally occurring diterpenoids, dehydroabietylamine and abietic acid, and their synthetic derivatives was assessed for antimalarial activity. Dehydroabietylamine and its N-trifluoroacetyl, N-tribromoacetyl, N-benzoyl, and N-benzyl derivatives showed excellent activity against P. falciparum parasites with IC50 values of 0.36 to 2.6 µM. Interestingly, N-dehydroabietylbenzamide showed potent antimalarial activity (IC50 0.36), and negligible cytotoxicity (IC50 >100 µM) to mammalian cells; thus, this compound can be an important antimalarial drug. In contrast, abietic acid was only marginally effective, exhibiting an IC50 value of ~82 µM. Several carboxylic group-derivatives of abietic acid were moderately active with IC50 values of ~8.2 to ~13.3 µM. These results suggest that a detailed understanding of the structure-activity relationship of abietane diterpenoids might provide strategies to exploit this class of compounds for malaria treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Variations in atmospheric angular momentum and the length of day

    NASA Technical Reports Server (NTRS)

    Rosen, R. D.; Salstein, D. A.

    1982-01-01

    Six years of twice daily global analyses were used to create and study a lengthy time series of high temporal resolution angular momentum values. Changes in these atmospheric values were compared to independently determined charges in the rotation rate of the solid Earth. Finally, the atmospheric data was examined in more detail to determine the time and space scales on which variations in momentum occur within the atmosphere and which regions are contributing most to the changes found in the global integral. The data and techniques used to derive the time series of momentum values are described.

  8. Combining p-values in replicated single-case experiments with multivariate outcome.

    PubMed

    Solmi, Francesca; Onghena, Patrick

    2014-01-01

    Interest in combining probabilities has a long history in the global statistical community. The first steps in this direction were taken by Ronald Fisher, who introduced the idea of combining p-values of independent tests to provide a global decision rule when multiple aspects of a given problem were of interest. An interesting approach to this idea of combining p-values is the one based on permutation theory. The methods belonging to this particular approach exploit the permutation distributions of the tests to be combined, and use a simple function to combine probabilities. Combining p-values finds a very interesting application in the analysis of replicated single-case experiments. In this field the focus, while comparing different treatments effects, is more articulated than when just looking at the means of the different populations. Moreover, it is often of interest to combine the results obtained on the single patients in order to get more global information about the phenomenon under study. This paper gives an overview of how the concept of combining p-values was conceived, and how it can be easily handled via permutation techniques. Finally, the method of combining p-values is applied to a simulated replicated single-case experiment, and a numerical illustration is presented.

  9. Global Trophic Position Comparison of Two Dominant Mesopelagic Fish Families (Myctophidae, Stomiidae) Using Amino Acid Nitrogen Isotopic Analyses

    PubMed Central

    Choy, C. Anela; Davison, Peter C.; Drazen, Jeffrey C.; Flynn, Adrian; Gier, Elizabeth J.; Hoffman, Joel C.; McClain-Counts, Jennifer P.; Miller, Todd W.; Popp, Brian N.; Ross, Steve W.; Sutton, Tracey T.

    2012-01-01

    The δ15N values of organisms are commonly used across diverse ecosystems to estimate trophic position and infer trophic connectivity. We undertook a novel cross-basin comparison of trophic position in two ecologically well-characterized and different groups of dominant mid-water fish consumers using amino acid nitrogen isotope compositions. We found that trophic positions estimated from the δ15N values of individual amino acids are nearly uniform within both families of these fishes across five global regions despite great variability in bulk tissue δ15N values. Regional differences in the δ15N values of phenylalanine confirmed that bulk tissue δ15N values reflect region-specific water mass biogeochemistry controlling δ15N values at the base of the food web. Trophic positions calculated from amino acid isotopic analyses (AA-TP) for lanternfishes (family Myctophidae) (AA-TP ∼2.9) largely align with expectations from stomach content studies (TP ∼3.2), while AA-TPs for dragonfishes (family Stomiidae) (AA-TP ∼3.2) were lower than TPs derived from stomach content studies (TP∼4.1). We demonstrate that amino acid nitrogen isotope analysis can overcome shortcomings of bulk tissue isotope analysis across biogeochemically distinct systems to provide globally comparative information regarding marine food web structure. PMID:23209656

  10. Global trophic position comparison of two dominant mesopelagic fish families (Myctophidae, Stomiidae) using amino acid nitrogen isotopic analyses

    USGS Publications Warehouse

    Choy, C. Anela; Davison, Peter C.; Drazen, Jeffrey C.; Flynn, Adrian; Gier, Elizabeth J.; Hoffman, Joel C.; McClain-Counts, Jennifer P.; Miller, Todd W.; Popp, Brian N.; Ross, Steve W.; Sutton, Tracey T.

    2012-01-01

    The δ15N values of organisms are commonly used across diverse ecosystems to estimate trophic position and infer trophic connectivity. We undertook a novel cross-basin comparison of trophic position in two ecologically well-characterized and different groups of dominant mid-water fish consumers using amino acid nitrogen isotope compositions. We found that trophic positions estimated from the δ15N values of individual amino acids are nearly uniform within both families of these fishes across five global regions despite great variability in bulk tissue δ15N values. Regional differences in the δ15N values of phenylalanine confirmed that bulk tissue δ15N values reflect region-specific water mass biogeochemistry controlling δ15N values at the base of the food web. Trophic positions calculated from amino acid isotopic analyses (AA-TP) for lanternfishes (family Myctophidae) (AA-TP ~2.9) largely align with expectations from stomach content studies (TP ~3.2), while AA-TPs for dragonfishes (family Stomiidae) (AA-TP ~3.2) were lower than TPs derived from stomach content studies (TP~4.1). We demonstrate that amino acid nitrogen isotope analysis can overcome shortcomings of bulk tissue isotope analysis across biogeochemically distinct systems to provide globally comparative information regarding marine food web structure.

  11. On the global dynamics of a chronic myelogenous leukemia model

    NASA Astrophysics Data System (ADS)

    Krishchenko, Alexander P.; Starkov, Konstantin E.

    2016-04-01

    In this paper we analyze some features of global dynamics of a three-dimensional chronic myelogenous leukemia (CML) model with the help of the stability analysis and the localization method of compact invariant sets. The behavior of CML model is defined by concentrations of three cellpopulations circulating in the blood: naive T cells, effector T cells specific to CML and CML cancer cells. We prove that the dynamics of the CML system around the tumor-free equilibrium point is unstable. Further, we compute ultimate upper bounds for all three cell populations and provide the existence conditions of the positively invariant polytope. One ultimate lower bound is obtained as well. Moreover, we describe the iterative localization procedure for refining localization bounds; this procedure is based on cyclic using of localizing functions. Applying this procedure we obtain conditions under which the internal tumor equilibrium point is globally asymptotically stable. Our theoretical analyses are supplied by results of the numerical simulation.

  12. DNA Methylation and Hydroxymethylation Profile of CD34+-Enriched Cell Products Intended for Autologous CD34+ Cell Transplantation.

    PubMed

    Rozman, Jasmina-Ziva; Pohar Perme, Maja; Jez, Mojca; Malicev, Elvira; Krasna, Metka; Vrtovec, Bojan; Rozman, Primoz

    2017-09-01

    Epigenetic dysregulation has been shown to limit functional capacity of aging hematopoietic stem cells, which may contribute to impaired outcome of hematopoietic stem cell-based therapies. The aim of our study was to gain better insight into the epigenetic profile of CD34 + -enriched cell products intended for autologous CD34 + cell transplantation in patients with cardiomyopathy. We found global DNA methylation content significantly higher in immunoselected CD34 + cells compared to leukocytes in leukapheresis products (2.33 ± 1.03% vs. 1.84 ± 0.86%, p = 0.04). Global DNA hydroxymethylation content did not differ between CD34 + cells and leukocytes (p = 0.30). By measuring methylation levels of 94 stem cell transcription factors on a ready-to-use array, we identified 15 factors in which average promoter methylation was significantly different between leukocytes and CD34 + cells. The difference was highest for HOXC12 (58.18 ± 6.47% vs. 13.34 ± 24.18%, p = 0.0009) and NR2F2 (51.65 ± 25.89% vs. 7.66 ± 21.43%, p = 0.0045) genes. Our findings suggest that global DNA methylation and hydroxymethylation patterns as well as target methylation profile of selected genes in CD34 + -enriched cell products do not differ significantly compared to leukapheresis products and, thus, can tell us little about the functional capacity and regenerative properties of CD34 + cells. Future studies should examine other CD34 + cell graft characteristics, which may serve as prognostic tools for autologous CD34 + cell transplantation.

  13. Evaluation of the Ganglion Cell Complex and Retinal Nerve Fiber Layer in Low, Moderate, and High Myopia: A Study by RTVue Spectral Domain Optical Coherence Tomography.

    PubMed

    Sezgin Akcay, Betul Ilkay; Gunay, Betul Onal; Kardes, Esra; Unlu, Cihan; Ergin, Ahmet

    2017-01-01

    To assess the effect of low, moderate, and high myopia on the thickness of the retinal nerve fiber layer (RNFL) and Ganglion cell complex (GCC) measured by Spectral Domain Optical Coherence Tomography (SD-OCT) in non-glaucomatous subjects. The subjects were divided into three groups: low (n = 81, 35.6%), moderate (n = 79, 34.8%), and highly myopic eyes (n = 67, 29.5%). The RNFL thickness profile, including the average, superior, nasal, inferior, and temporal quadrant and each of the eight directional thicknesses, was measured. GCC parameters, including the average, superior, and inferior values, the focal loss volume (FLV), and the global loss volume (GLV), were measured. The correlation between the OCT measurements and the axial length was evaluated. The average, superior, inferior, and nasal RNFL thicknesses of low and moderate myopic eyes were found to be significantly higher than those of highly myopic eyes. The temporal RNFL thicknesses were not different among the three groups. The average, superior, and inferior ganglion cell complex values of low and moderate myopic eyes were significantly higher than those of highly myopic eyes. The FLV and GLV of low and moderate myopic eyes were significantly higher than those of highly myopic eyes (p = 0.001 for all). In the moderate and high myopia groups, the average RNFL thickness and GCC thickness were both negatively correlated with the axial length. Highly myopic subjects tend to have thinner RNFL and GCC thicknesses than subjects with low and moderate myopia.

  14. Cellular dosimetry of (111)In using monte carlo N-particle computer code: comparison with analytic methods and correlation with in vitro cytotoxicity.

    PubMed

    Cai, Zhongli; Pignol, Jean-Philippe; Chan, Conrad; Reilly, Raymond M

    2010-03-01

    Our objective was to compare Monte Carlo N-particle (MCNP) self- and cross-doses from (111)In to the nucleus of breast cancer cells with doses calculated by reported analytic methods (Goddu et al. and Farragi et al.). A further objective was to determine whether the MCNP-predicted surviving fraction (SF) of breast cancer cells exposed in vitro to (111)In-labeled diethylenetriaminepentaacetic acid human epidermal growth factor ((111)In-DTPA-hEGF) could accurately predict the experimentally determined values. MCNP was used to simulate the transport of electrons emitted by (111)In from the cell surface, cytoplasm, or nucleus. The doses to the nucleus per decay (S values) were calculated for single cells, closely packed monolayer cells, or cell clusters. The cell and nucleus dimensions of 6 breast cancer cell lines were measured, and cell line-specific S values were calculated. For self-doses, MCNP S values of nucleus to nucleus agreed very well with those of Goddu et al. (ratio of S values using analytic methods vs. MCNP = 0.962-0.995) and Faraggi et al. (ratio = 1.011-1.024). MCNP S values of cytoplasm and cell surface to nucleus compared fairly well with the reported values (ratio = 0.662-1.534 for Goddu et al.; 0.944-1.129 for Faraggi et al.). For cross doses, the S values to the nucleus were independent of (111)In subcellular distribution but increased with cluster size. S values for monolayer cells were significantly different from those of single cells and cell clusters. The MCNP-predicted SF for monolayer MDA-MB-468, MDA-MB-231, and MCF-7 cells agreed with the experimental data (relative error of 3.1%, -1.0%, and 1.7%). The single-cell and cell cluster models were less accurate in predicting the SF. For MDA-MB-468 cells, relative error was 8.1% using the single-cell model and -54% to -67% using the cell cluster model. Individual cell-line dimensions had large effects on S values and were needed to estimate doses and SF accurately. MCNP simulation compared well with the reported analytic methods in the calculation of subcellular S values for single cells and cell clusters. Application of a monolayer model was most accurate in predicting the SF of breast cancer cells exposed in vitro to (111)In-DTPA-hEGF.

  15. Present and future global distributions of the marine Cyanobacteria Prochlorococcus and Synechococcus

    PubMed Central

    Flombaum, Pedro; Gallegos, José L.; Gordillo, Rodolfo A.; Rincón, José; Zabala, Lina L.; Jiao, Nianzhi; Karl, David M.; Li, William K. W.; Lomas, Michael W.; Veneziano, Daniele; Vera, Carolina S.; Vrugt, Jasper A.; Martiny, Adam C.

    2013-01-01

    The Cyanobacteria Prochlorococcus and Synechococcus account for a substantial fraction of marine primary production. Here, we present quantitative niche models for these lineages that assess present and future global abundances and distributions. These niche models are the result of neural network, nonparametric, and parametric analyses, and they rely on >35,000 discrete observations from all major ocean regions. The models assess cell abundance based on temperature and photosynthetically active radiation, but the individual responses to these environmental variables differ for each lineage. The models estimate global biogeographic patterns and seasonal variability of cell abundance, with maxima in the warm oligotrophic gyres of the Indian and the western Pacific Oceans and minima at higher latitudes. The annual mean global abundances of Prochlorococcus and Synechococcus are 2.9 ± 0.1 × 1027 and 7.0 ± 0.3 × 1026 cells, respectively. Using projections of sea surface temperature as a result of increased concentration of greenhouse gases at the end of the 21st century, our niche models projected increases in cell numbers of 29% and 14% for Prochlorococcus and Synechococcus, respectively. The changes are geographically uneven but include an increase in area. Thus, our global niche models suggest that oceanic microbial communities will experience complex changes as a result of projected future climate conditions. Because of the high abundances and contributions to primary production of Prochlorococcus and Synechococcus, these changes may have large impacts on ocean ecosystems and biogeochemical cycles. PMID:23703908

  16. High order cell-centered scheme totally based on cell average

    NASA Astrophysics Data System (ADS)

    Liu, Ze-Yu; Cai, Qing-Dong

    2018-05-01

    This work clarifies the concept of cell average by pointing out the differences between cell average and cell centroid value, which are averaged cell-centered value and pointwise cell-centered value, respectively. Interpolation based on cell averages is constructed and high order QUICK-like numerical scheme is designed for such interpolation. A new approach of error analysis is introduced in this work, which is similar to Taylor’s expansion.

  17. Analysis of inter-country input-output table based on citation network: How to measure the competition and collaboration between industrial sectors on the global value chain

    PubMed Central

    2017-01-01

    The input-output table is comprehensive and detailed in describing the national economic system with complex economic relationships, which embodies information of supply and demand among industrial sectors. This paper aims to scale the degree of competition/collaboration on the global value chain from the perspective of econophysics. Global Industrial Strongest Relevant Network models were established by extracting the strongest and most immediate industrial relevance in the global economic system with inter-country input-output tables and then transformed into Global Industrial Resource Competition Network/Global Industrial Production Collaboration Network models embodying the competitive/collaborative relationships based on bibliographic coupling/co-citation approach. Three indicators well suited for these two kinds of weighted and non-directed networks with self-loops were introduced, including unit weight for competitive/collaborative power, disparity in the weight for competitive/collaborative amplitude and weighted clustering coefficient for competitive/collaborative intensity. Finally, these models and indicators were further applied to empirically analyze the function of sectors in the latest World Input-Output Database, to reveal inter-sector competitive/collaborative status during the economic globalization. PMID:28873432

  18. Globalization and health care: global justice and the role of physicians.

    PubMed

    Toumi, Rabee

    2014-02-01

    In today's globalized world, nations cannot be totally isolated from or indifferent to their neighbors, especially in regards to medicine and health. While globalization has brought prosperity to millions, disparities among nations and nationals are growing raising once again the question of justice. Similarly, while medicine has developed dramatically over the past few decades, health disparities at the global level are staggering. Seemingly, what our humanity could achieve in matters of scientific development is not justly distributed to benefit everyone. In this paper, it will be argued that a global theoretical agreement on principles of justice may prove unattainable; however, a grass-roots change is warranted to change the current situation. The UNESCO Declaration on Bioethics and Human Rights will be considered as a starting point to achieve this change through extracting the main values embedded in its principles. These values, namely, respecting human dignity and tending to human vulnerability with a hospitable attitude, should then be revived in medical practice. Medical education will be one possible venue to achieve that, especially through role models. Future physicians will then become the fervent advocates for a global and just distribution of health care.

  19. Analysis of inter-country input-output table based on citation network: How to measure the competition and collaboration between industrial sectors on the global value chain.

    PubMed

    Xing, Lizhi

    2017-01-01

    The input-output table is comprehensive and detailed in describing the national economic system with complex economic relationships, which embodies information of supply and demand among industrial sectors. This paper aims to scale the degree of competition/collaboration on the global value chain from the perspective of econophysics. Global Industrial Strongest Relevant Network models were established by extracting the strongest and most immediate industrial relevance in the global economic system with inter-country input-output tables and then transformed into Global Industrial Resource Competition Network/Global Industrial Production Collaboration Network models embodying the competitive/collaborative relationships based on bibliographic coupling/co-citation approach. Three indicators well suited for these two kinds of weighted and non-directed networks with self-loops were introduced, including unit weight for competitive/collaborative power, disparity in the weight for competitive/collaborative amplitude and weighted clustering coefficient for competitive/collaborative intensity. Finally, these models and indicators were further applied to empirically analyze the function of sectors in the latest World Input-Output Database, to reveal inter-sector competitive/collaborative status during the economic globalization.

  20. 3-D DNA methylation phenotypes correlate with cytotoxicity levels in prostate and liver cancer cell models

    PubMed Central

    2013-01-01

    Background The spatial organization of the genome is being evaluated as a novel indicator of toxicity in conjunction with drug-induced global DNA hypomethylation and concurrent chromatin reorganization. 3D quantitative DNA methylation imaging (3D-qDMI) was applied as a cell-by-cell high-throughput approach to investigate this matter by assessing genome topology through represented immunofluorescent nuclear distribution patterns of 5-methylcytosine (MeC) and global DNA (4,6-diamidino-2-phenylindole = DAPI) in labeled nuclei. Methods Differential progression of global DNA hypomethylation was studied by comparatively dosing zebularine (ZEB) and 5-azacytidine (AZA). Treated and untreated (control) human prostate and liver cancer cells were subjected to confocal scanning microscopy and dedicated 3D image analysis for the following features: differential nuclear MeC/DAPI load and codistribution patterns, cell similarity based on these patterns, and corresponding differences in the topology of low-intensity MeC (LIM) and low in intensity DAPI (LID) sites. Results Both agents generated a high fraction of similar MeC phenotypes across applied concentrations. ZEB exerted similar effects at 10–100-fold higher drug concentrations than its AZA analogue: concentration-dependent progression of global cytosine demethylation, validated by measuring differential MeC levels in repeat sequences using MethyLight, and the concurrent increase in nuclear LIM densities correlated with cellular growth reduction and cytotoxicity. Conclusions 3D-qDMI demonstrated the capability of quantitating dose-dependent drug-induced spatial progression of DNA demethylation in cell nuclei, independent from interphase cell-cycle stages and in conjunction with cytotoxicity. The results support the notion of DNA methylation topology being considered as a potential indicator of causal impacts on chromatin distribution with a conceivable application in epigenetic drug toxicology. PMID:23394161

  1. Development and Preliminary Validation of a New Measure of Values in Scientific Work.

    PubMed

    English, Tammy; Antes, Alison L; Baldwin, Kari A; DuBois, James M

    2018-04-01

    In this paper we describe the development and initial psychometric evaluation of a new measure, the values in scientific work (VSW). This scale assesses the level of importance that investigators attach to different VSW. It taps a broad range of intrinsic, extrinsic, and social values that motivate the work of scientists, including values specific to scientific work (e.g., truth and integrity) and more classic work values (e.g., security and prestige) in the context of science. Notably, the values represented in this scale are relevant to scientists regardless of their career stage and research focus. We administered the VSW and a measure of global values to 203 NIH-funded investigators. Exploratory factor analyses suggest the delineation of eight VSW, including autonomy, research ethics, social impact, income, collaboration, innovation and growth, conserving relationships, and job security. These VSW showed predictable and distinct associations with global values. Implications of these findings for work on research integrity and scientific misconduct are discussed.

  2. Multidatabase Query Processing with Uncertainty in Global Keys and Attribute Values.

    ERIC Educational Resources Information Center

    Scheuermann, Peter; Li, Wen-Syan; Clifton, Chris

    1998-01-01

    Presents an approach for dynamic database integration and query processing in the absence of information about attribute correspondences and global IDs. Defines different types of equivalence conditions for the construction of global IDs. Proposes a strategy based on ranked role-sets that makes use of an automated semantic integration procedure…

  3. Executive Perceptions on International Education in a Globalized Environment: The Travel Industry's Point of View

    ERIC Educational Resources Information Center

    Munoz, J. Mark; Katsioloudes, Marios I.

    2004-01-01

    Research on globalization has determined travel executives' perceptions of the psychological implications brought about by an interconnected global environment and the implications on international education. With the concepts of Clyne and Rizvi (1998) and Pittaway, Ferguson, and Breen (1998) on the value of cross-cultural interaction as a…

  4. Simulating REAL LIVES: Promoting Global Empathy and Interest in Learning through Simulation Games

    ERIC Educational Resources Information Center

    Bachen, Christine M.; Hernandez-Ramos, Pedro F.; Raphael, Chad

    2012-01-01

    In response to an increasingly interdependent world, educators are demonstrating a growing interest in educating for global citizenship. Many definitions of the "good global citizen" value empathy as an especially important disposition for understanding others across national borders and cultural divides. Yet it may be difficult for…

  5. Global Perspectives in Higher Education: Taking the Agenda Forward in the United Kingdom

    ERIC Educational Resources Information Center

    Lunn, Jenny

    2008-01-01

    The economic, social, and cultural interests of the nation demand that graduates have sound knowledge of global issues, the skills for working in an international context, and the values of a "global citizen." Research funded by the British government's Department for International Development sought to assess how such "global…

  6. Comparing the model-simulated global warming signal to observations using empirical estimates of unforced noise

    USDA-ARS?s Scientific Manuscript database

    The comparison of observed global mean surface air temperature (GMT) change to the mean change simulated by climate models has received much attention. For a given global warming signal produced by a climate model ensemble, there exists an envelope of GMT values representing the range of possible un...

  7. Global Market Access in the Internet Era: South Africa's Wood Furniture Industry.

    ERIC Educational Resources Information Center

    Moodley, Sagren

    2002-01-01

    Explores the link between Internet connectivity and access to global markets, and uses the South African wood furniture producers as they are integrated into global value chains and exposed to the demands of more sophisticated markets. Articulates policy recommendations to promote greater diffusion of e-commerce technologies in the wood furniture…

  8. Global Citizenship Education in a Secondary Geography Course: The Students' Perspectives

    ERIC Educational Resources Information Center

    Massey, Kyle

    2014-01-01

    Global citizenship education is increasingly appreciated in Ontario, Canada, as an important component of formal schooling. Although all disciplinary areas have a role to play in global citizenship education, geography provides an especially relevant context in which to foster the values and attitudes often cited as important for global…

  9. High frequency electromagnetic fields (GSM signals) affect gene expression levels in tumor suppressor p53-deficient embryonic stem cells.

    PubMed

    Czyz, Jaroslaw; Guan, Kaomei; Zeng, Qinghua; Nikolova, Teodora; Meister, Armin; Schönborn, Frank; Schuderer, Jürgen; Kuster, Niels; Wobus, Anna M

    2004-05-01

    Effects of electromagnetic fields (EMF) simulating exposure to the Global System for Mobile Communications (GSM) signals were studied using pluripotent embryonic stem (ES) cells in vitro. Wild-type ES cells and ES cells deficient for the tumor suppressor p53 were exposed to pulse modulated EMF at 1.71 GHz, lower end of the uplink band of GSM 1800, under standardized and controlled conditions, and transcripts of regulatory genes were analyzed during in vitro differentiation. Two dominant GSM modulation schemes (GSM-217 and GSM-Talk), which generate temporal changes between GSM-Basic (active during talking phases) and GSM-DTX (active during listening phases thus simulating a typical conversation), were applied to the cells at and below the basic safety limits for local exposures as defined for the general public by the International Commission on Nonionizing Radiation Protection (ICNIRP). GSM-217 EMF induced a significant upregulation of mRNA levels of the heat shock protein, hsp70 of p53-deficient ES cells differentiating in vitro, paralleled by a low and transient increase of c-jun, c-myc, and p21 levels in p53-deficient, but not in wild-type cells. No responses were observed in either cell type after EMF exposure to GSM-Talk applied at similar slot-averaged specific absorption rates (SAR), but at lower time-averaged SAR values. Cardiac differentiation and cell cycle characteristics were not affected in embryonic stem and embryonic carcinoma cells after exposure to GSM-217 EMF signals. Our data indicate that the genetic background determines cellular responses to GSM modulated EMF. Bioelectromagnetics 25:296-307, 2004. Copyright 2004 Wiley-Liss, Inc.

  10. Gene expression profiling of immune-competent human cells exposed to engineered zinc oxide or titanium dioxide nanoparticles.

    PubMed

    Tuomela, Soile; Autio, Reija; Buerki-Thurnherr, Tina; Arslan, Osman; Kunzmann, Andrea; Andersson-Willman, Britta; Wick, Peter; Mathur, Sanjay; Scheynius, Annika; Krug, Harald F; Fadeel, Bengt; Lahesmaa, Riitta

    2013-01-01

    A comprehensive in vitro assessment of two commercial metal oxide nanoparticles, TiO2 and ZnO, was performed using human monocyte-derived macrophages (HMDM), monocyte-derived dendritic cells (MDDC), and Jurkat T cell leukemia-derived cell line. TiO2 nanoparticles were found to be non-toxic whereas ZnO nanoparticles caused dose-dependent cell death. Subsequently, global gene expression profiling was performed to identify transcriptional response underlying the cytotoxicity caused by ZnO nanoparticles. Analysis was done with doses 1 µg/ml and 10 µg/ml after 6 and 24 h of exposure. Interestingly, 2703 genes were significantly differentially expressed in HMDM upon exposure to 10 µg/ml ZnO nanoparticles, while in MDDCs only 12 genes were affected. In Jurkat cells, 980 genes were differentially expressed. It is noteworthy that only the gene expression of metallothioneins was upregulated in all the three cell types and a notable proportion of the genes were regulated in a cell type-specific manner. Gene ontology analysis revealed that the top biological processes disturbed in HMDM and Jurkat cells were regulating cell death and growth. In addition, genes controlling immune system development were affected. Using a panel of modified ZnO nanoparticles, we obtained an additional support that the cellular response to ZnO nanoparticles is largely dependent on particle dissolution and show that the ligand used to modify ZnO nanoparticles modulates Zn(2+) leaching. Overall, the study provides an extensive resource of transcriptional markers for mediating ZnO nanoparticle-induced toxicity for further mechanistic studies, and demonstrates the value of assessing nanoparticle responses through a combined transcriptomics and bioinformatics approach.

  11. Gene Expression Profiling of Immune-Competent Human Cells Exposed to Engineered Zinc Oxide or Titanium Dioxide Nanoparticles

    PubMed Central

    Tuomela, Soile; Autio, Reija; Buerki-Thurnherr, Tina; Arslan, Osman; Kunzmann, Andrea; Andersson-Willman, Britta; Wick, Peter; Mathur, Sanjay; Scheynius, Annika; Krug, Harald F.; Fadeel, Bengt; Lahesmaa, Riitta

    2013-01-01

    A comprehensive in vitro assessment of two commercial metal oxide nanoparticles, TiO2 and ZnO, was performed using human monocyte-derived macrophages (HMDM), monocyte-derived dendritic cells (MDDC), and Jurkat T cell leukemia-derived cell line. TiO2 nanoparticles were found to be non-toxic whereas ZnO nanoparticles caused dose-dependent cell death. Subsequently, global gene expression profiling was performed to identify transcriptional response underlying the cytotoxicity caused by ZnO nanoparticles. Analysis was done with doses 1 µg/ml and 10 µg/ml after 6 and 24 h of exposure. Interestingly, 2703 genes were significantly differentially expressed in HMDM upon exposure to 10 µg/ml ZnO nanoparticles, while in MDDCs only 12 genes were affected. In Jurkat cells, 980 genes were differentially expressed. It is noteworthy that only the gene expression of metallothioneins was upregulated in all the three cell types and a notable proportion of the genes were regulated in a cell type-specific manner. Gene ontology analysis revealed that the top biological processes disturbed in HMDM and Jurkat cells were regulating cell death and growth. In addition, genes controlling immune system development were affected. Using a panel of modified ZnO nanoparticles, we obtained an additional support that the cellular response to ZnO nanoparticles is largely dependent on particle dissolution and show that the ligand used to modify ZnO nanoparticles modulates Zn2+ leaching. Overall, the study provides an extensive resource of transcriptional markers for mediating ZnO nanoparticle-induced toxicity for further mechanistic studies, and demonstrates the value of assessing nanoparticle responses through a combined transcriptomics and bioinformatics approach. PMID:23894303

  12. Global Intraurban Intake Fractions for Primary Air Pollutants from Vehicles and Other Distributed Sources

    PubMed Central

    2012-01-01

    We model intraurban intake fraction (iF) values for distributed ground-level emissions in all 3646 global cities with more than 100 000 inhabitants, encompassing a total population of 2.0 billion. For conserved primary pollutants, population-weighted median, mean, and interquartile range iF values are 26, 39, and 14–52 ppm, respectively, where 1 ppm signifies 1 g inhaled/t emitted. The global mean urban iF reported here is roughly twice as large as previous estimates for cities in the United States and Europe. Intake fractions vary among cities owing to differences in population size, population density, and meteorology. Sorting by size, population-weighted mean iF values are 65, 35, and 15 ppm, respectively, for cities with populations larger than 3, 0.6–3, and 0.1–0.6 million. The 20 worldwide megacities (each >10 million people) have a population-weighted mean iF of 83 ppm. Mean intraurban iF values are greatest in Asia and lowest in land-rich high-income regions. Country-average iF values vary by a factor of 3 among the 10 nations with the largest urban populations. PMID:22332712

  13. Global three-dimensional simulation of Earth's dayside reconnection using a two-way coupled magnetohydrodynamics with embedded particle-in-cell model: initial results: 3D MHD-EPIC simulation of magnetosphere

    DOE PAGES

    Chen, Yuxi; Tóth, Gábor; Cassak, Paul; ...

    2017-09-18

    Here, we perform a three-dimensional (3D) global simulation of Earth's magnetosphere with kinetic reconnection physics to study the flux transfer events (FTEs) and dayside magnetic reconnection with the recently developed magnetohydrodynamics with embedded particle-in-cell model (MHD-EPIC). During the one-hour long simulation, the FTEs are generated quasi-periodically near the subsolar point and move toward the poles. We also find the magnetic field signature of FTEs at their early formation stage is similar to a ‘crater FTE’, which is characterized by a magnetic field strength dip at the FTE center. After the FTE core field grows to a significant value, it becomesmore » an FTE with typical flux rope structure. When an FTE moves across the cusp, reconnection between the FTE field lines and the cusp field lines can dissipate the FTE. The kinetic features are also captured by our model. A crescent electron phase space distribution is found near the reconnection site. A similar distribution is found for ions at the location where the Larmor electric field appears. The lower hybrid drift instability (LHDI) along the current sheet direction also arises at the interface of magnetosheath and magnetosphere plasma. Finally, the LHDI electric field is about 8 mV/m and its dominant wavelength relative to the electron gyroradius agrees reasonably with MMS observations.« less

  14. Global three-dimensional simulation of Earth's dayside reconnection using a two-way coupled magnetohydrodynamics with embedded particle-in-cell model: initial results: 3D MHD-EPIC simulation of magnetosphere

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chen, Yuxi; Tóth, Gábor; Cassak, Paul

    Here, we perform a three-dimensional (3D) global simulation of Earth's magnetosphere with kinetic reconnection physics to study the flux transfer events (FTEs) and dayside magnetic reconnection with the recently developed magnetohydrodynamics with embedded particle-in-cell model (MHD-EPIC). During the one-hour long simulation, the FTEs are generated quasi-periodically near the subsolar point and move toward the poles. We also find the magnetic field signature of FTEs at their early formation stage is similar to a ‘crater FTE’, which is characterized by a magnetic field strength dip at the FTE center. After the FTE core field grows to a significant value, it becomesmore » an FTE with typical flux rope structure. When an FTE moves across the cusp, reconnection between the FTE field lines and the cusp field lines can dissipate the FTE. The kinetic features are also captured by our model. A crescent electron phase space distribution is found near the reconnection site. A similar distribution is found for ions at the location where the Larmor electric field appears. The lower hybrid drift instability (LHDI) along the current sheet direction also arises at the interface of magnetosheath and magnetosphere plasma. Finally, the LHDI electric field is about 8 mV/m and its dominant wavelength relative to the electron gyroradius agrees reasonably with MMS observations.« less

  15. Automatic Fault Recognition of Photovoltaic Modules Based on Statistical Analysis of Uav Thermography

    NASA Astrophysics Data System (ADS)

    Kim, D.; Youn, J.; Kim, C.

    2017-08-01

    As a malfunctioning PV (Photovoltaic) cell has a higher temperature than adjacent normal cells, we can detect it easily with a thermal infrared sensor. However, it will be a time-consuming way to inspect large-scale PV power plants by a hand-held thermal infrared sensor. This paper presents an algorithm for automatically detecting defective PV panels using images captured with a thermal imaging camera from an UAV (unmanned aerial vehicle). The proposed algorithm uses statistical analysis of thermal intensity (surface temperature) characteristics of each PV module to verify the mean intensity and standard deviation of each panel as parameters for fault diagnosis. One of the characteristics of thermal infrared imaging is that the larger the distance between sensor and target, the lower the measured temperature of the object. Consequently, a global detection rule using the mean intensity of all panels in the fault detection algorithm is not applicable. Therefore, a local detection rule based on the mean intensity and standard deviation range was developed to detect defective PV modules from individual array automatically. The performance of the proposed algorithm was tested on three sample images; this verified a detection accuracy of defective panels of 97 % or higher. In addition, as the proposed algorithm can adjust the range of threshold values for judging malfunction at the array level, the local detection rule is considered better suited for highly sensitive fault detection compared to a global detection rule.

  16. Genome Wide DNA Methylation Profiles Provide Clues to the Origin and Pathogenesis of Germ Cell Tumors

    PubMed Central

    Rijlaarsdam, Martin A.; Tax, David M. J.; Gillis, Ad J. M.; Dorssers, Lambert C. J.; Koestler, Devin C.; de Ridder, Jeroen; Looijenga, Leendert H. J.

    2015-01-01

    The cell of origin of the five subtypes (I-V) of germ cell tumors (GCTs) are assumed to be germ cells from different maturation stages. This is (potentially) reflected in their methylation status as fetal maturing primordial germ cells are globally demethylated during migration from the yolk sac to the gonad. Imprinted regions are erased in the gonad and later become uniparentally imprinted according to fetal sex. Here, 91 GCTs (type I-IV) and four cell lines were profiled (Illumina’s HumanMethylation450BeadChip). Data was pre-processed controlling for cross hybridization, SNPs, detection rate, probe-type bias and batch effects. The annotation was extended, covering snRNAs/microRNAs, repeat elements and imprinted regions. A Hidden Markov Model-based genome segmentation was devised to identify differentially methylated genomic regions. Methylation profiles allowed for separation of clusters of non-seminomas (type II), seminomas/dysgerminomas (type II), spermatocytic seminomas (type III) and teratomas/dermoid cysts (type I/IV). The seminomas, dysgerminomas and spermatocytic seminomas were globally hypomethylated, in line with previous reports and their demethylated precursor. Differential methylation and imprinting status between subtypes reflected their presumed cell of origin. Ovarian type I teratomas and dermoid cysts showed (partial) sex specific uniparental maternal imprinting. The spermatocytic seminomas showed uniparental paternal imprinting while testicular teratomas exhibited partial imprinting erasure. Somatic imprinting in type II GCTs might indicate a cell of origin after global demethylation but before imprinting erasure. This is earlier than previously described, but agrees with the totipotent/embryonic stem cell like potential of type II GCTs and their rare extra-gonadal localization. The results support the common origin of the type I teratomas and show strong similarity between ovarian type I teratomas and dermoid cysts. In conclusion, we identified specific and global methylation differences between GCT subtypes, providing insight into their developmental timing and underlying developmental biology. Data and extended annotation are deposited at GEO (GSE58538 and GPL18809). PMID:25859847

  17. Selective inhibition of receptor activator of NF-κB ligand (RANKL) in hematopoietic cells improves outcome after experimental myocardial infarction.

    PubMed

    Slavic, Svetlana; Andrukhova, Olena; Ford, Kristopher; Handschuh, Stephan; Latic, Nejla; Reichart, Ursula; Sasgary, Soleman; Bergow, Claudia; Hofbauer, Lorenz C; Kostenuik, Paul J; Erben, Reinhold G

    2018-05-08

    The RANK (receptor activator of nuclear factor κB)/RANKL (RANK ligand)/OPG (osteoprotegerin) axis is activated after myocardial infarction (MI), but its pathophysiological role is not well understood. Here, we investigated how global and cell compartment-selective inhibition of RANKL affects cardiac function and remodeling after MI in mice. Global RANKL inhibition was achieved by treatment of human RANKL knock-in (huRANKL-KI) mice with the monoclonal antibody AMG161. huRANKL-KI mice express a chimeric RANKL protein wherein part of the RANKL molecule is humanized. AMG161 inhibits human and chimeric but not murine RANKL. To dissect the pathophysiological role of RANKL derived from hematopoietic and mesenchymal cells, we selectively exchanged the hematopoietic cell compartment by lethal irradiation and across-genotype bone marrow transplantation between wild-type and huRANKL-KI mice, exploiting the specificity of AMG161. After permanent coronary artery ligation, mice were injected with AMG161 or an isotype control antibody over 4 weeks post-MI. MI increased RANKL expression mainly in cardiomyocytes and scar-infiltrating cells 4 weeks after MI. Only inhibition of RANKL derived from hematopoietic cellular sources, but not global or mesenchymal RANKL inhibition, improved post-infarct survival and cardiac function. Mechanistically, hematopoietic RANKL inhibition reduced expression of the pro-inflammatory cytokine IL-1ß in the cardiac cellular infiltrate. In conclusion, inhibition of RANKL derived from hematopoietic cellular sources is beneficial to maintain post-ischemic cardiac function by reduction of pro-inflammatory cytokine production. Experimental myocardial infarction (MI) augments cardiac RANKL expression in mice. RANKL expression is increased in cardiomyocytes and scar-infiltrating cells after MI. Global or mesenchymal cell RANKL inhibition has no influence on cardiac function after MI. Inhibition of RANKL derived from hematopoietic cells improves heart function post-MI. Hematopoietic RANKL inhibition reduces pro-inflammatory cytokines in scar-infiltrating cells.

  18. East/West Perspectives on Education for Peace and Security. Conference Report of the International Network for Global Education (INGE) (New Paltz, New York, November 8-12, 1986).

    ERIC Educational Resources Information Center

    Global Perspectives in Education, Inc., New York, NY.

    The purpose of the International Network for Global Education (INGE) is to promote global education within the educational systems of network member countries. Areas of study are listed under the following headings: Peace Studies; East/West Relations; North/South Relations; Human Rights; Global Environment; Human Values; and Cross-cultural Issues.…

  19. Two dimensional wavefront retrieval using lateral shearing interferometry

    NASA Astrophysics Data System (ADS)

    Mancilla-Escobar, B.; Malacara-Hernández, Z.; Malacara-Hernández, D.

    2018-06-01

    A new zonal two-dimensional method for wavefront retrieval from a surface under test using lateral shearing interferometry is presented. A modified Saunders method and phase shifting techniques are combined to generate a method for wavefront reconstruction. The result is a wavefront with an error below 0.7 λ and without any global high frequency filtering. A zonal analysis over square cells along the surfaces is made, obtaining a polynomial expression for the wavefront deformations over each cell. The main advantage of this method over previously published methods is that a global filtering of high spatial frequencies is not present. Thus, a global smoothing of the wavefront deformations is avoided, allowing the detection of deformations with relatively small extensions, that is, with high spatial frequencies. Additionally, local curvature and low order aberration coefficients are obtained in each cell.

  20. Proteome of Caulobacter crescentus cell cycle publicly accessible on SWICZ server.

    PubMed

    Vohradsky, Jiri; Janda, Ivan; Grünenfelder, Björn; Berndt, Peter; Röder, Daniel; Langen, Hanno; Weiser, Jaroslav; Jenal, Urs

    2003-10-01

    Here we present the Swiss-Czech Proteomics Server (SWICZ), which hosts the proteomic database summarizing information about the cell cycle of the aquatic bacterium Caulobacter crescentus. The database provides a searchable tool for easy access of global protein synthesis and protein stability data as examined during the C. crescentus cell cycle. Protein synthesis data collected from five different cell cycle stages were determined for each protein spot as a relative value of the total amount of [(35)S]methionine incorporation. Protein stability of pulse-labeled extracts were measured during a chase period equivalent to one cell cycle unit. Quantitative information for individual proteins together with descriptive data such as protein identities, apparent molecular masses and isoelectric points, were combined with information on protein function, genomic context, and the cell cycle stage, and were then assembled in a relational database with a world wide web interface (http://proteom.biomed.cas.cz), which allows the database records to be searched and displays the recovered information. A total of 1250 protein spots were reproducibly detected on two-dimensional gel electropherograms, 295 of which were identified by mass spectroscopy. The database is accessible either through clickable two-dimensional gel electrophoretic maps or by means of a set of dedicated search engines. Basic characterization of the experimental procedures, data processing, and a comprehensive description of the web site are presented. In its current state, the SWICZ proteome database provides a platform for the incorporation of new data emerging from extended functional studies on the C. crescentus proteome.

  1. Optical imaging the redox status change during cell apoptosis

    NASA Astrophysics Data System (ADS)

    Su, Ting; Zhang, Zhihong; Lin, Juqiang; Luo, Qingming

    2007-02-01

    Many cellular events involve the alteration in redox equilibrium, globally or locally. In many cases, excessive reactive oxygen species (ROS) production is the underlying cause. Several green fluoresecence protein based indicators are constructed to measure redox status in cells, e.g, rxYFP and roGFPs, which allow real time detection. reduction and oxidization-sensitive GFP (RoGFPs) are more useful due to ratiometric variation by excitation, making the measurement more accurate. Utilizing one of those roGFPs called roGFP1, we establish a mitochondrial redox state probing platform in HeLa cells with laser scan confocal microscopy (LSCM) as detection system. Control experiments confirmed that our platform could produce stable ratiometric values, which made the data more accurately reflect the real environmental changes of redox status that roGFP1 probed. Using exogenous H IIO II and DTT, we evaluated the reactivity and reversibility of roGFP1. The minimal hydrogen peroxide concentration that roGFP1 could show detectable ratiometric changes in our system was about 200μM. Preliminarily applying our platform to exploring the redox status during apoptosis, we observed an increase in ratiometric, suggesting an excessive ROS production.

  2. Annealing characteristics of amorphous silicon alloy solar cells irradiated with 1.00 MeV protons

    NASA Technical Reports Server (NTRS)

    Abdulaziz, Salman S.; Woodyard, James R.

    1991-01-01

    Amorphous Si:H and amorphous Si sub x, Ge sub (1-x):H solar cells were irradiated with 1.00 MeV proton fluences in the range of 1.00E14 to 1.25E15 cm (exp -2). Annealing of the short circuit current density was studied at 0, 22, 50, 100, and 150 C. Annealing times ranged from an hour to several days. The measurements confirmed that annealing occurs at 0 C and the initial characteristics of the cells are restored by annealing at 200 C. The rate of annealing does not appear to follow a simple nth order reaction rate model. Calculations of the short-circuit current density using quantum efficiency measurements and the standard AM1.5 global spectrum compare favorably with measured values. It is proposed that the degradation in J sub sc with irradiation is due to carrier recombination through the fraction of D (o) states bounded by the quasi-Fermi energies. The time dependence of the rate of annealing of J sub sc does appear to be consistent with the interpretation that there is a thermally activated dispersive transport mechanism which leads to the passivation of the irradiation induced defects.

  3. Gamabufotalin triggers c-Myc degradation via induction of WWP2 in multiple myeloma cells.

    PubMed

    Yu, Zhenlong; Li, Tao; Wang, Chao; Deng, Sa; Zhang, Baojing; Huo, Xiaokui; Zhang, Bo; Wang, Xiaobo; Zhong, Yuping; Ma, Xiaochi

    2016-03-29

    Deciding appropriate therapy for multiple myeloma (MM) is challenging because of the occurrence of multiple chromosomal changes and the fatal nature of the disease. In the current study, gamabufotalin (GBT) was isolated from toad venom, and its tumor-specific cytotoxicity was investigated in human MM cells. We found GBT inhibited cell growth and induced apoptosis with the IC50 values <50 nM. Mechanistic studies using functional approaches identified GBT as an inhibitor of c-Myc. Further analysis showed that GBT especially evoked the ubiquitination and degradation of c-Myc protein, thereby globally repressing the expression of c-Myc target genes. GBT treatment inhibited ERK and AKT signals, while stimulating the activation of JNK cascade. An E3 ubiquitin-protein ligase, WWP2, was upregulated following JNK activation and played an important role in c-Myc ubiquitination and degradation through direct protein-protein interaction. The antitumor effect of GBT was validated in a xenograft mouse model and the suppression of MM-induced osteolysis was verified in a SCID-hu model in vivo. Taken together, our study identified the potential of GBT as a promising therapeutic agent in the treatment of MM.

  4. Ocean acidification increases the toxic effects of TiO2 nanoparticles on the marine microalga Chlorella vulgaris.

    PubMed

    Xia, Bin; Sui, Qi; Sun, Xuemei; Han, Qian; Chen, Bijuan; Zhu, Lin; Qu, Keming

    2018-03-15

    Concerns about the environmental effects of engineered nanoparticles (NPs) on marine ecosystems are increasing. Meanwhile, ocean acidification (OA) has become a global environmental problem. However, the combined effects of NPs and OA on marine organisms are still not well understood. In this study, we investigated the effects of OA (pH values of 7.77 and 7.47) on the bioavailability and toxicity of TiO 2 NPs to the marine microalga Chlorella vulgaris. The results showed that OA enhanced the growth inhibition of algal cells caused by TiO 2 NPs. We observed synergistic interactive effects of pH and TiO 2 NPs on oxidative stress, indicating that OA significantly increased the oxidative damage of TiO 2 NPs on the algal cells. Importantly, the elevated toxicity of TiO 2 NPs associated with OA could be explained by the enhanced internalization of NPs in algal cells, which was attributed to the slighter aggregation and more suspended particles in acidified seawater. Overall, these findings provide useful information on marine environmental risk assessments of NPs under near future OA conditions. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Aspartame Attenuates 2, 4-Dinitrofluorobenzene-Induced Atopic Dermatitis-Like Clinical Symptoms in NC/Nga Mice.

    PubMed

    Kim, Gun-Dong; Park, Yong Seek; Ahn, Hyun-Jong; Cho, Jeong-Je; Park, Cheung-Seog

    2015-11-01

    Atopic dermatitis (AD) is a common multifactorial chronic skin disease that has a multiple and complex pathogenesis. AD is gradually increasing in prevalence globally. In NC/Nga mice, repetitive applications of 2, 4-dinitrofluorobenzene (DNFB) evoke AD-like clinical symptoms similar to human AD. Aspartame (N-L-α-aspartyl-L-phenylalanine 1-methyl ester) is a methyl ester of a dipeptide, which is used as an artificial non-nutritive sweetener. Aspartame has analgesic and anti-inflammatory functions that are similar to the function of nonsteroidal anti-inflammatory drugs such as aspirin. We investigated whether aspartame can relieve AD-like clinical symptoms induced by DNFB treatment in NC/Nga mice. Sucrose did not relieve AD-like symptoms, whereas aspartame at doses of 0.5 μg kg(-1) and 0.5 mg kg(-1) inhibited ear swelling and relieved AD-like clinical symptoms. Aspartame inhibited infiltration of inflammatory cells including eosinophils, mast cells, and CD4(+) T cells, and suppressed the expression of cytokines including IL-4 and IFN-γ, and total serum IgE levels. Aspartame may have therapeutic value in the treatment of AD.

  6. Global patterns of the isotopic composition of soil and plant nitrogen

    USGS Publications Warehouse

    Amundson, Ronald; Austin, A.T.; Schuur, E.A.G.; Yoo, K.; Matzek, V.; Kendall, C.; Uebersax, A.; Brenner, D.; Baisden, W.T.

    2003-01-01

    We compiled new and published data on the natural abundance N isotope composition (??15N values) of soil and plant organic matter from around the world. Across a broad range of climate and ecosystem types, we found that soil and plant ??15N values systematically decreased with increasing mean annual precipitation (MAP) and decreasing mean annual temperature (MAT). Because most undisturbed soils are near N steady state, the observations suggest that an increasing fraction of ecosystem N losses are 15N-depleted forms (NO3, N2O, etc.) with decreasing MAP and increasing MAT. Wetter and colder ecosystems appear to be more efficient in conserving and recycling mineral N. Globally, plant ??15N values are more negative than soils, but the difference Nitrogen isotopes reflect time integrated measures of the controls on N storage that are critical for predictions of how these ecosystems will respond to human-mediated disturbances of the global N cycle.

  7. The value of human life in contemporary society. The global biography project.

    PubMed

    Nary, G

    1997-12-01

    The closing address at the 1997 First International Conference on Healthcare Resource Allocation for HIV/AIDS and Other Life-Threatening Illnesses is presented. The address discusses the extrinsic value of life and the three forms of material value: spiritual, economic, and political, placed on life by an outside source. It is argued that if spiritual currency, rather than economic or political currency, drove public policy there would be greater progress in reducing the global rate of HIV and more options for care. Further, lack of identity of those afflicted with HIV reduces them to mere statistics, thus decreasing their economic and political clout. Giving identities to people who are sick not only increases empathy but also increases their survivability. The establishment of the Global Biography Project seeks to reestablish spiritual currency as the international currency that underlies every nation's healthcare policies.

  8. A Comparison of Satellite Based, Modeled Derived Daily Solar Radiation Data with Observed Data for the Continental US

    NASA Technical Reports Server (NTRS)

    White, Jeffrey W.; Hoogenboom, Gerrit; Wilkens, Paul W.; Stackhouse, Paul W., Jr.; Hoell, James M.

    2010-01-01

    Many applications of simulation models and related decision support tools for agriculture and natural resource management require daily meteorological data as inputs. Availability and quality of such data, however, often constrain research and decision support activities that require use of these tools. Daily solar radiation (SRAD) data are especially problematic because the instruments require electronic integrators, accurate sensors are expensive, and calibration standards are seldom available. The Prediction Of Worldwide Energy Resources (NASA/POWER; power.larc.nasa.gov) project at the NASA Langley Research Center estimates daily solar radiation based on data that are derived from satellite observations of outgoing visible radiances and atmospheric parameters based upon satellite observations and assimilation models. The solar data are available for a global 1 degree x 1 degree coordinate grid. SRAD can also be estimated based on attenuation of extraterrestrial radiation (Q0) using daily temperature and rainfall data to estimate the optical thickness of the atmosphere. This study compares daily solar radiation data from NASA/POWER (SRADNP) with instrument readings from 295 stations (SRADOB), as well as with values that were estimated with the WGENR solar generator. WGENR was used both with daily temperature and precipitation records from the stations reporting solar data and records from the NOAA Cooperative Observer Program (COOP), thus providing two additional sources of solar data, SRADWG and SRADCO. Values of SRADNP for different grid cells consistently showed higher correlations (typically 0.85 to 0.95) with SRADOB data than did SRADWG or SRADCO for sites within the corresponding cells. Mean values of SRADOB, SRADWG and SRADNP for sites within a grid cell usually were within 1 MJm-2d-1 of each other, but NASA/POWER values averaged 1.1 MJm-2d-1 lower than SRADOB. The magnitude of this bias was greater at lower latitudes and during summer months and may be at least partially explained by assumptions in ambient aerosol properties. Overall, the NASA/POWER solar radiation data are a promising resource for regional modeling studies where realistic accounting of historic variation is required.

  9. Influence of water stress on the carbon isotopic composition of modern plants: Implications for C4 plant appearance in Indian subcontinent

    NASA Astrophysics Data System (ADS)

    Basu, S.; Ghosh, S.; Sanyal, P.

    2016-12-01

    The carbon isotopic composition (d13C) of modern terrestrial plants (C3 and C4) provides the baseline to understand past vegetation composition, paleodietary changes and animal migration etc. Accuracy of past environment reconstruction is dependent on the end-member d13C values of plants which found to vary in regional scale. For instance, the d13C values of Indian C3 plants (d13CC3) are 1 to 2‰ more negative compared to global mean. As observed, most of the previous database is devoid of samples from tropical monsoon realm (like India) and the difference between global and regional mean may introduce errors in vegetation reconstruction. To constrain end-member d13CC3 value, published and newly generated results from wide range of mean annual precipitation (MAP: 1-11,700 mm) are compiled which is ca. 1.5 higher in sample size (n=2440) compared to previous database. Using logarithmic function, new relationship between d13C value and MAP (d13CC3 (‰) =20.1585(0.3061)-1.1276(0.0489)ln(MAP+700)) is proposed. The modeled mean d13CC3 value (-28.9‰) is close to average d13CC3 value for Indian plants (-29.1‰) and suggests the importance of vegetation from low-latitudinal tropical region in global compilation. It was observed that C3 plants, on a global scale, are less sensitive to wet climate relative to dry condition. This inference is in agreement with the paleoclimatic data from Indian subcontinent for the late Quaternary period. Despite well established correlation between d13CC3 value and MAP, previous investigation from Indian subcontinent used fixed end-member values to reconstruct past vegetation and total change in the d13C value of proxies was attributed to changes in relative abundance of C3 and C4 plants. Using region-specific mean d13C value of plants, after correcting for changing MAP and error propagation, existence of C4 before ca. 11 Ma plant is observed; earlier to previous reported timing.

  10. Graph Theory-Based Analysis of the Lymph Node Fibroblastic Reticular Cell Network.

    PubMed

    Novkovic, Mario; Onder, Lucas; Bocharov, Gennady; Ludewig, Burkhard

    2017-01-01

    Secondary lymphoid organs have developed segregated niches that are able to initiate and maintain effective immune responses. Such global organization requires tight control of diverse cellular components, specifically those that regulate lymphocyte trafficking. Fibroblastic reticular cells (FRCs) form a densely interconnected network in lymph nodes and provide key factors necessary for T cell migration and retention, and foster subsequent interactions between T cells and dendritic cells. Development of integrative systems biology approaches has made it possible to elucidate this multilevel complexity of the immune system. Here, we present a graph theory-based analysis of the FRC network in murine lymph nodes, where generation of the network topology is performed using high-resolution confocal microscopy and 3D reconstruction. This approach facilitates the analysis of physical cell-to-cell connectivity, and estimation of topological robustness and global behavior of the network when it is subjected to perturbation in silico.

  11. Proteomic analysis of the bacterial cell cycle

    PubMed Central

    Grünenfelder, Björn; Rummel, Gabriele; Vohradsky, Jiri; Röder, Daniel; Langen, Hanno; Jenal, Urs

    2001-01-01

    A global approach was used to analyze protein synthesis and stability during the cell cycle of the bacterium Caulobacter crescentus. Approximately one-fourth (979) of the estimated C. crescentus gene products were detected by two-dimensional gel electrophoresis, 144 of which showed differential cell cycle expression patterns. Eighty-one of these proteins were identified by mass spectrometry and were assigned to a wide variety of functional groups. Pattern analysis revealed that coexpression groups were functionally clustered. A total of 48 proteins were rapidly degraded in the course of one cell cycle. More than half of these unstable proteins were also found to be synthesized in a cell cycle-dependent manner, establishing a strong correlation between rapid protein turnover and the periodicity of the bacterial cell cycle. This is, to our knowledge, the first evidence for a global role of proteolysis in bacterial cell cycle control. PMID:11287652

  12. Prokaryotic regulatory systems biology: Common principles governing the functional architectures of Bacillus subtilis and Escherichia coli unveiled by the natural decomposition approach.

    PubMed

    Freyre-González, Julio A; Treviño-Quintanilla, Luis G; Valtierra-Gutiérrez, Ilse A; Gutiérrez-Ríos, Rosa María; Alonso-Pavón, José A

    2012-10-31

    Escherichia coli and Bacillus subtilis are two of the best-studied prokaryotic model organisms. Previous analyses of their transcriptional regulatory networks have shown that they exhibit high plasticity during evolution and suggested that both converge to scale-free-like structures. Nevertheless, beyond this suggestion, no analyses have been carried out to identify the common systems-level components and principles governing these organisms. Here we show that these two phylogenetically distant organisms follow a set of common novel biologically consistent systems principles revealed by the mathematically and biologically founded natural decomposition approach. The discovered common functional architecture is a diamond-shaped, matryoshka-like, three-layer (coordination, processing, and integration) hierarchy exhibiting feedback, which is shaped by four systems-level components: global transcription factors (global TFs), locally autonomous modules, basal machinery and intermodular genes. The first mathematical criterion to identify global TFs, the κ-value, was reassessed on B. subtilis and confirmed its high predictive power by identifying all the previously reported, plus three potential, master regulators and eight sigma factors. The functionally conserved cores of modules, basal cell machinery, and a set of non-orthologous common physiological global responses were identified via both orthologous genes and non-orthologous conserved functions. This study reveals novel common systems principles maintained between two phylogenetically distant organisms and provides a comparison of their lifestyle adaptations. Our results shed new light on the systems-level principles and the fundamental functions required by bacteria to sustain life. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Nucleotide Excision Repair and Transcription-coupled DNA Repair Abrogate the Impact of DNA Damage on Transcription.

    PubMed

    Nadkarni, Aditi; Burns, John A; Gandolfi, Alberto; Chowdhury, Moinuddin A; Cartularo, Laura; Berens, Christian; Geacintov, Nicholas E; Scicchitano, David A

    2016-01-08

    DNA adducts derived from carcinogenic polycyclic aromatic hydrocarbons like benzo[a]pyrene (B[a]P) and benzo[c]phenanthrene (B[c]Ph) impede replication and transcription, resulting in aberrant cell division and gene expression. Global nucleotide excision repair (NER) and transcription-coupled DNA repair (TCR) are among the DNA repair pathways that evolved to maintain genome integrity by removing DNA damage. The interplay between global NER and TCR in repairing the polycyclic aromatic hydrocarbon-derived DNA adducts (+)-trans-anti-B[a]P-N(6)-dA, which is subject to NER and blocks transcription in vitro, and (+)-trans-anti-B[c]Ph-N(6)-dA, which is a poor substrate for NER but also blocks transcription in vitro, was tested. The results show that both adducts inhibit transcription in human cells that lack both NER and TCR. The (+)-trans-anti-B[a]P-N(6)-dA lesion exhibited no detectable effect on transcription in cells proficient in NER but lacking TCR, indicating that NER can remove the lesion in the absence of TCR, which is consistent with in vitro data. In primary human cells lacking NER, (+)-trans-anti-B[a]P-N(6)-dA exhibited a deleterious effect on transcription that was less severe than in cells lacking both pathways, suggesting that TCR can repair the adduct but not as effectively as global NER. In contrast, (+)-trans-anti-B[c]Ph-N(6)-dA dramatically reduces transcript production in cells proficient in global NER but lacking TCR, indicating that TCR is necessary for the removal of this adduct, which is consistent with in vitro data showing that it is a poor substrate for NER. Hence, both global NER and TCR enhance the recovery of gene expression following DNA damage, and TCR plays an important role in removing DNA damage that is refractory to NER. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Nucleotide Excision Repair and Transcription-coupled DNA Repair Abrogate the Impact of DNA Damage on Transcription*

    PubMed Central

    Nadkarni, Aditi; Burns, John A.; Gandolfi, Alberto; Chowdhury, Moinuddin A.; Cartularo, Laura; Berens, Christian; Geacintov, Nicholas E.; Scicchitano, David A.

    2016-01-01

    DNA adducts derived from carcinogenic polycyclic aromatic hydrocarbons like benzo[a]pyrene (B[a]P) and benzo[c]phenanthrene (B[c]Ph) impede replication and transcription, resulting in aberrant cell division and gene expression. Global nucleotide excision repair (NER) and transcription-coupled DNA repair (TCR) are among the DNA repair pathways that evolved to maintain genome integrity by removing DNA damage. The interplay between global NER and TCR in repairing the polycyclic aromatic hydrocarbon-derived DNA adducts (+)-trans-anti-B[a]P-N6-dA, which is subject to NER and blocks transcription in vitro, and (+)-trans-anti-B[c]Ph-N6-dA, which is a poor substrate for NER but also blocks transcription in vitro, was tested. The results show that both adducts inhibit transcription in human cells that lack both NER and TCR. The (+)-trans-anti-B[a]P-N6-dA lesion exhibited no detectable effect on transcription in cells proficient in NER but lacking TCR, indicating that NER can remove the lesion in the absence of TCR, which is consistent with in vitro data. In primary human cells lacking NER, (+)-trans-anti-B[a]P-N6-dA exhibited a deleterious effect on transcription that was less severe than in cells lacking both pathways, suggesting that TCR can repair the adduct but not as effectively as global NER. In contrast, (+)-trans-anti-B[c]Ph-N6-dA dramatically reduces transcript production in cells proficient in global NER but lacking TCR, indicating that TCR is necessary for the removal of this adduct, which is consistent with in vitro data showing that it is a poor substrate for NER. Hence, both global NER and TCR enhance the recovery of gene expression following DNA damage, and TCR plays an important role in removing DNA damage that is refractory to NER. PMID:26559971

  15. Positive biodiversity-productivity relationship predominant in global forests.

    PubMed

    Liang, Jingjing; Crowther, Thomas W; Picard, Nicolas; Wiser, Susan; Zhou, Mo; Alberti, Giorgio; Schulze, Ernst-Detlef; McGuire, A David; Bozzato, Fabio; Pretzsch, Hans; de-Miguel, Sergio; Paquette, Alain; Hérault, Bruno; Scherer-Lorenzen, Michael; Barrett, Christopher B; Glick, Henry B; Hengeveld, Geerten M; Nabuurs, Gert-Jan; Pfautsch, Sebastian; Viana, Helder; Vibrans, Alexander C; Ammer, Christian; Schall, Peter; Verbyla, David; Tchebakova, Nadja; Fischer, Markus; Watson, James V; Chen, Han Y H; Lei, Xiangdong; Schelhaas, Mart-Jan; Lu, Huicui; Gianelle, Damiano; Parfenova, Elena I; Salas, Christian; Lee, Eungul; Lee, Boknam; Kim, Hyun Seok; Bruelheide, Helge; Coomes, David A; Piotto, Daniel; Sunderland, Terry; Schmid, Bernhard; Gourlet-Fleury, Sylvie; Sonké, Bonaventure; Tavani, Rebecca; Zhu, Jun; Brandl, Susanne; Vayreda, Jordi; Kitahara, Fumiaki; Searle, Eric B; Neldner, Victor J; Ngugi, Michael R; Baraloto, Christopher; Frizzera, Lorenzo; Bałazy, Radomir; Oleksyn, Jacek; Zawiła-Niedźwiecki, Tomasz; Bouriaud, Olivier; Bussotti, Filippo; Finér, Leena; Jaroszewicz, Bogdan; Jucker, Tommaso; Valladares, Fernando; Jagodzinski, Andrzej M; Peri, Pablo L; Gonmadje, Christelle; Marthy, William; O'Brien, Timothy; Martin, Emanuel H; Marshall, Andrew R; Rovero, Francesco; Bitariho, Robert; Niklaus, Pascal A; Alvarez-Loayza, Patricia; Chamuya, Nurdin; Valencia, Renato; Mortier, Frédéric; Wortel, Verginia; Engone-Obiang, Nestor L; Ferreira, Leandro V; Odeke, David E; Vasquez, Rodolfo M; Lewis, Simon L; Reich, Peter B

    2016-10-14

    The biodiversity-productivity relationship (BPR) is foundational to our understanding of the global extinction crisis and its impacts on ecosystem functioning. Understanding BPR is critical for the accurate valuation and effective conservation of biodiversity. Using ground-sourced data from 777,126 permanent plots, spanning 44 countries and most terrestrial biomes, we reveal a globally consistent positive concave-down BPR, showing that continued biodiversity loss would result in an accelerating decline in forest productivity worldwide. The value of biodiversity in maintaining commercial forest productivity alone-US$166 billion to 490 billion per year according to our estimation-is more than twice what it would cost to implement effective global conservation. This highlights the need for a worldwide reassessment of biodiversity values, forest management strategies, and conservation priorities. Copyright © 2016, American Association for the Advancement of Science.

  16. Internationalizing Medical Education: The Special Track Curriculum 'Global Health' at Justus Liebig University Giessen.

    PubMed

    Knipper, Michael; Baumann, Adrian; Hofstetter, Christine; Korte, Rolf; Krawinkel, Michael

    2015-01-01

    Internationalizing higher education is considered to be a major goal for universities in Germany and many medical students aspire to include international experiences into their academic training. However, the exact meaning of "internationalizing" medical education is still poorly defined, just as is the possible pedagogic impact and effects. Against this background, this article presents the special track curriculum on global health (in German: Schwerpunktcurriculum Global Health, short: SPC) at Justus Liebig University Giessen, which was established in 2011 as a comprehensive teaching program to integrate international perspectives and activities systematically into the clinical years of the medical curriculum. The report of the structure, content, didactic principles and participants' evaluations of the SPC is embedded into a larger discussion of the pedagogic value of a broad and interdisciplinary perspective on "global health" in medical education, that explicitly includes attention for health inequities, social determinants of health and the cultural dimensions of medicine and health abroad and "at home" (e.g. in relation to migration). We conclude that if properly defined, the emerging field of "global health" represents a didactically meaningful approach for adding value to medical education through internationalizing the curriculum, especially in regard to themes that despite of their uncontested value are often rather weak within medical education. The concrete curricular structures, however, have always to be developed locally. The "SPC" at Giessen University Medical School is only one possible way of addressing these globally relevant issues in one particular local academic setting.

  17. A new method to estimate average hourly global solar radiation on the horizontal surface

    NASA Astrophysics Data System (ADS)

    Pandey, Pramod K.; Soupir, Michelle L.

    2012-10-01

    A new model, Global Solar Radiation on Horizontal Surface (GSRHS), was developed to estimate the average hourly global solar radiation on the horizontal surfaces (Gh). The GSRHS model uses the transmission function (Tf,ij), which was developed to control hourly global solar radiation, for predicting solar radiation. The inputs of the model were: hour of day, day (Julian) of year, optimized parameter values, solar constant (H0), latitude, and longitude of the location of interest. The parameter values used in the model were optimized at a location (Albuquerque, NM), and these values were applied into the model for predicting average hourly global solar radiations at four different locations (Austin, TX; El Paso, TX; Desert Rock, NV; Seattle, WA) of the United States. The model performance was assessed using correlation coefficient (r), Mean Absolute Bias Error (MABE), Root Mean Square Error (RMSE), and coefficient of determinations (R2). The sensitivities of parameter to prediction were estimated. Results show that the model performed very well. The correlation coefficients (r) range from 0.96 to 0.99, while coefficients of determination (R2) range from 0.92 to 0.98. For daily and monthly prediction, error percentages (i.e. MABE and RMSE) were less than 20%. The approach we proposed here can be potentially useful for predicting average hourly global solar radiation on the horizontal surface for different locations, with the use of readily available data (i.e. latitude and longitude of the location) as inputs.

  18. Circulating soluble adhesion molecules in patients with giant cell arteritis. Correlation between soluble intercellular adhesion molecule-1 (sICAM-1) concentrations and disease activity

    PubMed Central

    Coll-Vinent, B.; Vilardell, C.; Font, C.; Oristrell, J.; Hernandez-Rodrigu..., J.; Yague, J.; Urbano-Marquez, A.; Grau, J.; Cid, M.

    1999-01-01

    OBJECTIVE—To evaluate whether changes in concentrations of circulating adhesion molecules are related to disease activity in patients with giant cell arteritis (GCA).
METHODS—A sandwich ELISA was used to measure soluble intercellular adhesion molecule-1 (sICAM-1), sICAM-3, vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-selectin), and L-selectin (sL-selectin) in serum and plasma samples from patients with GCA. A cross sectional study was performed on 64 GCA patients at different activity stages and on 35 age and sex matched healthy donors. Thirteen of these patients were evaluated at the time of diagnosis and serially during follow up.
RESULTS—At the time of diagnosis, sICAM-1 concentrations were significantly higher in active GCA patients than in controls (mean (SD) 360.55 (129.78) ng/ml versus 243.25 (47.43) ng/ml, p<0.001). In contrast, sICAM-3, sVCAM-1, sE-selectin, and sL-selectin values did not differ from those obtained in normal donors. With corticosteroid administration, a decrease in sICAM-1 concentrations was observed, reaching normal values when clinical remission was achieved (263.18 (92.7) ng/ml globally, 293.59 (108.39) ng/ml in the group of patients in recent remission, and 236.83 (70.02) ng/ml in those in long term remission). In the 13 patients followed up longitudinally, sICAM-1 values also normalised with clinical remission (225.87 (64.25) ng/ml in patients in recent remission, and 256.29 (75.15) ng/ml in those in long term remission).
CONCLUSIONS—Circulating sICAM-1 concentrations clearly correlate with clinically apparent disease activity in GCA patients. Differences with results previously found in patients with other vasculitides may indicate that different pathogenic mechanisms contribute to vascular inflammation in different disorders.

 Keywords: adhesion molecules; giant cell arteritis; inflammation PMID:10364919

  19. Global mammal beta diversity shows parallel assemblage structure in similar but isolated environments

    PubMed Central

    Graham, Catherine H.; Brooks, Thomas M.; Rondinini, Carlo; Hedges, S. Blair; Davidson, Ana D.; Costa, Gabriel C.

    2016-01-01

    The taxonomic, phylogenetic and trait dimensions of beta diversity each provide us unique insights into the importance of historical isolation and environmental conditions in shaping global diversity. These three dimensions should, in general, be positively correlated. However, if similar environmental conditions filter species with similar trait values, then assemblages located in similar environmental conditions, but separated by large dispersal barriers, may show high taxonomic, high phylogenetic, but low trait beta diversity. Conversely, we expect lower phylogenetic diversity, but higher trait biodiversity among assemblages that are connected but are in differing environmental conditions. We calculated all pairwise comparisons of approximately 110 × 110 km grid cells across the globe for more than 5000 mammal species (approx. 70 million comparisons). We considered realms as units representing geographical distance and historical isolation and biomes as units with similar environmental conditions. While beta diversity dimensions were generally correlated, we highlight geographical regions of decoupling among beta diversity dimensions. Our analysis shows that assemblages from tropical forests in different realms had low trait dissimilarity while phylogenetic beta diversity was significantly higher than expected, suggesting potential convergent evolution. Low trait beta diversity was surprisingly not found between isolated deserts, despite harsh environmental conditions. Overall, our results provide evidence for parallel assemblage structure of mammal assemblages driven by environmental conditions at a global scale. PMID:27559061

  20. Short Chemical Ischemia Triggers Phosphorylation of eIF2α and Death of SH-SY5Y Cells but not Proteasome Stress and Heat Shock Protein Response in both SH-SY5Y and T98G Cells.

    PubMed

    Klacanova, Katarina; Pilchova, Ivana; Klikova, Katarina; Racay, Peter

    2016-04-01

    Both translation arrest and proteasome stress associated with accumulation of ubiquitin-conjugated protein aggregates were considered as a cause of delayed neuronal death after transient global brain ischemia; however, exact mechanisms as well as possible relationships are not fully understood. The aim of this study was to compare the effect of chemical ischemia and proteasome stress on cellular stress responses and viability of neuroblastoma SH-SY5Y and glioblastoma T98G cells. Chemical ischemia was induced by transient treatment of the cells with sodium azide in combination with 2-deoxyglucose. Proteasome stress was induced by treatment of the cells with bortezomib. Treatment of SH-SY5Y cells with sodium azide/2-deoxyglucose for 15 min was associated with cell death observed 24 h after treatment, while glioblastoma T98G cells were resistant to the same treatment. Treatment of both SH-SY5Y and T98G cells with bortezomib was associated with cell death, accumulation of ubiquitin-conjugated proteins, and increased expression of Hsp70. These typical cellular responses to proteasome stress, observed also after transient global brain ischemia, were not observed after chemical ischemia. Finally, chemical ischemia, but not proteasome stress, was in SH-SY5Y cells associated with increased phosphorylation of eIF2α, another typical cellular response triggered after transient global brain ischemia. Our results showed that short chemical ischemia of SH-SY5Y cells is not sufficient to induce both proteasome stress associated with accumulation of ubiquitin-conjugated proteins and stress response at the level of heat shock proteins despite induction of cell death and eIF2α phosphorylation.

  1. The Tick Cell Biobank: A global resource for in vitro research on ticks, other arthropods and the pathogens they transmit.

    PubMed

    Bell-Sakyi, Lesley; Darby, Alistair; Baylis, Matthew; Makepeace, Benjamin L

    2018-05-31

    Tick cell lines are increasingly used in many fields of tick and tick-borne disease research. The Tick Cell Biobank was established in 2009 to facilitate the development and uptake of these unique and valuable resources. As well as serving as a repository for existing and new ixodid and argasid tick cell lines, the Tick Cell Biobank supplies cell lines and training in their maintenance to scientists worldwide and generates novel cultures from tick species not already represented in the collection. Now part of the Institute of Infection and Global Health at the University of Liverpool, the Tick Cell Biobank has embarked on a new phase of activity particularly targeted at research on problems caused by ticks, other arthropods and the diseases they transmit in less-developed, lower- and middle-income countries. We are carrying out genotypic and phenotypic characterisation of selected cell lines derived from tropical tick species. We continue to expand the culture collection, currently comprising 63 cell lines derived from 18 ixodid and argasid tick species and one each from the sand fly Lutzomyia longipalpis and the biting midge Culicoides sonorensis, and are actively engaging with collaborators to obtain starting material for primary cell cultures from other midge species, mites, tsetse flies and bees. Outposts of the Tick Cell Biobank will be set up in Malaysia, Kenya and Brazil to facilitate uptake and exploitation of cell lines and associated training by scientists in these and neighbouring countries. Thus the Tick Cell Biobank will continue to underpin many areas of global research into biology and control of ticks, other arthropods and vector-borne viral, bacterial and protozoan pathogens. Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.

  2. EFFECTS OF THE ANTIMUTAGENS VANILLIN AND CINNAMALDEHYDE ON SPONTANEOUS MUTATION IN E. COLI LACL STRAINS AND ON GLOBAL GENE EXPRESSION IN SALMONELLA TA104 AND HUMAN HEPG2 CELLS

    EPA Science Inventory

    Effects of the Antimutagens Vanillin and Cinnamaldehyde on Spontaneous Mutation in E. coli lacI Strains and on Global Gene Epression in Salmonella TAlO4 and Human HepG2 Cells

    In previous work we have shown that vanillin (VAN) and cinnamaldehyde (CIN) are dietary antimutag...

  3. Global health justice and governance.

    PubMed

    Ruger, Jennifer Prah

    2012-01-01

    While there is a growing body of work on moral issues and global governance in the fields of global justice and international relations, little work has connected principles of global health justice with those of global health governance for a theory of global health. Such a theory would enable analysis and evaluation of the current global health system and would ethically and empirically ground proposals for reforming it to more closely align with moral values. Global health governance has been framed as an issue of national security, human security, human rights, and global public goods. The global health governance literature is essentially untethered to a theorized framework to illuminate or evaluate governance. This article ties global health justice and ethics to principles for governing the global health realm, developing a theoretical framework for global and domestic institutions and actors.

  4. Smaller global and regional carbon emissions from gross land use change when considering sub-grid secondary land cohorts in a global dynamic vegetation model

    NASA Astrophysics Data System (ADS)

    Yue, Chao; Ciais, Philippe; Li, Wei

    2018-02-01

    Several modelling studies reported elevated carbon emissions from historical land use change (ELUC) by including bidirectional transitions on the sub-grid scale (termed gross land use change), dominated by shifting cultivation and other land turnover processes. However, most dynamic global vegetation models (DGVMs) that have implemented gross land use change either do not account for sub-grid secondary lands, or often have only one single secondary land tile over a model grid cell and thus cannot account for various rotation lengths in shifting cultivation and associated secondary forest age dynamics. Therefore, it remains uncertain how realistic the past ELUC estimations are and how estimated ELUC will differ between the two modelling approaches with and without multiple sub-grid secondary land cohorts - in particular secondary forest cohorts. Here we investigated historical ELUC over 1501-2005 by including sub-grid forest age dynamics in a DGVM. We run two simulations, one with no secondary forests (Sageless) and the other with sub-grid secondary forests of six age classes whose demography is driven by historical land use change (Sage). Estimated global ELUC for 1501-2005 is 176 Pg C in Sage compared to 197 Pg C in Sageless. The lower ELUC values in Sage arise mainly from shifting cultivation in the tropics under an assumed constant rotation length of 15 years, being 27 Pg C in Sage in contrast to 46 Pg C in Sageless. Estimated cumulative ELUC values from wood harvest in the Sage simulation (31 Pg C) are however slightly higher than Sageless (27 Pg C) when the model is forced by reconstructed harvested areas because secondary forests targeted in Sage for harvest priority are insufficient to meet the prescribed harvest area, leading to wood harvest being dominated by old primary forests. An alternative approach to quantify wood harvest ELUC, i.e. always harvesting the close-to-mature forests in both Sageless and Sage, yields similar values of 33 Pg C by both simulations. The lower ELUC from shifting cultivation in Sage simulations depends on the predefined forest clearing priority rules in the model and the assumed rotation length. A set of sensitivity model runs over Africa reveal that a longer rotation length over the historical period likely results in higher emissions. Our results highlight that although gross land use change as a former missing emission component is included by a growing number of DGVMs, its contribution to overall ELUC remains uncertain and tends to be overestimated when models ignore sub-grid secondary forests.

  5. Limits to the precision of gradient sensing with spatial communication and temporal integration.

    PubMed

    Mugler, Andrew; Levchenko, Andre; Nemenman, Ilya

    2016-02-09

    Gradient sensing requires at least two measurements at different points in space. These measurements must then be communicated to a common location to be compared, which is unavoidably noisy. Although much is known about the limits of measurement precision by cells, the limits placed by the communication are not understood. Motivated by recent experiments, we derive the fundamental limits to the precision of gradient sensing in a multicellular system, accounting for communication and temporal integration. The gradient is estimated by comparing a "local" and a "global" molecular reporter of the external concentration, where the global reporter is exchanged between neighboring cells. Using the fluctuation-dissipation framework, we find, in contrast to the case when communication is ignored, that precision saturates with the number of cells independently of the measurement time duration, because communication establishes a maximum length scale over which sensory information can be reliably conveyed. Surprisingly, we also find that precision is improved if the local reporter is exchanged between cells as well, albeit more slowly than the global reporter. The reason is that whereas exchange of the local reporter weakens the comparison, it decreases the measurement noise. We term such a model "regional excitation-global inhibition." Our results demonstrate that fundamental sensing limits are necessarily sharpened when the need to communicate information is taken into account.

  6. The "Growing" Reality of the Neurological Complications of Global "Stem Cell Tourism".

    PubMed

    Julian, Katie; Yuhasz, Nick; Hollingsworth, Ethan; Imitola, Jaime

    2018-04-01

    "Stem cell tourism" is defined as the unethical practice of offering unproven cellular preparations to patients suffering from various medical conditions. This phenomenon is rising in the field of neurology as patients are requesting information and opportunities for treatment with stem cells for incurable conditions such as multiple sclerosis and amyotrophic lateral sclerosis, despite their clinical research and experimental designation. Here, we review the recent trends in "stem cell tourism" in both the United States and abroad, and discuss the recent reports of neurological complications from these activities. Finally, we frame critical questions for the field of neurology regarding training in the ethical, legal, and societal issues of the global "stem cell tourism," as well as suggest strategies to alleviate this problem. Although there are ongoing legitimate clinical trials with stem cells for neurological diseases, procedures offered by "stem cell clinics" cannot be defined as clinical research. They lack the experimental and state-of-the-art framework defined by peers and the FDA that focus on human research that safeguard the protection of human subjects against economical exploitation, unwanted side effects, and futility of unproven procedures. "Stem cell tourism" ultimately exploits therapeutic hope of patients and families with incurable neurological diseases and can put in danger the legitimacy of stem cell research as a whole. We posit that an improvement in education, regulation, legislation, and involvement of authorities in global health in neurology and neurosurgery is required. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  7. Global threshold dynamics of an SIVS model with waning vaccine-induced immunity and nonlinear incidence.

    PubMed

    Yang, Junyuan; Martcheva, Maia; Wang, Lin

    2015-10-01

    Vaccination is the most effective method of preventing the spread of infectious diseases. For many diseases, vaccine-induced immunity is not life long and the duration of immunity is not always fixed. In this paper, we propose an SIVS model taking the waning of vaccine-induced immunity and general nonlinear incidence into consideration. Our analysis shows that the model exhibits global threshold dynamics in the sense that if the basic reproduction number is less than 1, then the disease-free equilibrium is globally asymptotically stable implying the disease dies out; while if the basic reproduction number is larger than 1, then the endemic equilibrium is globally asymptotically stable indicating that the disease persists. This global threshold result indicates that if the vaccination coverage rate is below a critical value, then the disease always persists and only if the vaccination coverage rate is above the critical value, the disease can be eradicated. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Interpretable dimensionality reduction of single cell transcriptome data with deep generative models.

    PubMed

    Ding, Jiarui; Condon, Anne; Shah, Sohrab P

    2018-05-21

    Single-cell RNA-sequencing has great potential to discover cell types, identify cell states, trace development lineages, and reconstruct the spatial organization of cells. However, dimension reduction to interpret structure in single-cell sequencing data remains a challenge. Existing algorithms are either not able to uncover the clustering structures in the data or lose global information such as groups of clusters that are close to each other. We present a robust statistical model, scvis, to capture and visualize the low-dimensional structures in single-cell gene expression data. Simulation results demonstrate that low-dimensional representations learned by scvis preserve both the local and global neighbor structures in the data. In addition, scvis is robust to the number of data points and learns a probabilistic parametric mapping function to add new data points to an existing embedding. We then use scvis to analyze four single-cell RNA-sequencing datasets, exemplifying interpretable two-dimensional representations of the high-dimensional single-cell RNA-sequencing data.

  9. The Lack of Utility of Circulating Biomarkers of Inflammation and Endothelial Dysfunction for Type 2 Diabetes Risk Prediction Among Postmenopausal Women

    PubMed Central

    Chao, Chun; Song, Yiqing; Cook, Nancy; Tseng, Chi-Hong; Manson, JoAnn E.; Eaton, Charles; Margolis, Karen L.; Rodriguez, Beatriz; Phillips, Lawrence S.; Tinker, Lesley F.; Liu, Simin

    2011-01-01

    Background Recent studies have linked plasma markers of inflammation and endothelial dysfunction to type 2 diabetes mellitus (DM) development. However, the utility of these novel biomarkers for type 2 DM risk prediction remains uncertain. Methods The Women’s Health Initiative Observational Study (WHIOS), a prospective cohort, and a nested case-control study within the WHIOS of 1584 incident type 2 DM cases and 2198 matched controls were used to evaluate the utility of plasma markers of inflammation and endothelial dysfunction for type 2 DM risk prediction. Between September 1994 and December 1998, 93 676 women aged 50 to 79 years were enrolled in the WHIOS. Fasting plasma levels of glucose, insulin, white blood cells, tumor necrosis factor receptor 2, interleukin 6, high-sensitivity C-reactive protein, E-selectin, soluble intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 were measured using blood samples collected at baseline. A series of prediction models including traditional risk factors and novel plasma markers were evaluated on the basis of global model fit, model discrimination, net reclassification improvement, and positive and negative predictive values. Results Although white blood cell count and levels of interleukin 6, high-sensitivity C-reactive protein, and soluble intercellular adhesion molecule 1 significantly enhanced model fit, none of the inflammatory and endothelial dysfunction markers improved the ability of model discrimination (area under the receiver operating characteristic curve, 0.93 vs 0.93), net reclassification, or predictive values (positive, 0.22 vs 0.24; negative, 0.99 vs 0.99 [using 15% 6-year type 2 DM risk as the cutoff]) compared with traditional risk factors. Similar results were obtained in ethnic-specific analyses. Conclusion Beyond traditional risk factors, measurement of plasma markers of systemic inflammation and endothelial dysfunction contribute relatively little additional value in clinical type 2 DM risk prediction in a multiethnic cohort of postmenopausal women. PMID:20876407

  10. The vertical profile of radar reflectivity of convective cells: A strong indicator of storm intensity and lightning probability?

    NASA Technical Reports Server (NTRS)

    Zipser, Edward J.; Lutz, Kurt R.

    1994-01-01

    Reflectivity data from Doppler radars are used to construct vertical profiles of radar reflectivity (VPRR) of convective cells in mesoscale convective systems (MCSs) in three different environmental regimes. The National Center for Atmospheric Research CP-3 and CP-4 radars are used to calculate median VPRR for MCSs in the Oklahoma-Kansas Preliminary Regional Experiment for STORM-Central in 1985. The National Oceanic and Atmospheric Administration-Tropical Ocean Global Atmosphere radar in Darwin, Australia, is used to calculate VPRR for MCSs observed both in oceanic, monsoon regimes and in continental, break period regimes during the wet seasons of 1987/88 and 1988/89. The midlatitude and tropical continental VPRRs both exhibit maximum reflectivity somewhat above the surface and have a gradual decrease in reflectivity with height above the freezing level. In sharp contrast, the tropical oceanic profile has a maximum reflectivity at the lowest level and a very rapid decrease in reflectivity with height beginning just above the freezing level. The tropical oceanic profile in the Darwin area is almost the same shape as that for two other tropical oceanic regimes, leading to the conclustion that it is characteristic. The absolute values of reflectivity in the 0 to 20 C range are compared with values in the literature thought to represent a threshold for rapid storm electrification leading to lightning, about 40 dBZ at -10 C. The large negative vertical gradient of reflectivity in this temperature range for oceanic storms is hypothesized to be a direct result of the characteristically weaker vertical velocities observed in MCSs over tropical oceans. It is proposed, as a necessary condition for rapid electrification, that a convective cell must have its updraft speed exceed some threshold value. Based upon field program data, a tentative estimate for the magnitude of this threshold is 6-7 m/s for mean speed and 10-12 m/s for peak speed.

  11. Gene expression profiling of single cells on large-scale oligonucleotide arrays

    PubMed Central

    Hartmann, Claudia H.; Klein, Christoph A.

    2006-01-01

    Over the last decade, important insights into the regulation of cellular responses to various stimuli were gained by global gene expression analyses of cell populations. More recently, specific cell functions and underlying regulatory networks of rare cells isolated from their natural environment moved to the center of attention. However, low cell numbers still hinder gene expression profiling of rare ex vivo material in biomedical research. Therefore, we developed a robust method for gene expression profiling of single cells on high-density oligonucleotide arrays with excellent coverage of low abundance transcripts. The protocol was extensively tested with freshly isolated single cells of very low mRNA content including single epithelial, mature and immature dendritic cells and hematopoietic stem cells. Quantitative PCR confirmed that the PCR-based global amplification method did not change the relative ratios of transcript abundance and unsupervised hierarchical cluster analysis revealed that the histogenetic origin of an individual cell is correctly reflected by the gene expression profile. Moreover, the gene expression data from dendritic cells demonstrate that cellular differentiation and pathway activation can be monitored in individual cells. PMID:17071717

  12. Fast globally optimal segmentation of cells in fluorescence microscopy images.

    PubMed

    Bergeest, Jan-Philip; Rohr, Karl

    2011-01-01

    Accurate and efficient segmentation of cells in fluorescence microscopy images is of central importance for the quantification of protein expression in high-throughput screening applications. We propose a new approach for segmenting cell nuclei which is based on active contours and convex energy functionals. Compared to previous work, our approach determines the global solution. Thus, the approach does not suffer from local minima and the segmentation result does not depend on the initialization. We also suggest a numeric approach for efficiently computing the solution. The performance of our approach has been evaluated using fluorescence microscopy images of different cell types. We have also performed a quantitative comparison with previous segmentation approaches.

  13. Cultural values and cross-cultural video consumption on YouTube.

    PubMed

    Park, Minsu; Park, Jaram; Baek, Young Min; Macy, Michael

    2017-01-01

    Video-sharing social media like YouTube provide access to diverse cultural products from all over the world, making it possible to test theories that the Web facilitates global cultural convergence. Drawing on a daily listing of YouTube's most popular videos across 58 countries, we investigate the consumption of popular videos in countries that differ in cultural values, language, gross domestic product, and Internet penetration rate. Although online social media facilitate global access to cultural products, we find this technological capability does not result in universal cultural convergence. Instead, consumption of popular videos in culturally different countries appears to be constrained by cultural values. Cross-cultural convergence is more advanced in cosmopolitan countries with cultural values that favor individualism and power inequality.

  14. Global exponential periodicity and stability of discrete-time complex-valued recurrent neural networks with time-delays.

    PubMed

    Hu, Jin; Wang, Jun

    2015-06-01

    In recent years, complex-valued recurrent neural networks have been developed and analysed in-depth in view of that they have good modelling performance for some applications involving complex-valued elements. In implementing continuous-time dynamical systems for simulation or computational purposes, it is quite necessary to utilize a discrete-time model which is an analogue of the continuous-time system. In this paper, we analyse a discrete-time complex-valued recurrent neural network model and obtain the sufficient conditions on its global exponential periodicity and exponential stability. Simulation results of several numerical examples are delineated to illustrate the theoretical results and an application on associative memory is also given. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Global Mittag-Leffler stability and synchronization analysis of fractional-order quaternion-valued neural networks with linear threshold neurons.

    PubMed

    Yang, Xujun; Li, Chuandong; Song, Qiankun; Chen, Jiyang; Huang, Junjian

    2018-05-04

    This paper talks about the stability and synchronization problems of fractional-order quaternion-valued neural networks (FQVNNs) with linear threshold neurons. On account of the non-commutativity of quaternion multiplication resulting from Hamilton rules, the FQVNN models are separated into four real-valued neural network (RVNN) models. Consequently, the dynamic analysis of FQVNNs can be realized by investigating the real-valued ones. Based on the method of M-matrix, the existence and uniqueness of the equilibrium point of the FQVNNs are obtained without detailed proof. Afterwards, several sufficient criteria ensuring the global Mittag-Leffler stability for the unique equilibrium point of the FQVNNs are derived by applying the Lyapunov direct method, the theory of fractional differential equation, the theory of matrix eigenvalue, and some inequality techniques. In the meanwhile, global Mittag-Leffler synchronization for the drive-response models of the addressed FQVNNs are investigated explicitly. Finally, simulation examples are designed to verify the feasibility and availability of the theoretical results. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Integrating Proteomics and Enzyme Kinetics Reveals Tissue-Specific Types of the Glycolytic and Gluconeogenic Pathways.

    PubMed

    Wiśniewski, Jacek R; Gizak, Agnieszka; Rakus, Dariusz

    2015-08-07

    Glycolysis is the core metabolic pathway supplying energy to cells. Whereas the vast majority of studies focus on specific aspects of the process, global analyses characterizing simultaneously all enzymes involved in the process are scarce. Here, we demonstrate that quantitative label- and standard-free proteomics allows accurate determination of titers of metabolic enzymes and enables simultaneous measurements of titers and maximal enzymatic activities (Amax) of all glycolytic enzymes and the gluconeogenic fructose 1,6-bisphosphatase in mouse brain, liver and muscle. Despite occurrence of tissue-specific isoenzymes bearing different kinetic properties, the enzyme titers often correlated well with the Amax values. To provide a more general picture of energy metabolism, we analyzed titers of the enzymes in additional 7 mouse organs and in human cells. Across the analyzed samples, we identified two basic profiles: a "fast glucose uptake" one in brain and heart, and a "gluconeogenic rich" one occurring in liver. In skeletal muscles and other organs, we found intermediate profiles. Obtained data highlighted the glucose-flux-limiting role of hexokinase which activity was always 10- to 100-fold lower than the average activity of all other glycolytic enzymes. A parallel determination of enzyme titers and maximal enzymatic activities allowed determination of kcat values without enzyme purification. Results of our in-depth proteomic analysis of the mouse organs did not support the concepts of regulation of glycolysis by lysine acetylation.

  17. 40 CFR 52.1873 - Approval status.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... greenhouse gases in the pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from...

  18. 40 CFR 52.2222 - Approval status.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... greenhouse gases in the pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from...

  19. 40 CFR 52.2372 - Approval status.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... greenhouse gases in the pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from...

  20. 40 CFR 52.2072 - Approval status.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... greenhouse gases in the pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from...

  1. 40 CFR 52.1772 - Approval status.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... greenhouse gases in the pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from...

  2. 40 CFR 52.773 - Approval status.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... greenhouse gases in the pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from...

  3. 40 CFR 52.1323 - Approval status.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... greenhouse gases in the pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from...

  4. 40 CFR 52.822 - Approval status.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... greenhouse gases in the pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from...

  5. 40 CFR 52.2072 - Approval status.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... greenhouse gases in the pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from...

  6. 40 CFR 52.2372 - Approval status.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... greenhouse gases in the pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from...

  7. 40 CFR 52.2122 - Approval status.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... greenhouse gases in the pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from...

  8. 40 CFR 52.1873 - Approval status.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... greenhouse gases in the pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from...

  9. 40 CFR 52.1873 - Approval status.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... greenhouse gases in the pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from...

  10. 40 CFR 52.2072 - Approval status.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... greenhouse gases in the pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from...

  11. 40 CFR 52.1873 - Approval status.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... greenhouse gases in the pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from...

  12. Global meaning in people with stroke: Content and changes

    PubMed Central

    Littooij, Elsbeth; Dekker, Joost; Vloothuis, Judith; Leget, Carlo JW; Widdershoven, Guy AM

    2016-01-01

    After a traumatic event like a stroke, people need to find meaning and control again. This study enhances knowledge on one of the driving principles behind meaning-making processes: global meaning. Global meaning refers to individuals’ general orienting systems, comprising fundamental beliefs and life goals. Little is known about global meaning in people with stroke and whether global meaning changes after stroke. In this qualitative study, five aspects of global meaning were found: core values, relationships, worldview, identity and inner posture. Continuity in all aspects was reported, but worldview, identity and inner posture were also subjected to change. PMID:28815054

  13. Global meaning in people with stroke: Content and changes.

    PubMed

    Littooij, Elsbeth; Dekker, Joost; Vloothuis, Judith; Leget, Carlo Jw; Widdershoven, Guy Am

    2016-07-01

    After a traumatic event like a stroke, people need to find meaning and control again. This study enhances knowledge on one of the driving principles behind meaning-making processes: global meaning. Global meaning refers to individuals' general orienting systems, comprising fundamental beliefs and life goals. Little is known about global meaning in people with stroke and whether global meaning changes after stroke. In this qualitative study, five aspects of global meaning were found: core values, relationships, worldview, identity and inner posture. Continuity in all aspects was reported, but worldview, identity and inner posture were also subjected to change.

  14. Reflections on the Process of Bilingual Education in Latin America: A Perspective from Globalization

    ERIC Educational Resources Information Center

    Joya, Magdalena; Cerón, Alejandra

    2013-01-01

    This paper intends to explain how education can be understood as a process that involves the transmission of culture, knowledge, manners and values; meanwhile, globalization implies an evolving process of constructing a global system of languages. In this way, the relationship between the educational and economic systems can become stronger…

  15. Doing More with Less: Civic Practices for Longer-Term Impact in Global Service-Learning

    ERIC Educational Resources Information Center

    Alonso García, Nuria; Longo, Nicholas V.

    2017-01-01

    This essay explores the potential value of short-term study abroad experiences within the unique framework of a new global service-learning program at Providence College which connects international with local engagement as a way to "do more with less." The authors first introduce a typology for global service-learning, illustrating how…

  16. H. pylori modifies methylation of global genomic DNA and the gastrin gene promoter in gastric mucosal cells and gastric cancer cells.

    PubMed

    Xie, Yuan; Zhou, Jian Jiang; Zhao, Yan; Zhang, Ting; Mei, Liu Zheng

    2017-07-01

    The aim of this study was to evaluate the correlation between H. pylori infection and global DNA methylation, as well as the methylation levels of the gastrin promoters. We constructed a eukaryotic expression vector, pcDNA3.1::cagA, and transfected it into GES-1 gastric mucosal cells and SGC-7901 gastric cancer cells. Both cell lines were infected with the H. pylori/CagA + strain NCTC11637. Then, we detected global DNA methylation by capture and detection antibodies, followed by colorimetric quantification. The methylation levels of the gastrin promoter were evaluated by base-specific cleavage and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. In H. pylori/CagA + -infected GES-1 and SGC-7901 cells, the methylation levels of genomic DNA decreased by 49.4% and 18.8%, and in GES-1 and SGC-7901 cells transfected with pcDNA3.1::cagA, the methylation levels of genomic DNA decreased by 17.05% and 25.6%, respectively. Among 24 methylation sites detected in the gastrin promoter region, the methylation levels of 9 CpG sites were significantly decreased in H. pylori/CagA+-infected and pcDNA3.1:: cagA-transfected cells in comparison to corresponding control cells. These results indicate that H. pylori/CagA + decreases the methylation of the genome and the gastrin promoter at some CpG sites in gastric mucosal and gastric cancer cells. Copyright © 2017. Published by Elsevier Ltd.

  17. Evolution of Microbial Quorum Sensing to Human Global Quorum Sensing: An Insight into How Gap Junctional Intercellular Communication Might Be Linked to the Global Metabolic Disease Crisis.

    PubMed

    Trosko, James E

    2016-06-15

    The first anaerobic organism extracted energy for survival and reproduction from its source of nutrients, with the genetic means to ensure protection of its individual genome but also its species survival. While it had a means to communicate with its community via simple secreted molecules ("quorum sensing"), the eventual shift to an aerobic environment led to multi-cellular metazoan organisms, with evolutionary-selected genes to form extracellular matrices, stem cells, stem cell niches, and a family of gap junction or "connexin" genes. These germinal and somatic stem cells responded to extracellular signals that triggered intra-cellular signaling to regulate specific genes out of the total genome. These extra-cellular induced intra-cellular signals also modulated gap junctional intercellular communication (GJIC) in order to regulate the new cellular functions of symmetrical and asymmetrical cell division, cell differentiation, modes of cell death, and senescence. Within the hierarchical and cybernetic concepts, differentiated by neurons organized in the brain of the Homo sapiens, the conscious mind led to language, abstract ideas, technology, myth-making, scientific reasoning, and moral decision-making, i.e., the creation of culture. Over thousands of years, this has created the current collision between biological and cultural evolution, leading to the global "metabolic disease" crisis.

  18. Global Existence of Classical Solutions to the Equations of Motion for Materials with Fading Memory.

    DTIC Science & Technology

    1984-02-01

    influence function , history value problems, classical solutions, global existence, decay. Work Unit Number 1 - Applied Analysis Sponsored by the United...introduce an " influence function " h, intended to JIN. characterize the rate at which memory fades, and construct an LP-type space of admissible...histories using the influence function as a weight. Here we use the term influence function to mean a positive, nonincreasing, real-valued function h e L (0

  19. Initial-boundary value problem to 2D Boussinesq equations for MHD convection with stratification effects

    NASA Astrophysics Data System (ADS)

    Bian, Dongfen; Liu, Jitao

    2017-12-01

    This paper is concerned with the initial-boundary value problem to 2D magnetohydrodynamics-Boussinesq system with the temperature-dependent viscosity, thermal diffusivity and electrical conductivity. First, we establish the global weak solutions under the minimal initial assumption. Then by imposing higher regularity assumption on the initial data, we obtain the global strong solution with uniqueness. Moreover, the exponential decay rates of weak solutions and strong solution are obtained respectively.

  20. Fourier transform infra-red spectroscopic signatures for lung cells' epithelial mesenchymal transition: A preliminary report

    NASA Astrophysics Data System (ADS)

    Sarkar, Atasi; Sengupta, Sanghamitra; Mukherjee, Anirban; Chatterjee, Jyotirmoy

    2017-02-01

    Infra red (IR) spectral characterization can provide label-free cellular metabolic signatures of normal and diseased circumstances in a rapid and non-invasive manner. Present study endeavoured to enlist Fourier transform infra red (FTIR) spectroscopic signatures for lung normal and cancer cells during chemically induced epithelial mesenchymal transition (EMT) for which global metabolic dimension is not well reported yet. Occurrence of EMT was validated with morphological and immunocytochemical confirmation. Pre-processed spectral data was analyzed using ANOVA and principal component analysis-linear discriminant analysis (PCA-LDA). Significant differences observed in peak area corresponding to biochemical fingerprint (900-1800 cm- 1) and high wave-number (2800-3800 cm- 1) regions contributed to adequate PCA-LDA segregation of cells undergoing EMT. The findings were validated by re-analysis of data using another in-house built binary classifier namely vector valued regularized kernel approximation (VVRKFA), in order to understand EMT progression. To improve the classification accuracy, forward feature selection (FFS) tool was employed in extracting potent spectral signatures by eliminating undesirable noise. Gradual increase in classification accuracy with EMT progression of both cell types indicated prominence of the biochemical alterations. Rapid changes in cellular metabolome noted in cancer cells within first 24 h of EMT induction along with higher classification accuracy for cancer cell groups in comparison to normal cells might be attributed to inherent differences between them. Spectral features were suggestive of EMT triggered changes in nucleic acid, protein, lipid and bound water contents which can emerge as the useful markers to capture EMT related cellular characteristics.

  1. Global QSAR modeling of logP values of phenethylamines acting as adrenergic alpha-1 receptor agonists.

    PubMed

    Yadav, Mukesh; Joshi, Shobha; Nayarisseri, Anuraj; Jain, Anuja; Hussain, Aabid; Dubey, Tushar

    2013-06-01

    Global QSAR models predict biological response of molecular structures which are generic in particular class. A global QSAR dataset admits structural features derived from larger chemical space, intricate to model but more applicable in medicinal chemistry. The present work is global in either sense of structural diversity in QSAR dataset or large number of descriptor input. Forty phenethylamine structure derivatives were selected from a large pool (904) of similar phenethylamines available in Pubchem database. LogP values of selected candidates were collected from physical properties database (PHYSPROP) determined in identical set of conditions. Attempts to model logP value have produced significant QSAR models. MLR aided linear one-variable and two-variable QSAR models with their respective R(2) (0.866, 0.937), R(2)A (0.862, 0.932), F-stat (181.936, 199.812) and Standard Error (0.365, 0.255) are statistically fit and found predictive after internal validation and external validation. The descriptors chosen after improvisation and optimization reveal mechanistic part of work in terms of Verhaar model of Fish base-line toxicity from MLOGP, i.e. (BLTF96) and 3D-MoRSE -signal 15 /unweighted molecular descriptor calculated by summing atom weights viewed by a different angular scattering function (Mor15u) are crucial in regulation of logP values of phenethylamines.

  2. Diagnostic power of longitudinal strain at rest for the detection of obstructive coronary artery disease in patients with type 2 diabetes mellitus.

    PubMed

    Zuo, Houjuan; Yan, Jiangtao; Zeng, Hesong; Li, Wenyu; Li, Pengcheng; Liu, Zhengxiang; Cui, Guanglin; Lv, Jiagao; Wang, Daowen; Wang, Hong

    2015-01-01

    Global longitudinal strain (GLS) measured by 2-D speckle-tracking echocardiography (2-D STE) at rest has been recognized as a sensitive parameter in the detection of significant coronary artery disease (CAD). However, the diagnostic power of 2-D STE in the detection of significant CAD in patients with diabetes mellitus is unknown. Two-dimensional STE features were studied in total of 143 consecutive patients who underwent echocardiography and coronary angiography. Left ventricular global and segmental peak systolic longitudinal strains (PSLSs) were quantified by speckle-tracking imaging. In the presence of obstructive CAD (defined as stenosis ≥75%), global PSLS was significantly lower in patients with diabetes mellitus than in patients without (16.65 ± 2.29% vs. 17.32 ± 2.27%, p < 0.05). Receiver operating characteristic analysis revealed that global PSLS could effectively detect obstructive CAD in patients without diabetes mellitus (cutoff value: -18.35%, sensitivity: 78.8%, specificity: 77.5%). However, global PSLS could detect obstructive CAD in diabetic patients at a lower cutoff value with inadequate sensitivity and specificity (cutoff value: -17.15%; sensitivity: 61.1%, specificity: 52.9%). In addition, the results for segmental PSLS were similar to those for global PSLS. In conclusion, global and segmental PSLSs at rest were significantly lower in patients with both obstructive CAD and diabetes mellitus than in patients with obstructive CAD only; thus, PSLSs at rest might not be a useful parameter in the detection of obstructive CAD in patients with diabetes mellitus. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  3. Diffusion maps for high-dimensional single-cell analysis of differentiation data.

    PubMed

    Haghverdi, Laleh; Buettner, Florian; Theis, Fabian J

    2015-09-15

    Single-cell technologies have recently gained popularity in cellular differentiation studies regarding their ability to resolve potential heterogeneities in cell populations. Analyzing such high-dimensional single-cell data has its own statistical and computational challenges. Popular multivariate approaches are based on data normalization, followed by dimension reduction and clustering to identify subgroups. However, in the case of cellular differentiation, we would not expect clear clusters to be present but instead expect the cells to follow continuous branching lineages. Here, we propose the use of diffusion maps to deal with the problem of defining differentiation trajectories. We adapt this method to single-cell data by adequate choice of kernel width and inclusion of uncertainties or missing measurement values, which enables the establishment of a pseudotemporal ordering of single cells in a high-dimensional gene expression space. We expect this output to reflect cell differentiation trajectories, where the data originates from intrinsic diffusion-like dynamics. Starting from a pluripotent stage, cells move smoothly within the transcriptional landscape towards more differentiated states with some stochasticity along their path. We demonstrate the robustness of our method with respect to extrinsic noise (e.g. measurement noise) and sampling density heterogeneities on simulated toy data as well as two single-cell quantitative polymerase chain reaction datasets (i.e. mouse haematopoietic stem cells and mouse embryonic stem cells) and an RNA-Seq data of human pre-implantation embryos. We show that diffusion maps perform considerably better than Principal Component Analysis and are advantageous over other techniques for non-linear dimension reduction such as t-distributed Stochastic Neighbour Embedding for preserving the global structures and pseudotemporal ordering of cells. The Matlab implementation of diffusion maps for single-cell data is available at https://www.helmholtz-muenchen.de/icb/single-cell-diffusion-map. fbuettner.phys@gmail.com, fabian.theis@helmholtz-muenchen.de Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  4. Can Education Add Value to Values? A Study of Law Students

    ERIC Educational Resources Information Center

    Palermo, Josephine; Evans, Adrian

    2004-01-01

    In the global market place the value of education takes on many meanings. In transnational education forums it relates to the market's assessment (in dollar terms) of a qualification. But can we measure the value-addedness of tertiary education in existential terms? Can we measure the value that tertiary education provides to the enhancement of…

  5. Statistical analysis of global horizontal solar irradiation GHI in Fez city, Morocco

    NASA Astrophysics Data System (ADS)

    Bounoua, Z.; Mechaqrane, A.

    2018-05-01

    An accurate knowledge of the solar energy reaching the ground is necessary for sizing and optimizing the performances of solar installations. This paper describes a statistical analysis of the global horizontal solar irradiation (GHI) at Fez city, Morocco. For better reliability, we have first applied a set of check procedures to test the quality of hourly GHI measurements. We then eliminate the erroneous values which are generally due to measurement or the cosine effect errors. Statistical analysis show that the annual mean daily values of GHI is of approximately 5 kWh/m²/day. Daily monthly mean values and other parameter are also calculated.

  6. Global stability and tumor clearance conditions for a cancer chemotherapy system

    NASA Astrophysics Data System (ADS)

    Valle, Paul A.; Starkov, Konstantin E.; Coria, Luis N.

    2016-11-01

    In this paper we study the global dynamics of a cancer chemotherapy system presented by de Pillis et al. (2007). This mathematical model describes the interaction between tumor cells, effector-immune cells, circulating lymphocytes and chemotherapy treatment. By applying the localization method of compact invariant sets, we find lower and upper bounds for these three cells populations. Further, we define a bounded domain in R+,04 where all compact invariant sets of the system are located and provide conditions under which this domain is positively invariant. We apply LaSalle's invariance principle and one result concerning two-dimensional competitive systems in order to derive sufficient conditions for tumor clearance and global asymptotic stability of the tumor-free equilibrium point. These conditions are computed by using bounds of the localization domain and they are given in terms of the chemotherapy treatment. Finally, we perform numerical simulations in order to illustrate our results.

  7. The Representation of Tropical Cyclones Within the Global William Putman Non-Hydrostatic Goddard Earth Observing System Model (GEOS-5) at Cloud-Permitting Resolutions

    NASA Technical Reports Server (NTRS)

    Putman, William M.

    2010-01-01

    The Goddard Earth Observing System Model (GEOS-S), an earth system model developed in the NASA Global Modeling and Assimilation Office (GMAO), has integrated the non-hydrostatic finite-volume dynamical core on the cubed-sphere grid. The extension to a non-hydrostatic dynamical framework and the quasi-uniform cubed-sphere geometry permits the efficient exploration of global weather and climate modeling at cloud permitting resolutions of 10- to 4-km on today's high performance computing platforms. We have explored a series of incremental increases in global resolution with GEOS-S from irs standard 72-level 27-km resolution (approx.5.5 million cells covering the globe from the surface to 0.1 hPa) down to 3.5-km (approx. 3.6 billion cells).

  8. The CrowdMag App - turning your smartphone into a travelling magnetic observatory

    NASA Astrophysics Data System (ADS)

    Saltus, Richard; Nair, Manoj

    2017-04-01

    In 2014, we started the "CrowdMag" Project to collect vector magnetic data from digital magnetometers in smartphones. In October 2014, we released our first-generation Android and iOS apps. Currently, the CrowdMag Project has more than 15,000 enthusiastic users contributing more than 12 million magnetic data points from around the world. NOAA's National Centers for Environmental Information (NCEI), in partnership with the University of Colorado's Cooperative Institute for Research in the Environmental Sciences (CIRES) develops magnetic field models to aid navigation, resource exploration and scientific research. We use observatories, satellites and ship/airborne surveys to measure the magnetic data. However, the measurements leave gaps in coverage, particularly for short-wavelength urban noise. Our ultimate goal is to use data from the CrowdMag Project to improve global magnetic data coverage. Here we present some early results from the analysis of the crowdsourced magnetic data. A global magnetic model derived solely based on CrowdMag data is generally consistent with satellite-derived models such as World Magnetic Model. A unique contribution of the CrowdMag Project is the collection of ground level magnetic data in densely populated regions with an unprecedented spatial resolution. For example, we show a magnetic map (by binning the data collected into 100x100m cells) of central Boulder using 170,000 data points collected by about 60 devices over the duration October 2014- January 2016. The median magnetic field value is consistent with the expected magnitude of the Earth's background magnetic field. The standard deviation of the CrowdMag total field (F) values is much higher than the expected natural (i.e., diurnal and geologic) magnetic field variation. However, the phone's magnetometer is sensitive enough to capture the larger magnitude magnetic signature from the urban magnetic sources. We discuss the reliability of crowdsourced magnetic maps and their applications to navigation, global models, and local geologic or environmental investigations.

  9. Commensurate comparisons of models with energy budget observations reveal consistent climate sensitivities

    NASA Astrophysics Data System (ADS)

    Armour, K.

    2017-12-01

    Global energy budget observations have been widely used to constrain the effective, or instantaneous climate sensitivity (ICS), producing median estimates around 2°C (Otto et al. 2013; Lewis & Curry 2015). A key question is whether the comprehensive climate models used to project future warming are consistent with these energy budget estimates of ICS. Yet, performing such comparisons has proven challenging. Within models, values of ICS robustly vary over time, as surface temperature patterns evolve with transient warming, and are generally smaller than the values of equilibrium climate sensitivity (ECS). Naively comparing values of ECS in CMIP5 models (median of about 3.4°C) to observation-based values of ICS has led to the suggestion that models are overly sensitive. This apparent discrepancy can partially be resolved by (i) comparing observation-based values of ICS to model values of ICS relevant for historical warming (Armour 2017; Proistosescu & Huybers 2017); (ii) taking into account the "efficacies" of non-CO2 radiative forcing agents (Marvel et al. 2015); and (iii) accounting for the sparseness of historical temperature observations and differences in sea-surface temperature and near-surface air temperature over the oceans (Richardson et al. 2016). Another potential source of discrepancy is a mismatch between observed and simulated surface temperature patterns over recent decades, due to either natural variability or model deficiencies in simulating historical warming patterns. The nature of the mismatch is such that simulated patterns can lead to more positive radiative feedbacks (higher ICS) relative to those engendered by observed patterns. The magnitude of this effect has not yet been addressed. Here we outline an approach to perform fully commensurate comparisons of climate models with global energy budget observations that take all of the above effects into account. We find that when apples-to-apples comparisons are made, values of ICS in models are consistently in good agreement with values of ICS inferred from global energy budget constraints. This suggests that the current generation of coupled climate models are not overly sensitive. However, since global energy budget observations do not constrain ECS, it is less certain whether model ECS values are realistic.

  10. Rapid and coordinated processing of global motion images by local clusters of retinal ganglion cells.

    PubMed

    Matsumoto, Akihiro; Tachibana, Masao

    2017-01-01

    Even when the body is stationary, the whole retinal image is always in motion by fixational eye movements and saccades that move the eye between fixation points. Accumulating evidence indicates that the brain is equipped with specific mechanisms for compensating for the global motion induced by these eye movements. However, it is not yet fully understood how the retina processes global motion images during eye movements. Here we show that global motion images evoke novel coordinated firing in retinal ganglion cells (GCs). We simultaneously recorded the firing of GCs in the goldfish isolated retina using a multi-electrode array, and classified each GC based on the temporal profile of its receptive field (RF). A moving target that accompanied the global motion (simulating a saccade following a period of fixational eye movements) modulated the RF properties and evoked synchronized and correlated firing among local clusters of the specific GCs. Our findings provide a novel concept for retinal information processing during eye movements.

  11. 40 CFR 52.1073 - Approval status.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from paragraph (h)(4)(ii)(A) of...

  12. 40 CFR 52.1272 - Approval status.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from paragraph (b)(4)(ii)(A) of...

  13. 40 CFR 52.2172 - Approval status.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from paragraph (b)(4)(ii)(A) of...

  14. 40 CFR 52.323 - Approval status.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from paragraph (b)(4)(ii)(A) of...

  15. 40 CFR 52.2323 - Approval status.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from paragraph (b)(4)(ii)(A) of...

  16. 40 CFR 52.1522 - Approval status.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... gases in the pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from paragraph (c)(4...

  17. 40 CFR 52.572 - Approval status.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from paragraph (b)(4)(ii)(A) of...

  18. 40 CFR 52.1929 - Significant deterioration of air quality.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... greenhouse gases in the pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from...

  19. 40 CFR 52.1022 - Approval status.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from paragraph (b)(4)(ii)(A) of...

  20. 40 CFR 52.1929 - Significant deterioration of air quality.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... greenhouse gases in the pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from...

  1. 40 CFR 52.1929 - Significant deterioration of air quality.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... greenhouse gases in the pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from...

  2. 40 CFR 52.2323 - Approval status.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from paragraph (b)(4)(ii)(A) of...

  3. 40 CFR 52.323 - Approval status.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from paragraph (b)(4)(ii)(A) of...

  4. 40 CFR 52.1022 - Approval status.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from paragraph (b)(4)(ii)(A) of...

  5. 40 CFR 52.1272 - Approval status.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from paragraph (b)(4)(ii)(A) of...

  6. 40 CFR 52.323 - Approval status.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from paragraph (b)(4)(ii)(A) of...

  7. 40 CFR 52.1272 - Approval status.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from paragraph (b)(4)(ii)(A) of...

  8. 40 CFR 52.2172 - Approval status.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from paragraph (b)(4)(ii)(A) of...

  9. 40 CFR 52.1929 - Significant deterioration of air quality.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... greenhouse gases in the pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from...

  10. 40 CFR 52.2323 - Approval status.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from paragraph (b)(4)(ii)(A) of...

  11. 40 CFR 52.1022 - Approval status.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from paragraph (b)(4)(ii)(A) of...

  12. 40 CFR 52.1022 - Approval status.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from paragraph (b)(4)(ii)(A) of...

  13. 40 CFR 52.2323 - Approval status.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from paragraph (b)(4)(ii)(A) of...

  14. 40 CFR 52.2172 - Approval status.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from paragraph (b)(4)(ii)(A) of...

  15. 40 CFR 52.2172 - Approval status.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from paragraph (b)(4)(ii)(A) of...

  16. 40 CFR 52.1073 - Approval status.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from paragraph (h)(4)(ii)(A) of...

  17. 40 CFR 52.323 - Approval status.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... pollutant GHGs, by the gas's associated global warming potential published at Table A-1 to subpart A of 40 CFR part 98—Global Warming Potentials. (B) Sum the resultant value from paragraph (b)(4)(ii)(A) of...

  18. Low-dose carbon-based nanoparticle-induced effects in A549 lung cells determined by biospectroscopy are associated with increases in genomic methylation

    NASA Astrophysics Data System (ADS)

    Li, Junyi; Tian, Meiping; Cui, Li; Dwyer, John; Fullwood, Nigel J.; Shen, Heqing; Martin, Francis L.

    2016-02-01

    Nanotechnology has introduced many manufactured carbon-based nanoparticles (CNPs) into our environment, generating a debate into their risks and benefits. Numerous nanotoxicology investigations have been carried, and nanoparticle-induced toxic effects have been reported. However, there remain gaps in our knowledge, primarily regarding mechanism. Herein, we assessed the global alterations induced by CNPs in A549 lung cells using biospectroscopy techniques, including attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy and surface-enhanced Raman spectroscopy (SERS). A549 cells were treated with fullerene (C60), long or short multi-walled carbon nanotubes, or single-walled carbon nanotubes at concentrations of 0.1 mg/L, 0.01 mg/L and 0.001 mg/L. Exposed cells were then analysed by ATR-FTIR spectroscopy and SERS. Spectra were pre-processed via computational analysis, and information on biochemical alterations in exposed cells were identified. Additionally, global DNA methylation levels in cells exposed to CNPs at 0.1 mg/L were determined using HPLC-MS and genetic regulators (for DNA methylation) were checked by quantitative real-time RT-PCR. It was found that CNPs exert marked effects in A549 cells and also contribute to increases in global DNA methylation. For the first time, this study highlights that real-world levels of nanoparticles can alter the methylome of exposed cells; this could have enormous implications for their regulatory assessment.

  19. A metadata initiative for global information discovery

    USGS Publications Warehouse

    Christian, E.

    2001-01-01

    The Global Information Locator Service (GILS) encompasses a global vision framed by the fundamental values of open societies. Societal values such as a free flow of information impose certain requirements on the society's information infrastructure. These requirements in turn shape the various laws, policies, standards, and technologies that determine the infrastructure design. A particular focus of GILS is the requirement to provide the means for people to discover sources of data and information. Information discovery in the GILS vision is designed to be decentralized yet coherent, and globally comprehensive yet useful for detailed data. This article introduces basic concepts and design issues, with emphasis on the techniques by which GILS supports interoperability. It explains the practical implications of GILS for the common roles of organizations involved in handling information, from content provider through system engineer and intermediary to searcher. The article provides examples of GILS initiatives in various types of communities: bibliographic, geographic, environmental, and government. ?? 2001 Elsevier Science Inc.

  20. Global, Energy-Dependent Ring Current Response During Two Large Storms

    NASA Astrophysics Data System (ADS)

    Goldstein, J.; Angelopoulos, V.; Burch, J. L.; De Pascuale, S.; Fuselier, S. A.; Genestreti, K. J.; Kurth, W. S.; LLera, K.; McComas, D. J.; Reeves, G. D.; Spence, H. E.; Valek, P. W.

    2015-12-01

    Two recent large (~200 nT) geomagnetic storms occurred during 17--18 March 2015 and 22--23 June 2015. The global, energy-dependent ring current response to these two extreme events is investigated using both global imaging and multi-point in situ observations. Energetic neutral atom (ENA) imaging by the Two Wide-angle Imaging Neutral-atom Spectrometers (TWINS) mission provides a global view of ring current ions. Local measurements are provided by two multi-spacecraft missions. The two Van Allen Probes measure in situ plasma (including ion composition) and fields at ring current and plasmaspheric L values. The recently launched Magnetospheric Multiscale (MMS) comprises four spacecraft that have just begun to measure particles (including ion composition) and fields at outer magnetospheric L-values. We analyze the timing and energetics of the stormtime evolution of ring current ions, both trapped and precipitating, using TWINS ENA images and in situ data by the Van Allen Probes and MMS.

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