How important is biomass burning in Canada to mercury contamination?

NASA Astrophysics Data System (ADS)

Fraser, Annemarie; Dastoor, Ashu; Ryjkov, Andrei

2018-05-01

Wildfire frequency has increased in past four decades in Canada and is expected to increase in future as a result of climate change (Wotton et al., 2010). Mercury (Hg) emissions from biomass burning are known to be significant; however, the impact of biomass burning on air concentration and deposition fluxes in Canada has not been previously quantified. We use estimates of burned biomass from FINN (Fire INventory from NCAR) and vegetation-specific emission factors (EFs) of mercury to investigate the spatiotemporal variability of Hg emissions in Canada. We use Environment and Climate Change Canada's GEM-MACH-Hg (Global Environmental Multi-scale, Modelling Air quality and Chemistry model, mercury version) to quantify the impact of biomass burning in Canada on spatiotemporal variability of air concentrations and deposition fluxes of mercury in Canada. We use North American gaseous elemental mercury (GEM) observations (2010-2015), GEM-MACH-Hg, and an inversion technique to optimize the EFs for GEM for five vegetation types represented in North American fires to constrain the biomass burning impacts of mercury. The inversion results suggest that EFs representing more vegetation types - specifically peatland - are required. This is currently limited by the sparseness of measurements of Hg from biomass burning plumes. More measurements of Hg concentration in the air, specifically downwind of fires, would improve the inversions. We use three biomass burning Hg emissions scenarios in Canada to conduct three sets of model simulations for 2010-2015: two scenarios where Hg is emitted only as GEM using literature or optimized EFs and a third scenario where Hg is emitted as GEM using literature EFs and particle bound mercury (PBM) emitted using the average GEM/PBM ratio from lab measurements. The three biomass burning emission scenarios represent a range of possible values for the impacts of Hg emissions from biomass burning in Canada on Hg concentration and deposition. We find total biomass burning Hg emissions to be highly variable from year to year and estimate average 2010-2015 total atmospheric biomass burning emissions of Hg in Canada to be between 6 and 14 t during the biomass burning season (i.e. from May to September), which is 3-7 times the mercury emission from anthropogenic sources in Canada for this period. On average, 65 % of the emissions occur in the provinces west of Ontario. We find that while emissions from biomass burning have a small impact on surface air concentrations of GEM averaged over individual provinces/territories, the impact at individual sites can be as high as 95 % during burning events. We estimate average annual mercury deposition from biomass burning in Canada to be between 0.3 and 2.8 t, compared to 0.14 t of mercury deposition from anthropogenic sources during the biomass burning season in Canada. Compared to the biomass burning emissions, the relative impact of fires on mercury deposition is shifted eastward, with on average 54 % percent of the deposition occurring in provinces west of Ontario. While the relative contribution of Canadian biomass burning to the total mercury deposition over each province/territory is no more than 9 % between 2010 and 2015, the local contribution in some locations (including areas downwind of biomass burning) can be as high as 80 % (e.g. northwest of Great Slave Lake in 2014) from May to September. We find that northern Alberta and Saskatchewan, central British Columbia, and the area around Great Slave Lake in the Northwest Territories are at greater risk of mercury contamination from biomass burning. GEM is considered to be the dominant mercury species emitted from biomass burning; however, there remains an uncertainty in the speciation of mercury released from biomass burning. We find that the impact of biomass burning emissions on mercury deposition is significantly affected by the uncertainty in speciation of emitted mercury because PBM is more readily deposited closer to the emission sources than GEM; an addition of ˜ 18 % percent of mercury emission from biomass burning in the form of PBM in the model increases the 6-year average deposition by ˜ 4 times.

The Canadian Precipitation Analysis (CaPA): Evaluation of the statistical interpolation scheme

NASA Astrophysics Data System (ADS)

Evans, Andrea; Rasmussen, Peter; Fortin, Vincent

2013-04-01

CaPA (Canadian Precipitation Analysis) is a data assimilation system which employs statistical interpolation to combine observed precipitation with gridded precipitation fields produced by Environment Canada's Global Environmental Multiscale (GEM) climate model into a final gridded precipitation analysis. Precipitation is important in many fields and applications, including agricultural water management projects, flood control programs, and hydroelectric power generation planning. Precipitation is a key input to hydrological models, and there is a desire to have access to the best available information about precipitation in time and space. The principal goal of CaPA is to produce this type of information. In order to perform the necessary statistical interpolation, CaPA requires the estimation of a semi-variogram. This semi-variogram is used to describe the spatial correlations between precipitation innovations, defined as the observed precipitation amounts minus the GEM forecasted amounts predicted at the observation locations. Currently, CaPA uses a single isotropic variogram across the entire analysis domain. The present project investigates the implications of this choice by first conducting a basic variographic analysis of precipitation innovation data across the Canadian prairies, with specific interest in identifying and quantifying potential anisotropy within the domain. This focus is further expanded by identifying the effect of storm type on the variogram. The ultimate goal of the variographic analysis is to develop improved semi-variograms for CaPA that better capture the spatial complexities of precipitation over the Canadian prairies. CaPA presently applies a Box-Cox data transformation to both the observations and the GEM data, prior to the calculation of the innovations. The data transformation is necessary to satisfy the normal distribution assumption, but introduces a significant bias. The second part of the investigation aims at devising a bias correction scheme based on a moving-window averaging technique. For both the variogram and bias correction components of this investigation, a series of trial runs are conducted to evaluate the impact of these changes on the resulting CaPA precipitation analyses.

Toward a 35-years North American Precipitation and Surface Reanalysis

NASA Astrophysics Data System (ADS)

Gasset, N.; Fortin, V.

2017-12-01

In support of the International Watersheds Initiative (IWI) of the International Joint Commission (IJC), a 35-years precipitation and surface reanalysis covering North America at a 3-hours and 15-km resolution is currently being developed at the Canadian Meteorological Centre (CMC). A deterministic reforecast / dynamical downscaling approach is followed where a global reanalysis (ERA-Interim) is used as initial condition of the Global Environmental Multi-scale model (GEM). Moreover, the latter is coupled with precipitation and surface data assimilation systems, i.e. the Canadian Precipitation Analysis (CaPA) and the Canadian Land Data Assimilation System (CaLDAS). While optimized to be more computationally efficient in the context of a reforecast experiment, all systems used are closely related to model versions and configurations currently run operationally at CMC, meaning they have undergone a strict and thorough validation procedure.As a proof of concept and in order to identify the optimal set-up before achieving the 35-years reanalysis, several configurations of the approach are evaluated for the years 2010-2014 using both standard CMC validation methodology as well as more dedicated scores such as comparison against the currently available products (North American Regional Reanalysis, MERRA-Land and the newly released ERA5 reanalysis). A special attention is dedicated to the evaluation of analysed variables, i.e. precipitation, snow depth, surface/ground temperature and moisture over the whole domain of interest. Results from these preliminary samples are very encouraging and the optimal set-up is identified. The coupled approach, i.e. GEM+CaPA/CaLDAS, always shows clear improvements over classical reforecast and dynamical downscaling where surface observations are present. Furthermore, results are inline or better than currently available products and the reference CMC operational approach that was operated from 2012 to 2016 (GEM 3.3, 10-km resolution). This reanalysis will allow for bias correction of current estimates and forecasts, and help decision maker understand and communicate by how much the current forecasted state of the system differs from the recent past.

Gravity model improvement using GEOS-3 (GEM 9 and 10)

NASA Technical Reports Server (NTRS)

Lerch, F. J.; Klosko, S. M.; Laubscher, R. E.; Wagner, C. A.

1977-01-01

The use of collocation permitted GEM 9 to be a larger field than previous derived satellite models, GEM 9 having harmonics complete to 20 x 20 with selected higher degree terms. The satellite data set has approximately 840,000 observations, of which 200,000 are laser ranges taken on 9 satellites equipped with retroreflectors. GEM 10 is complete to 22 x 22 with selected higher degree terms out to degree and order 30 amounting to a total of 592 coefficients. Comparisons with surface gravity and altimeter data indicate a substantial improvement in GEM 9 over previous satellite solutions; GEM 9 is in even closer agreement with surface data than the previously published GEM 6 solution which contained surface gravity. In particular the free air gravity anomalies calculated from GEM 9 and a surface gravity solution are in excellent agreement for the high degree terms.

Gemcitabine-based polymer-drug conjugate for enhanced anticancer effect in colon cancer.

PubMed

Liang, Tie-Jun; Zhou, Zhong-Mei; Cao, Ying-Qing; Ma, Ming-Ze; Wang, Xiao-Jun; Jing, Kai

2016-11-20

In this study, we have demonstrated gemcitabine (GEM)-conjugated amphiphilic biodegradable polymeric drug carriers. Our aim was to increase the chemotherapeutic potential of GEM in colon cancer by forming a unique polymer-drug conjugates. The polymer-drug conjugate micelles were nanosized with a typical spherical shape. The GEM-conjugated methoxy poly(ethylene glycol)-poly(lactic acid) (GEM-PL) exhibited a controlled release of drug in both the pH conditions. The developed GEM-PL efficiently killed the HT29 cancers cells in a typical time dependent manner. The clonogenic assay further confirmed the superior anticancer effect of GEM-PL which showed least number of colonies. GEM-PL formulation exhibited a significantly higher apoptosis of cancer cells (∼25%) when stained using Annexin-V/PI kit. Conjugation of GEM to the mPEG-PLA significantly enhanced the blood circulation potential in animal model compared to that of free GEM. GEM-PL could prevent quick elimination of the drug and can provide sufficient time for the greater accumulation of GEM at the tumor sites. GEM-PL showed a remarkable tumor regression effect as evident from the lowest tumor volume in HT-29 containing tumor model. Overall, mPEG-PLA/GEM conjugates showed the potential of polymer-based drug targeting and might hold significant clinical potential in the treatment of colon cancers. Copyright © 2016 Elsevier B.V. All rights reserved.

Overview of the Gems Model of Volunteer Administration (Generate, Educate, Mobilize and Sustain)

ERIC Educational Resources Information Center

Culp, Ken, III

2012-01-01

To organize and coordinate the efforts of many volunteers, a framework for volunteer engagement is needed. The "GEMS" Model of volunteer administration was developed to assist Extension professionals and volunteer coordinators to effectively administer volunteer programs without delivering the program themselves. The GEMS Model is…

Synthesis of GEMS from Shock-accelerated Crystalline Dust in Superbubbles: Model and Predictions

NASA Technical Reports Server (NTRS)

Westphal, Andrew J.; Bradley, John P.

2005-01-01

GEMS (Glass Embedded with Metals and Sulfides) are highly enigmatic yet common components of anhydrous IDPs. We have recently proposed a model of GEMS formation from shock-accelerated crystalline dust in superbubbles[1] which explains the three most perplexing properties of GEMS: pseudomorphism[2], their chemistry[3], and their size range. In this Abstract, we briefly review the main points of the model, and suggest tests that will either prove or rule out this hypothesis.

Simulation of the West African monsoon onset using the HadGEM3-RA regional climate model

NASA Astrophysics Data System (ADS)

Diallo, Ismaïla; Bain, Caroline L.; Gaye, Amadou T.; Moufouma-Okia, Wilfran; Niang, Coumba; Dieng, Mame D. B.; Graham, Richard

2014-08-01

The performance of the Hadley Centre Global Environmental Model version 3 regional climate model (HadGEM3-RA) in simulating the West African monsoon (WAM) is investigated. We focus on performance for monsoon onset timing and for rainfall totals over the June-July-August (JJA) season and on the model's representation of the underlying dynamical processes. Experiments are driven by the ERA-Interim reanalysis and follow the CORDEX experimental protocol. Simulations with the HadGEM3 global model, which shares a common physical formulation with HadGEM3-RA, are used to gain insight into the causes of HadGEM3-RA simulation errors. It is found that HadGEM3-RA simulations of monsoon onset timing are realistic, with an error in mean onset date of two pentads. However, the model has a dry bias over the Sahel during JJA of 15-20 %. Analysis suggests that this is related to errors in the positioning of the Saharan heat low, which is too far south in HadGEM3-RA and associated with an insufficient northward reach of the south-westerly low-level monsoon flow and weaker moisture convergence over the Sahel. Despite these biases HadGEM3-RA's representation of the general rainfall distribution during the WAM appears superior to that of ERA-Interim when using Global Precipitation Climatology Project or Tropical Rain Measurement Mission data as reference. This suggests that the associated dynamical features seen in HadGEM3-RA can complement the physical picture available from ERA-Interim. This approach is supported by the fact that the global HadGEM3 model generates realistic simulations of the WAM without the benefit of pseudo-observational forcing at the lateral boundaries; suggesting that the physical formulation shared with HadGEM3-RA, is able to represent the driving processes. HadGEM3-RA simulations confirm previous findings that the main rainfall peak near 10°N during June-August is maintained by a region of mid-tropospheric ascent located, latitudinally, between the cores of the African Easterly Jet and Tropical Easterly Jet that intensifies around the time of onset. This region of ascent is weaker and located further south near 5°N in the driving ERA-Interim reanalysis, for reasons that may be related to the coarser resolution or the physics of the underlying model, and this is consistent with a less realistic latitudinal rainfall profile than found in the HadGEM3-RA simulations.

Geopotential models of the Earth from satellite tracking, altimeter and surface gravity observations: GEM-T3 and GEM-T3S

NASA Technical Reports Server (NTRS)

Lerch, F. J.; Nerem, R. S.; Putney, B. H.; Felsentreger, T. L.; Sanchez, B. V.; Klosko, S. M.; Patel, G. B.; Williamson, R. G.; Chinn, D. S.; Chan, J. C.

1992-01-01

Improved models of the Earth's gravitational field have been developed from conventional tracking data and from a combination of satellite tracking, satellite altimeter and surface gravimetric data. This combination model represents a significant improvement in the modeling of the gravity field at half-wavelengths of 300 km and longer. Both models are complete to degree and order 50. The Goddard Earth Model-T3 (GEM-T3) provides more accurate computation of satellite orbital effects as well as giving superior geoidal representation from that achieved in any previous GEM. A description of the models, their development and an assessment of their accuracy is presented. The GEM-T3 model used altimeter data from previous satellite missions in estimating the orbits, geoid, and dynamic height fields. Other satellite tracking data are largely the same as was used to develop GEM-T2, but contain certain important improvements in data treatment and expanded laser tracking coverage. Over 1300 arcs of tracking data from 31 different satellites have been used in the solution. Reliable estimates of the model uncertainties via error calibration and optimal data weighting techniques are discussed.

Gaseous Elemental Mercury (GEM) Emissions from Snow Surfaces in Northern New York

PubMed Central

Maxwell, J. Alexander; Holsen, Thomas M.; Mondal, Sumona

2013-01-01

Snow surface-to-air exchange of gaseous elemental mercury (GEM) was measured using a modified Teflon fluorinated ethylene propylene (FEP) dynamic flux chamber (DFC) in a remote, open site in Potsdam, New York. Sampling was conducted during the winter months of 2011. The inlet and outlet of the DFC were coupled with a Tekran Model 2537A mercury (Hg) vapor analyzer using a Tekran Model 1110 two port synchronized sampler. The surface GEM flux ranged from −4.47 ng m−2 hr−1 to 9.89 ng m−2 hr−1. For most sample periods, daytime GEM flux was strongly correlated with solar radiation. The average nighttime GEM flux was slightly negative and was not well correlated with any of the measured meteorological variables. Preliminary, empirical models were developed to estimate GEM emissions from snow surfaces in northern New York. These models suggest that most, if not all, of the Hg deposited with and to snow is reemitted to the atmosphere. PMID:23874951

Gaseous elemental mercury (GEM) emissions from snow surfaces in northern New York.

PubMed

Maxwell, J Alexander; Holsen, Thomas M; Mondal, Sumona

2013-01-01

Snow surface-to-air exchange of gaseous elemental mercury (GEM) was measured using a modified Teflon fluorinated ethylene propylene (FEP) dynamic flux chamber (DFC) in a remote, open site in Potsdam, New York. Sampling was conducted during the winter months of 2011. The inlet and outlet of the DFC were coupled with a Tekran Model 2537A mercury (Hg) vapor analyzer using a Tekran Model 1110 two port synchronized sampler. The surface GEM flux ranged from -4.47 ng m(-2) hr(-1) to 9.89 ng m(-2) hr(-1). For most sample periods, daytime GEM flux was strongly correlated with solar radiation. The average nighttime GEM flux was slightly negative and was not well correlated with any of the measured meteorological variables. Preliminary, empirical models were developed to estimate GEM emissions from snow surfaces in northern New York. These models suggest that most, if not all, of the Hg deposited with and to snow is reemitted to the atmosphere.

Superior therapeutic efficacy of nab-paclitaxel over cremophor-based paclitaxel in locally advanced and metastatic models of human pancreatic cancer.

PubMed

Rajeshkumar, N V; Yabuuchi, Shinichi; Pai, Shweta G; Tong, Zeen; Hou, Shihe; Bateman, Scott; Pierce, Daniel W; Heise, Carla; Von Hoff, Daniel D; Maitra, Anirban; Hidalgo, Manuel

2016-08-09

Albumin-bound paclitaxel (nab-paclitaxel, nab-PTX) plus gemcitabine (GEM) combination has demonstrated efficient antitumour activity and statistically significant overall survival of patients with metastatic pancreatic ductal adenocarcinoma (PDAC) compared with GEM monotherapy. This regimen is currently approved as a standard of care treatment option for patients with metastatic PDAC. It is unclear whether cremophor-based PTX combined with GEM provide a similar level of therapeutic efficacy in PDAC. We comprehensively explored the antitumour efficacy, effect on metastatic dissemination, tumour stroma and survival advantage following GEM, PTX and nab-PTX as monotherapy or in combination with GEM in a locally advanced, and a highly metastatic orthotopic model of human PDAC. Nab-PTX treatment resulted in significantly higher paclitaxel tumour plasma ratio (1.98-fold), robust stromal depletion, antitumour efficacy (3.79-fold) and survival benefit compared with PTX treatment. PTX plus GEM treatment showed no survival gain over GEM monotherapy. However, nab-PTX in combination with GEM decreased primary tumour burden, metastatic dissemination and significantly increased median survival of animals compared with either agents alone. These therapeutic effects were accompanied by depletion of dense fibrotic tumour stroma and decreased proliferation of carcinoma cells. Notably, nab-PTX monotherapy was equivalent to nab-PTX plus GEM in providing survival advantage to mice in a highly aggressive metastatic PDAC model, indicating that nab-PTX could potentially stop the progression of late-stage pancreatic cancer. Our data confirmed that therapeutic efficacy of PTX and nab-PTX vary widely, and the contention that these agents elicit similar antitumour response was not supported. The addition of PTX to GEM showed no survival advantage, concluding that a clinical combination of PTX and GEM may unlikely to provide significant survival advantage over GEM monotherapy and may not be a viable alternative to the current standard-of-care nab-PTX plus GEM regimen for the treatment of PDAC patients.

Gravity model improvement using GEOS 3 /GEM 9 and 10/. [and Seasat altimetry data

NASA Technical Reports Server (NTRS)

Lerch, F. J.; Wagner, C. A.; Klosko, S. M.; Laubscher, R. E.

1979-01-01

Although errors in previous gravity models have produced large uncertainties in the orbital position of GEOS 3, significant improvement has been obtained with new geopotential solutions, Goddard Earth Model (GEM) 9 and 10. The GEM 9 and 10 solutions for the potential coefficients and station coordinates are presented along with a discussion of the new techniques employed. Also presented and discussed are solutions for three fundamental geodetic reference parameters, viz. the mean radius of the earth, the gravitational constant, and mean equatorial gravity. Evaluation of the gravity field is examined together with evaluation of GEM 9 and 10 for orbit determination accuracy. The major objectives of GEM 9 and 10 are achieved. GEOS 3 orbital accuracies from these models are about 1 m in their radial components for 5-day arc lengths. Both models yield significantly improved results over GEM solutions when compared to surface gravimetry, Skylab and GEOS 3 altimetry, and highly accurate BE-C (Beacon Explorer-C) laser ranges. The new values of the parameters discussed are given.

Gravitational field modes GEM 3 and 4

NASA Technical Reports Server (NTRS)

Lerch, F. J.; Wagner, C. A.; Putney, B. H.; Sandson, M. L.; Brownd, J. E.; Richardson, J. A.; Taylor, W. A.

1972-01-01

A refinement in the satellite geopotential solution for a Goddard Earth Model (GEM 3) was obtained. The solution includes the addition of two low inclination satellites, SAS at 3 deg and PEOLE at 15 deg, and is based upon 27 close earth satellites containing some 400,000 observations of electronic, laser, and optical data. In addition, a new combination satellite/gravimetry solution (GEM 4) was derived. The new model includes 61 center of mass tracking station locations with data from GRARR, Laser, MOTS, Baker-Nunn, and NWL Tranet Doppler tracking sites. Improvement was obtained for the zonal coefficients of the new models and is shown by tests on the long period perturbations of the orbits. Individual zonal coefficients agree very closely among different models that contain low inclination satellites. Tests of models with surface gravity data show that the GEM 3 satellite model has significantly better agreement with the gravimetry data than the GEM 1 satellite model, and that it also has better agreement with the gravimetry data than the 1969 SAO Standard Earth 2 model.

Comparative verification between GEM model and official aviation terminal forecasts

NASA Technical Reports Server (NTRS)

Miller, Robert G.

1988-01-01

The Generalized Exponential Markov (GEM) model uses the local standard airways observation (SAO) to predict hour-by-hour the following elements: temperature, pressure, dew point depression, first and second cloud-layer height and amount, ceiling, total cloud amount, visibility, wind, and present weather conditions. GEM is superior to persistence at all projections for all elements in a large independent sample. A minute-by-minute GEM forecasting system utilizing the Automated Weather Observation System (AWOS) is under development.

Hyaluronic acid-coated, prodrug-based nanostructured lipid carriers for enhanced pancreatic cancer therapy.

PubMed

Lu, Zhihe; Su, Jingrong; Li, Zhengrong; Zhan, Yuzhu; Ye, Decai

2017-01-01

Gemcitabine (GEM) and Baicalein (BCL) are reported to have anti-tumor effects including pancreatic cancer. Hyaluronic acid (HA) can bind to over-expressed receptors in various kinds of cancer cells. The aim of this study is to develop prodrugs containing HA, BCL and GEM, and construct nanomedicine incorporate GEM and BCL in the core and HA on the surface. This system could target the cancer cells and co-deliver the drugs. GEM-stearic acid lipid prodrug (GEM-SA) and hyaluronic acid-amino acid-baicalein prodrug (HA-AA-BCL) were synthesized. Then, GEM and BCL prodrug-based targeted nanostructured lipid carriers (HA-GEM-BCL NLCs) were prepared by the nanoprecipitation technique. The in vitro cytotoxicity studies of the NLCs were evaluated on AsPC1 pancreatic cancer cell line. In vivo anti-tumor effects were observed on the murine-bearing pancreatic cancer model. HA-GEM-BCL NLCs were effective in entering pancreatic cancer cells over-expressing HA receptors, and showed cytotoxicity of tumor cells in vitro. In vivo study revealed significant tumor growth inhibition ability of HA-GEM-BCL NLCs in murine pancreatic cancer model. It could be concluded that HA-GEM-BCL NLCs could be featured as promising co-delivery, tumor-targeted nanomedicine for the treatment of cancers.

Comment on "The shape and composition of interstellar silicate grains"

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

Bradley, J P; Ishii, H

2007-09-27

In the paper entitled 'The shape and composition of interstellar silicate grains' (A & A, 462, 667-676 (2007)), Min et al. explore non-spherical grain shape and composition in modeling the interstellar 10 and 20 {micro}m extinction features. This progression towards more realistic models is vitally important to enabling valid comparisons between dust observations and laboratory measurements. Min et al. proceed to compare their model results with GEMS (glass with embedded metals and sulfides) from IDPs (interplanetary dust particles) and to discuss the nature and origin of GEMS. Specifically, they evaluate the hypothesis of Bradley (1994) that GEMS are interstellar (IS)more » amorphous silicates. From a comparison of the mineralogy, chemical compositions, and infrared (IR) spectral properties of GEMS with their modeling results, Min et al. conclude: 'GEMS are, in general, not unprocessed leftovers from the diffuse ISM'. This conclusion is based, however, on erroneous and incomplete GEMS data. It is important to clarify first that Bradley (1994) never proposed that GEMS are unprocessed leftovers from the diffuse ISM, nor did he suggest that individual subnanogram mass GEMS are a representative sampling of the enormous mass of silicates in the diffuse ISM. Bradley (1994) simply showed that GEMS properties are consistent with those of IS amorphous silicates. It is widely accepted that circumstellar outflows are important sources of IS silicates, and whether GEMS are processed or not, the circumstellar heritage of some has been rigorously confirmed through measurements of non-solar oxygen (O) isotope abundances (Messenger et al., 2003; Floss et al., 2006). Keller et al. (2000) assert that even GEMS without detectable O isotope anomalies are probably also extrasolar IS silicates because they are embedded in carbonaceous material with non-solar D/H isotopic composition. (Much of the silicate dust in the ISM may be isotopically homogenized (Zhukovska et al., 2007)). Recent measurements show that the elemental compositions of GEMS with non-solar isotopic compositions are 'remarkably similar' to those with solar isotopic compositions (Keller & Messenger, 2007). About 80% of all isotopically anomalous IS silicates identified to date are GEMS with detectable and variable O isotopic memories of a circumstellar ancestry (Messenger, 2007). Bradley (1999) proposed that GEMS are IS silicates from 'a presolar interstellar molecular cloud, presumably the local molecular cloud from which the solar system formed'. Although based on incorrect data (detailed below), Min et al. propose that most GEMS actually formed in the presolar molecular cloud, and they further propose that none of them are IS silicates. IS silicate sources include molecular clouds, circumstellar outflows, supernovae, and even recently discovered black hole winds (Molster & Waters; 2003; Jones, 2005; Zhukovska et al. 2007; Markwick-Kemper et al. 2007). The average IS 10 {micro}m extinction feature observed along lines of sight towards the galactic center (modeled by Min et al.) presumably provides a good average for IS silicates, but it cannot distinguish amorphous silicates originating in the presolar molecular cloud from amorphous silicates originating in other interstellar molecular clouds or indeed other sources of amorphous IS silicates. Even if most GEMS accreted in the presolar molecular cloud, then they must also be representatives of some portion of the IS amorphous silicate population. Laboratory heating experiments indicate it is highly unlikely that GEMS were modified in a protoplanetary accretion disk environment (Brownlee et al. 2005). In summary, Min et al. conclude from their modeling of the shape and composition of IS silicates that the properties of GEMS are generally inconsistent with those of IS silicates. First, it has been rigorously confirmed via ion microprobe measurements that some GEMS are indeed presolar IS silicates. Second, regardless of whether GEMS, or components of GEMS, originated in presolar circumstellar outflows or a presolar molecular cloud they are all IS silicates. Third, key GEMS data reported in Min et al. are inaccurate. Had complete isotopic, chemical, mineralogical and infrared (IR) spectral properties of GEMS been considered, Min et al. may have concluded that the properties of GEMS, although not an exact match, are generally consistent with those of amorphous silicates in the ISM.« less

High resolution modeling of the upper troposphere and lower stratosphere region over the Arctic - GEM-AC simulations for the future climate with and without aviation emissions.

NASA Astrophysics Data System (ADS)

Porebska, Magdalena; Struzewska, Joanna; Kaminski, Jacek W.

2016-04-01

Upper troposphere and lower stratosphere (UTLS) region is a layer around the tropopause. Perturbation of the chemical composition in the UTLS region can impact physical and dynamical processes that can lead to changes in cloudiness, precipitation, radiative forcing, stratosphere-troposphere exchange and zonal flow. The objective of this study is to investigate the potential impacts of aviation emissions on the upper troposphere and lower stratosphere. In order to assess the impact of the aviation emissions we will focus on changes in atmospheric dynamic due to changes in chemical composition in the UTLS over the Arctic. Specifically, we will assess perturbations in the distribution of the wind, temperature and pressure fields in the UTLS region. Our study will be based on simulations using a high resolution chemical weather model for four scenarios of current (2006) and future (2050) climate: with and without aircraft emissions. The tool that we use is the GEM-AC (Global Environmental Multiscale with Atmospheric Chemistry) chemical weather model where air quality, free tropospheric and stratospheric chemistry processes are on-line and interactive in an operational weather forecast model of Environment Canada. In vertical, the model domain is defined on 70 hybrid levels with model top at 0.1 mb. The gas-phase chemistry includes detailed reactions of Ox, NOx, HOx, CO, CH4, ClOx and BrO. Also, the model can address aerosol microphysics and gas-aerosol partitioning. Aircraft emissions are from the AEDT 2006 database developed by the Federal Aviation Administration (USA) and the future climate simulations are based on RCP8.5 projection presented by the IPCC in the fifth Assessment Report AR5. Results from model simulations on a global variable grid with 0.5o x 0.5o uniform resolution over the Arctic will be presented.

A gravity model for crustal dynamics (GEM-L2)

NASA Technical Reports Server (NTRS)

Lerch, F. J.; Klosko, S. M.; Patel, G. B.; Wagner, C. A.

1985-01-01

The Laser Geodynamics Satellite (Lageos) was the first NASA satellite which was placed into orbit exclusively for laser ranging applications. Lageos was designed to permit extremely accurate measurements of the earth's rotation and the movement of the tectonic plates. The Goddard earth model, GEM-L2, was derived mainly on the basis of the precise laser ranging data taken on many satellites. Douglas et al. (1984) have demonstrated the utility of GEM-L2 in detecting the broadest ocean circulations. As Lageos data constitute the most extensive set of satellite laser observations ever collected, the incorporation of 2-1/2 years of these data into the Goddard earth models (GEM) has substantially advanced the geodynamical objectives. The present paper discusses the products of the GEM-L2 solution.

Building Single-Cell Models of Planktonic Metabolism Using PSAMM

NASA Astrophysics Data System (ADS)

Dufault-Thompson, K.; Zhang, Y.; Steffensen, J. L.

2016-02-01

The Genome-scale models (GEMs) of metabolic networks simulate the metabolic activities of individual cells by integrating omics data with biochemical and physiological measurements. GEMs were applied in the simulation of various photo-, chemo-, and heterotrophic organisms and provide significant insights into the function and evolution of planktonic cells. Despite the quick accumulation of GEMs, challenges remain in assembling the individual cell-based models into community-level models. Among various problems, the lack of consistencies in model representation and model quality checking has hindered the integration of individual GEMs and can lead to erroneous conclusions in the development of new modeling algorithms. Here, we present a Portable System for the Analysis of Metabolic Models (PSAMM). Along with the software a novel format of model representation was developed to enhance the readability of model files and permit the inclusion of heterogeneous, model-specific annotation information. A number of quality checking procedures was also implemented in PSAMM to ensure stoichiometric balance and to identify unused reactions. Using a case study of Shewanella piezotolerans WP3, we demonstrated the application of PSAMM in simulating the coupling of carbon utilization and energy production pathways under low-temperature and high-pressure stress. Applying PSAMM, we have also analyzed over 50 GEMs in the current literature and released an updated collection of the models with corrections on a number of common inconsistencies. Overall, PSAMM opens up new opportunities for integrating individual GEMs for the construction and mathematical simulation of community-level models in the scope of entire ecosystems.

GEM System: automatic prototyping of cell-wide metabolic pathway models from genomes.

PubMed

Arakawa, Kazuharu; Yamada, Yohei; Shinoda, Kosaku; Nakayama, Yoichi; Tomita, Masaru

2006-03-23

Successful realization of a "systems biology" approach to analyzing cells is a grand challenge for our understanding of life. However, current modeling approaches to cell simulation are labor-intensive, manual affairs, and therefore constitute a major bottleneck in the evolution of computational cell biology. We developed the Genome-based Modeling (GEM) System for the purpose of automatically prototyping simulation models of cell-wide metabolic pathways from genome sequences and other public biological information. Models generated by the GEM System include an entire Escherichia coli metabolism model comprising 968 reactions of 1195 metabolites, achieving 100% coverage when compared with the KEGG database, 92.38% with the EcoCyc database, and 95.06% with iJR904 genome-scale model. The GEM System prototypes qualitative models to reduce the labor-intensive tasks required for systems biology research. Models of over 90 bacterial genomes are available at our web site.

Genetically engineered mouse models of melanoma.

PubMed

Pérez-Guijarro, Eva; Day, Chi-Ping; Merlino, Glenn; Zaidi, M Raza

2017-06-01

Melanoma is a complex disease that exhibits highly heterogeneous etiological, histopathological, and genetic features, as well as therapeutic responses. Genetically engineered mouse (GEM) models provide powerful tools to unravel the molecular mechanisms critical for melanoma development and drug resistance. Here, we expound briefly the basis of the mouse modeling design, the available technology for genetic engineering, and the aspects influencing the use of GEMs to model melanoma. Furthermore, we describe in detail the currently available GEM models of melanoma. Cancer 2017;123:2089-103. © 2017 American Cancer Society. © 2017 American Cancer Society.

Development of a transplantable glioma tumour model from genetically engineered mice: MRI/MRS/MRSI characterisation.

PubMed

Ciezka, Magdalena; Acosta, Milena; Herranz, Cristina; Canals, Josep M; Pumarola, Martí; Candiota, Ana Paula; Arús, Carles

2016-08-01

The initial aim of this study was to generate a transplantable glial tumour model of low-intermediate grade by disaggregation of a spontaneous tumour mass from genetically engineered models (GEM). This should result in an increased tumour incidence in comparison to GEM animals. An anaplastic oligoastrocytoma (OA) tumour of World Health Organization (WHO) grade III was obtained from a female GEM mouse with the S100β-v-erbB/inK4a-Arf (+/-) genotype maintained in the C57BL/6 background. The tumour tissue was disaggregated; tumour cells from it were grown in aggregates and stereotactically injected into C57BL/6 mice. Tumour development was followed using Magnetic Resonance Imaging (MRI), while changes in the metabolomics pattern of the masses were evaluated by Magnetic Resonance Spectroscopy/Spectroscopic Imaging (MRS/MRSI). Final tumour grade was evaluated by histopathological analysis. The total number of tumours generated from GEM cells from disaggregated tumour (CDT) was 67 with up to 100 % penetrance, as compared to 16 % in the local GEM model, with an average survival time of 66 ± 55 days, up to 4.3-fold significantly higher than the standard GL261 glioblastoma (GBM) tumour model. Tumours produced by transplantation of cells freshly obtained from disaggregated GEM tumour were diagnosed as WHO grade III anaplastic oligodendroglioma (ODG) and OA, while tumours produced from a previously frozen sample were diagnosed as WHO grade IV GBM. We successfully grew CDT and generated tumours from a grade III GEM glial tumour. Freezing and cell culture protocols produced progression to grade IV GBM, which makes the developed transplantable model qualify as potential secondary GBM model in mice.

Facilitation of endoglin-targeting cancer therapy by development/utilization of a novel genetically engineered mouse model expressing humanized endoglin (CD105).

PubMed

Toi, Hirofumi; Tsujie, Masanori; Haruta, Yuro; Fujita, Kanako; Duzen, Jill; Seon, Ben K

2015-01-15

Endoglin (ENG) is a TGF-β coreceptor and essential for vascular development and angiogenesis. A chimeric antihuman ENG (hENG) monoclonal antibody (mAb) c-SN6j (also known as TRC105) shows promising safety and clinical efficacy features in multiple clinical trials of patients with various advanced solid tumors. Here we developed a novel genetically engineered mouse model to optimize the ENG-targeting clinical trials. We designed a new targeting vector that contains exons 4-8 of hENG gene to generate novel genetically engineered mice (GEMs) expressing functional human/mouse chimeric (humanized) ENG with desired epitopes. Genotyping of the generated mice confirmed that we generated the desired GEMs. Immunohistochemical analysis demonstrated that humanized ENG protein of the GEMs expresses epitopes defined by 7 of our 8 anti-hENG mAbs tested. Surprisingly the homozygous GEMs develop normally and are healthy. Established breast and colon tumors as well as metastasis and tumor microvessels in the GEMs were effectively suppressed by systemic administration of anti-hENG mAbs. Additionally, test result indicates that synergistic potentiation of antitumor efficacy can be induced by simultaneous targeting of two distinct epitopes by anti-hENG mAbs. Sorafenib and capecitabine also showed antitumor efficacy in the GEMs. The presented novel GEMs are the first GEMs that express the targetable humanized ENG. Test results indicate utility of the GEMs for the clinically relevant studies. Additionally, we generated GEMs expressing a different humanized ENG containing exons 5-6 of hENG gene, and the homozygous GEMs develop normally and are healthy. © 2014 UICC.

Grohar: Automated Visualization of Genome-Scale Metabolic Models and Their Pathways.

PubMed

Moškon, Miha; Zimic, Nikolaj; Mraz, Miha

2018-05-01

Genome-scale metabolic models (GEMs) have become a powerful tool for the investigation of the entire metabolism of the organism in silico. These models are, however, often extremely hard to reconstruct and also difficult to apply to the selected problem. Visualization of the GEM allows us to easier comprehend the model, to perform its graphical analysis, to find and correct the faulty relations, to identify the parts of the system with a designated function, etc. Even though several approaches for the automatic visualization of GEMs have been proposed, metabolic maps are still manually drawn or at least require large amount of manual curation. We present Grohar, a computational tool for automatic identification and visualization of GEM (sub)networks and their metabolic fluxes. These (sub)networks can be specified directly by listing the metabolites of interest or indirectly by providing reference metabolic pathways from different sources, such as KEGG, SBML, or Matlab file. These pathways are identified within the GEM using three different pathway alignment algorithms. Grohar also supports the visualization of the model adjustments (e.g., activation or inhibition of metabolic reactions) after perturbations are induced.

Genome-Scale Metabolic Modeling of Archaea Lends Insight into Diversity of Metabolic Function

PubMed Central

2017-01-01

Decades of biochemical, bioinformatic, and sequencing data are currently being systematically compiled into genome-scale metabolic reconstructions (GEMs). Such reconstructions are knowledge-bases useful for engineering, modeling, and comparative analysis. Here we review the fifteen GEMs of archaeal species that have been constructed to date. They represent primarily members of the Euryarchaeota with three-quarters comprising representative of methanogens. Unlike other reviews on GEMs, we specially focus on archaea. We briefly review the GEM construction process and the genealogy of the archaeal models. The major insights gained during the construction of these models are then reviewed with specific focus on novel metabolic pathway predictions and growth characteristics. Metabolic pathway usage is discussed in the context of the composition of each organism's biomass and their specific energy and growth requirements. We show how the metabolic models can be used to study the evolution of metabolism in archaea. Conservation of particular metabolic pathways can be studied by comparing reactions using the genes associated with their enzymes. This demonstrates the utility of GEMs to evolutionary studies, far beyond their original purpose of metabolic modeling; however, much needs to be done before archaeal models are as extensively complete as those for bacteria. PMID:28133437

An improved model of the Earth's gravity field - GEM-T3

NASA Technical Reports Server (NTRS)

Nerem, R. S.; Lerch, F. J.; Putney, B. H.; Klosko, S. M.; Patel, G. B.; Williamson, R. G.; Pavlis, E. C.

1992-01-01

An improved model of the Earth's gravitational field is developed from a combination of conventional satellite tracking, satellite altimeter measurements, and surface gravimetric data (GEM-T3). This model gives improved performance for the computation of satellite orbital effects as well as a superior representation of the geoid from that achieved in any previous Goddard Earth Model. The GEM-T3 model uses altimeter data directly to define the orbits, geoid, and dynamic height fields. Altimeter data acquired during the GEOS-3 (1975-1976), SEASAT (1978), and GEOSAT (1986-1987) missions were used to compute GEM-T3. In order to accommodate the non-gravitational signal mapped by these altimeters, spherical harmonic models of the dynamic height of the ocean surface were recovered for each mission simultaneously with the gravitational field. The tracking data utilized in the solution includes more than 1300 arcs of data encompassing 31 different satellites. The observational data base is highly dependent on SLR, but also includes TRANET Doppler, optical, S-Band average range-rate and satellite-to-satellite tracking acquired between ATS-6 and GEOS-3. The GEM-T3 model has undergone extensive error calibration.

A COMSOL-GEMS interface for modeling coupled reactive-transport geochemical processes

NASA Astrophysics Data System (ADS)

Azad, Vahid Jafari; Li, Chang; Verba, Circe; Ideker, Jason H.; Isgor, O. Burkan

2016-07-01

An interface was developed between COMSOL MultiphysicsTM finite element analysis software and (geo)chemical modeling platform, GEMS, for the reactive-transport modeling of (geo)chemical processes in variably saturated porous media. The two standalone software packages are managed from the interface that uses a non-iterative operator splitting technique to couple the transport (COMSOL) and reaction (GEMS) processes. The interface allows modeling media with complex chemistry (e.g. cement) using GEMS thermodynamic database formats. Benchmark comparisons show that the developed interface can be used to predict a variety of reactive-transport processes accurately. The full functionality of the interface was demonstrated to model transport processes, governed by extended Nernst-Plank equation, in Class H Portland cement samples in high pressure and temperature autoclaves simulating systems that are used to store captured carbon dioxide (CO2) in geological reservoirs.

Unsupervised Gaussian Mixture-Model With Expectation Maximization for Detecting Glaucomatous Progression in Standard Automated Perimetry Visual Fields.

PubMed

Yousefi, Siamak; Balasubramanian, Madhusudhanan; Goldbaum, Michael H; Medeiros, Felipe A; Zangwill, Linda M; Weinreb, Robert N; Liebmann, Jeffrey M; Girkin, Christopher A; Bowd, Christopher

2016-05-01

To validate Gaussian mixture-model with expectation maximization (GEM) and variational Bayesian independent component analysis mixture-models (VIM) for detecting glaucomatous progression along visual field (VF) defect patterns (GEM-progression of patterns (POP) and VIM-POP). To compare GEM-POP and VIM-POP with other methods. GEM and VIM models separated cross-sectional abnormal VFs from 859 eyes and normal VFs from 1117 eyes into abnormal and normal clusters. Clusters were decomposed into independent axes. The confidence limit (CL) of stability was established for each axis with a set of 84 stable eyes. Sensitivity for detecting progression was assessed in a sample of 83 eyes with known progressive glaucomatous optic neuropathy (PGON). Eyes were classified as progressed if any defect pattern progressed beyond the CL of stability. Performance of GEM-POP and VIM-POP was compared to point-wise linear regression (PLR), permutation analysis of PLR (PoPLR), and linear regression (LR) of mean deviation (MD), and visual field index (VFI). Sensitivity and specificity for detecting glaucomatous VFs were 89.9% and 93.8%, respectively, for GEM and 93.0% and 97.0%, respectively, for VIM. Receiver operating characteristic (ROC) curve areas for classifying progressed eyes were 0.82 for VIM-POP, 0.86 for GEM-POP, 0.81 for PoPLR, 0.69 for LR of MD, and 0.76 for LR of VFI. GEM-POP was significantly more sensitive to PGON than PoPLR and linear regression of MD and VFI in our sample, while providing localized progression information. Detection of glaucomatous progression can be improved by assessing longitudinal changes in localized patterns of glaucomatous defect identified by unsupervised machine learning.

Modeling prostate cancer in mice: something old, something new, something premalignant, something metastatic.

PubMed

Irshad, Shazia; Abate-Shen, Cory

2013-06-01

More than 15 years ago, the first generation of genetically engineered mouse (GEM) models of prostate cancer was introduced. These transgenic models utilized prostate-specific promoters to express SV40 oncogenes specifically in prostate epithelium. Since the description of these initial models, there have been a plethora of GEM models of prostate cancer representing various perturbations of oncogenes or tumor suppressors, either alone or in combination. This review describes these GEM models, focusing on their relevance for human prostate cancer and highlighting their strengths and limitations, as well as opportunities for the future.

An improved model of the Earth's gravitational field: GEM-T1

NASA Technical Reports Server (NTRS)

Marsh, J. G.; Lerch, F. J.; Christodoulidis, D. C.; Putney, B. H.; Felsentreger, T. L.; Sanchez, B. V.; Smith, D. E.; Klosko, S. M.; Martin, T. V.; Pavlis, E. C.

1987-01-01

Goddard Earth Model T1 (GEM-T1), which was developed from an analysis of direct satellite tracking observations, is the first in a new series of such models. GEM-T1 is complete to degree and order 36. It was developed using consistent reference parameters and extensive earth and ocean tidal models. It was simultaneously solved for gravitational and tidal terms, earth orientation parameters, and the orbital parameters of 580 individual satellite arcs. The solution used only satellite tracking data acquired on 17 different satellites and is predominantly based upon the precise laser data taken by third generation systems. In all, 800,000 observations were used. A major improvement in field accuracy was obtained. For marine geodetic applications, long wavelength geoidal modeling is twice as good as in earlier satellite-only GEM models. Orbit determination accuracy has also been substantially advanced over a wide range of satellites that have been tested.

The GEMS Model of Volunteer Administration.

ERIC Educational Resources Information Center

Culp, Ken, III; Deppe, Catherine A.; Castillo, Jaime X.; Wells, Betty J.

1998-01-01

Describes GEMS, a spiral model that profiles volunteer administration. Components include Generate, Educate, Mobilize, and Sustain, four sets of processes that span volunteer recruitment and selection to retention or disengagement. (SK)

Use of Excel ion exchange equilibrium solver with WinGEMS to model and predict NPE distribution in the Mead/Westvaco Evandale, TX, hardwood bleach plant

Treesearch

Christopher Litvay; Alan Rudie; Peter Hart

2003-01-01

An Excel spreadsheet developed to solve the ion-exchange equilibrium in wood pulps has been linked by dynamic data exchange to WinGEMS and used to model the non-process elements in the hardwood bleach plant of the Mead/Westvaco Evandale mill. Pulp and filtrate samples were collected from the diffusion washers and final wash press of the bleach plant. A WinGEMS model of...

The Landscape of Somatic Chromosomal Copy Number Aberrations in GEM Models of Prostate Carcinoma

PubMed Central

Bianchi-Frias, Daniella; Hernandez, Susana A.; Coleman, Roger; Wu, Hong; Nelson, Peter S.

2015-01-01

Human prostate cancer (PCa) is known to harbor recurrent genomic aberrations consisting of chromosomal losses, gains, rearrangements and mutations that involve oncogenes and tumor suppressors. Genetically engineered mouse (GEM) models have been constructed to assess the causal role of these putative oncogenic events and provide molecular insight into disease pathogenesis. While GEM models generally initiate neoplasia by manipulating a single gene, expression profiles of GEM tumors typically comprise hundreds of transcript alterations. It is unclear whether these transcriptional changes represent the pleiotropic effects of single oncogenes, and/or cooperating genomic or epigenomic events. Therefore, it was determined if structural chromosomal alterations occur in GEM models of PCa and whether the changes are concordant with human carcinomas. Whole genome array-based comparative genomic hybridization (CGH) was used to identify somatic chromosomal copy number aberrations (SCNAs) in the widely used TRAMP, Hi-Myc, Pten-null and LADY GEM models. Interestingly, very few SCNAs were identified and the genomic architecture of Hi-Myc, Pten-null and LADY tumors were essentially identical to the germline. TRAMP neuroendocrine carcinomas contained SCNAs, which comprised three recurrent aberrations including a single copy loss of chromosome 19 (encoding Pten). In contrast, cell lines derived from the TRAMP, Hi-Myc, and Pten-null tumors were notable for numerous SCNAs that included copy gains of chromosome 15 (encoding Myc) and losses of chromosome 11 (encoding p53). PMID:25298407

The General Ensemble Biogeochemical Modeling System (GEMS) and its applications to agricultural systems in the United States: Chapter 18

USGS Publications Warehouse

Liu, Shuguang; Tan, Zhengxi; Chen, Mingshi; Liu, Jinxun; Wein, Anne; Li, Zhengpeng; Huang, Shengli; Oeding, Jennifer; Young, Claudia; Verma, Shashi B.; Suyker, Andrew E.; Faulkner, Stephen P.

2012-01-01

The General Ensemble Biogeochemical Modeling System (GEMS) was es in individual models, it uses multiple site-scale biogeochemical models to perform model simulations. Second, it adopts Monte Carlo ensemble simulations of each simulation unit (one site/pixel or group of sites/pixels with similar biophysical conditions) to incorporate uncertainties and variability (as measured by variances and covariance) of input variables into model simulations. In this chapter, we illustrate the applications of GEMS at the site and regional scales with an emphasis on incorporating agricultural practices. Challenges in modeling soil carbon dynamics and greenhouse emissions are also discussed.

Unique attributes of cyanobacterial metabolism revealed by improved genome-scale metabolic modeling and essential gene analysis

DOE PAGES

Broddrick, Jared T.; Rubin, Benjamin E.; Welkie, David G.; ...

2016-12-20

The model cyanobacterium, Synechococcus elongatus PCC 7942, is a genetically tractable obligate phototroph that is being developed for the bioproduction of high-value chemicals. Genome-scale models (GEMs) have been successfully used to assess and engineer cellular metabolism; however, GEMs of phototrophic metabolism have been limited by the lack of experimental datasets for model validation and the challenges of incorporating photon uptake. In this paper, we develop a GEM of metabolism in S. elongatus using random barcode transposon site sequencing (RB-TnSeq) essential gene and physiological data specific to photoautotrophic metabolism. The model explicitly describes photon absorption and accounts for shading, resulting inmore » the characteristic linear growth curve of photoautotrophs. GEM predictions of gene essentiality were compared with data obtained from recent dense-transposon mutagenesis experiments. This dataset allowed major improvements to the accuracy of the model. Furthermore, discrepancies between GEM predictions and the in vivo dataset revealed biological characteristics, such as the importance of a truncated, linear TCA pathway, low flux toward amino acid synthesis from photorespiration, and knowledge gaps within nucleotide metabolism. Finally, coupling of strong experimental support and photoautotrophic modeling methods thus resulted in a highly accurate model of S. elongatus metabolism that highlights previously unknown areas of S. elongatus biology.« less

Unique attributes of cyanobacterial metabolism revealed by improved genome-scale metabolic modeling and essential gene analysis

PubMed Central

Broddrick, Jared T.; Rubin, Benjamin E.; Welkie, David G.; Du, Niu; Mih, Nathan; Diamond, Spencer; Lee, Jenny J.; Golden, Susan S.; Palsson, Bernhard O.

2016-01-01

The model cyanobacterium, Synechococcus elongatus PCC 7942, is a genetically tractable obligate phototroph that is being developed for the bioproduction of high-value chemicals. Genome-scale models (GEMs) have been successfully used to assess and engineer cellular metabolism; however, GEMs of phototrophic metabolism have been limited by the lack of experimental datasets for model validation and the challenges of incorporating photon uptake. Here, we develop a GEM of metabolism in S. elongatus using random barcode transposon site sequencing (RB-TnSeq) essential gene and physiological data specific to photoautotrophic metabolism. The model explicitly describes photon absorption and accounts for shading, resulting in the characteristic linear growth curve of photoautotrophs. GEM predictions of gene essentiality were compared with data obtained from recent dense-transposon mutagenesis experiments. This dataset allowed major improvements to the accuracy of the model. Furthermore, discrepancies between GEM predictions and the in vivo dataset revealed biological characteristics, such as the importance of a truncated, linear TCA pathway, low flux toward amino acid synthesis from photorespiration, and knowledge gaps within nucleotide metabolism. Coupling of strong experimental support and photoautotrophic modeling methods thus resulted in a highly accurate model of S. elongatus metabolism that highlights previously unknown areas of S. elongatus biology. PMID:27911809

Unique attributes of cyanobacterial metabolism revealed by improved genome-scale metabolic modeling and essential gene analysis

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

Broddrick, Jared T.; Rubin, Benjamin E.; Welkie, David G.

The model cyanobacterium, Synechococcus elongatus PCC 7942, is a genetically tractable obligate phototroph that is being developed for the bioproduction of high-value chemicals. Genome-scale models (GEMs) have been successfully used to assess and engineer cellular metabolism; however, GEMs of phototrophic metabolism have been limited by the lack of experimental datasets for model validation and the challenges of incorporating photon uptake. In this paper, we develop a GEM of metabolism in S. elongatus using random barcode transposon site sequencing (RB-TnSeq) essential gene and physiological data specific to photoautotrophic metabolism. The model explicitly describes photon absorption and accounts for shading, resulting inmore » the characteristic linear growth curve of photoautotrophs. GEM predictions of gene essentiality were compared with data obtained from recent dense-transposon mutagenesis experiments. This dataset allowed major improvements to the accuracy of the model. Furthermore, discrepancies between GEM predictions and the in vivo dataset revealed biological characteristics, such as the importance of a truncated, linear TCA pathway, low flux toward amino acid synthesis from photorespiration, and knowledge gaps within nucleotide metabolism. Finally, coupling of strong experimental support and photoautotrophic modeling methods thus resulted in a highly accurate model of S. elongatus metabolism that highlights previously unknown areas of S. elongatus biology.« less

Improving the Canadian Precipitation Analysis Estimates through an Observing System Simulation Experiment

NASA Astrophysics Data System (ADS)

Abbasnezhadi, K.; Rasmussen, P. F.; Stadnyk, T.

2014-12-01

To gain a better understanding of the spatiotemporal distribution of rainfall over the Churchill River basin, this study was undertaken. The research incorporates gridded precipitation data from the Canadian Precipitation Analysis (CaPA) system. CaPA has been developed by Environment Canada and provides near real-time precipitation estimates on a 10 km by 10 km grid over North America at a temporal resolution of 6 hours. The spatial fields are generated by combining forecasts from the Global Environmental Multiscale (GEM) model with precipitation observations from the network of synoptic weather stations. CaPA's skill is highly influenced by the number of weather stations in the region of interest as well as by the quality of the observations. In an attempt to evaluate the performance of CaPA as a function of the density of the weather station network, a dual-stage design algorithm to simulate CaPA is proposed which incorporates generated weather fields. More specifically, we are adopting a controlled design algorithm which is generally known as Observing System Simulation Experiment (OSSE). The advantage of using the experiment is that one can define reference precipitation fields assumed to represent the true state of rainfall over the region of interest. In the first stage of the defined OSSE, a coupled stochastic model of precipitation and temperature gridded fields is calibrated and validated. The performance of the generator is then validated by comparing model statistics with observed statistics and by using the generated samples as input to the WATFLOOD™ hydrologic model. In the second stage of the experiment, in order to account for the systematic error of station observations and GEM fields, representative errors are to be added to the reference field using by-products of CaPA's variographic analysis. These by-products explain the variance of station observations and background errors.

OMI satellite observations of decadal changes in ground-level sulfur dioxide over North America

NASA Astrophysics Data System (ADS)

Kharol, Shailesh K.; McLinden, Chris A.; Sioris, Christopher E.; Shephard, Mark W.; Fioletov, Vitali; van Donkelaar, Aaron; Philip, Sajeev; Martin, Randall V.

2017-05-01

Sulfur dioxide (SO2) has a significant impact on the environment and human health. We estimated ground-level sulfur dioxide (SO2) concentrations from the Ozone Monitoring Instrument (OMI) using SO2 profiles from the Global Environmental Multi-scale - Modelling Air quality and CHemistry (GEM-MACH) model over North America for the period of 2005-2015. OMI-derived ground-level SO2 concentrations (r = 0. 61) and trends (r = 0. 74) correlated well with coincident in situ measurements from air quality networks over North America. We found a strong decreasing trend in coincidently sampled ground-level SO2 from OMI (-81 ± 19 %) and in situ measurements (-86 ± 13 %) over the eastern US for the period of 2005-2015, which reflects the implementation of stricter pollution control laws, including flue-gas desulfurization (FGD) devices in power plants. The spatially and temporally contiguous OMI-derived ground-level SO2 concentrations can be used to assess the impact of long-term exposure to SO2 on the health of humans and the environment.

Greenhouse Gas Emissions Model (GEM) for Medium- and Heavy-Duty Vehicle Compliance

EPA Pesticide Factsheets

EPA’s Greenhouse Gas Emissions Model (GEM) is a free, desktop computer application that estimates the greenhouse gas (GHG) emissions and fuel efficiency performance of specific aspects of heavy-duty vehicles.

Selective efficacy of zoledronic acid on metastasis in a patient-derived orthotopic xenograph (PDOX) nude-mouse model of human pancreatic cancer.

PubMed

Hiroshima, Yukihiko; Maawy, Ali A; Katz, Matthew H G; Fleming, Jason B; Bouvet, Michael; Endo, Itaru; Hoffman, Robert M

2015-03-01

Patient-derived orthotopic xenograft (PDOX) nude-mouse models replicate the behavior of clinical cancer, including metastasis. The objective of the study was to determine the efficacy of zoledronic acid (ZA) on metastasis of a patient-derived orthotopic xenograft (PDOX) nude-mouse model of pancreatic cancer. In the present study, we examined the efficacy of ZA on pancreatic cancer growth and metastasis in a PDOX nude-mouse model. ZA monotherapy did not significantly suppress primary tumor growth. However, the primary tumor weight of gemcitabine (GEM) and combination GEM + ZA-treated mice was significantly decreased compared to the control group (GEM: P = 0.003; GEM + ZA: P = 0.002). The primary tumor weight of GEM + ZA-treated mice was significantly decreased compared to GEM-treated mice (P = 0.016). The metastasis weight decreased in ZA- or GEM-treated mice compared to the control group (ZA: P = 0.009; GEM: P = 0.007. No metastasis was detected in combination GEM + ZA-treated mice compared to the control group (GEM + ZA; P = 0.005). The results of the present study indicate that ZA can selectively target metastasis in a pancreatic cancer PDOX model and that the combination of ZA and GEM should be evaluated clinically in the near future for this highly treatment-resistant disease. © 2014 Wiley Periodicals, Inc.

C4GEM, a Genome-Scale Metabolic Model to Study C4 Plant Metabolism1[W][OA

PubMed Central

de Oliveira Dal’Molin, Cristiana Gomes; Quek, Lake-Ee; Palfreyman, Robin William; Brumbley, Stevens Michael; Nielsen, Lars Keld

2010-01-01

Leaves of C4 grasses (such as maize [Zea mays], sugarcane [Saccharum officinarum], and sorghum [Sorghum bicolor]) form a classical Kranz leaf anatomy. Unlike C3 plants, where photosynthetic CO2 fixation proceeds in the mesophyll (M), the fixation process in C4 plants is distributed between two cell types, the M cell and the bundle sheath (BS) cell. Here, we develop a C4 genome-scale model (C4GEM) for the investigation of flux distribution in M and BS cells during C4 photosynthesis. C4GEM, to our knowledge, is the first large-scale metabolic model that encapsulates metabolic interactions between two different cell types. C4GEM is based on the Arabidopsis (Arabidopsis thaliana) model (AraGEM) but has been extended by adding reactions and transporters responsible to represent three different C4 subtypes (NADP-ME [for malic enzyme], NAD-ME, and phosphoenolpyruvate carboxykinase). C4GEM has been validated for its ability to synthesize 47 biomass components and consists of 1,588 unique reactions, 1,755 metabolites, 83 interorganelle transporters, and 29 external transporters (including transport through plasmodesmata). Reactions in the common C4 model have been associated with well-annotated C4 species (NADP-ME subtypes): 3,557 genes in sorghum, 11,623 genes in maize, and 3,881 genes in sugarcane. The number of essential reactions not assigned to genes is 131, 135, and 156 in sorghum, maize, and sugarcane, respectively. Flux balance analysis was used to assess the metabolic activity in M and BS cells during C4 photosynthesis. Our simulations were consistent with chloroplast proteomic studies, and C4GEM predicted the classical C4 photosynthesis pathway and its major effect in organelle function in M and BS. The model also highlights differences in metabolic activities around photosystem I and photosystem II for three different C4 subtypes. Effects of CO2 leakage were also explored. C4GEM is a viable framework for in silico analysis of cell cooperation between M and BS cells during photosynthesis and can be used to explore C4 plant metabolism. PMID:20974891

Acute and delayed toxicity of gemcitabine administered during isolated lung perfusion: a preclinical dose-escalation study in pigs.

PubMed

Pagès, Pierre-Benoit; Derangere, Valentin; Bouchot, Olivier; Magnin, Guy; Charon-Barra, Céline; Lokiec, François; Ghiringhelli, François; Bernard, Alain

2015-08-01

Colorectal cancer is the third most commonly diagnosed cancer worldwide, with up to 25% of patients presenting with metastases at the time of diagnosis. Despite pulmonary metastasectomy many patients go on to develop pulmonary recurrence, which might be linked to the presence of lung micrometastases. In this setting, the adjuvant administration of high-dose chemotherapy by isolated lung perfusion (ILP) has shown encouraging results. However, the tolerance to and efficacy of modern gemcitabine (GEM)-based chemotherapy regimens during adjuvant ILP remain unknown. We conducted a dose-escalating preclinical study to evaluate the immediate and delayed toxicity of GEM in a pig model to define dose-limiting toxicity (DLT) and maximum tolerated concentration. Twenty-three pigs were given increasing concentrations of GEM during ILP, and were awakened at the end of the procedure. The concentrations of GEM were 40, 80, 160, 320, 640 and 1280 µg/ml. Serum and lung samples were taken to measure GEM concentrations. Pulmonary damage was evaluated by histological examination and cleaved caspase-3 detection. Immediate and delayed (1 month) toxicity were recorded. All of the animals underwent successful ILP with GEM. No systemic leak was observed. The three pigs that received a concentration of GEM of 1280 µg/ml died of hypoxia after lung recirculation at the end of the procedure. Eleven pigs survived for 1 month. Major lung toxicity was observed for the concentration of GEM of 640 µg/ml, both at the end of the procedure and after 1 month. DLT was defined at the concentration of 640 µg/ml and the maximum tolerated dose (MTD) was defined at the concentration of 320 µg/ml. ILP with GEM is a safe and reproducible technique in this large-animal model, which includes 1 month of survival. The MTD in this pig model was a concentration of GEM of 320 µg/ml. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

A geopotential model from satellite tracking, altimeter, and surface gravity data: GEM-T3

NASA Technical Reports Server (NTRS)

Lerch, F. J.; Nerem, R. S.; Putney, B. H.; Felsentreger, T. L.; Sanchez, B. V.; Marshall, J. A.; Klosko, S. M.; Patel, G. B.; Williamson, R. G.; Chinn, D. S.

1994-01-01

An improved model of Earth's gravitational field, Goddard Earth Model T-3 (GEM-T3), has been developed from a combination of satellite tracking, satellite altimeter, and surface gravimetric data. GEM-T3 provides a significant improvement in the modeling of the gravity field at half wavelengths of 400 km and longer. This model, complete to degree and order 50, yields more accurate satellite orbits and an improved geoid representation than previous Goddard Earth Models. GEM-T3 uses altimeter data from GEOS 3 (1975-1976), Seasat (1978) and Geosat (1986-1987). Tracking information used in the solution includes more than 1300 arcs of data encompassing 31 different satellites. The recovery of the long-wavelength components of the solution relies mostly on highly precise satellite laser ranging (SLR) data, but also includes Tracking Network (TRANET) Doppler, optical, and satellite-to-satellite tracking acquired between the ATS 6 and GEOS 3 satellites. The main advances over GEM-T2 (beyond the inclusion of altimeter and surface gravity information which is essential for the resolution of the shorter wavelength geoid) are some improved tracking data analysis approaches and additional SLR data. Although the use of altimeter data has greatly enhanced the modeling of the ocean geoid between 65 deg N and 60 deg S latitudes in GEM-T3, the lack of accurate detailed surface gravimetry leaves poor geoid resolution over many continental regions of great tectonic interest (e.g., Himalayas, Andes). Estimates of polar motion, tracking station coordinates, and long-wavelength ocean tidal terms were also made (accounting for 6330 parameters). GEM-T3 has undergone error calibration using a technique based on subset solutions to produce reliable error estimates. The calibration is based on the condition that the expected mean square deviation of a subset gravity solution from the full set values is predicted by the solutions' error covariances. Data weights are iteratively adjusted until this condition for the error calibration is satisfied. In addition, gravity field tests were performed on strong satellite data sets withheld from the solution (thereby ensuring their independence). In these tests, the performance of the subset models on the withheld observations is compared to error projections based on their calibrated error covariances. These results demonstrate that orbit accuracy projections are reliable for new satellites which were not included in GEM-T3.

Public release of the ISC-GEM Global Instrumental Earthquake Catalogue (1900-2009)

USGS Publications Warehouse

Storchak, Dmitry A.; Di Giacomo, Domenico; Bondára, István; Engdahl, E. Robert; Harris, James; Lee, William H.K.; Villaseñor, Antonio; Bormann, Peter

2013-01-01

The International Seismological Centre–Global Earthquake Model (ISC–GEM) Global Instrumental Earthquake Catalogue (1900–2009) is the result of a special effort to substantially extend and improve currently existing global catalogs to serve the requirements of specific user groups who assess and model seismic hazard and risk. The data from the ISC–GEM Catalogue would be used worldwide yet will prove absolutely essential in those regions where a high seismicity level strongly correlates with a high population density.

An improved error assessment for the GEM-T1 gravitational model

NASA Technical Reports Server (NTRS)

Lerch, F. J.; Marsh, J. G.; Klosko, S. M.; Pavlis, E. C.; Patel, G. B.; Chinn, D. S.; Wagner, C. A.

1988-01-01

Several tests were designed to determine the correct error variances for the Goddard Earth Model (GEM)-T1 gravitational solution which was derived exclusively from satellite tracking data. The basic method employs both wholly independent and dependent subset data solutions and produces a full field coefficient estimate of the model uncertainties. The GEM-T1 errors were further analyzed using a method based upon eigenvalue-eigenvector analysis which calibrates the entire covariance matrix. Dependent satellite and independent altimetric and surface gravity data sets, as well as independent satellite deep resonance information, confirm essentially the same error assessment. These calibrations (utilizing each of the major data subsets within the solution) yield very stable calibration factors which vary by approximately 10 percent over the range of tests employed. Measurements of gravity anomalies obtained from altimetry were also used directly as observations to show that GEM-T1 is calibrated. The mathematical representation of the covariance error in the presence of unmodeled systematic error effects in the data is analyzed and an optimum weighting technique is developed for these conditions. This technique yields an internal self-calibration of the error model, a process which GEM-T1 is shown to approximate.

The histone methyltransferase G9a as a therapeutic target to override gemcitabine resistance in pancreatic cancer

PubMed Central

Pan, Mei-Ren; Hsu, Ming-Chuan; Luo, Chi-Wen; Chen, Li-Tzong; Shan, Yan-Shen; Hung, Wen-Chun

2016-01-01

Gemcitabine (GEM) resistance is a critical issue for pancreatic cancer treatment. The involvement of epigenetic modification in GEM resistance is still unclear. We established a GEM-resistant subline PANC-1-R from the parental PANC-1 pancreatic cancer cells and found the elevation of various chromatin-modifying enzymes including G9a in GEM-resistant cells. Ectopic expression of G9a in PANC-1 cells increased GEM resistance while inactivation of G9a in PANC-1-R cells reduced it. Challenge of PANC-1 cells with GEM increased the expression of stemness markers including CD133, nestin and Lgr5 and promoted sphere forming activity suggesting chemotherapy enriched cancer cells with stem-like properties. Inhibition of G9a in PANC-1-R cells reduced stemness and invasiveness and sensitized the cells to GEM. We revealed interleukin-8 (IL-8) is a downstream effector of G9a to increase GEM resistance. G9a-overexpressing PANC-1-R cells exhibited autocrine IL-8/CXCR1/2 stimulation to increase GEM resistance which could be decreased by anti-IL-8 antibody and G9a inhibitor. IL-8 released by cancer cells also activated pancreatic stellate cell (PSC) to increase GEM resistance. In orthotopic animal model, GEM could not suppress tumor growth of PANC-1-R cells and eventually promoted tumor metastasis. Combination with G9a inhibitor and GEM reduced tumor growth, metastasis, IL-8 expression and PSC activation in animals. Finally, we showed that overexpression of G9a correlated with poor survival and early recurrence in pancreatic cancer patients. Collectively, our results suggest G9a is a therapeutic target to override GEM resistance in the treatment of pancreatic cancer. PMID:27531902

Toward improved guideline quality: using the COGS statement with GEM.

PubMed

Shiffman, Richard N; Michel, Georges

2004-01-01

The Conference on Guideline Standardization (COGS) was convened to create a standardized documentation checklist for clinical practice guidelines in an effort to promote guideline quality and facilitate implementation. The statement was created by a multidisciplinary panel using a rigorous consensus development methodology. The Guideline Elements Model (GEM) provides a standardized approach to representing guideline documents using XML. In this work, we demonstrate the sufficiency of GEM for describing COGS components. Using the mapping between COGS and GEM elements we built an XSLT application to examine a guideline's adherence (or non-adherence) to the COGS checklist. Once a guideline has been marked up according to the GEM hierarchy, its knowledge content can be reused in multiple ways.

Sensitivity analysis of the GEMS soil organic carbon model to land cover land use classification uncertainties under different climate scenarios in Senegal

USGS Publications Warehouse

Dieye, A.M.; Roy, David P.; Hanan, N.P.; Liu, S.; Hansen, M.; Toure, A.

2012-01-01

Spatially explicit land cover land use (LCLU) change information is needed to drive biogeochemical models that simulate soil organic carbon (SOC) dynamics. Such information is increasingly being mapped using remotely sensed satellite data with classification schemes and uncertainties constrained by the sensing system, classification algorithms and land cover schemes. In this study, automated LCLU classification of multi-temporal Landsat satellite data were used to assess the sensitivity of SOC modeled by the Global Ensemble Biogeochemical Modeling System (GEMS). The GEMS was run for an area of 1560 km2 in Senegal under three climate change scenarios with LCLU maps generated using different Landsat classification approaches. This research provides a method to estimate the variability of SOC, specifically the SOC uncertainty due to satellite classification errors, which we show is dependent not only on the LCLU classification errors but also on where the LCLU classes occur relative to the other GEMS model inputs.

Genetically engineered mice as experimental tools to dissect the critical events in breast cancer.

PubMed

Menezes, Mitchell E; Das, Swadesh K; Emdad, Luni; Windle, Jolene J; Wang, Xiang-Yang; Sarkar, Devanand; Fisher, Paul B

2014-01-01

Elucidating the mechanism of pathogenesis of breast cancer has greatly benefited from breakthrough advances in both genetically engineered mouse (GEM) models and xenograft transplantation technologies. The vast array of breast cancer mouse models currently available is testimony to the complexity of mammary tumorigenesis and attempts by investigators to accurately portray the heterogeneity and intricacies of this disease. Distinct molecular changes that drive various aspects of tumorigenesis, such as alterations in tumor cell proliferation and apoptosis, invasion and metastasis, angiogenesis, and drug resistance have been evaluated using the currently available GEM breast cancer models. GEM breast cancer models are also being exploited to evaluate and validate the efficacy of novel therapeutics, vaccines, and imaging modalities for potential use in the clinic. This review provides a synopsis of the various GEM models that are expanding our knowledge of the nuances of breast cancer development and progression and can be instrumental in the development of novel prevention and therapeutic approaches for this disease. © 2014 Elsevier Inc. All rights reserved.

Genetically Engineered Mice as Experimental Tools to Dissect the Critical Events in Breast Cancer

PubMed Central

Menezes, Mitchell E.; Das, Swadesh K.; Emdad, Luni; Windle, Jolene J.; Wang, Xiang-Yang; Sarkar, Devanand; Fisher, Paul B.

2015-01-01

Elucidating the mechanism of pathogenesis of breast cancer has greatly benefited from breakthrough advances in both genetically engineered mouse (GEM) models and xenograft transplantation technologies. The vast array of breast cancer mouse models currently available is testimony to the complexity of mammary tumorigenesis and attempts by investigators to accurately portray the heterogeneity and intricacies of this disease. Distinct molecular changes that drive various aspects of tumorigenesis, such as alterations in tumor cell proliferation and apoptosis, invasion and metastasis, angiogenesis, and drug resistance have been evaluated using the currently available GEM breast cancer models. GEM breast cancer models are also being exploited to evaluate and validate the efficacy of novel therapeutics, vaccines, and imaging modalities for potential use in the clinic. This review provides a synopsis of the various GEM models that are expanding our knowledge of the nuances of breast cancer development and progression and can be instrumental in the development of novel prevention and therapeutic approaches for this disease. PMID:24889535

The untapped potential of genetically-engineered mouse models in chemoprevention research: Opportunities and challenges

PubMed Central

Abate-Shen, Cory; Brown, Powel H.; Colburn, Nancy H.; Gerner, Eugene W.; Green, Jeffery E.; Lipkin, Martin; Nelson, William G.; Threadgill, David

2009-01-01

Summary The past decade has witnessed the unveiling of a powerful new generation of genetically-engineered mouse (GEM) models of human cancer, which are proving to be highly effective for elucidating cancer mechanisms and interrogating novel experimental therapeutics. This new generation of GEM models are well-suited for chemoprevention research, particularly for investigating progressive stages of carcinogenesis, identifying biomarkers for early detection and intervention, and pre-clinical assessment of novel agents or combinations of agents. Here we discuss opportunities and challenges for the application of GEM models in prevention research, as well as strategies to maximize their relevance for human cancer. PMID:19138951

Genetic consultation embedded in a gynecologic oncology clinic improves compliance with guideline-based care.

PubMed

Senter, Leigha; O'Malley, David M; Backes, Floor J; Copeland, Larry J; Fowler, Jeffery M; Salani, Ritu; Cohn, David E

2017-10-01

Analyze the impact of embedding genetic counseling services in gynecologic oncology on clinician referral and patient uptake of cancer genetics services. Data were reviewed for a total of 737 newly diagnosed epithelial ovarian cancer patients seen in gynecologic oncology at a large academic medical center including 401 from 11/2011-7/2014 (a time when cancer genetics services were provided as an off-site consultation). These data were compared to data from 8/2014-9/2016 (n=336), when the model changed to the genetics embedded model (GEM), incorporating a cancer genetic counselor on-site in the gynecologic oncology clinic. A statistically significant difference in proportion of patients referred pre- and post-GEM was observed (21% vs. 44%, p<0.0001). Pre-GEM, only 38% of referred patients were actually scheduled for genetics consultation and post-GEM 82% were scheduled (p<0.00001). The difference in the time from referral to scheduling in genetics was also statistically significant (3.92months pre-GEM vs. 0.79months post-GEM, p<0.00001) as was the time from referral to completion of genetics consultation (2.52months pre-GEM vs. 1.67months post-GEM, p<0.01). Twenty-five percent of patients referred post GEM were seen by the genetic counselor on the same day as the referral. Providing cancer genetics services on-site in gynecologic oncology and modifying the process by which patients are referred and scheduled significantly increases referral to cancer genetics and timely completion of genetics consultation, improving compliance with guideline-based care. Practice changes are critical given the impact of genetic test results on treatment and familial cancer risks. Copyright © 2017 Elsevier Inc. All rights reserved.

Impact of Initial Condition Errors and Precipitation Forecast Bias on Drought Simulation and Prediction in the Huaihe River Basin

NASA Astrophysics Data System (ADS)

Xu, H.; Luo, L.; Wu, Z.

2016-12-01

Drought, regarded as one of the major disasters all over the world, is not always easy to detect and forecast. Hydrological models coupled with Numerical Weather Prediction (NWP) has become a relatively effective method for drought monitoring and prediction. The accuracy of hydrological initial condition (IC) and the skill of NWP precipitation forecast can both heavily affect the quality and skill of hydrological forecast. In the study, the Variable Infiltration Capacity (VIC) model and Global Environmental Multi-scale (GEM) model were used to investigate the roles of IC and NWP forecast accuracy on hydrological predictions. A rev-ESP type experiment was conducted for a number of drought events in the Huaihe river basin. The experiment suggests that errors in ICs indeed affect the drought simulations by VIC and thus the drought monitoring. Although errors introduced in the ICs diminish gradually, the influence sometimes can last beyond 12 months. Using the soil moisture anomaly percentage index (SMAPI) as the metric to measure drought severity for the study region, we are able to quantify that time scale of influence from IC ranges. The analysis shows that the time scale is directly related to the magnitude of the introduced IC range and the average precipitation intensity. In order to explore how systematic bias correction in GEM forecasted precipitation can affect precipitation and hydrological forecast, we then both used station and gridded observations to eliminate biases of forecasted data. Meanwhile, different precipitation inputs with corrected data during drought process were conducted by VIC to investigate the changes of drought simulations, thus demonstrated short-term rolling drought prediction using a better performed corrected precipitation forecast. There is a word limit on the length of the abstract. So make sure your abstract fits the requirement. If this version is too long, try to shorten it as much as you can.

Comments on Lambeck and Coleman - 'The earth's shape and gravity field: A report of progress from 1958 to 1982'

NASA Technical Reports Server (NTRS)

Lerch, F. J.; Klosko, S. M.; Wagner, C. A.

1986-01-01

The accuracy and validation of global gravity models based on satellite data are discussed, responding to the statistical analysis of Lambeck and Coleman (1983) (LC). Included are an evaluation of the LC error spectra, a summary of independent-observation calibrations of the error estimates of the Goddard Earth Models (GEM) 9 and L2 (Lerch et al., 1977, 1979, 1982, 1983, and 1985), a comparison of GEM-L2 with GRIM-3B (Reigber et al., 1983), a comparison of recent models with LAGEOS laser ranging, and a summary of resonant-orbit model tests. It is concluded that the accuracy of GEMs 9, 10, and L2 is much higher than claimed by LC, that the GEMs are in good agreement with independent observations and with GRIM-3B, and that the GEM calibrations were adequate. In a reply by LC, a number of specific questions regarding the error estimates are addressed, and it is pointed out that the intermodel discrepancies of the greatest geophysical interest are those in the higher-order coefficients, not discussed in the present comment. It is argued that the differences among the geoid heights of even the most recent models are large enough to call for considerable improvements.

GAS eleven node thermal model (GEM)

NASA Technical Reports Server (NTRS)

Butler, Dan

1988-01-01

The Eleven Node Thermal Model (GEM) of the Get Away Special (GAS) container was originally developed based on the results of thermal tests of the GAS container. The model was then used in the thermal analysis and design of several NASA/GSFC GAS experiments, including the Flight Verification Payload, the Ultraviolet Experiment, and the Capillary Pumped Loop. The model description details the five cu ft container both with and without an insulated end cap. Mass specific heat values are also given so that transient analyses can be performed. A sample problem for each configuration is included as well so that GEM users can verify their computations. The model can be run on most personal computers with a thermal analyzer solution routine.

Idealized climate change simulations with a high-resolution physical model: HadGEM3-GC2

NASA Astrophysics Data System (ADS)

Senior, Catherine A.; Andrews, Timothy; Burton, Chantelle; Chadwick, Robin; Copsey, Dan; Graham, Tim; Hyder, Pat; Jackson, Laura; McDonald, Ruth; Ridley, Jeff; Ringer, Mark; Tsushima, Yoko

2016-06-01

Idealized climate change simulations with a new physical climate model, HadGEM3-GC2 from The Met Office Hadley Centre are presented and contrasted with the earlier MOHC model, HadGEM2-ES. The role of atmospheric resolution is also investigated. The Transient Climate Response (TCR) is 1.9 K/2.1 K at N216/N96 and Effective Climate Sensitivity (ECS) is 3.1 K/3.2 K at N216/N96. These are substantially lower than HadGEM2-ES (TCR: 2.5 K; ECS: 4.6 K) arising from a combination of changes in the size of climate feedbacks. While the change in the net cloud feedback between HadGEM3 and HadGEM2 is relatively small, there is a change in sign of its longwave and a strengthening of its shortwave components. At a global scale, there is little impact of the increase in atmospheric resolution on the future climate change signal and even at a broad regional scale, many features are robust including tropical rainfall changes, however, there are some significant exceptions. For the North Atlantic and western Europe, the tripolar pattern of winter storm changes found in most CMIP5 models is little impacted by resolution but for the most intense storms, there is a larger percentage increase in number at higher resolution than at lower resolution. Arctic sea-ice sensitivity shows a larger dependence on resolution than on atmospheric physics.

GEM - The Global Earthquake Model

NASA Astrophysics Data System (ADS)

Smolka, A.

2009-04-01

Over 500,000 people died in the last decade due to earthquakes and tsunamis, mostly in the developing world, where the risk is increasing due to rapid population growth. In many seismic regions, no hazard and risk models exist, and even where models do exist, they are intelligible only by experts, or available only for commercial purposes. The Global Earthquake Model (GEM) answers the need for an openly accessible risk management tool. GEM is an internationally sanctioned public private partnership initiated by the Organisation for Economic Cooperation and Development (OECD) which will establish an authoritative standard for calculating and communicating earthquake hazard and risk, and will be designed to serve as the critical instrument to support decisions and actions that reduce earthquake losses worldwide. GEM will integrate developments on the forefront of scientific and engineering knowledge of earthquakes, at global, regional and local scale. The work is organized in three modules: hazard, risk, and socio-economic impact. The hazard module calculates probabilities of earthquake occurrence and resulting shaking at any given location. The risk module calculates fatalities, injuries, and damage based on expected shaking, building vulnerability, and the distribution of population and of exposed values and facilities. The socio-economic impact module delivers tools for making educated decisions to mitigate and manage risk. GEM will be a versatile online tool, with open source code and a map-based graphical interface. The underlying data will be open wherever possible, and its modular input and output will be adapted to multiple user groups: scientists and engineers, risk managers and decision makers in the public and private sectors, and the public-at- large. GEM will be the first global model for seismic risk assessment at a national and regional scale, and aims to achieve broad scientific participation and independence. Its development will occur in a coordinated global network of regional centers, with a high degree of interaction among the centers and the central secretariat. Broad acceptance of the models will be ensured by including local knowledge in all aspects of hazard and risk assessment and securing participation of local experts throughout development. All GEM efforts will be carried out using a common global software infrastructure and consensus standards. In accordance with principles of open-source development, and to ensure comprehensive global representation, contributions are welcomed and encouraged from a broad group of participants. To ensure uniformity and conformance with the highest scientific standards, all contributions, including models, tools, and data, will be rigorously vetted and independently tested. Recently the EUCENTRE in Pavia/Italy has been selected as the host institution of the GEM secretariat. The project will formally launch in early 2009 by creating the non-profit GEM foundation. While GEM serves a humanitarian imperative it is considered as offering a key to long-term economic development. GEM will enhance risk awareness at global, national and local scales. Greater risk awareness is a precondition for motivating public and private parties to investing into risk reduction and loss prevention, and to promote a greater use of financial risk transfer instruments.

Cost-effectiveness analysis of treatments for metastatic pancreatic cancer based on PRODIGE and MPACT trials.

PubMed

Zhou, Jing; Zhao, Rongce; Wen, Feng; Zhang, Pengfei; Wu, Yifan; Tang, Ruilei; Chen, Hongdou; Zhang, Jian; Li, Qiu

2016-06-02

Fluorouracil, leucovorin, irinotecan, oxaliplatin (FOLFIRINOX) and gemcitabine plus nab-paclitaxel (GEM-N) have shown a significant survival benefit for the treatment of metastatic pancreatic cancer. The objective of this study was to assess the cost-effectiveness of FOLFIRINOX versus GEM-N for treating metastatic pancreatic cancer based on the PRODIGE and MPACT trials. A decision model was performed to compare FOLFIRINOX with GEM-N. Primary base case data were identified from PRODIGE and MPACT trials. Costs were estimated and incremental cost-effectiveness ratio (ICER) was calculated at West China Hospital, Sichuan University, China. Survival benefits were reported in quality-adjusted life-years (QALY). Finally, sensitive analysis was performed by varying potentially modifiable parameters in the model. The base-case analysis showed that FOLFIRINOX cost $37,203.75 and yielded a survival of 0.67 QALY, and GEM-N cost $32,080.59 and yielded a survival of 0.51 QALY in the entire treatment. Thus, the ICER of FOLFIRINOX versus GEM-N was $32,019.75 per QALY gained. The GEM-N regimen was more cost-effective compared with the FOLFIRINOX regimen for the treatment of metastatic pancreatic cancer from a Chinese perspective.

Validation of PHITS Spallation Models from the Perspective of the Shielding Design of Transmutation Experimental Facility

NASA Astrophysics Data System (ADS)

Iwamoto, Hiroki; Meigo, Shin-ichiro

2017-09-01

The impact of different spallation models implemented in the particle transport code PHITS on the shielding design of Transmutation Experimental Facility is investigated. For 400-MeV proton incident on a lead-bismuth eutectic target, an effective dose rate at the end of a thick radiation shield (3-m-thick iron and 3-m-thick concrete) calculated by the Liège intranuclear cascade (INC) model version 4.6 (INCL4.6) coupled with the GEMcode (INCL4.6/GEM) yields about twice as high as the Bertini INC model (Bertini/GEM). A comparison with experimental data for 500-MeV proton incident on a thick lead target suggest that the prediction accuracy of INCL4.6/GEM would be better than that of Bertini/GEM. In contrast, it is found that the dose rates in beam ducts in front of targets calculated by the INCL4.6/GEMare lower than those by the Bertini/GEM. Since both models underestimate the experimental results for neutron-production doubledifferential cross sections at 180° for 140-MeV proton incident on carbon, iron, and gold targets, it is concluded that it is necessary to allow a margin for uncertainty caused by the spallation models, which is a factor of two, in estimating the dose rate induced by neutron streaming through a beam duct.

The Global Earthquake Model - Past, Present, Future

NASA Astrophysics Data System (ADS)

Smolka, Anselm; Schneider, John; Stein, Ross

2014-05-01

The Global Earthquake Model (GEM) is a unique collaborative effort that aims to provide organizations and individuals with tools and resources for transparent assessment of earthquake risk anywhere in the world. By pooling data, knowledge and people, GEM acts as an international forum for collaboration and exchange. Sharing of data and risk information, best practices, and approaches across the globe are key to assessing risk more effectively. Through consortium driven global projects, open-source IT development and collaborations with more than 10 regions, leading experts are developing unique global datasets, best practice, open tools and models for seismic hazard and risk assessment. The year 2013 has seen the completion of ten global data sets or components addressing various aspects of earthquake hazard and risk, as well as two GEM-related, but independently managed regional projects SHARE and EMME. Notably, the International Seismological Centre (ISC) led the development of a new ISC-GEM global instrumental earthquake catalogue, which was made publicly available in early 2013. It has set a new standard for global earthquake catalogues and has found widespread acceptance and application in the global earthquake community. By the end of 2014, GEM's OpenQuake computational platform will provide the OpenQuake hazard/risk assessment software and integrate all GEM data and information products. The public release of OpenQuake is planned for the end of this 2014, and will comprise the following datasets and models: • ISC-GEM Instrumental Earthquake Catalogue (released January 2013) • Global Earthquake History Catalogue [1000-1903] • Global Geodetic Strain Rate Database and Model • Global Active Fault Database • Tectonic Regionalisation Model • Global Exposure Database • Buildings and Population Database • Earthquake Consequences Database • Physical Vulnerabilities Database • Socio-Economic Vulnerability and Resilience Indicators • Seismic Source Models • Ground Motion (Attenuation) Models • Physical Exposure Models • Physical Vulnerability Models • Composite Index Models (social vulnerability, resilience, indirect loss) • Repository of national hazard models • Uniform global hazard model Armed with these tools and databases, stakeholders worldwide will then be able to calculate, visualise and investigate earthquake risk, capture new data and to share their findings for joint learning. Earthquake hazard information will be able to be combined with data on exposure (buildings, population) and data on their vulnerability, for risk assessment around the globe. Furthermore, for a truly integrated view of seismic risk, users will be able to add social vulnerability and resilience indices and estimate the costs and benefits of different risk management measures. Having finished its first five-year Work Program at the end of 2013, GEM has entered into its second five-year Work Program 2014-2018. Beyond maintaining and enhancing the products developed in Work Program 1, the second phase will have a stronger focus on regional hazard and risk activities, and on seeing GEM products used for risk assessment and risk management practice at regional, national and local scales. Furthermore GEM intends to partner with similar initiatives underway for other natural perils, which together are needed to meet the need for advanced risk assessment methods, tools and data to underpin global disaster risk reduction efforts under the Hyogo Framework for Action #2 to be launched in Sendai/Japan in spring 2015

3D Observation of GEMS by Electron Tomography

NASA Technical Reports Server (NTRS)

Matsuno, Junya; Miyake, Akira; Tsuchiyama, Akira; Nakamura-Messenger, Keiko; Messenger, Scott

2014-01-01

Amorphous silicates in chondritic porous interplanetary dust particles (CP-IDPs) coming from comets are dominated by glass with embedded metal and sulfides (GEMS). GEMS grains are submicron-sized rounded objects (typically 100-500) nm in diameter) with anaometer-sized (10-50 nm) Fe-Ni metal and sulfide grains embedded in an amorphous silicate matrix. Several formation processes for GEMS grains have been proposed so far, but these models are still being debated [2-5]. Bradley et al. proposed that GEMS grains are interstellar silicate dust that survived various metamorphism or alteration processes in the protoplanetary disk and that they are amorphiation products of crystalline silicates in the interstellar medium by sputter-deposition of cosmic ray irradiation, similar to space weathering [2,4]. This consideration is based on the observation of nano-sized crystals (approximately 10 nm) called relict grains in GEMS grains and their shapes are pseudomorphs to the host GEMS grains. On the other hand, Keller and Messenger proposed that most GEMS formed in the protoplanetary disk as condensates from high temperature gas [3,5]. This model is based on the fact that most GEMS grains have solar isotopic compositions and have extremely heterogeneous and non-solar elemental compositions. Keller and Messenger (2011) also reported that amorphous silicates in GEMS grains are surrounded by sulfide grains, which formed as sulfidization of metallic iron grains located on the GEMS surface. The previous studies were performed with 2D observation by using transmission electron microscopy (TEM) or scanning TEM (STEM). In order to understand the structure of GEMS grains described above more clearly, we observed 3D structure of GEMS grains by electron tomography using a TEM/STEM (JEM-2100F, JEOL) at Kyoto University. Electron tomography gives not only 3D structures but also gives higher spatial resolution (approximately a few nm) than that in conventional 2D image, which is restricted by sample thickness ) approx. or greater than 50 nm). Three cluster IDPs (L2036AA5 cluster4, L2009L8 cluster 13 and W726A2) were used for the observations. ID W726A2 was collected without silicon oil, which is ordinary used to collect IDPs, so this sample has no possibility of contaminations caused by silicon oil or solvent to rinse it [6]. The samples were embedded in epoxy risin and sliced into ultrathin sections (50-300 nm) using an ultramicotome. The sections were observed by BF-TEM and HAADF-STEM (high angle annular dark field-scanning TEM) modes. Images were obtained by rotating the sample tilt angle over a range of +/- 65 deg in 1 deg steps. The obtained images were reconstructed to slice images. Mineral phases in the slice images were estimated by comparing with a 2D elemental map obtained by an EDS (energy dispersive X-ray spectroscopy) system equipped in the TEM/STEM. Careful examination of the slice images confirmed that iron grains are embedded in the amorphous silicate matrix of the GEMS grains, but sulfide grains were mainly present on the surface of the amorphous silicate. These results are consistent with the model that GEMS grains formed as condensates [3,5], although more data are needed to conclude the origin of GEMS grains. The present study is the first successful example adapting the electron tomography to the IDPs. This type of analysis will be important for planetary material sciences in the future.

[Effects of Cultivation Soil Properties on the Transport of Genetically Engineered Microorganism in Huabei Plain].

PubMed

Zhang, Jing; Liu, Ping; Liu, Chun; Chen, Xiao-xuan; Zhang, Lei

2015-12-01

The transport of genetically engineered microorganism (GEM) in the soil is considered to be the important factor influencing the enhanced bioremediation of polluted soil. The transport of an atrazine-degrading GEM and its influencing factors were investigated in the saturated cultivation soil of Huabei Plain. The results showed that horizontal infiltration was the main mechanism of GEM transport in the saturated cultivation soil. The transport process could be simulated using the filtration model. Soil properties showed significant effects on pore water flow and GEM transport in saturated soil. When particle size, porosity and sand component of the soil increased, the hydraulic conductivity constant increased and filtration coefficient of GEM decreased in saturated soil, indicating the reduced retention of GEM in the soil. An increase in infiltration flow also increased hydraulic conductivity constant in saturated soil and consequently decreased filtration coefficient of GEM. When hydraulic conductivity constants ranged from 5.02 m · d⁻¹ to 6.70 m · d⁻¹ in the saturated soil, the filtration coefficients of GEM varied from 0.105 to 0.274. There was a significantly negative correlation between them.

A refined gravity model from Lageos /GEM-L2/

NASA Technical Reports Server (NTRS)

Lerch, F. J.; Klosko, S. M.; Patel, G. B.

1982-01-01

Lageos satellite laser ranging (SLR) data taken over a 2.5 yr period were employed to develop the Goddard Earth Model GEM-L2, a refined gravity field model. Additional data was gathered with 30 other satellites, resulting in spherical harmonics through degree and order 20, based on over 600,000 measurements. The Lageos data was accurate down to 10 cm, after which the GEM 9 data were used to make adjustments past order 7. The resolution of long wavelength activity, through degree and order 4, was made possible by the Lageos data. The GEM-L2 model features a 20 x 20 geopotential, tracking station coordinates (20), 5-day polar motion and A1-UT1 values, and a GM value of 398,600.607 cu km/sq sec. The accuracy of station positioning has been raised to within 6 cm total position globally and within 1.8 cm in baselines. It is concluded that SLR is useful for measuring tectonic plate motions and inter-plate deformations.

Teamwork tools and activities within the hazard component of the Global Earthquake Model

NASA Astrophysics Data System (ADS)

Pagani, M.; Weatherill, G.; Monelli, D.; Danciu, L.

2013-05-01

The Global Earthquake Model (GEM) is a public-private partnership aimed at supporting and fostering a global community of scientists and engineers working in the fields of seismic hazard and risk assessment. In the hazard sector, in particular, GEM recognizes the importance of local ownership and leadership in the creation of seismic hazard models. For this reason, over the last few years, GEM has been promoting different activities in the context of seismic hazard analysis ranging, for example, from regional projects targeted at the creation of updated seismic hazard studies to the development of a new open-source seismic hazard and risk calculation software called OpenQuake-engine (http://globalquakemodel.org). In this communication we'll provide a tour of the various activities completed, such as the new ISC-GEM Global Instrumental Catalogue, and of currently on-going initiatives like the creation of a suite of tools for the creation of PSHA input models. Discussion, comments and criticism by the colleagues in the audience will be highly appreciated.

Code and Solution Verification of 3D Numerical Modeling of Flow in the Gust Erosion Chamber

NASA Astrophysics Data System (ADS)

Yuen, A.; Bombardelli, F. A.

2014-12-01

Erosion microcosms are devices commonly used to investigate the erosion and transport characteristics of sediments at the bed of rivers, lakes, or estuaries. In order to understand the results these devices provide, the bed shear stress and flow field need to be accurately described. In this research, the UMCES Gust Erosion Microcosm System (U-GEMS) is numerically modeled using Finite Volume Method. The primary aims are to simulate the bed shear stress distribution at the surface of the sediment core/bottom of the microcosm, and to validate the U-GEMS produces uniform bed shear stress at the bottom of the microcosm. The mathematical model equations are solved by on a Cartesian non-uniform grid. Multiple numerical runs were developed with different input conditions and configurations. Prior to developing the U-GEMS model, the General Moving Objects (GMO) model and different momentum algorithms in the code were verified. Code verification of these solvers was done via simulating the flow inside the top wall driven square cavity on different mesh sizes to obtain order of convergence. The GMO model was used to simulate the top wall in the top wall driven square cavity as well as the rotating disk in the U-GEMS. Components simulated with the GMO model were rigid bodies that could have any type of motion. In addition cross-verification was conducted as results were compared with numerical results by Ghia et al. (1982), and good agreement was found. Next, CFD results were validated by simulating the flow within the conventional microcosm system without suction and injection. Good agreement was found when the experimental results by Khalili et al. (2008) were compared. After the ability of the CFD solver was proved through the above code verification steps. The model was utilized to simulate the U-GEMS. The solution was verified via classic mesh convergence study on four consecutive mesh sizes, in addition to that Grid Convergence Index (GCI) was calculated and based on that the computation uncertainty was quantified. The numerical results reveal that the bed shear stress distribution for the U-GEMS model was not uniform. The mean and standard deviation of the bed shear stress for the U-GEMS model was 0.04 and 0.019 Pa respectively.

Properties of the Flight Model Gas Electron Multiplier for the GEMS Mission

NASA Technical Reports Server (NTRS)

Takeuchi, Yoko; Kitaguchi, Takao; Hayato, Asami; Tamagawa, Toru; Iwakiri, Wataru; Asami, Fumi; Yoshikawa, Akifumi; Kaneko, Kenta; Enoto, Teruaki; Black, Kevin;

GEMS Revealed: Spectrum Imaging of Aggregate Grains in Interplanetary Dust

NASA Technical Reports Server (NTRS)

Keller, L. P.; Messenger, S.; Christoffersen, R.

2005-01-01

Anhydrous interplanetary dust particles (IDPs) of cometary origin contain abundant materials that formed in the early solar nebula. These materials were transported outward and subsequently mixed with molecular cloud materials and presolar grains in the region where comets accreted [1]. GEMS (glass with embedded metal and sulfides) grains are a major component of these primitive anhydrous IDPs, along with crystalline Mg-rich silicates, Fe-Ni sulfides, carbonaceous material, and other trace phases. Some GEMS grains (5%) are demonstrably presolar based on their oxygen isotopic compositions [2]. However, most GEMS grains are isotopically solar and have bulk chemical compositions that are incompatible with inferred compositions of interstellar dust, suggesting a solar system origin [3]. An alternative hypothesis is that GEMS grains represent highly irradiated interstellar grains whose oxygen isotopic compositions were homogenized through processing in the interstellar medium (ISM) [4]. We have obtained the first quantitative X-ray maps (spectrum images) showing the distribution of major and minor elements in individual GEMS grains. Nanometer-scale chemical maps provide critical data required to evaluate the differing models regarding the origin of GEMS grains.

Evaluation and intercomparison of five major dry deposition ...

EPA Pesticide Factsheets

Dry deposition of various pollutants needs to be quantified in air quality monitoring networks as well as in chemical transport models. The inferential method is the most commonly used approach in which the dry deposition velocity (Vd) is empirically parameterized as a function of meteorological and biological conditions and pollutant species’ chemical properties. Earlier model intercomparison studies suggested that existing dry deposition algorithms produce quite different Vd values, e.g., up to a factor of 2 for monthly to annual average values for ozone, and sulfur and nitrogen species (Flechard et al., 2011; Schwede et al., 2011; Wu et al., 2011). To further evaluate model discrepancies using available flux data, this study compared the five dry deposition algorithms commonly used in North America and evaluated the models using five-year Vd(O3) and Vd(SO2) data generated from concentration gradient measurements above a temperate mixed forest in Canada. The five algorithms include: (1) the one used in the Canadian Air and Precipitation Monitoring Network (CAPMoN) and several Canadian air quality models based on Zhang et al. (2003), (2) the one used in the US Clean Air Status and Trends Network (CASTNET) based on Meyers et al. (1998), (3) the one used in the Community Multiscale Air Quality (CMAQ) model described in Pleim and Ran (2011), (4) the Noah land surface model coupled with a photosynthesis-based Gas Exchange Model (Noah-GEM) described in Wu et a

Validation and comparison of four models to calculate pretest probability of obstructive coronary artery disease in a Chinese population: A coronary computed tomographic angiography study.

PubMed

Zhou, Jia; Liu, Yujie; Huang, Lingyu; Tan, Yahang; Li, Xingchen; Zhang, Hong; Ma, Yanhe; Zhang, Ying

We sought to compare the performance of the updated Diamond-Forrester method (UDFM), Duke clinical score (DCS), Genders clinical model (GCM) and Genders extended model (GEM) in a Chinese population referred to coronary computed tomography angiography (coronary CTA). The reliability of existing models to calculate the pretest proability (PTP) of obstructive coronary artery disease (CAD) have not been fully investigated, especially in a Chinese population. We identified 5743 consecutive patients with suspected stable CAD who underwent coronary calcium scoring (CCS) and coronary CCTA. Obstructive CAD was defined as with the presence of ≥50% diameter stenosis in coronary CTA or unassessable segments due to severe calcification. Area under the receiver operating characteristic curve (AUC), integrated discrimination improvement (IDI), net reclassification improvement (NRI) and Hosmer-Lemeshow goodness-of-fit statistic (H-L χ 2 ) were assessed to validate and compare these models. Overall, 1872 (32%) patients had obstructive CAD and 2467 (43%) had a CCS of 0. GEM demonstrated improved discrimination over the other models through the largest AUC (0.816 for GEM, 0.774 for GCM, 0.772 for DCS and 0.765 for UDFM). UDFM (-0.3255, p < 0.0001), DCS (-0.3149, p < 0.0001) and GCM (-0.2264, p < 0.0001) showed negative IDI compared to GEM. The NRI was significantly higher for GEM than the other models (0.7152, p < 0.0001, 0.5595, p < 0.0001 and 0.3195, p < 0.0001, respectively). All of the four models overestimated the prevalence of obstructive CAD, with unsatisfactory (p < 0.01 for all) calibration for UDFM (H-L χ 2  = 137.82), DCS (H-L χ 2  = 156.70), GCM (H-L χ 2  = 51.17) and GEM (H-L χ 2  = 29.67), respectively. Although GEM was superior for calculating PTP in a Chinese population referred for coronary CTA, developing new models allowing for more accurate and operational estimation are warranted. Copyright © 2017 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

Projection of Changes in Regional Climate and Air Quality in the Great Lakes Basin between 2000 and 2050 for the RCP8.5 Emissions Scenario using the GEM-AQ Model

NASA Astrophysics Data System (ADS)

Lupu, A.; Semeniuk, K.; McConnell, J. C.; Kaminski, J. W.; Toyota, K.; Neary, L.

2012-12-01

The Global Environmental Multiscale Air Quality (GEM-AQ) model was run in global and limited area model (LAM) modes for the baseline year 2000 and one future year, 2050, on three different horizontal grids of increasing resolution from global (1.5°) to North American (LAM, 0.45°) to Ontario regional scale (LAM, 0.15°). For the future simulation we used the high greenhouse emissions scenario RCP8.5. Boundary conditions for the LAM runs were taken from the coarser resolution runs. All simulations had 54 vertical sigma-pressure hybrid levels from the ground to the stratopause (˜50 km), which should give a good representation of ozone injection to the troposphere from the stratosphere. The model uses the interactive land surface scheme ISBA. Sea surface and lake temperatures are prescribed, but ice cover is partially interactive based on prescribed fields. A lake model, FLAKE, was coupled to GEM-AQ in order to capture the impacts of the Great Lakes on the meteorology when the model is run at high resolution. For the Ontario regional simulation the interactive lake model allowed for self-consistent water temperatures and moisture fluxes. The simulation for the year 2000 shows that the model is able to reproduce the observed monthly surface temperatures across the US. The monthly surface ozone is reproduced at the level of detail of most other air quality models with year 2000 weather as opposed to a free run forced by SSTs. Our year 2050 simulation shows that ozone levels during the summer throughout most of Ontario and Canada will increase. Regions south of the latitude of Lake Superior will generally see decreased levels of summer (JJA) ozone, except for around large urban areas such as Toronto, Chicago and Montreal. However, NOx levels will decrease during the summer, reflecting decreased emissions. Ozone levels in the US will generally improve. Other indices rather than simple averages yield a different perspective. If the MDA8 ozone metric and NO2 one-hour 98th percentile are used, then it is found that air quality across Canada and US will generally improve. From the perspective of meteorology, the most significant surface warming that is likely to occur by 2050 is during winter. The winter warming also reflects changes in large scale circulation with baroclinic eddy storm tracks moving north. Winter warming contributes to a surface ozone increase by 2050 in spite of reduced emissions. In addition, we note that in the Ontario region and environs for 2050 there is a significant increase (˜40) in the number of DD5 days, i.e. days where the temperature is above 5°C, a metric useful for the length of the growing season for agriculture. This also means that conditions that impact forests and movement of disease vectors will also change.

Metadata for selecting or submitting generic seismic vulnerability functions via GEM's vulnerability database

USGS Publications Warehouse

Jaiswal, Kishor

2013-01-01

This memo lays out a procedure for the GEM software to offer an available vulnerability function for any acceptable set of attributes that the user specifies for a particular building category. The memo also provides general guidelines on how to submit the vulnerability or fragility functions to the GEM vulnerability repository, stipulating which attributes modelers must provide so that their vulnerability or fragility functions can be queried appropriately by the vulnerability database. An important objective is to provide users guidance on limitations and applicability by providing the associated modeling assumptions and applicability of each vulnerability or fragility function.

The Mitochondrial GTPase Gem1 Contributes to the Cell Wall Stress Response and Invasive Growth of Candida albicans.

PubMed

Koch, Barbara; Tucey, Timothy M; Lo, Tricia L; Novakovic, Stevan; Boag, Peter; Traven, Ana

2017-01-01

The interactions of mitochondria with the endoplasmic reticulum (ER) are crucial for maintaining proper mitochondrial morphology, function and dynamics. This enables cells to utilize their mitochondria optimally for energy production and anabolism, and it further provides for metabolic control over developmental decisions. In fungi, a key mechanism by which ER and mitochondria interact is via a membrane tether, the protein complex ERMES (ER-Mitochondria Encounter Structure). In the model yeast Saccharomyces cerevisiae , the mitochondrial GTPase Gem1 interacts with ERMES, and it has been proposed to regulate its activity. Here we report on the first characterization of Gem1 in a human fungal pathogen. We show that in Candida albicans Gem1 has a dominant role in ensuring proper mitochondrial morphology, and our data is consistent with Gem1 working with ERMES in this role. Mitochondrial respiration and steady state cellular phospholipid homeostasis are not impacted by inactivation of GEM1 in C. albicans . There are two major virulence-related consequences of disrupting mitochondrial morphology by GEM1 inactivation: C. albicans becomes hypersusceptible to cell wall stress, and is unable to grow invasively. In the gem1 Δ / Δ mutant, it is specifically the invasive capacity of hyphae that is compromised, not the ability to transition from yeast to hyphal morphology, and this phenotype is shared with ERMES mutants. As a consequence of the hyphal invasion defect, the gem1 Δ / Δ mutant is drastically hypovirulent in the worm infection model. Activation of the mitogen activated protein (MAP) kinase Cek1 is reduced in the gem1 Δ / Δ mutant, and this function could explain both the susceptibility to cell wall stress and lack of invasive growth. This result establishes a new, respiration-independent mechanism of mitochondrial control over stress signaling and hyphal functions in C. albicans . We propose that ER-mitochondria interactions and the ER-Mitochondria Organizing Network (ERMIONE) play important roles in adaptive responses in fungi, in particular cell surface-related mechanisms that drive invasive growth and stress responsive behaviors that support fungal pathogenicity.

The Mitochondrial GTPase Gem1 Contributes to the Cell Wall Stress Response and Invasive Growth of Candida albicans

PubMed Central

Koch, Barbara; Tucey, Timothy M.; Lo, Tricia L.; Novakovic, Stevan; Boag, Peter; Traven, Ana

2017-01-01

The interactions of mitochondria with the endoplasmic reticulum (ER) are crucial for maintaining proper mitochondrial morphology, function and dynamics. This enables cells to utilize their mitochondria optimally for energy production and anabolism, and it further provides for metabolic control over developmental decisions. In fungi, a key mechanism by which ER and mitochondria interact is via a membrane tether, the protein complex ERMES (ER-Mitochondria Encounter Structure). In the model yeast Saccharomyces cerevisiae, the mitochondrial GTPase Gem1 interacts with ERMES, and it has been proposed to regulate its activity. Here we report on the first characterization of Gem1 in a human fungal pathogen. We show that in Candida albicans Gem1 has a dominant role in ensuring proper mitochondrial morphology, and our data is consistent with Gem1 working with ERMES in this role. Mitochondrial respiration and steady state cellular phospholipid homeostasis are not impacted by inactivation of GEM1 in C. albicans. There are two major virulence-related consequences of disrupting mitochondrial morphology by GEM1 inactivation: C. albicans becomes hypersusceptible to cell wall stress, and is unable to grow invasively. In the gem1Δ/Δ mutant, it is specifically the invasive capacity of hyphae that is compromised, not the ability to transition from yeast to hyphal morphology, and this phenotype is shared with ERMES mutants. As a consequence of the hyphal invasion defect, the gem1Δ/Δ mutant is drastically hypovirulent in the worm infection model. Activation of the mitogen activated protein (MAP) kinase Cek1 is reduced in the gem1Δ/Δ mutant, and this function could explain both the susceptibility to cell wall stress and lack of invasive growth. This result establishes a new, respiration-independent mechanism of mitochondrial control over stress signaling and hyphal functions in C. albicans. We propose that ER-mitochondria interactions and the ER-Mitochondria Organizing Network (ERMIONE) play important roles in adaptive responses in fungi, in particular cell surface-related mechanisms that drive invasive growth and stress responsive behaviors that support fungal pathogenicity. PMID:29326680

Computational modelling of genome-scale metabolic networks and its application to CHO cell cultures.

PubMed

Rejc, Živa; Magdevska, Lidija; Tršelič, Tilen; Osolin, Timotej; Vodopivec, Rok; Mraz, Jakob; Pavliha, Eva; Zimic, Nikolaj; Cvitanović, Tanja; Rozman, Damjana; Moškon, Miha; Mraz, Miha

2017-09-01

Genome-scale metabolic models (GEMs) have become increasingly important in recent years. Currently, GEMs are the most accurate in silico representation of the genotype-phenotype link. They allow us to study complex networks from the systems perspective. Their application may drastically reduce the amount of experimental and clinical work, improve diagnostic tools and increase our understanding of complex biological phenomena. GEMs have also demonstrated high potential for the optimisation of bio-based production of recombinant proteins. Herein, we review the basic concepts, methods, resources and software tools used for the reconstruction and application of GEMs. We overview the evolution of the modelling efforts devoted to the metabolism of Chinese Hamster Ovary (CHO) cells. We present a case study on CHO cell metabolism under different amino acid depletions. This leads us to the identification of the most influential as well as essential amino acids in selected CHO cell lines. Copyright © 2017 Elsevier Ltd. All rights reserved.

Depletion of atmospheric gaseous elemental mercury by plant uptake at Mt. Changbai, Northeast China

NASA Astrophysics Data System (ADS)

Fu, Xuewu; Zhu, Wei; Zhang, Hui; Sommar, Jonas; Yu, Ben; Yang, Xu; Wang, Xun; Lin, Che-Jen; Feng, Xinbin

2016-10-01

There exists observational evidence that gaseous elemental mercury (GEM) can be readily removed from the atmosphere via chemical oxidation followed by deposition in the polar and sub-polar regions, free troposphere, lower stratosphere, and marine boundary layer under specific environmental conditions. Here we report GEM depletions in a temperate mixed forest at Mt. Changbai, Northeast China. The strong depletions occurred predominantly at night during the leaf-growing season and in the absence of gaseous oxidized mercury (GOM) enrichment (GOM < 3 pg m-3). Vertical gradients of decreasing GEM concentrations from layers above to under forest canopy suggest in situ loss of GEM to forest canopy at Mt. Changbai. Foliar GEM flux measurements showed that the foliage of two predominant tree species is a net sink of GEM at night, with a mean flux of -1.8 ± 0.3 ng m2 h-1 over Fraxinus mandshurica (deciduous tree species) and -0.1 ± 0.2 ng m2 h-1 over Pinus Koraiensis (evergreen tree species). Daily integrated GEM δ202Hg, Δ199Hg, and Δ200Hg at Mt. Changbai during 8-18 July 2013 ranged from -0.34 to 0.91 ‰, from -0.11 to -0.04 ‰ and from -0.06 to 0.01 ‰, respectively. A large positive shift in GEM δ202Hg occurred during the strong GEM depletion events, whereas Δ199Hg and Δ200Hg remained essentially unchanged. The observational findings and box model results show that uptake of GEM by forest canopy plays a predominant role in the GEM depletion at Mt. Changbai forest. Such depletion events of GEM are likely to be a widespread phenomenon, suggesting that the forest ecosystem represents one of the largest sinks ( ˜ 1930 Mg) of atmospheric Hg on a global scale.

Defeating Earthquakes

NASA Astrophysics Data System (ADS)

Stein, R. S.

2012-12-01

The 2004 M=9.2 Sumatra earthquake claimed what seemed an unfathomable 228,000 lives, although because of its size, we could at least assure ourselves that it was an extremely rare event. But in the short space of 8 years, the Sumatra quake no longer looks like an anomaly, and it is no longer even the worst disaster of the Century: 80,000 deaths in the 2005 M=7.6 Pakistan quake; 88,000 deaths in the 2008 M=7.9 Wenchuan, China quake; 316,000 deaths in the M=7.0 Haiti, quake. In each case, poor design and construction were unable to withstand the ferocity of the shaken earth. And this was compounded by inadequate rescue, medical care, and shelter. How could the toll continue to mount despite the advances in our understanding of quake risk? The world's population is flowing into megacities, and many of these migration magnets lie astride the plate boundaries. Caught between these opposing demographic and seismic forces are 50 cities of at least 3 million people threatened by large earthquakes, the targets of chance. What we know for certain is that no one will take protective measures unless they are convinced they are at risk. Furnishing that knowledge is the animating principle of the Global Earthquake Model, launched in 2009. At the very least, everyone should be able to learn what his or her risk is. At the very least, our community owes the world an estimate of that risk. So, first and foremost, GEM seeks to raise quake risk awareness. We have no illusions that maps or models raise awareness; instead, earthquakes do. But when a quake strikes, people need a credible place to go to answer the question, how vulnerable am I, and what can I do about it? The Global Earthquake Model is being built with GEM's new open source engine, OpenQuake. GEM is also assembling the global data sets without which we will never improve our understanding of where, how large, and how frequently earthquakes will strike, what impacts they will have, and how those impacts can be lessened by our actions. Using these global datasets will help to make the model as uniform as possible. The model must be built by scientists in the affected countries with GEM's support, augmented by their insights and data. The model will launch in 2014; to succeed it must be open, international, independent, and continuously tested. But the mission of GEM is not just the likelihood of ground shaking, but also gaging the economic and social consequences of earthquakes, which greatly amplify the losses. For example, should the municipality of Istanbul retrofit schools, or increase its insurance reserves and recovery capacity? Should a homeowner in a high-risk area move or strengthen her building? This is why GEM is a public-private partnership. GEM's fourteen public sponsors and eight non-governmental organization members are standing for the developing world. To extend GEM into the financial world, we draw upon the expertise of companies. GEM's ten private sponsors have endorsed the acquisition of public knowledge over private gain. In a competitive world, this is a courageous act. GEM is but one link in a chain of preparedness: from earth science and engineering research, through groups like GEM, to mitigation, retrofit or relocate decisions, building codes and insurance, and finally to prepared hospitals, schools, and homes. But it is a link that our community can make strong.

Transparent Global Seismic Hazard and Risk Assessment

NASA Astrophysics Data System (ADS)

Smolka, Anselm; Schneider, John; Pinho, Rui; Crowley, Helen

2013-04-01

Vulnerability to earthquakes is increasing, yet advanced reliable risk assessment tools and data are inaccessible to most, despite being a critical basis for managing risk. Also, there are few, if any, global standards that allow us to compare risk between various locations. The Global Earthquake Model (GEM) is a unique collaborative effort that aims to provide organizations and individuals with tools and resources for transparent assessment of earthquake risk anywhere in the world. By pooling data, knowledge and people, GEM acts as an international forum for collaboration and exchange, and leverages the knowledge of leading experts for the benefit of society. Sharing of data and risk information, best practices, and approaches across the globe is key to assessing risk more effectively. Through global projects, open-source IT development and collaborations with more than 10 regions, leading experts are collaboratively developing unique global datasets, best practice, open tools and models for seismic hazard and risk assessment. Guided by the needs and experiences of governments, companies and citizens at large, they work in continuous interaction with the wider community. A continuously expanding public-private partnership constitutes the GEM Foundation, which drives the collaborative GEM effort. An integrated and holistic approach to risk is key to GEM's risk assessment platform, OpenQuake, that integrates all above-mentioned contributions and will become available towards the end of 2014. Stakeholders worldwide will be able to calculate, visualise and investigate earthquake risk, capture new data and to share their findings for joint learning. Homogenized information on hazard can be combined with data on exposure (buildings, population) and data on their vulnerability, for loss assessment around the globe. Furthermore, for a true integrated view of seismic risk, users can add social vulnerability and resilience indices to maps and estimate the costs and benefits of different risk management measures. The following global data, models and methodologies will be available in the platform. Some of these will be released to the public already before, such as the ISC-GEM global instrumental catalogue (released January 2013). Datasets: • Global Earthquake History Catalogue [1000-1903] • Global Instrumental Catalogue [1900-2009] • Global Geodetic Strain Rate Model • Global Active Fault Database • Tectonic Regionalisation • Buildings and Population Database • Earthquake Consequences Database • Physical Vulnerability Database • Socio-Economic Vulnerability and Resilience Indicators Models: • Seismic Source Models • Ground Motion (Attenuation) Models • Physical Exposure Models • Physical Vulnerability Models • Composite Index Models (social vulnerability, resilience, indirect loss) The aforementioned models developed under the GEM framework will be combined to produce estimates of hazard and risk at a global scale. Furthermore, building on many ongoing efforts and knowledge of scientists worldwide, GEM will integrate state-of-the-art data, models, results and open-source tools into a single platform that is to serve as a "clearinghouse" on seismic risk. The platform will continue to increase in value, in particular for use in local contexts, through contributions and collaborations with scientists and organisations worldwide.

Multiscale Modeling: A Review

NASA Astrophysics Data System (ADS)

Horstemeyer, M. F.

This review of multiscale modeling covers a brief history of various multiscale methodologies related to solid materials and the associated experimental influences, the various influence of multiscale modeling on different disciplines, and some examples of multiscale modeling in the design of structural components. Although computational multiscale modeling methodologies have been developed in the late twentieth century, the fundamental notions of multiscale modeling have been around since da Vinci studied different sizes of ropes. The recent rapid growth in multiscale modeling is the result of the confluence of parallel computing power, experimental capabilities to characterize structure-property relations down to the atomic level, and theories that admit multiple length scales. The ubiquitous research that focus on multiscale modeling has broached different disciplines (solid mechanics, fluid mechanics, materials science, physics, mathematics, biological, and chemistry), different regions of the world (most continents), and different length scales (from atoms to autos).

Climate Projections over Mediterranean Basin under RCP8.5 and RCP4.5 emission scenarios

NASA Astrophysics Data System (ADS)

Ilhan, Asli; Ünal, Yurdanur S.

2017-04-01

Climate Projections over Mediterranean Basin under RCP8.5 and RCP4.5 emission scenarios A. ILHAN ve Y. S. UNAL Istanbul Technical University, Department of Meteorology In the study, 50 km resolution downscaled results of two different Earth System Models (ESM) HadGEM2-ES and MPI-ESM with regional climate model of RegCM are used to estimate present and future climate conditions over Mediterranean Basin. The purpose of this study is to compare the projections of two ESMs under Representative Concentration Pathways 4.5 (RCP4.5) and 8.5 (RCP8.5) over the region of interest seasonally and annually with 50 km resolution. Temperature and precipitation parameters for reference period (1971-2000) and future (2015-2100) are analyzed. The average temperature and total precipitation distributions of each downscaled ESM simulations were compared with observation data (Climate Research Unit-CRU data) to explore the capability of each model for the representation of the current climate. According to reference period values of CRU, HadGEM2-ES and MPI-ESM, it is seen that both models are warmer and wetter than observations and have positive temperature biases only around Caspian Sea and positive precipitation biases over Eastern and Central Europe. The future projections (from 2015 to 2100) of HadGEM2-ES and MPI-ESM-MR simulations under RCP4.5 and RCP8.5 emission scenarios are compared with reference period (from 1971 to 2000) and analyzed for temperature and precipitation parameters. The downscaled HadGEM2-ES forced by RCP8.5 scenario produces higher temperatures than the MPI-ESM-MR. The reasons of this warming can be sensitivity of HadGEM2-ES to greenhouse gases and high radiative forcing (+8.5 W/m2). On the other hand, MPI-ESM produce more precipitation than HadGEM2-ES. In order to analyze regional responses of the climate model chains, five main regions are selected which are Turkey, Central Europe, Western Europe, Eastern Europe and North Africa. The average biases of the HadGEM2-ES+RegCM and MPI-ESM-MR+RegCM model chains are also calculated for temperature and precipitation variables, and future expectations in each region are discussed under RCP4.5 and RCP8.5 scenarios. According to the regional analysis, North Africa is the warmest region for HadGEM2-ES and MPI-ESM-MR, and Central Europe warms up similar to North Africa in MPI-ESM-MR coupled simulations under both RCPs. In addition, Eastern Europe is expected to be the wettest region in both models and in both emission scenarios. On the other hand, the driest conditions are expected over Western Europe for MPI-ESM-MR and over Turkey for HadGEM2-ES under RCPs.

Small-animal research imaging devices.

PubMed

Fine, Eugene J; Herbst, Lawrence; Jelicks, Linda A; Koba, Wade; Theele, Daniel

2014-01-01

The scientific study of living animals may be dated to Aristotle's original dissections, but modern animal studies are perhaps a century in the making, and advanced animal imaging has emerged only during the past few decades. In vivo imaging now occupies a growing role in the scientific research paradigm. Imaging of small animals has been particularly useful to help understand human molecular biology and pathophysiology using rodents, especially using genetically engineered mice (GEM) with spontaneous diseases that closely mimic human diseases. Specific examples of GEM models of veterinary diseases exist, but in general, GEM for veterinary research has lagged behind human research applications. However, the development of spontaneous disease models from GEM may also hold potential for veterinary research. The imaging techniques most widely used in small-animal research are CT, PET, single-photon emission CT, MRI, and optical fluorescent and luminescent imaging. Copyright © 2014 Elsevier Inc. All rights reserved.

Student involvement in the Geospace Environment Modeling (GEM) workshop

NASA Astrophysics Data System (ADS)

Allen, R. C.; Cohen, I. J.

2014-12-01

The Geospace Environment Modeling (GEM) workshop is a unique venue for students to begin to integrate into the magnetospheric community. GEM, an annual workshop funded by the NSF, allows students to present their research in a collaborative atmosphere and to engage with senior scientists as peers. This builds confidence in the students, while also allowing them to share ideas and strengthen their research. Each GEM workshop starts with a student-run and organized "student day", in which older students volunteer to present tutorials on different magnetospheric systems and processes. These tutorials strive to put the upcoming week of talks and posters in context while providing an overarching base understanding of the magnetospheric system. By starting the week with student taught tutorials, as well as icebreaker activities, the students become comfortable with asking questions and set the tone for the less formal student and discussion-oriented workshop.

Reactive transport simulation via combination of a multiphase-capable transport code for unstructured meshes with a Gibbs energy minimization solver of geochemical equilibria

NASA Astrophysics Data System (ADS)

Fowler, S. J.; Driesner, T.; Hingerl, F. F.; Kulik, D. A.; Wagner, T.

2011-12-01

We apply a new, C++-based computational model for hydrothermal fluid-rock interaction and scale formation in geothermal reservoirs. The model couples the Complex System Modelling Platform (CSMP++) code for fluid flow in porous and fractured media (Matthai et al., 2007) with the Gibbs energy minimization numerical kernel GEMS3K of the GEM-Selektor (GEMS3) geochemical modelling package (Kulik et al., 2010) in a modular fashion. CSMP++ includes interfaces to commercial file formats, accommodating complex geometry construction using CAD (Rhinoceros) and meshing (ANSYS) software. The CSMP++ approach employs finite element-finite volume spatial discretization, implicit or explicit time discretization, and operator splitting. GEMS3K can calculate complex fluid-mineral equilibria based on a variety of equation of state and activity models. A selection of multi-electrolyte aqueous solution models, such as extended Debye-Huckel, Pitzer (Harvie et al., 1984), EUNIQUAC (Thomsen et al., 1996), and the new ELVIS model (Hingerl et al., this conference), makes it well-suited for application to a wide range of geothermal conditions. An advantage of the GEMS3K solver is simultaneous consideration of complex solid solutions (e.g., clay minerals), gases, fluids, and aqueous solutions. Each coupled simulation results in a thermodynamically-based description of the geochemical and physical state of a hydrothermal system evolving along a complex P-T-X path. The code design allows efficient, flexible incorporation of numerical and thermodynamic database improvements. We demonstrate the coupled code workflow and applicability to compositionally and physically complex natural systems relevant to enhanced geothermal systems, where temporally and spatially varying chemical interactions may take place within diverse lithologies of varying geometry. Engesgaard, P. & Kipp, K. L. (1992). Water Res. Res. 28: 2829-2843. Harvie, C. E.; Møller, N. & Weare, J. H. (1984). Geochim. Cosmochim. Acta 48: 723-751. Kulik, D. A., Wagner, T., Dmytrieva S. V, et al. (2010). GEM-Selektor home page, Paul Scherrer Institut. Available at http://gems.web.psi.ch. Matthäi, S. K., Geiger, S., Roberts, S. G., Paluszny, A., Belayneh, M., Burri, A., Mezentsev, A., Lu, H., Coumou, D., Driesner, T. & Heinrich C. A. (2007). Geol. Soc. London, Spec. Publ. 292: 405-429. Thomsen, K. Rasmussen, P. & Gani, R. (1996). Chem. Eng. Sci. 51: 3675-3683.

Cost-effectiveness analysis of gemcitabine, S-1 and gemcitabine plus S-1 for treatment of advanced pancreatic cancer based on GEST study.

PubMed

Zhou, Jing; Zhao, Rongce; Wen, Feng; Zhang, Pengfei; Tang, Ruilei; Du, Zedong; He, Xiaofeng; Zhang, Jian; Li, Qiu

2015-04-01

Gemcitabine (GEM) alone, S-1 alone and gemcitabine plus S-1 (GS) have shown a marginal clinical benefit for the treatment of advanced pancreatic cancer. However, there is no clearly defined optimal cost-effectiveness treatment. The objective of this study was to assess the cost-effectiveness of GEM alone, S-1 alone and GS for the treatment of advanced pancreatic cancer based on GEST study for public payers. A decision model compared GEM alone, S-1 alone and GS. Primary base case data were identified using the GEST study and the literatures. Costs were estimated from West China Hospital, Sichuan University, China, and incremental cost-effectiveness ratios (ICERs) were calculated. Survival benefits were reported in quality-adjusted life-months (QALMs). Sensitive analyses were performed by varying potentially modifiable parameters of the model. The base case analysis showed that the GEM cost $21,912 and yielded survival of 6.93 QALMs, S-1 cost $19,371 and yielded survival of 7.90 QALMs and GS cost $22,943 and yielded survival of 7.46 QALMs in the entire treatment. The one-way sensitivity analyses showed that the ICER of S-1 was driven mostly by the S-1 group utility score of stable state compared with GEM, and the GEM group utility score of progressed state played a key role on the ICER of GS compared with GEM. S-1 represents an attractive cost-effective treatment for advanced pancreatic cancer, given the favorable cost per QALM and improvement in clinical efficacy, especially the limited available treatment options.

AlgaGEM – a genome-scale metabolic reconstruction of algae based on the Chlamydomonas reinhardtii genome

PubMed Central

2011-01-01

Background Microalgae have the potential to deliver biofuels without the associated competition for land resources. In order to realise the rates and titres necessary for commercial production, however, system-level metabolic engineering will be required. Genome scale metabolic reconstructions have revolutionized microbial metabolic engineering and are used routinely for in silico analysis and design. While genome scale metabolic reconstructions have been developed for many prokaryotes and model eukaryotes, the application to less well characterized eukaryotes such as algae is challenging not at least due to a lack of compartmentalization data. Results We have developed a genome-scale metabolic network model (named AlgaGEM) covering the metabolism for a compartmentalized algae cell based on the Chlamydomonas reinhardtii genome. AlgaGEM is a comprehensive literature-based genome scale metabolic reconstruction that accounts for the functions of 866 unique ORFs, 1862 metabolites, 2249 gene-enzyme-reaction-association entries, and 1725 unique reactions. The reconstruction was compartmentalized into the cytoplasm, mitochondrion, plastid and microbody using available data for algae complemented with compartmentalisation data for Arabidopsis thaliana. AlgaGEM describes a functional primary metabolism of Chlamydomonas and significantly predicts distinct algal behaviours such as the catabolism or secretion rather than recycling of phosphoglycolate in photorespiration. AlgaGEM was validated through the simulation of growth and algae metabolic functions inferred from literature. Using efficient resource utilisation as the optimality criterion, AlgaGEM predicted observed metabolic effects under autotrophic, heterotrophic and mixotrophic conditions. AlgaGEM predicts increased hydrogen production when cyclic electron flow is disrupted as seen in a high producing mutant derived from mutational studies. The model also predicted the physiological pathway for H2 production and identified new targets to further improve H2 yield. Conclusions AlgaGEM is a viable and comprehensive framework for in silico functional analysis and can be used to derive new, non-trivial hypotheses for exploring this metabolically versatile organism. Flux balance analysis can be used to identify bottlenecks and new targets to metabolically engineer microalgae for production of biofuels. PMID:22369158

Estimation of Item Parameters and the GEM Algorithm.

ERIC Educational Resources Information Center

Tsutakawa, Robert K.

The models and procedures discussed in this paper are related to those presented in Bock and Aitkin (1981), where they considered the 2-parameter probit model and approximated a normally distributed prior distribution of abilities by a finite and discrete distribution. One purpose of this paper is to clarify the nature of the general EM (GEM)…

Development of the GEM-MACH-FireWork System: An Air Quality Model with On-line Wildfire Emissions within the Canadian Operational Air Quality Forecast System

NASA Astrophysics Data System (ADS)

Pavlovic, Radenko; Chen, Jack; Beaulieu, Paul-Andre; Anselmp, David; Gravel, Sylvie; Moran, Mike; Menard, Sylvain; Davignon, Didier

2014-05-01

A wildfire emissions processing system has been developed to incorporate near-real-time emissions from wildfires and large prescribed burns into Environment Canada's real-time GEM-MACH air quality (AQ) forecast system. Since the GEM-MACH forecast domain covers Canada and most of the U.S.A., including Alaska, fire location information is needed for both of these large countries. During AQ model runs, emissions from individual fire sources are injected into elevated model layers based on plume-rise calculations and then transport and chemistry calculations are performed. This "on the fly" approach to the insertion of the fire emissions provides flexibility and efficiency since on-line meteorology is used and computational overhead in emissions pre-processing is reduced. GEM-MACH-FireWork, an experimental wildfire version of GEM-MACH, was run in real-time mode for the summers of 2012 and 2013 in parallel with the normal operational version. 48-hour forecasts were generated every 12 hours (at 00 and 12 UTC). Noticeable improvements in the AQ forecasts for PM2.5 were seen in numerous regions where fire activity was high. Case studies evaluating model performance for specific regions and computed objective scores will be included in this presentation. Using the lessons learned from the last two summers, Environment Canada will continue to work towards the goal of incorporating near-real-time intermittent wildfire emissions into the operational air quality forecast system.

Reconstruction of 24 Penicillium genome-scale metabolic models shows diversity based on their secondary metabolism.

PubMed

Prigent, Sylvain; Nielsen, Jens Christian; Frisvad, Jens Christian; Nielsen, Jens

2018-06-05

Modelling of metabolism at the genome-scale have proved to be an efficient method for explaining observed phenotypic traits in living organisms. Further, it can be used as a means of predicting the effect of genetic modifications e.g. for development of microbial cell factories. With the increasing amount of genome sequencing data available, a need exists to accurately and efficiently generate such genome-scale metabolic models (GEMs) of non-model organisms, for which data is sparse. In this study, we present an automatic reconstruction approach applied to 24 Penicillium species, which have potential for production of pharmaceutical secondary metabolites or used in the manufacturing of food products such as cheeses. The models were based on the MetaCyc database and a previously published Penicillium GEM, and gave rise to comprehensive genome-scale metabolic descriptions. The models proved that while central carbon metabolism is highly conserved, secondary metabolic pathways represent the main diversity among the species. The automatic reconstruction approach presented in this study can be applied to generate GEMs of other understudied organisms, and the developed GEMs are a useful resource for the study of Penicillium metabolism, for example with the scope of developing novel cell factories. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Neuropathology of genetically engineered mice: consensus report and recommendations from an international forum.

PubMed

Weiss, William A; Israel, Mark; Cobbs, Charles; Holland, Eric; James, C David; Louis, David N; Marks, Cheryl; McClatchey, Andrea I; Roberts, Tim; Van Dyke, Terry; Wetmore, Cynthia; Chiu, Ing-Ming; Giovannini, Marco; Guha, Abhijit; Higgins, Robert J; Marino, Silvia; Radovanovic, Ivan; Reilly, Karlyne; Aldape, Ken

2002-10-24

The Mouse Models of Cancer Consortium of the NCI sponsored a meeting of neuropathologists and veterinary pathologists in New York City in November of 2000. A rapidly growing number of genetically engineered mice (GEM) predisposed to tumors of the nervous system have led to a concomitant need for neuropathological evaluation and validation of these models. A panel of 13 pathologists reviewed material representing most of the available published and unpublished GEM models of medulloblastoma, primitive neuroectodermal tumor, astrocytoma, oligodendroglioma, mixed glioma, and tumors of the peripheral nerve. The GEM tumors were found to have many similarities and some distinct differences with respect to human disease. After review of the biology and pathology for all models presented, participants were split into groups reflective of clinical expertise in human pathology, tumor biology, neuroimaging, or treatment/intervention. Recommendations were made detailing an extensive and complete neuropathological characterization of animals. Importance was placed on including information on strains, tumor clonality, and examination for genetic mutation or altered gene expression characteristics of the corresponding human malignancy. Specific proposals were made to incorporate GEM models in emerging neuroradiological modalities. Recommendations were also made for preclinical validation of these models in cancer therapeutics, and for incorporation of surrogate markers of tumor burden to facilitate preclinical evaluation of new therapies.

Using genome-scale metabolic models to compare serovars of the foodborne pathogen Listeria monocytogenes.

PubMed

Metz, Zachary P; Ding, Tong; Baumler, David J

2018-01-01

Listeria monocytogenes is a microorganism of great concern for the food industry and the cause of human foodborne disease. Therefore, novel methods of control are needed, and systems biology is one such approach to identify them. Using a combination of computational techniques and laboratory methods, genome-scale metabolic models (GEMs) can be created, validated, and used to simulate growth environments and discern metabolic capabilities of microbes of interest, including L. monocytogenes. The objective of the work presented here was to generate GEMs for six different strains of L. monocytogenes, and to both qualitatively and quantitatively validate these GEMs with experimental data to examine the diversity of metabolic capabilities of numerous strains from the three different serovar groups most associated with foodborne outbreaks and human disease. Following qualitative validation, 57 of the 95 carbon sources tested experimentally were present in the GEMs, and; therefore, these were the compounds from which comparisons could be drawn. Of these 57 compounds, agreement between in silico predictions and in vitro results for carbon source utilization ranged from 80.7% to 91.2% between strains. Nutrient utilization agreement between in silico predictions and in vitro results were also conducted for numerous nitrogen, phosphorous, and sulfur sources. Additionally, quantitative validation showed that the L. monocytogenes GEMs were able to generate in silico predictions for growth rate and growth yield that were strongly and significantly (p < 0.0013 and p < 0.0015, respectively) correlated with experimental results. These findings are significant because they show that these GEMs for L. monocytogenes are comparable to published GEMs of other organisms for agreement between in silico predictions and in vitro results. Therefore, as with the other GEMs, namely those for Escherichia coli, Staphylococcus aureus, Vibrio vulnificus, and Salmonella spp., they can be used to determine new methods of growth control and disease treatment.

The physiological basis of Glottal electromagnetic micropower sensors (GEMS) and their use in defining an excitation function for the human vocal tract

NASA Astrophysics Data System (ADS)

Burnett, Gregory Clell

1999-10-01

The definition, use, and physiological basis of Glottal Electromagnetic Micropower Sensors (GEMS) is presented. These sensors are a new type of low power (<20 milliwatts radiated) microwave regime (900 MHz to 2.5 GHz) multi-purpose motion sensor developed at the Lawrence Livermore National Laboratory. The GEMS are sensitive to movement in an adjustable field of view (FOV) surrounding the antennae. In this thesis, the GEMS has been utilized for speech research, targeted to receive motion signals from the subglottal region of the trachea. The GEMS signal is analyzed to determine the physiological source of the signal, and this information is used to calculate the subglottal pressure, effectively an excitation function for the human vocal tract. For the first time, an excitation function may be calculated in near real time using a noninvasive procedure. Several experiments and models are presented to demonstrate that the GEMS signal is representative of the motion of the subglottal posterior wall of the trachea as it vibrates in response to the pressure changes caused by the folds as they modulate the airflow supplied by the lungs. The vibrational properties of the tracheal wall are modeled using a lumped-element circuit model. Taking the output of the vocal tract to be the audio pressure captured by a microphone and the input to be the subglottal pressure, the transfer function of the vocal tract (including the nasal cavities) can be approximated every 10-30 milliseconds using an autoregressive moving-average model. Unlike the currently utilized method of transfer function approximation, this new method only involves noninvasive GEMS measurements and digital signal processing and does not demand the difficult task of obtaining precise physical measurements of the tract and subsequent estimation of the transfer function using its cross-sectional area. The ability to measure the physical motion of the trachea enables a significant number of potential applications, ranging from very accurate pitch detection to speech synthesis, speaker verification, and speech recognition.

ENED-GEM: A Conceptual Framework Model for Psychological Enjoyment Factors and Learning Mechanisms in Educational Games about the Environment.

PubMed

Fjællingsdal, Kristoffer S; Klöckner, Christian A

2017-01-01

Based on a thorough review of psychological literature, this article seeks to develop a model of game enjoyment and environmental learning (ENvironmental EDucational Game Enjoyment Model, ENED-GEM) and delineate psychological processes that might facilitate learning and inspire behavioral change from educational games about the environment. A critically acclaimed digital educational game about environmental issues (Fate of the World by Red Redemption/Soothsayer Games) was used as a case study. Two hundred forty-nine reviews of the game from the popular gaming and reviewing platform known as Steam were analyzed by means of a thematic content analysis in order to identify key player enjoyment factors believed to be relevant to the process of learning from games, as well as to gain an understanding of positive and negative impressions about the game's general content. The end results of the thematic analysis were measured up to the suggested ENED-GEM framework. Initial results generally support the main elements of the ENED-GEM, and future research into the importance of these individual core factors is outlined.

ENED-GEM: A Conceptual Framework Model for Psychological Enjoyment Factors and Learning Mechanisms in Educational Games about the Environment

PubMed Central

Fjællingsdal, Kristoffer S.; Klöckner, Christian A.

2017-01-01

Based on a thorough review of psychological literature, this article seeks to develop a model of game enjoyment and environmental learning (ENvironmental EDucational Game Enjoyment Model, ENED-GEM) and delineate psychological processes that might facilitate learning and inspire behavioral change from educational games about the environment. A critically acclaimed digital educational game about environmental issues (Fate of the World by Red Redemption/Soothsayer Games) was used as a case study. Two hundred forty-nine reviews of the game from the popular gaming and reviewing platform known as Steam were analyzed by means of a thematic content analysis in order to identify key player enjoyment factors believed to be relevant to the process of learning from games, as well as to gain an understanding of positive and negative impressions about the game’s general content. The end results of the thematic analysis were measured up to the suggested ENED-GEM framework. Initial results generally support the main elements of the ENED-GEM, and future research into the importance of these individual core factors is outlined. PMID:28701988

The Global Earthquake Model and Disaster Risk Reduction

NASA Astrophysics Data System (ADS)

Smolka, A. J.

2015-12-01

Advanced, reliable and transparent tools and data to assess earthquake risk are inaccessible to most, especially in less developed regions of the world while few, if any, globally accepted standards currently allow a meaningful comparison of risk between places. The Global Earthquake Model (GEM) is a collaborative effort that aims to provide models, datasets and state-of-the-art tools for transparent assessment of earthquake hazard and risk. As part of this goal, GEM and its global network of collaborators have developed the OpenQuake engine (an open-source software for hazard and risk calculations), the OpenQuake platform (a web-based portal making GEM's resources and datasets freely available to all potential users), and a suite of tools to support modelers and other experts in the development of hazard, exposure and vulnerability models. These resources are being used extensively across the world in hazard and risk assessment, from individual practitioners to local and national institutions, and in regional projects to inform disaster risk reduction. Practical examples for how GEM is bridging the gap between science and disaster risk reduction are: - Several countries including Switzerland, Turkey, Italy, Ecuador, Papua-New Guinea and Taiwan (with more to follow) are computing national seismic hazard using the OpenQuake-engine. In some cases these results are used for the definition of actions in building codes. - Technical support, tools and data for the development of hazard, exposure, vulnerability and risk models for regional projects in South America and Sub-Saharan Africa. - Going beyond physical risk, GEM's scorecard approach evaluates local resilience by bringing together neighborhood/community leaders and the risk reduction community as a basis for designing risk reduction programs at various levels of geography. Actual case studies are Lalitpur in the Kathmandu Valley in Nepal and Quito/Ecuador. In agreement with GEM's collaborative approach, all projects are undertaken with strong involvement of local scientific and risk reduction communities. Open-source software and careful documentation of the methodologies create full transparency of the modelling process, so that results can be reproduced any time by third parties.

Integration and Validation of the Genome-Scale Metabolic Models of Pichia pastoris: A Comprehensive Update of Protein Glycosylation Pathways, Lipid and Energy Metabolism

PubMed Central

Tomàs-Gamisans, Màrius; Ferrer, Pau; Albiol, Joan

2016-01-01

Motivation Genome-scale metabolic models (GEMs) are tools that allow predicting a phenotype from a genotype under certain environmental conditions. GEMs have been developed in the last ten years for a broad range of organisms, and are used for multiple purposes such as discovering new properties of metabolic networks, predicting new targets for metabolic engineering, as well as optimizing the cultivation conditions for biochemicals or recombinant protein production. Pichia pastoris is one of the most widely used organisms for heterologous protein expression. There are different GEMs for this methylotrophic yeast of which the most relevant and complete in the published literature are iPP668, PpaMBEL1254 and iLC915. However, these three models differ regarding certain pathways, terminology for metabolites and reactions and annotations. Moreover, GEMs for some species are typically built based on the reconstructed models of related model organisms. In these cases, some organism-specific pathways could be missing or misrepresented. Results In order to provide an updated and more comprehensive GEM for P. pastoris, we have reconstructed and validated a consensus model integrating and merging all three existing models. In this step a comprehensive review and integration of the metabolic pathways included in each one of these three versions was performed. In addition, the resulting iMT1026 model includes a new description of some metabolic processes. Particularly new information described in recently published literature is included, mainly related to fatty acid and sphingolipid metabolism, glycosylation and cell energetics. Finally the reconstructed model was tested and validated, by comparing the results of the simulations with available empirical physiological datasets results obtained from a wide range of experimental conditions, such as different carbon sources, distinct oxygen availability conditions, as well as producing of two different recombinant proteins. In these simulations, the iMT1026 model has shown a better performance than the previous existing models. PMID:26812499

Integration and Validation of the Genome-Scale Metabolic Models of Pichia pastoris: A Comprehensive Update of Protein Glycosylation Pathways, Lipid and Energy Metabolism.

PubMed

Tomàs-Gamisans, Màrius; Ferrer, Pau; Albiol, Joan

2016-01-01

Genome-scale metabolic models (GEMs) are tools that allow predicting a phenotype from a genotype under certain environmental conditions. GEMs have been developed in the last ten years for a broad range of organisms, and are used for multiple purposes such as discovering new properties of metabolic networks, predicting new targets for metabolic engineering, as well as optimizing the cultivation conditions for biochemicals or recombinant protein production. Pichia pastoris is one of the most widely used organisms for heterologous protein expression. There are different GEMs for this methylotrophic yeast of which the most relevant and complete in the published literature are iPP668, PpaMBEL1254 and iLC915. However, these three models differ regarding certain pathways, terminology for metabolites and reactions and annotations. Moreover, GEMs for some species are typically built based on the reconstructed models of related model organisms. In these cases, some organism-specific pathways could be missing or misrepresented. In order to provide an updated and more comprehensive GEM for P. pastoris, we have reconstructed and validated a consensus model integrating and merging all three existing models. In this step a comprehensive review and integration of the metabolic pathways included in each one of these three versions was performed. In addition, the resulting iMT1026 model includes a new description of some metabolic processes. Particularly new information described in recently published literature is included, mainly related to fatty acid and sphingolipid metabolism, glycosylation and cell energetics. Finally the reconstructed model was tested and validated, by comparing the results of the simulations with available empirical physiological datasets results obtained from a wide range of experimental conditions, such as different carbon sources, distinct oxygen availability conditions, as well as producing of two different recombinant proteins. In these simulations, the iMT1026 model has shown a better performance than the previous existing models.

Geoengineering by stratospheric SO2 injection: results from the Met Office HadGEM2 climate model and comparison with the Goddard Institute for Space Studies ModelE

NASA Astrophysics Data System (ADS)

Jones, A.; Haywood, J.; Boucher, O.; Kravitz, B.; Robock, A.

2010-03-01

We examine the response of the Met Office Hadley Centre's HadGEM2-AO climate model to simulated geoengineering by continuous injection of SO2 into the lower stratosphere, and compare the results with those from the Goddard Institute for Space Studies ModelE. The HadGEM2 simulations suggest that the SO2 injection rate considered here (5 Tg[SO2] yr-1) could defer the amount of global warming predicted under the Intergovernmental Panel on Climate Change's A1B scenario by approximately 30-35 years, although both models indicate rapid warming if geoengineering is not sustained. We find a broadly similar geographic distribution of the response to geoengineering in both models in terms of near-surface air temperature and mean June-August precipitation. The simulations also suggest that significant changes in regional climate would be experienced even if geoengineering was successful in maintaining global-mean temperature near current values.

Development of Semantic Description for Multiscale Models of Thermo-Mechanical Treatment of Metal Alloys

NASA Astrophysics Data System (ADS)

Macioł, Piotr; Regulski, Krzysztof

2016-08-01

We present a process of semantic meta-model development for data management in an adaptable multiscale modeling framework. The main problems in ontology design are discussed, and a solution achieved as a result of the research is presented. The main concepts concerning the application and data management background for multiscale modeling were derived from the AM3 approach—object-oriented Agile multiscale modeling methodology. The ontological description of multiscale models enables validation of semantic correctness of data interchange between submodels. We also present a possibility of using the ontological model as a supervisor in conjunction with a multiscale model controller and a knowledge base system. Multiscale modeling formal ontology (MMFO), designed for describing multiscale models' data and structures, is presented. A need for applying meta-ontology in the MMFO development process is discussed. Examples of MMFO application in describing thermo-mechanical treatment of metal alloys are discussed. Present and future applications of MMFO are described.

Comparison of Multiscale Method of Cells-Based Models for Predicting Elastic Properties of Filament Wound C/C-SiC

NASA Technical Reports Server (NTRS)

Pineda, Evan J.; Fassin, Marek; Bednarcyk, Brett A.; Reese, Stefanie; Simon, Jaan-Willem

2017-01-01

Three different multiscale models, based on the method of cells (generalized and high fidelity) micromechanics models were developed and used to predict the elastic properties of C/C-SiC composites. In particular, the following multiscale modeling strategies were employed: Concurrent multiscale modeling of all phases using the generalized method of cells, synergistic (two-way coupling in space) multiscale modeling with the generalized method of cells, and hierarchical (one-way coupling in space) multiscale modeling with the high fidelity generalized method of cells. The three models are validated against data from a hierarchical multiscale finite element model in the literature for a repeating unit cell of C/C-SiC. Furthermore, the multiscale models are used in conjunction with classical lamination theory to predict the stiffness of C/C-SiC plates manufactured via a wet filament winding and liquid silicon infiltration process recently developed by the German Aerospace Institute.

Nebraska NativeGEM (Geospatial Extension Model)

NASA Technical Reports Server (NTRS)

Bowen, Brent

2004-01-01

This proposal, Nebraska NativeGEM (Geospatial Extension Model) features a unique diversity component stemming from the exceptional reputation NNSGC has built by delivering geospatial science experiences to Nebraska s Native Americans. For 7 years, NNSGC has partner4 with the 2 tribal colleges and 4 reservation school districts in Nebraska to form the Nebraska Native American Outreach Program (NNAOP), a partnership among tribal community leaders, academia, tribal schools, and industry reaching close to 1,OOO Native American youth, over 1,200 community members (Lehrer & Zendajas, 2001).NativeGEM addresses all three key components of Cooperative State Research, Education, and Extension Service (CSREES) goals for advancing decision support, education, and workforce development through the GES. The existing long term commitments that the NNSGC and the GES have in these areas allow for the pursuit of a broad range of activities. NativeGEM builds upon these existing successful programs and collaborations. Outcomes and metrics for each proposed project are detailed in the Approach section of this document.

Investigation of processes controlling summertime gaseous elemental mercury oxidation at midlatitudinal marine, coastal, and inland sites

NASA Astrophysics Data System (ADS)

Ye, Zhuyun; Mao, Huiting; Lin, Che-Jen; Kim, Su Youn

2016-07-01

A box model incorporating a state-of-the-art chemical mechanism for atmospheric mercury (Hg) cycling was developed to investigate the oxidation of gaseous elemental mercury (GEM) at three locations in the northeastern United States: Appledore Island (AI; marine), Thompson Farm (TF; coastal, rural), and Pack Monadnock (PM; inland, rural, elevated). The chemical mechanism in this box model included the most up-to-date Hg and halogen chemistry. As a result, the box model was able to simulate reasonably the observed diurnal cycles of gaseous oxidized mercury (GOM) and chemical speciation bearing distinct differences between the three sites. In agreement with observations, simulated GOM diurnal cycles at AI and TF showed significant daytime peaks in the afternoon and nighttime minimums compared to flat GOM diurnal cycles at PM. Moreover, significant differences in the magnitude of GOM diurnal amplitude (AI > TF > PM) were captured in modeled results. At the coastal and inland sites, GEM oxidation was predominated by O3 and OH, contributing 80-99 % of total GOM production during daytime. H2O2-initiated GEM oxidation was significant (˜ 33 % of the total GOM) at the inland site during nighttime. In the marine boundary layer (MBL) atmosphere, Br and BrO became dominant GEM oxidants, with mixing ratios reaching 0.1 and 1 pptv, respectively, and contributing ˜ 70 % of the total GOM production during midday, while O3 dominated GEM oxidation (50-90 % of GOM production) over the remaining day when Br and BrO mixing ratios were diminished. The majority of HgBr produced from GEM+Br was oxidized by NO2 and HO2 to form brominated GOM species. Relative humidity and products of the CH3O2+BrO reaction possibly significantly affected the mixing ratios of Br or BrO radicals and subsequently GOM formation. Gas-particle partitioning could potentially be important in the production of GOM as well as Br and BrO at the marine site.

Natural and anthropogenic atmospheric mercury in the European Arctic: a speciation study

NASA Astrophysics Data System (ADS)

Steen, A. O.; Berg, T.; Dastoor, A. P.; Durnford, D. A.; Hole, L. R.; Pfaffhuber, K. A.

2010-11-01

It is agreed that gaseous elemental mercury (GEM) is converted to reactive gaseous mercury (RGM) during springtime Atmospheric Mercury Depletion Event (AMDE). RGM is associated with aerosols (PHg) provided that there are sufficient aerosols available for the conversion from RGM to PHg to occur. This study reports the longest time series of GEM, RGM and PHg concentrations from a European Arctic site. From 27 April 2007 until 31 December 2008 composite GEM, RGM and PHg measurements were conducted in Ny-Ålesund (78°54' N, 11°53' E). The average concentrations of the complete dataset were 1.62±0.3 ng m-3, 8±13 pgm-3 and 8±25 pgm-3 for GEM, RGM and PHg, respectively. The study revealed a clear seasonal distribution of GEM, RGM and PHg previously undiscovered. For the complete dataset the atmospheric mercury distribution was 99% GEM, whereas RGM and PHg constituted <1%. Increased PHg concentration occurred exclusively from March through April, and constituted on average 75% of the reactive mercury species in the respective period. RGM was suggested as the precursor for the PHg existence, but long range transportation of PHg has to be taken into consideration. Surprisingly, RGM was not solely formed during the spring AMDE season. Environment Canada's Global/Regional Atmospheric Heavy Metal model (GRAHM) suggested that in situ oxidation of GEM by ozone may be producing the increased RGM concentrations from March through August. Most likely, in situ oxidation of GEM by BrO produced the observed RGM from March through August. The AMDEs occurred from late March until mid June and were thought to be of non-local origin, with GEM being transported to the study site by a wide variety of air masses. With some exceptions, no clear meteorological regime was associated with the GEM, RGM and PHg concentrations.

Complete Tem-Tomography: 3D Structure of Gems Cluster

NASA Technical Reports Server (NTRS)

Matsuno, J.; Miyake, A.; Tsuchiyama, A.; Messenger, S.; Nakamura-Messenger, K.

2015-01-01

GEMS (glass with embedded metal and sulfide) grains in interplanetary dust particles (IDPs) are considered to be one of the ubiquitous and fundamental building blocks of solids in the Solar System. They have been considered to be interstellar silicate dust that survived various metamorphism or alteration processes in the protoplanetary disk but the elemental and isotopic composition measurements suggest that most of them have been formed in the protoplanetary disk as condensates from high temperature gas. This formation model is also supported by the formation of GEMS-like grains with respect to the size, mineral assemblage, texture and infrared spectrum by condensation experiments from mean GEMS composition materials. Previous GEMS studies were performed only with 2D observation by transmission electron microscopy (TEM) or scanning TEM (STEM). However, the 3D shape and structure of GEMS grains and the spatial distribution of Fe/FeS's has critical information about their formation and origin. Recently, the 3D structure of GEMS grains in ultrathin sections of cluster IDPs was revealed by electron tomography using a TEM/STEM (JEM-2100F, JEOL). However, CT images of thin sections mounted on Cu grids acquired by conventional TEM-tomography are limited to low tilt angles (e. g., less than absolute value of 75 deg. In fact, previous 3D TEM observations of GEMS were affected by some artifacts related to the limited tilt range in the TEM used. Complete tomographic images should be acquired by rotating the sample tilt angle over a range of more than absolute value of 80 deg otherwise the CT images lose their correct structures. In order to constrain the origin and formation process of GEMS grains more clearly, we performed complete electron tomography for GEMS grains. Here we report the sample preparation method we have developed for this study, and the preliminary results.

Modeling of serial data acquisition structure for GEM detector system in Matlab

NASA Astrophysics Data System (ADS)

Kolasinski, Piotr; Pozniak, Krzysztof T.; Czarski, Tomasz; Chernyshova, Maryna; Kasprowicz, Grzegorz; Krawczyk, Rafal D.; Wojenski, Andrzej; Zabolotny, Wojciech; Byszuk, Adrian

2016-09-01

This article presents method of modeling in Matlab hardware architecture dedicated for FPGA created by languages like VHDL or Verilog. Purposes of creating such type of model with its advantages and disadvantages are described. Rules presented in this article were exploited to create model of Serial Data Acquisition algorithm used in X-ray GEM detector system. Result were compared to real working model implemented in VHDL. After testing of basic structure, other two structures were modeled to see influence parameters of the structure on its behavior.

Simulation of the GEM detector for BM@N experiment

NASA Astrophysics Data System (ADS)

Baranov, Dmitriy; Rogachevsky, Oleg

2017-03-01

The Gas Electron Multiplier (GEM) detector is one of the basic parts of the BM@N experiment included in the NICA project. The simulation model that takes into account features of signal generation process in an ionization GEM chamber is presented in this article. Proper parameters for the simulation were extracted from data retrieved with the help of Garfield++ (a toolkit for the detailed simulation of particle detectors). Due to this, we are able to generate clusters in layers of the micro-strip readout that correspond to clusters retrieved from a real physics experiment.

Parallelization of fine-scale computation in Agile Multiscale Modelling Methodology

NASA Astrophysics Data System (ADS)

Macioł, Piotr; Michalik, Kazimierz

2016-10-01

Nowadays, multiscale modelling of material behavior is an extensively developed area. An important obstacle against its wide application is high computational demands. Among others, the parallelization of multiscale computations is a promising solution. Heterogeneous multiscale models are good candidates for parallelization, since communication between sub-models is limited. In this paper, the possibility of parallelization of multiscale models based on Agile Multiscale Methodology framework is discussed. A sequential, FEM based macroscopic model has been combined with concurrently computed fine-scale models, employing a MatCalc thermodynamic simulator. The main issues, being investigated in this work are: (i) the speed-up of multiscale models with special focus on fine-scale computations and (ii) on decreasing the quality of computations enforced by parallel execution. Speed-up has been evaluated on the basis of Amdahl's law equations. The problem of `delay error', rising from the parallel execution of fine scale sub-models, controlled by the sequential macroscopic sub-model is discussed. Some technical aspects of combining third-party commercial modelling software with an in-house multiscale framework and a MPI library are also discussed.

The Value of Survival Gains in Pancreatic Cancer from Novel Treatment Regimens.

PubMed

MacEwan, Joanna P; Yin, Wes; Kaura, Satyin; Khan, Zeba M

2017-02-01

Metastatic pancreatic cancer (mPC) is associated with low survival, with less than 10% of patients surviving 5 years. Recent therapies improve survival outcomes where few alternative therapies exist, but few economic analyses measure the value of survival gains attributable to new therapies. To estimate the value of survival gains in advanced or mPC attributable to the introduction of novel treatment regimens. Multivariate Cox proportional hazards models were used to estimate real-world survival gains associated with the introduction of gemcitabine (GEM) for patients diagnosed with stage IV or unstaged mPC in the Surveillance, Epidemiology, and End Results Program cancer registries. Then, evidence from clinical trials was used to evaluate the survival gains associated with nab-paclitaxel + gemcitabine (nP +GEM) and FOLFIRINOX (FFX) relative to GEM. The survival estimates and clinical trial evidence were used to calibrate an economic model and assess the cumulative value of survival gains in mPC to patients. Costs of treatment were calculated based on published cost-effectiveness studies. We estimated that the introduction of GEM in 1996 was associated with a hazard ratio of 0.920 (P < 0.05) and an increase in median survival from 3.1 to 4.5 months. Results suggested that the value of survival gains attributable to GEM equaled about $71,000 per patient, while the value attributable to nP + GEM was an additional $56,700. Estimates for the value of survival gains per patient, net of total incremental lifetime treatment costs (drugs, adverse events, and other costs), were $50,294 for GEM and an additional $31,900 for nP + GEM. Clinical trials and cost-effectiveness studies reported an overall survival gain from FFX that was larger than, but statistically similar to, nP + GEM and had greater risk of adverse events and total incremental costs. We estimated that the total value of survival gains to mPC patients, net of total costs, associated with GEM was up to $47.6 billion, and the additional values attributable to nP+GEM and FFX were up to $39.0 billion and $26.3 billion, respectively. Historically, mPC patients have faced high disease burden and had few treatment options. Treatments introduced since 1996 have led to improved survival, with varying costs associated with treatment and adverse events. Accounting for total incremental costs, the majority of the value of survival gains from GEM and nP+GEM was retained by mPC patients, highlighting the value of innovation in settings where survival is low and few alternative therapies exist. Support for this research was provided by Celgene. Precision Health Economics was compensated by Celgene for work on this study. MacEwan is an employee of, and Yin is a consultant to, Precision Health Economics. Kaura and Khan are employees of Celgene. Study concept and design were contributed primarily by Yin and MacEwan, along with Kaura and Khan. MacEwan collected the data, and data interpretation was performed primarily by MacEwan and Yin, along with Kaura and Khan. The manuscript was written and revised by MacEwan, Yin, Kaura, and Khan.

The GED4GEM project: development of a Global Exposure Database for the Global Earthquake Model initiative

USGS Publications Warehouse

Gamba, P.; Cavalca, D.; Jaiswal, K.S.; Huyck, C.; Crowley, H.

2012-01-01

In order to quantify earthquake risk of any selected region or a country of the world within the Global Earthquake Model (GEM) framework (www.globalquakemodel.org/), a systematic compilation of building inventory and population exposure is indispensable. Through the consortium of leading institutions and by engaging the domain-experts from multiple countries, the GED4GEM project has been working towards the development of a first comprehensive publicly available Global Exposure Database (GED). This geospatial exposure database will eventually facilitate global earthquake risk and loss estimation through GEM’s OpenQuake platform. This paper provides an overview of the GED concepts, aims, datasets, and inference methodology, as well as the current implementation scheme, status and way forward.

Multiscale measurement error models for aggregated small area health data.

PubMed

Aregay, Mehreteab; Lawson, Andrew B; Faes, Christel; Kirby, Russell S; Carroll, Rachel; Watjou, Kevin

2016-08-01

Spatial data are often aggregated from a finer (smaller) to a coarser (larger) geographical level. The process of data aggregation induces a scaling effect which smoothes the variation in the data. To address the scaling problem, multiscale models that link the convolution models at different scale levels via the shared random effect have been proposed. One of the main goals in aggregated health data is to investigate the relationship between predictors and an outcome at different geographical levels. In this paper, we extend multiscale models to examine whether a predictor effect at a finer level hold true at a coarser level. To adjust for predictor uncertainty due to aggregation, we applied measurement error models in the framework of multiscale approach. To assess the benefit of using multiscale measurement error models, we compare the performance of multiscale models with and without measurement error in both real and simulated data. We found that ignoring the measurement error in multiscale models underestimates the regression coefficient, while it overestimates the variance of the spatially structured random effect. On the other hand, accounting for the measurement error in multiscale models provides a better model fit and unbiased parameter estimates. © The Author(s) 2016.

Aqueous-core PEG-coated PLA nanocapsules for an efficient entrapment of water soluble anticancer drugs and a smart therapeutic response.

PubMed

Cosco, Donato; Paolino, Donatella; De Angelis, Francesco; Cilurzo, Felisa; Celia, Christian; Di Marzio, Luisa; Russo, Diego; Tsapis, Nicolas; Fattal, Elias; Fresta, Massimo

2015-01-01

Novel PEGylated PLA nanocapsules (PEG-AcPLA nanocapsules), loading high percentage of water soluble drugs have been formulated by using multiple emulsion technique without using conventional stabilizers. In particular, sodium deoxycholate hydrate has been used to obtain nanocapsules having a mean diameter of about 200 nm and a polydispersity index of ∼ 0.1. Gemcitabine hydrochloride (GEM) was used as a model of hydrophilic drug. GEM-loaded PEG-AcPLA nanocapsules demonstrated a high encapsulation efficacy and the drug-release followed a zero-order kinetic. MTT-assay evidenced an increased antitumor effect of GEM-loaded PEG-AcPLA nanocapsules compared to the free drug on different cancer cell lines and confocal laser scanning microscopy showed a significant improvement of cell interaction at 6h of incubation. In vivo anticancer activity of GEM-loaded PEG-AcPLA nanocapsules using two xenograft murine models of human solid tumors further supported the efficacy of this nano-drug, thus providing preliminary results about the potential clinical application of this innovative nanotherapeutic. Copyright © 2014 Elsevier B.V. All rights reserved.

Lorentz violation, gravitoelectromagnetic field and Bhabha scattering

NASA Astrophysics Data System (ADS)

Santos, A. F.; Khanna, Faqir C.

2018-01-01

Lorentz symmetry is a fundamental symmetry in the Standard Model (SM) and in General Relativity (GR). This symmetry holds true for all models at low energies. However, at energies near the Planck scale, it is conjectured that there may be a very small violation of Lorentz symmetry. The Standard Model Extension (SME) is a quantum field theory that includes a systematic description of Lorentz symmetry violations in all sectors of particle physics and gravity. In this paper, SME is considered to study the physical process of Bhabha Scattering in the Gravitoelectromagnetism (GEM) theory. GEM is an important formalism that is valid in a suitable approximation of general relativity. A new nonminimal coupling term that violates Lorentz symmetry is used in this paper. Differential cross-section for gravitational Bhabha scattering is calculated. The Lorentz violation contributions to this GEM scattering cross-section are small and are similar in magnitude to the case of the electromagnetic field.

Nongenetically modified Lactococcus lactis-adjuvanted vaccination enhanced innate immunity against Helicobacter pylori.

PubMed

Liu, Wei; Tan, Zhoulin; Liu, Hai; Zeng, Zhiqin; Luo, Shuanghui; Yang, Huimin; Zheng, Lufeng; Xi, Tao; Xing, Yingying

2017-10-01

Gram-positive enhancer matrix particles (GEM) produced by Lactococcus lactis can enhance vaccine-induced immune response. However, the mechanism under which this adjuvant mounts the efficacy of orally administered vaccines remains unexplored. We used a prophylactic mice model to investigate the mechanism of GEM-adjuvanted vaccination. Helicobacter pylori urease-specific antibody response was monitored and detected in murine serum by ELISA. Urease-specific splenic cytokine profile was examined. Gastric inflammatory responses were measured on day 43 or 71 by quantitative real-time PCR, flow cytometry and histology. We found that GEM enhanced the efficiency of oral H. pylori vaccine by promoting innate immunity. The vaccine CUE-GEM composed of GEM particles and recombinant antigen CTB-UE provided protection of immunized mice against H. pylori insult. The protective response was associated with induction of postimmunization gastritis and local Th1/Th17 cell-medicated immune response. We showed that innate inflammatory responses including neutrophil chemokines CXCL1-2, neutrophils, and antimicrobial proteins S100A8 and MUC1 were significantly elevated. Within all infected mice, S100A8 and MUC1 levels were negatively correlated with H. pylori burden. Strikingly, mice receiving GEM also show reduction of colonization, possibly through natural host response pathways to recruit CD4 + T cells and promote S100A8 expression. These findings suggest that GEM-based vaccine may impact Th1/Th17 immunity to orchestrate innate immune response against H. pylori infection. © 2017 John Wiley & Sons Ltd.

Downregulation of STAT3/NF-κB potentiates gemcitabine activity in pancreatic cancer cells.

PubMed

Gong, Jingjing; Muñoz, Amanda R; Pingali, Subramanya; Payton-Stewart, Florastina; Chan, Daniel E; Freeman, James W; Ghosh, Rita; Kumar, Addanki P

2017-02-01

There is an unmet need to develop new agents or strategies against therapy resistant pancreatic cancer (PanCA). Recent studies from our laboratory showed that STAT3 negatively regulates NF-κB and that inhibition of this crosstalk using Nexrutine® (Nx) reduces transcriptional activity of COX-2. Inhibition of these molecular interactions impedes pancreatic cancer cell growth as well as reduces fibrosis in a preclinical animal model. Nx is an extract derived from the bark of Phellodendron amurense and has been utilized in traditional Chinese medicine as antidiarrheal, astringent, and anti-inflammatory agent for centuries. We hypothesized that "Nx-mediated inhibition of survival molecules like STAT3 and NF-κB in pancreatic cancer cells will improve the efficacy of the conventional chemotherapeutic agent, gemcitabine (GEM)." Therefore, we explored the utility of Nx, one of its active constituents berberine and its derivatives, to enhance the effects of GEM. Using multiple human pancreatic cancer cells we found that combination treatment with Nx and GEM resulted in significant alterations of proteins in the STAT3/NF-κB signaling axis culminating in growth inhibition in a synergistic manner. Furthermore, GEM resistant cells were more sensitive to Nx treatment than their parental GEM-sensitive cells. Interestingly, although berberine, the Nx active component used, and its derivatives were biologically active in GEM sensitive cells they did not potentiate GEM activity when used in combination. Taken together, these results suggest that the natural extract, Nx, but not its active component, berberine, has the potential to improve GEM sensitivity, perhaps by down regulating STAT3/NF-κB signaling. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Multiscale Modeling in Computational Biomechanics: Determining Computational Priorities and Addressing Current Challenges

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

Tawhai, Merryn; Bischoff, Jeff; Einstein, Daniel R.

2009-05-01

Abstract In this article, we describe some current multiscale modeling issues in computational biomechanics from the perspective of the musculoskeletal and respiratory systems and mechanotransduction. First, we outline the necessity of multiscale simulations in these biological systems. Then we summarize challenges inherent to multiscale biomechanics modeling, regardless of the subdiscipline, followed by computational challenges that are system-specific. We discuss some of the current tools that have been utilized to aid research in multiscale mechanics simulations, and the priorities to further the field of multiscale biomechanics computation.

Atmospheric mercury speciation in Shanghai, China.

PubMed

Duan, Lian; Wang, Xiaohao; Wang, Dongfang; Duan, Yusen; Cheng, Na; Xiu, Guangli

2017-02-01

GEM (Gaseous elemental mercury), fine fraction (<2.5μm) PBM (Particle-bound mercury) and GOM (Gaseous oxidized mercury) were continuously monitored from Jun 1 to Dec 31 2014 at a suburban site in Shanghai. The average concentrations of GEM, PBM and GOM were 4.19±9.13ng·m -3 , 197±877pg·m -3 , 21±100pg·m -3 , respectively, which were all much higher than those at urban sites in Europe and North America and rural areas of China, but lower than those at urban sites of China. The concentrations of the three mercury species were all found with the highest concentration in December than those in summer. Overall, GEM varied little and PBM exhibited higher level during the night, while GOM typically peaked in the noon and afternoon which is consistent with that of ozone, indicating that GOM may depend on the stronger photochemical reactions during the daytime. Despite of the weak correlations of GEM with SO 2 (r=0.14, p<0.0001) and NO X (r=0.17, p<0.0001), GEM, PBM, SO 2 and NO x exhibited similar diurnal trend, suggesting that coal combustion might be the important sources of mercury in Shanghai because there is no mercury mining companies and few mercuric manufacturers in Shanghai. The strong correlation of PBM with GEM and GOM showed that directly anthropogenic emission was an important source of GEM and PBM, but the gas-particle partitioning of GOM and GEM might be also another source of PBM. The lower GEM/CO ratio of 3.9 (ng·m -3 ·ppmv -1 ) in Shanghai than that for mainland China and non-ferrous smelting factories were related to the few non-ferrous smelting factories around Shanghai. The results from the potential source contribution function (PSCF) model furtherly illustrated that in Shanghai the concentration of GEM in summer and autumn might be highly impacted by the local and regional source but wasn't heavily affected by long-range transport. Copyright © 2016 Elsevier B.V. All rights reserved.

Towards an automatic wind speed and direction profiler for Wide Field adaptive optics systems

NASA Astrophysics Data System (ADS)

Sivo, G.; Turchi, A.; Masciadri, E.; Guesalaga, A.; Neichel, B.

2018-05-01

Wide Field Adaptive Optics (WFAO) systems are among the most sophisticated adaptive optics (AO) systems available today on large telescopes. Knowledge of the vertical spatio-temporal distribution of wind speed (WS) and direction (WD) is fundamental to optimize the performance of such systems. Previous studies already proved that the Gemini Multi-Conjugated AO system (GeMS) is able to retrieve measurements of the WS and WD stratification using the SLOpe Detection And Ranging (SLODAR) technique and to store measurements in the telemetry data. In order to assess the reliability of these estimates and of the SLODAR technique applied to such complex AO systems, in this study we compared WS and WD values retrieved from GeMS with those obtained with the atmospheric model Meso-NH on a rich statistical sample of nights. It has previously been proved that the latter technique provided excellent agreement with a large sample of radiosoundings, both in statistical terms and on individual flights. It can be considered, therefore, as an independent reference. The excellent agreement between GeMS measurements and the model that we find in this study proves the robustness of the SLODAR approach. To bypass the complex procedures necessary to achieve automatic measurements of the wind with GeMS, we propose a simple automatic method to monitor nightly WS and WD using Meso-NH model estimates. Such a method can be applied to whatever present or new-generation facilities are supported by WFAO systems. The interest of this study is, therefore, well beyond the optimization of GeMS performance.

A complete categorization of multiscale models of infectious disease systems.

PubMed

Garira, Winston

2017-12-01

Modelling of infectious disease systems has entered a new era in which disease modellers are increasingly turning to multiscale modelling to extend traditional modelling frameworks into new application areas and to achieve higher levels of detail and accuracy in characterizing infectious disease systems. In this paper we present a categorization framework for categorizing multiscale models of infectious disease systems. The categorization framework consists of five integration frameworks and five criteria. We use the categorization framework to give a complete categorization of host-level immuno-epidemiological models (HL-IEMs). This categorization framework is also shown to be applicable in categorizing other types of multiscale models of infectious diseases beyond HL-IEMs through modifying the initial categorization framework presented in this study. Categorization of multiscale models of infectious disease systems in this way is useful in bringing some order to the discussion on the structure of these multiscale models.

Observations of reactive gaseous mercury in the free troposphere at the Mount Bachelor Observatory

NASA Astrophysics Data System (ADS)

Swartzendruber, P. C.; Jaffe, D. A.; Prestbo, E. M.; Weiss-Penzias, P.; Selin, N. E.; Park, R.; Jacob, D. J.; Strode, S.; Jaeglé, L.

2006-12-01

We measured gaseous elemental mercury (GEM), particulate mercury (PHg), and reactive gaseous mercury (RGM), along with CO, ozone, and aerosol scatter at the Mount Bachelor Observatory (2.7 km above sea level), Oregon, from May to August 2005. The mean mercury concentrations (at standard conditions) were 1.54 ng/m3 (GEM), 5.2 pg/m3 (PHg), and 43 pg/m3 (RGM). RGM enhancements, up to 600 pg/m3, occurred at night and were linked to a diurnal pattern of upslope and downslope flows that mixed in boundary layer air during the day and free tropospheric air at night. During the night, RGM was inversely correlated (P < 0.0001) with CO (r = -0.36), GEM (r = -0.73), and H2O (r = -0.44), was positively correlated with ozone (r = 0.38), and could not be linked to recent anthropogenic emissions from local sources or long-range transport. Principal component analysis and a composite of change in RGM versus change in GEM during RGM enhancements indicate that a nearly quantitative shift in speciation is associated with increases in ozone and decreases in water vapor and CO. This argues that high concentrations of RGM are present in the free troposphere because of in situ oxidation of GEM to RGM. A global chemical transport model reproduces the RGM mean and diurnal pattern but underestimates the magnitude of the largest observed enhancements. Since the only modeled, in situ RGM production mechanisms are oxidation of GEM by ozone and OH, this implies that there are faster reaction rates or additional RGM production mechanisms in the free troposphere.

Empowerment of women and its association with the health of the community.

PubMed

Varkey, Prathibha; Mbbs; Kureshi, Sarah; Lesnick, Timothy

2010-01-01

Empowerment and opportunities to experience power and control in one's life contribute to health and wellness. Although studies have assessed specific factors related to women's empowerment and their influence on health outcomes, there is a dearth of published literature assessing the relationship of the empowerment of women with the overall health of a community. By means of this article, we aim to assess the relationship of women's empowerment with health in 75 countries. We used the gender empowerment measure (GEM), a composite index measuring gender inequality in economic participation and decision making, political participation and decision making, and power over economic resources. All 75 countries with GEM values in the 2006 Human Development Report (HDR) were included in the study. Association between the GEM values and seven health indicators was evaluated using descriptive statistics, scatter plots, and simple and multiple linear regression models. We also controlled for gross domestic product (GDP) as a possible confounding factor and included this variable in the multiple regression models. When GDP was not considered, GEM had a statistically significant association with all health indicator variables except for proportion of 1-year-olds immunized against measles (correlation coefficient 0.063, p = 0.597). After adjusting for GDP, GEM was significantly associated with low birth weight, fertility rate, infant mortality, and age

Isotopic Composition of Gaseous Elemental Mercury in the Free Troposphere of the Pic du Midi Observatory, France.

PubMed

Fu, Xuewu; Marusczak, Nicolas; Wang, Xun; Gheusi, François; Sonke, Jeroen E

2016-06-07

Understanding the sources and transformations of mercury (Hg) in the free troposphere is a critical aspect of global Hg research. Here we present one year of observations of atmospheric Hg speciation and gaseous elemental Hg (GEM) isotopic composition at the high-altitude Pic du Midi Observatory (2860 m above sea level) in France. Biweekly integrated GEM from February 2012 to January 2013 revealed significant variations in δ(202)HgGEM (-0.04‰ to 0.52‰) but not in Δ(199)HgGEM (-0.17‰ to -0.27‰) or Δ(200)HgGEM (-0.10‰ to 0.05‰). δ(202)HgGEM was negatively correlated with CO and reflected air mass origins from Europe (high CO, low δ(202)HgGEM) and from the Atlantic Ocean (low CO, high δ(202)HgGEM). We suggest that the δ(202)HgGEM variations represent mixing of recent low δ(202)HgGEM European anthropogenic emissions with high δ(202)HgGEM northern hemispheric background GEM. In addition, Atlantic Ocean free troposphere air masses showed a positive correlation between δ(202)HgGEM and gaseous oxidized Hg (GOM) concentrations, indicative of mass-dependent Hg isotope fractionation during GEM oxidation. On the basis of atmospheric δ(202)HgGEM and speciated Hg observations, we suggest that the oceanic free troposphere is a reservoir within which GEM is readily oxidized to GOM.

Quantification of Gaseous Elemental Mercury Dry Deposition to Environmental Surfaces using Mercury Stable Isotopes in a Controlled Environment

NASA Astrophysics Data System (ADS)

Rutter, A. P.; Schauer, J. J.; Shafer, M. M.; Olson, M.; Robinson, M.; Vanderveer, P.; Creswell, J. E.; Parman, A.; Mallek, J.; Gorski, P.

2009-12-01

Andrew P. Rutter (1) * *, James J, Schauer (1,2) *, Martin M. Shafer(1,2), Michael R. Olson (1), Michael Robinson (1), Peter Vanderveer (3), Joel Creswell (1), Justin L. Mallek (1), Andrew M. Parman (1) (1) Environmental Chemistry and Technology Program, 660 N. Park St, Madison, WI 53705. (2) Wisconsin State Laboratory of Hygiene, 2601 Agriculture Drive, Madison, WI 53718. (3) Biotron, University of Wisconsin - Madison, 2115 Observatory Drive, Madison, WI 53706 * Correspond author(jjschauer@wisc.edu) * *Presenting author (aprutter@wisc.edu) Abstract Gaseous elemental mercury (GEM) is the predominant component of atmospheric mercury outside of arctic depletion events, and locations where anthropogenic point sources are not influencing atmospheric concentrations. GEM constitutes greater than 99% of the mercury mass in most rural and remote locations. While dry and wet deposition of atmospheric mercury is thought to be dominated by oxidized mercury (a.k.a. reactive mercury), only small GEM uptake to environmental surfaces could impact the input of mercury to terrestrial and aquatic ecosystems. Dry deposition and subsequent re-emission of gaseous elemental mercury is a pathway from the atmosphere that remains only partially understood from a mechanistic perspective. In order to properly model GEM dry deposition and re-emission an understanding of its dependence on irradiance, temperature, and relative humidity must be measured and parameterized for a broad spectrum of environmental surfaces colocated with surrogate deposition surfaces used to make field based dry deposition measurements. Measurements of isotopically enriched GEM dry deposition were made with a variety of environmental surfaces in a controlled environment room at the University of Wisconsin Biotron. The experimental set up allowed dry deposition components which are not easily separated in the field to be decoupled. We were able to isolate surface transfer processes from variabilities caused by atmospheric turbulence and wind speed. GEM enriched in stable isotope 198 (GEM-198) was released into the room from source at elevated but environmentally relevant concentrations of GEM-198 for several days. Uptake of GEM-198 from deciduous and conifer trees, grass turf, 3 types of soil, sand, concrete, asphalt, and adsorbent coated deposition coupons were quantified over several days. Exposures were conducted between 10oC and 30oC, in dark and light conditions. Mercury was recovered from the samples using acidic digestions and surface leaches, and then analyzed for the content of GEM-198 by high resolution ICPMS. Experimental results demonstrated that uptake by White Ash, White Spruce, and Kentucky bluegrass were significantly higher than uptakes measured for two Wisconsin soils, peat, sand, concrete and asphalt at all of the conditions studied. Deposition resistances for surface transfer processes for were calculated for each of the substrates across the conditions studied for use in atmospheric model simulations.

Microphysics in Multi-scale Modeling System with Unified Physics

NASA Technical Reports Server (NTRS)

Tao, Wei-Kuo

2012-01-01

Recently, a multi-scale modeling system with unified physics was developed at NASA Goddard. It consists of (1) a cloud-resolving model (Goddard Cumulus Ensemble model, GCE model), (2) a regional scale model (a NASA unified weather research and forecast, WRF), (3) a coupled CRM and global model (Goddard Multi-scale Modeling Framework, MMF), and (4) a land modeling system. The same microphysical processes, long and short wave radiative transfer and land processes and the explicit cloud-radiation, and cloud-land surface interactive processes are applied in this multi-scale modeling system. This modeling system has been coupled with a multi-satellite simulator to use NASA high-resolution satellite data to identify the strengths and weaknesses of cloud and precipitation processes simulated by the model. In this talk, a review of developments and applications of the multi-scale modeling system will be presented. In particular, the microphysics development and its performance for the multi-scale modeling system will be presented.

Community Multiscale Air Quality Model

EPA Science Inventory

The U.S. EPA developed the Community Multiscale Air Quality (CMAQ) system to apply a “one atmosphere” multiscale and multi-pollutant modeling approach based mainly on the “first principles” description of the atmosphere. The multiscale capability is supported by the governing di...

The Place of Global Reality in Interdisciplinary Settings: Using Modern Technology to Link Classrooms for Globalization.

ERIC Educational Resources Information Center

Morton, Chris; Mojkowski, Charles

The Global Education Model (GEM) Project, an undertaking of the Putnam-Northern Westchester Board of Cooperative Educational Services, is part of a larger effort to link students throughout the United States with their counterparts in other countries. GEM's educational technology is augmented by implementing, testing and analyzing nationally…

Novel Multiscale Modeling Tool Applied to Pseudomonas aeruginosa Biofilm Formation

PubMed Central

Biggs, Matthew B.; Papin, Jason A.

2013-01-01

Multiscale modeling is used to represent biological systems with increasing frequency and success. Multiscale models are often hybrids of different modeling frameworks and programming languages. We present the MATLAB-NetLogo extension (MatNet) as a novel tool for multiscale modeling. We demonstrate the utility of the tool with a multiscale model of Pseudomonas aeruginosa biofilm formation that incorporates both an agent-based model (ABM) and constraint-based metabolic modeling. The hybrid model correctly recapitulates oxygen-limited biofilm metabolic activity and predicts increased growth rate via anaerobic respiration with the addition of nitrate to the growth media. In addition, a genome-wide survey of metabolic mutants and biofilm formation exemplifies the powerful analyses that are enabled by this computational modeling tool. PMID:24147108

Novel multiscale modeling tool applied to Pseudomonas aeruginosa biofilm formation.

PubMed

Biggs, Matthew B; Papin, Jason A

2013-01-01

Multiscale modeling is used to represent biological systems with increasing frequency and success. Multiscale models are often hybrids of different modeling frameworks and programming languages. We present the MATLAB-NetLogo extension (MatNet) as a novel tool for multiscale modeling. We demonstrate the utility of the tool with a multiscale model of Pseudomonas aeruginosa biofilm formation that incorporates both an agent-based model (ABM) and constraint-based metabolic modeling. The hybrid model correctly recapitulates oxygen-limited biofilm metabolic activity and predicts increased growth rate via anaerobic respiration with the addition of nitrate to the growth media. In addition, a genome-wide survey of metabolic mutants and biofilm formation exemplifies the powerful analyses that are enabled by this computational modeling tool.

Impact of Ozone Radiative Feedbacks on Global Weather Forecasting

NASA Astrophysics Data System (ADS)

Ivanova, I.; de Grandpré, J.; Rochon, Y. J.; Sitwell, M.

2017-12-01

A coupled Chemical Data Assimilation system for ozone is being developed at Environment and Climate Change Canada (ECCC) with the goals to improve the forecasting of UV index and the forecasting of air quality with the Global Environmental Multi-scale (GEM) Model for Air quality and Chemistry (MACH). Furthermore, this system provides an opportunity to evaluate the benefit of ozone assimilation for improving weather forecasting with the ECCC Global Deterministic Prediction System (GDPS) for Numerical Weather Prediction (NWP). The present UV index forecasting system uses a statistical approach for evaluating the impact of ozone in clear-sky and cloudy conditions, and the use of real-time ozone analysis and ozone forecasts is highly desirable. Improving air quality forecasting with GEM-MACH further necessitates the development of integrated dynamical-chemical assimilation system. Upon its completion, real-time ozone analysis and ozone forecasts will also be available for piloting the regional air quality system, and for the computation of ozone heating rates, in replacement of the monthly mean ozone distribution currently used in the GDPS. Experiments with ozone radiative feedbacks were run with the GDPS at 25km resolution and 84 levels with a lid at 0.1 hPa and were initialized with ozone analysis that has assimilated total ozone column from OMI, OMPS, and GOME satellite instruments. The results show that the use of prognostic ozone for the computation of the heating/cooling rates has a significant impact on the temperature distribution throughout the stratosphere and upper troposphere regions. The impact of ozone assimilation is especially significant in the tropopause region, where ozone heating in the infrared wavelengths is important and ozone lifetime is relatively long. The implementation of the ozone radiative feedback in the GDPS requires addressing various issues related to model biases (temperature and humidity) and biases in equilibrium state (ozone mixing ratio, air temperature and overhead column ozone) used for the calculation of the linearized photochemical production and loss of ozone. Furthermore the radiative budget in the tropopause region is strongly affected by water vapor cooling, which impact requires further evaluation for the use in chemically coupled operational NWP systems.

Evaluation of advanced geopotential models for operational orbit determination

NASA Technical Reports Server (NTRS)

Radomski, M. S.; Davis, B. E.; Samii, M. V.; Engel, C. J.; Doll, C. E.

1988-01-01

To meet future orbit determination accuracy requirements for different NASA projects, analyses are performed using Tracking and Data Relay Satellite System (TDRSS) tracking measurements and orbit determination improvements in areas such as the modeling of the Earth's gravitational field. Current operational requirements are satisfied using the Goddard Earth Model-9 (GEM-9) geopotential model with the harmonic expansion truncated at order and degree 21 (21-by-21). This study evaluates the performance of 36-by-36 geopotential models, such as the GEM-10B and Preliminary Goddard Solution-3117 (PGS-3117) models. The Earth Radiation Budget Satellite (ERBS) and LANDSAT-5 are the spacecraft considered in this study.

An approach to multiscale modelling with graph grammars.

PubMed

Ong, Yongzhi; Streit, Katarína; Henke, Michael; Kurth, Winfried

2014-09-01

Functional-structural plant models (FSPMs) simulate biological processes at different spatial scales. Methods exist for multiscale data representation and modification, but the advantages of using multiple scales in the dynamic aspects of FSPMs remain unclear. Results from multiscale models in various other areas of science that share fundamental modelling issues with FSPMs suggest that potential advantages do exist, and this study therefore aims to introduce an approach to multiscale modelling in FSPMs. A three-part graph data structure and grammar is revisited, and presented with a conceptual framework for multiscale modelling. The framework is used for identifying roles, categorizing and describing scale-to-scale interactions, thus allowing alternative approaches to model development as opposed to correlation-based modelling at a single scale. Reverse information flow (from macro- to micro-scale) is catered for in the framework. The methods are implemented within the programming language XL. Three example models are implemented using the proposed multiscale graph model and framework. The first illustrates the fundamental usage of the graph data structure and grammar, the second uses probabilistic modelling for organs at the fine scale in order to derive crown growth, and the third combines multiscale plant topology with ozone trends and metabolic network simulations in order to model juvenile beech stands under exposure to a toxic trace gas. The graph data structure supports data representation and grammar operations at multiple scales. The results demonstrate that multiscale modelling is a viable method in FSPM and an alternative to correlation-based modelling. Advantages and disadvantages of multiscale modelling are illustrated by comparisons with single-scale implementations, leading to motivations for further research in sensitivity analysis and run-time efficiency for these models.

An approach to multiscale modelling with graph grammars

PubMed Central

Ong, Yongzhi; Streit, Katarína; Henke, Michael; Kurth, Winfried

2014-01-01

Background and Aims Functional–structural plant models (FSPMs) simulate biological processes at different spatial scales. Methods exist for multiscale data representation and modification, but the advantages of using multiple scales in the dynamic aspects of FSPMs remain unclear. Results from multiscale models in various other areas of science that share fundamental modelling issues with FSPMs suggest that potential advantages do exist, and this study therefore aims to introduce an approach to multiscale modelling in FSPMs. Methods A three-part graph data structure and grammar is revisited, and presented with a conceptual framework for multiscale modelling. The framework is used for identifying roles, categorizing and describing scale-to-scale interactions, thus allowing alternative approaches to model development as opposed to correlation-based modelling at a single scale. Reverse information flow (from macro- to micro-scale) is catered for in the framework. The methods are implemented within the programming language XL. Key Results Three example models are implemented using the proposed multiscale graph model and framework. The first illustrates the fundamental usage of the graph data structure and grammar, the second uses probabilistic modelling for organs at the fine scale in order to derive crown growth, and the third combines multiscale plant topology with ozone trends and metabolic network simulations in order to model juvenile beech stands under exposure to a toxic trace gas. Conclusions The graph data structure supports data representation and grammar operations at multiple scales. The results demonstrate that multiscale modelling is a viable method in FSPM and an alternative to correlation-based modelling. Advantages and disadvantages of multiscale modelling are illustrated by comparisons with single-scale implementations, leading to motivations for further research in sensitivity analysis and run-time efficiency for these models. PMID:25134929

Piperlongumine potentiates the effects of gemcitabine in in vitro and in vivo human pancreatic cancer models

PubMed Central

Mohammad, Jiyan; Dhillon, Harsharan; Chikara, Shireen; Mamidi, Sujan; Sreedasyam, Avinash; Chittem, Kishore; Orr, Megan; Wilkinson, John C.; Reindl, Katie M.

2018-01-01

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers due to a late diagnosis and poor response to available treatments. There is a need to identify complementary treatment strategies that will enhance the efficacy and reduce the toxicity of currently used therapeutic approaches. We investigated the ability of a known ROS inducer, piperlongumine (PL), to complement the modest anti-cancer effects of the approved chemotherapeutic agent gemcitabine (GEM) in PDAC cells in vitro and in vivo. PDAC cells treated with PL + GEM showed reduced cell viability, clonogenic survival, and growth on Matrigel compared to control and individually-treated cells. Nude mice bearing orthotopically implanted MIA PaCa-2 cells treated with both PL (5 mg/kg) and GEM (25 mg/kg) had significantly lower tumor weight and volume compared to control and single agent-treated mice. RNA sequencing (RNA-Seq) revealed that PL + GEM resulted in significant changes in p53-responsive genes that play a role in cell death, cell cycle, oxidative stress, and DNA repair pathways. Cell culture assays confirmed PL + GEM results in elevated ROS levels, arrests the cell cycle in the G0/G1 phase, and induces PDAC cell death. We propose a mechanism for the complementary anti-tumor effects of PL and GEM in PDAC cells through elevation of ROS and transcription of cell cycle arrest and cell death-associated genes. Collectively, our results suggest that PL has potential to be combined with GEM to more effectively treat PDAC. PMID:29535819

Species-related exposure of phase II metabolite gemfibrozil 1-O-β-glucuronide between human and mice: A net induction of mouse P450 activity was revealed.

PubMed

Luo, Min; Dai, Manyun; Lin, Hante; Xie, Minzhu; Lin, Jiao; Liu, Aiming; Yang, Julin

2017-12-01

Gemfibrozil is a fibrate drug used widely for dyslipidemia associated with atherosclerosis. Clinically, both gemfibrozil and its phase II metabolite gemfibrozil 1-O-β-glucuronide (gem-glu) are involved in drug-drug interaction (DDI). But the DDI risk caused by gem-glu between human and mice has not been compared. In this study, six volunteers were recruited and took a therapeutic dose of gemfibrozil for 3 days for examination of the gemfibrozil and gem-glu level in human. Male mice were fed a gemfibrozil diet (0.75%) for 7 days, following which a cocktail-based inhibitory DDI experiment was performed. Plasma samples and liver tissues from mice were collected for determination of gemfibrozil, gem-glu concentration and cytochrome p450 enzyme (P450) induction analysis. In human, the molar ratio of gem-glu/gemfibrozil was 15% and 10% at the trough concentration and the concentration at 1.5 h after the 6th dose. In contrast, this molar ratio at steady state in mice was 91%, demonstrating a 6- to 9-fold difference compared with that in human. Interestingly, a net induction of P450 activity and in vivo inductive DDI potential in mice was revealed. The P450 activity was not inhibited although the gem-glu concentration was high. These data suggested species difference of relative gem-glu exposure between human and mice, as well as a net inductive DDI potential of gemfibrozil in mouse model. Copyright © 2017 John Wiley & Sons, Ltd.

Impact of ship emissions on air pollution and AOD over North Atlantic and European Arctic

NASA Astrophysics Data System (ADS)

Kaminski, Jacek W.; Struzewska, Joanna; Jefimow, Maciej; Durka, Pawel

2016-04-01

The iAREA project is combined of experimental and theoretical research in order to contribute to the new knowledge on the impact of absorbing aerosols on the climate system in the European Arctic (http://www.igf.fuw.edu.pl/iAREA). A tropospheric chemistry model GEM-AQ (Global Environmental Multiscale Air Quality) was used as a computational tool. The core of the model is based on a weather prediction model with environmental processes (chemistry and aerosols) implanted on-line and are interactive (i.e. providing feedback of chemistry on radiation and dynamics). The numerical grid covered the Euro-Atlantic region with the resolution of 50 km. Emissions developed by NILU in the ECLIPSE project was used (Klimont et al., 2013). The model was run for two 1-year scenarios. 2014 was chosen as a base year for simulations and analysis. Scenarios include a base run with most up-to-date emissions and a run without maritime emissions. The analysis will focus on the contribution of maritime emissions on levels of particulate matter and gaseous pollutants over the European Arctic, North Atlantic and coastal areas. The annual variability will be assessed based on monthly mean near-surface concentration fields. Analysis of shipping transport on near-surface air pollution over the Euro-Atlantic region will be assessed for ozone, NO2, SO2, CO, PM10, PM2.5. Also, a contribution of ship emissions to AOD will be analysed.

ISC-GEM: Global Instrumental Earthquake Catalogue (1900-2009), III. Re-computed MS and mb, proxy MW, final magnitude composition and completeness assessment

NASA Astrophysics Data System (ADS)

Di Giacomo, Domenico; Bondár, István; Storchak, Dmitry A.; Engdahl, E. Robert; Bormann, Peter; Harris, James

2015-02-01

This paper outlines the re-computation and compilation of the magnitudes now contained in the final ISC-GEM Reference Global Instrumental Earthquake Catalogue (1900-2009). The catalogue is available via the ISC website (http://www.isc.ac.uk/iscgem/). The available re-computed MS and mb provided an ideal basis for deriving new conversion relationships to moment magnitude MW. Therefore, rather than using previously published regression models, we derived new empirical relationships using both generalized orthogonal linear and exponential non-linear models to obtain MW proxies from MS and mb. The new models were tested against true values of MW, and the newly derived exponential models were then preferred to the linear ones in computing MW proxies. For the final magnitude composition of the ISC-GEM catalogue, we preferred directly measured MW values as published by the Global CMT project for the period 1976-2009 (plus intermediate-depth earthquakes between 1962 and 1975). In addition, over 1000 publications have been examined to obtain direct seismic moment M0 and, therefore, also MW estimates for 967 large earthquakes during 1900-1978 (Lee and Engdahl, 2015) by various alternative methods to the current GCMT procedure. In all other instances we computed MW proxy values by converting our re-computed MS and mb values into MW, using the newly derived non-linear regression models. The final magnitude composition is an improvement in terms of magnitude homogeneity compared to previous catalogues. The magnitude completeness is not homogeneous over the 110 years covered by the ISC-GEM catalogue. Therefore, seismicity rate estimates may be strongly affected without a careful time window selection. In particular, the ISC-GEM catalogue appears to be complete down to MW 5.6 starting from 1964, whereas for the early instrumental period the completeness varies from ∼7.5 to 6.2. Further time and resources would be necessary to homogenize the magnitude of completeness over the entire catalogue length.

S/G-1: an ab initio force-field blending frozen Hermite Gaussian densities and distributed multipoles. Proof of concept and first applications to metal cations.

PubMed

Chaudret, Robin; Gresh, Nohad; Narth, Christophe; Lagardère, Louis; Darden, Thomas A; Cisneros, G Andrés; Piquemal, Jean-Philip

2014-09-04

We demonstrate as a proof of principle the capabilities of a novel hybrid MM'/MM polarizable force field to integrate short-range quantum effects in molecular mechanics (MM) through the use of Gaussian electrostatics. This lead to a further gain in accuracy in the representation of the first coordination shell of metal ions. It uses advanced electrostatics and couples two point dipole polarizable force fields, namely, the Gaussian electrostatic model (GEM), a model based on density fitting, which uses fitted electronic densities to evaluate nonbonded interactions, and SIBFA (sum of interactions between fragments ab initio computed), which resorts to distributed multipoles. To understand the benefits of the use of Gaussian electrostatics, we evaluate first the accuracy of GEM, which is a pure density-based Gaussian electrostatics model on a test Ca(II)-H2O complex. GEM is shown to further improve the agreement of MM polarization with ab initio reference results. Indeed, GEM introduces nonclassical effects by modeling the short-range quantum behavior of electric fields and therefore enables a straightforward (and selective) inclusion of the sole overlap-dependent exchange-polarization repulsive contribution by means of a Gaussian damping function acting on the GEM fields. The S/G-1 scheme is then introduced. Upon limiting the use of Gaussian electrostatics to metal centers only, it is shown to be able to capture the dominant quantum effects at play on the metal coordination sphere. S/G-1 is able to accurately reproduce ab initio total interaction energies within closed-shell metal complexes regarding each individual contribution including the separate contributions of induction, polarization, and charge-transfer. Applications of the method are provided for various systems including the HIV-1 NCp7-Zn(II) metalloprotein. S/G-1 is then extended to heavy metal complexes. Tested on Hg(II) water complexes, S/G-1 is shown to accurately model polarization up to quadrupolar response level. This opens up the possibility of embodying explicit scalar relativistic effects in molecular mechanics thanks to the direct transferability of ab initio pseudopotentials. Therefore, incorporating GEM-like electron density for a metal cation enable the introduction of nonambiguous short-range quantum effects within any point-dipole based polarizable force field without the need of an extensive parametrization.

Computational methods for reactive transport modeling: A Gibbs energy minimization approach for multiphase equilibrium calculations

NASA Astrophysics Data System (ADS)

Leal, Allan M. M.; Kulik, Dmitrii A.; Kosakowski, Georg

2016-02-01

We present a numerical method for multiphase chemical equilibrium calculations based on a Gibbs energy minimization approach. The method can accurately and efficiently determine the stable phase assemblage at equilibrium independently of the type of phases and species that constitute the chemical system. We have successfully applied our chemical equilibrium algorithm in reactive transport simulations to demonstrate its effective use in computationally intensive applications. We used FEniCS to solve the governing partial differential equations of mass transport in porous media using finite element methods in unstructured meshes. Our equilibrium calculations were benchmarked with GEMS3K, the numerical kernel of the geochemical package GEMS. This allowed us to compare our results with a well-established Gibbs energy minimization algorithm, as well as their performance on every mesh node, at every time step of the transport simulation. The benchmark shows that our novel chemical equilibrium algorithm is accurate, robust, and efficient for reactive transport applications, and it is an improvement over the Gibbs energy minimization algorithm used in GEMS3K. The proposed chemical equilibrium method has been implemented in Reaktoro, a unified framework for modeling chemically reactive systems, which is now used as an alternative numerical kernel of GEMS.

The GTP binding proteins Gem and Rad are negative regulators of the Rho–Rho kinase pathway

PubMed Central

Ward, Yvona; Yap, Seow-Fong; Ravichandran, V.; Matsumura, Fumio; Ito, Masaaki; Spinelli, Beth; Kelly, Kathleen

2002-01-01

The cytoskeletal changes that alter cellular morphogenesis and motility depend upon a complex interplay among molecules that regulate actin, myosin, and other cytoskeletal components. The Rho family of GTP binding proteins are important upstream mediators of cytoskeletal organization. Gem and Rad are members of another family of small GTP binding proteins (the Rad, Gem, and Kir family) for which biochemical functions have been mostly unknown. Here we show that Gem and Rad interface with the Rho pathway through association with the Rho effectors, Rho kinase (ROK) α and β. Gem binds ROKβ independently of RhoA in the ROKβ coiled-coil region adjacent to the Rho binding domain. Expression of Gem inhibited ROKβ-mediated phosphorylation of myosin light chain and myosin phosphatase, but not LIM kinase, suggesting that Gem acts by modifying the substrate specificity of ROKβ. Gem or Rad expression led to cell flattening and neurite extension in N1E-115 neuroblastoma cells. In interference assays, Gem opposed ROKβ- and Rad opposed ROKα-mediated cell rounding and neurite retraction. Gem did not oppose cell rounding initiated by ROKβ containing a deletion of the Gem binding region, demonstrating that Gem binding to ROKβ is required for the effects observed. In epithelial or fibroblastic cells, Gem or Rad expression resulted in stress fiber and focal adhesion disassembly. In addition, Gem reverted the anchorage-independent growth and invasiveness of Dbl-transformed fibroblasts. These results identify physiological roles for Gem and Rad in cytoskeletal regulation mediated by ROK. PMID:11956230

Towards a Multiscale Approach to Cybersecurity Modeling

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

Hogan, Emilie A.; Hui, Peter SY; Choudhury, Sutanay

2013-11-12

We propose a multiscale approach to modeling cyber networks, with the goal of capturing a view of the network and overall situational awareness with respect to a few key properties--- connectivity, distance, and centrality--- for a system under an active attack. We focus on theoretical and algorithmic foundations of multiscale graphs, coming from an algorithmic perspective, with the goal of modeling cyber system defense as a specific use case scenario. We first define a notion of \\emph{multiscale} graphs, in contrast with their well-studied single-scale counterparts. We develop multiscale analogs of paths and distance metrics. As a simple, motivating example ofmore » a common metric, we present a multiscale analog of the all-pairs shortest-path problem, along with a multiscale analog of a well-known algorithm which solves it. From a cyber defense perspective, this metric might be used to model the distance from an attacker's position in the network to a sensitive machine. In addition, we investigate probabilistic models of connectivity. These models exploit the hierarchy to quantify the likelihood that sensitive targets might be reachable from compromised nodes. We believe that our novel multiscale approach to modeling cyber-physical systems will advance several aspects of cyber defense, specifically allowing for a more efficient and agile approach to defending these systems.« less

Filters for Improvement of Multiscale Data from Atomistic Simulations

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

Gardner, David J.; Reynolds, Daniel R.

Multiscale computational models strive to produce accurate and efficient numerical simulations of systems involving interactions across multiple spatial and temporal scales that typically differ by several orders of magnitude. Some such models utilize a hybrid continuum-atomistic approach combining continuum approximations with first-principles-based atomistic models to capture multiscale behavior. By following the heterogeneous multiscale method framework for developing multiscale computational models, unknown continuum scale data can be computed from an atomistic model. Concurrently coupling the two models requires performing numerous atomistic simulations which can dominate the computational cost of the method. Furthermore, when the resulting continuum data is noisy due tomore » sampling error, stochasticity in the model, or randomness in the initial conditions, filtering can result in significant accuracy gains in the computed multiscale data without increasing the size or duration of the atomistic simulations. In this work, we demonstrate the effectiveness of spectral filtering for increasing the accuracy of noisy multiscale data obtained from atomistic simulations. Moreover, we present a robust and automatic method for closely approximating the optimum level of filtering in the case of additive white noise. By improving the accuracy of this filtered simulation data, it leads to a dramatic computational savings by allowing for shorter and smaller atomistic simulations to achieve the same desired multiscale simulation precision.« less

Filters for Improvement of Multiscale Data from Atomistic Simulations

DOE PAGES

Gardner, David J.; Reynolds, Daniel R.

2017-01-05

Multiscale computational models strive to produce accurate and efficient numerical simulations of systems involving interactions across multiple spatial and temporal scales that typically differ by several orders of magnitude. Some such models utilize a hybrid continuum-atomistic approach combining continuum approximations with first-principles-based atomistic models to capture multiscale behavior. By following the heterogeneous multiscale method framework for developing multiscale computational models, unknown continuum scale data can be computed from an atomistic model. Concurrently coupling the two models requires performing numerous atomistic simulations which can dominate the computational cost of the method. Furthermore, when the resulting continuum data is noisy due tomore » sampling error, stochasticity in the model, or randomness in the initial conditions, filtering can result in significant accuracy gains in the computed multiscale data without increasing the size or duration of the atomistic simulations. In this work, we demonstrate the effectiveness of spectral filtering for increasing the accuracy of noisy multiscale data obtained from atomistic simulations. Moreover, we present a robust and automatic method for closely approximating the optimum level of filtering in the case of additive white noise. By improving the accuracy of this filtered simulation data, it leads to a dramatic computational savings by allowing for shorter and smaller atomistic simulations to achieve the same desired multiscale simulation precision.« less

Gas Electron Multipler (GEM) detectors for parity-violating electron scattering experiments at Jefferson Lab

NASA Astrophysics Data System (ADS)

Matter, John; Gnanvo, Kondo; Liyanage, Nilanga; Solid Collaboration; Moller Collaboration

2017-09-01

The JLab Parity Violation In Deep Inelastic Scattering (PVDIS) experiment will use the upgraded 12 GeV beam and proposed Solenoidal Large Intensity Device (SoLID) to measure the parity-violating electroweak asymmetry in DIS of polarized electrons with high precision in order to search for physics beyond the Standard Model. Unlike many prior Parity-Violating Electron Scattering (PVES) experiments, PVDIS is a single-particle tracking experiment. Furthermore the experiment's high luminosity combined with the SoLID spectrometer's open configuration creates high-background conditions. As such, the PVDIS experiment has the most demanding tracking detector needs of any PVES experiment to date, requiring precision detectors capable of operating at high-rate conditions in PVDIS's full production luminosity. Developments in large-area GEM detector R&D and SoLID simulations have demonstrated that GEMs provide a cost-effective solution for PVDIS's tracking needs. The integrating-detector-based JLab Measurement Of Lepton Lepton Electroweak Reaction (MOLLER) experiment requires high-precision tracking for acceptance calibration. Large-area GEMs will be used as tracking detectors for MOLLER as well. The conceptual designs of GEM detectors for the PVDIS and MOLLER experiments will be presented.

Neonatal mucosal immunization with a non-living, non-genetically modified Lactococcus lactis vaccine carrier induces systemic and local Th1-type immunity and protects against lethal bacterial infection

PubMed Central

Ramirez, Karina; Ditamo, Yanina; Rodriguez, Liliana; Picking, Wendy L.; van Roosmalen, Maarten L.; Leenhouts, Kees; Pasetti, Marcela F.

2010-01-01

Safe and effective immunization of newborns and infants can significantly reduce childhood mortality, yet conventional vaccines have been largely unsuccessful in stimulating the neonatal immune system. We explored the capacity of a novel mucosal antigen delivery system consisting of non-living, non-genetically modified Lactococcus lactis particles, designated Gram-positive Enhancer Matrix (GEM), to induce immune responses in the neonatal setting. Yersinia pestis LcrV, used as model protective antigen, was displayed on the GEM particles. Newborn mice immunized intranasally with GEM-LcrV developed LcrV-specific antibodies, Th1-type cell-mediated immunity, and were protected against lethal Y. pestis (plague) infection. The GEM particles activated and enhanced the maturation of neonatal dendritic cells both in vivo and in vitro. These dendritic cells showed increased capacities for secretion of pro-inflammatory and Th1-cell polarizing cytokines, antigen presentation and stimulation of CD4+ and CD8+ T cells. These data show that mucosal immunization with L. lactis GEM particles carrying vaccine antigens represents a promising approach to prevent infectious diseases early in life. PMID:19924118

Benzylic oxidation of gemfibrozil-1-O-beta-glucuronide by P450 2C8 leads to heme alkylation and irreversible inhibition.

PubMed

Baer, Brian R; DeLisle, Robert Kirk; Allen, Andrew

2009-07-01

Gemfibrozil-1-O-beta-glucuronide (GEM-1-O-gluc), a major metabolite of the antihyperlipidemic drug gemfibrozil, is a mechanism-based inhibitor of P450 2C8 in vitro, and this irreversible inactivation may lead to clinical drug-drug interactions between gemfibrozil and other P450 2C8 substrates. In light of this in vitro finding and the observation that the glucuronide conjugate does not contain any obvious structural alerts, the current study was conducted to determine the potential site of GEM-1-O-gluc bioactivation and the subsequent mechanism of P450 2C8 inhibition (i.e., modification of apoprotein or heme). LC/MS analysis of a reaction mixture containing recombinant P450 2C8 and GEM-1-O-gluc revealed that the substrate was covalently linked to the heme prosthetic heme group during catalysis. A combination of mass spectrometry and deuterium isotope effects revealed that a benzylic carbon on the 2',5'-dimethylphenoxy group of GEM-1-O-gluc was covalently bound to the heme of P450 2C8. The regiospecificity of substrate addition to the heme group was not confirmed experimentally, but computational modeling experiments indicated that the gamma-meso position was the most likely site of modification. The metabolite profile, which consisted of two benzyl alcohol metabolites and a 4'-hydroxy-GEM-1-O-gluc metabolite, indicated that oxidation of GEM-1-O-gluc was limited to the 2',5'-dimethylphenoxy group. These results are consistent with an inactivation mechanism wherein GEM-1-O-gluc is oxidized to a benzyl radical intermediate, which evades oxygen rebound, and adds to the gamma-meso position of heme. Mechanism-based inhibition of P450 2C8 can be rationalized by the formation of the GEM-1-O-gluc-heme adduct and the consequential restriction of additional substrate access to the catalytic iron center.

Facing the challenges of multiscale modelling of bacterial and fungal pathogen–host interactions

PubMed Central

Schleicher, Jana; Conrad, Theresia; Gustafsson, Mika; Cedersund, Gunnar; Guthke, Reinhard

2017-01-01

Abstract Recent and rapidly evolving progress on high-throughput measurement techniques and computational performance has led to the emergence of new disciplines, such as systems medicine and translational systems biology. At the core of these disciplines lies the desire to produce multiscale models: mathematical models that integrate multiple scales of biological organization, ranging from molecular, cellular and tissue models to organ, whole-organism and population scale models. Using such models, hypotheses can systematically be tested. In this review, we present state-of-the-art multiscale modelling of bacterial and fungal infections, considering both the pathogen and host as well as their interaction. Multiscale modelling of the interactions of bacteria, especially Mycobacterium tuberculosis, with the human host is quite advanced. In contrast, models for fungal infections are still in their infancy, in particular regarding infections with the most important human pathogenic fungi, Candida albicans and Aspergillus fumigatus. We reflect on the current availability of computational approaches for multiscale modelling of host–pathogen interactions and point out current challenges. Finally, we provide an outlook for future requirements of multiscale modelling. PMID:26857943

Recognizing patterns of visual field loss using unsupervised machine learning

NASA Astrophysics Data System (ADS)

Yousefi, Siamak; Goldbaum, Michael H.; Zangwill, Linda M.; Medeiros, Felipe A.; Bowd, Christopher

2014-03-01

Glaucoma is a potentially blinding optic neuropathy that results in a decrease in visual sensitivity. Visual field abnormalities (decreased visual sensitivity on psychophysical tests) are the primary means of glaucoma diagnosis. One form of visual field testing is Frequency Doubling Technology (FDT) that tests sensitivity at 52 points within the visual field. Like other psychophysical tests used in clinical practice, FDT results yield specific patterns of defect indicative of the disease. We used Gaussian Mixture Model with Expectation Maximization (GEM), (EM is used to estimate the model parameters) to automatically separate FDT data into clusters of normal and abnormal eyes. Principal component analysis (PCA) was used to decompose each cluster into different axes (patterns). FDT measurements were obtained from 1,190 eyes with normal FDT results and 786 eyes with abnormal (i.e., glaucomatous) FDT results, recruited from a university-based, longitudinal, multi-center, clinical study on glaucoma. The GEM input was the 52-point FDT threshold sensitivities for all eyes. The optimal GEM model separated the FDT fields into 3 clusters. Cluster 1 contained 94% normal fields (94% specificity) and clusters 2 and 3 combined, contained 77% abnormal fields (77% sensitivity). For clusters 1, 2 and 3 the optimal number of PCA-identified axes were 2, 2 and 5, respectively. GEM with PCA successfully separated FDT fields from healthy and glaucoma eyes and identified familiar glaucomatous patterns of loss.

ONE-ATMOSPHERE DYNAMICS DESCRIPTION IN THE MODELS-3 COMMUNITY MULTI-SCALE QUALITY (CMAQ) MODELING SYSTEM

EPA Science Inventory

This paper proposes a general procedure to link meteorological data with air quality models, such as U.S. EPA's Models-3 Community Multi-scale Air Quality (CMAQ) modeling system. CMAQ is intended to be used for studying multi-scale (urban and regional) and multi-pollutant (ozon...

Multi-model study of mercury dispersion in the atmosphere: atmospheric processes and model evaluation

NASA Astrophysics Data System (ADS)

Travnikov, Oleg; Angot, Hélène; Artaxo, Paulo; Bencardino, Mariantonia; Bieser, Johannes; D'Amore, Francesco; Dastoor, Ashu; De Simone, Francesco; Diéguez, María del Carmen; Dommergue, Aurélien; Ebinghaus, Ralf; Feng, Xin Bin; Gencarelli, Christian N.; Hedgecock, Ian M.; Magand, Olivier; Martin, Lynwill; Matthias, Volker; Mashyanov, Nikolay; Pirrone, Nicola; Ramachandran, Ramesh; Read, Katie Alana; Ryjkov, Andrei; Selin, Noelle E.; Sena, Fabrizio; Song, Shaojie; Sprovieri, Francesca; Wip, Dennis; Wängberg, Ingvar; Yang, Xin

2017-04-01

Current understanding of mercury (Hg) behavior in the atmosphere contains significant gaps. Some key characteristics of Hg processes, including anthropogenic and geogenic emissions, atmospheric chemistry, and air-surface exchange, are still poorly known. This study provides a complex analysis of processes governing Hg fate in the atmosphere involving both measured data from ground-based sites and simulation results from chemical transport models. A variety of long-term measurements of gaseous elemental Hg (GEM) and reactive Hg (RM) concentration as well as Hg wet deposition flux have been compiled from different global and regional monitoring networks. Four contemporary global-scale transport models for Hg were used, both in their state-of-the-art configurations and for a number of numerical experiments to evaluate particular processes. Results of the model simulations were evaluated against measurements. As follows from the analysis, the interhemispheric GEM gradient is largely formed by the prevailing spatial distribution of anthropogenic emissions in the Northern Hemisphere. The contributions of natural and secondary emissions enhance the south-to-north gradient, but their effect is less significant. Atmospheric chemistry has a limited effect on the spatial distribution and temporal variation of GEM concentration in surface air. In contrast, RM air concentration and wet deposition are largely defined by oxidation chemistry. The Br oxidation mechanism can reproduce successfully the observed seasonal variation of the RM / GEM ratio in the near-surface layer, but it predicts a wet deposition maximum in spring instead of in summer as observed at monitoring sites in North America and Europe. Model runs with OH chemistry correctly simulate both the periods of maximum and minimum values and the amplitude of observed seasonal variation but shift the maximum RM / GEM ratios from spring to summer. O3 chemistry does not predict significant seasonal variation of Hg oxidation. Hence, the performance of the Hg oxidation mechanisms under study differs in the extent to which they can reproduce the various observed parameters. This variation implies possibility of more complex chemistry and multiple Hg oxidation pathways occurring concurrently in various parts of the atmosphere.

The Gem GTP-binding protein promotes morphological differentiation in neuroblastoma.

PubMed

Leone, A; Mitsiades, N; Ward, Y; Spinelli, B; Poulaki, V; Tsokos, M; Kelly, K

2001-05-31

Gem is a small GTP-binding protein within the Ras superfamily whose function has not been determined. We report here that ectopic Gem expression is sufficient to stimulate cell flattening and neurite extension in N1E-115 and SH-SY5Y neuroblastoma cells, suggesting a role for Gem in cytoskeletal rearrangement and/or morphological differentiation of neurons. Consistent with this potential function, in clinical samples of neuroblastoma, Gem protein was most highly expressed within cells which had differentiated to express ganglionic morphology. Gem was also observed in developing trigeminal nerve ganglia in 12.5 day mouse embryos, demonstrating that Gem expression is a property of normal ganglionic development. Although Gem expression is rare in epithelial and hematopoietic cancer cell lines, constitutive Gem levels were detected in several neuroblastoma cell lines and could be further induced as much as 10-fold following treatment with PMA or the acetylcholine muscarinic agonist, carbachol.

Integrating Multiscale Modeling with Drug Effects for Cancer Treatment.

PubMed

Li, Xiangfang L; Oduola, Wasiu O; Qian, Lijun; Dougherty, Edward R

2015-01-01

In this paper, we review multiscale modeling for cancer treatment with the incorporation of drug effects from an applied system's pharmacology perspective. Both the classical pharmacology and systems biology are inherently quantitative; however, systems biology focuses more on networks and multi factorial controls over biological processes rather than on drugs and targets in isolation, whereas systems pharmacology has a strong focus on studying drugs with regard to the pharmacokinetic (PK) and pharmacodynamic (PD) relations accompanying drug interactions with multiscale physiology as well as the prediction of dosage-exposure responses and economic potentials of drugs. Thus, it requires multiscale methods to address the need for integrating models from the molecular levels to the cellular, tissue, and organism levels. It is a common belief that tumorigenesis and tumor growth can be best understood and tackled by employing and integrating a multifaceted approach that includes in vivo and in vitro experiments, in silico models, multiscale tumor modeling, continuous/discrete modeling, agent-based modeling, and multiscale modeling with PK/PD drug effect inputs. We provide an example application of multiscale modeling employing stochastic hybrid system for a colon cancer cell line HCT-116 with the application of Lapatinib drug. It is observed that the simulation results are similar to those observed from the setup of the wet-lab experiments at the Translational Genomics Research Institute.

The Ohio State 1991 geopotential and sea surface topography harmonic coefficient models

NASA Technical Reports Server (NTRS)

Rapp, Richard H.; Wang, Yan Ming; Pavlis, Nikolaos K.

1991-01-01

The computation is described of a geopotential model to deg 360, a sea surface topography model to deg 10/15, and adjusted Geosat orbits for the first year of the exact repeat mission (ERM). This study started from the GEM-T2 potential coefficient model and it's error covariance matrix and Geosat orbits (for 22 ERMs) computed by Haines et al. using the GEM-T2 model. The first step followed the general procedures which use a radial orbit error theory originally developed by English. The Geosat data was processed to find corrections to the a priori geopotential model, corrections to a radial orbit error model for 76 Geosat arcs, and coefficients of a harmonic representation of the sea surface topography. The second stage of the analysis took place by doing a combination of the GEM-T2 coefficients with 30 deg gravity data derived from surface gravity data and anomalies obtained from altimeter data. The analysis has shown how a high degree spherical harmonic model can be determined combining the best aspects of two different analysis techniques. The error analysis was described that has led to the accuracy estimates for all the coefficients to deg 360. Significant work is needed to improve the modeling effort.

Impact of a Genetically Engineered Bacterium with Enhanced Alkaline Phosphatase Activity on Marine Phytoplankton Communities

PubMed Central

Sobecky, P. A.; Schell, M. A.; Moran, M. A.; Hodson, R. E.

1996-01-01

An indigenous marine Achromobacter sp. was isolated from coastal Georgia seawater and modified in the laboratory by introduction of a plasmid with a phoA hybrid gene that directed constitutive overproduction of alkaline phosphatase. The effects of this "indigenous" genetically engineered microorganism (GEM) on phosphorus cycling were determined in seawater microcosms following the addition of a model dissolved organic phosphorus compound, glycerol 3-phosphate, at a concentration of 1 or 10 (mu)M. Within 48 h, a 2- to 10-fold increase in the concentration of inorganic phosphate occurred in microcosms containing the GEM (added at an initial density equivalent to 8% of the total bacterial population) relative to controls containing only natural microbial populations, natural populations with the unmodified Achromobacter sp., or natural populations with the Achromobacter sp. containing the plasmid but not the phoA gene. Secondary effects of the GEM on the phytoplankton community were observed after several days, evident as sustained increases in phytoplankton biomass (up to 14-fold) over that in controls. Even in the absence of added glycerol 3-phosphate, a numerically stable GEM population (averaging 3 to 5% of culturable bacteria) was established within 2 to 3 weeks of introduction into seawater. Moreover, alkaline phosphatase activity in microcosms with the GEM was substantially higher than that in controls for up to 25 days, and microcosms containing the GEM maintained the potential for net phosphate accumulation above control levels for longer than 1 month. PMID:16535222

Gaseous elemental mercury in the marine boundary layer and air-sea flux in the Southern Ocean in austral summer.

PubMed

Wang, Jiancheng; Xie, Zhouqing; Wang, Feiyue; Kang, Hui

2017-12-15

Gaseous elemental mercury (GEM) in the marine boundary layer (MBL), and dissolved gaseous mercury (DGM) in surface seawater of the Southern Ocean were measured in the austral summer from December 13, 2014 to February 1, 2015. GEM concentrations in the MBL ranged from 0.4 to 1.9ngm -3 (mean±standard deviation: 0.9±0.2ngm -3 ), whereas DGM concentrations in surface seawater ranged from 7.0 to 75.9pgL -1 (mean±standard deviation: 23.7±13.2pgL -1 ). The occasionally observed low GEM in the MBL suggested either the occurrence of atmospheric mercury depletion in summer, or the transport of GEM-depleted air from the Antarctic Plateau. Elevated GEM concentrations in the MBL and DGM concentrations in surface seawater were consistently observed in the ice-covered region of the Ross Sea implying the influence of the sea ice environment. Diminishing sea ice could cause more mercury evasion from the ocean to the air. Using the thin film gas exchange model, the air-sea fluxes of gaseous mercury in non-ice-covered area during the study period were estimated to range from 0.0 to 6.5ngm -2 h -1 with a mean value of 1.5±1.8ngm -2 h -1 , revealing GEM (re-)emission from the East Southern Ocean in summer. Copyright © 2017 Elsevier B.V. All rights reserved.

The GAAIN Entity Mapper: An Active-Learning System for Medical Data Mapping.

PubMed

Ashish, Naveen; Dewan, Peehoo; Toga, Arthur W

2015-01-01

This work is focused on mapping biomedical datasets to a common representation, as an integral part of data harmonization for integrated biomedical data access and sharing. We present GEM, an intelligent software assistant for automated data mapping across different datasets or from a dataset to a common data model. The GEM system automates data mapping by providing precise suggestions for data element mappings. It leverages the detailed metadata about elements in associated dataset documentation such as data dictionaries that are typically available with biomedical datasets. It employs unsupervised text mining techniques to determine similarity between data elements and also employs machine-learning classifiers to identify element matches. It further provides an active-learning capability where the process of training the GEM system is optimized. Our experimental evaluations show that the GEM system provides highly accurate data mappings (over 90% accuracy) for real datasets of thousands of data elements each, in the Alzheimer's disease research domain. Further, the effort in training the system for new datasets is also optimized. We are currently employing the GEM system to map Alzheimer's disease datasets from around the globe into a common representation, as part of a global Alzheimer's disease integrated data sharing and analysis network called GAAIN. GEM achieves significantly higher data mapping accuracy for biomedical datasets compared to other state-of-the-art tools for database schema matching that have similar functionality. With the use of active-learning capabilities, the user effort in training the system is minimal.

The GAAIN Entity Mapper: An Active-Learning System for Medical Data Mapping

PubMed Central

Ashish, Naveen; Dewan, Peehoo; Toga, Arthur W.

2016-01-01

This work is focused on mapping biomedical datasets to a common representation, as an integral part of data harmonization for integrated biomedical data access and sharing. We present GEM, an intelligent software assistant for automated data mapping across different datasets or from a dataset to a common data model. The GEM system automates data mapping by providing precise suggestions for data element mappings. It leverages the detailed metadata about elements in associated dataset documentation such as data dictionaries that are typically available with biomedical datasets. It employs unsupervised text mining techniques to determine similarity between data elements and also employs machine-learning classifiers to identify element matches. It further provides an active-learning capability where the process of training the GEM system is optimized. Our experimental evaluations show that the GEM system provides highly accurate data mappings (over 90% accuracy) for real datasets of thousands of data elements each, in the Alzheimer's disease research domain. Further, the effort in training the system for new datasets is also optimized. We are currently employing the GEM system to map Alzheimer's disease datasets from around the globe into a common representation, as part of a global Alzheimer's disease integrated data sharing and analysis network called GAAIN1. GEM achieves significantly higher data mapping accuracy for biomedical datasets compared to other state-of-the-art tools for database schema matching that have similar functionality. With the use of active-learning capabilities, the user effort in training the system is minimal. PMID:26793094

The role of evaporites in the formation of gems during metamorphism of carbonate platforms: a review

NASA Astrophysics Data System (ADS)

Giuliani, Gaston; Dubessy, Jean; Ohnenstetter, Daniel; Banks, David; Branquet, Yannick; Feneyrol, Julien; Fallick, Anthony E.; Martelat, Jean-Emmanuel

2018-01-01

The mineral and fluid inclusions trapped by gemstones during the metamorphism of carbonate platform successions are precious markers for the understanding of gem genesis. The nature and chemical composition of inclusions highlight the major contribution of evaporites through dissolution or fusion, depending on the temperature of formation from greenschist to granulite facies. The fluids are highly saline NaCl-brines circulating either in an open system in the greenschist facies (Colombian and Afghan emeralds) and with huge fluid-rock metasomatic interactions, or sulphurous fluids (ruby, garnet tsavorite, zoisite tanzanite and lapis-lazuli) or molten salts formed in a closed system with a low fluid mobility (ruby in marble) in the conditions of the amphibolite to granulite facies. These chloride-fluoride-sulphate ± carbonate-rich fluids scavenged the metals essential for gem formation. At high temperature, the anions SO4 2-, NO3 -, BO3 - and F- are powerful fluxes which lower the temperature of chloride- and fluoride-rich ionic liquids. They provided transport over a very short distance of aluminium and/or silica and transition metals which are necessary for gem growth. In summary, the genetic models proposed for these high-value and ornamental gems underline the importance of the metamorphism of evaporites formed on continental carbonate shelves and emphasise the chemical power accompanying metamorphism at moderate to high temperatures of evaporite-rich and organic matter-rich protoliths to form gem minerals.

A Generalized Hybrid Multiscale Modeling Approach for Flow and Reactive Transport in Porous Media

NASA Astrophysics Data System (ADS)

Yang, X.; Meng, X.; Tang, Y. H.; Guo, Z.; Karniadakis, G. E.

2017-12-01

Using emerging understanding of biological and environmental processes at fundamental scales to advance predictions of the larger system behavior requires the development of multiscale approaches, and there is strong interest in coupling models at different scales together in a hybrid multiscale simulation framework. A limited number of hybrid multiscale simulation methods have been developed for subsurface applications, mostly using application-specific approaches for model coupling. The proposed generalized hybrid multiscale approach is designed with minimal intrusiveness to the at-scale simulators (pre-selected) and provides a set of lightweight C++ scripts to manage a complex multiscale workflow utilizing a concurrent coupling approach. The workflow includes at-scale simulators (using the lattice-Boltzmann method, LBM, at the pore and Darcy scale, respectively), scripts for boundary treatment (coupling and kriging), and a multiscale universal interface (MUI) for data exchange. The current study aims to apply the generalized hybrid multiscale modeling approach to couple pore- and Darcy-scale models for flow and mixing-controlled reaction with precipitation/dissolution in heterogeneous porous media. The model domain is packed heterogeneously that the mixing front geometry is more complex and not known a priori. To address those challenges, the generalized hybrid multiscale modeling approach is further developed to 1) adaptively define the locations of pore-scale subdomains, 2) provide a suite of physical boundary coupling schemes and 3) consider the dynamic change of the pore structures due to mineral precipitation/dissolution. The results are validated and evaluated by comparing with single-scale simulations in terms of velocities, reactive concentrations and computing cost.

Projection of Carbon Dynamics in the Marine West Coast Forests under Climate and Land Cover changes Using General Ensemble Biogeochemical Modeling System (GEMS)

NASA Astrophysics Data System (ADS)

WU, Y.; Liu, S.; Li, Z.; Young, C.; Werner, J.; Dahal, D.; Liu, J.; Schmidt, G.

2012-12-01

Climate and land cover changes may influence the capacity of the terrestrial ecosystems to be carbon sinks or sources. The objective of this study was to investigate the potential change of the carbon sequestration in the Marine West Coast Forests ecoregion in the Pacific Northwest United States using the General Ensemble Biogeochemical Modeling System (GEMS). In GEMS, the underlying biogeochemical model, Erosion and Deposition Carbon Model (EDCM), was used and calibrated using MODIS net primary production (NPP) and grain yield data during the baseline period from 2002 to 2005, and then validated with another four-year period from 2006 to 2009. GEMS-EDCM was driven using projected climate from three General Circulation Models (GCMs) under three IPCC scenarios (A2, A1B, and B1) and derived land cover data from the FORecasting SCEnarios (FORE-SCE) model under the same three IPCC scenarios for the period from 2006 to 2050. This ecoregion, two-thirds of which is covered by forest, was projected to continue to gain carbon from 2005 to 2050, with an annual carbon sequestration of about -3 Tg C. It was also predicted that live biomass and soil organic carbon (SOC) would contain about 48% and 33% of the total carbon storage by 2050, respectively. In addition, forest carbon sequestration (-2 Tg C yr-1) demonstrated to be the largest sink among all ecosystems, accounting for 73% of the total, followed by grass/shrub and agriculture. Overall, results about predicted dynamics of carbon storage and sequestration can be informative to policy makers for seeking mitigation plans to reduce greenhouse gases emissions.

Petascale computation performance of lightweight multiscale cardiac models using hybrid programming models.

PubMed

Pope, Bernard J; Fitch, Blake G; Pitman, Michael C; Rice, John J; Reumann, Matthias

2011-01-01

Future multiscale and multiphysics models must use the power of high performance computing (HPC) systems to enable research into human disease, translational medical science, and treatment. Previously we showed that computationally efficient multiscale models will require the use of sophisticated hybrid programming models, mixing distributed message passing processes (e.g. the message passing interface (MPI)) with multithreading (e.g. OpenMP, POSIX pthreads). The objective of this work is to compare the performance of such hybrid programming models when applied to the simulation of a lightweight multiscale cardiac model. Our results show that the hybrid models do not perform favourably when compared to an implementation using only MPI which is in contrast to our results using complex physiological models. Thus, with regards to lightweight multiscale cardiac models, the user may not need to increase programming complexity by using a hybrid programming approach. However, considering that model complexity will increase as well as the HPC system size in both node count and number of cores per node, it is still foreseeable that we will achieve faster than real time multiscale cardiac simulations on these systems using hybrid programming models.

Not Your Ordinary GEM

NASA Technical Reports Server (NTRS)

2001-01-01

Through Small Business Innovation Research (SBIR) funding from NASA's Stennis Space Center, Geophex devised a new design for broadband electromagnetic sensors. Geophex developed a patented sensing technology, capable not only of coastal monitoring, but also a variety of other functions, including environmental pollution characterization, groundwater contamination detection, archaeological study, and mineral detection. The new technology is offered in several of the company's products the GEM-2, GEM-2A, and the GEM-3. The Geophex products consist of two primary electromagnetic coils, which are stimulated by alternating currents that generate a magnetic field in the object targeted for investigation. GEM-2 is a handheld, lightweight, programmable, digital device. GEM-2A is an airborne version of the sensor. Suspended from a helicopter, the GEM-2A is used to search for mineral deposits and to survey large tracts of land. The GEM-3 is capable of detecting buried landmines and other active munitions. GEM-3 identifies landmines by their brand names. Because each landmine has its own unique electromagnetic response to the broad frequency band emitted by the GEM-3, bomb identification and disposal strategies are made easier.

Improving the phenotype predictions of a yeast genome-scale metabolic model by incorporating enzymatic constraints

DOE PAGES

Sánchez, Benjamín J.; Zhang, Cheng; Nilsson, Avlant; ...

2017-03-08

Genome-scale metabolic models (GEMs) are widely used to calculate metabolic phenotypes. They rely on defining a set of constraints, the most common of which is that the production of metabolites and/or growth are limited by the carbon source uptake rate. However, enzyme abundances and kinetics, which act as limitations on metabolic fluxes, are not taken into account. Here, we present GECKO, a method that enhances a GEM to account for enzymes as part of reactions, thereby ensuring that each metabolic flux does not exceed its maximum capacity, equal to the product of the enzyme's abundance and turnover number. We appliedmore » GECKO to a Saccharomyces cerevisiae GEM and demonstrated that the new model could correctly describe phenotypes that the previous model could not, particularly under high enzymatic pressure conditions, such as yeast growing on different carbon sources in excess, coping with stress, or overexpressing a specific pathway. GECKO also allows to directly integrate quantitative proteomics data; by doing so, we significantly reduced flux variability of the model, in over 60% of metabolic reactions. Additionally, the model gives insight into the distribution of enzyme usage between and within metabolic pathways. The developed method and model are expected to increase the use of model-based design in metabolic engineering.« less

Improving the phenotype predictions of a yeast genome-scale metabolic model by incorporating enzymatic constraints

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

Sánchez, Benjamín J.; Zhang, Cheng; Nilsson, Avlant

Genome-scale metabolic models (GEMs) are widely used to calculate metabolic phenotypes. They rely on defining a set of constraints, the most common of which is that the production of metabolites and/or growth are limited by the carbon source uptake rate. However, enzyme abundances and kinetics, which act as limitations on metabolic fluxes, are not taken into account. Here, we present GECKO, a method that enhances a GEM to account for enzymes as part of reactions, thereby ensuring that each metabolic flux does not exceed its maximum capacity, equal to the product of the enzyme's abundance and turnover number. We appliedmore » GECKO to a Saccharomyces cerevisiae GEM and demonstrated that the new model could correctly describe phenotypes that the previous model could not, particularly under high enzymatic pressure conditions, such as yeast growing on different carbon sources in excess, coping with stress, or overexpressing a specific pathway. GECKO also allows to directly integrate quantitative proteomics data; by doing so, we significantly reduced flux variability of the model, in over 60% of metabolic reactions. Additionally, the model gives insight into the distribution of enzyme usage between and within metabolic pathways. The developed method and model are expected to increase the use of model-based design in metabolic engineering.« less

Origins of GEMS Grains

NASA Technical Reports Server (NTRS)

Messenger, S.; Walker, R. M.

2012-01-01

Interplanetary dust particles (IDPs) collected in the Earth s stratosphere contain high abundances of submicrometer amorphous silicates known as GEMS grains. From their birth as condensates in the outflows of oxygen-rich evolved stars, processing in interstellar space, and incorporation into disks around new stars, amorphous silicates predominate in most astrophysical environments. Amorphous silicates were a major building block of our Solar System and are prominent in infrared spectra of comets. Anhydrous interplanetary dust particles (IDPs) thought to derive from comets contain abundant amorphous silicates known as GEMS (glass with embedded metal and sulfides) grains. GEMS grains have been proposed to be isotopically and chemically homogenized interstellar amorphous silicate dust. We evaluated this hypothesis through coordinated chemical and isotopic analyses of GEMS grains in a suite of IDPs to constrain their origins. GEMS grains show order of magnitude variations in Mg, Fe, Ca, and S abundances. GEMS grains do not match the average element abundances inferred for ISM dust containing on average, too little Mg, Fe, and Ca, and too much S. GEMS grains have complementary compositions to the crystalline components in IDPs suggesting that they formed from the same reservoir. We did not observe any unequivocal microstructural or chemical evidence that GEMS grains experienced prolonged exposure to radiation. We identified four GEMS grains having O isotopic compositions that point to origins in red giant branch or asymptotic giant branch stars and supernovae. Based on their O isotopic compositions, we estimate that 1-6% of GEMS grains are surviving circumstellar grains. The remaining 94-99% of GEMS grains have O isotopic compositions that are indistinguishable from terrestrial materials and carbonaceous chondrites. These isotopically solar GEMS grains either formed in the Solar System or were completely homogenized in the interstellar medium (ISM). However, the chemical compositions of GEMS grains are extremely heterogeneous and seem to rule out this possibility. Based on their solar isotopic compositions and their non-solar elemental compositions we propose that most GEMS grains formed in the nebula as late-stage non-equilibrium condensates.

Building a better methane generation model: Validating models with methane recovery rates from 35 Canadian landfills.

PubMed

Thompson, Shirley; Sawyer, Jennifer; Bonam, Rathan; Valdivia, J E

2009-07-01

The German EPER, TNO, Belgium, LandGEM, and Scholl Canyon models for estimating methane production were compared to methane recovery rates for 35 Canadian landfills, assuming that 20% of emissions were not recovered. Two different fractions of degradable organic carbon (DOC(f)) were applied in all models. Most models performed better when the DOC(f) was 0.5 compared to 0.77. The Belgium, Scholl Canyon, and LandGEM version 2.01 models produced the best results of the existing models with respective mean absolute errors compared to methane generation rates (recovery rates + 20%) of 91%, 71%, and 89% at 0.50 DOC(f) and 171%, 115%, and 81% at 0.77 DOC(f). The Scholl Canyon model typically overestimated methane recovery rates and the LandGEM version 2.01 model, which modifies the Scholl Canyon model by dividing waste by 10, consistently underestimated methane recovery rates; this comparison suggested that modifying the divisor for waste in the Scholl Canyon model between one and ten could improve its accuracy. At 0.50 DOC(f) and 0.77 DOC(f) the modified model had the lowest absolute mean error when divided by 1.5 yielding 63 +/- 45% and 2.3 yielding 57 +/- 47%, respectively. These modified models reduced error and variability substantially and both have a strong correlation of r = 0.92.

YIP: Generic Environment Models (GEMs) for Agile Marine Autonomy

DTIC Science & Technology

2013-09-30

2012, and spring 2013, SC for a related NSF project: “Mechanisms of nutrient input at the shelf margin supporting persistent winter phytoplankton blooms...the Shelf Margin Supporting Persistent Winter Phytoplankton Blooms Downstream of the Charleston Bump. We will deploy underwater gliders in Long Bay...SC to study mechanisms of nutrient input at the shelf margin supporting persistent winter phytoplankton blooms downstream of the Charleston Bump. GEM

The gut microbiota modulates host amino acid and glutathione metabolism in mice

PubMed Central

Mardinoglu, Adil; Shoaie, Saeed; Bergentall, Mattias; Ghaffari, Pouyan; Zhang, Cheng; Larsson, Erik; Bäckhed, Fredrik; Nielsen, Jens

2015-01-01

The gut microbiota has been proposed as an environmental factor that promotes the progression of metabolic diseases. Here, we investigated how the gut microbiota modulates the global metabolic differences in duodenum, jejunum, ileum, colon, liver, and two white adipose tissue depots obtained from conventionally raised (CONV-R) and germ-free (GF) mice using gene expression data and tissue-specific genome-scale metabolic models (GEMs). We created a generic mouse metabolic reaction (MMR) GEM, reconstructed 28 tissue-specific GEMs based on proteomics data, and manually curated GEMs for small intestine, colon, liver, and adipose tissues. We used these functional models to determine the global metabolic differences between CONV-R and GF mice. Based on gene expression data, we found that the gut microbiota affects the host amino acid (AA) metabolism, which leads to modifications in glutathione metabolism. To validate our predictions, we measured the level of AAs and N-acetylated AAs in the hepatic portal vein of CONV-R and GF mice. Finally, we simulated the metabolic differences between the small intestine of the CONV-R and GF mice accounting for the content of the diet and relative gene expression differences. Our analyses revealed that the gut microbiota influences host amino acid and glutathione metabolism in mice. PMID:26475342

Intercomparison of Multiscale Modeling Approaches in Simulating Subsurface Flow and Transport

NASA Astrophysics Data System (ADS)

Yang, X.; Mehmani, Y.; Barajas-Solano, D. A.; Song, H. S.; Balhoff, M.; Tartakovsky, A. M.; Scheibe, T. D.

2016-12-01

Hybrid multiscale simulations that couple models across scales are critical to advance predictions of the larger system behavior using understanding of fundamental processes. In the current study, three hybrid multiscale methods are intercompared: multiscale loose-coupling method, multiscale finite volume (MsFV) method and multiscale mortar method. The loose-coupling method enables a parallel workflow structure based on the Swift scripting environment that manages the complex process of executing coupled micro- and macro-scale models without being intrusive to the at-scale simulators. The MsFV method applies microscale and macroscale models over overlapping subdomains of the modeling domain and enforces continuity of concentration and transport fluxes between models via restriction and prolongation operators. The mortar method is a non-overlapping domain decomposition approach capable of coupling all permutations of pore- and continuum-scale models with each other. In doing so, Lagrange multipliers are used at interfaces shared between the subdomains so as to establish continuity of species/fluid mass flux. Subdomain computations can be performed either concurrently or non-concurrently depending on the algorithm used. All the above methods have been proven to be accurate and efficient in studying flow and transport in porous media. However, there has not been any field-scale applications and benchmarking among various hybrid multiscale approaches. To address this challenge, we apply all three hybrid multiscale methods to simulate water flow and transport in a conceptualized 2D modeling domain of the hyporheic zone, where strong interactions between groundwater and surface water exist across multiple scales. In all three multiscale methods, fine-scale simulations are applied to a thin layer of riverbed alluvial sediments while the macroscopic simulations are used for the larger subsurface aquifer domain. Different numerical coupling methods are then applied between scales and inter-compared. Comparisons are drawn in terms of velocity distributions, solute transport behavior, algorithm-induced numerical error and computing cost. The intercomparison work provides support for confidence in a variety of hybrid multiscale methods and motivates further development and applications.

Multiscale Materials Modeling Workshop Summary

DOT National Transportation Integrated Search

2013-12-01

This report summarizes a 2-day workshop held to share information on multiscale material modeling. The aim was to gain expert feedback on the state of the art and identify Exploratory Advanced Research (EAR) Program opportunities for multiscale mater...

Hepatic Disposition of Gemfibrozil and Its Major Metabolite Gemfibrozil 1-O-β-Glucuronide.

PubMed

Kimoto, Emi; Li, Rui; Scialis, Renato J; Lai, Yurong; Varma, Manthena V S

2015-11-02

Gemfibrozil (GEM), which decreases serum triglycerides and low density lipoprotein, perpetrates drug-drug interactions (DDIs) with several drugs. These DDIs are primarily attributed to the inhibition of drug transporters and metabolic enzymes, particularly cytochrome P450 (CYP) 2C8 by the major circulating metabolite gemfibrozil 1-O-β-glucuronide (GG). Here, we characterized the transporter-mediated hepatic disposition of GEM and GG using sandwich-cultured human hepatocytes (SCHH) and transporter-transfect systems. Significant active uptake was noted in SCHH for the metabolite. GG, but not GEM, showed substrate affinity to organic anion transporting polypeptide (OATP) 1B1, 1B3, and 2B1. In SCHH, glucuronidation was characterized affinity constants (Km) of 7.9 and 61.4 μM, and biliary excretion of GG was observed. Furthermore, GG showed active basolateral efflux from preloaded SCHH and ATP-dependent uptake into membrane vesicles overexpressing multidrug resistance-associated protein (MRP) 2, MRP3, and MRP4. A mathematical model was developed to estimate hepatic uptake and efflux kinetics of GEM and GG based on SCHH studies. Collectively, the hepatic transporters play a key role in the disposition and thus determine the local concentrations of GEM and more so for GG, which is the predominant inhibitory species against CYP2C8 and OATP1B1.

Multiscale molecular dynamics/hydrodynamics implementation of two dimensional "Mercedes Benz" water model

NASA Astrophysics Data System (ADS)

Scukins, A.; Nerukh, D.; Pavlov, E.; Karabasov, S.; Markesteijn, A.

2015-09-01

A multiscale Molecular Dynamics/Hydrodynamics implementation of the 2D Mercedes Benz (MB or BN2D) [1] water model is developed and investigated. The concept and the governing equations of multiscale coupling together with the results of the two-way coupling implementation are reported. The sensitivity of the multiscale model for obtaining macroscopic and microscopic parameters of the system, such as macroscopic density and velocity fluctuations, radial distribution and velocity autocorrelation functions of MB particles, is evaluated. Critical issues for extending the current model to large systems are discussed.

Automated analysis of flow cytometric data for measuring neutrophil CD64 expression using a multi-instrument compatible probability state model.

PubMed

Wong, Linda; Hill, Beth L; Hunsberger, Benjamin C; Bagwell, C Bruce; Curtis, Adam D; Davis, Bruce H

2015-01-01

Leuko64™ (Trillium Diagnostics) is a flow cytometric assay that measures neutrophil CD64 expression and serves as an in vitro indicator of infection/sepsis or the presence of a systemic acute inflammatory response. Leuko64 assay currently utilizes QuantiCALC, a semiautomated software that employs cluster algorithms to define cell populations. The software reduces subjective gating decisions, resulting in interanalyst variability of <5%. We evaluated a completely automated approach to measuring neutrophil CD64 expression using GemStone™ (Verity Software House) and probability state modeling (PSM). Four hundred and fifty-seven human blood samples were processed using the Leuko64 assay. Samples were analyzed on four different flow cytometer models: BD FACSCanto II, BD FACScan, BC Gallios/Navios, and BC FC500. A probability state model was designed to identify calibration beads and three leukocyte subpopulations based on differences in intensity levels of several parameters. PSM automatically calculates CD64 index values for each cell population using equations programmed into the model. GemStone software uses PSM that requires no operator intervention, thus totally automating data analysis and internal quality control flagging. Expert analysis with the predicate method (QuantiCALC) was performed. Interanalyst precision was evaluated for both methods of data analysis. PSM with GemStone correlates well with the expert manual analysis, r(2) = 0.99675 for the neutrophil CD64 index values with no intermethod bias detected. The average interanalyst imprecision for the QuantiCALC method was 1.06% (range 0.00-7.94%), which was reduced to 0.00% with the GemStone PSM. The operator-to-operator agreement in GemStone was a perfect correlation, r(2) = 1.000. Automated quantification of CD64 index values produced results that strongly correlate with expert analysis using a standard gate-based data analysis method. PSM successfully evaluated flow cytometric data generated by multiple instruments across multiple lots of the Leuko64 kit in all 457 cases. The probability-based method provides greater objectivity, higher data analysis speed, and allows for greater precision for in vitro diagnostic flow cytometric assays. © 2015 International Clinical Cytometry Society.

Multiscale Cancer Modeling

PubMed Central

Macklin, Paul; Cristini, Vittorio

2013-01-01

Simulating cancer behavior across multiple biological scales in space and time, i.e., multiscale cancer modeling, is increasingly being recognized as a powerful tool to refine hypotheses, focus experiments, and enable more accurate predictions. A growing number of examples illustrate the value of this approach in providing quantitative insight on the initiation, progression, and treatment of cancer. In this review, we introduce the most recent and important multiscale cancer modeling works that have successfully established a mechanistic link between different biological scales. Biophysical, biochemical, and biomechanical factors are considered in these models. We also discuss innovative, cutting-edge modeling methods that are moving predictive multiscale cancer modeling toward clinical application. Furthermore, because the development of multiscale cancer models requires a new level of collaboration among scientists from a variety of fields such as biology, medicine, physics, mathematics, engineering, and computer science, an innovative Web-based infrastructure is needed to support this growing community. PMID:21529163

Sharing behavioral data through a grid infrastructure using data standards

PubMed Central

Min, Hua; Ohira, Riki; Collins, Michael A; Bondy, Jessica; Avis, Nancy E; Tchuvatkina, Olga; Courtney, Paul K; Moser, Richard P; Shaikh, Abdul R; Hesse, Bradford W; Cooper, Mary; Reeves, Dianne; Lanese, Bob; Helba, Cindy; Miller, Suzanne M; Ross, Eric A

2014-01-01

Objective In an effort to standardize behavioral measures and their data representation, the present study develops a methodology for incorporating measures found in the National Cancer Institute's (NCI) grid-enabled measures (GEM) portal, a repository for behavioral and social measures, into the cancer data standards registry and repository (caDSR). Methods The methodology consists of four parts for curating GEM measures into the caDSR: (1) develop unified modeling language (UML) models for behavioral measures; (2) create common data elements (CDE) for UML components; (3) bind CDE with concepts from the NCI thesaurus; and (4) register CDE in the caDSR. Results UML models have been developed for four GEM measures, which have been registered in the caDSR as CDE. New behavioral concepts related to these measures have been created and incorporated into the NCI thesaurus. Best practices for representing measures using UML models have been utilized in the practice (eg, caDSR). One dataset based on a GEM-curated measure is available for use by other systems and users connected to the grid. Conclusions Behavioral and population science data can be standardized by using and extending current standards. A new branch of CDE for behavioral science was developed for the caDSR. It expands the caDSR domain coverage beyond the clinical and biological areas. In addition, missing terms and concepts specific to the behavioral measures addressed in this paper were added to the NCI thesaurus. A methodology was developed and refined for curation of behavioral and population science data. PMID:24076749

Gas electron multiplier (GEM) foil test, repair and effective gain calculation

NASA Astrophysics Data System (ADS)

Tahir, Muhammad; Zubair, Muhammad; Khan, Tufail A.; Khan, Ashfaq; Malook, Asad

2018-06-01

The focus of my research is based on the gas electron multiplier (GEM) foil test, repairing and effective gain calculation of GEM detector. During my research work define procedure of GEM foil testing short-circuit, detection short-circuits in the foil. Study different ways to remove the short circuits in the foils. Set and define the GEM foil testing procedures in the open air, and with nitrogen gas. Measure the leakage current of the foil and applying different voltages with specified step size. Define the Quality Control (QC) tests and different components of GEM detectors before assembly. Calculate the effective gain of GEM detectors using 109Cd and 55Fe radioactive source.

[Construction of Lactobacillus rhamnosus GG particles surface display system].

PubMed

Su, Runyu; Nie, Boyao; Yuan, Shengling; Tao, Haoxia; Liu, Chunjie; Yang, Bailiang; Wang, Yanchun

2017-01-25

To describe a novel particles surface display system which is consisted of gram-positive enhancer matrix (GEM) particles and anchor proteins for bacteria-like particles vaccines, we treated Lactobacillus rhamnosus GG bacteria with 10% heated-TCA for preparing GEM particles, and then identified the harvested GEM particles by electron microscopy, RT-PCR and SDS-PAGE. Meanwhile, Escherichia coli was induced to express hybrid proteins PA3-EGFP and P60-EGFP, and GEM particles were incubated with them. Then binding of anchor proteins were determined by Western blotting, transmission electron microscopy, fluorescence microscopy and spectrofluorometry. GEM particles preserved original size and shape, and proteins and DNA contents of GEM particles were released substantially. The two anchor proteins both had efficiently immobilized on the surface of GEM. GEM particles that were bounded by anchor proteins were brushy. The fluorescence of GEM particles anchoring PA3 was slightly brighter than P60, but the difference was not significant (P>0.05). GEM particles prepared from L. rhamnosus GG have a good binding efficiency with anchor proteins PA3-EGFP and P60-EGFP. Therefore, this novel foreign protein surface display system could be used for bacteria-like particle vaccines.

Multi-Scale Models for the Scale Interaction of Organized Tropical Convection

NASA Astrophysics Data System (ADS)

Yang, Qiu

Assessing the upscale impact of organized tropical convection from small spatial and temporal scales is a research imperative, not only for having a better understanding of the multi-scale structures of dynamical and convective fields in the tropics, but also for eventually helping in the design of new parameterization strategies to improve the next-generation global climate models. Here self-consistent multi-scale models are derived systematically by following the multi-scale asymptotic methods and used to describe the hierarchical structures of tropical atmospheric flows. The advantages of using these multi-scale models lie in isolating the essential components of multi-scale interaction and providing assessment of the upscale impact of the small-scale fluctuations onto the large-scale mean flow through eddy flux divergences of momentum and temperature in a transparent fashion. Specifically, this thesis includes three research projects about multi-scale interaction of organized tropical convection, involving tropical flows at different scaling regimes and utilizing different multi-scale models correspondingly. Inspired by the observed variability of tropical convection on multiple temporal scales, including daily and intraseasonal time scales, the goal of the first project is to assess the intraseasonal impact of the diurnal cycle on the planetary-scale circulation such as the Hadley cell. As an extension of the first project, the goal of the second project is to assess the intraseasonal impact of the diurnal cycle over the Maritime Continent on the Madden-Julian Oscillation. In the third project, the goals are to simulate the baroclinic aspects of the ITCZ breakdown and assess its upscale impact on the planetary-scale circulation over the eastern Pacific. These simple multi-scale models should be useful to understand the scale interaction of organized tropical convection and help improve the parameterization of unresolved processes in global climate models.

An analysis platform for multiscale hydrogeologic modeling with emphasis on hybrid multiscale methods.

PubMed

Scheibe, Timothy D; Murphy, Ellyn M; Chen, Xingyuan; Rice, Amy K; Carroll, Kenneth C; Palmer, Bruce J; Tartakovsky, Alexandre M; Battiato, Ilenia; Wood, Brian D

2015-01-01

One of the most significant challenges faced by hydrogeologic modelers is the disparity between the spatial and temporal scales at which fundamental flow, transport, and reaction processes can best be understood and quantified (e.g., microscopic to pore scales and seconds to days) and at which practical model predictions are needed (e.g., plume to aquifer scales and years to centuries). While the multiscale nature of hydrogeologic problems is widely recognized, technological limitations in computation and characterization restrict most practical modeling efforts to fairly coarse representations of heterogeneous properties and processes. For some modern problems, the necessary level of simplification is such that model parameters may lose physical meaning and model predictive ability is questionable for any conditions other than those to which the model was calibrated. Recently, there has been broad interest across a wide range of scientific and engineering disciplines in simulation approaches that more rigorously account for the multiscale nature of systems of interest. In this article, we review a number of such approaches and propose a classification scheme for defining different types of multiscale simulation methods and those classes of problems to which they are most applicable. Our classification scheme is presented in terms of a flowchart (Multiscale Analysis Platform), and defines several different motifs of multiscale simulation. Within each motif, the member methods are reviewed and example applications are discussed. We focus attention on hybrid multiscale methods, in which two or more models with different physics described at fundamentally different scales are directly coupled within a single simulation. Very recently these methods have begun to be applied to groundwater flow and transport simulations, and we discuss these applications in the context of our classification scheme. As computational and characterization capabilities continue to improve, we envision that hybrid multiscale modeling will become more common and also a viable alternative to conventional single-scale models in the near future. © 2014, National Ground Water Association.

Multiscale Modeling of Structurally-Graded Materials Using Discrete Dislocation Plasticity Models and Continuum Crystal Plasticity Models

NASA Technical Reports Server (NTRS)

Saether, Erik; Hochhalter, Jacob D.; Glaessgen, Edward H.

2012-01-01

A multiscale modeling methodology that combines the predictive capability of discrete dislocation plasticity and the computational efficiency of continuum crystal plasticity is developed. Single crystal configurations of different grain sizes modeled with periodic boundary conditions are analyzed using discrete dislocation plasticity (DD) to obtain grain size-dependent stress-strain predictions. These relationships are mapped into crystal plasticity parameters to develop a multiscale DD/CP model for continuum level simulations. A polycrystal model of a structurally-graded microstructure is developed, analyzed and used as a benchmark for comparison between the multiscale DD/CP model and the DD predictions. The multiscale DD/CP model follows the DD predictions closely up to an initial peak stress and then follows a strain hardening path that is parallel but somewhat offset from the DD predictions. The difference is believed to be from a combination of the strain rate in the DD simulation and the inability of the DD/CP model to represent non-monotonic material response.

Derivation of the Schwartzchild Metric From the ``Self Censorship'' of the ZPF (Zero Point Energy) in the GEM Theory

NASA Astrophysics Data System (ADS)

Brandenburg, John

2012-10-01

The GEM theory (1) links the EM stress tensor directly to the metric tensor by the principle of ``self censorship'' of the ZPF (2) where the definition of guv = FuwF^wv/ 4 for Planck scale fields makes the stress tensor vanish even when fields are present. The first order form of the metric is recovered as Lorentzian due to alternating regions of strong electric and magnetic fields similar to that seen in models of spacetime in ``Loop Gravity,'' where the model admits perturbations. The GEM ExB drift models of gravity is used The first order perturbations on the fields are considered to be of the order of the fine structure constant alpha. Radiation fields due to a single charged particle of mass M fall off as 1/r and give the values (G=c=1) gtt = 1-2M/r and grr = (1-2M/r). (1) Brandenburg, J.E. (2012)., (2) STAIF II Conference Albuquerque NM 2.Brandenburg, J.E. (2007). IEEE Transactions On Plasma Science, Vol. 35, No. 4., p845.

Isolated Lung Perfusion as an Adjuvant Treatment of Colorectal Cancer Lung Metastases: A Preclinical Study in a Pig Model

PubMed Central

Pagès, Pierre-Benoit; Facy, Olivier; Mordant, Pierre; Ladoire, Sylvain; Magnin, Guy; Lokiec, Francois; Ghiringhelli, Francois; Bernard, Alain

2013-01-01

Background The lung is a frequent site of colorectal cancer (CRC) metastases. After surgical resection, lung metastases recurrences have been related to the presence of micrometastases, potentially accessible to a high dose chemotherapy administered via adjuvant isolated lung perfusion (ILP). We sought to determine in vitro the most efficient drug when administered to CRC cell lines during a short exposure and in vivo its immediate and delayed tolerance when administered via ILP. Methods First, efficacy of various cytotoxic molecules against a panel of human CRC cell lines was tested in vitro using cytotoxic assay after a 30-minute exposure. Then, early (operative) and delayed (1 month) tolerance of two concentrations of the molecule administered via ILP was tested on 19 adult pigs using hemodynamic, biological and histological criteria. Results In vitro, gemcitabine (GEM) was the most efficient drug against selected CRC cell lines. In vivo, GEM was administered via ILP at regular (20 µg/ml) or high (100 µg/ml) concentrations. GEM administration was associated with transient and dose-dependant pulmonary vasoconstriction, leading to a voluntary decrease in pump inflow in order to maintain a stable pulmonary artery pressure. After this modulation, ILP using GEM was not associated with any systemic leak, systemic damage, and acute or delayed histological pulmonary toxicity. Pharmacokinetics studies revealed dose-dependant uptake associated with heterogenous distribution of the molecule into the lung parenchyma, and persistent cytotoxicity of venous effluent. Conclusions GEM is effective against CRC cells even after a short exposure. ILP with GEM is a safe and reproducible technique. PMID:23527205

Impacts of Wildfires on Mercury Contamination in Canada

NASA Astrophysics Data System (ADS)

Dastoor, A.; Fraser, A.; Ryjkov, A.

2017-12-01

Wildfires frequency has increased in past four decades in Canada, and is expected to increase in future as a result of climate change. Biomass Burning Mercury Emissions (BBMEs) are known to be significant; however, the impact of biomass burning on Mercury (Hg) burden in Canada has not been previously quantified. We investigated the spatio-temporal variability of BBME in Canada, and used Environment and Climate Change Canada's air quality and mercury model, GEM-MACH-Hg, to quantify the impacts of BBME on spatio-temporal variability of air concentrations and deposition fluxes of Hg in Canada. We optimized the biomass burning Emission Factors (EFs) for gaseous elemental mercury (GEM) using observations, GEM-MACH-Hg and an inversion technique for five vegetation types represented in North American fires to constrain the BBME impacts of Hg. We used three BBME scenarios (i.e., two scenarios where mercury is emitted only as GEM using literature or optimized EFs, and a third scenario where mercury is emitted as GEM using literature EFs and particle bound mercury (PBM) emitted using a GEM/PBM ratio from lab measurements) in Canada to conduct three sets of model simulations for 2010-2015. The three BBME scenarios represent the range of possible values for the impacts of BBME in Canada on mercury concentration and deposition. We found total BBME and its spatial distribution to be highly variable from year to year, and total atmospheric BBME averaged for 2010-2015 in Canada to be between 6 - 14 tonnes, which is 3 - 7 times the mercury emission from anthropogenic sources in Canada during the biomass burning season (i.e., from May to September). We found that while BBME have a small impact on surface air concentrations of GEM and total Hg deposition averaged over individual provinces/territories, these impacts for individual ecosystems can be as high as 95% during the burning season. We found that northern Alberta and Saskatchewan, central British Columbia, and the area around Great Slave Lake in the Northwest Territories are at greater risk of mercury contamination from biomass burning. We analysed the uncertainties in BBME, and found that reducing uncertainty in the speciation of Hg in BBME would provide the largest benefit to constraining the mercury contamination from biomass burning source to Canadian ecosystems.

A high-order multiscale finite-element method for time-domain acoustic-wave modeling

NASA Astrophysics Data System (ADS)

Gao, Kai; Fu, Shubin; Chung, Eric T.

2018-05-01

Accurate and efficient wave equation modeling is vital for many applications in such as acoustics, electromagnetics, and seismology. However, solving the wave equation in large-scale and highly heterogeneous models is usually computationally expensive because the computational cost is directly proportional to the number of grids in the model. We develop a novel high-order multiscale finite-element method to reduce the computational cost of time-domain acoustic-wave equation numerical modeling by solving the wave equation on a coarse mesh based on the multiscale finite-element theory. In contrast to existing multiscale finite-element methods that use only first-order multiscale basis functions, our new method constructs high-order multiscale basis functions from local elliptic problems which are closely related to the Gauss-Lobatto-Legendre quadrature points in a coarse element. Essentially, these basis functions are not only determined by the order of Legendre polynomials, but also by local medium properties, and therefore can effectively convey the fine-scale information to the coarse-scale solution with high-order accuracy. Numerical tests show that our method can significantly reduce the computation time while maintain high accuracy for wave equation modeling in highly heterogeneous media by solving the corresponding discrete system only on the coarse mesh with the new high-order multiscale basis functions.

A high-order multiscale finite-element method for time-domain acoustic-wave modeling

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

Gao, Kai; Fu, Shubin; Chung, Eric T.

Accurate and efficient wave equation modeling is vital for many applications in such as acoustics, electromagnetics, and seismology. However, solving the wave equation in large-scale and highly heterogeneous models is usually computationally expensive because the computational cost is directly proportional to the number of grids in the model. We develop a novel high-order multiscale finite-element method to reduce the computational cost of time-domain acoustic-wave equation numerical modeling by solving the wave equation on a coarse mesh based on the multiscale finite-element theory. In contrast to existing multiscale finite-element methods that use only first-order multiscale basis functions, our new method constructsmore » high-order multiscale basis functions from local elliptic problems which are closely related to the Gauss–Lobatto–Legendre quadrature points in a coarse element. Essentially, these basis functions are not only determined by the order of Legendre polynomials, but also by local medium properties, and therefore can effectively convey the fine-scale information to the coarse-scale solution with high-order accuracy. Numerical tests show that our method can significantly reduce the computation time while maintain high accuracy for wave equation modeling in highly heterogeneous media by solving the corresponding discrete system only on the coarse mesh with the new high-order multiscale basis functions.« less

A high-order multiscale finite-element method for time-domain acoustic-wave modeling

DOE PAGES

Gao, Kai; Fu, Shubin; Chung, Eric T.

2018-02-04

Accurate and efficient wave equation modeling is vital for many applications in such as acoustics, electromagnetics, and seismology. However, solving the wave equation in large-scale and highly heterogeneous models is usually computationally expensive because the computational cost is directly proportional to the number of grids in the model. We develop a novel high-order multiscale finite-element method to reduce the computational cost of time-domain acoustic-wave equation numerical modeling by solving the wave equation on a coarse mesh based on the multiscale finite-element theory. In contrast to existing multiscale finite-element methods that use only first-order multiscale basis functions, our new method constructsmore » high-order multiscale basis functions from local elliptic problems which are closely related to the Gauss–Lobatto–Legendre quadrature points in a coarse element. Essentially, these basis functions are not only determined by the order of Legendre polynomials, but also by local medium properties, and therefore can effectively convey the fine-scale information to the coarse-scale solution with high-order accuracy. Numerical tests show that our method can significantly reduce the computation time while maintain high accuracy for wave equation modeling in highly heterogeneous media by solving the corresponding discrete system only on the coarse mesh with the new high-order multiscale basis functions.« less

GEM: a dynamic tracking model for mesoscale eddies in the ocean

NASA Astrophysics Data System (ADS)

Li, Qiu-Yang; Sun, Liang; Lin, Sheng-Fu

2016-12-01

The Genealogical Evolution Model (GEM) presented here is an efficient logical model used to track dynamic evolution of mesoscale eddies in the ocean. It can distinguish between different dynamic processes (e.g., merging and splitting) within a dynamic evolution pattern, which is difficult to accomplish using other tracking methods. To this end, the GEM first uses a two-dimensional (2-D) similarity vector (i.e., a pair of ratios of overlap area between two eddies to the area of each eddy) rather than a scalar to measure the similarity between eddies, which effectively solves the "missing eddy" problem (temporarily lost eddy in tracking). Second, for tracking when an eddy splits, the GEM uses both "parent" (the original eddy) and "child" (eddy split from parent) and the dynamic processes are described as the birth and death of different generations. Additionally, a new look-ahead approach with selection rules effectively simplifies computation and recording. All of the computational steps are linear and do not include iteration. Given the pixel number of the target region L, the maximum number of eddies M, the number N of look-ahead time steps, and the total number of time steps T, the total computer time is O(LM(N + 1)T). The tracking of each eddy is very smooth because we require that the snapshots of each eddy on adjacent days overlap one another. Although eddy splitting or merging is ubiquitous in the ocean, they have different geographic distributions in the North Pacific Ocean. Both the merging and splitting rates of the eddies are high, especially at the western boundary, in currents and in "eddy deserts". The GEM is useful not only for satellite-based observational data, but also for numerical simulation outputs. It is potentially useful for studying dynamic processes in other related fields, e.g., the dynamics of cyclones in meteorology.

An Analysis Platform for Multiscale Hydrogeologic Modeling with Emphasis on Hybrid Multiscale Methods

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

Scheibe, Timothy D.; Murphy, Ellyn M.; Chen, Xingyuan

2015-01-01

One of the most significant challenges facing hydrogeologic modelers is the disparity between those spatial and temporal scales at which fundamental flow, transport and reaction processes can best be understood and quantified (e.g., microscopic to pore scales, seconds to days) and those at which practical model predictions are needed (e.g., plume to aquifer scales, years to centuries). While the multiscale nature of hydrogeologic problems is widely recognized, technological limitations in computational and characterization restrict most practical modeling efforts to fairly coarse representations of heterogeneous properties and processes. For some modern problems, the necessary level of simplification is such that modelmore » parameters may lose physical meaning and model predictive ability is questionable for any conditions other than those to which the model was calibrated. Recently, there has been broad interest across a wide range of scientific and engineering disciplines in simulation approaches that more rigorously account for the multiscale nature of systems of interest. In this paper, we review a number of such approaches and propose a classification scheme for defining different types of multiscale simulation methods and those classes of problems to which they are most applicable. Our classification scheme is presented in terms of a flow chart (Multiscale Analysis Platform or MAP), and defines several different motifs of multiscale simulation. Within each motif, the member methods are reviewed and example applications are discussed. We focus attention on hybrid multiscale methods, in which two or more models with different physics described at fundamentally different scales are directly coupled within a single simulation. Very recently these methods have begun to be applied to groundwater flow and transport simulations, and we discuss these applications in the context of our classification scheme. As computational and characterization capabilities continue to improve, we envision that hybrid multiscale modeling will become more common and may become a viable alternative to conventional single-scale models in the near future.« less

Estimation of speciated and total mercury dry deposition at monitoring locations in eastern and central North America

USGS Publications Warehouse

Zhang, L.; Blanchard, P.; Gay, D.A.; Prestbo, E.M.; Risch, M.R.; Johnson, D.; Narayan, J.; Zsolway, R.; Holsen, T.M.; Miller, E.K.; Castro, M.S.; Graydon, J.A.; St. Louis, V.L.; Dalziel, J.

2012-01-01

Dry deposition of speciated mercury, i.e., gaseous oxidized mercury (GOM), particulate-bound mercury (PBM), and gaseous elemental mercury (GEM), was estimated for the year 2008–2009 at 19 monitoring locations in eastern and central North America. Dry deposition estimates were obtained by combining monitored two- to four-hourly speciated ambient concentrations with modeled hourly dry deposition velocities (Vd) calculated using forecasted meteorology. Annual dry deposition of GOM+PBM was estimated to be in the range of 0.4 to 8.1 μg m−2 at these locations with GOM deposition being mostly five to ten times higher than PBM deposition, due to their different modeled Vd values. Net annual GEM dry deposition was estimated to be in the range of 5 to 26 μg m−2 at 18 sites and 33 μg m−2 at one site. The estimated dry deposition agrees very well with limited surrogate-surface dry deposition measurements of GOM and PBM, and also agrees with litterfall mercury measurements conducted at multiple locations in eastern and central North America. This study suggests that GEM contributes much more than GOM+PBM to the total dry deposition at the majority of the sites considered here; the only exception is at locations close to significant point sources where GEM and GOM+PBM contribute equally to the total dry deposition. The relative magnitude of the speciated dry deposition and their good comparisons with litterfall deposition suggest that mercury in litterfall originates primarily from GEM, which is consistent with the limited number of previous field studies. The study also supports previous analyses suggesting that total dry deposition of mercury is equal to, if not more important than, wet deposition of mercury on a regional scale in eastern North America.

GEMS (Gravity Electro-Magnetism Strong) SU(5) Theory and The Prediction of Exchange Boson Masses

NASA Astrophysics Data System (ADS)

Brandenburg, John

2012-10-01

The GEMS SU(5) [1] theory includes short range Nuclear Forces in the GEM unification theory [2], where the importance of the square root of the proton-electron mass ratio: σ = 42.8503 was found. The creation of mass by a Higgs field coupling must, by the Equivalence Principle, be viewed in the context of General Relativity. This is done here using Kaluza-Klein theory in a Feynman-Hawkings path integral formalism. GEM theory, quantum concepts of virtual particles, and ZPF (Zero Point Fluctuation) allow understanding of the Strong Force and Weak forces as the extension of electrodynamics in the quantum limit. The Strong and Weak forces are found to be associated with EM models of the electron and proton as finite sized structures respectively. Higher order Mie resonances off the EM ``mass at a distance'' structures associated with the electron, proton and fifth dimension generate the quanta with masses of the pion mπ = 2 me /α 140.0 MeV and Z boson: mZ = 2σ mp = 80.4 GeV. The ηc meson mη = 2980 GeV is identified with the 5^th dimension compactification force mediated by the Radion field. Another particle associated with this mass inducing field is the ``Radion'' or Higgs scattering quanta off the fifth dimension with a mass σmη 128.6 GeV which is the Higgs Boson. A GEMS SU(5) Georgi-Glashow model, is proposed, where the unification energy is now the Planck energy.[0pt] [1] Brandenburg, J.E. (2012)., STAIF II Conference Albuquerque NM[0pt] [2] Brandenburg, J.E. (2007). IEEE Transactions On Plasma Science, Vol. 35, No. 4., p845.

Optimum data weighting and error calibration for estimation of gravitational parameters

NASA Technical Reports Server (NTRS)

Lerch, Francis J.

1989-01-01

A new technique was developed for the weighting of data from satellite tracking systems in order to obtain an optimum least-squares solution and an error calibration for the solution parameters. Data sets from optical, electronic, and laser systems on 17 satellites in GEM-T1 Goddard Earth Model-T1 (GEM-T1) were employed toward application of this technique for gravity field parameters. Also GEM-T2 (31 satellites) was recently computed as a direct application of the method and is summarized. The method employs subset solutions of the data associated with the complete solution to agree with their error estimates. With the adjusted weights the process provides for an automatic calibration of the error estimates for the solution parameters. The data weights derived are generally much smaller than corresponding weights obtained from nominal values of observation accuracy or residuals. Independent tests show significant improvement for solutions with optimal weighting. The technique is general and may be applied to orbit parameters, station coordinates, or other parameters than the gravity model.

The delineation and interpretation of the Earth's gravity field

NASA Technical Reports Server (NTRS)

Marsh, B. D.

1983-01-01

The observed changes in velocity with time are reduced relative to the well-determined low degree and order GEM field model and accelerations are found by analytical differentiation of the range rates. This new map is essentially identical to the first map and we have produced a composite map by combining all 90 passes of SST data. The resolution of the map is at worst about 5 deg and much better in most places. A comparison of this map with conventional GEM models shows very good agreement. A reduction of the SEASAT altimeter data has also been carried out for an additional comparison. Although the SEASAT geoid contains much more high frequency information, it agrees very well with both the SST and GEM fields. The maps are dominated (especially in the east) by a pattern of roughly east-west anomalies with a transverse wavelength of about 2000 km. A further comparison with regional bathymetric data shows a remarkably close correlation with plate age.

Formation kinetics of gemfibrozil chlorination reaction products: analysis and application.

PubMed

Krkosek, Wendy H; Peldszus, Sigrid; Huck, Peter M; Gagnon, Graham A

2014-07-01

Aqueous chlorination kinetics of the lipid regulator gemfibrozil and the formation of reaction products were investigated in deionized water over the pH range 3 to 9, and in two wastewater matrices. Chlorine oxidation of gemfibrozil was found to be highly dependent on pH. No statistically significant degradation of gemfibrozil was observed at pH values greater than 7. Gemfibrozil oxidation between pH 4 and 7 was best represented by first order kinetics. At pH 3, formation of three reaction products was observed. 4'-C1Gem was the only reaction product formed from pH 4-7 and was modeled with zero order kinetics. Chlorine oxidation of gemfibrozil in two wastewater matrices followed second order kinetics. 4'-C1Gem was only formed in wastewater with pH below 7. Deionized water rate kinetic models were applied to two wastewater effluents with gemfibrozil concentrations reported in literature in order to calculate potential mass loading rates of 4'C1Gem to the receiving water.

GEMS and New Pre-Accretionally Irradiated RELICT Grains in Interplanetary Dust - The Plot Thickens

NASA Astrophysics Data System (ADS)

Bradley, J.

1995-09-01

The hypothesis that GEMS (glass with embedded metal and sulfides) in interplanetary dust particles (IDPs) might be the long-sought interstellar silicate grains is undergoing close scrutiny [1-3]. GEMS are proposed to be interstellar because: (a) they are abundant in cometary IDPs; (b) they were irradiated prior to incorporation into IDPs; (c) both their size distribution and Oamorphous silicate" microstructures are consistent with those of interstellar silicates; (d) they contain nanometer-sized (superparamagnetic) alpha-iron inclusions, which provides a simple explanation for the observed interstellar grain alignment and polarization [4,5]. Challenges to the GEMS hypothesis include the following: (a) GEMS may have formed and been irradiated in the solar nebula rather than a presolar interstellar environment; (b) non-solar isotope abundances have yet to be measured in GEMS; (c) the irradiation regime required to produce the observed effects in GEMS might be incompatible with the interstellar medium; (b) relationships between GEMS and carbon (e.g. core/mantle) need clarification; (c) major element abundances in GEMS should be consistent with observed interstellar gas phase depletions [2,3]. GEMS may indeed have formed in the solar nebula, in which case they would be the oldest known solar nebula solids [2]. An interstellar origin for GEMS does not require detection of non-solar isotope abundances [6]. Irradiation experiments are in progress to simulate the properties of GEMS. The petrographic relationship between GEMS and carbon in IDPs is being investigated (by examining IDPs embedded and thin-sectioned in carbon-free media). Major element abundances in GEMS are being evaluated in terms on interstellar gas phase abundances. For example, sulfur is not highly depleted in the interstellar gas, implying that it must be significantly depleted in interstellar grains [3]. GEMS are significantly depleted in sulfur relative to solar abundances. Analytical electron microscopic studies of the local petrographic environment of GEMS in IDPs are continuing. There is evidence of a population of relict grains associated with GEMS. Some of these relict grains have distinctive compositions and they appear to have functioned as (pre-existing) depositional substrates while GEMS were being formed. Thus, it may be possible to begin to assign a chronology to the seemingly complex admixture of grains that make up the ultrafine-grained matrices of anhydrous chondritic IDPs. References: [1] Bradley J. P. (1994) Science, 265, 925-929. [2] Flynn G. J. (1994) Nature, 371, 287-288. [3] Martin P. G. (1995) Astrophys. J., 445, L63-L66. [4] Mathis J. S. (1986) Astrophys. J., 308, 281-287. [5] Mathis J. S. (1993) Rept. Prog. Phys., 56, 605-652. [6] Walker R. M. (1994) in Analysis of Interplanetary Dust (M. E. Zolensky et al., eds.), pp. 203-209, AIP Conf. Proc. 310.

Strategies for efficient numerical implementation of hybrid multi-scale agent-based models to describe biological systems

PubMed Central

Cilfone, Nicholas A.; Kirschner, Denise E.; Linderman, Jennifer J.

2015-01-01

Biologically related processes operate across multiple spatiotemporal scales. For computational modeling methodologies to mimic this biological complexity, individual scale models must be linked in ways that allow for dynamic exchange of information across scales. A powerful methodology is to combine a discrete modeling approach, agent-based models (ABMs), with continuum models to form hybrid models. Hybrid multi-scale ABMs have been used to simulate emergent responses of biological systems. Here, we review two aspects of hybrid multi-scale ABMs: linking individual scale models and efficiently solving the resulting model. We discuss the computational choices associated with aspects of linking individual scale models while simultaneously maintaining model tractability. We demonstrate implementations of existing numerical methods in the context of hybrid multi-scale ABMs. Using an example model describing Mycobacterium tuberculosis infection, we show relative computational speeds of various combinations of numerical methods. Efficient linking and solution of hybrid multi-scale ABMs is key to model portability, modularity, and their use in understanding biological phenomena at a systems level. PMID:26366228

Multiscale hidden Markov models for photon-limited imaging

NASA Astrophysics Data System (ADS)

Nowak, Robert D.

1999-06-01

Photon-limited image analysis is often hindered by low signal-to-noise ratios. A novel Bayesian multiscale modeling and analysis method is developed in this paper to assist in these challenging situations. In addition to providing a very natural and useful framework for modeling an d processing images, Bayesian multiscale analysis is often much less computationally demanding compared to classical Markov random field models. This paper focuses on a probabilistic graph model called the multiscale hidden Markov model (MHMM), which captures the key inter-scale dependencies present in natural image intensities. The MHMM framework presented here is specifically designed for photon-limited imagin applications involving Poisson statistics, and applications to image intensity analysis are examined.

Expected trace gas and aerosol retrieval accuracy of the Geostationary Environment Monitoring Spectrometer

NASA Astrophysics Data System (ADS)

Jeong, U.; Kim, J.; Liu, X.; Lee, K. H.; Chance, K.; Song, C. H.

2015-12-01

The predicted accuracy of the trace gases and aerosol retrievals from the geostationary environment monitoring spectrometer (GEMS) was investigated. The GEMS is one of the first sensors to monitor NO2, SO2, HCHO, O3, and aerosols onboard geostationary earth orbit (GEO) over Asia. Since the GEMS is not launched yet, the simulated measurements and its precision were used in this study. The random and systematic component of the measurement error was estimated based on the instrument design. The atmospheric profiles were obtained from Model for Ozone And Related chemical Tracers (MOZART) simulations and surface reflectances were obtained from climatology of OMI Lambertian equivalent reflectance. The uncertainties of the GEMS trace gas and aerosol products were estimated based on the OE method using the atmospheric profile and surface reflectance. Most of the estimated uncertainties of NO2, HCHO, stratospheric and total O3 products satisfied the user's requirements with sufficient margin. However, about 26% of the estimated uncertainties of SO2 and about 30% of the estimated uncertainties of tropospheric O3 do not meet the required precision. Particularly the estimated uncertainty of SO2 is high in winter, when the emission is strong in East Asia. Further efforts are necessary in order to improve the retrieval accuracy of SO2 and tropospheric O3 in order to reach the scientific goal of GEMS. Random measurement error of GEMS was important for the NO2, SO2, and HCHO retrieval, while both the random and systematic measurement errors were important for the O3 retrievals. The degree of freedom for signal of tropospheric O3 was 0.8 ± 0.2 and that for stratospheric O3 was 2.9 ± 0.5. The estimated uncertainties of the aerosol retrieval from GEMS measurements were predicted to be lower than the required precision for the SZA range of the trace gas retrievals.

Gemfibrozil and carbamazepine decrease steroid production in zebrafish testes (Danio rerio).

PubMed

Fraz, Shamaila; Lee, Abigail H; Wilson, Joanna Y

2018-05-01

Gemfibrozil (GEM) and carbamazepine (CBZ) are two environmentally relevant pharmaceuticals and chronic exposure of fish to these compounds has decreased androgen levels and fish reproduction in laboratory studies. The main focus of this study was to examine the effects of GEM and CBZ on testicular steroid production, using zebrafish as a model species. Chronic water borne exposures of adult zebrafish to 10 μg/L of GEM and CBZ were conducted and the dosing was confirmed by chemical analysis of water as 17.5 ± 1.78 and 11.2 ± 1.08 μg/L respectively. A 67 day exposure led to reduced reproductive output and lowered whole body, plasma, and testicular 11-ketotestosterone (11-KT). Testicular production of 11-KT was examined post exposure (42 days) using ex vivo cultures to determine basal and stimulated steroid production. The goal was to ascertain the step impaired in the steroidogenic pathway by each compound. Ex vivo 11-KT production in testes from males chronically exposed to GEM and CBZ was lower than that from unexposed males. Although hCG, 25-OH cholesterol, and pregnenolone stimulation increased 11-KT production in all treatment groups over basal levels, hCG stimulated 11-KT production remained significantly less in testes from exposed males compared to controls. 25-OH cholesterol and pregnenolone stimulated 11-KT production was similar between GEM and control groups but the CBZ group had lower 11-KT production than controls with both stimulants. We therefore propose that chronic GEM and CBZ exposure can reduce production of 11-KT in testes through direct effects independent of mediation through HPG axis. The biochemical processes for steroid production appear un-impacted by GEM exposure; while CBZ exposure may influence steroidogenic enzyme expression or function. Copyright © 2018 Elsevier B.V. All rights reserved.

Targeting SMN to Cajal bodies and nuclear gems during neuritogenesis

PubMed Central

Navascues, Joaquin; Berciano, Maria T.; Tucker, Karen E.

2006-01-01

Neurite outgrowth is a central feature of neuronal differentiation. PC12 cells are a good model system for studying the peripheral nervous system and the outgrowth of neurites. In addition to the dramatic changes observed in the cytoplasm, neuronal differentiation is also accompanied by striking changes in nuclear morphology. The large and sustained increase in nuclear transcription during neuronal differentiation requires synthesis of a large number of factors involved in pre-mRNA processing. We show that the number and composition of the nuclear subdomains called Cajal bodies and gems changes during the course of N-ras-induced neuritogenesis in the PC12-derived cell line UR61. The Cajal bodies found in undifferentiated cells are largely devoid of the survival of motor neurons (SMN) protein product. As cells shift to a differentiated state, SMN is not only globally upregulated, but is progressively recruited to Cajal bodies. Additional SMN foci (also known as Gemini bodies, gems) can also be detected. Using dual-immunogold labeling electron microscopy and mouse embryonic fibroblasts lacking the coilin protein, we show that gems clearly represent a distinct category of nuclear body. PMID:15164213

State-Space Analysis of Granger-Geweke Causality Measures with Application to fMRI.

PubMed

Solo, Victor

2016-05-01

The recent interest in the dynamics of networks and the advent, across a range of applications, of measuring modalities that operate on different temporal scales have put the spotlight on some significant gaps in the theory of multivariate time series. Fundamental to the description of network dynamics is the direction of interaction between nodes, accompanied by a measure of the strength of such interactions. Granger causality and its associated frequency domain strength measures (GEMs) (due to Geweke) provide a framework for the formulation and analysis of these issues. In pursuing this setup, three significant unresolved issues emerge. First, computing GEMs involves computing submodels of vector time series models, for which reliable methods do not exist. Second, the impact of filtering on GEMs has never been definitively established. Third, the impact of downsampling on GEMs has never been established. In this work, using state-space methods, we resolve all these issues and illustrate the results with some simulations. Our analysis is motivated by some problems in (fMRI) brain imaging, to which we apply it, but it is of general applicability.

State-Space Analysis of Granger-Geweke Causality Measures with Application to fMRI

PubMed Central

Solo, Victor

2017-01-01

The recent interest in the dynamics of networks and the advent, across a range of applications, of measuring modalities that operate on different temporal scales have put the spotlight on some significant gaps in the theory of multivariate time series. Fundamental to the description of network dynamics is the direction of interaction between nodes, accompanied by a measure of the strength of such interactions. Granger causality and its associated frequency domain strength measures (GEMs) (due to Geweke) provide a framework for the formulation and analysis of these issues. In pursuing this setup, three significant unresolved issues emerge. First, computing GEMs involves computing submodels of vector time series models, for which reliable methods do not exist. Second, the impact of filtering on GEMs has never been definitively established. Third, the impact of downsampling on GEMs has never been established. In this work, using state-space methods, we resolve all these issues and illustrate the results with some simulations. Our analysis is motivated by some problems in (fMRI) brain imaging, to which we apply it, but it is of general applicability. PMID:26942749

Emergence of microbial diversity due to cross-feeding interactions in a spatial model of gut microbial metabolism.

PubMed

Hoek, Milan J A van; Merks, Roeland M H

2017-05-16

The human gut contains approximately 10 14 bacteria, belonging to hundreds of different species. Together, these microbial species form a complex food web that can break down nutrient sources that our own digestive enzymes cannot handle, including complex polysaccharides, producing short chain fatty acids and additional metabolites, e.g., vitamin K. Microbial diversity is important for colonic health: Changes in the composition of the microbiota have been associated with inflammatory bowel disease, diabetes, obesity and Crohn's disease, and make the microbiota more vulnerable to infestation by harmful species, e.g., Clostridium difficile. To get a grip on the controlling factors of microbial diversity in the gut, we here propose a multi-scale, spatiotemporal dynamic flux-balance analysis model to study the emergence of metabolic diversity in a spatial gut-like, tubular environment. The model features genome-scale metabolic models (GEM) of microbial populations, resource sharing via extracellular metabolites, and spatial population dynamics and evolution. In this model, cross-feeding interactions emerge readily, despite the species' ability to metabolize sugars autonomously. Interestingly, the community requires cross-feeding for producing a realistic set of short-chain fatty acids from an input of glucose, If we let the composition of the microbial subpopulations change during invasion of adjacent space, a complex and stratified microbiota evolves, with subspecies specializing on cross-feeding interactions via a mechanism of compensated trait loss. The microbial diversity and stratification collapse if the flux through the gut is enhanced to mimic diarrhea. In conclusion, this in silico model is a helpful tool in systems biology to predict and explain the controlling factors of microbial diversity in the gut. It can be extended to include, e.g., complex nutrient sources, and host-microbiota interactions via the intestinal wall.

OpenGeoSys-GEMS: Hybrid parallelization of a reactive transport code with MPI and threads

NASA Astrophysics Data System (ADS)

Kosakowski, G.; Kulik, D. A.; Shao, H.

2012-04-01

OpenGeoSys-GEMS is a generic purpose reactive transport code based on the operator splitting approach. The code couples the Finite-Element groundwater flow and multi-species transport modules of the OpenGeoSys (OGS) project (http://www.ufz.de/index.php?en=18345) with the GEM-Selektor research package to model thermodynamic equilibrium of aquatic (geo)chemical systems utilizing the Gibbs Energy Minimization approach (http://gems.web.psi.ch/). The combination of OGS and the GEM-Selektor kernel (GEMS3K) is highly flexible due to the object-oriented modular code structures and the well defined (memory based) data exchange modules. Like other reactive transport codes, the practical applicability of OGS-GEMS is often hampered by the long calculation time and large memory requirements. • For realistic geochemical systems which might include dozens of mineral phases and several (non-ideal) solid solutions the time needed to solve the chemical system with GEMS3K may increase exceptionally. • The codes are coupled in a sequential non-iterative loop. In order to keep the accuracy, the time step size is restricted. In combination with a fine spatial discretization the time step size may become very small which increases calculation times drastically even for small 1D problems. • The current version of OGS is not optimized for memory use and the MPI version of OGS does not distribute data between nodes. Even for moderately small 2D problems the number of MPI processes that fit into memory of up-to-date workstations or HPC hardware is limited. One strategy to overcome the above mentioned restrictions of OGS-GEMS is to parallelize the coupled code. For OGS a parallelized version already exists. It is based on a domain decomposition method implemented with MPI and provides a parallel solver for fluid and mass transport processes. In the coupled code, after solving fluid flow and solute transport, geochemical calculations are done in form of a central loop over all finite element nodes with calls to GEMS3K and consecutive calculations of changed material parameters. In a first step the existing MPI implementation was utilized to parallelize this loop. Calculations were split between the MPI processes and afterwards data was synchronized by using MPI communication routines. Furthermore, multi-threaded calculation of the loop was implemented with help of the boost thread library (http://www.boost.org). This implementation provides a flexible environment to distribute calculations between several threads. For each MPI process at least one and up to several dozens of worker threads are spawned. These threads do not replicate the complete OGS-GEM data structure and use only a limited amount of memory. Calculation of the central geochemical loop is shared between all threads. Synchronization between the threads is done by barrier commands. The overall number of local threads times MPI processes should match the number of available computing nodes. The combination of multi-threading and MPI provides an effective and flexible environment to speed up OGS-GEMS calculations while limiting the required memory use. Test calculations on different hardware show that for certain types of applications tremendous speedups are possible.

Systems biology of the structural proteome.

PubMed

Brunk, Elizabeth; Mih, Nathan; Monk, Jonathan; Zhang, Zhen; O'Brien, Edward J; Bliven, Spencer E; Chen, Ke; Chang, Roger L; Bourne, Philip E; Palsson, Bernhard O

2016-03-11

The success of genome-scale models (GEMs) can be attributed to the high-quality, bottom-up reconstructions of metabolic, protein synthesis, and transcriptional regulatory networks on an organism-specific basis. Such reconstructions are biochemically, genetically, and genomically structured knowledge bases that can be converted into a mathematical format to enable a myriad of computational biological studies. In recent years, genome-scale reconstructions have been extended to include protein structural information, which has opened up new vistas in systems biology research and empowered applications in structural systems biology and systems pharmacology. Here, we present the generation, application, and dissemination of genome-scale models with protein structures (GEM-PRO) for Escherichia coli and Thermotoga maritima. We show the utility of integrating molecular scale analyses with systems biology approaches by discussing several comparative analyses on the temperature dependence of growth, the distribution of protein fold families, substrate specificity, and characteristic features of whole cell proteomes. Finally, to aid in the grand challenge of big data to knowledge, we provide several explicit tutorials of how protein-related information can be linked to genome-scale models in a public GitHub repository ( https://github.com/SBRG/GEMPro/tree/master/GEMPro_recon/). Translating genome-scale, protein-related information to structured data in the format of a GEM provides a direct mapping of gene to gene-product to protein structure to biochemical reaction to network states to phenotypic function. Integration of molecular-level details of individual proteins, such as their physical, chemical, and structural properties, further expands the description of biochemical network-level properties, and can ultimately influence how to model and predict whole cell phenotypes as well as perform comparative systems biology approaches to study differences between organisms. GEM-PRO offers insight into the physical embodiment of an organism's genotype, and its use in this comparative framework enables exploration of adaptive strategies for these organisms, opening the door to many new lines of research. With these provided tools, tutorials, and background, the reader will be in a position to run GEM-PRO for their own purposes.

Multiscale modelling in immunology: a review.

PubMed

Cappuccio, Antonio; Tieri, Paolo; Castiglione, Filippo

2016-05-01

One of the greatest challenges in biomedicine is to get a unified view of observations made from the molecular up to the organism scale. Towards this goal, multiscale models have been highly instrumental in contexts such as the cardiovascular field, angiogenesis, neurosciences and tumour biology. More recently, such models are becoming an increasingly important resource to address immunological questions as well. Systematic mining of the literature in multiscale modelling led us to identify three main fields of immunological applications: host-virus interactions, inflammatory diseases and their treatment and development of multiscale simulation platforms for immunological research and for educational purposes. Here, we review the current developments in these directions, which illustrate that multiscale models can consistently integrate immunological data generated at several scales, and can be used to describe and optimize therapeutic treatments of complex immune diseases. © The Author 2015. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Coupling the Canadian Terrestrial Ecosystem Model (CTEM v. 2.0) to Environment and Climate Change Canada's greenhouse gas forecast model (v.107-glb)

NASA Astrophysics Data System (ADS)

Badawy, Bakr; Polavarapu, Saroja; Jones, Dylan B. A.; Deng, Feng; Neish, Michael; Melton, Joe R.; Nassar, Ray; Arora, Vivek K.

2018-02-01

The Canadian Land Surface Scheme and the Canadian Terrestrial Ecosystem Model (CLASS-CTEM) together form the land surface component in the family of Canadian Earth system models (CanESMs). Here, CLASS-CTEM is coupled to Environment and Climate Change Canada (ECCC)'s weather and greenhouse gas forecast model (GEM-MACH-GHG) to consistently model atmosphere-land exchange of CO2. The coupling between the land and the atmospheric transport model ensures consistency between meteorological forcing of CO2 fluxes and CO2 transport. The procedure used to spin up carbon pools for CLASS-CTEM for multi-decadal simulations needed to be significantly altered to deal with the limited availability of consistent meteorological information from a constantly changing operational environment in the GEM-MACH-GHG model. Despite the limitations in the spin-up procedure, the simulated fluxes obtained by driving the CLASS-CTEM model with meteorological forcing from GEM-MACH-GHG were comparable to those obtained from CLASS-CTEM when it is driven with standard meteorological forcing from the Climate Research Unit (CRU) combined with reanalysis fields from the National Centers for Environmental Prediction (NCEP) to form CRU-NCEP dataset. This is due to the similarity of the two meteorological datasets in terms of temperature and radiation. However, notable discrepancies in the seasonal variation and spatial patterns of precipitation estimates, especially in the tropics, were reflected in the estimated carbon fluxes, as they significantly affected the magnitude of the vegetation productivity and, to a lesser extent, the seasonal variations in carbon fluxes. Nevertheless, the simulated fluxes based on the meteorological forcing from the GEM-MACH-GHG model are consistent to some extent with other estimates from bottom-up or top-down approaches. Indeed, when simulated fluxes obtained by driving the CLASS-CTEM model with meteorological data from the GEM-MACH-GHG model are used as prior estimates for an atmospheric CO2 inversion analysis using the adjoint of the GEOS-Chem model, the retrieved CO2 flux estimates are comparable to those obtained from other systems in terms of the global budget and the total flux estimates for the northern extratropical regions, which have good observational coverage. In data-poor regions, as expected, differences in the retrieved fluxes due to the prior fluxes become apparent. Coupling CLASS-CTEM into the Environment Canada Carbon Assimilation System (EC-CAS) is considered an important step toward understanding how meteorological uncertainties affect both CO2 flux estimates and modeled atmospheric transport. Ultimately, such an approach will provide more direct feedback to the CLASS-CTEM developers and thus help to improve the performance of CLASS-CTEM by identifying the model limitations based on atmospheric constraints.

GEM2Net: from gene expression modeling to -omics networks, a new CATdb module to investigate Arabidopsis thaliana genes involved in stress response.

PubMed

Zaag, Rim; Tamby, Jean Philippe; Guichard, Cécile; Tariq, Zakia; Rigaill, Guillem; Delannoy, Etienne; Renou, Jean-Pierre; Balzergue, Sandrine; Mary-Huard, Tristan; Aubourg, Sébastien; Martin-Magniette, Marie-Laure; Brunaud, Véronique

2015-01-01

CATdb (http://urgv.evry.inra.fr/CATdb) is a database providing a public access to a large collection of transcriptomic data, mainly for Arabidopsis but also for other plants. This resource has the rare advantage to contain several thousands of microarray experiments obtained with the same technical protocol and analyzed by the same statistical pipelines. In this paper, we present GEM2Net, a new module of CATdb that takes advantage of this homogeneous dataset to mine co-expression units and decipher Arabidopsis gene functions. GEM2Net explores 387 stress conditions organized into 18 biotic and abiotic stress categories. For each one, a model-based clustering is applied on expression differences to identify clusters of co-expressed genes. To characterize functions associated with these clusters, various resources are analyzed and integrated: Gene Ontology, subcellular localization of proteins, Hormone Families, Transcription Factor Families and a refined stress-related gene list associated to publications. Exploiting protein-protein interactions and transcription factors-targets interactions enables to display gene networks. GEM2Net presents the analysis of the 18 stress categories, in which 17,264 genes are involved and organized within 681 co-expression clusters. The meta-data analyses were stored and organized to compose a dynamic Web resource. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

New error calibration tests for gravity models using subset solutions and independent data - Applied to GEM-T3

NASA Technical Reports Server (NTRS)

Lerch, F. J.; Nerem, R. S.; Chinn, D. S.; Chan, J. C.; Patel, G. B.; Klosko, S. M.

1993-01-01

A new method has been developed to provide a direct test of the error calibrations of gravity models based on actual satellite observations. The basic approach projects the error estimates of the gravity model parameters onto satellite observations, and the results of these projections are then compared with data residual computed from the orbital fits. To allow specific testing of the gravity error calibrations, subset solutions are computed based on the data set and data weighting of the gravity model. The approach is demonstrated using GEM-T3 to show that the gravity error estimates are well calibrated and that reliable predictions of orbit accuracies can be achieved for independent orbits.

Performance of distributed multiscale simulations

PubMed Central

Borgdorff, J.; Ben Belgacem, M.; Bona-Casas, C.; Fazendeiro, L.; Groen, D.; Hoenen, O.; Mizeranschi, A.; Suter, J. L.; Coster, D.; Coveney, P. V.; Dubitzky, W.; Hoekstra, A. G.; Strand, P.; Chopard, B.

2014-01-01

Multiscale simulations model phenomena across natural scales using monolithic or component-based code, running on local or distributed resources. In this work, we investigate the performance of distributed multiscale computing of component-based models, guided by six multiscale applications with different characteristics and from several disciplines. Three modes of distributed multiscale computing are identified: supplementing local dependencies with large-scale resources, load distribution over multiple resources, and load balancing of small- and large-scale resources. We find that the first mode has the apparent benefit of increasing simulation speed, and the second mode can increase simulation speed if local resources are limited. Depending on resource reservation and model coupling topology, the third mode may result in a reduction of resource consumption. PMID:24982258

GEM Building Taxonomy (Version 2.0)

USGS Publications Warehouse

Brzev, S.; Scawthorn, C.; Charleson, A.W.; Allen, L.; Greene, M.; Jaiswal, Kishor; Silva, V.

2013-01-01

/7/8/IRRE9/10/RSH3+RWO211/FW12/13/ which can be read as (1) Direction = [DX or DY] (the building has the same lateral load-resisting system in both directions); (2) Material = [Unreinforced Masonry + solid fired clay bricks + cement: lime mortar]; (3) Lateral Load-Resisting System = [Wall]; (4) Date of construction = [pre-1939]; (5) Heaight = [exactly 2 storeys]; (6) Occupancy = [residential, unknown type]; (7) Building Position = [unknown = no entry]; (8) Shape of building plan = [unknown = no entry]; (9) Structural irregularity = [regular]; (10) Exterior walls = [unknown = no entry]; (11) Roof = [Shape: pitched and hipped, Roof covering: clay tiles, Roof system material: wood, Roof system type: wood trusses]; (12) Floor = [Floor system: Wood, unknown]; (13) Foundation = [unknown = no entry]. Mapping of GEM Building Taxonomy to selected taxonomies is included in the report -- for example, the above building would be referenced by previous structural taxonomies as: PAGER-STR as UFB or UFB4, by the World Housing Encyclopedia as 7 or 8 and by the European Macroseismic Scale (98) as M5. The Building Taxonomy data model is highly flexible and has been incorporated within a relational database architecture. Due to its ability to represent building typologies using a shorthand form, it is also possible to use the taxonomy for non-database applications, and we discuss possible application of adaptation for Building Information Modelling (BIM) systems, and for the insurance industry. The GEM Building Taxonomy was independently evaluated and tested by the Earthquake Engineering Research Institute (EERI), which received 217 TaxT reports from 49 countries, representing a wide range of building typologies, including single and multi-storey buildings, reinforced and unreinforced masonry, confined masonry, concrete, steel, wood, and earthern buildings used for residential, commercial, industrial, and educational occupancy. Based on these submissions and other feedback, the EERI team validated that the GEM Building Taxonomy is highly functional, robust and able to describe different buildings around the world. The GEM Building Taxonomy is accompanied by supplementary resources. All terms have been explained in a companion online Glossary, which provides both text and graphic descriptions. The Taxonomy is accompanied by TaxT, a computer application that enables a user record information about a building or a building typology using the attributes of the GEM Building Taxonomy v2.0. TaxT can generate a taxonomy string and enable a user to generate a report in PDF format which summarizes the attribute values (s)he has chosen as representative of the building typology under consideration. The report concludes with recommendations for future development of the GEM Building Taxonomy. Appendices provide the detailed GEM Building Taxonomy tables and additional resource, as well as mappings to other taxonomies.

SPICE Work Package 3: Modelling the Effects of Stratospheric Aerosol Geoengineering

NASA Astrophysics Data System (ADS)

Driscoll, Simon

2015-04-01

This talk presents the results of the SPICE Work Package 3. There is an obvious need for methods to verify the accuracy of geoengineering given no observations of a geoengineering programme. Accordingly, model ability in reproducing the observed dynamical response to volcanic eruptions is discussed using analysis of CMIP5 data and different configurations of the HadGEM2 model. With the HadGEM2-L60 model shown to be substantially better in reproducing the observed dynamical response to volcanic eruptions, simulations of GeoMIP's G4 scenario are performed. Simulated impacts of geoengineering are described, and asymmetries between the immediate onset and immediate cessation ('termination') of geoengineering are analysed. Whilst a rapid large increase in stratospheric sulphate aerosols (such as from volcanic eruptions) can cause substantial damage, most volcanic eruptions in general are not catastrophic. One may therefore suspect that an 'equal but opposite' change in radiative forcing from termination may therefore not be catastrophic, if the climatic response is simulated to be symmetric. HadGEM2 simulations reveal a substantially more rapid change in variables such as near-surface temperature and precipitation following termination than the onset, indicating that termination may be substantially more damaging and even catastrophic. Some suggestions for hemispherically asymmetric geoengineering have been proposed as a way to reduce Northern Hemisphere sea ice, for example, with lesser impacts on the rest of the climate. However, HadGEM2 simulations are performed and observations analysed following volcanic eruptions. Both indicate substantial averse consequences from hemispherically asymmetric loading of stratospheric loading on precipitation in the Sahelian region - a vulnerable region where drought has caused hundreds of thousands of deaths and created millions of refugees in the past.

Sharing behavioral data through a grid infrastructure using data standards.

PubMed

Min, Hua; Ohira, Riki; Collins, Michael A; Bondy, Jessica; Avis, Nancy E; Tchuvatkina, Olga; Courtney, Paul K; Moser, Richard P; Shaikh, Abdul R; Hesse, Bradford W; Cooper, Mary; Reeves, Dianne; Lanese, Bob; Helba, Cindy; Miller, Suzanne M; Ross, Eric A

2014-01-01

In an effort to standardize behavioral measures and their data representation, the present study develops a methodology for incorporating measures found in the National Cancer Institute's (NCI) grid-enabled measures (GEM) portal, a repository for behavioral and social measures, into the cancer data standards registry and repository (caDSR). The methodology consists of four parts for curating GEM measures into the caDSR: (1) develop unified modeling language (UML) models for behavioral measures; (2) create common data elements (CDE) for UML components; (3) bind CDE with concepts from the NCI thesaurus; and (4) register CDE in the caDSR. UML models have been developed for four GEM measures, which have been registered in the caDSR as CDE. New behavioral concepts related to these measures have been created and incorporated into the NCI thesaurus. Best practices for representing measures using UML models have been utilized in the practice (eg, caDSR). One dataset based on a GEM-curated measure is available for use by other systems and users connected to the grid. Behavioral and population science data can be standardized by using and extending current standards. A new branch of CDE for behavioral science was developed for the caDSR. It expands the caDSR domain coverage beyond the clinical and biological areas. In addition, missing terms and concepts specific to the behavioral measures addressed in this paper were added to the NCI thesaurus. A methodology was developed and refined for curation of behavioral and population science data. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Quantitative Analysis of Complex Drug-Drug Interactions Between Repaglinide and Cyclosporin A/Gemfibrozil Using Physiologically Based Pharmacokinetic Models With In Vitro Transporter/Enzyme Inhibition Data.

PubMed

Kim, Soo-Jin; Toshimoto, Kota; Yao, Yoshiaki; Yoshikado, Takashi; Sugiyama, Yuichi

2017-09-01

Quantitative analysis of transporter- and enzyme-mediated complex drug-drug interactions (DDIs) is challenging. Repaglinide (RPG) is transported into the liver by OATP1B1 and then is metabolized by CYP2C8 and CYP3A4. The purpose of this study was to describe the complex DDIs of RPG quantitatively based on unified physiologically based pharmacokinetic (PBPK) models using in vitro K i values for OATP1B1, CYP3A4, and CYP2C8. Cyclosporin A (CsA) or gemfibrozil (GEM) increased the blood concentrations of RPG. The time profiles of RPG and the inhibitors were analyzed by PBPK models, considering the inhibition of OATP1B1 and CYP3A4 by CsA or OATP1B1 inhibition by GEM and its glucuronide and the mechanism-based inhibition of CYP2C8 by GEM glucuronide. RPG-CsA interaction was closely predicted using a reported in vitro K i,OATP1B1 value in the presence of CsA preincubation. RPG-GEM interaction was underestimated compared with observed data, but the simulation was improved with the increase of f m,CYP2C8 . These results based on in vitro K i values for transport and metabolism suggest the possibility of a bottom-up approach with in vitro inhibition data for the prediction of complex DDIs using unified PBPK models and in vitro f m value of a substrate for multiple enzymes should be considered carefully for the prediction. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

The current status of the Gas Electron Multiplier (GEM) research at Kasetsart University, Thailand

NASA Astrophysics Data System (ADS)

Kumpiranon, P.; Kulasri, K.; Rittirong, A.; Saenboonruang, K.

2017-06-01

During the past decade, Gas Electron Multiplier (GEM) detectors have been greatly developed and utilized in numbers of applications including advanced nuclear and particle researches, medical imaging, astrophysics, and neutron detection for national security. Our GEM research group at the Department of Applied Radiation and Isotopes, Faculty of Science, Kasetsart University, Thailand, realized in its excellent properties/potentials and started extensive researches on GEM detectors. To build a strong foundation on our research group, two 10 cm × 10 cm triple GEM detectors were characterized on their important properties including absolute gains and detection uniformity. Moreover, to widen applications of the GEM detector, our group had modified the GEM detector by introducing either solid or gaseous neutron converters to the detector so that the detector could effectively detect neutrons. These modifications included coating a thin film of 10B and natB to the GEM drift cathode for thermal neutron detection and flowing a gas mixture of He/CO2 (80:20 and 70:30) and C4H10/He/CO2 (7:70:23) for fast neutron detection. Results showed that the modified GEM-based neutron detector could detect both types of neutrons with different relative efficiencies and gains depending on thicknesses and types of neutron converters. This article discusses basic knowledge of the GEM detector, construction and testing procedures, results, and discussion.

Measuring gravel transport and dispersion in a mountain river using passive radio tracers

USGS Publications Warehouse

Bradley, D. N.; Tucker, G. E.

2012-01-01

Random walk models of fluvial sediment transport recognize that grains move intermittently, with short duration steps separated by rests that are comparatively long. These models are built upon the probability distributions of the step length and the resting time. Motivated by these models, tracer experiments have attempted to measure directly the steps and rests of sediment grains in natural streams. This paper describes results from a large tracer experiment designed to test stochastic transport models. We used passive integrated transponder (PIT) tags to label 893 coarse gravel clasts and placed them in Halfmoon Creek, a small alpine stream near Leadville, Colorado, USA. The PIT tags allow us to locate and identify tracers without picking them up or digging them out of the streambed. They also enable us to find a very high percentage of our rocks, 98% after three years and 96% after the fourth year. We use the annual tracer displacement to test two stochastic transport models, the Einstein–Hubbell–Sayre (EHS) model and the Yang–Sayre gamma-exponential model (GEM). We find that the GEM is a better fit to the observations, particularly for slower moving tracers and suggest that the strength of the GEM is that the gamma distribution of step lengths approximates a compound Poisson distribution. Published in 2012. This article is a US Government work and is in the public domain in the USA.

Multiscale Mathematics for Biomass Conversion to Renewable Hydrogen

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

Plechac, Petr; Vlachos, Dionisios; Katsoulakis, Markos

2013-09-05

The overall objective of this project is to develop multiscale models for understanding and eventually designing complex processes for renewables. To the best of our knowledge, our work is the first attempt at modeling complex reacting systems, whose performance relies on underlying multiscale mathematics. Our specific application lies at the heart of biofuels initiatives of DOE and entails modeling of catalytic systems, to enable economic, environmentally benign, and efficient conversion of biomass into either hydrogen or valuable chemicals. Specific goals include: (i) Development of rigorous spatio-temporal coarse-grained kinetic Monte Carlo (KMC) mathematics and simulation for microscopic processes encountered in biomassmore » transformation. (ii) Development of hybrid multiscale simulation that links stochastic simulation to a deterministic partial differential equation (PDE) model for an entire reactor. (iii) Development of hybrid multiscale simulation that links KMC simulation with quantum density functional theory (DFT) calculations. (iv) Development of parallelization of models of (i)-(iii) to take advantage of Petaflop computing and enable real world applications of complex, multiscale models. In this NCE period, we continued addressing these objectives and completed the proposed work. Main initiatives, key results, and activities are outlined.« less

Multiscale Modeling in the Clinic: Drug Design and Development

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

Clancy, Colleen E.; An, Gary; Cannon, William R.

A wide range of length and time scales are relevant to pharmacology, especially in drug development, drug design and drug delivery. Therefore, multi-scale computational modeling and simulation methods and paradigms that advance the linkage of phenomena occurring at these multiple scales have become increasingly important. Multi-scale approaches present in silico opportunities to advance laboratory research to bedside clinical applications in pharmaceuticals research. This is achievable through the capability of modeling to reveal phenomena occurring across multiple spatial and temporal scales, which are not otherwise readily accessible to experimentation. The resultant models, when validated, are capable of making testable predictions tomore » guide drug design and delivery. In this review we describe the goals, methods, and opportunities of multi-scale modeling in drug design and development. We demonstrate the impact of multiple scales of modeling in this field. We indicate the common mathematical techniques employed for multi-scale modeling approaches used in pharmacology and present several examples illustrating the current state-of-the-art regarding drug development for: Excitable Systems (Heart); Cancer (Metastasis and Differentiation); Cancer (Angiogenesis and Drug Targeting); Metabolic Disorders; and Inflammation and Sepsis. We conclude with a focus on barriers to successful clinical translation of drug development, drug design and drug delivery multi-scale models.« less

Assessing the contribution of different factors in RegCM4.3 regional climate model projections using the Factor Separation method over the Med-CORDEX domain

NASA Astrophysics Data System (ADS)

Zsolt Torma, Csaba; Giorgi, Filippo

2014-05-01

A set of regional climate model (RCM) simulations applying dynamical downscaling of global climate model (GCM) simulations over the Mediterranean domain specified by the international initiative Coordinated Regional Downscaling Experiment (CORDEX) were completed with the Regional Climate Model RegCM, version RegCM4.3. Two GCMs were selected from the Coupled Model Intercomparison Project Phase 5 (CMIP5) ensemble to provide the driving fields for the RegCM: HadGEM2-ES (HadGEM) and MPI-ESM-MR (MPI). The simulations consist of an ensemble including multiple physics configurations and different "Reference Concentration Pathways" (RCP4.5 and RCP8.5). In total 15 simulations were carried out with 7 model physics configurations with varying convection and land surface schemes. The horizontal grid spacing of the RCM simulations is 50 km and the simulated period in all cases is 1970-2100 (1970-2099 in case of HadGEM driven simulations). This ensemble includes a combination of experiments in which different model components are changed individually and in combination, and thus lends itself optimally to the application of the Factor Separation (FS) method. This study applies the FS method to investigate the contributions of different factors, along with their synergy, on a set of regional climate model (RCM) projections for the Mediterranean region. The FS method is applied to 6 projections for the period 1970-2100 performed with the regional model RegCM4.3 over the Med-CORDEX domain. Two different sets of factors are intercompared, namely the driving global climate model (HadGEM and MPI) boundary conditions against two model physics settings (convection scheme and irrigation). We find that both the GCM driving conditions and the model physics provide important contributions, depending on the variable analyzed (surface air temperature and precipitation), season (winter vs. summer) and time horizon into the future, while the synergy term mostly tends to counterbalance the contributions of the individual factors. We demonstrate the usefulness of the FS method to assess different sources of uncertainty in RCM-based regional climate projections.

Incorporating big data into treatment plan evaluation: Development of statistical DVH metrics and visualization dashboards.

PubMed

Mayo, Charles S; Yao, John; Eisbruch, Avraham; Balter, James M; Litzenberg, Dale W; Matuszak, Martha M; Kessler, Marc L; Weyburn, Grant; Anderson, Carlos J; Owen, Dawn; Jackson, William C; Haken, Randall Ten

2017-01-01

To develop statistical dose-volume histogram (DVH)-based metrics and a visualization method to quantify the comparison of treatment plans with historical experience and among different institutions. The descriptive statistical summary (ie, median, first and third quartiles, and 95% confidence intervals) of volume-normalized DVH curve sets of past experiences was visualized through the creation of statistical DVH plots. Detailed distribution parameters were calculated and stored in JavaScript Object Notation files to facilitate management, including transfer and potential multi-institutional comparisons. In the treatment plan evaluation, structure DVH curves were scored against computed statistical DVHs and weighted experience scores (WESs). Individual, clinically used, DVH-based metrics were integrated into a generalized evaluation metric (GEM) as a priority-weighted sum of normalized incomplete gamma functions. Historical treatment plans for 351 patients with head and neck cancer, 104 with prostate cancer who were treated with conventional fractionation, and 94 with liver cancer who were treated with stereotactic body radiation therapy were analyzed to demonstrate the usage of statistical DVH, WES, and GEM in a plan evaluation. A shareable dashboard plugin was created to display statistical DVHs and integrate GEM and WES scores into a clinical plan evaluation within the treatment planning system. Benchmarking with normal tissue complication probability scores was carried out to compare the behavior of GEM and WES scores. DVH curves from historical treatment plans were characterized and presented, with difficult-to-spare structures (ie, frequently compromised organs at risk) identified. Quantitative evaluations by GEM and/or WES compared favorably with the normal tissue complication probability Lyman-Kutcher-Burman model, transforming a set of discrete threshold-priority limits into a continuous model reflecting physician objectives and historical experience. Statistical DVH offers an easy-to-read, detailed, and comprehensive way to visualize the quantitative comparison with historical experiences and among institutions. WES and GEM metrics offer a flexible means of incorporating discrete threshold-prioritizations and historic context into a set of standardized scoring metrics. Together, they provide a practical approach for incorporating big data into clinical practice for treatment plan evaluations.

GEM Detector Performance Assessment in the BM@N Experiment

NASA Astrophysics Data System (ADS)

Kapishin, Mikhail; Karjavin, Vladimir; Kulish, Elena; Lenivenko, Vasilisa; Makankin, Alexander; Maksymchuk, Anna; Palichik, Vladimir; Vasiliev, Sergey

2018-02-01

The Gas Electron Multiplier (GEM) chambers are developed for modern purposes in the elementary particle physics. In the BM@N experiment, a GEM system is used for the reconstruction of the trajectories of the charged particles. The investigation of GEM performance (efficiency and spatial resolution) is presented.

Multiscale Shannon's Entropy Modeling of Orientation and Distance in Steel Fiber Micro-Tomography Data.

PubMed

Chiverton, John P; Ige, Olubisi; Barnett, Stephanie J; Parry, Tony

2017-11-01

This paper is concerned with the modeling and analysis of the orientation and distance between steel fibers in X-ray micro-tomography data. The advantage of combining both orientation and separation in a model is that it helps provide a detailed understanding of how the steel fibers are arranged, which is easy to compare. The developed models are designed to summarize the randomness of the orientation distribution of the steel fibers both locally and across an entire volume based on multiscale entropy. Theoretical modeling, simulation, and application to real imaging data are shown here. The theoretical modeling of multiscale entropy for orientation includes a proof showing the final form of the multiscale taken over a linear range of scales. A series of image processing operations are also included to overcome interslice connectivity issues to help derive the statistical descriptions of the orientation distributions of the steel fibers. The results demonstrate that multiscale entropy provides unique insights into both simulated and real imaging data of steel fiber reinforced concrete.

Study of the GEM detector performance in BM@N experiment

NASA Astrophysics Data System (ADS)

Bazylev, Sergei; Kapishin, Mikhail; Kapusniak, Kacper; Karjavine, Vladimir; Khabarov, Sergei; Kolesnikov, Alexander; Kulish, Elena; Lenivenko, Vasilisa; Makankin, Alexander; Maksymchuk, Anna; Mehl, Bertrand; De Oliveira, Rui; Palchik, Vladimir; Pokatashkin, Gleb; Rodriguez, A.; Rufanov, Igor; Shutov, Alexander; Slepnev, Ilya; Slepnev, Vyacheslav; Vasiliev, Sergei; Zinchenko, Alexander

2018-04-01

BM@N is the fixed target experiment at the accelerator complex NICA-Nuclotron aimed to study nuclear matter in the relativistic heavy ion collisions. Triple-GEM detectors were identified as appropriate for the BM@N tracking system located inside the analyzing magnet. Seven GEM chambers are integrated into the BM@N experimental setup and data acquisition system. GEM construction, main characteristics and first obtained results of the GEM tracking system performance in the technical run with the deuteron beam are shortly reviewed.

Role of resolution in regional climate change projections over China

NASA Astrophysics Data System (ADS)

Shi, Ying; Wang, Guiling; Gao, Xuejie

2017-11-01

This paper investigates the sensitivity of projected future climate changes over China to the horizontal resolution of a regional climate model RegCM4.4 (RegCM), using RCP8.5 as an example. Model validation shows that RegCM performs better in reproducing the spatial distribution and magnitude of present-day temperature, precipitation and climate extremes than the driving global climate model HadGEM2-ES (HadGEM, at 1.875° × 1.25° degree resolution), but little difference is found between the simulations at 50 and 25 km resolutions. Comparison with observational data at different resolutions confirmed the added value of the RCM and finer model resolutions in better capturing the probability distribution of precipitation. However, HadGEM and RegCM at both resolutions project a similar pattern of significant future warming during both winter and summer, and a similar pattern of winter precipitation changes including dominant increase in most areas of northern China and little change or decrease in the southern part. Projected precipitation changes in summer diverge among the three models, especially over eastern China, with a general increase in HadGEM, little change in RegCM at 50 km, and a mix of increase and decrease in RegCM at 25 km resolution. Changes of temperature-related extremes (annual total number of daily maximum temperature > 25 °C, the maximum value of daily maximum temperature, the minimum value of daily minimum temperature in the three simulations especially in the two RegCM simulations are very similar to each other; so are the precipitation-related extremes (maximum consecutive dry days, maximum consecutive 5-day precipitation and extremely wet days' total amount). Overall, results from this study indicate a very low sensitivity of projected changes in this region to model resolution. While fine resolution is critical for capturing the spatial variability of the control climate, it may not be as important for capturing the climate response to homogeneous forcing (in this case greenhouse gas concentration changes).

Characterization of Cyclohexanone Inclusions in Class 1 RDX

DTIC Science & Technology

2014-06-01

characterized with respect to solvent inclusions in support of a U.S. Army Research Laboratory (ARL) program to model Multiscale Response of Energetic...pertinent to their modeling effort under the Multiscale Response of Energetic Materials (MREM) program, and the Weapons and Materials Research...support of a U.S. Army Research Laboratory (ARL) initiative called “ Multiscale Modeling of Energetic Materials” (MREM). The MREM program aims, for

Structural and Practical Identifiability Issues of Immuno-Epidemiological Vector-Host Models with Application to Rift Valley Fever.

PubMed

Tuncer, Necibe; Gulbudak, Hayriye; Cannataro, Vincent L; Martcheva, Maia

2016-09-01

In this article, we discuss the structural and practical identifiability of a nested immuno-epidemiological model of arbovirus diseases, where host-vector transmission rate, host recovery, and disease-induced death rates are governed by the within-host immune system. We incorporate the newest ideas and the most up-to-date features of numerical methods to fit multi-scale models to multi-scale data. For an immunological model, we use Rift Valley Fever Virus (RVFV) time-series data obtained from livestock under laboratory experiments, and for an epidemiological model we incorporate a human compartment to the nested model and use the number of human RVFV cases reported by the CDC during the 2006-2007 Kenya outbreak. We show that the immunological model is not structurally identifiable for the measurements of time-series viremia concentrations in the host. Thus, we study the non-dimensionalized and scaled versions of the immunological model and prove that both are structurally globally identifiable. After fixing estimated parameter values for the immunological model derived from the scaled model, we develop a numerical method to fit observable RVFV epidemiological data to the nested model for the remaining parameter values of the multi-scale system. For the given (CDC) data set, Monte Carlo simulations indicate that only three parameters of the epidemiological model are practically identifiable when the immune model parameters are fixed. Alternatively, we fit the multi-scale data to the multi-scale model simultaneously. Monte Carlo simulations for the simultaneous fitting suggest that the parameters of the immunological model and the parameters of the immuno-epidemiological model are practically identifiable. We suggest that analytic approaches for studying the structural identifiability of nested models are a necessity, so that identifiable parameter combinations can be derived to reparameterize the nested model to obtain an identifiable one. This is a crucial step in developing multi-scale models which explain multi-scale data.

Gemcitabine-loaded albumin nanospheres (GEM-ANPs) inhibit PANC-1 cells in vitro and in vivo

NASA Astrophysics Data System (ADS)

Li, Ji; Di, Yang; Jin, Chen; Fu, Deliang; Yang, Feng; Jiang, Yongjian; Yao, Lie; Hao, Sijie; Wang, Xiaoyi; Subedi, Sabin; Ni, Quanxing

2013-04-01

With the development of nanotechnology, special attention has been given to the nanomaterial application in tumor treatment. Here, a modified desolvation-cross-linking method was successfully applied to fabricate gemcitabine-loaded albumin nanospheres (GEM-ANPs), with 110 and 406 nm of mean diameter, respectively. The aim of this study was to assess the drug distribution, side effects, and antitumor activity of GEM-ANPs in vivo. The metabolic viability and flow cytometry analysis revealed that both GEM-ANPs, especially 406-nm GEM-ANPs, could effectively inhibit the metabolism and proliferation and promote the apoptosis of human pancreatic carcinoma (PANC-1) in vitro. Intravenous injection of 406-nm GEM-ANPs exhibited a significant increase of gemcitabine in the pancreas, liver, and spleen of Sprague-Dawley rats ( p < 0.05). Moreover, no signs of toxic side effects analyzed by blood parameter changes were observed after 3 weeks of administration although a high dose (200 mg/kg) of GEM-ANPs were used. Additionally, in PANC-1-induced tumor mice, intravenous injection of 406-nm GEM-ANPs also could effectively reduce the tumor volume by comparison with free gemcitabine. With these findings, albumin nanosphere-loading approach might be efficacious to improve the antitumor activity of gemcitabine, and the efficacy is associated with the size of GEM-ANPs.

Evaluation of the Cloud Fields in the UK Met Office HadGEM3-UKCA Model Using the CCCM Satellite Data Product to Advance Our Understanding of the Influence of Clouds on Tropospheric Composition and Chemistry

NASA Technical Reports Server (NTRS)

Varma, Sunil; Voulgarakis, Apostolos; Liu, Hongyu; Crawford, James H.; White, James

2016-01-01

To determine the role of clouds in driving inter-annual and inter-seasonal variability of trace gases in the troposphere and lower stratosphere with a particular focus on the importance of cloud modification of photolysis. To evaluate the cloud fields and their vertical distribution in the HadGEM3 model utilizing CCCM, a unique 3-D cloud data product merged from multiple A-Train satellites (CERES, CloudSat, CALIPSO, and MODIS) developed at the NASA Langley Research Center.

Reentrant and Isostructural Transitions in the Cluster-Crystal Forming GEM-4

NASA Astrophysics Data System (ADS)

Zhang, Kai; Charbonneau, Patrick; Mladek, Bianca

2011-03-01

Systems governed by soft, bounded, purely repulsive interactions show two possible equilibrium behaviors under compression: reentrant melting, as in the Gaussian core model (GCM), or clustering, as in the penetrable sphere model (PSM). The generalized exponential model of power 4 (GEM-4), which is the intermedia of the GCM and PSM with a simple isotropic pair interaction u (r) ~e-r4 , is thought to belong to the second family and was indeed found to form clusters at sufficiently high densities at high temperatures. Here, we present the low-temperature behavior of GEM-4 through Monte Carlo simulations using a specially developed free energy integration scheme. We find the phase behavior to be hybrid between the GCM and the PSM limits, showing a surprisingly rich phase behavior in spite of the simplicity of the interaction form. For instance, S- shaped doubly reentrant phase sequences and evidence of a cascade of critical isostructural transitions between crystals of different average lattice site occupancy are observed. The possible annihilation of lattice sites and accompanying clustering moreover leads to an unusual softening upon compression, which suggest that these materials may have interesting mechanical properties. We discuss possible experimental realizations and challenges of this class of materials.

EMIC wave events during the four QARBM challenge intervals

NASA Astrophysics Data System (ADS)

Engebretson, M. J.; Posch, J. L.; Braun, D.; Li, W.; Angelopoulos, V.; Kellerman, A. C.; Kletzing, C.; Lessard, M.; Mann, I. R.; Tero, R.; Shiokawa, K.; Wygant, J. R.

2017-12-01

We present observations of EMIC waves from multiple data sources during the four GEM challenge events in 2013 selected by the GEM focus group on Quantitative Assessment of Radiation Belt Modeling: March 17-18 (Stormtime Enhancement), May 31-June 2 (Stormtime Dropout), September 19-20 (Non-storm Enhancement), and September 23-25 (Non-storm Dropout). Observations include EMIC wave data from the Van Allen Probes and THEMIS spacecraft in the inner magnetosphere and from several arrays of ground-based search coil magnetometers worldwide, as well as localized ring current proton precipitation data from the low-altitude POES spacecraft. Each of these data sets provides only limited spatial coverage, but their combination reveals consistent occurrence patterns, which are then used to evaluate the effectiveness of EMIC waves in causing dropouts of radiation belt electrons during these GEM events.

Multiscale Models in the Biomechanics of Plant Growth

PubMed Central

Fozard, John A.

2015-01-01

Plant growth occurs through the coordinated expansion of tightly adherent cells, driven by regulated softening of cell walls. It is an intrinsically multiscale process, with the integrated properties of multiple cell walls shaping the whole tissue. Multiscale models encode physical relationships to bring new understanding to plant physiology and development. PMID:25729061

The influence of gemfibrozil on malondialdehyde level and paraoxonase 1 activity in wistar and fisher rats.

PubMed

Macan, Marija; Marija, Macan; Konjevoda, Paško; Paško, Konjevoda; Lovric, Jasna; Jasna, Lovrić; Koprivanac, Marijan; Marijan, Koprivanac; Kelava, Marta; Marta, Kelava; Vrkic, Nada; Nada, Vrkić; Bradamante, Vlasta; Vlasta, Bradamante

2011-06-01

There are diverse experimental data about the influence of gemfibrozil (GEM) on the production of hydrogen peroxide (H(2)O(2)) and antioxidant enzymes. We investigated the influence of GEM treatment on the production of malondialdehyde (MDA) level in tissues of normolipidaemic Wistar and Fisher rats which is an index of lipid peroxidation. Because serum paraoxonase 1 (PON1) is an important enzyme with specific protective function on metabolism of lipid peroxides, we examined the influence of GEM on PON1 activity in liver and serum. MDA level and enzyme activities were also determined 10 days after withdrawal of GEM treatment. The significantly increased levels of MDA in liver, kidney and heart of both rat strains were obtained after 3 weeks of GEM treatment. We propose two possibilities for the increase of MDA levels caused by GEM, induction of peroxisome proliferation and activities of enzymes that participated in occurrence of H(2)O(2) and possible reduction of enzyme activities including in H(2)O(2) metabolism. Ten days after withdrawal of GEM treatment, MDA levels in all tissue levels of both rat strains were less in comparison with GEM treatment. GEM caused a significant drop of PON1 activity in serum and liver of Fisher rats, and in liver of Wistar rats. We suggest that GEM, through induction of lipid peroxidation, caused the damage of hepatocytes with consequent reduction of PON1 synthesis. The increase in PON1 activity in serum and tissues of both rat strains 10 days after withdrawal of GEM treatment shows the fast recovery of enzyme synthesis. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.

CONKO-005: Adjuvant Chemotherapy With Gemcitabine Plus Erlotinib Versus Gemcitabine Alone in Patients After R0 Resection of Pancreatic Cancer: A Multicenter Randomized Phase III Trial.

PubMed

Sinn, Marianne; Bahra, Marcus; Liersch, Torsten; Gellert, Klaus; Messmann, Helmut; Bechstein, Wolf; Waldschmidt, Dirk; Jacobasch, Lutz; Wilhelm, Martin; Rau, Bettina M; Grützmann, Robert; Weinmann, Arndt; Maschmeyer, Georg; Pelzer, Uwe; Stieler, Jens M; Striefler, Jana K; Ghadimi, Michael; Bischoff, Sven; Dörken, Bernd; Oettle, Helmut; Riess, Hanno

2017-10-10

Purpose Gemcitabine is standard of care in the adjuvant treatment of resectable pancreatic ductal adenocarcinoma (PDAC). The epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in combination with gemcitabine has shown efficacy in the treatment of advanced PDAC and was considered to improve survival in patients with primarily resectable PDAC after R0 resection. Patients and Methods In an open-label, multicenter trial, patients were randomly assigned to one of two study arms: gemcitabine 1,000 mg/m 2 days 1, 8, 15, every 4 weeks plus erlotinib 100 mg once per day (GemErlo) or gemcitabine (Gem) alone for six cycles. The primary end point of the study was to improve disease-free survival (DFS) from 14 to 18 months by adding erlotinib to gemcitabine. Results In all, 436 patients were randomly assigned at 57 study centers between April 2008 and July 2013. A total of 361 instances (83%) of disease recurrence were observed after a median follow-up of 54 months. Median treatment duration was 22 weeks in both arms. There was no difference in median DFS (GemErlo 11.4 months; Gem 11.4 months) or median overall survival (GemErlo 24.5 months; Gem 26.5 months). There was a trend toward long-term survival in favor of GemErlo (estimated survival after 1, 2, and 5 years for GemErlo was 77%, 53%, and 25% v 79%, 54%, and 20% for Gem, respectively). The occurrence or the grade of rash was not associated with a better survival in the GemErlo arm. Conclusion To the best of our knowledge, CONKO-005 is the first study to investigate the combination of chemotherapy and a targeted therapy in the adjuvant treatment of PDAC. GemErlo for 24 weeks did not improve DFS or overall survival over Gem.

Systems oncology: towards patient-specific treatment regimes informed by multiscale mathematical modelling.

PubMed

Powathil, Gibin G; Swat, Maciej; Chaplain, Mark A J

2015-02-01

The multiscale complexity of cancer as a disease necessitates a corresponding multiscale modelling approach to produce truly predictive mathematical models capable of improving existing treatment protocols. To capture all the dynamics of solid tumour growth and its progression, mathematical modellers need to couple biological processes occurring at various spatial and temporal scales (from genes to tissues). Because effectiveness of cancer therapy is considerably affected by intracellular and extracellular heterogeneities as well as by the dynamical changes in the tissue microenvironment, any model attempt to optimise existing protocols must consider these factors ultimately leading to improved multimodal treatment regimes. By improving existing and building new mathematical models of cancer, modellers can play important role in preventing the use of potentially sub-optimal treatment combinations. In this paper, we analyse a multiscale computational mathematical model for cancer growth and spread, incorporating the multiple effects of radiation therapy and chemotherapy in the patient survival probability and implement the model using two different cell based modelling techniques. We show that the insights provided by such multiscale modelling approaches can ultimately help in designing optimal patient-specific multi-modality treatment protocols that may increase patients quality of life. Copyright © 2014 Elsevier Ltd. All rights reserved.

Use of short-term breath measures to estimate daily methane production by cattle.

PubMed

Velazco, J I; Mayer, D G; Zimmerman, S; Hegarty, R S

2016-01-01

Methods to measure enteric methane (CH4) emissions from individual ruminants in their production environment are required to validate emission inventories and verify mitigation claims. Estimates of daily methane production (DMP) based on consolidated short-term emission measurements are developing, but method verification is required. Two cattle experiments were undertaken to test the hypothesis that DMP estimated by averaging multiple short-term breath measures of methane emission rate did not differ from DMP measured in respiration chambers (RC). Short-term emission rates were obtained from a GreenFeed Emissions Monitoring (GEM) unit, which measured emission rate while cattle consumed a dispensed supplement. In experiment 1 (Expt. 1), four non-lactating cattle (LW=518 kg) were adapted for 18 days then measured for six consecutive periods. Each period consisted of 2 days of ad libitum intake and GEM emission measurement followed by 1 day in the RC. A prototype GEM unit releasing water as an attractant (GEM water) was also evaluated in Expt. 1. Experiment 2 (Expt. 2) was a larger study based on similar design with 10 cattle (LW=365 kg), adapted for 21 days and GEM measurement was extended to 3 days in each of the six periods. In Expt. 1, there was no difference in DMP estimated by the GEM unit relative to the RC (209.7 v. 215.1 g CH(4)/day) and no difference between these methods in methane yield (MY, 22.7 v. 23.7 g CH(4)/kg of dry matter intake, DMI). In Expt. 2, the correlation between GEM and RC measures of DMP and MY were assessed using 95% confidence intervals, with no difference in DMP or MY between methods and high correlations between GEM and RC measures for DMP (r=0.85; 215 v. 198 g CH(4)/day SEM=3.0) and for MY (r=0.60; 23.8 v. 22.1 g CH(4)/kg DMI SEM=0.42). When data from both experiments was combined neither DMP nor MY differed between GEM- and RC-based measures (P>0.05). GEM water-based estimates of DMP and MY were lower than RC and GEM (P<0.05). Cattle accessed the GEM water unit with similar frequency to the GEM unit (2.8 v. 3.5 times/day, respectively) but eructation frequency was reduced from 1.31 times/min (GEM) to once every 2.6 min (GEM water). These studies confirm the hypothesis that DMP estimated by averaging multiple short-term breath measures of methane emission rate using GEM does not differ from measures of DMP obtained from RCs. Further, combining many short-term measures of methane production rate during supplement consumption provides an estimate of DMP, which can be usefully applied in estimating MY.

Multi-scale Modeling in Clinical Oncology: Opportunities and Barriers to Success.

PubMed

Yankeelov, Thomas E; An, Gary; Saut, Oliver; Luebeck, E Georg; Popel, Aleksander S; Ribba, Benjamin; Vicini, Paolo; Zhou, Xiaobo; Weis, Jared A; Ye, Kaiming; Genin, Guy M

2016-09-01

Hierarchical processes spanning several orders of magnitude of both space and time underlie nearly all cancers. Multi-scale statistical, mathematical, and computational modeling methods are central to designing, implementing and assessing treatment strategies that account for these hierarchies. The basic science underlying these modeling efforts is maturing into a new discipline that is close to influencing and facilitating clinical successes. The purpose of this review is to capture the state-of-the-art as well as the key barriers to success for multi-scale modeling in clinical oncology. We begin with a summary of the long-envisioned promise of multi-scale modeling in clinical oncology, including the synthesis of disparate data types into models that reveal underlying mechanisms and allow for experimental testing of hypotheses. We then evaluate the mathematical techniques employed most widely and present several examples illustrating their application as well as the current gap between pre-clinical and clinical applications. We conclude with a discussion of what we view to be the key challenges and opportunities for multi-scale modeling in clinical oncology.

Multi-scale Modeling in Clinical Oncology: Opportunities and Barriers to Success

PubMed Central

Yankeelov, Thomas E.; An, Gary; Saut, Oliver; Luebeck, E. Georg; Popel, Aleksander S.; Ribba, Benjamin; Vicini, Paolo; Zhou, Xiaobo; Weis, Jared A.; Ye, Kaiming; Genin, Guy M.

2016-01-01

Hierarchical processes spanning several orders of magnitude of both space and time underlie nearly all cancers. Multi-scale statistical, mathematical, and computational modeling methods are central to designing, implementing and assessing treatment strategies that account for these hierarchies. The basic science underlying these modeling efforts is maturing into a new discipline that is close to influencing and facilitating clinical successes. The purpose of this review is to capture the state-of-the-art as well as the key barriers to success for multi-scale modeling in clinical oncology. We begin with a summary of the long-envisioned promise of multi-scale modeling in clinical oncology, including the synthesis of disparate data types into models that reveal underlying mechanisms and allow for experimental testing of hypotheses. We then evaluate the mathematical techniques employed most widely and present several examples illustrating their application as well as the current gap between pre-clinical and clinical applications. We conclude with a discussion of what we view to be the key challenges and opportunities for multi-scale modeling in clinical oncology. PMID:27384942

Modeling Framework for Fracture in Multiscale Cement-Based Material Structures

PubMed Central

Qian, Zhiwei; Schlangen, Erik; Ye, Guang; van Breugel, Klaas

2017-01-01

Multiscale modeling for cement-based materials, such as concrete, is a relatively young subject, but there are already a number of different approaches to study different aspects of these classical materials. In this paper, the parameter-passing multiscale modeling scheme is established and applied to address the multiscale modeling problem for the integrated system of cement paste, mortar, and concrete. The block-by-block technique is employed to solve the length scale overlap challenge between the mortar level (0.1–10 mm) and the concrete level (1–40 mm). The microstructures of cement paste are simulated by the HYMOSTRUC3D model, and the material structures of mortar and concrete are simulated by the Anm material model. Afterwards the 3D lattice fracture model is used to evaluate their mechanical performance by simulating a uniaxial tensile test. The simulated output properties at a lower scale are passed to the next higher scale to serve as input local properties. A three-level multiscale lattice fracture analysis is demonstrated, including cement paste at the micrometer scale, mortar at the millimeter scale, and concrete at centimeter scale. PMID:28772948

Multiscale modeling and simulation of brain blood flow

NASA Astrophysics Data System (ADS)

Perdikaris, Paris; Grinberg, Leopold; Karniadakis, George Em

2016-02-01

The aim of this work is to present an overview of recent advances in multi-scale modeling of brain blood flow. In particular, we present some approaches that enable the in silico study of multi-scale and multi-physics phenomena in the cerebral vasculature. We discuss the formulation of continuum and atomistic modeling approaches, present a consistent framework for their concurrent coupling, and list some of the challenges that one needs to overcome in achieving a seamless and scalable integration of heterogeneous numerical solvers. The effectiveness of the proposed framework is demonstrated in a realistic case involving modeling the thrombus formation process taking place on the wall of a patient-specific cerebral aneurysm. This highlights the ability of multi-scale algorithms to resolve important biophysical processes that span several spatial and temporal scales, potentially yielding new insight into the key aspects of brain blood flow in health and disease. Finally, we discuss open questions in multi-scale modeling and emerging topics of future research.

Great Explorations in Math and Science[R] (GEMS[R]) Space Science. What Works Clearinghouse Intervention Report

ERIC Educational Resources Information Center

What Works Clearinghouse, 2012

2012-01-01

"Great Explorations in Math and Science[R] (GEMS[R]) Space Science" is an instructional sequence for grades 3-5 that covers fundamental concepts, including planetary sizes and distance, the Earth's shape and movement, gravity, and moon phases and eclipses. Part of the "GEMS"[R] core curriculum, "GEMS[R] Space Science"…

Possible Gems and Ultra-Fine Grained Polyphase Units in Comet Wild 2.

NASA Technical Reports Server (NTRS)

Gainsforth, Z.; Butterworth, A. L.; Jilly-Rehak, C. E.; Westphal, A. J.; Brownlee, D. E.; Joswiak, D.; Ogliore, R. C.; Zolensky, M. E.; Bechtel, H. A.; Ebel, D. S.;

On the Origin of GEMS

NASA Technical Reports Server (NTRS)

Keller, L. P.; Messenger, S.

2004-01-01

GEMS (glass with embedded metal and sulfides) are a major component of anhydrous interplanetary dust particles (IDPs) their physical and chemical characteristics show marked similarities to contemporary interstellar dust. Recent oxygen isotopic measurements confirm that at least a small fraction (less than 5%) of GEMS are demonstrably presolar, while the remainder have ratios that are indistinguishable from solar values. GEMS with solar oxygen isotopic compositions either (1) had their isotopic compositions homogenized through processing in the interstellar medium (ISM), or (2) formed in the early solar system. Isotopic homogenization necessarily implies chemical homogenization, so (interstellar) GEMS compositions should reflect the average composition of dust in the local ISM. We performed a systematic examination of the bulk chemistry of GEMS in primitive IDPs in order to test this hypothesis.

Generalized multiscale finite-element method (GMsFEM) for elastic wave propagation in heterogeneous, anisotropic media

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

Gao, Kai; Fu, Shubin; Gibson, Richard L.

It is important to develop fast yet accurate numerical methods for seismic wave propagation to characterize complex geological structures and oil and gas reservoirs. However, the computational cost of conventional numerical modeling methods, such as finite-difference method and finite-element method, becomes prohibitively expensive when applied to very large models. We propose a Generalized Multiscale Finite-Element Method (GMsFEM) for elastic wave propagation in heterogeneous, anisotropic media, where we construct basis functions from multiple local problems for both the boundaries and interior of a coarse node support or coarse element. The application of multiscale basis functions can capture the fine scale mediummore » property variations, and allows us to greatly reduce the degrees of freedom that are required to implement the modeling compared with conventional finite-element method for wave equation, while restricting the error to low values. We formulate the continuous Galerkin and discontinuous Galerkin formulation of the multiscale method, both of which have pros and cons. Applications of the multiscale method to three heterogeneous models show that our multiscale method can effectively model the elastic wave propagation in anisotropic media with a significant reduction in the degrees of freedom in the modeling system.« less

Generalized Multiscale Finite-Element Method (GMsFEM) for elastic wave propagation in heterogeneous, anisotropic media

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

Gao, Kai, E-mail: kaigao87@gmail.com; Fu, Shubin, E-mail: shubinfu89@gmail.com; Gibson, Richard L., E-mail: gibson@tamu.edu

It is important to develop fast yet accurate numerical methods for seismic wave propagation to characterize complex geological structures and oil and gas reservoirs. However, the computational cost of conventional numerical modeling methods, such as finite-difference method and finite-element method, becomes prohibitively expensive when applied to very large models. We propose a Generalized Multiscale Finite-Element Method (GMsFEM) for elastic wave propagation in heterogeneous, anisotropic media, where we construct basis functions from multiple local problems for both the boundaries and interior of a coarse node support or coarse element. The application of multiscale basis functions can capture the fine scale mediummore » property variations, and allows us to greatly reduce the degrees of freedom that are required to implement the modeling compared with conventional finite-element method for wave equation, while restricting the error to low values. We formulate the continuous Galerkin and discontinuous Galerkin formulation of the multiscale method, both of which have pros and cons. Applications of the multiscale method to three heterogeneous models show that our multiscale method can effectively model the elastic wave propagation in anisotropic media with a significant reduction in the degrees of freedom in the modeling system.« less

Generalized multiscale finite-element method (GMsFEM) for elastic wave propagation in heterogeneous, anisotropic media

DOE PAGES

Gao, Kai; Fu, Shubin; Gibson, Richard L.; ...

2015-04-14

It is important to develop fast yet accurate numerical methods for seismic wave propagation to characterize complex geological structures and oil and gas reservoirs. However, the computational cost of conventional numerical modeling methods, such as finite-difference method and finite-element method, becomes prohibitively expensive when applied to very large models. We propose a Generalized Multiscale Finite-Element Method (GMsFEM) for elastic wave propagation in heterogeneous, anisotropic media, where we construct basis functions from multiple local problems for both the boundaries and interior of a coarse node support or coarse element. The application of multiscale basis functions can capture the fine scale mediummore » property variations, and allows us to greatly reduce the degrees of freedom that are required to implement the modeling compared with conventional finite-element method for wave equation, while restricting the error to low values. We formulate the continuous Galerkin and discontinuous Galerkin formulation of the multiscale method, both of which have pros and cons. Applications of the multiscale method to three heterogeneous models show that our multiscale method can effectively model the elastic wave propagation in anisotropic media with a significant reduction in the degrees of freedom in the modeling system.« less

Measuring Men's Gender Norms and Gender Role Conflict/Stress in a High HIV-Prevalence South African Setting.

PubMed

Gottert, Ann; Barrington, Clare; Pettifor, Audrey; McNaughton-Reyes, Heath Luz; Maman, Suzanne; MacPhail, Catherine; Kahn, Kathleen; Selin, Amanda; Twine, Rhian; Lippman, Sheri A

2016-08-01

Gender norms and gender role conflict/stress may influence HIV risk behaviors among men; however scales measuring these constructs need further development and evaluation in African settings. We conducted exploratory and confirmatory factor analyses to evaluate the Gender Equitable Men's Scale (GEMS) and the Gender Role Conflict/Stress (GRC/S) scale among 581 men in rural northeast South Africa. The final 17-item GEMS was unidimensional, with adequate model fit and reliability (alpha = 0.79). Factor loadings were low (0.2-0.3) for items related to violence and sexual relationships. The final 24-item GRC/S scale was multidimensional with four factors: Success, power, competition; Subordination to women; Restrictive emotionality; and Sexual prowess. The scale had adequate model fit and good reliability (alpha = 0.83). While GEMS is a good measure of inequitable gender norms, new or revised scale items may need to be explored in the South African context. Adding the GRC/S scale to capture men's strain related to gender roles could provide important insights into men's risk behaviors.

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

Not Available

The GEM collaboration was formed in June 1991 to develop a major detector for the SSC. The primary physics objectives of GEM are those central to the motivation for the SSC, to study high p{sub T} physics - exemplified by the search for Higgs bosons - and to search for new physics beyond the standard model. The authors present in this Technical Design Report (TDR) a detector with broad capabilities for the discovery and subsequent study of electroweak symmetry breaking, the origin of mass and flavor, and other physics requiring precise measurements of gammas, electrons, and muons - hence themore » name, GEM. In addition, as a design goal, they have taken care to provide the robustness needed to do the physics that requires high luminosity. Finally, good coverage and hermeticity allow the detection of missing transverse energy, E{sub T}. The GEM design emphasizes clean identification and high resolution measurement of the primary physics signatures for high p{sub T} physics. The approach is to make precise energy measurements that maximize the sensitivity to rare narrow resonances, to detect the elementary interaction products (quarks, leptons, and photons), and to build in the features required to reduce backgrounds.« less

Shaken but not stirred: Multiscale habitat suitability modeling of sympatric marten species (Martes martes and Martes foina) in the northern Iberian Peninsula

Treesearch

Maria Vergara; Samuel A. Cushman; Fermin Urra; Aritz Ruiz-Gonzalez

2016-01-01

Multispecies and multiscale habitat suitability models (HSM) are important to identify the environmental variables and scales influencing habitat selection and facilitate the comparison of closely related species with different ecological requirements. Objectives This study explores the multiscale relationships of habitat suitability for the pine (Martes...

Microphysics in the Multi-Scale Modeling Systems with Unified Physics

NASA Technical Reports Server (NTRS)

Tao, Wei-Kuo; Chern, J.; Lamg, S.; Matsui, T.; Shen, B.; Zeng, X.; Shi, R.

2011-01-01

In recent years, exponentially increasing computer power has extended Cloud Resolving Model (CRM) integrations from hours to months, the number of computational grid points from less than a thousand to close to ten million. Three-dimensional models are now more prevalent. Much attention is devoted to precipitating cloud systems where the crucial 1-km scales are resolved in horizontal domains as large as 10,000 km in two-dimensions, and 1,000 x 1,000 km2 in three-dimensions. Cloud resolving models now provide statistical information useful for developing more realistic physically based parameterizations for climate models and numerical weather prediction models. It is also expected that NWP and mesoscale model can be run in grid size similar to cloud resolving model through nesting technique. Recently, a multi-scale modeling system with unified physics was developed at NASA Goddard. It consists of (l) a cloud-resolving model (Goddard Cumulus Ensemble model, GCE model), (2) a regional scale model (a NASA unified weather research and forecast, WRF), (3) a coupled CRM and global model (Goddard Multi-scale Modeling Framework, MMF), and (4) a land modeling system. The same microphysical processes, long and short wave radiative transfer and land processes and the explicit cloud-radiation, and cloud-surface interactive processes are applied in this multi-scale modeling system. This modeling system has been coupled with a multi-satellite simulator to use NASA high-resolution satellite data to identify the strengths and weaknesses of cloud and precipitation processes simulated by the model. In this talk, the microphysics developments of the multi-scale modeling system will be presented. In particular, the results from using multi-scale modeling system to study the heavy precipitation processes will be presented.

A genome-scale metabolic flux model of Escherichia coli K–12 derived from the EcoCyc database

PubMed Central

2014-01-01

Background Constraint-based models of Escherichia coli metabolic flux have played a key role in computational studies of cellular metabolism at the genome scale. We sought to develop a next-generation constraint-based E. coli model that achieved improved phenotypic prediction accuracy while being frequently updated and easy to use. We also sought to compare model predictions with experimental data to highlight open questions in E. coli biology. Results We present EcoCyc–18.0–GEM, a genome-scale model of the E. coli K–12 MG1655 metabolic network. The model is automatically generated from the current state of EcoCyc using the MetaFlux software, enabling the release of multiple model updates per year. EcoCyc–18.0–GEM encompasses 1445 genes, 2286 unique metabolic reactions, and 1453 unique metabolites. We demonstrate a three-part validation of the model that breaks new ground in breadth and accuracy: (i) Comparison of simulated growth in aerobic and anaerobic glucose culture with experimental results from chemostat culture and simulation results from the E. coli modeling literature. (ii) Essentiality prediction for the 1445 genes represented in the model, in which EcoCyc–18.0–GEM achieves an improved accuracy of 95.2% in predicting the growth phenotype of experimental gene knockouts. (iii) Nutrient utilization predictions under 431 different media conditions, for which the model achieves an overall accuracy of 80.7%. The model’s derivation from EcoCyc enables query and visualization via the EcoCyc website, facilitating model reuse and validation by inspection. We present an extensive investigation of disagreements between EcoCyc–18.0–GEM predictions and experimental data to highlight areas of interest to E. coli modelers and experimentalists, including 70 incorrect predictions of gene essentiality on glucose, 80 incorrect predictions of gene essentiality on glycerol, and 83 incorrect predictions of nutrient utilization. Conclusion Significant advantages can be derived from the combination of model organism databases and flux balance modeling represented by MetaFlux. Interpretation of the EcoCyc database as a flux balance model results in a highly accurate metabolic model and provides a rigorous consistency check for information stored in the database. PMID:24974895

A Liver-centric Multiscale Modeling Framework for Xenobiotics ...

EPA Pesticide Factsheets

We describe a multi-scale framework for modeling acetaminophen-induced liver toxicity. Acetaminophen is a widely used analgesic. Overdose of acetaminophen can result in liver injury via its biotransformation into toxic product, which further induce massive necrosis. Our study focuses on developing a multi-scale computational model to characterize both phase I and phase II metabolism of acetaminophen, by bridging Physiologically Based Pharmacokinetic (PBPK) modeling at the whole body level, cell movement and blood flow at the tissue level and cell signaling and drug metabolism at the sub-cellular level. To validate the model, we estimated our model parameters by fi?tting serum concentrations of acetaminophen and its glucuronide and sulfate metabolites to experiments, and carried out sensitivity analysis on 35 parameters selected from three modules. Our study focuses on developing a multi-scale computational model to characterize both phase I and phase II metabolism of acetaminophen, by bridging Physiologically Based Pharmacokinetic (PBPK) modeling at the whole body level, cell movement and blood flow at the tissue level and cell signaling and drug metabolism at the sub-cellular level. This multiscale model bridges the CompuCell3D tool used by the Virtual Tissue project with the httk tool developed by the Rapid Exposure and Dosimetry project.

Transcriptomics-based strain optimization tool for designing secondary metabolite overproducing strains of Streptomyces coelicolor.

PubMed

Kim, Minsuk; Yi, Jeong Sang; Lakshmanan, Meiyappan; Lee, Dong-Yup; Kim, Byung-Gee

2016-03-01

In silico model-driven analysis using genome-scale model of metabolism (GEM) has been recognized as a promising method for microbial strain improvement. However, most of the current GEM-based strain design algorithms based on flux balance analysis (FBA) heavily rely on the steady-state and optimality assumptions without considering any regulatory information. Thus, their practical usage is quite limited, especially in its application to secondary metabolites overproduction. In this study, we developed a transcriptomics-based strain optimization tool (tSOT) in order to overcome such limitations by integrating transcriptomic data into GEM. Initially, we evaluated existing algorithms for integrating transcriptomic data into GEM using Streptomyces coelicolor dataset, and identified iMAT algorithm as the only and the best algorithm for characterizing the secondary metabolism of S. coelicolor. Subsequently, we developed tSOT platform where iMAT is adopted to predict the reaction states, and successfully demonstrated its applicability to secondary metabolites overproduction by designing actinorhodin (ACT), a polyketide antibiotic, overproducing strain of S. coelicolor. Mutants overexpressing tSOT targets such as ribulose 5-phosphate 3-epimerase and NADP-dependent malic enzyme showed 2 and 1.8-fold increase in ACT production, thereby validating the tSOT prediction. It is expected that tSOT can be used for solving other metabolic engineering problems which could not be addressed by current strain design algorithms, especially for the secondary metabolite overproductions. © 2015 Wiley Periodicals, Inc.

Performance verification of the Gravity and Extreme Magnetism Small explorer (GEMS) x-ray polarimeter

NASA Astrophysics Data System (ADS)

Enoto, Teruaki; Black, J. Kevin; Kitaguchi, Takao; Hayato, Asami; Hill, Joanne E.; Jahoda, Keith; Tamagawa, Toru; Kaneko, Kenta; Takeuchi, Yoko; Yoshikawa, Akifumi; Marlowe, Hannah; Griffiths, Scott; Kaaret, Philip E.; Kenward, David; Khalid, Syed

2014-07-01

Polarimetry is a powerful tool for astrophysical observations that has yet to be exploited in the X-ray band. For satellite-borne and sounding rocket experiments, we have developed a photoelectric gas polarimeter to measure X-ray polarization in the 2-10 keV range utilizing a time projection chamber (TPC) and advanced micro-pattern gas electron multiplier (GEM) techniques. We carried out performance verification of a flight equivalent unit (1/4 model) which was planned to be launched on the NASA Gravity and Extreme Magnetism Small Explorer (GEMS) satellite. The test was performed at Brookhaven National Laboratory, National Synchrotron Light Source (NSLS) facility in April 2013. The polarimeter was irradiated with linearly-polarized monochromatic X-rays between 2.3 and 10.0 keV and scanned with a collimated beam at 5 different detector positions. After a systematic investigation of the detector response, a modulation factor >=35% above 4 keV was obtained with the expected polarization angle. At energies below 4 keV where the photoelectron track becomes short, diffusion in the region between the GEM and readout strips leaves an asymmetric photoelectron image. A correction method retrieves an expected modulation angle, and the expected modulation factor, ~20% at 2.7 keV. Folding the measured values of modulation through an instrument model gives sensitivity, parameterized by minimum detectable polarization (MDP), nearly identical to that assumed at the preliminary design review (PDR).

Multiscale Modeling of PEEK Using Reactive Molecular Dynamics Modeling and Micromechanics

NASA Technical Reports Server (NTRS)

Pisani, William A.; Radue, Matthew; Chinkanjanarot, Sorayot; Bednarcyk, Brett A.; Pineda, Evan J.; King, Julia A.; Odegard, Gregory M.

2018-01-01

Polyether ether ketone (PEEK) is a high-performance, semi-crystalline thermoplastic that is used in a wide range of engineering applications, including some structural components of aircraft. The design of new PEEK-based materials requires a precise understanding of the multiscale structure and behavior of semi-crystalline PEEK. Molecular Dynamics (MD) modeling can efficiently predict bulk-level properties of single phase polymers, and micromechanics can be used to homogenize those phases based on the overall polymer microstructure. In this study, MD modeling was used to predict the mechanical properties of the amorphous and crystalline phases of PEEK. The hierarchical microstructure of PEEK, which combines the aforementioned phases, was modeled using a multiscale modeling approach facilitated by NASA's MSGMC. The bulk mechanical properties of semi-crystalline PEEK predicted using MD modeling and MSGMC agree well with vendor data, thus validating the multiscale modeling approach.

Does GEM-encoding clinical practice guidelines improve the quality of knowledge bases? A study with the rule-based formalism.

PubMed

Georg, Georg; Séroussi, Brigitte; Bouaud, Jacques

2003-01-01

The aim of this work was to determine whether the GEM-encoding step could improve the representation of clinical practice guidelines as formalized knowledge bases. We used the 1999 Canadian recommendations for the management of hypertension, chosen as the knowledge source in the ASTI project. We first clarified semantic ambiguities of therapeutic sequences recommended in the guideline by proposing an interpretative framework of therapeutic strategies. Then, after a formalization step to standardize the terms used to characterize clinical situations, we created the GEM-encoded instance of the guideline. We developed a module for the automatic derivation of a rule base, BR-GEM, from the instance. BR-GEM was then compared to the rule base, BR-ASTI, embedded within the critic mode of ASTI, and manually built by two physicians from the same Canadian guideline. As compared to BR-ASTI, BR-GEM is more specific and covers more clinical situations. When evaluated on 10 patient cases, the GEM-based approach led to promising results.

gem-Difluoroolefination of diaryl ketones and enolizable aldehydes with difluoromethyl 2-pyridyl sulfone: new insights into the Julia-Kocienski reaction.

PubMed

Gao, Bing; Zhao, Yanchuan; Hu, Mingyou; Ni, Chuanfa; Hu, Jinbo

2014-06-16

The direct conversion of diaryl ketones and enolizable aliphatic aldehydes into gem-difluoroalkenes has been a long-standing challenge in organofluorine chemistry. Herein, we report efficient strategies to tackle this problem by using difluoromethyl 2-pyridyl sulfone as a general gem-difluoroolefination reagent. The gem-difluoroolefination of diaryl ketones proceeds by acid-promoted Smiles rearrangement of the carbinol intermediate; the gem-difluoroolefination is otherwise difficult to achieve through a conventional Julia-Kocienski olefination protocol under basic conditions due to the retro-aldol type decomposition of the key intermediate. Efficient gem-difluoroolefination of aliphatic aldehydes was achieved by the use of an amide base generated in situ (from CsF and tris(trimethylsilyl)amine), which diminishes the undesired enolization of aliphatic aldehydes and provides a powerful synthetic method for chemoselective gem-difluoroolefination of multi-carbonyl compounds. Our results provide new insights into the mechanistic understanding of the classical Julia-Kocienski reaction. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Improving care coordination for community-dwelling older Australians: a longitudinal qualitative study.

PubMed

Harvey, Desley; Foster, Michele; Strivens, Edward; Quigley, Rachel

2017-05-01

Objective The aim of the present study was to describe the care transition experiences of older people who transfer between subacute and primary care, and to identify factors that influence these experiences. A further aim of the study was to identify ways to enhance the Geriatric Evaluation and Management (GEM) model of care and improve local coordination of services for older people. Methods The present study was an exploratory, longitudinal case study involving repeat interviews with 19 patients and carers, patient chart audits and three focus groups with service providers. Interview transcripts were coded and synthesised to identify recurring themes. Results Patients and carers experienced care transitions as dislocating and unpredictable within a complex and turbulent service context. The experience was characterised by precarious self-management in the community, floundering with unmet needs and holistic care within the GEM service. Patient and carer attitudes to seeking help, quality and timeliness of communication and information exchange, and system pressure affected care transition experiences. Conclusion Further policy and practice attention, including embedding early intervention and prevention, strengthening links between levels of care by building on existing programs and educative and self-help initiatives for patients and carers is recommended to improve care transition experiences and optimise the impact of the GEM model of care. What is known about the topic? Older people with complex care needs experience frequent care transitions because of fluctuating health and fragmentation of aged care services in Australia. The GEM model of care promotes multidisciplinary, coordinated care to improve care transitions and outcomes for older people with complex care needs. What does this paper add? The present study highlights the crucial role of the GEM service, but found there is a lack of systemised linkages within and across levels of care that disrupts coordinated care and affects care transition experiences. There are underutilised opportunities for early intervention and prevention across the system, including the emergency department and general practice. What are the implications for practitioners? Comprehensive screening, assessment and intervention in primary and acute care, formalised transition processes and enhanced support for patients and carers to access timely, appropriate care is required to achieve quality, coordinated care transitions for older people.

Integrated multiscale biomaterials experiment and modelling: a perspective

PubMed Central

Buehler, Markus J.; Genin, Guy M.

2016-01-01

Advances in multiscale models and computational power have enabled a broad toolset to predict how molecules, cells, tissues and organs behave and develop. A key theme in biological systems is the emergence of macroscale behaviour from collective behaviours across a range of length and timescales, and a key element of these models is therefore hierarchical simulation. However, this predictive capacity has far outstripped our ability to validate predictions experimentally, particularly when multiple hierarchical levels are involved. The state of the art represents careful integration of multiscale experiment and modelling, and yields not only validation, but also insights into deformation and relaxation mechanisms across scales. We present here a sampling of key results that highlight both challenges and opportunities for integrated multiscale experiment and modelling in biological systems. PMID:28981126

Outcomes after helicopter versus ground emergency medical services for major trauma--propensity score and instrumental variable analyses: a retrospective nationwide cohort study.

PubMed

Tsuchiya, Asuka; Tsutsumi, Yusuke; Yasunaga, Hideo

2016-11-29

Because of a lack of randomized controlled trials and the methodological weakness of currently available observational studies, the benefits of helicopter emergency medical services (HEMS) over ground emergency medical services (GEMS) for major trauma patients remain uncertain. The aim of this retrospective nationwide cohort study was to compare the mortality of adults with serious traumatic injuries who were transported by HEMS and GEMS, and to analyze the effects of HEMS in various subpopulations. Using the Japan Trauma Data Bank, we evaluated all adult patients who had an injury severity score ≥ 16 transported by HEMS or GEMS during the daytime between 2004 and 2014. We compared in-hospital mortality between patients transported by HEMS and GEMS using propensity score matching, inverse probability of treatment weighting and instrumental variable analyses to adjust for measured and unmeasured confounding factors. Eligible patients (n = 21,286) from 192 hospitals included 4128 transported by HEMS and 17,158 transported by GEMS. In the propensity score-matched model, there was a significant difference in the in-hospital mortality between HEMS and GEMS groups (22.2 vs. 24.5%, risk difference -2.3% [95% confidence interval, -4.2 to -0.5]; number needed to treat, 43 [95% confidence interval, 24 to 220]). The inverse probability of treatment weighting (20.8% vs. 23.9%; risk difference, -3.9% [95% confidence interval, -5.7 to -2.1]; number needed to treat, 26 [95% confidence interval, 17 to 48]) and instrumental variable analyses showed similar results (risk difference, -6.5% [95% confidence interval, -9.2 to -3.8]; number needed to treat, 15 [95% confidence interval, 11 to 27]). HEMS transport was significantly associated with lower in-hospital mortality after falls, compression injuries, severe chest injuries, extremity (including pelvic) injuries, and traumatic arrest on arrival to the emergency department. HEMS was associated with a significantly lower mortality than GEMS in adult patients with major traumatic injuries after adjusting for measured and unmeasured confounders.

PLC-controlled cryostats for the BlackGEM and MeerLICHT detectors

NASA Astrophysics Data System (ADS)

Raskin, Gert; Morren, Johan; Pessemier, Wim; Bloemen, Steven; Klein-Wolt, Marc; Roelfsema, Ronald; Groot, Paul; Aerts, Conny

2016-08-01

BlackGEM is an array of telescopes, currently under development at the Radboud University Nijmegen and at NOVA (Netherlands Research School for Astronomy). It targets the detection of the optical counterparts of gravitational waves. The first three BlackGEM telescopes are planned to be installed in 2018 at the La Silla observatory (Chile). A single prototype telescope, named MeerLICHT, will already be commissioned early 2017 in Sutherland (South Africa) to provide an optical complement for the MeerKAT radio array. The BlackGEM array consists of, initially, a set of three robotic 65-cm wide-field telescopes. Each telescope is equipped with a single STA1600 CCD detector with 10.5k x 10.5k 9-micron pixels that covers a 2.7 square degrees field of view. The cryostats for housing these detectors are developed and built at the KU Leuven University (Belgium). The operational model of BlackGEM requires long periods of reliable hands-off operation. Therefore, we designed the cryostats for long vacuum hold time and we make use of a closed-cycle cooling system, based on Polycold PCC Joule-Thomson coolers. A single programmable logic controller (PLC) controls the cryogenic systems of several BlackGEM telescopes simultaneously, resulting in a highly reliable, cost-efficient and maintenance-friendly system. PLC-based cryostat control offers some distinct advantages, especially for a robotic facility. Apart of temperature monitoring and control, the PLC also monitors the vacuum quality, the power supply and the status of the PCC coolers (compressor power consumption and temperature, pressure in the gas lines, etc.). Furthermore, it provides an alarming system and safe and reproducible procedures for automatic cool down and warm up. The communication between PLC and higher-level software takes place via the OPC-UA protocol, offering a simple to implement, yet very powerful interface. Finally, a touch-panel display on the PLC provides the operator with a user-friendly and robust technical interface. In this contribution, we present the design of the BlackGEM cryostats and of the PLC-based control system.

Nonlocal and Mixed-Locality Multiscale Finite Element Methods

DOE PAGES

Costa, Timothy B.; Bond, Stephen D.; Littlewood, David J.

2018-03-27

In many applications the resolution of small-scale heterogeneities remains a significant hurdle to robust and reliable predictive simulations. In particular, while material variability at the mesoscale plays a fundamental role in processes such as material failure, the resolution required to capture mechanisms at this scale is often computationally intractable. Multiscale methods aim to overcome this difficulty through judicious choice of a subscale problem and a robust manner of passing information between scales. One promising approach is the multiscale finite element method, which increases the fidelity of macroscale simulations by solving lower-scale problems that produce enriched multiscale basis functions. Here, inmore » this study, we present the first work toward application of the multiscale finite element method to the nonlocal peridynamic theory of solid mechanics. This is achieved within the context of a discontinuous Galerkin framework that facilitates the description of material discontinuities and does not assume the existence of spatial derivatives. Analysis of the resulting nonlocal multiscale finite element method is achieved using the ambulant Galerkin method, developed here with sufficient generality to allow for application to multiscale finite element methods for both local and nonlocal models that satisfy minimal assumptions. Finally, we conclude with preliminary results on a mixed-locality multiscale finite element method in which a nonlocal model is applied at the fine scale and a local model at the coarse scale.« less

Nonlocal and Mixed-Locality Multiscale Finite Element Methods

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

Costa, Timothy B.; Bond, Stephen D.; Littlewood, David J.

In many applications the resolution of small-scale heterogeneities remains a significant hurdle to robust and reliable predictive simulations. In particular, while material variability at the mesoscale plays a fundamental role in processes such as material failure, the resolution required to capture mechanisms at this scale is often computationally intractable. Multiscale methods aim to overcome this difficulty through judicious choice of a subscale problem and a robust manner of passing information between scales. One promising approach is the multiscale finite element method, which increases the fidelity of macroscale simulations by solving lower-scale problems that produce enriched multiscale basis functions. Here, inmore » this study, we present the first work toward application of the multiscale finite element method to the nonlocal peridynamic theory of solid mechanics. This is achieved within the context of a discontinuous Galerkin framework that facilitates the description of material discontinuities and does not assume the existence of spatial derivatives. Analysis of the resulting nonlocal multiscale finite element method is achieved using the ambulant Galerkin method, developed here with sufficient generality to allow for application to multiscale finite element methods for both local and nonlocal models that satisfy minimal assumptions. Finally, we conclude with preliminary results on a mixed-locality multiscale finite element method in which a nonlocal model is applied at the fine scale and a local model at the coarse scale.« less

Current understanding of the driving mechanisms for spatiotemporal variations of atmospheric speciated mercury: a review

NASA Astrophysics Data System (ADS)

Mao, Huiting; Cheng, Irene; Zhang, Leiming

2016-10-01

Atmospheric mercury (Hg) is a global pollutant and thought to be the main source of mercury in oceanic and remote terrestrial systems, where it becomes methylated and bioavailable; hence, atmospheric mercury pollution has global consequences for both human and ecosystem health. Understanding of spatial and temporal variations of atmospheric speciated mercury can advance our knowledge of mercury cycling in various environments. This review summarized spatiotemporal variations of total gaseous mercury or gaseous elemental mercury (TGM/GEM), gaseous oxidized mercury (GOM), and particulate-bound mercury (PBM) in various environments including oceans, continents, high elevation, the free troposphere, and low to high latitudes. In the marine boundary layer (MBL), the oxidation of GEM was generally thought to drive the diurnal and seasonal variations of TGM/GEM and GOM in most oceanic regions, leading to lower GEM and higher GOM from noon to afternoon and higher GEM during winter and higher GOM during spring-summer. At continental sites, the driving mechanisms of TGM/GEM diurnal patterns included surface and local emissions, boundary layer dynamics, GEM oxidation, and for high-elevation sites mountain-valley winds, while oxidation of GEM and entrainment of free tropospheric air appeared to control the diurnal patterns of GOM. No pronounced diurnal variation was found for Tekran measured PBM at MBL and continental sites. Seasonal variations in TGM/GEM at continental sites were attributed to increased winter combustion and summertime surface emissions, and monsoons in Asia, while those in GOM were controlled by GEM oxidation, free tropospheric transport, anthropogenic emissions, and wet deposition. Increased PBM at continental sites during winter was primarily due to local/regional coal and wood combustion emissions. Long-term TGM measurements from the MBL and continental sites indicated an overall declining trend. Limited measurements suggested TGM/GEM increasing from the Southern Hemisphere (SH) to the Northern Hemisphere (NH) due largely to the vast majority of mercury emissions in the NH, and the latitudinal gradient was insignificant in summer probably as a result of stronger meridional mixing. Aircraft measurements showed no significant vertical variation in GEM over the field campaign regions; however, depletion of GEM was observed in stratospherically influenced air masses. In examining the remaining questions and issues, recommendations for future research needs were provided, and among them is the most imminent need for GOM speciation measurements and fundamental understanding of multiphase redox kinetics.

Immunogenicity and immunoprotection of porcine circovirus type 2 (PCV2) Cap protein displayed by Lactococcus lactis.

PubMed

Li, Peng-Cheng; Qiao, Xu-Wen; Zheng, Qi-Sheng; Hou, Ji-Bo

2016-01-27

The capsid (Cap) protein, an important immunoprotective protein of porcine circovirus type 2 (PCV2), was expressed on the cell surface of the Gram-positive food-grade bacterium, Lactococcus lactis. Cap protein was fused to the peptidoglycan binding domain (known as the protein anchor domain, PA) of the lactococcal AcmA cell-wall hydrolase. The Cap protein fusion was non-covalently rebound to the surface of non-genetically modified, non-living high-binder L. lactis cells (designated Gram-positive enhancer matrix (GEM) particles). Expression of the recombinant GEM-displaying capsid protein (GEM-PA-Cap) was verified by Western blotting and immunofluorescence and transmission electron microscopy assays. To evaluate the immunogenicity of the recombinant Cap protein (rCap), 20 PCV2-seronegative piglets were immunized with the GEM-PA-Cap subunit vaccine, GEM alone, or phosphate-buffered saline (PBS, challenge control and empty control). Each group consisted of five piglets. The results showed that the level of PCV2-specific antibodies in piglets immunized with the GEM-PA-Cap subunit vaccine was significantly higher than that of the piglets immunized with GEM alone or the control group at all the time points post-vaccination (P<0.01). After challenge with the PCV2 wild-type strain, piglets that received the GEM-PA-Cap subunit vaccine showed significantly higher average daily weight gain (DWG) and shorter fever duration than the other two groups (P<0.001). Furthermore, a significant reduction in the gross lung lesion scores and lymph node lesion scores was noted in the GEM-PA-Cap-immunized group compared with the scores of the GEM or PBS-treated group (P<0.01). The results suggest that recombinant rCap displayed by L. lactis GEM particles provided the piglets with significant immunoprotection from PCV2-associated disease. Thus, the novel GEM-PA-Cap subunit vaccine has potential to be considered an effective and safe candidate vaccine against PCV2 infection in piglets. Copyright © 2015. Published by Elsevier Ltd.

Emissions of mercury in Southern Africa derived from long-term observations at Cape Point, South Africa

NASA Astrophysics Data System (ADS)

Brunke, E.-G.; Ebinghaus, R.; Kock, H. H.; Labuschagne, C.; Slemr, F.

2012-05-01

Mercury emissions in South Africa have so far been estimated only by a bottom-up approach from activities and emission factors for different processes. In this paper we derive GEM/CO (GEM being gaseous elemental mercury, Hg0), GEM/CO2, GEM/CH4, CO/CO2, CH4/CO2, and CH4/CO emission ratios from plumes observed during long-term monitoring of these species at Cape Point between March 2007 and December 2009. The average observed GEM/CO, GEM/CO2, GEM/CH4, CO/CO2, CH4/CO2, and CH4/CO emission ratios were 2.40 ± 2.65 pg m-3 ppb-1 (n = 47), 62.7 ± 80.2 pg m-3 ppb-1 (n = 44), 3.61 ± 4.66 pg m-3 ppb-1 (n = 46), 35.6 ± 25.4 ppb ppm-1 (n = 52), 20.2 ± 15.5 ppb ppm-1 (n=48), and 0.876 ± 1.106 ppb ppm-1 (n=42), respectively. The observed CO/CO2, CH4/CO2, and CH4/CO emission ratios agree within the combined uncertainties of the observations and emissions with the ratios calculated from EDGAR (version 4.2) CO2, CO, and CH4 inventories for South Africa and Southern Africa (South Africa, Lesotho, Swaziland, Namibia, Botswana, Zimbabwe, and Mozambique) in 2007 and 2008 (inventories for 2009 are not available yet). Total elemental mercury emission of 13.1, 15.2, and 16.1 t Hg yr-1 are estimated independently using the GEM/CO, GEM/CO2, and GEM/CH4 emission ratios and the annual mean CO, CO2, and CH4 emissions, respectively, of South Africa in 2007 and 2008. The average of these independent estimates of 14.8 ± 1.5 t GEM yr-1 is much less than the total emission of 257 t Hg yr-1 from older inventories. Considering that emission of GEM represents only 50-78% of all mercury emissions, our estimates come close to the total mercury emission estimates ranging between 40-50 t Hg yr-1 from more recent inventories.

Extending the ISC-GEM Global Earthquake Instrumental Catalogue

NASA Astrophysics Data System (ADS)

Di Giacomo, Domenico; Engdhal, Bob; Storchak, Dmitry; Villaseñor, Antonio; Harris, James

2015-04-01

After a 27-month project funded by the GEM Foundation (www.globalquakemodel.org), in January 2013 we released the ISC-GEM Global Instrumental Earthquake Catalogue (1900 2009) (www.isc.ac.uk/iscgem/index.php) as a special product to use for seismic hazard studies. The new catalogue was necessary as improved seismic hazard studies necessitate that earthquake catalogues are homogeneous (to the largest extent possible) over time in their fundamental parameters, such as location and magnitude. Due to time and resource limitation, the ISC-GEM catalogue (1900-2009) included earthquakes selected according to the following time-variable cut-off magnitudes: Ms=7.5 for earthquakes occurring before 1918; Ms=6.25 between 1918 and 1963; and Ms=5.5 from 1964 onwards. Because of the importance of having a reliable seismic input for seismic hazard studies, funding from GEM and two commercial companies in the US and UK allowed us to start working on the extension of the ISC-GEM catalogue both for earthquakes that occurred beyond 2009 and for earthquakes listed in the International Seismological Summary (ISS) which fell below the cut-off magnitude of 6.25. This extension is part of a four-year program that aims at including in the ISC-GEM catalogue large global earthquakes that occurred before the beginning of the ISC Bulletin in 1964. In this contribution we present the updated ISC GEM catalogue, which will include over 1000 more earthquakes that occurred in 2010 2011 and several hundreds more between 1950 and 1959. The catalogue extension between 1935 and 1949 is currently underway. The extension of the ISC-GEM catalogue will also be helpful for regional cross border seismic hazard studies as the ISC-GEM catalogue should be used as basis for cross-checking the consistency in location and magnitude of those earthquakes listed both in the ISC GEM global catalogue and regional catalogues.

Temporal distribution and potential sources of atmospheric mercury measured at a high-elevation background station in Taiwan

NASA Astrophysics Data System (ADS)

Sheu, Guey-Rong; Lin, Neng-Huei; Wang, Jia-Lin; Lee, Chung-Te; Ou Yang, Chang-Feng; Wang, Sheng-Hsiang

2010-07-01

Measurements of gaseous elemental mercury (GEM), reactive gaseous mercury (RGM), and particulate mercury (PHg) have been conducted at Lulin Atmospheric Background Station (LABS) in Taiwan since April 2006. This was the first long-term free tropospheric atmospheric Hg monitoring program in the downwind region of East Asia, which is a major Hg emission source region. Between April 13, 2006 and December 31, 2007, the mean concentrations of GEM, RGM, and PHg were 1.73 ng m -3, 12.1 pg m -3, and 2.3 pg m -3, respectively. A diurnal pattern was observed for GEM with afternoon peaks and nighttime lows, whereas the diurnal pattern of RGM was opposite to that of GEM. Spikes of RGM were frequently observed between midnight and early morning with concurrent decreases in GEM and relative humidity and increases in O 3, suggesting the oxidation of GEM and formation of RGM in free troposphere (FT). Upslope movement of boundary layer (BL) air in daytime and subsidence of FT air at night resulted in these diurnal patterns. Considering only the nighttime data, which were more representative of FT air, the composite monthly mean GEM concentrations ranged between 1.06 and 2.06 ng m -3. Seasonal variation in nighttime GEM was evident, with lower concentrations usually occurring in summer when clean marine air masses prevailed. Between fall and spring, air masses passed the East Asian continent prior to reaching LABS, contributing to the elevated GEM concentrations. Analysis of GEM/CO correlation tends to support the argument. Good GEM/CO correlations were observed in fall, winter, and spring, suggesting influence of anthropogenic emission sources. Our results demonstrate the significance of East Asian Hg emissions, including both anthropogenic and biomass burning emissions, and their long-range transport in the FT. Because of the pronounced seasonal monsoon activity and the seasonal variation in regional wind field, export of the Asian Hg emissions to Taiwan occurs mainly during fall, winter, and spring.

Impaired clinical utility of sequential patient GEM blood gas measurements associated with calibration schedule.

PubMed

Cembrowski, George S; Xu, Qian; Cembrowski, Adam R; Mei, Junyi; Sadrzadeh, Hossein

2017-11-01

Within- and/or between-instrument variation may falsely indicate patient trends or obscure real trends. We employ a methodology that transforms sequential intra-patient results into estimates of biologic and analytic variation. We previously derived realistic biologic variation (s b ) of blood gas (BG) and hematology analytes. We extend this methodology to derive the imprecision of two GEM 4000 BG analyzers. A laboratory data repository provided arterial BG, electrolyte and metabolite results generated by two GEM 4000s on ICU patients in 2012-2013. We tabulated consecutive pairs of intra-patient results separated by increasing time interval between consecutive tests. The average between pair variations were regressed against time with the y-intercept representing the sum of the biologic variation and short term analytic variation: y o 2 =s b 2 +s a 2 . Using an equivalent equation for the Radiometer ABL, the imprecision of the two GEMs was calculated: s aGEM =(y oGEM 2 -y oABL 2 +s aABL 2 ) 1/2 . This analysis was performed for nearly all measurements, regardless of time as well for values obtained over two 12h mutually exclusive periods, starting either at 2am or 2pm. Regression graphs were derived from 1800 patients' blood gas results with least 10,000 data pairs grouped into 2h intervals. The calculated s aGEM exceed the directly measured s aABL with many GEM sigma ratios of biologic variation/analytic variation being close to unity. All of the afternoon s aGEM exceeded their morning counterparts with pH, pCO 2 , K and bicarbonate being statistically significant. For many analytes, the average analytical variation of tandem GEMs approximates the biologic variation, indicating impaired clinical usefulness of tandem sequential measurements. A significant component of this variation is due to increased variation of the GEMs between 2pm and 2am. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Photodegradation of gemfibrozil in aqueous solution under UV irradiation: kinetics, mechanism, toxicity, and degradation pathways.

PubMed

Ma, Jingshuai; Lv, Wenying; Chen, Ping; Lu, Yida; Wang, Fengliang; Li, Fuhua; Yao, Kun; Liu, Guoguang

2016-07-01

The lipid regulator gemfibrozil (GEM) has been reported to be persistent in conventional wastewater treatment plants. This study investigated the photolytic behavior, toxicity of intermediate products, and degradation pathways of GEM in aqueous solutions under UV irradiation. The results demonstrated that the photodegradation of GEM followed pseudo-first-order kinetics, and the pseudo-first-order rate constant was decreased markedly with increasing initial concentrations of GEM and initial pH. The photodegradation of GEM included direct photolysis via (3)GEM(*) and self-sensitization via ROS, where the contribution rates of degradation were 0.52, 90.05, and 8.38 % for ·OH, (1)O2, and (3)GEM(*), respectively. Singlet oxygen ((1)O2) was evidenced by the molecular probe compound, furfuryl alcohol (FFA), and was identified as the primary reactive species in the photolytic process. The steady-state concentrations of (1)O2 increased from (0.324 ± 0.014) × 10(-12) to (1.021 ± 0.040) × 10(-12) mol L(-1), as the initial concentrations of GEM were increased from 5 to 20 mg L(-1). The second-order rate constant for the reaction of GEM with (1)O2 was calculated to be 2.55 × 10(6) M(-1) s(-1). The primary transformation products were identified using HPLC-MS/MS, and possible photodegradation pathways were proposed by hydroxylation, aldehydes reactions, as well as the cleavage of ether side chains. The toxicity of phototransformation product evaluation revealed that photolysis potentially provides a critical pathway for GEM toxicity reduction in potable water and wastewater treatment facilities.

Community effort endorsing multiscale modelling, multiscale data science and multiscale computing for systems medicine.

PubMed

Zanin, Massimiliano; Chorbev, Ivan; Stres, Blaz; Stalidzans, Egils; Vera, Julio; Tieri, Paolo; Castiglione, Filippo; Groen, Derek; Zheng, Huiru; Baumbach, Jan; Schmid, Johannes A; Basilio, José; Klimek, Peter; Debeljak, Nataša; Rozman, Damjana; Schmidt, Harald H H W

2017-12-05

Systems medicine holds many promises, but has so far provided only a limited number of proofs of principle. To address this road block, possible barriers and challenges of translating systems medicine into clinical practice need to be identified and addressed. The members of the European Cooperation in Science and Technology (COST) Action CA15120 Open Multiscale Systems Medicine (OpenMultiMed) wish to engage the scientific community of systems medicine and multiscale modelling, data science and computing, to provide their feedback in a structured manner. This will result in follow-up white papers and open access resources to accelerate the clinical translation of systems medicine. © The Author 2017. Published by Oxford University Press.

Multi-element least square HDMR methods and their applications for stochastic multiscale model reduction

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

Jiang, Lijian, E-mail: ljjiang@hnu.edu.cn; Li, Xinping, E-mail: exping@126.com

Stochastic multiscale modeling has become a necessary approach to quantify uncertainty and characterize multiscale phenomena for many practical problems such as flows in stochastic porous media. The numerical treatment of the stochastic multiscale models can be very challengeable as the existence of complex uncertainty and multiple physical scales in the models. To efficiently take care of the difficulty, we construct a computational reduced model. To this end, we propose a multi-element least square high-dimensional model representation (HDMR) method, through which the random domain is adaptively decomposed into a few subdomains, and a local least square HDMR is constructed in eachmore » subdomain. These local HDMRs are represented by a finite number of orthogonal basis functions defined in low-dimensional random spaces. The coefficients in the local HDMRs are determined using least square methods. We paste all the local HDMR approximations together to form a global HDMR approximation. To further reduce computational cost, we present a multi-element reduced least-square HDMR, which improves both efficiency and approximation accuracy in certain conditions. To effectively treat heterogeneity properties and multiscale features in the models, we integrate multiscale finite element methods with multi-element least-square HDMR for stochastic multiscale model reduction. This approach significantly reduces the original model's complexity in both the resolution of the physical space and the high-dimensional stochastic space. We analyze the proposed approach, and provide a set of numerical experiments to demonstrate the performance of the presented model reduction techniques. - Highlights: • Multi-element least square HDMR is proposed to treat stochastic models. • Random domain is adaptively decomposed into some subdomains to obtain adaptive multi-element HDMR. • Least-square reduced HDMR is proposed to enhance computation efficiency and approximation accuracy in certain conditions. • Integrating MsFEM and multi-element least square HDMR can significantly reduce computation complexity.« less

Identity in agent-based models : modeling dynamic multiscale social processes.

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

Ozik, J.; Sallach, D. L.; Macal, C. M.

Identity-related issues play central roles in many current events, including those involving factional politics, sectarianism, and tribal conflicts. Two popular models from the computational-social-science (CSS) literature - the Threat Anticipation Program and SharedID models - incorporate notions of identity (individual and collective) and processes of identity formation. A multiscale conceptual framework that extends some ideas presented in these models and draws other capabilities from the broader CSS literature is useful in modeling the formation of political identities. The dynamic, multiscale processes that constitute and transform social identities can be mapped to expressive structures of the framework

Performance of hybrid programming models for multiscale cardiac simulations: preparing for petascale computation.

PubMed

Pope, Bernard J; Fitch, Blake G; Pitman, Michael C; Rice, John J; Reumann, Matthias

2011-10-01

Future multiscale and multiphysics models that support research into human disease, translational medical science, and treatment can utilize the power of high-performance computing (HPC) systems. We anticipate that computationally efficient multiscale models will require the use of sophisticated hybrid programming models, mixing distributed message-passing processes [e.g., the message-passing interface (MPI)] with multithreading (e.g., OpenMP, Pthreads). The objective of this study is to compare the performance of such hybrid programming models when applied to the simulation of a realistic physiological multiscale model of the heart. Our results show that the hybrid models perform favorably when compared to an implementation using only the MPI and, furthermore, that OpenMP in combination with the MPI provides a satisfactory compromise between performance and code complexity. Having the ability to use threads within MPI processes enables the sophisticated use of all processor cores for both computation and communication phases. Considering that HPC systems in 2012 will have two orders of magnitude more cores than what was used in this study, we believe that faster than real-time multiscale cardiac simulations can be achieved on these systems.

Multi-scale signed envelope inversion

NASA Astrophysics Data System (ADS)

Chen, Guo-Xin; Wu, Ru-Shan; Wang, Yu-Qing; Chen, Sheng-Chang

2018-06-01

Envelope inversion based on modulation signal mode was proposed to reconstruct large-scale structures of underground media. In order to solve the shortcomings of conventional envelope inversion, multi-scale envelope inversion was proposed using new envelope Fréchet derivative and multi-scale inversion strategy to invert strong contrast models. In multi-scale envelope inversion, amplitude demodulation was used to extract the low frequency information from envelope data. However, only to use amplitude demodulation method will cause the loss of wavefield polarity information, thus increasing the possibility of inversion to obtain multiple solutions. In this paper we proposed a new demodulation method which can contain both the amplitude and polarity information of the envelope data. Then we introduced this demodulation method into multi-scale envelope inversion, and proposed a new misfit functional: multi-scale signed envelope inversion. In the numerical tests, we applied the new inversion method to the salt layer model and SEG/EAGE 2-D Salt model using low-cut source (frequency components below 4 Hz were truncated). The results of numerical test demonstrated the effectiveness of this method.

2008 GEM Modeling Challenge: Metrics Study of the Dst Index in Physics-Based Magnetosphere and Ring Current Models and in Statistical and Analytic Specifications

NASA Technical Reports Server (NTRS)

Rastaetter, L.; Kuznetsova, M.; Hesse, M.; Pulkkinen, A.; Glocer, A.; Yu, Y.; Meng, X.; Raeder, J.; Wiltberger, M.; Welling, D.;

Genome-scale modeling of human metabolism - a systems biology approach.

PubMed

Mardinoglu, Adil; Gatto, Francesco; Nielsen, Jens

2013-09-01

Altered metabolism is linked to the appearance of various human diseases and a better understanding of disease-associated metabolic changes may lead to the identification of novel prognostic biomarkers and the development of new therapies. Genome-scale metabolic models (GEMs) have been employed for studying human metabolism in a systematic manner, as well as for understanding complex human diseases. In the past decade, such metabolic models - one of the fundamental aspects of systems biology - have started contributing to the understanding of the mechanistic relationship between genotype and phenotype. In this review, we focus on the construction of the Human Metabolic Reaction database, the generation of healthy cell type- and cancer-specific GEMs using different procedures, and the potential applications of these developments in the study of human metabolism and in the identification of metabolic changes associated with various disorders. We further examine how in silico genome-scale reconstructions can be employed to simulate metabolic flux distributions and how high-throughput omics data can be analyzed in a context-dependent fashion. Insights yielded from this mechanistic modeling approach can be used for identifying new therapeutic agents and drug targets as well as for the discovery of novel biomarkers. Finally, recent advancements in genome-scale modeling and the future challenge of developing a model of whole-body metabolism are presented. The emergent contribution of GEMs to personalized and translational medicine is also discussed. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Experimenting with the GMAO 4D Data Assimilation

NASA Technical Reports Server (NTRS)

Todling, R.; El Akkraoui, A.; Errico, R. M.; Guo, J.; Kim, J.; Kliest, D.; Parrish, D. F.; Suarez, M.; Trayanov, A.; Tremolet, Yannick;

Dst Index in the 2008 GEM Modeling Challenge - Model Performance for Moderate and Strong Magnetic Storms

NASA Technical Reports Server (NTRS)

Rastaetter, Lutz; Kuznetsova, Maria; Hesse, Michael; Chulaki, Anna; Pulkkinen, Antti; Ridley, Aaron J.; Gombosi, Tamas; Vapirev, Alexander; Raeder, Joachim; Wiltberger, Michael James;

A dynamic multi-scale Markov model based methodology for remaining life prediction

NASA Astrophysics Data System (ADS)

Yan, Jihong; Guo, Chaozhong; Wang, Xing

2011-05-01

The ability to accurately predict the remaining life of partially degraded components is crucial in prognostics. In this paper, a performance degradation index is designed using multi-feature fusion techniques to represent deterioration severities of facilities. Based on this indicator, an improved Markov model is proposed for remaining life prediction. Fuzzy C-Means (FCM) algorithm is employed to perform state division for Markov model in order to avoid the uncertainty of state division caused by the hard division approach. Considering the influence of both historical and real time data, a dynamic prediction method is introduced into Markov model by a weighted coefficient. Multi-scale theory is employed to solve the state division problem of multi-sample prediction. Consequently, a dynamic multi-scale Markov model is constructed. An experiment is designed based on a Bently-RK4 rotor testbed to validate the dynamic multi-scale Markov model, experimental results illustrate the effectiveness of the methodology.

Multi-scale Mexican spotted owl (Strix occidentalis lucida) nest/roost habitat selection in Arizona and a comparison with single-scale modeling results

Treesearch

Brad C. Timm; Kevin McGarigal; Samuel A. Cushman; Joseph L. Ganey

2016-01-01

Efficacy of future habitat selection studies will benefit by taking a multi-scale approach. In addition to potentially providing increased explanatory power and predictive capacity, multi-scale habitat models enhance our understanding of the scales at which species respond to their environment, which is critical knowledge required to implement effective...

Multiscale Modeling of Damage Processes in fcc Aluminum: From Atoms to Grains

NASA Technical Reports Server (NTRS)

Glaessgen, E. H.; Saether, E.; Yamakov, V.

2008-01-01

Molecular dynamics (MD) methods are opening new opportunities for simulating the fundamental processes of material behavior at the atomistic level. However, current analysis is limited to small domains and increasing the size of the MD domain quickly presents intractable computational demands. A preferred approach to surmount this computational limitation has been to combine continuum mechanics-based modeling procedures, such as the finite element method (FEM), with MD analyses thereby reducing the region of atomic scale refinement. Such multiscale modeling strategies can be divided into two broad classifications: concurrent multiscale methods that directly incorporate an atomistic domain within a continuum domain and sequential multiscale methods that extract an averaged response from the atomistic simulation for later use as a constitutive model in a continuum analysis.

Does GEM-Encoding Clinical Practice Guidelines Improve the Quality of Knowledge Bases? A Study with the Rule-Based Formalism

PubMed Central

Georg, Gersende; Séroussi, Brigitte; Bouaud, Jacques

2003-01-01

The aim of this work was to determine whether the GEM-encoding step could improve the representation of clinical practice guidelines as formalized knowledge bases. We used the 1999 Canadian recommendations for the management of hypertension, chosen as the knowledge source in the ASTI project. We first clarified semantic ambiguities of therapeutic sequences recommended in the guideline by proposing an interpretative framework of therapeutic strategies. Then, after a formalization step to standardize the terms used to characterize clinical situations, we created the GEM-encoded instance of the guideline. We developed a module for the automatic derivation of a rule base, BR-GEM, from the instance. BR-GEM was then compared to the rule base, BR-ASTI, embedded within the critic mode of ASTI, and manually built by two physicians from the same Canadian guideline. As compared to BR-ASTI, BR-GEM is more specific and covers more clinical situations. When evaluated on 10 patient cases, the GEM-based approach led to promising results. PMID:14728173

Data Analysis And Polarization Measurements With GEMS

NASA Technical Reports Server (NTRS)

Stohmayer, Tod

2011-01-01

The Gravity and Extreme Magnetism SMEX (GEMS) mission was selected by NASA for flight in 2014. GEMS will make the first sensitive survey of X-ray polarization across a wide range of source classes including black hole and neutron star binaries, AGN of different types, rotation and accretion-powered pulsars, magnetars, shell supernova remnants and pulsar wind nebulae. GEMS employs grazing-incidence foil mirrors and novel time-projection chamber (TPC) polarimeters leveraging the photoelectric effect. The GEMS detectors image the charge tracks of photoelectrons produced by 2 - 10 keV X-rays. The initial direction of the photoelectron is determined by the linear polarization of the photon. We present an overview of the data analysis challenges and methods for GEMS, including procedures for producing optimally filtered images of the charge tracks and estimating their initial directions. We illustrate our methods using laboratory measurements of polarized and unpolarized X-rays with flight-like detectors as well as from simulated tracks. We also present detailed simulations exploring the statistics of polarization measurements appropriate for GEMS, and make comparisons with previous work.

Microvesicle removal of anticancer drugs contributes to drug resistance in human pancreatic cancer cells

PubMed Central

Muralidharan-Chari, Vandhana; Kohan, Hamed Gilzad; Asimakopoulos, Alexandros G.; Sudha, Thangirala; Sell, Stewart; Kannan, Kurunthachalam; Boroujerdi, Mehdi; Davis, Paul J.; Mousa, Shaker A.

2016-01-01

High mortality in pancreatic cancer patients is partly due to resistance to chemotherapy. We describe that human pancreatic cancer cells acquire drug resistance by a novel mechanism in which they expel and remove chemotherapeutic drugs from the microenvironment via microvesicles (MVs). Using human pancreatic cancer cells that exhibit varied sensitivity to gemcitabine (GEM), we show that GEM exposure triggers the cancer cells to release MVs in an amount that correlates with that cell line's sensitivity to GEM. The importance of MV-release in gaining drug resistance in GEM-resistant pancreatic cancer cells was confirmed when the inhibition of MV-release sensitized the cells to GEM treatment, both in vitro and in vivo. Mechanistically, MVs remove drugs that are internalized into the cells and that are in the microenvironment. The differences between the drug-resistant and drug-sensitive pancreatic cancer cell lines tested here are explained based on the variable content of influx/efflux proteins present on MVs, which directly dictates the ability of MVs either to trap GEM or to allow GEM to flow back to the microenvironment. PMID:27391262

Integrating remotely sensed land cover observations and a biogeochemical model for estimating forest ecosystem carbon dynamics

USGS Publications Warehouse

Liu, J.; Liu, S.; Loveland, Thomas R.; Tieszen, L.L.

2008-01-01

Land cover change is one of the key driving forces for ecosystem carbon (C) dynamics. We present an approach for using sequential remotely sensed land cover observations and a biogeochemical model to estimate contemporary and future ecosystem carbon trends. We applied the General Ensemble Biogeochemical Modelling System (GEMS) for the Laurentian Plains and Hills ecoregion in the northeastern United States for the period of 1975-2025. The land cover changes, especially forest stand-replacing events, were detected on 30 randomly located 10-km by 10-km sample blocks, and were assimilated by GEMS for biogeochemical simulations. In GEMS, each unique combination of major controlling variables (including land cover change history) forms a geo-referenced simulation unit. For a forest simulation unit, a Monte Carlo process is used to determine forest type, forest age, forest biomass, and soil C, based on the Forest Inventory and Analysis (FIA) data and the U.S. General Soil Map (STATSGO) data. Ensemble simulations are performed for each simulation unit to incorporate input data uncertainty. Results show that on average forests of the Laurentian Plains and Hills ecoregion have been sequestrating 4.2 Tg C (1 teragram = 1012 gram) per year, including 1.9 Tg C removed from the ecosystem as the consequences of land cover change. ?? 2008 Elsevier B.V.

GEMS X-ray Polarimeter Performance Simulations

NASA Technical Reports Server (NTRS)

Baumgartner, Wayne H.; Strohmayer, Tod; Kallman, Tim; Black, J. Kevin; Hill, Joanne; Swank, Jean

2012-01-01

The Gravity and Extreme Magnetism Small explorer (GEMS) is an X-ray polarization telescope selected as a NASA small explorer satellite mission. The X-ray Polarimeter on GEMS uses a Time Projection Chamber gas proportional counter to measure the polarization of astrophysical X-rays in the 2-10 keV band by sensing the direction of the track of the primary photoelectron excited by the incident X-ray. We have simulated the expected sensitivity of the polarimeter to polarized X-rays. We use the simulation package Penelope to model the physics of the interaction of the initial photoelectron with the detector gas and to determine the distribution of charge deposited in the detector volume. We then model the charge diffusion in the detector,and produce simulated track images. Within the track reconstruction algorithm we apply cuts on the track shape and focus on the initial photoelectron direction in order to maximize the overall sensitivity of the instrument, using this technique we have predicted instrument modulation factors nu(sub 100) for 100% polarized X-rays ranging from 10% to over 60% across the 2-10 keV X-ray band. We also discuss the simulation program used to develop and model some of the algorithms used for triggering, and energy measurement of events in the polarimeter.

Towards the virtual artery: a multiscale model for vascular physiology at the physics-chemistry-biology interface.

PubMed

Hoekstra, Alfons G; Alowayyed, Saad; Lorenz, Eric; Melnikova, Natalia; Mountrakis, Lampros; van Rooij, Britt; Svitenkov, Andrew; Závodszky, Gábor; Zun, Pavel

2016-11-13

This discussion paper introduces the concept of the Virtual Artery as a multiscale model for arterial physiology and pathologies at the physics-chemistry-biology (PCB) interface. The cellular level is identified as the mesoscopic level, and we argue that by coupling cell-based models with other relevant models on the macro- and microscale, a versatile model of arterial health and disease can be composed. We review the necessary ingredients, both models of arteries at many different scales, as well as generic methods to compose multiscale models. Next, we discuss how this can be combined into the virtual artery. Finally, we argue that the concept of models at the PCB interface could or perhaps should become a powerful paradigm, not only as in our case for studying physiology, but also for many other systems that have such PCB interfaces.This article is part of the themed issue 'Multiscale modelling at the physics-chemistry-biology interface'. © 2016 The Authors.

ISC-GEM: Global Instrumental Earthquake Catalogue (1900-2009), II. Location and seismicity patterns

NASA Astrophysics Data System (ADS)

Bondár, I.; Engdahl, E. Robert; Villaseñor, A.; Harris, James; Storchak, D.

2015-02-01

We present the final results of a two-year project sponsored by the Global Earthquake Model (GEM) Foundation. The ISC-GEM global catalogue consists of some 19 thousand instrumentally recorded, moderate to large earthquakes, spanning 110 years of seismicity. We relocated all events in the catalogue using a two-tier approach. The EHB location methodology (Engdahl et al., 1998) was applied first to obtain improved hypocentres with special focus on the depth determination. The locations were further refined in the next step by fixing the depths to those from the EHB analysis and applying the new International Seismological Centre (ISC) location algorithm (Bondár and Storchak, 2011) that reduces location bias by accounting for correlated travel-time prediction error structure. To facilitate the relocation effort, some one million seismic P and S wave arrival-time data were added to the ISC database for the period between 1904 and 1970, either from original station bulletins in the ISC archive or by digitizing the scanned images of the International Seismological Summary (ISS) bulletin (Villaseñor and Engdahl, 2005, 2007). Although no substantial amount of new phase data were acquired for the modern period (1964-2009), the number of phases used in the location has still increased by three millions, owing to fact that both the EHB and ISC locators use most well-recorded ak135 (Kennett et al., 1995) phases in the location. We show that the relocation effort yielded substantially improved locations, especially in the first half of the 20th century; we demonstrate significant improvements in focal depth estimates in subduction zones and other seismically active regions; and we show that the ISC-GEM catalogue provides an improved view of 110 years of global seismicity of the Earth. The ISC-GEM Global Instrumental Earthquake Catalogue represents the final product of one of the ten global components in the GEM program, and is available to researchers at the ISC (http://www.isc.ac.uk).

Atmospheric mercury in the Southern Hemisphere tropics: seasonal and diurnal variations and influence of inter-hemispheric transport

NASA Astrophysics Data System (ADS)

Howard, Dean; Nelson, Peter F.; Edwards, Grant C.; Morrison, Anthony L.; Fisher, Jenny A.; Ward, Jason; Harnwell, James; van der Schoot, Marcel; Atkinson, Brad; Chambers, Scott D.; Griffiths, Alan D.; Werczynski, Sylvester; Williams, Alastair G.

2017-09-01

Mercury is a toxic element of serious concern for human and environmental health. Understanding its natural cycling in the environment is an important goal towards assessing its impacts and the effectiveness of mitigation strategies. Due to the unique chemical and physical properties of mercury, the atmosphere is the dominant transport pathway for this heavy metal, with the consequence that regions far removed from sources can be impacted. However, there exists a dearth of long-term monitoring of atmospheric mercury, particularly in the tropics and Southern Hemisphere. This paper presents the first 2 years of gaseous elemental mercury (GEM) measurements taken at the Australian Tropical Atmospheric Research Station (ATARS) in northern Australia, as part of the Global Mercury Observation System (GMOS). Annual mean GEM concentrations determined at ATARS (0.95 ± 0.12 ng m-3) are consistent with recent observations at other sites in the Southern Hemisphere. Comparison with GEM data from other Australian monitoring sites suggests a concentration gradient that decreases with increasing latitude. Seasonal analysis shows that GEM concentrations at ATARS are significantly lower in the distinct wet monsoon season than in the dry season. This result provides insight into alterations of natural mercury cycling processes as a result of changes in atmospheric humidity, oceanic/terrestrial fetch, and convective mixing, and invites future investigation using wet mercury deposition measurements. Due to its location relative to the atmospheric equator, ATARS intermittently samples air originating from the Northern Hemisphere, allowing an opportunity to gain greater understanding of inter-hemispheric transport of mercury and other atmospheric species. Diurnal cycles of GEM at ATARS show distinct nocturnal depletion events that are attributed to dry deposition under stable boundary layer conditions. These cycles provide strong further evidence supportive of a multi-hop model of GEM cycling, characterised by multiple surface depositions and re-emissions, in addition to long-range transport through the atmosphere.

Multiscale Mathematics for Biomass Conversion to Renewable Hydrogen

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

Plechac, Petr

2016-03-01

The overall objective of this project was to develop multiscale models for understanding and eventually designing complex processes for renewables. To the best of our knowledge, our work is the first attempt at modeling complex reacting systems, whose performance relies on underlying multiscale mathematics and developing rigorous mathematical techniques and computational algorithms to study such models. Our specific application lies at the heart of biofuels initiatives of DOE and entails modeling of catalytic systems, to enable economic, environmentally benign, and efficient conversion of biomass into either hydrogen or valuable chemicals.

Modeling and simulation of high dimensional stochastic multiscale PDE systems at the exascale

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

Zabaras, Nicolas J.

2016-11-08

Predictive Modeling of multiscale and Multiphysics systems requires accurate data driven characterization of the input uncertainties, and understanding of how they propagate across scales and alter the final solution. This project develops a rigorous mathematical framework and scalable uncertainty quantification algorithms to efficiently construct realistic low dimensional input models, and surrogate low complexity systems for the analysis, design, and control of physical systems represented by multiscale stochastic PDEs. The work can be applied to many areas including physical and biological processes, from climate modeling to systems biology.

Report of the proceedings of the Colloquium and Workshop on Multiscale Coupled Modeling

NASA Technical Reports Server (NTRS)

Koch, Steven E. (Editor)

1993-01-01

The Colloquium and Workshop on Multiscale Coupled Modeling was held for the purpose of addressing modeling issues of importance to planning for the Cooperative Multiscale Experiment (CME). The colloquium presentations attempted to assess the current ability of numerical models to accurately simulate the development and evolution of mesoscale cloud and precipitation systems and their cycling of water substance, energy, and trace species. The primary purpose of the workshop was to make specific recommendations for the improvement of mesoscale models prior to the CME, their coupling with cloud, cumulus ensemble, hydrology, air chemistry models, and the observational requirements to initialize and verify these models.

Multiscale modeling of nerve agent hydrolysis mechanisms: a tale of two Nobel Prizes

NASA Astrophysics Data System (ADS)

Field, Martin J.; Wymore, Troy W.

2014-10-01

The 2013 Nobel Prize in Chemistry was awarded for the development of multiscale models for complex chemical systems, whereas the 2013 Peace Prize was given to the Organisation for the Prohibition of Chemical Weapons for their efforts to eliminate chemical warfare agents. This review relates the two by introducing the field of multiscale modeling and highlighting its application to the study of the biological mechanisms by which selected chemical weapon agents exert their effects at an atomic level.

16 CFR 23.25 - Misuse of the word “gem.”

Code of Federal Regulations, 2014 CFR

2014-01-01

... stones possess the necessary qualifications to properly be termed “gems.” Imitation diamonds and other imitation stones should not be described as “gems.” Not all diamonds or natural stones, including those...

16 CFR 23.25 - Misuse of the word “gem.”

Code of Federal Regulations, 2013 CFR

2013-01-01

... stones possess the necessary qualifications to properly be termed “gems.” Imitation diamonds and other imitation stones should not be described as “gems.” Not all diamonds or natural stones, including those...

16 CFR 23.25 - Misuse of the word “gem.”

Code of Federal Regulations, 2011 CFR

2011-01-01

... stones possess the necessary qualifications to properly be termed “gems.” Imitation diamonds and other imitation stones should not be described as “gems.” Not all diamonds or natural stones, including those...

16 CFR 23.25 - Misuse of the word “gem.”

Code of Federal Regulations, 2012 CFR

2012-01-01

... stones possess the necessary qualifications to properly be termed “gems.” Imitation diamonds and other imitation stones should not be described as “gems.” Not all diamonds or natural stones, including those...

Gravitational induction

NASA Astrophysics Data System (ADS)

Bini, Donato; Cherubini, Christian; Chicone, Carmen; Mashhoon, Bahram

2008-11-01

We study the linear post-Newtonian approximation to general relativity known as gravitoelectromagnetism (GEM); in particular, we examine the similarities and differences between GEM and electrodynamics. Notwithstanding some significant differences between them, we find that a special nonstationary metric in GEM can be employed to show explicitly that it is possible to introduce gravitational induction within GEM in close analogy with Faraday's law of induction and Lenz's law in electrodynamics. Some of the physical implications of gravitational induction are briefly discussed.

Multiscale analysis of neural spike trains.

PubMed

Ramezan, Reza; Marriott, Paul; Chenouri, Shojaeddin

2014-01-30

This paper studies the multiscale analysis of neural spike trains, through both graphical and Poisson process approaches. We introduce the interspike interval plot, which simultaneously visualizes characteristics of neural spiking activity at different time scales. Using an inhomogeneous Poisson process framework, we discuss multiscale estimates of the intensity functions of spike trains. We also introduce the windowing effect for two multiscale methods. Using quasi-likelihood, we develop bootstrap confidence intervals for the multiscale intensity function. We provide a cross-validation scheme, to choose the tuning parameters, and study its unbiasedness. Studying the relationship between the spike rate and the stimulus signal, we observe that adjusting for the first spike latency is important in cross-validation. We show, through examples, that the correlation between spike trains and spike count variability can be multiscale phenomena. Furthermore, we address the modeling of the periodicity of the spike trains caused by a stimulus signal or by brain rhythms. Within the multiscale framework, we introduce intensity functions for spike trains with multiplicative and additive periodic components. Analyzing a dataset from the retinogeniculate synapse, we compare the fit of these models with the Bayesian adaptive regression splines method and discuss the limitations of the methodology. Computational efficiency, which is usually a challenge in the analysis of spike trains, is one of the highlights of these new models. In an example, we show that the reconstruction quality of a complex intensity function demonstrates the ability of the multiscale methodology to crack the neural code. Copyright © 2013 John Wiley & Sons, Ltd.

Emissions of mercury in southern Africa derived from long-term observations at Cape Point, South Africa

NASA Astrophysics Data System (ADS)

Brunke, E.-G.; Ebinghaus, R.; Kock, H. H.; Labuschagne, C.; Slemr, F.

2012-08-01

Mercury emissions in South Africa have so far been estimated only by a bottom-up approach from activities and emission factors for different processes. In this paper we derive GEM/CO (GEM being gaseous elemental mercury, Hg0), GEM/CO2, GEM/CH4, CO/CO2, CH4/CO2, and CH4/CO emission ratios from plumes observed during long-term monitoring of these species at Cape Point between March 2007 and December 2009. The average observed GEM/CO, GEM/CO2, GEM/CH4, CO/CO2, CH4/CO2, and CH4/CO emission ratios were 2.40 ± 2.65 pg m-3 ppb-1 (n = 47), 62.7 ± 80.2 pg m-3 ppm-1 (n = 44), 3.61 ± 4.66 pg m-3 ppb-1 (n = 46), 35.6 ± 25.4 ppb ppm-1 (n = 52), 20.2 ± 15.5 ppb ppm-1 (n = 48), and 0.876 ± 1.106 ppb ppb-1 (n = 42), respectively. The observed CO/CO2, CH4/CO2, and CH4/CO emission ratios agree within the combined uncertainties of the observations and emissions with the ratios calculated from EDGAR (version 4.2) CO2, CO, and CH4 inventories for South Africa and southern Africa (South Africa, Lesotho, Swaziland, Namibia, Botswana, Zimbabwe, and Mozambique) in 2007 and 2008 (inventories for 2009 are not available yet). Total elemental mercury emission of 13.1, 15.2, and 16.1 t Hg yr-1 are estimated independently using the GEM/CO, GEM/CO2, and GEM/CH4 emission ratios and the annual mean CO, CO2, and CH4 emissions, respectively, of South Africa in 2007 and 2008. The average of these independent estimates of 14.8 t GEM yr-1 is much less than the total emission of 257 t Hg yr-1 shown by older inventories which are now considered to be wrong. Considering the uncertainties of our emission estimate, of the emission inventories, and the fact that emission of GEM represents 50-78 % of all mercury emissions, our estimate is comparable to the currently cited GEM emissions in 2004 and somewhat smaller than emissions in 2006. A further increase of mercury emissions due to increasing electricity consumption will lead to a more pronounced difference. A quantitative assessment of the difference and its significance, however, will require emission inventories for the years of observations (2007-2009) as well as better data on the speciation of the total mercury emissions in South Africa.

Time-resolved Spectroscopy of RS CVn Binaries and dMe Flare Stars

NASA Astrophysics Data System (ADS)

Brown, Alexander

One of the most striking feature of the first two years of EUVE spectroscopy is the frequent occurrence of largescale coronal variability, in the form of stellar flares and slower changes in activity level due to rotational modulation and evolution of active regions. We propose EUVE observations of a set of RS CVn and dMe star binaries, most with short (< 2 days) periods, to investigate the coronal conditions and physical processes associated with this variability. EUVE flare outbursts have mostly been long duration events lasting many satellite orbits and been readily studied using time-resolved spectroscopy. Our targets are the dMe binaries YY Gem, CC Eri and Gliese 2123, and the RS CVn systems EI Eri, AR Psc, and TY Pyx. YY Gem and TY Pyx are eclipsing systems and Deep Survey photometry will be used to investigate the size of the coronal emitting regions. Situated 73 arcmin from YY Gem is Castor (Alpha Gem) another X-ray source that can be observed (and spatially resolved) simultaneously. We shall use the DS lightcurve to guide our time resolved spectral analysis. Changes in the coronal emission measure as a function of temperature and possibly changes in coronal density will be used to constrain magnetic loop models.

Adaptation of a Fast Optimal Interpolation Algorithm to the Mapping of Oceangraphic Data

NASA Technical Reports Server (NTRS)

Menemenlis, Dimitris; Fieguth, Paul; Wunsch, Carl; Willsky, Alan

1997-01-01

A fast, recently developed, multiscale optimal interpolation algorithm has been adapted to the mapping of hydrographic and other oceanographic data. This algorithm produces solution and error estimates which are consistent with those obtained from exact least squares methods, but at a small fraction of the computational cost. Problems whose solution would be completely impractical using exact least squares, that is, problems with tens or hundreds of thousands of measurements and estimation grid points, can easily be solved on a small workstation using the multiscale algorithm. In contrast to methods previously proposed for solving large least squares problems, our approach provides estimation error statistics while permitting long-range correlations, using all measurements, and permitting arbitrary measurement locations. The multiscale algorithm itself, published elsewhere, is not the focus of this paper. However, the algorithm requires statistical models having a very particular multiscale structure; it is the development of a class of multiscale statistical models, appropriate for oceanographic mapping problems, with which we concern ourselves in this paper. The approach is illustrated by mapping temperature in the northeastern Pacific. The number of hydrographic stations is kept deliberately small to show that multiscale and exact least squares results are comparable. A portion of the data were not used in the analysis; these data serve to test the multiscale estimates. A major advantage of the present approach is the ability to repeat the estimation procedure a large number of times for sensitivity studies, parameter estimation, and model testing. We have made available by anonymous Ftp a set of MATLAB-callable routines which implement the multiscale algorithm and the statistical models developed in this paper.

Antitumor activity of the investigational proteasome inhibitor MLN9708 in mouse models of B-cell and plasma cell malignancies.

PubMed

Lee, Edmund C; Fitzgerald, Michael; Bannerman, Bret; Donelan, Jill; Bano, Kristen; Terkelsen, Jennifer; Bradley, Daniel P; Subakan, Ozlem; Silva, Matthew D; Liu, Ray; Pickard, Michael; Li, Zhi; Tayber, Olga; Li, Ping; Hales, Paul; Carsillo, Mary; Neppalli, Vishala T; Berger, Allison J; Kupperman, Erik; Manfredi, Mark; Bolen, Joseph B; Van Ness, Brian; Janz, Siegfried

2011-12-01

The clinical success of the first-in-class proteasome inhibitor bortezomib (VELCADE) has validated the proteasome as a therapeutic target for treating human cancers. MLN9708 is an investigational proteasome inhibitor that, compared with bortezomib, has improved pharmacokinetics, pharmacodynamics, and antitumor activity in preclinical studies. Here, we focused on evaluating the in vivo activity of MLN2238 (the biologically active form of MLN9708) in a variety of mouse models of hematologic malignancies, including tumor xenograft models derived from a human lymphoma cell line and primary human lymphoma tissue, and genetically engineered mouse (GEM) models of plasma cell malignancies (PCM). Both cell line-derived OCI-Ly10 and primary human lymphoma-derived PHTX22L xenograft models of diffuse large B-cell lymphoma were used to evaluate the pharmacodynamics and antitumor effects of MLN2238 and bortezomib. The iMyc(Cα)/Bcl-X(L) GEM model was used to assess their effects on de novo PCM and overall survival. The newly developed DP54-Luc-disseminated model of iMyc(Cα)/Bcl-X(L) was used to determine antitumor activity and effects on osteolytic bone disease. MLN2238 has an improved pharmacodynamic profile and antitumor activity compared with bortezomib in both OCI-Ly10 and PHTX22L models. Although both MLN2238 and bortezomib prolonged overall survival, reduced splenomegaly, and attenuated IgG2a levels in the iMyc(Cα)/Bcl-X(L) GEM model, only MLN2238 alleviated osteolytic bone disease in the DP54-Luc model. Our results clearly showed the antitumor activity of MLN2238 in a variety of mouse models of B-cell lymphoma and PCM, supporting its clinical development. MLN9708 is being evaluated in multiple phase I and I/II trials. ©2011 AACR.

A Multi-scale Modeling System with Unified Physics to Study Precipitation Processes

NASA Astrophysics Data System (ADS)

Tao, W. K.

2017-12-01

In recent years, exponentially increasing computer power has extended Cloud Resolving Model (CRM) integrations from hours to months, the number of computational grid points from less than a thousand to close to ten million. Three-dimensional models are now more prevalent. Much attention is devoted to precipitating cloud systems where the crucial 1-km scales are resolved in horizontal domains as large as 10,000 km in two-dimensions, and 1,000 x 1,000 km2 in three-dimensions. Cloud resolving models now provide statistical information useful for developing more realistic physically based parameterizations for climate models and numerical weather prediction models. It is also expected that NWP and mesoscale model can be run in grid size similar to cloud resolving model through nesting technique. Recently, a multi-scale modeling system with unified physics was developed at NASA Goddard. It consists of (1) a cloud-resolving model (Goddard Cumulus Ensemble model, GCE model), (2) a regional scale model (a NASA unified weather research and forecast, WRF), and (3) a coupled CRM and global model (Goddard Multi-scale Modeling Framework, MMF). The same microphysical processes, long and short wave radiative transfer and land processes and the explicit cloud-radiation, and cloud-land surface interactive processes are applied in this multi-scale modeling system. This modeling system has been coupled with a multi-satellite simulator to use NASA high-resolution satellite data to identify the strengths and weaknesses of cloud and precipitation processes simulated by the model. In this talk, a review of developments and applications of the multi-scale modeling system will be presented. In particular, the results from using multi-scale modeling system to study the precipitation, processes and their sensitivity on model resolution and microphysics schemes will be presented. Also how to use of the multi-satellite simulator to improve precipitation processes will be discussed.

Using Multi-Scale Modeling Systems and Satellite Data to Study the Precipitation Processes

NASA Technical Reports Server (NTRS)

Tao, Wei-Kuo; Chern, J.; Lamg, S.; Matsui, T.; Shen, B.; Zeng, X.; Shi, R.

2011-01-01

In recent years, exponentially increasing computer power has extended Cloud Resolving Model (CRM) integrations from hours to months, the number of computational grid points from less than a thousand to close to ten million. Three-dimensional models are now more prevalent. Much attention is devoted to precipitating cloud systems where the crucial 1-km scales are resolved in horizontal domains as large as 10,000 km in two-dimensions, and 1,000 x 1,000 km2 in three-dimensions. Cloud resolving models now provide statistical information useful for developing more realistic physically based parameterizations for climate models and numerical weather prediction models. It is also expected that NWP and mesoscale model can be run in grid size similar to cloud resolving model through nesting technique. Recently, a multi-scale modeling system with unified physics was developed at NASA Goddard. It consists of (l) a cloud-resolving model (Goddard Cumulus Ensemble model, GCE model), (2) a regional scale model (a NASA unified weather research and forecast, WRF), (3) a coupled CRM and global model (Goddard Multi-scale Modeling Framework, MMF), and (4) a land modeling system. The same microphysical processes, long and short wave radiative transfer and land processes and the explicit cloud-radiation, and cloud-land surface interactive processes are applied in this multi-scale modeling system. This modeling system has been coupled with a multi-satellite simulator to use NASA high-resolution satellite data to identify the strengths and weaknesses of cloud and precipitation processes simulated by the model. In this talk, the recent developments and applications of the multi-scale modeling system will be presented. In particular, the results from using multi-scale modeling system to study the precipitating systems and hurricanes/typhoons will be presented. The high-resolution spatial and temporal visualization will be utilized to show the evolution of precipitation processes. Also how to use of the multi-satellite simulator tqimproy precipitation processes will be discussed.

Using Multi-Scale Modeling Systems and Satellite Data to Study the Precipitation Processes

NASA Technical Reports Server (NTRS)

Tao, Wei--Kuo; Chern, J.; Lamg, S.; Matsui, T.; Shen, B.; Zeng, X.; Shi, R.

2010-01-01

In recent years, exponentially increasing computer power extended Cloud Resolving Model (CRM) integrations from hours to months, the number of computational grid points from less than a thousand to close to ten million. Three-dimensional models are now more prevalent. Much attention is devoted to precipitating cloud systems where the crucial 1-km scales are resolved in horizontal domains as large as 10,000 km in two-dimensions, and 1,000 x 1,000 sq km in three-dimensions. Cloud resolving models now provide statistical information useful for developing more realistic physically based parameterizations for climate models and numerical weather prediction models. It is also expected that NWP and mesoscale models can be run in grid size similar to cloud resolving models through nesting technique. Recently, a multi-scale modeling system with unified physics was developed at NASA Goddard. It consists of (1) a cloud-resolving model (Goddard Cumulus Ensemble model, GCE model). (2) a regional scale model (a NASA unified weather research and forecast, W8F). (3) a coupled CRM and global model (Goddard Multi-scale Modeling Framework, MMF), and (4) a land modeling system. The same microphysical processes, long and short wave radiative transfer and land processes and the explicit cloud-radiation and cloud-land surface interactive processes are applied in this multi-scale modeling system. This modeling system has been coupled with a multi-satellite simulator to use NASA high-resolution satellite data to identify the strengths and weaknesses of cloud and precipitation processes simulated by the model. In this talk, a review of developments and applications of the multi-scale modeling system will be presented. In particular, the results from using multi-scale modeling systems to study the interactions between clouds, precipitation, and aerosols will be presented. Also how to use the multi-satellite simulator to improve precipitation processes will be discussed.

Using Multi-Scale Modeling Systems to Study the Precipitation Processes

NASA Technical Reports Server (NTRS)

Tao, Wei-Kuo

2010-01-01

In recent years, exponentially increasing computer power has extended Cloud Resolving Model (CRM) integrations from hours to months, the number of computational grid points from less than a thousand to close to ten million. Three-dimensional models are now more prevalent. Much attention is devoted to precipitating cloud systems where the crucial 1-km scales are resolved in horizontal domains as large as 10,000 km in two-dimensions, and 1,000 x 1,000 km2 in three-dimensions. Cloud resolving models now provide statistical information useful for developing more realistic physically based parameterizations for climate models and numerical weather prediction models. It is also expected that NWP and mesoscale model can be run in grid size similar to cloud resolving model through nesting technique. Recently, a multi-scale modeling system with unified physics was developed at NASA Goddard. It consists of (1) a cloud-resolving model (Goddard Cumulus Ensemble model, GCE model), (2) a regional scale model (a NASA unified weather research and forecast, WRF), (3) a coupled CRM and global model (Goddard Multi-scale Modeling Framework, MMF), and (4) a land modeling system. The same microphysical processes, long and short wave radiative transfer and land processes and the explicit cloud-radiation, and cloud-land surface interactive processes are applied in this multi-scale modeling system. This modeling system has been coupled with a multi-satellite simulator to use NASA high-resolution satellite data to identify the strengths and weaknesses of cloud and precipitation processes simulated by the model. In this talk, a review of developments and applications of the multi-scale modeling system will be presented. In particular, the results from using multi-scale modeling system to study the interactions between clouds, precipitation, and aerosols will be presented. Also how to use of the multi-satellite simulator to improve precipitation processes will be discussed.

Wavelet-based multiscale performance analysis: An approach to assess and improve hydrological models

NASA Astrophysics Data System (ADS)

Rathinasamy, Maheswaran; Khosa, Rakesh; Adamowski, Jan; ch, Sudheer; Partheepan, G.; Anand, Jatin; Narsimlu, Boini

2014-12-01

The temporal dynamics of hydrological processes are spread across different time scales and, as such, the performance of hydrological models cannot be estimated reliably from global performance measures that assign a single number to the fit of a simulated time series to an observed reference series. Accordingly, it is important to analyze model performance at different time scales. Wavelets have been used extensively in the area of hydrological modeling for multiscale analysis, and have been shown to be very reliable and useful in understanding dynamics across time scales and as these evolve in time. In this paper, a wavelet-based multiscale performance measure for hydrological models is proposed and tested (i.e., Multiscale Nash-Sutcliffe Criteria and Multiscale Normalized Root Mean Square Error). The main advantage of this method is that it provides a quantitative measure of model performance across different time scales. In the proposed approach, model and observed time series are decomposed using the Discrete Wavelet Transform (known as the à trous wavelet transform), and performance measures of the model are obtained at each time scale. The applicability of the proposed method was explored using various case studies-both real as well as synthetic. The synthetic case studies included various kinds of errors (e.g., timing error, under and over prediction of high and low flows) in outputs from a hydrologic model. The real time case studies investigated in this study included simulation results of both the process-based Soil Water Assessment Tool (SWAT) model, as well as statistical models, namely the Coupled Wavelet-Volterra (WVC), Artificial Neural Network (ANN), and Auto Regressive Moving Average (ARMA) methods. For the SWAT model, data from Wainganga and Sind Basin (India) were used, while for the Wavelet Volterra, ANN and ARMA models, data from the Cauvery River Basin (India) and Fraser River (Canada) were used. The study also explored the effect of the choice of the wavelets in multiscale model evaluation. It was found that the proposed wavelet-based performance measures, namely the MNSC (Multiscale Nash-Sutcliffe Criteria) and MNRMSE (Multiscale Normalized Root Mean Square Error), are a more reliable measure than traditional performance measures such as the Nash-Sutcliffe Criteria (NSC), Root Mean Square Error (RMSE), and Normalized Root Mean Square Error (NRMSE). Further, the proposed methodology can be used to: i) compare different hydrological models (both physical and statistical models), and ii) help in model calibration.

Vertical structure of aerosol distribution and radiative properties over Svalbard - observations and modelling

NASA Astrophysics Data System (ADS)

Kaminski, Jacek W.; Struzewska, Joanna; Markowicz, Krzysztof; Jefimow, Maciej

2015-04-01

In the scope of the iAREA projects (Impact of absorbing aerosols on radiative forcing in the European Arctic - http://www.igf.fuw.edu.pl/iAREA) a field campaign was undertaken in March and April 2014 on Spitzbergen. Analysis of measurements was supported by the GEM-AQ model simulations. The GEM-AQ model is a chemical weather model. The core of the model is based on a weather prediction model with environmental processes (chemistry and aerosols) implanted on-line and are interactive (i.e. providing feedback of chemistry on radiation and dynamics). Numerical experiments were performed with the computational grid resolution of ˜15 km. The emission inventory developed by NILU in the ECLIPSE project was used. Preliminary analysis revealed small but systematic overestimation of modelled AOD and background BC levels. We will present the analysis of the vertical distribution of different aerosol species and its contribution to AOD for two stations on Svalbard. Also, changes of modelled chemical composition of aerosols with altitude will be analyzed.

The Bisa GEM-Mars GCM

NASA Astrophysics Data System (ADS)

Neary, Lori; Daerden, Frank

2013-04-01

GEM-Mars is a three-dimensional general circulation model of the Mars atmosphere extending from the surface to approximately 170 km based on the latest version of the GEM (Global Environmental Mesoscale) model, the operational data assimilation and weather forecasting system for Canada [Côté et al., 1998]. The dynamical core is an implicit two-time-level semi-Lagrangian scheme on an Arakawa C-grid with a terrain-following, log-hydrostatic-pressure vertical coordinate discretized on a Charney-Phillips grid. The model has both a hydrostatic and non-hydrostatic formulation, providing a single platform for simulations on a variety of horizontal scales. The model code is fully parallelized using OMP and MPI. The GCM includes the relevant physical processes such as CO2 condensation, planetary boundary layer mixing, gravity wave drag and surface parameterizations. A simple water cycle, basic gas-phase chemistry and passive tracers are also included in the model. Because of the vertical extent of the model, UV heating, non-LTE effects and molecular diffusion are also included. Dust is prescribed using the MGS scenario for total opacities and a Conrath profile shape. In the dust radiative transfer code, dust optical properties are based on the Wolff et al [2006, 2009] data. Temperatures in the lower and middle atmosphere have been evaluated using TES [Smith, 2004] and MCS [Kleinbohl et al. 2009] data. Winds and atmospheric circulation (mass stream functions) have been compared with the literature and show a good correspondence to other Mars GCMs. In parallel, active lifting and settling of size-distributed dust has also been implemented. The soil model has been improved to better match surface and near-surface temperatures from the Viking Landers, Phoenix [Davy et al. 2010], and TES. Near-surface winds and friction velocities have been compared with the literature and show reasonable performance. Condensation of CO2 in surface ice has been validated using CO2 ice mass data from HEND [Litvak et al. 2004] and GRS [Kelly et al. 2006]. The effect of the polar cap formation on the pressure cycle is found to be in very good agreement with the Viking Landers and Phoenix [Taylor et al. 2010] data. References: Côté J., S. Gravel, A. Méthot, A. Patoine, M. Roch and A. Staniforth, The operational CMC-MRB Global Environmental Multiscale (GEM) model: Part I - Design considerations and formulation, Mon. Wea. Rev., 126, 1373-1395. Davy, R., J. A. Davis, P. A. Taylor, C. F. Lange, W. Weng, J. Whiteway, and H. P. Gunnlaugson (2010), Initial analysis of air temperature and related data from the Phoenix MET station and their use in estimating turbulent heat fluxes, J. Geophys. Res., 115, E00E13, doi:10.1029/2009JE003444. Kelly, N. J., W. V. Boynton, K. Kerry, D. Hamara, D. Janes, R. C. Reedy, K. J. Kim, and R. M. Haberle (2006), Seasonal polar carbon dioxide frost on Mars: CO2 mass and columnar thickness distribution, J. Geophys. Res., 111, E03S07, doi:10.1029/2006JE002678 [printed 112(E3), 2007]. Kleinbohl, A., J. T. Schofield, D. M. Kass, W. A. Abdou, C. R. Backus, B. Sen, J. H. Shirley,W. G. Lawson, M. I. Richardson, F. W. Taylor, N. A. Teanby, and D. J. McCleese (2009). "Mars Climate Sounder limb profile retrieval of atmospheric temperature, pressure, dust and water ice opacity," J. Geophys. Res., 114, E10006, doi:10.1029/2009JE003358. Litvak, M. L., et al. (2004), Seasonal carbon dioxide depositions on the Martian surface as revealed from neutron measurements by the HEND instrument onboard the 2001 Mars Odyssey Spacecraft, Sol. Syst. Res., 38, 167 - 177. Smith M. D. (2004), Interannual variability in TES atmospheric observations of Mars during 1999-2003, Icarus 167, 148 -165. Taylor, P. A., et al. (2010), On pressure measurement and seasonal pressure variations during the Phoenix mission, J. Geophys. Res., 115, E00E15, doi:10.1029/2009JE003422. Wolff, M. J., et al. (2006), Constraints on dust aerosols from the Mars Exploration Rovers using MGS overflights and Mini-TES, J. Geophys. Res., 111, E12S17, doi:10.1029/2006JE002786 Wolff, M. J., M. D. Smith, R. T. Clancy, R. Arvidson, M. Kahre, F. Seelos, S. Murchie, and H. Savijärvi (2009), Wavelength dependence of dust aerosol single scattering albedo as observed by the Compact Reconnaissance Imaging Spectrometer, J. Geophys. Res., 114, E00D04, doi:10.1029/2009JE003350

Performance of GEM Detectors in the DarkLight Experiment at LERF

NASA Astrophysics Data System (ADS)

Mohammed Prem Nazeer, Sahara Jesmin; DarkLight Collaboration

2017-01-01

The DarkLight experiment has been proposed to search for a heavy photon A' in the mass range of 10-100 MeV/c2 produced in electron-proton collisions. Phase-I of DarkLight has started to take place in 2016 at the Low Energy Recirculator Facility (LERF) at Jefferson Lab. LERF delivered a 100 MeV electron beam onto a windowless hydrogen gas target. The phase-I detector tracks leptons inside the DarkLight solenoid with a set of Gas Electron Multiplier (GEM) detectors, combined with segmented scintillators for triggering. The GEM telescope consists of four 10 × 10 cm2 triple layer GEM chambers with 2D readout strips, mounted in a slightly angled fixed frame about 12 cm tall. The GEM data are read out with analog pipeline front-end cards (APV-25) each of which can process 128 readout channels. Each GEM chamber has 250 channels for each coordinate axis, read out with two APVs on each side, resulting in 2000 readout channels for the GEM stack, processed by 16 APVs. One Multi Purpose Digitizer (MPD) module is used to read out all of the 16 APV-25 cards. The current run status of DarkLight experiment and the performance of GEMs in the experiment will be discussed. This work has been supported by NSF PHY-1436680 and PHY-1505934.

Self-Delivery Nanoparticles of Amphiphilic Methotrexate-Gemcitabine Prodrug for Synergistic Combination Chemotherapy via Effect of Deoxyribonucleotide Pools.

PubMed

Wang, Yao; Huang, Ping; Hu, Minxi; Huang, Wei; Zhu, Xinyuan; Yan, Deyue

2016-11-16

The distinct and complementary biochemical mechanisms of folic acid analog methotrexate (MTX) and cytidine analog gemcitabine (GEM) make their synergistic combination effective. Unfortunately, such a combination faces severe pharmacokinetic problems and several transportation barriers. To overcome these problems, a new strategy of amphiphilic small molecule prodrug (ASMP) is developed to improve their synergistic combination effect. The ASMP was prepared by the amidation of the hydrophilic GEM with the hydrophobic MTX at a fixed ratio. Owing to its inherent amphiphilicity, the MTX-GEM ASMP self-assembled into stable nanoparticles (ASMP-NPs) with high drug loading capacity (100%), in which the MTX and GEM could self-deliver without any carriers and release synchronously in cancer cells. In vitro studies showed that the MTX-GEM ASMP-NPs could greatly improve the synergistic combination effects by the reason of arresting more S phase of the cell cycle and reducing levels of deoxythymidine triphosphate (dTTP), deoxyadenosine triphosphate (dATP), and deoxycytidine triphosphate (dCTP). The stronger synergistic effects caused the higher cell cytotoxicity and apoptotic ratio, and circumvented the multidrug resistance (MDR) of tumor cells. Additionally, MTX-GEM ASMP-NPs could achieve the same anticancer effect with the greatly reduced dosage compared with the free drugs according to the dose-reduction index (DRI) values of MTX and GEM in MTX-GEM ASMP-NPs, which may be beneficial for reducing the side effects.

Gaseous elemental mercury (GEM) fluxes over canopy of two typical subtropical forests in south China

NASA Astrophysics Data System (ADS)

Yu, Qian; Luo, Yao; Wang, Shuxiao; Wang, Zhiqi; Hao, Jiming; Duan, Lei

2018-01-01

Mercury (Hg) exchange between forests and the atmosphere plays an important role in global Hg cycling. The present estimate of global emission of Hg from natural source has large uncertainty, partly due to the lack of chronical and valid field data, particularly for terrestrial surfaces in China, the most important contributor to global atmospheric Hg. In this study, the micrometeorological method (MM) was used to continuously observe gaseous elemental mercury (GEM) fluxes over forest canopy at a mildly polluted site (Qianyanzhou, QYZ) and a moderately polluted site (Huitong, HT, near a large Hg mine) in subtropical south China for a full year from January to December in 2014. The GEM flux measurements over forest canopy in QYZ and HT showed net emission with annual average values of 6.67 and 0.30 ng m-2 h-1, respectively. Daily variations of GEM fluxes showed an increasing emission with the increasing air temperature and solar radiation in the daytime to a peak at 13:00, and decreasing emission thereafter, even as a GEM sink or balance at night. High temperature and low air Hg concentration resulted in the high Hg emission in summer. Low temperature in winter and Hg absorption by plant in spring resulted in low Hg emission, or even adsorption in the two seasons. GEM fluxes were positively correlated with air temperature, soil temperature, wind speed, and solar radiation, while it is negatively correlated with air humidity and atmospheric GEM concentration. The lower emission fluxes of GEM at the moderately polluted site (HT) when compared with that in the mildly polluted site (QYZ) may result from a much higher adsorption fluxes at night in spite of a similar or higher emission fluxes during daytime. This shows that the higher atmospheric GEM concentration at HT restricted the forest GEM emission. Great attention should be paid to forests as a crucial increasing Hg emission source with the decreasing atmospheric GEM concentration in polluted areas because of Hg emission abatement in the future.

Limitations and opportunities of whole blood bilirubin measurements by GEM premier 4000®.

PubMed

Wang, Li; Albert, Arianne Y K; Jung, Benjamin; Hadad, Keyvan; Lyon, Martha E; Basso, Melanie

2017-03-29

Neonatal hyperbilirubinemia has traditionally been screened by either total serum bilirubin or transcutaneous bilirubin. Whole blood bilirubin (TwB) by the GEM Premier 4000® blood gas analyzer (GEM) is a relatively new technology and it provides fast bilirubin results with a small sample volume and can measure co-oximetry and other analytes. Our clinical study was to evaluate the reliability of TwB measured by the GEM and identify analytical and clinical factors that may contribute to possible bias. 440 consecutive healthy newborn samples that had plasma bilirubin ordered for neonatal hyperbilirubinemia screening were included. TwB was first measured using the GEM, after which the remainder of the blood was spun and plasma neonatal bilirubin was measured using the VITROS 5600® (VITROS). 62 samples (14%) were excluded from analysis due to failure in obtaining GEM results. Passing-Bablok regression suggested that the GEM results were negatively biased at low concentrations of bilirubin and positively biased at higher concentrations relative to the VITROS results (y = 1.43x-61.13). Bland-Altman plots showed an overall negative bias of the GEM bilirubin with a wide range of differences compared to VITROS. Both hemoglobin concentration and hemolysis affected the accuracy of the GEM results. Clinically, male infants had higher mean bilirubin levels, and infants delivered by caesarean section had lower hemoglobin levels. When comparing the number of results below the 40th percentile and above the 95th percentile cut-offs in the Bhutani nomogram which would trigger discharge or treatment, GEM bilirubin exhibited poor sensitivity and poor specificity in contrast to VITROS bilirubin. An imperfect correlation was observed between whole blood bilirubin measured on the GEM4000® and plasma bilirubin on the VITROS 5600®. The contributors to the observed differences between the two instruments were specimen hemolysis and the accuracy of hemoglobin measurements, the latter of which affects the calculation of plasma-equivalent bilirubin. Additionally, the lack of standardization of total bilirubin calibration particularly in newborn specimens, may also account for some of the disagreement in results.

MODELS-3 COMMUNITY MULTISCALE AIR QUALITY (CMAQ) MODEL AEROSOL COMPONENT 1: MODEL DESCRIPTION

EPA Science Inventory

The aerosol component of the Community Multiscale Air Quality (CMAQ) model is designed to be an efficient and economical depiction of aerosol dynamics in the atmosphere. The approach taken represents the particle size distribution as the superposition of three lognormal subdis...

Evaluation of the Community Multiscale Air Quality model version 5.1

EPA Science Inventory

The Community Multiscale Air Quality model is a state-of-the-science air quality model that simulates the emission, transport and fate of numerous air pollutants, including ozone and particulate matter. The Atmospheric Modeling and Analysis Division (AMAD) of the U.S. Environment...

Multiscale modeling of multi-decadal trends in air pollutant concentrations and their radiative properties: the role of models in an integrated observing system

NASA Astrophysics Data System (ADS)

Mathur, R.; Xing, J.; Szykman, J.; Gan, C. M.; Hogrefe, C.; Pleim, J. E.

2015-12-01

Air Pollution simulation models must address the increasing complexity arising from new model applications that treat multi-pollutant interactions across varying space and time scales. Setting and attaining lower ambient air quality standards requires an improved understanding and quantification of source attribution amongst the multiple anthropogenic and natural sources, on time scales ranging from episodic to annual and spatial scales ranging from urban to continental. Changing emission patterns over the developing regions of the world are likely to exacerbate the impacts of long-range pollutant transport on background pollutant levels, which may then impact the attainment of local air quality standards. Thus, strategies for reduction of pollution levels of surface air over a region are complicated not only by the interplay of local emissions sources and several complex physical, chemical, dynamical processes in the atmosphere, but also hemispheric background levels of pollutants. Additionally, as short-lived climate forcers, aerosols and ozone exert regionally heterogeneous radiative forcing and influence regional climate trends. EPA's coupled WRF-CMAQ modeling system is applied over a domain encompassing the northern hemisphere for the period spanning 1990-2010. This period has witnessed significant reductions in anthropogenic emissions in North America and Europe as a result of implementation of control measures and dramatic increases across Asia associated with economic and population growth, resulting in contrasting trends in air pollutant distributions and transport patterns across the northern hemisphere. Model results (trends in pollutant concentrations, optical and radiative characteristics) across the northern hemisphere are analyzed in conjunction with surface, aloft and remote sensing measurements to contrast the differing trends in air pollution and aerosol-radiation interactions in these regions over the past two decades. Given the future LEO (TropOMI) and GEO (Sentinel-4, GEMS, and TEMPO) atmospheric chemistry satellite observing capabilities, the results from these model applications will be discussed in the context of how the new satellite observations could help constrain and reduce uncertainties in the models.

Towards Personalized Cardiology: Multi-Scale Modeling of the Failing Heart

PubMed Central

Amr, Ali; Neumann, Dominik; Georgescu, Bogdan; Seegerer, Philipp; Kamen, Ali; Haas, Jan; Frese, Karen S.; Irawati, Maria; Wirsz, Emil; King, Vanessa; Buss, Sebastian; Mereles, Derliz; Zitron, Edgar; Keller, Andreas; Katus, Hugo A.; Comaniciu, Dorin; Meder, Benjamin

2015-01-01

Background Despite modern pharmacotherapy and advanced implantable cardiac devices, overall prognosis and quality of life of HF patients remain poor. This is in part due to insufficient patient stratification and lack of individualized therapy planning, resulting in less effective treatments and a significant number of non-responders. Methods and Results State-of-the-art clinical phenotyping was acquired, including magnetic resonance imaging (MRI) and biomarker assessment. An individualized, multi-scale model of heart function covering cardiac anatomy, electrophysiology, biomechanics and hemodynamics was estimated using a robust framework. The model was computed on n=46 HF patients, showing for the first time that advanced multi-scale models can be fitted consistently on large cohorts. Novel multi-scale parameters derived from the model of all cases were analyzed and compared against clinical parameters, cardiac imaging, lab tests and survival scores to evaluate the explicative power of the model and its potential for better patient stratification. Model validation was pursued by comparing clinical parameters that were not used in the fitting process against model parameters. Conclusion This paper illustrates how advanced multi-scale models can complement cardiovascular imaging and how they could be applied in patient care. Based on obtained results, it becomes conceivable that, after thorough validation, such heart failure models could be applied for patient management and therapy planning in the future, as we illustrate in one patient of our cohort who received CRT-D implantation. PMID:26230546

Gemfibrozil, a lipid-lowering drug, upregulates IL-1 receptor antagonist in mouse cortical neurons: implications for neuronal self-defense.

PubMed

Corbett, Grant T; Roy, Avik; Pahan, Kalipada

2012-07-15

Chronic inflammation is becoming a hallmark of several neurodegenerative disorders and accordingly, IL-1β, a proinflammatory cytokine, is implicated in the pathogenesis of neurodegenerative diseases. Although IL-1β binds to its high-affinity receptor, IL-1R, and upregulates proinflammatory signaling pathways, IL-1R antagonist (IL-1Ra) adheres to the same receptor and inhibits proinflammatory cell signaling. Therefore, upregulation of IL-1Ra is considered important in attenuating inflammation. The present study underlines a novel application of gemfibrozil (gem), a Food and Drug Administration-approved lipid-lowering drug, in increasing the expression of IL-1Ra in primary mouse and human neurons. Gem alone induced an early and pronounced increase in the expression of IL-1Ra in primary mouse cortical neurons. Activation of type IA p110α PI3K and Akt by gem and abrogation of gem-induced upregulation of IL-1Ra by inhibitors of PI3K and Akt indicate a role of the PI3K-Akt pathway in the upregulation of IL-1Ra. Gem also induced the activation of CREB via the PI3K-Akt pathway, and small interfering RNA attenuation of CREB abolished the gem-mediated increase in IL-1Ra. Furthermore, gem was able to protect neurons from IL-1β insult. However, small interfering RNA knockdown of neuronal IL-1Ra abrogated the protective effect of gem against IL-1β, suggesting that this drug increases the defense mechanism of cortical neurons via upregulation of IL-1Ra. Taken together, these results highlight the importance of the PI3K-Akt-CREB pathway in mediating gem-induced upregulation of IL-1Ra in neurons and suggest gem as a possible therapeutic treatment for propagating neuronal self-defense in neuroinflammatory and neurodegenerative disorders.

The development and evaluation of mini-GEMs - short, focused, online e-learning videos in geriatric medicine.

PubMed

Garside, Mark J; Fisher, James M; Blundell, Adrian G; Gordon, Adam L

2018-01-01

Mini Geriatric E-Learning Modules (Mini-GEMs) are short, focused, e-learning videos on geriatric medicine topics, hosted on YouTube, which are targeted at junior doctors working with older people. This study aimed to explore how these resources are accessed and used. The authors analyzed the viewing data from 22 videos published over the first 18 months of the Mini-GEM project. We conducted a focus group of U.K. junior doctors considering their experiences with Mini-GEMS. The Mini-GEMs were viewed 10,291 times over 18 months, equating to 38,435 minutes of total viewing time. The average viewing time for each video was 3.85 minutes. Learners valued the brevity and focused nature of the Mini-GEMs and reported that they watched them in a variety of settings to supplement clinical experiences and consolidate learning. Watching the videos led to an increase in self-reported confidence in managing older patients. Mini-GEMs can effectively disseminate clinical teaching material to a wide audience. The videos are valued by junior doctors due to their accessibility and ease of use.

COMMUNITY MULTISCALE AIR QUALITY MODELING SYSTEM (ONE ATMOSPHERE)

EPA Science Inventory

This task supports ORD's strategy by providing responsive technical support of EPA's mission and provides credible state of the art air quality models and guidance. This research effort is to develop and improve the Community Multiscale Air Quality (CMAQ) modeling system, a mu...

Stem cells in genetically-engineered mouse models of prostate cancer

PubMed Central

Shibata, Maho; Shen, Michael M.

2015-01-01

The cancer stem cell model proposes that tumors have a hierarchical organization in which tumorigenic cells give rise to non-tumorigenic cells, with only a subset of stem-like cells able to propagate the tumor. In the case of prostate cancer, recent analyses of genetically engineered mouse (GEM) models have provided evidence supporting the existence of cancer stem cells in vivo. These studies suggest that cancer stem cells capable of tumor propagation exist at various stages of tumor progression from prostatic intraepithelial neoplasia (PIN) to advanced metastatic and castration-resistant disease. However, studies of stem cells in prostate cancer have been limited by available approaches for evaluating their functional properties in cell culture and transplantation assays. Given the role of the tumor microenvironment and the putative cancer stem cell niche, future studies using GEM models to analyze cancer stem cells in their native tissue microenvironment are likely to be highly informative. PMID:26341780

GEM-CEDAR Study of Ionospheric Energy Input and Joule Dissipation

NASA Technical Reports Server (NTRS)

Rastaetter, Lutz; Kuznetsova, Maria M.; Shim, Jasoon

2012-01-01

We are studying ionospheric model performance for six events selected for the GEM-CEDAR modeling challenge. DMSP measurements of electric and magnetic fields are converted into Poynting Flux values that estimate the energy input into the ionosphere. Models generate rates of ionospheric Joule dissipation that are compared to the energy influx. Models include the ionosphere models CTIPe and Weimer and the ionospheric electrodynamic outputs of global magnetosphere models SWMF, LFM, and OpenGGCM. This study evaluates the model performance in terms of overall balance between energy influx and dissipation and tests the assumption that Joule dissipation occurs locally where electromagnetic energy flux enters the ionosphere. We present results in terms of skill scores now commonly used in metrics and validation studies and we can measure the agreement in terms of temporal and spatial distribution of dissipation (i.e, location of auroral activity) along passes of the DMSP satellite with the passes' proximity to the magnetic pole and solar wind activity level.

Description and evaluation of the Community Multiscale Air Quality (CMAQ) modeling system version 5.1

EPA Science Inventory

The Community Multiscale Air Quality (CMAQ) model is a comprehensive multipollutant air quality modeling system developed and maintained by the US Environmental Protection Agency's (EPA) Office of Research and Development (ORD). Recently, version 5.1 of the CMAQ model (v5.1) was ...

Method and apparatus for detecting gem-polyhalogenated hydrocarbons

DOEpatents

Anderson, deceased, William G.; Anderson, legal representative, Johanna S.

1990-01-01

A method and optrode for detecting gem polyhalogenated hydrocarbons in a sample fluid based on a single phase Fujiwara reaction as provided. The method comprises contacting a reaction mixture with a sample fluid which contains the gem-polyhalogenated hydrocarbons. The reaction mixture comprises an aqueous solution of pyridine or derivative thereof and a hindered nitrogen base. Upon contact a fluorescent and/or chromgenic reaction product forms whose fluorescence and/or absorbance is related to the concentration of gem-polyhalogenated hydrocarbons in the sample fluid.

Multiscale modeling methods in biomechanics.

PubMed

Bhattacharya, Pinaki; Viceconti, Marco

2017-05-01

More and more frequently, computational biomechanics deals with problems where the portion of physical reality to be modeled spans over such a large range of spatial and temporal dimensions, that it is impossible to represent it as a single space-time continuum. We are forced to consider multiple space-time continua, each representing the phenomenon of interest at a characteristic space-time scale. Multiscale models describe a complex process across multiple scales, and account for how quantities transform as we move from one scale to another. This review offers a set of definitions for this emerging field, and provides a brief summary of the most recent developments on multiscale modeling in biomechanics. Of all possible perspectives, we chose that of the modeling intent, which vastly affect the nature and the structure of each research activity. To the purpose we organized all papers reviewed in three categories: 'causal confirmation,' where multiscale models are used as materializations of the causation theories; 'predictive accuracy,' where multiscale modeling is aimed to improve the predictive accuracy; and 'determination of effect,' where multiscale modeling is used to model how a change at one scale manifests in an effect at another radically different space-time scale. Consistent with how the volume of computational biomechanics research is distributed across application targets, we extensively reviewed papers targeting the musculoskeletal and the cardiovascular systems, and covered only a few exemplary papers targeting other organ systems. The review shows a research subdomain still in its infancy, where causal confirmation papers remain the most common. WIREs Syst Biol Med 2017, 9:e1375. doi: 10.1002/wsbm.1375 For further resources related to this article, please visit the WIREs website. © 2017 The Authors. WIREs Systems Biology and Medicine published by Wiley Periodicals, Inc.

Multiscale Modeling and Simulation of Material Processing

DTIC Science & Technology

2006-07-01

As a re- GIMP simulations . Fig. 2 illustrates the contact algo- suit, MPM using a single mesh tends to induce early con- rithm for the contact pair ...21-07-2006 Final Performance Report 05-01-2003 - 04-30-2006 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Multiscale Modeling and Simulation of Material...development of scaling laws for multiscale simulations from atomistic to continuum using material testing techniques, such as tension and indentation

Multi-scale heat and mass transfer modelling of cell and tissue cryopreservation

PubMed Central

Xu, Feng; Moon, Sangjun; Zhang, Xiaohui; Shao, Lei; Song, Young Seok; Demirci, Utkan

2010-01-01

Cells and tissues undergo complex physical processes during cryopreservation. Understanding the underlying physical phenomena is critical to improve current cryopreservation methods and to develop new techniques. Here, we describe multi-scale approaches for modelling cell and tissue cryopreservation including heat transfer at macroscale level, crystallization, cell volume change and mass transport across cell membranes at microscale level. These multi-scale approaches allow us to study cell and tissue cryopreservation. PMID:20047939

USERS MANUAL: LANDFILL GAS EMISSIONS MODEL - VERSION 2.0

EPA Science Inventory

The document is a user's guide for a computer model, Version 2.0 of the Landfill Gas Emissions Model (LandGEM), for estimating air pollution emissions from municipal solid waste (MSW) landfills. The model can be used to estimate emission rates for methane, carbon dioxide, nonmet...

Two new sources of reactive gaseous mercury in the free troposphere

NASA Astrophysics Data System (ADS)

Timonen, H.; Ambrose, J. L.; Jaffe, D. A.

2012-11-01

Mercury (Hg) is a neurotoxin that bioaccumulates in the food chain. Mercury is emitted to the atmosphere primarily in its elemental form, which has a long lifetime allowing global transport. It is known that atmospheric oxidation of gaseous elemental mercury (GEM) generates reactive gaseous mercury (RGM) which plays an important role in the atmospheric mercury cycle by enhancing the rate of mercury deposition to ecosystems. However, the primary GEM oxidants, and the sources and chemical composition of RGM are poorly known. Using speciated mercury measurements conducted at the Mt. Bachelor Observatory since 2005 we present two previously unidentified sources of RGM to the free troposphere (FT). Firstly, we observed elevated RGM concentrations, large RGM/GEM-ratios, and anti-correlation between RGM and GEM during Asian long-rang transport events, demonstrating that RGM is formed from GEM by in-situ oxidation in some anthropogenic pollution plumes in the FT. During the Asian pollution events the measured RGM/GEM-ratios reached peak values, up to ~0.20, which are significantly larger than ratios typically measured (RGM/GEM < 0.05) in the Asian source region. Secondly, we observed very high RGM levels - the highest reported in the FT - in clean air masses that were processed upwind of Mt. Bachelor Observatory over the Pacific Ocean. The high RGM concentrations (up to 700 pg m-3), high RGM/GEM-ratios (up to 1), and very low ozone levels during these events provide the first observational evidence indicating significant GEM oxidation in the lower FT. The identification of these processes changes our conceptual understanding of the formation and distribution of oxidized Hg in the global atmosphere.

Modelling Active Faults in Probabilistic Seismic Hazard Analysis (PSHA) with OpenQuake: Definition, Design and Experience

NASA Astrophysics Data System (ADS)

Weatherill, Graeme; Garcia, Julio; Poggi, Valerio; Chen, Yen-Shin; Pagani, Marco

2016-04-01

The Global Earthquake Model (GEM) has, since its inception in 2009, made many contributions to the practice of seismic hazard modeling in different regions of the globe. The OpenQuake-engine (hereafter referred to simply as OpenQuake), GEM's open-source software for calculation of earthquake hazard and risk, has found application in many countries, spanning a diversity of tectonic environments. GEM itself has produced a database of national and regional seismic hazard models, harmonizing into OpenQuake's own definition the varied seismogenic sources found therein. The characterization of active faults in probabilistic seismic hazard analysis (PSHA) is at the centre of this process, motivating many of the developments in OpenQuake and presenting hazard modellers with the challenge of reconciling seismological, geological and geodetic information for the different regions of the world. Faced with these challenges, and from the experience gained in the process of harmonizing existing models of seismic hazard, four critical issues are addressed. The challenge GEM has faced in the development of software is how to define a representation of an active fault (both in terms of geometry and earthquake behaviour) that is sufficiently flexible to adapt to different tectonic conditions and levels of data completeness. By exploring the different fault typologies supported by OpenQuake we illustrate how seismic hazard calculations can, and do, take into account complexities such as geometrical irregularity of faults in the prediction of ground motion, highlighting some of the potential pitfalls and inconsistencies that can arise. This exploration leads to the second main challenge in active fault modeling, what elements of the fault source model impact most upon the hazard at a site, and when does this matter? Through a series of sensitivity studies we show how different configurations of fault geometry, and the corresponding characterisation of near-fault phenomena (including hanging wall and directivity effects) within modern ground motion prediction equations, can have an influence on the seismic hazard at a site. Yet we also illustrate the conditions under which these effects may be partially tempered when considering the full uncertainty in rupture behaviour within the fault system. The third challenge is the development of efficient means for representing both aleatory and epistemic uncertainties from active fault models in PSHA. In implementing state-of-the-art seismic hazard models into OpenQuake, such as those recently undertaken in California and Japan, new modeling techniques are needed that redefine how we treat interdependence of ruptures within the model (such as mutual exclusivity), and the propagation of uncertainties emerging from geology. Finally, we illustrate how OpenQuake, and GEM's additional toolkits for model preparation, can be applied to address long-standing issues in active fault modeling in PSHA. These include constraining the seismogenic coupling of a fault and the partitioning of seismic moment between the active fault surfaces and the surrounding seismogenic crust. We illustrate some of the possible roles that geodesy can play in the process, but highlight where this may introduce new uncertainties and potential biases into the seismic hazard process, and how these can be addressed.

Estimating Fallout Building Attributes from Architectural Features and Global Earthquake Model (GEM) Building Descriptions

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

Dillon, Michael B.; Kane, Staci R.

A nuclear explosion has the potential to injure or kill tens to hundreds of thousands (or more) of people through exposure to fallout (external gamma) radiation. Existing buildings can protect their occupants (reducing fallout radiation exposures) by placing material and distance between fallout particles and individuals indoors. Prior efforts have determined an initial set of building attributes suitable to reasonably assess a given building’s protection against fallout radiation. The current work provides methods to determine the quantitative values for these attributes from (a) common architectural features and data and (b) buildings described using the Global Earthquake Model (GEM) taxonomy. Thesemore » methods will be used to improve estimates of fallout protection for operational US Department of Defense (DoD) and US Department of Energy (DOE) consequence assessment models.« less

Multi-scale modelling of rubber-like materials and soft tissues: an appraisal

PubMed Central

Puglisi, G.

2016-01-01

We survey, in a partial way, multi-scale approaches for the modelling of rubber-like and soft tissues and compare them with classical macroscopic phenomenological models. Our aim is to show how it is possible to obtain practical mathematical models for the mechanical behaviour of these materials incorporating mesoscopic (network scale) information. Multi-scale approaches are crucial for the theoretical comprehension and prediction of the complex mechanical response of these materials. Moreover, such models are fundamental in the perspective of the design, through manipulation at the micro- and nano-scales, of new polymeric and bioinspired materials with exceptional macroscopic properties. PMID:27118927

COTHERM: Modelling fluid-rock interactions in Icelandic geothermal systems

NASA Astrophysics Data System (ADS)

Thien, Bruno; Kosakowski, Georg; Kulik, Dmitrii

2014-05-01

Mineralogical alteration of reservoir rocks, driven by fluid circulation in natural or enhanced geothermal systems, is likely to influence the long-term performance of geothermal power generation. A key factor is the change of porosity due to dissolution of primary minerals and precipitation of secondary phases. Porosity changes will affect fluid circulation and solute transport, which, in turn, influence mineralogical alteration. This study is part of the Sinergia COTHERM project (COmbined hydrological, geochemical and geophysical modeling of geotTHERMal systems) that is an integrative research project aimed at improving our understanding of the sub-surface processes in magmatically-driven natural geothermal systems. We model the mineralogical and porosity evolution of Icelandic geothermal systems with 1D and 2D reactive transport models. These geothermal systems are typically high enthalphy systems where a magmatic pluton is located at a few kilometers depth. The shallow plutons increase the geothermal gradient and trigger the circulation of hydrothermal waters with a steam cap forming at shallow depth. We investigate two contrasting geothermal systems: Krafla, for which the water recharge consists of meteoritic water; and Reykjanes, for which the water recharge mainly consists of seawater. The initial rock composition is a fresh basalt. We use the GEM-Selektor geochemical modeling package [1] for calculation of kinetically controlled mineral equilibria between the rock and the ingression water. We consider basalt minerals dissolution kinetics according to Palandri & Kharaka [2]. Reactive surface areas are assumed to be geometric surface areas, and are corrected using a spherical-particle surface/mass relationship. For secondary minerals, we consider the partial equilibrium assuming that the primary mineral dissolution is slow, and the secondary mineral precipitation is fast. Comparison of our modeling results with the mineralogical assemblages observed in the field by Gudmundsson & Arnorsson [3] and by Icelandic partners of the COTHERM project suggests that the concept of partial equilibrium with instantaneous precipitation of secondary minerals is not sufficient to satisfactorily describe the experimental data. Considering kinetic controls also for secondary minerals appears as indispensable to properly describe the geothermal system evolution using a reactive transport modelling approach [4]. [1] Kulik D.A., Wagner T., Dmytrieva S.V., Kosakowski G., Hingerl F.F., Chudnenko K.V., Berner U., 2013. GEM-Selektor geochemical modeling package: revised algorithm and GEMS3K numerical kernel for coupled simulation codes. Computational Geosciences 17, 1-24. http://gems.web.psi.ch. [2] Palandri, J.L., Kharaka, Y.K., 2004. A compilation of rate parameters of water-mineral interaction kinetics for application to geochemical modelling. U.S.Geological Survey, Menlo Park, CA, pp. 1-64. [3] Gudmundsson B.T., Arnorsson S., 2005. Secondary mineral-fluid equilibria in the Krafla and Namafjall geothermal systems, Iceland. Applied Geochememistry 20, 1607-1625. [4] Kosakowski, G., & Watanabe, N., 2013. OpenGeoSys-Gem: A numerical tool for calculating geochemical and porosity changes in saturated and partially saturated media. Physics and Chemistry of the Earth, Parts A/B/C. doi:10.1016/j.pce.2013.11.008

Development of Resistive Electrode Gas Electron Multiplier (RE-GEM)

NASA Technical Reports Server (NTRS)

Yoshikawa, A.; Tamagawa, T.; Iwahashi, T.; Asami, F.; Takeuchi, Y.; Hayato, A.; Hamagaki, H.; Gunji, T.; Akimoto, R.; Nukariya, A.;

Characterization of a hybrid GEM-Micromegas detector with respect to its application in a continuously read out TPC

NASA Astrophysics Data System (ADS)

Ratza, Viktor; Ball, Markus; Liebtrau, M.; Ketzer, Bernhard

2018-02-01

In the context of the upgrade of the LHC during the second long shutdown the interaction rate of the ALICE experiment will be increased up to 50 kHz for Pb-Pb collisions. As a consequence, a continuous read-out of the Time Projection Chamber (TPC) will be required. To keep the space-charge distortions at a manageable size, the ion backflow of the charge amplification system has to be significantly reduced. At the same time an excellent detector performance and stability of the system has to be maintained. A solution with four Gaseous Electron Multipliers (GEMs) has been adopted as baseline solution for the upgraded chambers. As an alternative approach a hybrid GEM-Micromegas detector consisting of one Micromegas (MM) and two GEMs has been investigated. The recent results of the study of the hybrid GEM-Micromegas detector will be presented and compared to measurements with four GEM foils.

Divergent Mechanistic Routes for the Formation of gem-Dimethyl Groups in the Biosynthesis of Complex Polyketides

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

Poust, S; Phelan, RM; Deng, K

The gem-dimethyl groups in polyketide-derived natural products add steric bulk and, accordingly, lend increased stability to medicinal compounds, however, our ability to rationally incorporate this functional group in modified natural products is limited. In order to characterize the mechanism of gem-dimethyl group formation, with a goal toward engineering of novel compounds containing this moiety, the gem-dimethyl group producing polyketide synthase (PKS) modules of yersiniabactin and epothilone were characterized using mass spectrometry. The work demonstrated, contrary to the canonical understanding of reaction order in PKSs, that methylation can precede condensation in gem-dimethyl group producing PKS modules. Experiments showed that both PKSsmore » are able to use dimethylmalonyl acyl carrier protein (ACP) as an extender unit. Interestingly, for epothilone module8, use of dimethylmalonyl-ACP appeared to be the sole route to form a gem-dimethylated product, while the yersiniabactin PKS could methylate before or after ketosynthase condensation.« less

Contributions of natural and anthropogenic sources to ambient ammonia in the Athabasca Oil Sands and north-western Canada

NASA Astrophysics Data System (ADS)

Whaley, Cynthia H.; Makar, Paul A.; Shephard, Mark W.; Zhang, Leiming; Zhang, Junhua; Zheng, Qiong; Akingunola, Ayodeji; Wentworth, Gregory R.; Murphy, Jennifer G.; Kharol, Shailesh K.; Cady-Pereira, Karen E.

2018-02-01

Atmospheric ammonia (NH3) is a short-lived pollutant that plays an important role in aerosol chemistry and nitrogen deposition. Dominant NH3 emissions are from agriculture and forest fires, both of which are increasing globally. Even remote regions with relatively low ambient NH3 concentrations, such as northern Alberta and Saskatchewan in northern Canada, may be of interest because of industrial oil sands emissions and a sensitive ecological system. A previous attempt to model NH3 in the region showed a substantial negative bias compared to satellite and aircraft observations. Known missing sources of NH3 in the model were re-emission of NH3 from plants and soils (bidirectional flux) and forest fire emissions, but the relative impact of these sources on NH3 concentrations was unknown. Here we have used a research version of the high-resolution air quality forecasting model, GEM-MACH, to quantify the relative impacts of semi-natural (bidirectional flux of NH3 and forest fire emissions) and direct anthropogenic (oil sand operations, combustion of fossil fuels, and agriculture) sources on ammonia volume mixing ratios, both at the surface and aloft, with a focus on the Athabasca Oil Sands region during a measurement-intensive campaign in the summer of 2013. The addition of fires and bidirectional flux to GEM-MACH has improved the model bias, slope, and correlation coefficients relative to ground, aircraft, and satellite NH3 measurements significantly.By running the GEM-MACH-Bidi model in three configurations and calculating their differences, we find that averaged over Alberta and Saskatchewan during this time period an average of 23.1 % of surface NH3 came from direct anthropogenic sources, 56.6 % (or 1.24 ppbv) from bidirectional flux (re-emission from plants and soils), and 20.3 % (or 0.42 ppbv) from forest fires. In the NH3 total column, an average of 19.5 % came from direct anthropogenic sources, 50.0 % from bidirectional flux, and 30.5 % from forest fires. The addition of bidirectional flux and fire emissions caused the overall average net deposition of NHx across the domain to be increased by 24.5 %. Note that forest fires are very episodic and their contributions will vary significantly for different time periods and regions.This study is the first use of the bidirectional flux scheme in GEM-MACH, which could be generalized for other volatile or semi-volatile species. It is also the first time CrIS (Cross-track Infrared Sounder) satellite observations of NH3 have been used for model evaluation, and the first use of fire emissions in GEM-MACH at 2.5 km resolution.

Improving the Algae Bloom Prediction through the Assimilation of the Remotely Sensed Chlorophyll-A Data in a Generic Ecological Model in the North Sea

NASA Astrophysics Data System (ADS)

El Serafy, Ghada

2010-05-01

Harmful algae can cause damage to co-existing organisms, tourism and farmers. Accurate predictions of algal future composition and abundance as well as when and where algal blooms may occur could help early warning and mitigating. The Generic Ecological Model, GEM, [Blauw et al 2008] is an instrument that can be applied to any water system (fresh, transitional or coastal) to calculate the primary production, chlorophyll-a concentration and phytoplankton species composition. It consists of physical, chemical and ecological model components which are coupled together to build one generic and flexible modeling tool. For the North Sea, the model has been analyzed to assess sensitivity of the simulated chlorophyll-a concentration to a subset of ecologically significant set of factors. The research led to the definition of the most significant set of parameters to the algae blooming process in the North Sea [Salacinska et al 2009]. In order to improve the prediction of the model, the set of parameters and the chlorophyll-a concentration can be further estimated through the use of data assimilation. In this research, the Ensemble Kalman Filter (EnKF) data assimilation technique is used to assimilate the chlorophyll-a data of the North Sea, retrieved from MEdium Resolution Imaging Sensor (MERIS) spectrometer data [Peters et al 2005], in the GEM model. The chlorophyll-a data includes concentrations and error information that enable their use in data assimilation. For the same purpose, the uncertainty of the ecological generic model, GEM has been quantified by means of Monte Carlo approach. Through a study covering the year of 2003, the research demonstrates that both data and model are sufficiently robust for a successful assimilation. The results show that through the assimilation of the satellite data, a better description of the algae bloom has been achieved and an improvement of the capability of the model to predict the algae bloom for the North Sea has been confirmed. Blauw A.N., Los F.J., Bokhorst M., Erftemeijer P.L.A., (2009), GEM: a Generic Ecological Model for estuaries and coastal waters. Journal of Hydrobiologia, Volume 618, Number 1, 175-198. Peters, S.W.M., Eleveld, M. Pasterkamp, R., Woerd, H. van der, Devolder, M., Jans, S., Park, Y., Ruddick, K., Block, T., Brockmann, C., Doerffer, R., Krasemann, H., Röttgers, R., Schönfeld, W., Jørgensen, P.V., Tilstone, G., Martinez-Vicente, V., Moore, G., Sørensen, K., Høkedal, J., Johnsen, T.M., Lømsland, E.R., Aas, E. (2005). Atlas of Chlorophyll-a concentration for the North Sea based on MERIS imagery of 2003. IVM report, Vrije Universiteit Amsterdam, 117 pp. ISBN 90-5192-026-1. Salacinska K., El Serafy G.Y., Blauw A., Los F.J., (2009) Sensitivity analysis of the two dimensional application of the Generic Ecological Model (GEM) to algal bloom prediction in the North Sea, Journal of Ecological Modeling, volume 221, 7, pp 178-190, DOI: 10.1016/j.ecolmodel.2009.10.001

The Effects of HSP27 on Gemcitabine-Resistant Pancreatic Cancer Cell Line Through Snail.

PubMed

Zhang, Song; Zhang, Xiao-qi; Huang, Shu-ling; Chen, Min; Shen, Shan-shan; Ding, Xi-wei; Lv, Ying; Zou, Xiao-ping

2015-10-01

To evaluate the regulation mechanism of heat shock protein 27 (HSP27) on gemcitabine (GEM) resistance of pancreatic cancer cell. The expression vectors pEGFP-C1-HSP27 and the vectors of MicroRNA targeting Snail were introduced into GEM-sensitive pancreatic cancer SW1990 cells, and the vectors of small hairpin RNA targeting HSP27 were transfected into SW1990 and GEM-resistant SW1990/GEM cells. The expressions of HSP27, p-HSP27 (Ser82), Snail, ERCC1, and E-cadherin were evaluated by Western blotting. The sensitivity of transfected cells to GEM was detected by CCK-8 assay and Annexin V-FITC apoptosis assay. As compared to SW1990, SW1990/GEM showed significantly increased expressions of HSP27, p-HSP27, Snail and ERCC1 with decreased expression of E-cadherin. By increasing HSP27 expression, we found increase of Snail and ERCC1 with reduction of E-cadherin expressions, while reduction of HSP27 expression caused reduction of Snail and ERCC1 but increase of E-cadherin expressions. Downregulation of Snail resulted in the reduction of ERCC1 expression and increase of E-cadherin. Furthermore, downregulation of HSP27 or snail caused increased GEM sensitivity of pancreatic cancer cells, and upregulation of HSP27 showed the opposite results. There is an inverse correlation between HSP27 expression and GEM sensitivity of SW1990 cells, which might be realized by regulating E-cadherin and ERCC1 expressions through Snail.

Multi-Scale Validation of a Nanodiamond Drug Delivery System and Multi-Scale Engineering Education

ERIC Educational Resources Information Center

Schwalbe, Michelle Kristin

2010-01-01

This dissertation has two primary concerns: (i) evaluating the uncertainty and prediction capabilities of a nanodiamond drug delivery model using Bayesian calibration and bias correction, and (ii) determining conceptual difficulties of multi-scale analysis from an engineering education perspective. A Bayesian uncertainty quantification scheme…

A preclinical orthotopic model for glioblastoma recapitulates key features of human tumors and demonstrates sensitivity to a combination of MEK and PI3K pathway inhibitors.

PubMed

El Meskini, Rajaa; Iacovelli, Anthony J; Kulaga, Alan; Gumprecht, Michelle; Martin, Philip L; Baran, Maureen; Householder, Deborah B; Van Dyke, Terry; Weaver Ohler, Zoë

2015-01-01

Current therapies for glioblastoma multiforme (GBM), the highest grade malignant brain tumor, are mostly ineffective, and better preclinical model systems are needed to increase the successful translation of drug discovery efforts into the clinic. Previous work describes a genetically engineered mouse (GEM) model that contains perturbations in the most frequently dysregulated networks in GBM (driven by RB, KRAS and/or PI3K signaling and PTEN) that induce development of Grade IV astrocytoma with properties of the human disease. Here, we developed and characterized an orthotopic mouse model derived from the GEM that retains the features of the GEM model in an immunocompetent background; however, this model is also tractable and efficient for preclinical evaluation of candidate therapeutic regimens. Orthotopic brain tumors are highly proliferative, invasive and vascular, and express histology markers characteristic of human GBM. Primary tumor cells were examined for sensitivity to chemotherapeutics and targeted drugs. PI3K and MAPK pathway inhibitors, when used as single agents, inhibited cell proliferation but did not result in significant apoptosis. However, in combination, these inhibitors resulted in a substantial increase in cell death. Moreover, these findings translated into the in vivo orthotopic model: PI3K or MAPK inhibitor treatment regimens resulted in incomplete pathway suppression and feedback loops, whereas dual treatment delayed tumor growth through increased apoptosis and decreased tumor cell proliferation. Analysis of downstream pathway components revealed a cooperative effect on target downregulation. These concordant results, together with the morphologic similarities to the human GBM disease characteristics of the model, validate it as a new platform for the evaluation of GBM treatment. © 2015. Published by The Company of Biologists Ltd.

A preclinical orthotopic model for glioblastoma recapitulates key features of human tumors and demonstrates sensitivity to a combination of MEK and PI3K pathway inhibitors

PubMed Central

El Meskini, Rajaa; Iacovelli, Anthony J.; Kulaga, Alan; Gumprecht, Michelle; Martin, Philip L.; Baran, Maureen; Householder, Deborah B.; Van Dyke, Terry; Weaver Ohler, Zoë

2015-01-01

Current therapies for glioblastoma multiforme (GBM), the highest grade malignant brain tumor, are mostly ineffective, and better preclinical model systems are needed to increase the successful translation of drug discovery efforts into the clinic. Previous work describes a genetically engineered mouse (GEM) model that contains perturbations in the most frequently dysregulated networks in GBM (driven by RB, KRAS and/or PI3K signaling and PTEN) that induce development of Grade IV astrocytoma with properties of the human disease. Here, we developed and characterized an orthotopic mouse model derived from the GEM that retains the features of the GEM model in an immunocompetent background; however, this model is also tractable and efficient for preclinical evaluation of candidate therapeutic regimens. Orthotopic brain tumors are highly proliferative, invasive and vascular, and express histology markers characteristic of human GBM. Primary tumor cells were examined for sensitivity to chemotherapeutics and targeted drugs. PI3K and MAPK pathway inhibitors, when used as single agents, inhibited cell proliferation but did not result in significant apoptosis. However, in combination, these inhibitors resulted in a substantial increase in cell death. Moreover, these findings translated into the in vivo orthotopic model: PI3K or MAPK inhibitor treatment regimens resulted in incomplete pathway suppression and feedback loops, whereas dual treatment delayed tumor growth through increased apoptosis and decreased tumor cell proliferation. Analysis of downstream pathway components revealed a cooperative effect on target downregulation. These concordant results, together with the morphologic similarities to the human GBM disease characteristics of the model, validate it as a new platform for the evaluation of GBM treatment. PMID:25431423

COMMUNITY MULTISCALE AIR QUALITY ( CMAQ ) MODEL - QUALITY ASSURANCE AND VERSION CONTROL

EPA Science Inventory

This presentation will be given to the EPA Exposure Modeling Workgroup on January 24, 2006. The quality assurance and version control procedures for the Community Multiscale Air Quality (CMAQ) Model are presented. A brief background of CMAQ is given, then issues related to qual...

Evaluation of the Community Multiscale Air Quality (CMAQ) Model Version 5.2

EPA Science Inventory

The Community Multiscale Air Quality (CMAQ) model is a state-of-the-science air quality model that simulates the emission, transport and fate of numerous air pollutants, including ozone and particulate matter. The Computational Exposure Division (CED) of the U.S. Environmental Pr...

Evaluation of the Community Multi-scale Air Quality Model Version 5.2

EPA Science Inventory

The Community Multiscale Air Quality (CMAQ) model is a state-of-the-science air quality model that simulates the emission, transport and fate of numerous air pollutants, including ozone and particulate matter. The Computational Exposure Division (CED) of the U.S. Environmental Pr...

Multiscale Simulation Framework for Coupled Fluid Flow and Mechanical Deformation

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

Hou, Thomas; Efendiev, Yalchin; Tchelepi, Hamdi

2016-05-24

Our work in this project is aimed at making fundamental advances in multiscale methods for flow and transport in highly heterogeneous porous media. The main thrust of this research is to develop a systematic multiscale analysis and efficient coarse-scale models that can capture global effects and extend existing multiscale approaches to problems with additional physics and uncertainties. A key emphasis is on problems without an apparent scale separation. Multiscale solution methods are currently under active investigation for the simulation of subsurface flow in heterogeneous formations. These procedures capture the effects of fine-scale permeability variations through the calculation of specialized coarse-scalemore » basis functions. Most of the multiscale techniques presented to date employ localization approximations in the calculation of these basis functions. For some highly correlated (e.g., channelized) formations, however, global effects are important and these may need to be incorporated into the multiscale basis functions. Other challenging issues facing multiscale simulations are the extension of existing multiscale techniques to problems with additional physics, such as compressibility, capillary effects, etc. In our project, we explore the improvement of multiscale methods through the incorporation of additional (single-phase flow) information and the development of a general multiscale framework for flows in the presence of uncertainties, compressible flow and heterogeneous transport, and geomechanics. We have considered (1) adaptive local-global multiscale methods, (2) multiscale methods for the transport equation, (3) operator-based multiscale methods and solvers, (4) multiscale methods in the presence of uncertainties and applications, (5) multiscale finite element methods for high contrast porous media and their generalizations, and (6) multiscale methods for geomechanics.« less

Multiscale analysis and computation for flows in heterogeneous media

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

Efendiev, Yalchin; Hou, T. Y.; Durlofsky, L. J.

Our work in this project is aimed at making fundamental advances in multiscale methods for flow and transport in highly heterogeneous porous media. The main thrust of this research is to develop a systematic multiscale analysis and efficient coarse-scale models that can capture global effects and extend existing multiscale approaches to problems with additional physics and uncertainties. A key emphasis is on problems without an apparent scale separation. Multiscale solution methods are currently under active investigation for the simulation of subsurface flow in heterogeneous formations. These procedures capture the effects of fine-scale permeability variations through the calculation of specialized coarse-scalemore » basis functions. Most of the multiscale techniques presented to date employ localization approximations in the calculation of these basis functions. For some highly correlated (e.g., channelized) formations, however, global effects are important and these may need to be incorporated into the multiscale basis functions. Other challenging issues facing multiscale simulations are the extension of existing multiscale techniques to problems with additional physics, such as compressibility, capillary effects, etc. In our project, we explore the improvement of multiscale methods through the incorporation of additional (single-phase flow) information and the development of a general multiscale framework for flows in the presence of uncertainties, compressible flow and heterogeneous transport, and geomechanics. We have considered (1) adaptive local-global multiscale methods, (2) multiscale methods for the transport equation, (3) operator-based multiscale methods and solvers, (4) multiscale methods in the presence of uncertainties and applications, (5) multiscale finite element methods for high contrast porous media and their generalizations, and (6) multiscale methods for geomechanics. Below, we present a brief overview of each of these contributions.« less

DEVELOPMENT OF AN AGGREGATION AND EPISODE SELECTION SCHEME TO SUPPORT THE MODELS-3 COMMUNITY MULTISCALE AIR QUALITY MODEL

EPA Science Inventory

The development of an episode selection and aggregation approach, designed to support distributional estimation of use with the Models-3 Community Multiscale Air Quality (CMAQ) model, is described. The approach utilized cluster analysis of the 700-hPa east-west and north-south...

APPLICATION OF THE MODELS-3 COMMUNITY MULTI-SCALE AIR QUALITY (CMAQ) MODEL SYSTEM TO SOS/NASHVILLE 1999

EPA Science Inventory

The Models-3 Community Multi-scale Air Quality (CMAQ) model, first released by the USEPA in 1999 (Byun and Ching. 1999), continues to be developed and evaluated. The principal components of the CMAQ system include a comprehensive emission processor known as the Sparse Matrix O...

Spatial analysis of future East Asian seasonal temperature using two regional climate model simulations

NASA Astrophysics Data System (ADS)

Kim, Yura; Jun, Mikyoung; Min, Seung-Ki; Suh, Myoung-Seok; Kang, Hyun-Suk

2016-05-01

CORDEX-East Asia, a branch of the coordinated regional climate downscaling experiment (CORDEX) initiative, provides high-resolution climate simulations for the domain covering East Asia. This study analyzes temperature data from regional climate models (RCMs) participating in the CORDEX - East Asia region, accounting for the spatial dependence structure of the data. In particular, we assess similarities and dissimilarities of the outputs from two RCMs, HadGEM3-RA and RegCM4, over the region and over time. A Bayesian functional analysis of variance (ANOVA) approach is used to simultaneously model the temperature patterns from the two RCMs for the current and future climate. We exploit nonstationary spatial models to handle the spatial dependence structure of the temperature variable, which depends heavily on latitude and altitude. For a seasonal comparison, we examine changes in the winter temperature in addition to the summer temperature data. We find that the temperature increase projected by RegCM4 tends to be smaller than the projection of HadGEM3-RA for summers, and that the future warming projected by HadGEM3-RA tends to be weaker for winters. Also, the results show that there will be a warming of 1-3°C over the region in 45 years. More specifically, the warming pattern clearly depends on the latitude, with greater temperature increases in higher latitude areas, which implies that warming may be more severe in the northern part of the domain.

Multi-Scale Computational Models for Electrical Brain Stimulation

PubMed Central

Seo, Hyeon; Jun, Sung C.

2017-01-01

Electrical brain stimulation (EBS) is an appealing method to treat neurological disorders. To achieve optimal stimulation effects and a better understanding of the underlying brain mechanisms, neuroscientists have proposed computational modeling studies for a decade. Recently, multi-scale models that combine a volume conductor head model and multi-compartmental models of cortical neurons have been developed to predict stimulation effects on the macroscopic and microscopic levels more precisely. As the need for better computational models continues to increase, we overview here recent multi-scale modeling studies; we focused on approaches that coupled a simplified or high-resolution volume conductor head model and multi-compartmental models of cortical neurons, and constructed realistic fiber models using diffusion tensor imaging (DTI). Further implications for achieving better precision in estimating cellular responses are discussed. PMID:29123476

The Ozone Layer. UNEP/GEMS Environment Library No. 2.

ERIC Educational Resources Information Center

United Nations Environment Programme, Nairobi (Kenya).

Since the United Nations Environment Program (UNEP) was created, more than a dozen years ago, public understanding of the environmental issues confronting our planet has increased enormously. The Global Environment Monitoring System (GEMS) has provided several environmental assessments. The aim of the UNEP/GEMS Environment Library is to provide…

Imaging Demonstration of a Glass Gas Electron Multiplier with Electronic Charge Readout

NASA Astrophysics Data System (ADS)

Mitsuya, Yuki; Thuiner, Patrik; Oliveri, Eraldo; Resnati, Filippo; Stenis, Miranda van; Fujiwara, Takeshi; Takahashi, Hiroyuki; Ropelewski, Leszek

2018-02-01

We have developed a Glass Gas Electron Multiplier (Glass GEM, G-GEM), which is composed of two copper electrodes separated by a photosensitive etchable glass substrate having holes arranged in a hexagonal pattern. In this paper, we report the result of imaging using a G-GEM combined with a 2D electronic charge readout. We used a crystallized photosensitive etchable glass as the G-GEM substrate. A precise X-ray image of a small mammal was successfully obtained with position resolutions of approximately 110 to 140 μm in RMS.

Discriminating cosmic muons and X-rays based on rise time using a GEM detector

NASA Astrophysics Data System (ADS)

Wu, Hui-Yin; Zhao, Sheng-Ying; Wang, Xiao-Dong; Zhang, Xian-Ming; Qi, Hui-Rong; Zhang, Wei; Wu, Ke-Yan; Hu, Bi-Tao; Zhang, Yi

2016-08-01

Gas electron multiplier (GEM) detectors have been used in cosmic muon scattering tomography and neutron imaging over the last decade. In this work, a triple GEM device with an effective readout area of 10 cm × 10 cm is developed, and a method of discriminating between cosmic muons and X-rays based on rise time is tested. The energy resolution of the GEM detector is tested by 55Fe ray source to prove the GEM detector has a good performance. Analysis of the complete signal-cycles allows us to get the rise time and pulse heights. The experiment result indicates that cosmic muons and X-rays can be discriminated with an appropriate rise time threshold. Supported by National Natural Science Foundation of China (11135002, 11275235, 11405077, 11575073)

Measurement Of Gas Electron Multiplier (GEM) Detector Characteristics

NASA Astrophysics Data System (ADS)

Park, Seongtae; Baldelomar, Edwin; Park, Kwangjune; Sosebee, Mark; White, Andy; Yu, Jaehoon

2011-06-01

The High Energy Physics group of the University of Texas at Arlington has been developing gas electron multiplier detectors to use them as sensitive gap detectors in digital hadron calorimeters for the International Linear Collider, a future high energy particle accelerator. For this purpose, we constructed numerous GEM detectors that employ double GEM layers. In this study, two kinds of prototype GEM detectors were tested; one with 28×28 cm2 active area double GEM structure with a 3 mm drift gap, a 1 mm transfer gap and a 1 mm induction gap and the other with two 3×3 cm2 GEM foils in the amplifier stage with a 5 mm drift gap, a 2 mm transfer gap and a 1 mm induction gap. The detectors' characteristics from exposure to high-energy charged particles and other radiations were measured using cosmic rays and 55Fe radioactive source. From the 55Fe tests, we observed two well separated characteristic X-ray emission peaks and confirmed the detectors' functionality. We also measured chamber gains to be over 6000 at a high voltage of 395 V across each GEM electrode. The responses to cosmic rays show the spectra that fit well to Landau distributions as expected from minimum ionizing particles.

Performance Evaluation of the COBRA GEM for the Application of the TPC

NASA Astrophysics Data System (ADS)

Terasaki, Kohei; Hamagaki, Hideki; Gunji, Taku; Yamaguchi, Yorito

2014-09-01

Suppression of the back-drifting ions from avalanche region to drift space (IBF: Ion Backflow) is the key for a Time Projection Chamber (TPC) since IBF easily distorts the drift field. To suppress IBF, Gating Grid system is widely used for the TPC but this limits the data taking rate. Gas Electron Multiplier (GEM) has advantages in the reduction of IBF and high rate capability. By adopting GEM, it is possible to run a TPC continuously under high rate and high multiplicity conditions. Motivated by the study of IBF reduction for RICH with Thick COBRA, which has been developed by F. A. Amero et al., we developed COBRA GEMs for the application of a TPC. With a stack configuration, IBF reaches about 0.1 ~ 0.5%, which is ×5--10 better IBF than the standard GEMs. However, the measured energy resolution with COBRA is 20% (σ) and this is much worse than the resolution with standard GEMs. Measurement of long-time stability of gain indicates that gain of COBRA varies significantly due to charging up effect. Simulation studies based on Garfield++ are performed for understanding quantitatively the reasons of worse energy resolution and instability of gain. In this presentation, we will report the simulation studies together with the measured performance of the COBRA GEM.

Transition between inverse and direct energy cascades in multiscale optical turbulence

DOE PAGES

Malkin, V. M.; Fisch, N. J.

2018-03-06

Transition between inverse and direct energy cascades in multiscale optical turbulence. Multiscale turbulence naturally develops and plays an important role in many fluid, gas, and plasma phenomena. Statistical models of multiscale turbulence usually employ Kolmogorov hypotheses of spectral locality of interactions (meaning that interactions primarily occur between pulsations of comparable scales) and scale-invariance of turbulent pulsations. However, optical turbulence described by the nonlinear Schrodinger equation exhibits breaking of both the Kolmogorov locality and scale-invariance. A weaker form of spectral locality that holds for multi-scale optical turbulence enables a derivation of simplified evolution equations that reduce the problem to a singlemore » scale modeling. We present the derivation of these equations for Kerr media with random inhomogeneities. Then, we find the analytical solution that exhibits a transition between inverse and direct energy cascades in optical turbulence.« less

Construction of multi-scale consistent brain networks: methods and applications.

PubMed

Ge, Bao; Tian, Yin; Hu, Xintao; Chen, Hanbo; Zhu, Dajiang; Zhang, Tuo; Han, Junwei; Guo, Lei; Liu, Tianming

2015-01-01

Mapping human brain networks provides a basis for studying brain function and dysfunction, and thus has gained significant interest in recent years. However, modeling human brain networks still faces several challenges including constructing networks at multiple spatial scales and finding common corresponding networks across individuals. As a consequence, many previous methods were designed for a single resolution or scale of brain network, though the brain networks are multi-scale in nature. To address this problem, this paper presents a novel approach to constructing multi-scale common structural brain networks from DTI data via an improved multi-scale spectral clustering applied on our recently developed and validated DICCCOLs (Dense Individualized and Common Connectivity-based Cortical Landmarks). Since the DICCCOL landmarks possess intrinsic structural correspondences across individuals and populations, we employed the multi-scale spectral clustering algorithm to group the DICCCOL landmarks and their connections into sub-networks, meanwhile preserving the intrinsically-established correspondences across multiple scales. Experimental results demonstrated that the proposed method can generate multi-scale consistent and common structural brain networks across subjects, and its reproducibility has been verified by multiple independent datasets. As an application, these multi-scale networks were used to guide the clustering of multi-scale fiber bundles and to compare the fiber integrity in schizophrenia and healthy controls. In general, our methods offer a novel and effective framework for brain network modeling and tract-based analysis of DTI data.

A perspective on modeling the multiscale response of energetic materials

NASA Astrophysics Data System (ADS)

Rice, Betsy M.

2017-01-01

The response of an energetic material to insult is perhaps one of the most difficult processes to model due to concurrent chemical and physical phenomena occurring over scales ranging from atomistic to continuum. Unraveling the interdependencies of these complex processes across the scales through modeling can only be done within a multiscale framework. In this paper, I will describe progress in the development of a predictive, experimentally validated multiscale reactive modeling capability for energetic materials at the Army Research Laboratory. I will also describe new challenges and research opportunities that have arisen in the course of our development which should be pursued in the future.

Evaluation of the Community Multi-scale Air Quality (CMAQ) Model Version 5.1

EPA Science Inventory

The Community Multiscale Air Quality (CMAQ) model is a state-of-the-science air quality model that simulates the emission, transport and fate of numerous air pollutants, including ozone and particulate matter. The Computational Exposure Division (CED) of the U.S. Environmental Pr...

Overview and Evaluation of the Community Multiscale Air Quality Model Version 5.2

EPA Science Inventory

The Community Multiscale Air Quality (CMAQ) model is a state-of-the-science air quality model that simulates the emission, transport and fate of numerous air pollutants, including ozone and particulate matter. The Computational Exposure Division (CED) of the U.S. Environmental Pr...

Evaluation of the Community Multi-scale Air Quality (CMAQ) Model Version 5.2

EPA Science Inventory

The Community Multiscale Air Quality (CMAQ) model is a state-of-the-science air quality model that simulates the emission, transport and fate of numerous air pollutants, including ozone and particulate matter. The Computational Exposure Division (CED) of the U.S. Environmental Pr...

Incremental Testing of the Community Multiscale Air Quality (CMAQ) Modeling System Version 4.7

EPA Science Inventory

This paper describes the scientific and structural updates to the latest release of the Community Multiscale Air Quality (CMAQ) modeling system version 4.7 (v4.7) and points the reader to additional resources for further details. The model updates were evaluated relative to obse...

Extending the Community Multiscale Air Quality (CMAQ) Modeling System to Hemispheric Scales: Overview of Process Considerations and Initial Applications

EPA Science Inventory

The Community Multiscale Air Quality (CMAQ) modeling system is extended to simulate ozone, particulate matter, and related precursor distributions throughout the Northern Hemisphere. Modeled processes were examined and enhanced to suitably represent the extended space and timesca...

Activity of convective coupled equatorial wave in tropical Tropopause layer in reanalysis and high-top CMIP5 models

NASA Astrophysics Data System (ADS)

Harza, Alia; Lubis, Sandro W.; Setiawan, Sonni

2018-05-01

The activity of convectively coupled equatorial waves (CCEWs), including Kelvin waves, Mixed Rossby-Gravity (MRG), and Equatorial Rossby (ER), in the tropical tropopause layer (TTL) is investigated in the Reanalysis and nine high-top CMIP5 models using the zonal wave number-frequency spectral analysis with equatorially symmetric-antisymmetric decomposition. We found that the TTL activities in the high-top CMIP5 models show significant difference among the high-top CMIP5 models with respect to the observation. The MIROC and HadGEM2-CC models work best in simulating Kelvin wave in the TTL, while the HadGEM2-CC and MPI-ESM-LR models work best in simulating MRG waves. The ER waves in TTL are best simulated in the MRI-CGCM model. None of the models are good in simulating all waves at once. It is concluded that the broad range of wave activity found in the different CMIP5 models depend on the convective parameterization used by each model and the representation of the tropical stratosphere variability, including the QBO.

Mechanical Properties of Graphene Nanoplatelet/Carbon Fiber/Epoxy Hybrid Composites: Multiscale Modeling and Experiments

NASA Technical Reports Server (NTRS)

Hadden, C. M.; Klimek-McDonald, D. R.; Pineda, E. J.; King, J. A.; Reichanadter, A. M.; Miskioglu, I.; Gowtham, S.; Odegard, G. M.

2015-01-01

Because of the relatively high specific mechanical properties of carbon fiber/epoxy composite materials, they are often used as structural components in aerospace applications. Graphene nanoplatelets (GNPs) can be added to the epoxy matrix to improve the overall mechanical properties of the composite. The resulting GNP/carbon fiber/epoxy hybrid composites have been studied using multiscale modeling to determine the influence of GNP volume fraction, epoxy crosslink density, and GNP dispersion on the mechanical performance. The hierarchical multiscale modeling approach developed herein includes Molecular Dynamics (MD) and micromechanical modeling, and it is validated with experimental testing of the same hybrid composite material system. The results indicate that the multiscale modeling approach is accurate and provides physical insight into the composite mechanical behavior. Also, the results quantify the substantial impact of GNP volume fraction and dispersion on the transverse mechanical properties of the hybrid composite while the effect on the axial properties is shown to be insignificant.

Mechanical Properties of Graphene Nanoplatelet/Carbon Fiber/Epoxy Hybrid Composites: Multiscale Modeling and Experiments

NASA Technical Reports Server (NTRS)

Hadden, C. M.; Klimek-McDonald, D. R.; Pineda, E. J.; King, J. A.; Reichanadter, A. M.; Miskioglu, I.; Gowtham, S.; Odegard, G. M.

2015-01-01

Because of the relatively high specific mechanical properties of carbon fiber/epoxy composite materials, they are often used as structural components in aerospace applications. Graphene nanoplatelets (GNPs) can be added to the epoxy matrix to improve the overall mechanical properties of the composite. The resulting GNP/carbon fiber/epoxy hybrid composites have been studied using multiscale modeling to determine the influence of GNP volume fraction, epoxy crosslink density, and GNP dispersion on the mechanical performance. The hierarchical multiscale modeling approach developed herein includes Molecular Dynamics (MD) and micromechanical modeling, and it is validated with experimental testing of the same hybrid composite material system. The results indicate that the multiscale modeling approach is accurate and provides physical insight into the composite mechanical behavior. Also, the results quantify the substantial impact of GNP volume fraction and dispersion on the transverse mechanical properties of the hybrid composite, while the effect on the axial properties is shown to be insignificant.

Mechanical Properties of Graphene Nanoplatelet Carbon Fiber Epoxy Hybrid Composites: Multiscale Modeling and Experiments

NASA Technical Reports Server (NTRS)

Hadden, Cameron M.; Klimek-McDonald, Danielle R.; Pineda, Evan J.; King, Julie A.; Reichanadter, Alex M.; Miskioglu, Ibrahim; Gowtham, S.; Odegard, Gregory M.

2015-01-01

Because of the relatively high specific mechanical properties of carbon fiber/epoxy composite materials, they are often used as structural components in aerospace applications. Graphene nanoplatelets (GNPs) can be added to the epoxy matrix to improve the overall mechanical properties of the composite. The resulting GNP/carbon fiber/epoxy hybrid composites have been studied using multiscale modeling to determine the influence of GNP volume fraction, epoxy crosslink density, and GNP dispersion on the mechanical performance. The hierarchical multiscale modeling approach developed herein includes Molecular Dynamics (MD) and micromechanical modeling, and it is validated with experimental testing of the same hybrid composite material system. The results indicate that the multiscale modeling approach is accurate and provides physical insight into the composite mechanical behavior. Also, the results quantify the substantial impact of GNP volume fraction and dispersion on the transverse mechanical properties of the hybrid composite, while the effect on the axial properties is shown to be insignificant.

High-resolution time-frequency representation of EEG data using multi-scale wavelets

NASA Astrophysics Data System (ADS)

Li, Yang; Cui, Wei-Gang; Luo, Mei-Lin; Li, Ke; Wang, Lina

2017-09-01

An efficient time-varying autoregressive (TVAR) modelling scheme that expands the time-varying parameters onto the multi-scale wavelet basis functions is presented for modelling nonstationary signals and with applications to time-frequency analysis (TFA) of electroencephalogram (EEG) signals. In the new parametric modelling framework, the time-dependent parameters of the TVAR model are locally represented by using a novel multi-scale wavelet decomposition scheme, which can allow the capability to capture the smooth trends as well as track the abrupt changes of time-varying parameters simultaneously. A forward orthogonal least square (FOLS) algorithm aided by mutual information criteria are then applied for sparse model term selection and parameter estimation. Two simulation examples illustrate that the performance of the proposed multi-scale wavelet basis functions outperforms the only single-scale wavelet basis functions or Kalman filter algorithm for many nonstationary processes. Furthermore, an application of the proposed method to a real EEG signal demonstrates the new approach can provide highly time-dependent spectral resolution capability.

Ground and Helicopter Emergency Medical Services Time Tradeoffs Assessed with Geographic Information.

PubMed

Widener, Michael J; Ginsberg, Zac; Schleith, Daniel; Floccare, Douglas J; Hirshon, Jon Mark; Galvagno, Samuel

2015-07-01

We describe how geographic information systems (GIS) can be used to assess and compare estimated transport time for helicopter and ground emergency medical services. Recent research shows that while the odds of a trauma patient's survival increase with helicopter emergency medical services (HEMS), they may not increase to the extent necessary to make HEMS cost effective. This study offers an analytic tool to objectively quantify the patient travel time advantage that HEMS offers compared to ground emergency medical services (GEMS). Using helicopter dispatch data from the Maryland State Police from 2000-2011, we computed transport time estimates for HEMS and GEMS, compare these results to a reference transport time of 60 min, and use geospatial interpolation to extrapolate the total response times for each mode across the study region. Mapping the region's trauma incidents and modeling response times, our findings indicate the GIS framework for calculating transportation time tradeoffs is useful in identifying which areas can be better served by HEMS or GEMS. The use of GIS and the analytical methodology described in this study present a method to compare transportation by air and ground in the prehospital setting that accounts for how mode, distance, and road infrastructure impact total transport time. Whether used to generate regional maps in advance or applied real-time, the presented framework provides a tool to identify earlier incident locations that favor HEMS over GEMS transport modes.

WW Geminorum: An Early B-type Eclipsing Binary Evolving into the Contact Phase

NASA Astrophysics Data System (ADS)

Yang, Y.-G.; Yang, Y.; Dai, H.-F.; Yin, X.-G.

2014-11-01

WW Gem is a B-type eclipsing binary with a period of 1.2378 days. The CCD photometry of this binary was performed in 2013 December using the 85 cm telescope at the Xinglong Stations of the National Astronomical Observatories of China. Using the updated W-D program, the photometric model was deduced from the VRI light curves. The results imply that WW Gem is a near-contact eclipsing binary whose primary component almost fills its Roche lobe. The photometric mass ratio is q ph = 0.48(± 0.05). All collected times of minimum light, including two new ones, were used for the period studies. The orbital period changes of WW Gem could be described by an upward parabola, possibly overlaid by a light-time orbit with a period of P mod = 7.41(± 0.04) yr and a semi-amplitude of A = 0.0079 days(± 0.0005 days), respectively. This kind of cyclic oscillation may be attributed to the light-travel time effect via the third body. The long-term period increases at a rate of dP/dt = +3.47(±0.04) × 10-8 day yr-1, which may be explained by the conserved mass transfer from the less massive component to the more massive one. With mass transfer, the massive binary WW Gem may be evolving into a contact binary.

Gemfibrozil, food and drug administration-approved lipid-lowering drug, increases longevity in mouse model of late infantile neuronal ceroid lipofuscinosis.

PubMed

Ghosh, Arunava; Rangasamy, Suresh Babu; Modi, Khushbu K; Pahan, Kalipada

2017-05-01

Late Infantile Neuronal Ceroid Lipofuscinosis (LINCL) is a rare neurodegenerative disease caused by mutations in the Cln2 gene that leads to deficiency or loss of function of the tripeptidyl peptidase 1 (TPP1) enzyme. TPP1 deficiency is known to cause the accumulation of autofluoroscent lipid-protein pigments in brain. Similar to other neurodegenerative disorders, LINCL is also associated with neuroinflammation and neuronal damage. Despite investigations, no effective therapy is currently available for LINCL. Therefore, we administered gemfibrozil (gem), an food and drug administration (FDA)-approved lipid-lowering drug, which has been shown to stimulate lysosomal biogenesis and induce anti-inflammation, orally, at a dose of 7.5 mg/kg body wt/day to Cln2 (-/-) mice. We observed that gem-fed Cln2 (-/-) mice lived longer by more than 10 weeks and had better motor activity compared to vehicle (0.1% Methyl cellulose) treatment. Gem treatment lowered the burden of storage materials, increased anti-inflammatory factors like SOCS3 and IL-1Ra, up-regulated anti-apoptotic molecule like phospho-Bad, and reduced neuronal apoptosis in the brain of Cln2 (-/-) mice. Collectively, this study reinforces a neuroprotective role of gem that may be of therapeutic interest in improving the quality of life in LINCL patients. © 2017 International Society for Neurochemistry.

Pre-accretional sorting of grains in the outer solar nebula

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

Wozniakiewicz, P. J.; Bradley, J. P.; Ishii, H. A.

2013-12-20

Despite their micrometer-scale dimensions and nanogram masses, chondritic porous interplanetary dust particles (CP IDPs) are an important class of extraterrestrial material since their properties are consistent with a cometary origin and they show no evidence of significant post-accretional parent body alteration. Consequently, they can provide information about grain accretion in the comet-forming region of the outer solar nebula. We have previously reported our comparative study of the sizes and size distributions of crystalline silicate and sulfide grains in CP IDPs, in which we found these components exhibit a size-density relationship consistent with having been sorted together prior to accretion. Heremore » we extend our data set and include GEMS (glass with embedded metal and sulfide), the most abundant amorphous silicate phase observed in CP IDPs. We find that while the silicate and sulfide sorting trend previously observed is maintained, the GEMS size data do not exhibit any clear relationship to these crystalline components. Therefore, GEMS do not appear to have been sorted with the silicate and sulfide crystals. The disparate sorting trends observed in GEMS and the crystalline grains in CP IDPs present an interesting challenge for modeling early transport and accretion processes. They may indicate that several sorting mechanisms operated on these CP IDP components, or alternatively, they may simply be a reflection of different source environments.« less

Multiscale asymmetric orthogonal wavelet kernel for linear programming support vector learning and nonlinear dynamic systems identification.

PubMed

Lu, Zhao; Sun, Jing; Butts, Kenneth

2014-05-01

Support vector regression for approximating nonlinear dynamic systems is more delicate than the approximation of indicator functions in support vector classification, particularly for systems that involve multitudes of time scales in their sampled data. The kernel used for support vector learning determines the class of functions from which a support vector machine can draw its solution, and the choice of kernel significantly influences the performance of a support vector machine. In this paper, to bridge the gap between wavelet multiresolution analysis and kernel learning, the closed-form orthogonal wavelet is exploited to construct new multiscale asymmetric orthogonal wavelet kernels for linear programming support vector learning. The closed-form multiscale orthogonal wavelet kernel provides a systematic framework to implement multiscale kernel learning via dyadic dilations and also enables us to represent complex nonlinear dynamics effectively. To demonstrate the superiority of the proposed multiscale wavelet kernel in identifying complex nonlinear dynamic systems, two case studies are presented that aim at building parallel models on benchmark datasets. The development of parallel models that address the long-term/mid-term prediction issue is more intricate and challenging than the identification of series-parallel models where only one-step ahead prediction is required. Simulation results illustrate the effectiveness of the proposed multiscale kernel learning.

A multiscale, model-based analysis of the multi-tissue interplay underlying blood glucose regulation in type I diabetes.

PubMed

Wadehn, Federico; Schaller, Stephan; Eissing, Thomas; Krauss, Markus; Kupfer, Lars

2016-08-01

A multiscale model for blood glucose regulation in diabetes type I patients is constructed by integrating detailed metabolic network models for fat, liver and muscle cells into a whole body physiologically-based pharmacokinetic/pharmacodynamic (pBPK/PD) model. The blood glucose regulation PBPK/PD model simulates the distribution and metabolization of glucose, insulin and glucagon on an organ and whole body level. The genome-scale metabolic networks in contrast describe intracellular reactions. The developed multiscale model is fitted to insulin, glucagon and glucose measurements of a 48h clinical trial featuring 6 subjects and is subsequently used to simulate (in silico) the influence of geneknockouts and drug-induced enzyme inhibitions on whole body blood glucose levels. Simulations of diabetes associated gene knockouts and impaired cellular glucose metabolism, resulted in elevated whole body blood-glucose levels, but also in a metabolic shift within the cell's reaction network. Such multiscale models have the potential to be employed in the exploration of novel drug-targets or to be integrated into control algorithms for artificial pancreas systems.

Modeling dynamic exchange of gaseous elemental mercury at polar sunrise.

PubMed

Dastoor, Ashu P; Davignon, Didier; Theys, Nicolas; Van Roozendael, Michel; Steffen, Alexandra; Ariya, Parisa A

2008-07-15

At polar sunrise, gaseous elemental mercury (GEM) undergoes an exceptional dynamic exchange in the air and at the snow surface during which GEM can be rapidly removed from the atmosphere (the so-called atmospheric mercury depletion events (AMDEs)) as well as re-emitted from the snow within a few hours to days in the Polar Regions. Although high concentrations of total mercury in snow following AMDEs is well documented, there is very little data available on the redox transformation processes of mercury in the snow and the fluxes of mercury at the air/snow interface. Therefore, the net gain of mercury in the Polar Regions as a result of AMDEs is still an open question. We developed a new version of the global mercury model, GRAHM, which includes for the first time bidirectional surface exchange of GEM in Polar Regions in spring and summer by developing schemes for mercury halogen oxidation, deposition, and re-emission. Also for the first time, GOME satellite data-derived boundary layer concentrations of BrO have been used in a global mercury model for representation of halogen mercury chemistry. Comparison of model simulated and measured atmospheric concentrations of GEM at Alert, Canada, for 3 years (2002-2004) shows the model's capability in simulating the rapid cycling of mercury during and after AMDEs. Brooks et al. (1) measured mercury deposition, reemission, and net surface gain fluxes of mercury at Barrow, AK, during an intensive measurement campaign for a 2 week period in spring (March 25 to April 7, 2003). They reported 1.7, 1.0 +/- 0.2, and 0.7 +/- 0.2 microg m(-2) deposition, re-emission, and net surface gain, respectively. Using the optimal configuration of the model, we estimated 1.8 microg m(-2) deposition, 1.0 microg m(-2) re-emission, and 0.8 microg m(-2) net surface gain of mercury for the same time period at Barrow. The estimated net annual accumulation of mercury within the Arctic Circle north of 66.5 degrees is approximately 174 t with +/-7 t of interannual variability for 2002-2004 using the optimal configuration. We estimated the uncertainty of the model results to the Hg/Br reaction rate coefficient to be approximately 6%. Springtime is clearly demonstrated as the most active period of mercury exchanges and net surface gain (approximately 46% of annual accumulation) in the Arctic.

A Liver-centric Multiscale Modeling Framework for Xenobiotics

EPA Science Inventory

We describe a multi-scale framework for modeling acetaminophen-induced liver toxicity. Acetaminophen is a widely used analgesic. Overdose of acetaminophen can result in liver injury via its biotransformation into toxic product, which further induce massive necrosis. Our study foc...

NCCAM/NCI Phase 1 Study of Mistletoe Extract and Gemcitabine in Patients with Advanced Solid Tumors

PubMed Central

Mansky, Patrick J.; Sannes, Timothy S.; Johnson, Laura Lee; Blackman, Marc R.; Grem, Jean L.; Swain, Sandra M.; Monahan, Brian P.

2013-01-01

Purpose. European Mistletoe (Viscum album L.) extracts (mistletoe) are commonly used for cancer treatment in Europe. This phase I study of gemcitabine (GEM) and mistletoe in advanced solid cancers (ASC) evaluated: (1) safety, toxicity, and maximum tolerated dose (MTD), (2) absolute neutrophil count (ANC) recovery, (3) formation of mistletoe lectin antibodies (ML ab), (4) cytokine plasma concentrations, (5) clinical response, and (6) pharmacokinetics of GEM. Methods. Design: increasing mistletoe and fixed GEM dose in stage I and increasing doses of GEM with a fixed dose of mistletoe in stage II. Dose limiting toxicities (DLT) were grade (G) 3 nonhematologic and G4 hematologic events; MTD was reached with 2 DLTs in one dosage level. Response in stage IV ASC was assessed with descriptive statistics. Statistical analyses examined clinical response/survival and ANC recovery. Results. DLTs were G4 neutropenia, G4 thrombocytopenia, G4 acute renal failure, and G3 cellulitis, attributed to mistletoe. GEM 1380 mg/m2 and mistletoe 250 mg combined were the MTD. Of 44 patients, 24 developed nonneutropenic fever and flu-like syndrome. GEM pharmacokinetics were unaffected by mistletoe. All patients developed ML3 IgG antibodies. ANC showed a trend to increase between baseline and cycle 2 in stage I dose escalation. 6% of patients showed partial response, 42% stable disease. Median survival was 200 days. Compliance with mistletoe injections was high. Conclusion. GEM plus mistletoe is well tolerated. No botanical/drug interactions were observed. Clinical response is similar to GEM alone. PMID:24285980

A MULTISCALE FRAMEWORK FOR THE STOCHASTIC ASSIMILATION AND MODELING OF UNCERTAINTY ASSOCIATED NCF COMPOSITE MATERIALS

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

Mehrez, Loujaine; Ghanem, Roger; McAuliffe, Colin

multiscale framework to construct stochastic macroscopic constitutive material models is proposed. A spectral projection approach, specifically polynomial chaos expansion, has been used to construct explicit functional relationships between the homogenized properties and input parameters from finer scales. A homogenization engine embedded in Multiscale Designer, software for composite materials, has been used for the upscaling process. The framework is demonstrated using non-crimp fabric composite materials by constructing probabilistic models of the homogenized properties of a non-crimp fabric laminate in terms of the input parameters together with the homogenized properties from finer scales.

Multi-scale Material Parameter Identification Using LS-DYNA® and LS-OPT®

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

Stander, Nielen; Basudhar, Anirban; Basu, Ushnish

2015-09-14

Ever-tightening regulations on fuel economy, and the likely future regulation of carbon emissions, demand persistent innovation in vehicle design to reduce vehicle mass. Classical methods for computational mass reduction include sizing, shape and topology optimization. One of the few remaining options for weight reduction can be found in materials engineering and material design optimization. Apart from considering different types of materials, by adding material diversity and composite materials, an appealing option in automotive design is to engineer steel alloys for the purpose of reducing plate thickness while retaining sufficient strength and ductility required for durability and safety. A project tomore » develop computational material models for advanced high strength steel is currently being executed under the auspices of the United States Automotive Materials Partnership (USAMP) funded by the US Department of Energy. Under this program, new Third Generation Advanced High Strength Steel (i.e., 3GAHSS) are being designed, tested and integrated with the remaining design variables of a benchmark vehicle Finite Element model. The objectives of the project are to integrate atomistic, microstructural, forming and performance models to create an integrated computational materials engineering (ICME) toolkit for 3GAHSS. The mechanical properties of Advanced High Strength Steels (AHSS) are controlled by many factors, including phase composition and distribution in the overall microstructure, volume fraction, size and morphology of phase constituents as well as stability of the metastable retained austenite phase. The complex phase transformation and deformation mechanisms in these steels make the well-established traditional techniques obsolete, and a multi-scale microstructure-based modeling approach following the ICME [0]strategy was therefore chosen in this project. Multi-scale modeling as a major area of research and development is an outgrowth of the Comprehensive Test Ban Treaty of 1996 which banned surface testing of nuclear devices [1]. This had the effect that experimental work was reduced from large scale tests to multiscale experiments to provide material models with validation at different length scales. In the subsequent years industry realized that multi-scale modeling and simulation-based design were transferable to the design optimization of any structural system. Horstemeyer [1] lists a number of advantages of the use of multiscale modeling. Among these are: the reduction of product development time by alleviating costly trial-and-error iterations as well as the reduction of product costs through innovations in material, product and process designs. Multi-scale modeling can reduce the number of costly large scale experiments and can increase product quality by providing more accurate predictions. Research tends to be focussed on each particular length scale, which enhances accuracy in the long term. This paper serves as an introduction to the LS-OPT and LS-DYNA methodology for multi-scale modeling. It mainly focuses on an approach to integrate material identification using material models of different length scales. As an example, a multi-scale material identification strategy, consisting of a Crystal Plasticity (CP) material model and a homogenized State Variable (SV) model, is discussed and the parameter identification of the individual material models of different length scales is demonstrated. The paper concludes with thoughts on integrating the multi-scale methodology into the overall vehicle design.« less

FIRST RESULTS FROM OPERATIONAL TESTING OF THE U.S. EPA MODELS-3 COMMUNITY MULTISCALE MODEL FOR AIR QUALITY (CMAQ)

EPA Science Inventory

The Models 3 / Community Multiscale Model for Air Quality (CMAQ) has been designed for one-atmosphere assessments for multiple pollutants including ozone (O3), particulate matter (PM10, PM2.5), and acid / nutrient deposition. In this paper we report initial results of our evalu...

EVALUATION OF THE COMMUNITY MULTISCALE AIR QUALITY (CMAQ) MODEL VERSION 4.5: UNCERTAINTIES AND SENSITIVITIES IMPACTING MODEL PERFORMANCE: PART I - OZONE

EPA Science Inventory

This study examines ozone (O₃) predictions from the Community Multiscale Air Quality (CMAQ) model version 4.5 and discusses potential factors influencing the model results. Daily maximum 8-hr average O₃ levels are largely underpredicted when observed O_...

Overview and Evaluation of the Community Multiscale Air Quality (CMAQ) Modeling System Version 5.2

EPA Science Inventory

A new version of the Community Multiscale Air Quality (CMAQ) model, version 5.2 (CMAQv5.2), is currently being developed, with a planned release date in 2017. The new model includes numerous updates from the previous version of the model (CMAQv5.1). Specific updates include a new...

Multi-scale modeling in cell biology

PubMed Central

Meier-Schellersheim, Martin; Fraser, Iain D. C.; Klauschen, Frederick

2009-01-01

Biomedical research frequently involves performing experiments and developing hypotheses that link different scales of biological systems such as, for instance, the scales of intracellular molecular interactions to the scale of cellular behavior and beyond to the behavior of cell populations. Computational modeling efforts that aim at exploring such multi-scale systems quantitatively with the help of simulations have to incorporate several different simulation techniques due to the different time and space scales involved. Here, we provide a non-technical overview of how different scales of experimental research can be combined with the appropriate computational modeling techniques. We also show that current modeling software permits building and simulating multi-scale models without having to become involved with the underlying technical details of computational modeling. PMID:20448808

The analysis of GEOS-3 altimeter data in the Tasman and Coral seas

NASA Technical Reports Server (NTRS)

Mather, R. S.

1977-01-01

A technique was developed for preprocessing GEOS-3 altimetry data to establish a model of the regional sea surface. The algorithms developed models for a 35,000,000 sq km area with an internal precision of + or - 1 m. There were discrepancies between the sea surface model so obtained and GEM6 based geoid profiles with wavelengths of approximately 2500 km and amplitudes of up to 5 m in this region. The amplitudes were smaller when compared with GEM10-based geoid determinations. However, the comparison of 14 pairs of overlapping passes in the region indicated altimeter resolution of the + or - 25 cm level if the wavelength corresponding to the Nyquist frequency were 30 km. The spectral analysis of such comparisons indicated the existence of significant signal strength in the discrepancies after least squares fitting, with wavelengths in excess of 200 km.

3D simulation of electron and ion transmission of GEM-based detectors

NASA Astrophysics Data System (ADS)

Bhattacharya, Purba; Mohanty, Bedangadas; Mukhopadhyay, Supratik; Majumdar, Nayana; da Luz, Hugo Natal

2017-10-01

Time Projection Chamber (TPC) has been chosen as the main tracking system in several high-flux and high repetition rate experiments. These include on-going experiments such as ALICE and future experiments such as PANDA at FAIR and ILC. Different R&D activities were carried out on the adoption of Gas Electron Multiplier (GEM) as the gas amplification stage of the ALICE-TPC upgrade version. The requirement of low ion feedback has been established through these activities. Low ion feedback minimizes distortions due to space charge and maintains the necessary values of detector gain and energy resolution. In the present work, Garfield simulation framework has been used to study the related physical processes occurring within single, triple and quadruple GEM detectors. Ion backflow and electron transmission of quadruple GEMs, made up of foils with different hole pitch under different electromagnetic field configurations (the projected solutions for the ALICE TPC) have been studied. Finally a new triple GEM detector configuration with low ion backflow fraction and good electron transmission properties has been proposed as a simpler GEM-based alternative suitable for TPCs for future collider experiments.

CTA1: Purified and display onto gram-positive enhancer matrix (GEM) particles as mucosal adjuvant.

PubMed

Zhang, Yuanpeng; Yu, Xiaoming; Hou, Liting; Chen, Jin; Li, Pengcheng; Qiao, Xuwen; Zheng, Qisheng; Hou, Jibo

2018-01-01

The A1 subunit of cholera toxin (CTA1) retains the adjuvant function of CT, without its toxic side effects, making the molecule a promising mucosal adjuvant. However, the methods required to obtain a pure product are both complicated and expensive, constricting its potential commercial applicability. Here, we fused the peptidoglycan binding domain (PA) to the C-terminus of CTA1, which enabled the fusion protein to be expressed by Bacillus subtilis, and secreted into the culture medium. CTA1 was then purified and displayed on GEM particles using a one step process, which resulted in the formation of CTA1-GEM complexes. Next, the CTA1-GEM complexes were used as an adjuvant to enhance the immune responses of mice to the influenza subunit vaccine. It was observed that the CTA1-GEM complexes enhanced specific systemic (IgG) and mucosal (IgA) immune responses against antigen, and induced cellular immune responses as well. The data presented here suggests that CTA1-GEM complexes can serve as a viable mucosal adjuvant. Copyright © 2017 Elsevier Inc. All rights reserved.

Gravitomagnetic acceleration of accretion disk matter to polar jets

NASA Astrophysics Data System (ADS)

Poirier, John; Mathews, Grant

2016-03-01

The motion of the masses of an accretion disk around a black hole creates a general relativistic, gravitomagnetic field (GEM) from the moving matter (be it charged or uncharged) of the accretion disk. This GEM field accelerates moving masses (neutral or charged) near the accretion disk vertically upward and away from the disk, and then inward toward the axis of the disk. As the accelerated material nears the axis with approximately vertical angles, a frame dragging effect contributes to the formation of narrow jets emanating from the poles. This GEM effect is numerically evaluated in the first post Newtonian (1PN) approximation from observable quantities like the mass and velocity of the disk. This GEM force is linear in the total mass of the accretion disk matter and quadratic in the velocity of matter near to the disk with approximately the same velocity. Since these masses and velocities can be quite high in astrophysical contexts, the GEM force, which in other contexts is weak, is quite significant. This GEM effect is compared to the ordinary electromagnetic effects applied to this problem in the past.

Gemfibrozil modulates cytochrome P450 and peroxisome proliferation-inducible enzymes in the liver of the yellow European eel (Anguilla anguilla).

PubMed

Lyssimachou, Angeliki; Thibaut, Rémi; Gisbert, Enric; Porte, Cinta

2014-01-01

The human lipid regulator gemfibrozil (GEM) has been shown to induce peroxisome proliferation in rodents leading to hepatocarcinogenesis. Since GEM is found at biological active concentrations in the aquatic environment, the present study investigates the effects of this drug on the yellow European eel (Anguilla anguilla). Eels were injected with different concentrations of GEM (0.1 to 200 μg/g) and sampled 24- and 96-h post-injection. GEM was shown to inhibit CYP1A, CYP3A and CYP2K-like catalytic activities 24-h post-injection, but at 96-h post-injection, only CYP1A was significantly altered in fish injected with the highest GEM dose. On the contrary, GEM had little effect on the phase II enzymes examined (UDP-glucuronyltransferase and glutathione-S-transferase). Peroxisome proliferation inducible enzymes (liver peroxisomal acyl-CoA oxidase and catalase) were very weakly induced. No evidence of a significant effect on the endocrine system of eels was observed in terms of plasmatic steroid levels or testosterone esterification in the liver.

Codelivery of dual drugs from polymeric micelles for simultaneous targeting of both cancer cells and cancer stem cells.

PubMed

Krishnamurthy, Sangeetha; Ng, Victor W L; Gao, Shujun; Tan, Min-Han; Hedrick, James L; Yang, Yi Yan

2015-01-01

Phenformin-loaded micelles (Phen M) were used in combination with gemcitabine-loaded micelles (Gem M) to study their combined effect against H460 human lung cancer cells and cancer stem cells (CSCs) in vitro and in vivo. Gem M and Phen M were prepared via self-assembly of a mixture of a diblock copolymer of PEG and urea-functionalized polycarbonate (PEG-PUC) and a diblock copolymer of PEG and acid-functionalized polycarbonate (PEG-PAC) through hydrogen bonding and ionic interactions. Gem M and Phen M were characterized and tested for efficacy both in vitro and in vivo against cancer cells and CSCs. The combination of Gem M/Phen M exhibited higher cytotoxicity against CSCs and non-CSCs than Gem M and Phen M alone, and showed significant cell cycle growth arrest in vitro. The combination therapy had superior tumor suppression and apoptosis in vivo without inducing toxicity to liver and kidney. The combination of Gem M and Phen M may be potentially used in lung cancer therapy.

Development of a scintillating G-GEM detector for a 6-MeV X-band Linac for medical applications

NASA Astrophysics Data System (ADS)

Fujiwara, T.; Tanaka, S.; Mitsuya, Y.; Takahashi, H.; Tagi, K.; Kusano, J.; Tanabe, E.; Yamamoto, M.; Nakamura, N.; Dobashi, K.; Tomita, H.; Uesaka, M.

2013-12-01

We recently developed glass gas electron multipliers (G-GEMs) with an entirely new process using photo-etchable glass. The photo-etchable glass used for the substrate is called PEG3 (Hoya Corporation). Taking advantage of low outgassing material, we have envisioned a medical application of G-GEMs. A two-dimensional position-sensitive dosimetry system based on a scintillating gas detector is being developed for real-time dose distribution monitoring in X-ray radiation therapy. The dosimetry system consists of a chamber filled with an Ar/CF4 scintillating gas mixture, inside of which G-GEM structures are mounted. Photons produced by the excited Ar/CF4 gas molecules during the gas multiplication in the GEM holes are detected by a mirror-lens-CCD-camera system. We found that the intensity distribution of the measured light spot is proportional to the 2D dose distribution. In this work, we report on the first results from a scintillating G-GEM detector for a position-sensitive X-ray beam dosimeter.

Large size GEM for Super Bigbite Spectrometer (SBS) polarimeter for Hall A 12GeV program at JLab

DOE PAGES

Gnanvo, Kondo; Liyanage, Nilanga; Nelyubin, Vladimir; ...

2015-05-01

We report on the R&D effort in the design and construction of a large size GEM chamber for the Proton Polarimeter of the Super Bigbite Spectrometer (SBS) in Hall A at Thomas Jefferson National Laboratory (JLab). The SBS Polarimeter trackers consist of two sets of four large chambers of size 200 cm x 60 cm 2. Each chamber is a vertical stack of four GEM modules with an active area of 60 cm x 50 cm. We have built and tested several GEM modules and we describe in this paper the design and construction of the final GEM as wellmore » as the preliminary results on performances from tests carried out in our detector lab and with test beams at (Fermilab).« less

Geostationary Environment Monitoring Spectrometer (gems) Over the Korea Peninsula and Asia-Pacific Region

NASA Astrophysics Data System (ADS)

Lasnik, J.; Stephens, M.; Baker, B.; Randall, C.; Ko, D. H.; Kim, S.; Kim, Y.; Lee, E. S.; Chang, S.; Park, J. M.; SEO, S. B.; Youk, Y.; Kong, J. P.; Lee, D.; Lee, S. H.; Kim, J.

2014-12-01

Introduction: The Geostationary Environment Monitoring Spectrometer (GEMS) is one of two instruments manifested aboard the South Korean Geostationary Earth Orbit KOrea Multi-Purpose SATellite-2B (GEO-KOMPSAT-2B or GK2B), which is scheduled to launch in 2018. Jointly developed/built by KARI and Ball Aerospace, GEMS is a geostationary UV-Vis hyperspectral imager designed to monitor trans-boundary tropospheric pollution events over the Korean peninsula and Asia-Pacific region. The spectrometer provides high temporal and spatial resolution (3.5 km N/S by 7.2 km E/W) measurements of ozone, its precursors, and aerosols. Over the short-term, hourly measurements by GEMS will improve early warnings for potentially dangerous pollution events and monitor population exposure. Over the 10-year mission-life, GEMS will serve to enhance our understanding of long-term climate change and broader air quality issues on both a regional and global scale. The GEMS sensor design and performance are discussed, which includes an overview of measurement capabilities and the on-orbit concept of operations. GEMS Sensor Overview: The GEMS hyperspectral imaging system consists of a telescope and Offner grating spectrometer that feeds a single CCD detector array. A spectral range of 300-500 nm and sampling of 0.2 nm enables NO2, SO2, HCHO, O3, and aerosol retrieval. The GEMS field of regard (FOR), which extends from 5°S to 45°N in latitude and 75°E to 145°E in longitude, is operationally achieved using an onboard two-axis scan mirror. On-orbit, the radiometric calibration is maintained using solar measurements, which are performed using two onboard diffusers: a working diffuser that is deployed routinely for the purpose of solar calibration, and a reference diffuser that is deployed sparingly for the purpose of monitoring working diffuser performance degradation.

CLIMATIC EFFECTS ON TUNDRA CARBON STORAGE INFERRED FROM EXPERIMENTAL DATA AND A MODEL

EPA Science Inventory

We used a process-based model of ecosystem carbon (C) and nitrogen (N)dynamics, MBL-GEM (Marine Biological Laboratory General Ecosystem Model), to integrated and analyze the results of several experiments that examined the response of arctic tussock tundra to manipulations of CO2...

Modeling Gameplay Enjoyment, Goal Orientations, and Individual Characteristics

ERIC Educational Resources Information Center

Quick, John M.; Atkinson, Robert K.

2014-01-01

The purpose of this study was to investigate the relationships between gameplay enjoyment, gaming goal orientations, and individual characteristics. A total of 301 participants were surveyed and the data were analyzed using structural equation modeling. This led to an expanded Gameplay Enjoyment Model (GEM) with 41 game design features that…

Multiscale geometric modeling of macromolecules II: Lagrangian representation

PubMed Central

Feng, Xin; Xia, Kelin; Chen, Zhan; Tong, Yiying; Wei, Guo-Wei

2013-01-01

Geometric modeling of biomolecules plays an essential role in the conceptualization of biolmolecular structure, function, dynamics and transport. Qualitatively, geometric modeling offers a basis for molecular visualization, which is crucial for the understanding of molecular structure and interactions. Quantitatively, geometric modeling bridges the gap between molecular information, such as that from X-ray, NMR and cryo-EM, and theoretical/mathematical models, such as molecular dynamics, the Poisson-Boltzmann equation and the Nernst-Planck equation. In this work, we present a family of variational multiscale geometric models for macromolecular systems. Our models are able to combine multiresolution geometric modeling with multiscale electrostatic modeling in a unified variational framework. We discuss a suite of techniques for molecular surface generation, molecular surface meshing, molecular volumetric meshing, and the estimation of Hadwiger’s functionals. Emphasis is given to the multiresolution representations of biomolecules and the associated multiscale electrostatic analyses as well as multiresolution curvature characterizations. The resulting fine resolution representations of a biomolecular system enable the detailed analysis of solvent-solute interaction, and ion channel dynamics, while our coarse resolution representations highlight the compatibility of protein-ligand bindings and possibility of protein-protein interactions. PMID:23813599

Editorial: Reviewer Selection Process and New Areas of Expertise in GEMS

NASA Technical Reports Server (NTRS)

Liemohn, Michael W.; Balikhin, Michael; Kepko, Larry; Rodger, Alan; Wang, Yuming

2016-01-01

One method of selecting potential reviewers for papers submitted to the Journal of Geophysical Research Space Physics is to filter the user database within the Geophysical Electronic Manuscript System (GEMS) by areas of expertise. The list of these areas in GEMS can be self selected by users in their profile settings. The Editors have added 18 new entries to this list, an increase of 33 more than the previous 55 entries. All space physicists are strongly encouraged to update their profile settings in GEMS, especially their areas of expertise selections, and details of how to do this are provided.

Editorial: Reviewer selection process and new areas of expertise in GEMS

NASA Astrophysics Data System (ADS)

Liemohn, Michael W.; Balikhin, Michael; Kepko, Larry; Rodger, Alan; Wang, Yuming

2016-06-01

One method of selecting potential reviewers for papers submitted to the Journal of Geophysical Research Space Physics is to filter the user database within the Geophysical Electronic Manuscript System (GEMS) by areas of expertise. The list of these areas in GEMS can be self selected by users in their profile settings. The Editors have added 18 new entries to this list, an increase of 33% more than the previous 55 entries. All space physicists are strongly encouraged to update their profile settings in GEMS, especially their areas of expertise selections, and details of how to do this are provided.

Multimodal properties and dynamics of gradient echo quantum memory.

PubMed

Hétet, G; Longdell, J J; Sellars, M J; Lam, P K; Buchler, B C

2008-11-14

We investigate the properties of a recently proposed gradient echo memory (GEM) scheme for information mapping between optical and atomic systems. We show that GEM can be described by the dynamic formation of polaritons in k space. This picture highlights the flexibility and robustness with regards to the external control of the storage process. Our results also show that, as GEM is a frequency-encoding memory, it can accurately preserve the shape of signals that have large time-bandwidth products, even at moderate optical depths. At higher optical depths, we show that GEM is a high fidelity multimode quantum memory.

Co-delivery of docetaxel and gemcitabine by anacardic acid modified self-assembled albumin nanoparticles for effective breast cancer management.

PubMed

Kushwah, Varun; Katiyar, Sameer S; Dora, Chander Parkash; Kumar Agrawal, Ashish; Lamprou, Dimitrios A; Gupta, Ramesh C; Jain, Sanyog

2018-06-01

In the present study, we have modified bovine serum albumin (BSA) by covalently conjugating with anacardic acid (AA) and gemcitabine (GEM) and further used for development of docetaxel (DTX) loaded nanoparticles (AA-GEM-BSA NPs). AA is supposed to provide tumor targeting through VEGF receptors overexpressed in tumors, while the combination of GEM and DTX is supposed to provide synergistic activity by targeting multiple pathways. The conjugate was synthesized via carbodiimide chemistry and characterized by 1 H NMR, FTIR, MALDI-TOF and elemental analysis. Conformational changes owing to conjugation of AA and GEM were estimated via fluorescence, Raman and CD spectroscopy, while changes in physiochemical properties were studied by differential scanning calorimetry (DSC), thermogravimetry (TGA) and contact angle goniometry (CAG). Synthesized conjugate was further transformed into DTX loaded NPs and freeze dried. Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM) demonstrated formation of spherical NPs having particle size, 163 ± 8 nm, PDI, 0.13 ± 0.09 and ZP, -27 ± 1 mV. Cellular uptake in MCF-7 and MDA-MB-231 revealed hNTs, OATP1B3 independent, clathrin mediated internalization followed via nuclear co-localization of C-6 loaded AA-GEM-BSA NPs, responsible for significantly higher apoptosis index. Pharmacokinetic profile of DTX loaded AA-GEM-BSA NPs revealed 6.12 and 3.27-fold and 6.28 and 8.9-fold higher AUC and T 1/2 values of DTX and GEM as compared to Taxotere® and Gemzar®, respectively. Interestingly, the developed NPs were found safe with no marked effect on RBCs, lower hepato and nephro toxicity. Data in hand suggest promising potential of developed NPs in ameliorating the pharmacokinetic and therapeutic profile of combinatorial regimen of DTX and GEM. The present report is the original state of art technology to selectively target dual drug (DTX and GEM) loaded BSA NPs via exploring tumor targeting potential of AA, having high affinity towards VEGF receptors (angiogenesis marker) overexpressed in tumor. The AA and GEM bio-conjugated BSA was synthesized and further used to develop DTX loaded nanoparticles (AA-GEM-BSA NPs). The optimized NPs were further evaluated via extensive in vitro and in vivo studies, demonstrating ameliorated cellular uptake, pharmacokinetic and toxicity profile of drugs. Conclusively, DTX loaded AA-GEM-BSA NPs, holds promising potential in increasing the therapeutic efficiency of drugs and overcoming solvent and drug mediated side effects and can be explored further as a scalable platform technology for difficult to deliver drugs. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

REVIEW OF THE GOVERNING EQUATIONS, COMPUTATIONAL ALGORITHMS, AND OTHER COMPONENTS OF THE MODELS-3 COMMUNITY MULTISCALE AIR QUALITY (CMAQ) MODELING SYSTEM

EPA Science Inventory

This article describes the governing equations, computational algorithms, and other components entering into the Community Multiscale Air Quality (CMAQ) modeling system. This system has been designed to approach air quality as a whole by including state-of-the-science capabiliti...

Models, Databases, and Simulation Tools Needed for the Realization of Integrated Computational Materials Engineering. Proceedings of the Symposium Held at Materials Science and Technology 2010

NASA Technical Reports Server (NTRS)

Arnold, Steven M. (Editor); Wong, Terry T. (Editor)

2011-01-01

Topics covered include: An Annotative Review of Multiscale Modeling and its Application to Scales Inherent in the Field of ICME; and A Multiscale, Nonlinear, Modeling Framework Enabling the Design and Analysis of Composite Materials and Structures.

Evaluation of the Community Multiscale Air Quality Model for Simulating Winter Ozone Formation in the Uinta Basin.

EPA Science Inventory

The Weather Research and Forecasting (WRF) and Community Multiscale Air Quality (CMAQ) models were used to simulate a 10 day high‐ozone episode observed during the 2013 Uinta Basin Winter Ozone Study (UBWOS). The baseline model had a large negative bias when compared to ozo...

Speciated atmospheric mercury and its potential source in Guiyang, China

NASA Astrophysics Data System (ADS)

Fu, Xuewu; Feng, Xinbin; Qiu, Guangle; Shang, Lihai; Zhang, Hui

2011-08-01

Speciated atmospheric mercury (Hg) including gaseous elemental mercury (GEM), particulate Hg (PHg), and reactive gaseous Hg (RGM) were continuously measured at an urban site in Guiyang city, southwest China from August to December 2009. The averaged concentrations for GEM, PHg, and RGM were 9.72 ± 10.2 ng m -3, 368 ± 676 pg m -3, and 35.7 ± 43.9 pg m -3, respectively, which were all highly elevated compared to observations at urban sites in Europe and North America. GEM and PHg were characterized by similar monthly and diurnal patterns, with elevated levels in cold months and nighttime, respectively. In contrast, RGM did not exhibit clear monthly and diurnal variations. The variations of GEM, PHg, and RGM indicate the sampling site was significantly impacted by sources in the city municipal area. Sources identification implied that both residential coal burning and large point sources were responsible to the elevated GEM and PHg concentrations; whereas point sources were the major contributors to elevated RGM concentrations. Point sources played a different role in regulating GEM, PHg, and RGM concentrations. Aside from residential emissions, PHg levels was mostly affected by small-scale coal combustion boilers situated to the east of the sampling site, which were scarcely equipped or lacking particulate control devices; whereas point sources situated to the east, southeast, and southwest of the sampling played an important role on the distribution of atmospheric GEM and RGM.

Hyperspectral imaging: gem identification and authentication

NASA Astrophysics Data System (ADS)

Gomez, Richard B.; Del Re, Nicholas

2005-01-01

Through the centuries gem materials have been highly prized and sought after. The varieties of gem materials run into the hundreds if not thousands, characterized by a gamut of material classes running from organic to inorganic and from crystalline to amorphous. All consisting of numerous chemical compositions and characterized by various physical and optical properties. In addition, most gem materials have been subject to numerous modifications to enhance and imitate the most pleasing of esthetic qualities, e.g., dyeing, impregnation, heating, reconstruction, high pressure and temperature, irradiation, and diffusion. Of concern is the ability not only to identify the gem material in question, but if applicable, the treatment. Up until recent, the main instruments utilized to detect these have been simple but quite effective such as a binocular microscope, refractometer, hand spectroscope, dichroscope, and measuring of specific gravity. New gem materials and techniques involved in treatments have become increasingly sophisticated such as ultraviolet-visible-infrared and Raman spectroscopy. In certain cases, some of the most recent techniques have become time consuming and expensive. Here is the opportunity to overview and utilize a powerful technology found in the field of remote sensing, i.e., Hyperspectral Imaging. This technology has been in effect for many years but only recently has it been used to focus on areas similar to the ones in this paper. In particular, hyperspectral imaging technology and its potential application to gem identification and authentication are covered in this paper.

An Initial Evaluation of Tablet Devices & What Are the Next Steps?

ERIC Educational Resources Information Center

McKillen, Tracey

2016-01-01

This paper describes an evaluation of tablet devices for a Graduate Entry Medical School (GEMS). The purpose of this evaluation is to assess what type of tablet device could meet the needs of a GEMS student. GEMS requirements for the evaluation include; using the tablet device to replace paper teaching resources in lectures and tutorials and…

Copper-Catalyzed SN2'-Selective Allylic Substitution Reaction of gem-Diborylalkanes.

PubMed

Zhang, Zhen-Qi; Zhang, Ben; Lu, Xi; Liu, Jing-Hui; Lu, Xiao-Yu; Xiao, Bin; Fu, Yao

2016-03-04

A Cu/(NHC)-catalyzed SN2'-selective substitution reaction of allylic electrophiles with gem-diborylalkanes is reported. Different substituted gem-diborylalkanes and allylic electrophiles can be employed in this reaction, and various synthetic valuable functional groups can be tolerated. The asymmetric version of this reaction was initially researched with chiral N-heterocyclic carbene (NHC) ligands.

77 FR 71776 - Certain Steel Threaded Rod From the People's Republic of China: Affirmative Preliminary...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-04

... more chromium, by weight, produced by Gem-Year Industrial Co., Ltd. (``Gem- Year''), and otherwise... greater than 1.25 percent chromium, by weight, and otherwise meeting the requirements of the scope of the... threaded rod products with 1.25 percent or more chromium, by weight, produced by Gem-Year, and otherwise...

Multiscale modeling of mucosal immune responses

PubMed Central

2015-01-01

Computational modeling techniques are playing increasingly important roles in advancing a systems-level mechanistic understanding of biological processes. Computer simulations guide and underpin experimental and clinical efforts. This study presents ENteric Immune Simulator (ENISI), a multiscale modeling tool for modeling the mucosal immune responses. ENISI's modeling environment can simulate in silico experiments from molecular signaling pathways to tissue level events such as tissue lesion formation. ENISI's architecture integrates multiple modeling technologies including ABM (agent-based modeling), ODE (ordinary differential equations), SDE (stochastic modeling equations), and PDE (partial differential equations). This paper focuses on the implementation and developmental challenges of ENISI. A multiscale model of mucosal immune responses during colonic inflammation, including CD4+ T cell differentiation and tissue level cell-cell interactions was developed to illustrate the capabilities, power and scope of ENISI MSM. Background Computational techniques are becoming increasingly powerful and modeling tools for biological systems are of greater needs. Biological systems are inherently multiscale, from molecules to tissues and from nano-seconds to a lifespan of several years or decades. ENISI MSM integrates multiple modeling technologies to understand immunological processes from signaling pathways within cells to lesion formation at the tissue level. This paper examines and summarizes the technical details of ENISI, from its initial version to its latest cutting-edge implementation. Implementation Object-oriented programming approach is adopted to develop a suite of tools based on ENISI. Multiple modeling technologies are integrated to visualize tissues, cells as well as proteins; furthermore, performance matching between the scales is addressed. Conclusion We used ENISI MSM for developing predictive multiscale models of the mucosal immune system during gut inflammation. Our modeling predictions dissect the mechanisms by which effector CD4+ T cell responses contribute to tissue damage in the gut mucosa following immune dysregulation. PMID:26329787

Multiscale modeling of mucosal immune responses.

PubMed

Mei, Yongguo; Abedi, Vida; Carbo, Adria; Zhang, Xiaoying; Lu, Pinyi; Philipson, Casandra; Hontecillas, Raquel; Hoops, Stefan; Liles, Nathan; Bassaganya-Riera, Josep

2015-01-01

Computational techniques are becoming increasingly powerful and modeling tools for biological systems are of greater needs. Biological systems are inherently multiscale, from molecules to tissues and from nano-seconds to a lifespan of several years or decades. ENISI MSM integrates multiple modeling technologies to understand immunological processes from signaling pathways within cells to lesion formation at the tissue level. This paper examines and summarizes the technical details of ENISI, from its initial version to its latest cutting-edge implementation. Object-oriented programming approach is adopted to develop a suite of tools based on ENISI. Multiple modeling technologies are integrated to visualize tissues, cells as well as proteins; furthermore, performance matching between the scales is addressed. We used ENISI MSM for developing predictive multiscale models of the mucosal immune system during gut inflammation. Our modeling predictions dissect the mechanisms by which effector CD4+ T cell responses contribute to tissue damage in the gut mucosa following immune dysregulation.Computational modeling techniques are playing increasingly important roles in advancing a systems-level mechanistic understanding of biological processes. Computer simulations guide and underpin experimental and clinical efforts. This study presents ENteric Immune Simulator (ENISI), a multiscale modeling tool for modeling the mucosal immune responses. ENISI's modeling environment can simulate in silico experiments from molecular signaling pathways to tissue level events such as tissue lesion formation. ENISI's architecture integrates multiple modeling technologies including ABM (agent-based modeling), ODE (ordinary differential equations), SDE (stochastic modeling equations), and PDE (partial differential equations). This paper focuses on the implementation and developmental challenges of ENISI. A multiscale model of mucosal immune responses during colonic inflammation, including CD4+ T cell differentiation and tissue level cell-cell interactions was developed to illustrate the capabilities, power and scope of ENISI MSM.

Recent Enhancements to the Community Multiscale Air Quality Modeling System (CMAQ)

EPA Science Inventory

EPA’s Office of Research and Development, Computational Exposure Division held a webinar on January 31, 2017 to present the recent scientific and computational updates made by EPA to the Community Multi-Scale Air Quality Model (CMAQ). Topics covered included: (1) Improveme...

Sensitivity of the Community Multiscale Air Quality (CMAQ) Model v4.7 Results for the Eastern United States to MM5 and WRF Meteorological Drivers

EPA Science Inventory

This paper presents a comparison of the operational performance of two Community Multiscale Air Quality (CMAQ) model v4.7 simulations that utilize input data from the 5th generation Mesoscale Model MM5 and the Weather Research and Forecasting (WRF) meteorological models.

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

Perdikaris, Paris, E-mail: parisp@mit.edu; Grinberg, Leopold, E-mail: leopoldgrinberg@us.ibm.com; Karniadakis, George Em, E-mail: george-karniadakis@brown.edu

The aim of this work is to present an overview of recent advances in multi-scale modeling of brain blood flow. In particular, we present some approaches that enable the in silico study of multi-scale and multi-physics phenomena in the cerebral vasculature. We discuss the formulation of continuum and atomistic modeling approaches, present a consistent framework for their concurrent coupling, and list some of the challenges that one needs to overcome in achieving a seamless and scalable integration of heterogeneous numerical solvers. The effectiveness of the proposed framework is demonstrated in a realistic case involving modeling the thrombus formation process takingmore » place on the wall of a patient-specific cerebral aneurysm. This highlights the ability of multi-scale algorithms to resolve important biophysical processes that span several spatial and temporal scales, potentially yielding new insight into the key aspects of brain blood flow in health and disease. Finally, we discuss open questions in multi-scale modeling and emerging topics of future research.« less

Quantifying Atmospheric Mercury Emissions Sources in coastal California from Shipboard Measurements During CalNex 2010

NASA Astrophysics Data System (ADS)

Weiss-Penzias, P. S.; Lerner, B. M.; Williams, E. J.; Bates, T. S.; Gaston, C. J.; Prather, K. A.

2011-12-01

Mercury is a neurotoxin that can bioaccumulate in aquatic ecosystems to levels that are unsafe for humans and biota. It has both natural and anthropogenic sources to the atmosphere, where it can be transported and undergo transformations that lead to its deposition in both wet and dry forms. Due to recent surveys of mercury in fish in California that show widespread contamination, there is great interest in knowing the source of this mercury, whether it be from local, regional, or global emissions. In this study we made simultaneous measurements of gaseous elemental mercury (GEM), CO2, CO, NOx, SO2, O3, and meteorology during the spring of 2010 (May 14-June 8) on board the research vessel Atlantis during the CalNex campaign. The goal of this study was to observe and quantify emissions of GEM from known and potential sources along the California coast, including an incinerator, oil refineries, cargo ships, and natural ocean emissions. Additionally, an understanding of the behavior of GEM in the marine boundary layer under land-sea breeze conditions was sought. Our results indicate that on at least one occasion when the ship was located in the San Pedro harbor, emissions from an incinerator were observed, as indicated by high concentrations of GEM and unique single particle chemical composition. Using the ratio of the enhancements in GEM and CO and the CO emissions inventory for this facility, it was estimated that the annual GEM emissions were 11 +/- 5 kg. This is a factor of 5 lower than the reported total mercury emissions inventory for this facility in 2008. The discrepancy may be explained if a significant fraction of the emissions were gaseous oxidized and particulate mercury, since only GEM was measured. Additionally, a plume from a cargo ship was intercepted and the GEM/CO2 enhancement ratio indicated that approximately 13 tonnes of GEM are emitted from shipping worldwide, assuming values for global fuel usage and a CO2/fuel burned mass ratio. In spite of these impacts from combustion sources, mean concentrations of GEM in the bight of the Los Angeles were 1.38 ± 0.19 ng m-3, which is less than recognized hemispheric mean of 1.5-1.7 ng m-3, indicating minimal impact from anthropogenic sources overall. In fact, a slight positive correlation was observed between GEM and DMS in seawater suggesting that the ocean productivity may be associated with a source of mercury in this region.

The structure of the GemC1 coiled coil and its interaction with the Geminin family of coiled-coil proteins

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

Caillat, Christophe; Fish, Alexander; Pefani, Dafni-Eleftheria

The GemC1 coiled-coil structure has subtle differences compared with its homologues Geminin and Idas. Co-expression experiments in cells and biophysical stability analysis of the Geminin-family coiled coils suggest that the GemC1 coiled coil alone is unstable. GemC1, together with Idas and Geminin, an important regulator of DNA-replication licensing and differentiation decisions, constitute a superfamily sharing a homologous central coiled-coil domain. To better understand this family of proteins, the crystal structure of a GemC1 coiled-coil domain variant engineered for better solubility was determined to 2.2 Å resolution. GemC1 shows a less typical coiled coil compared with the Geminin homodimer and themore » Geminin–Idas heterodimer structures. It is also shown that both in vitro and in cells GemC1 interacts with Geminin through its coiled-coil domain, forming a heterodimer that is more stable that the GemC1 homodimer. Comparative analysis of the thermal stability of all of the possible superfamily complexes, using circular dichroism to follow the unfolding of the entire helix of the coiled coil, or intrinsic tryptophan fluorescence of a unique conserved N-terminal tryptophan, shows that the unfolding of the coiled coil is likely to take place from the C-terminus towards the N-terminus. It is also shown that homodimers show a single-state unfolding, while heterodimers show a two-state unfolding, suggesting that the dimer first falls apart and the helices then unfold according to the stability of each protein. The findings argue that Geminin-family members form homodimers and heterodimers between them, and this ability is likely to be important for modulating their function in cycling and differentiating cells.« less

Natural and anthropogenic atmospheric mercury in the European Arctic: a fractionation study

NASA Astrophysics Data System (ADS)

Steen, A. O.; Berg, T.; Dastoor, A. P.; Durnford, D. A.; Engelsen, O.; Hole, L. R.; Pfaffhuber, K. A.

2011-07-01

Gaseous elemental mercury (GEM) is converted to reactive gaseous mercury (RGM) during springtime Atmospheric Mercury Depletion Events (AMDE). This study reports the longest time series of GEM, RGM and particle-bound mercury (PHg) concentrations from a European Arctic site. From 27 April 2007 until 31 December 2008 composite GEM, RGM and PHg measurements were conducted in Ny-Ålesund (78° 54' N, 11° 53' E). The average concentrations of the complete dataset were 1.6 ± 0.3 ng m-3, 8 ± 13 pg m-3 and 8 ± 25 pg m-3 for GEM, RGM and PHg, respectively. For the complete dataset the atmospheric mercury distribution was 99 % GEM, whereas RGM and PHg constituted <1 %. The study revealed a seasonal distribution of GEM, RGM and PHg previously undiscovered in the Arctic. Increased concentrations of RGM were observed during the insolation period from March through August, while increased PHg concentrations occurred almost exclusively during the spring AMDE period in March and April. The elevated RGM concentrations suggest that atmospheric RGM deposition also occurs during the polar summer. RGM was suggested as the precursor for the PHg existence, but long range transportation of PHg has to be taken into consideration. Still there remain gaps in the knowledge of how RGM and PHg are related in the environment. RGM and PHg accounted for on average about 10 % of the depleted GEM during AMDEs. Although speculative, the fairly low RGM and PHg concentrations supported by the predominance of PHg with respect to RGM and no clear meteorological regime associated with these AMDEs would all suggest the events to be of non-local origin. With some exceptions, no clear meteorological regime was associated with the GEM, RGM and PHg concentrations throughout the year.

Enhanced tumor targeting of cRGD peptide-conjugated albumin nanoparticles in the BxPC-3 cell line.

PubMed

Yu, Xinzhe; Song, Yunlong; Di, Yang; He, Hang; Fu, Deliang; Jin, Chen

2016-08-12

The emerging albumin nanoparticle brings new hope for the delivery of antitumor drugs. However, a lack of robust tumor targeting greatly limits its application. In this paper, cyclic arginine-glycine-aspartic-conjugated, gemcitabine-loaded human serum albumin nanoparticles (cRGD-Gem-HSA-NPs) were successfully prepared, characterized, and tested in vitro in the BxPC-3 cell line. Initially, 4-N-myristoyl-gemcitabine (Gem-C14) was formed by conjugating myristoyl to the 4-amino group of gemcitabine. Then, cRGD-HSA was synthesized using sulfosuccinimidyl-(4-N-maleimidomethyl)cyclohexane-1-carboxylate (Sulfo-SMCC) cross-linkers. Finally, cRGD-Gem-HSA-NPs were formulated based on the nanoparticle albumin-bound (nab) technology. The resulting NPs were characterized for particle size, zeta potential, morphology, encapsulation efficiency, and drug loading efficiency. In vitro cellular uptake and inhibition studies were conducted to compare Gem-HSA-NPs and cRGD-Gem-HSA-NPs in a human pancreatic cancer cell line (BxPC-3). The cRGD-Gem-HSA-NPs exhibited an average particle size of 160 ± 23 nm. The encapsulation rate and drug loading rate were approximately 83 ± 5.6% and 11 ± 4.2%, respectively. In vitro, the cRGD-anchored NPs exhibited a significantly greater affinity for the BxPC-3 cells compared to non-targeted NPs and free drug. The cRGD-Gem-HSA-NPs also showed the strongest inhibitory effect in the BxPC-3 cells among all the analyzed groups. The improved efficacy of cRGD-Gem-HSA-NPs in the BxPC-3 cell line warrants further in vivo investigations.

Gemcitabine-Based Chemotherapy in Adrenocortical Carcinoma: A Multicenter Study of Efficacy and Predictive Factors.

PubMed

Henning, Judith E K; Deutschbein, Timo; Altieri, Barbara; Steinhauer, Sonja; Kircher, Stefan; Sbiera, Silviu; Wild, Vanessa; Schlötelburg, Wiebke; Kroiss, Matthias; Perotti, Paola; Rosenwald, Andreas; Berruti, Alfredo; Fassnacht, Martin; Ronchi, Cristina L

2017-11-01

Adrenocortical carcinoma (ACC) is rare and confers an unfavorable prognosis in advanced stages. Other than combination chemotherapy with cisplatin, etoposide, doxorubicin, and mitotane, the second- and third-line regimens are not well-established. Gemcitabine (GEM)-based chemotherapy was suggested in a phase 2 clinical trial with 28 patients. In other solid tumors, human equilibrative nucleoside transporter type 1 (hENT1) and/or ribonucleotide reductase catalytic subunit M1 (RRM1) expression have been associated with resistance to GEM. To assess the efficacy of GEM-based chemotherapy in ACC in a real-world setting and the predictive role of molecular parameters. Retrospective multicenter study. Referral centers of university hospitals. A total of 145 patients with advanced ACC were treated with GEM-based chemotherapy (132 with concomitant capecitabine). Formalin-fixed paraffin-embedded tumor material was available for 70 patients for immunohistochemistry. The main outcome measures were progression-free survival (PFS) and an objective response to GEM-based chemotherapy. The secondary objective was the predictive role of hENT1 and RRM1. The median PFS for the patient population was 12 weeks (range, 1 to 94). A partial response or stable disease was achieved in 4.9% and 25.0% of cases, with a median duration of 26.8 weeks. Treatment was generally well tolerated, with adverse events of grade 3 or 4 occurring in 11.0% of cases. No substantial effect of hENT1 and/or RRM1 expression was observed in response to GEM-based chemotherapy. GEM-based chemotherapy is a well-tolerated, but modestly active, regimen against advanced ACC. No reliable molecular predictive factors could be identified. Owing to the scarce alternative therapeutic options, GEM-based chemotherapy remains an important option for salvage treatment for advanced ACC. Copyright © 2017 Endocrine Society

Monsoon-driven transport of atmospheric mercury to the South China Sea from the Chinese mainland and Southeast Asia-Observation of gaseous elemental mercury at a background station in South China.

PubMed

Liu, Ming; Chen, Laiguo; Xie, Donghai; Sun, Jiaren; He, Qiusheng; Cai, Limei; Gao, Zhiqiang; Zhang, Yiqiang

2016-11-01

Concentrations of gaseous elemental mercury (GEM) were continuously monitored from May 2011 to May 2012 at the Wuzhishan State Atmosphere Background Monitoring Station (109°29'30.2″ E, 18°50'11.0″ N) located in Hainan Island. This station is an ideal site for monitoring long-range transport of atmospheric pollutants from mainland China and Southeast Asia to South China Sea. Annual average GEM concentration was 1.58 ± 0.71 ng m -3 during the monitoring period, which was close to background values in the Northern Hemisphere. GEM concentrations showed a clear seasonal variation with relatively higher levels in autumn (1.86 ± 0.55 ng m -3 ) and winter (1.80 ± 0.62 ng m -3 ) and lower levels in spring (1.16 ± 0.45 ng m -3 ) and summer (1.43 ± 0.46 ng m -3 ). Long-range atmospheric transport dominated by monsoons was a dominant factor influencing the seasonal variations of GEM. The GEM diel trends were related to the wind speed and long-range atmospheric mercury transport. We observed 30 pollution episodes throughout the monitoring period. The analysis of wind direction and backward trajectory suggested that elevated GEM concentrations at the monitoring site were primarily related to the outflows of atmospheric Hg from mainland China and the Indochina peninsula. The △GEM/△CO values also suggested that GEM was significantly affected by the long-range transport from the anthropogenic sources and biomass burning in Asia and Indochina peninsula.

Atmospheric mercury measurements at a suburban site in the Mid-Atlantic United States: Inter-annual, seasonal and diurnal variations and source-receptor relationships

NASA Astrophysics Data System (ADS)

Ren, Xinrong; Luke, Winston T.; Kelley, Paul; Cohen, Mark D.; Artz, Richard; Olson, Mark L.; Schmeltz, David; Puchalski, Melissa; Goldberg, Daniel L.; Ring, Allison; Mazzuca, Gina M.; Cummings, Kristin A.; Wojdan, Lisa; Preaux, Sandra; Stehr, Jeff W.

2016-12-01

Different atmospheric mercury forms have been measured at a suburban site in Beltsville, Maryland in the Mid-Atlantic United States since 2007 to investigate their inter-annual, seasonal and diurnal variabilities. Average concentrations and standard deviations of hourly measurements from 2007 to 2015 were 1.41 ± 0.23 ng m-3 for gaseous elemental mercury (GEM), 4.6 ± 33.7 pg m-3 for gaseous oxidized mercury (GOM), and 8.6 ± 56.8 pg m-3 for particulate-bound mercury (PBM). Observations show that on average, the rates of decrease were 0.020 ± 0.007 ng m-3 yr-1 (or 1.3 ± 0.5% yr-1, statistically significant, p-value < 0.01) for GEM, 0.54 ± 0.19 pg m-3 yr-1 (or 7.3 ± 2.6% yr-1, statistically significant, p-value < 0.01) for GOM, and 0.15 ± 0.35 pg m-3 yr-1 (or 1.6 ± 3.8% yr-1, statistically insignificant, p-value > 0.01) for PBM over this nine-year period. In addition, the collocated annual mercury wet deposition decreased at a rate of 0.51 ± 0.24 μg m-2 yr-2 (or 4.2 ± 1.9% yr-1, statistically insignificant, p-value > 0.01). Diurnal variation of GEM shows a slight peak in the morning, likely due to the shallow boundary layer. Seasonal variation of GEM shows lower levels in fall. Both diurnal variations of GOM and PBM show peaks in the afternoon likely due to the photochemical production of reactive mercury from the oxidation of GEM and the influence of boundary layer processes. Seasonally, GOM measurements show high levels in spring and constant low levels in the other three seasons, while PBM measurements exhibit higher levels from late fall to early spring and lower levels from late spring to fall. These measurement data were analyzed using the HYSPLIT back trajectory model in order to examine possible source-receptor relationships at this suburban site. Trajectory frequency analysis shows that high GEM/GOM/PBM events were generally associated with high frequencies of the trajectories passing through areas with high mercury emissions, while low GEM/GOM/PBM levels were largely associated the trajectories passing through relatively clean areas. This study indicates that local and regional sources appear to have a significant impact on the site and these impacts appear to have changed over time, as the local/regional emissions have been reduced.

LANDFILL GAS EMISSIONS MODEL (LANDGEM) VERSION 3.02 USER'S GUIDE

EPA Science Inventory

The Landfill Gas Emissions Model (LandGEM) is an automated estimation tool with a Microsoft Excel interface that can be used to estimate emission rates for total landfill gas, methane, carbon dioxide, nonmethane organic compounds, and individual air pollutants from municipal soli...

eDNAoccupancy: An R package for multi-scale occupancy modeling of environmental DNA data

USGS Publications Warehouse

Dorazio, Robert; Erickson, Richard A.

2017-01-01

In this article we describe eDNAoccupancy, an R package for fitting Bayesian, multi-scale occupancy models. These models are appropriate for occupancy surveys that include three, nested levels of sampling: primary sample units within a study area, secondary sample units collected from each primary unit, and replicates of each secondary sample unit. This design is commonly used in occupancy surveys of environmental DNA (eDNA). eDNAoccupancy allows users to specify and fit multi-scale occupancy models with or without covariates, to estimate posterior summaries of occurrence and detection probabilities, and to compare different models using Bayesian model-selection criteria. We illustrate these features by analyzing two published data sets: eDNA surveys of a fungal pathogen of amphibians and eDNA surveys of an endangered fish species.

Multiscale Modeling and Uncertainty Quantification for Nuclear Fuel Performance

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

Estep, Donald; El-Azab, Anter; Pernice, Michael

2017-03-23

In this project, we will address the challenges associated with constructing high fidelity multiscale models of nuclear fuel performance. We (*) propose a novel approach for coupling mesoscale and macroscale models, (*) devise efficient numerical methods for simulating the coupled system, and (*) devise and analyze effective numerical approaches for error and uncertainty quantification for the coupled multiscale system. As an integral part of the project, we will carry out analysis of the effects of upscaling and downscaling, investigate efficient methods for stochastic sensitivity analysis of the individual macroscale and mesoscale models, and carry out a posteriori error analysis formore » computed results. We will pursue development and implementation of solutions in software used at Idaho National Laboratories on models of interest to the Nuclear Energy Advanced Modeling and Simulation (NEAMS) program.« less

An Emission Measure Analysis of Stars Near the Transition Region Dividing Line

NASA Astrophysics Data System (ADS)

Linsky, Jeffery L.

We request high dispersion, short wavelength IUE spectra for three of the stars beta Gem (K0III), alpha Tau (K5III), epsilon Gem (G81b) and beta Cam (G0Ib) with exposure times of 16 hours or greater. These data will allow the measurement of line profiles, widths and Doppler shifts as well as density sensitive and opacity sensitive line ratios. Models of chromospheric and transition region structure will be calculated by emission measure techniques and model atmosphere computations for optically thick resonance lines such as MgII h and k, including partial redistribution radiation transfer. The chromospheric models will be used to investigate the energy balance of the atmosphere and the nature of the energy deposition processes. These results will be considered in relation to the evolutionary status of the stars, and will be compared with the atmospheric model properties of other stars previously studied by the authors and their collaborators.

Exploring molecular genetics of bladder cancer: lessons learned from mouse models

PubMed Central

Ahmad, Imran; Sansom, Owen J.; Leung, Hing Y.

2012-01-01

Urothelial cell carcinoma (UCC) of the bladder is one of the most common malignancies worldwide, causing considerable morbidity and mortality. It is unusual among the epithelial carcinomas because tumorigenesis can occur by two distinct pathways: low-grade, recurring papillary tumours usually contain oncogenic mutations in FGFR3 or HRAS, whereas high-grade, muscle-invasive tumours with metastatic potential generally have defects in the pathways controlled by the tumour suppressors p53 and retinoblastoma (RB). Over the past 20 years, a plethora of genetically engineered mouse (GEM) models of UCC have been developed, containing deletions or mutations of key tumour suppressor genes or oncogenes. In this review, we provide an up-to-date summary of these GEM models, analyse their flaws and weaknesses, discuss how they have advanced our understanding of UCC at the molecular level, and comment on their translational potential. We also highlight recent studies supporting a role for dysregulated Wnt signalling in UCC and the development of mouse models that recapitulate this dysregulation. PMID:22422829

Multiscale virtual particle based elastic network model (MVP-ENM) for normal mode analysis of large-sized biomolecules.

PubMed

Xia, Kelin

2017-12-20

In this paper, a multiscale virtual particle based elastic network model (MVP-ENM) is proposed for the normal mode analysis of large-sized biomolecules. The multiscale virtual particle (MVP) model is proposed for the discretization of biomolecular density data. With this model, large-sized biomolecular structures can be coarse-grained into virtual particles such that a balance between model accuracy and computational cost can be achieved. An elastic network is constructed by assuming "connections" between virtual particles. The connection is described by a special harmonic potential function, which considers the influence from both the mass distributions and distance relations of the virtual particles. Two independent models, i.e., the multiscale virtual particle based Gaussian network model (MVP-GNM) and the multiscale virtual particle based anisotropic network model (MVP-ANM), are proposed. It has been found that in the Debye-Waller factor (B-factor) prediction, the results from our MVP-GNM with a high resolution are as good as the ones from GNM. Even with low resolutions, our MVP-GNM can still capture the global behavior of the B-factor very well with mismatches predominantly from the regions with large B-factor values. Further, it has been demonstrated that the low-frequency eigenmodes from our MVP-ANM are highly consistent with the ones from ANM even with very low resolutions and a coarse grid. Finally, the great advantage of MVP-ANM model for large-sized biomolecules has been demonstrated by using two poliovirus virus structures. The paper ends with a conclusion.

Planning for subacute care: predicting demand using acute activity data.

PubMed

Green, Janette P; McNamee, Jennifer P; Kobel, Conrad; Seraji, Md Habibur R; Lawrence, Suanne J

2016-01-01

Objective The aim of the present study was to develop a robust model that uses the concept of 'rehabilitation-sensitive' Diagnosis Related Groups (DRGs) in predicting demand for rehabilitation and geriatric evaluation and management (GEM) care following acute in-patient episodes provided in Australian hospitals. Methods The model was developed using statistical analyses of national datasets, informed by a panel of expert clinicians and jurisdictional advice. Logistic regression analysis was undertaken using acute in-patient data, published national hospital statistics and data from the Australasian Rehabilitation Outcomes Centre. Results The predictive model comprises tables of probabilities that patients will require rehabilitation or GEM care after an acute episode, with columns defined by age group and rows defined by grouped Australian Refined (AR)-DRGs. Conclusions The existing concept of rehabilitation-sensitive DRGs was revised and extended. When applied to national data, the model provided a conservative estimate of 83% of the activity actually provided. An example demonstrates the application of the model for service planning. What is known about the topic? Health service planning is core business for jurisdictions and local areas. With populations ageing and an acknowledgement of the underservicing of subacute care, it is timely to find improved methods of estimating demand for this type of care. Traditionally, age-sex standardised utilisation rates for individual DRGs have been applied to Australian Bureau of Statistics (ABS) population projections to predict the future need for subacute services. Improved predictions became possible when some AR-DRGs were designated 'rehabilitation-sensitive'. This improved methodology has been used in several Australian jurisdictions. What does this paper add? This paper presents a new tool, or model, to predict demand for rehabilitation and GEM services based on in-patient acute activity. In this model, the methodology based on rehabilitation-sensitive AR-DRGs has been extended by updating them to AR-DRG Version 7.0, quantifying the level of 'sensitivity' and incorporating the patient's age to improve the prediction of demand for subacute services. What are the implications for practitioners? The predictive model takes the form of tables of probabilities that patients will require rehabilitation or GEM care after an acute episode and can be applied to acute in-patient administrative datasets in any Australian jurisdiction or local area. The use of patient-level characteristics will enable service planners to improve their forecasting of demand for these services. Clinicians and jurisdictional representatives consulted during the project regarded the model favourably and believed that it was an improvement on currently available methods.

Antitumor Activity of the Investigational Proteasome Inhibitor MLN9708 in Mouse Models of B-cell and Plasma Cell Malignancies

PubMed Central

Lee, Edmund C.; Fitzgerald, Michael; Bannerman, Bret; Donelan, Jill; Bano, Kristen; Terkelsen, Jennifer; Bradley, Daniel P.; Subakan, Ozlem; Silva, Matthew D.; Liu, Ray; Pickard, Michael; Li, Zhi; Tayber, Olga; Li, Ping; Hales, Paul; Carsillo, Mary; Neppalli, Vishala T.; Berger, Allison J.; Kupperman, Erik; Manfredi, Mark; Bolen, Joseph B.; Van Ness, Brian; Janz, Siegfried

2012-01-01

Purpose The clinical success of the first-in-class proteasome inhibitor bortezomib (VELCADE) has validated the proteasome as a therapeutic target for treating human cancers. MLN9708 is an investigational proteasome inhibitor that, compared with bortezomib, has improved pharmacokinetics, pharmacodynamics, and antitumor activity in preclinical studies. Here, we focused on evaluating the in vivo activity of MLN2238 (the biologically active form of MLN9708) in a variety of mouse models of hematologic malignancies, including tumor xenograft models derived from a human lymphoma cell line and primary human lymphoma tissue, and genetically engineered mouse (GEM) models of plasma cell malignancies (PCM). Experimental Design Both cell line–derived OCI-Ly10 and primary human lymphoma–derived PHTX22L xenograft models of diffuse large B-cell lymphoma were used to evaluate the pharmacodynamics and antitumor effects of MLN2238 and bortezomib. The iMycCα/Bcl-XL GEM model was used to assess their effects on de novo PCM and overall survival. The newly developed DP54-Luc–disseminated model of iMycCα/ Bcl-XL was used to determine antitumor activity and effects on osteolytic bone disease. Results MLN2238 has an improved pharmacodynamic profile and antitumor activity compared with bortezomib in both OCI-Ly10 and PHTX22L models. Although both MLN2238 and bortezomib prolonged overall survival, reduced splenomegaly, and attenuated IgG2a levels in the iMycCα/Bcl-XL GEM model, only MLN2238 alleviated osteolytic bone disease in the DP54-Luc model. Conclusions Our results clearly showed the antitumor activity of MLN2238 in a variety of mouse models of B-cell lymphoma and PCM, supporting its clinical development. MLN9708 is being evaluated in multiple phase I and I/II trials. PMID:21903769

Multiscale Modeling of Ceramic Matrix Composites

NASA Technical Reports Server (NTRS)

Bednarcyk, Brett A.; Mital, Subodh K.; Pineda, Evan J.; Arnold, Steven M.

2015-01-01

Results of multiscale modeling simulations of the nonlinear response of SiC/SiC ceramic matrix composites are reported, wherein the microstructure of the ceramic matrix is captured. This micro scale architecture, which contains free Si material as well as the SiC ceramic, is responsible for residual stresses that play an important role in the subsequent thermo-mechanical behavior of the SiC/SiC composite. Using the novel Multiscale Generalized Method of Cells recursive micromechanics theory, the microstructure of the matrix, as well as the microstructure of the composite (fiber and matrix) can be captured.

Revisiting of Multiscale Static Analysis of Notched Laminates Using the Generalized Method of Cells

NASA Technical Reports Server (NTRS)

Naghipour Ghezeljeh, Paria; Arnold, Steven M.; Pineda, Evan J.

2016-01-01

Composite material systems generally exhibit a range of behavior on different length scales (from constituent level to macro); therefore, a multiscale framework is beneficial for the design and engineering of these material systems. The complex nature of the observed composite failure during experiments suggests the need for a three-dimensional (3D) multiscale model to attain a reliable prediction. However, the size of a multiscale three-dimensional finite element model can become prohibitively large and computationally costly. Two-dimensional (2D) models are preferred due to computational efficiency, especially if many different configurations have to be analyzed for an in-depth damage tolerance and durability design study. In this study, various 2D and 3D multiscale analyses will be employed to conduct a detailed investigation into the tensile failure of a given multidirectional, notched carbon fiber reinforced polymer laminate. Threedimensional finite element analysis is typically considered more accurate than a 2D finite element model, as compared with experiments. Nevertheless, in the absence of adequate mesh refinement, large differences may be observed between a 2D and 3D analysis, especially for a shear-dominated layup. This observed difference has not been widely addressed in previous literature and is the main focus of this paper.

Updating sea spray aerosol emissions in the Community Multiscale Air Quality (CMAQ) model

EPA Science Inventory

Sea spray aerosols (SSA) impact the particle mass concentration and gas-particle partitioning in coastal environments, with implications for human and ecosystem health. In this study, the Community Multiscale Air Quality (CMAQ) model is updated to enhance fine mode SSA emissions,...

Industrial process system assessment: bridging process engineering and life cycle assessment through multiscale modeling.

EPA Science Inventory

The Industrial Process System Assessment (IPSA) methodology is a multiple step allocation approach for connecting information from the production line level up to the facility level and vice versa using a multiscale model of process systems. The allocation procedure assigns inpu...

Cloud processing of gases and aerosols in the Community Multiscale Air Quality (CMAQ) model: Impacts of extended chemistry

EPA Science Inventory

Clouds and fogs can significantly impact the concentration and distribution of atmospheric gases and aerosols through chemistry, scavenging, and transport. This presentation summarizes the representation of cloud processes in the Community Multiscale Air Quality (CMAQ) modeling ...

Multi-scale habitat selection modeling: A review and outlook

Treesearch

Kevin McGarigal; Ho Yi Wan; Kathy A. Zeller; Brad C. Timm; Samuel A. Cushman

2016-01-01

Scale is the lens that focuses ecological relationships. Organisms select habitat at multiple hierarchical levels and at different spatial and/or temporal scales within each level. Failure to properly address scale dependence can result in incorrect inferences in multi-scale habitat selection modeling studies.

A Multi-Resolution Assessment of the Community Multiscale Air Quality (CMAQ) Model v4.7 Wet Deposition Estimates for 2002 - 2006

EPA Science Inventory

This paper examines the operational performance of the Community Multiscale Air Quality (CMAQ) model simulations for 2002 - 2006 using both 36-km and 12-km horizontal grid spacing, with a primary focus on the performance of the CMAQ model in predicting wet deposition of sulfate (...

Developing a novel hierarchical approach for multiscale structural reliability predictions for ultra-high consequence applications

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

Emery, John M.; Coffin, Peter; Robbins, Brian A.

Microstructural variabilities are among the predominant sources of uncertainty in structural performance and reliability. We seek to develop efficient algorithms for multiscale calcu- lations for polycrystalline alloys such as aluminum alloy 6061-T6 in environments where ductile fracture is the dominant failure mode. Our approach employs concurrent multiscale methods, but does not focus on their development. They are a necessary but not sufficient ingredient to multiscale reliability predictions. We have focused on how to efficiently use concurrent models for forward propagation because practical applications cannot include fine-scale details throughout the problem domain due to exorbitant computational demand. Our approach begins withmore » a low-fidelity prediction at the engineering scale that is sub- sequently refined with multiscale simulation. The results presented in this report focus on plasticity and damage at the meso-scale, efforts to expedite Monte Carlo simulation with mi- crostructural considerations, modeling aspects regarding geometric representation of grains and second-phase particles, and contrasting algorithms for scale coupling.« less

Copper-catalyzed cross-coupling reactions of epoxides with gem-diborylmethane: access to γ-hydroxyl boronic esters.

PubMed

Ebrahim-Alkhalil, Ahmed; Zhang, Zhen-Qi; Gong, Tian-Jun; Su, Wei; Lu, Xiao-Yu; Xiao, Bin; Fu, Yao

2016-04-07

Herein, we describe a novel copper-catalyzed epoxide opening reaction with gem-diborylmethane. Aliphatic, aromatic epoxides as well as aziridines are converted to the corresponding γ-pinacolboronate alcohols or amines in moderate to excellent yields. This new reaction provides beneficial applications for classic epoxide substrates as well as interesting gem-diborylalkane reagents.

Mountain Gem Russet: A medium to late season potato variety with high early and full season yield potential and excellent fresh market characteristics

USDA-ARS?s Scientific Manuscript database

Mountain Gem Russet is a medium to late maturing variety with both high early and full season yields of oblong-long, medium-russeted tubers having higher protein content than those of standard potato varieties. Mountain Gem Russet has greater resistance to tuber late blight, tuber malformations and ...

Development, characterization and qualification of first GEM foils produced in India

NASA Astrophysics Data System (ADS)

Shah, Aashaq; Ahmed, Asar; Gola, Mohit; Sharma, Ram Krishna; Malhotra, Shivali; Kumar, Ashok; Naimuddin, Md.; Menon, Pradeep; Srinivasan, K.

2018-06-01

The increasing demand for Gas Electron Multiplier (GEM) foils has been driven by their application in many current and proposed high-energy physics experiments. Micropack, a Bengaluru-based company, has established and commercialized GEM foils for the first time in India. Micropack used the double-mask etching technique to successfully produce 10 cm × 10 cm GEM foil. In this paper, we report on the development as well as the geometrical and electrical properties of these foils, including the size uniformity of the holes and leakage current measurements. Our characterization studies show that the foils are of good quality and satisfy all the necessary quality control criteria.

Gemcitabine inhibits proliferation and induces apoptosis in human pancreatic cancer PANC-1 cells.

PubMed

Yong-Xian, Gui; Xiao-Huan, Li; Fan, Zhang; Guo-Fang, Tian

2016-10-01

The aim of the study is to investigate the underlying molecular mechanisms by which gemcitabine (gem) inhibits proliferation and induces apoptosis in human pancreatic cancer PANC-1 cells in vitro. After PANC-1 cells had been treated by indicated concentration (0, 5, and 25 mg/L) of gem for 48 h, cell proliferation was evaluated by 3'-(4, 5 dimethyl-thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay; cell morphology was observed by transmission electron microscopy; Expression of c-IAP2 and Bcl-2 proteins was analyzed by Western blot; the activity of caspase-3 and -9 was detected by spectrophotometry. Gem significantly inhibited cell proliferation and could induce apoptosis of human pancreatic cancer PANC-1 cells, with a dose-dependent manner. Western blot analysis showed that gem significantly reduced c-IAP2 and Bcl-2 proteins expression level (P < 0.05). Spectrophotometric assay showed that gem significantly increased caspase-3 and -9 activity in PANC-1 cells. Gem could induce apoptosis of human pancreatic cancer PANC-1 cells, probably through downregulating c-IAP2 and Bcl-2 expression levels, and at the same time activating caspase-3 and -9.

Creation of a genetic calcium channel blocker by targeted gem gene transfer in the heart.

PubMed

Murata, Mitsushige; Cingolani, Eugenio; McDonald, Amy D; Donahue, J Kevin; Marbán, Eduardo

2004-08-20

Calcium channel blockers are among the most commonly used therapeutic drugs. Nevertheless, the utility of calcium channel blockers for heart disease is limited because of the potent vasodilatory effect that causes hypotension, and other side effects attributable to blockade of noncardiac channels. Therefore, focal calcium channel blockade by gene transfer is highly desirable. With a view to creating a focally applicable genetic calcium channel blocker, we overexpressed the ras-related small G-protein Gem in the heart by somatic gene transfer. Adenovirus-mediated delivery of Gem markedly decreased L-type calcium current density in ventricular myocytes, resulting in the abbreviation of action potential duration. Furthermore, transduction of Gem resulted in a significant shortening of the electrocardiographic QTc interval and reduction of left ventricular systolic function. Focal delivery of Gem to the atrioventricular (AV) node significantly slowed AV nodal conduction (prolongation of PR and AH intervals), which was effective in the reduction of heart rate during atrial fibrillation. Thus, these results indicate that gene transfer of Gem functions as a genetic calcium channel blocker, the local application of which can effectively modulate cardiac electrical and contractile function.

Does Comet WILD-2 contain Gems?

NASA Technical Reports Server (NTRS)

Chi, M.; Ishii, H.; Dai, Z. R.; Toppani, A.; Joswiak, D. J.; Leroux, H.; Zolensky, M.; Keller, L. P.; Browning, N. D.

2007-01-01

It is expected that Comet Wild-2 dust should resemble anhydrous carbon-rich, chondritic porous (CP) interplanetary dust particles (IDPs) collected in the stratosphere because some CP IDPs are suspected to be from comets. The rarity of carbonaceous grains and presolar silicates, as well as the presence of high-temperature inner solar nebula minerals in the Wild-2 sample (e.g. osbornite and melilite), appear incompatible with most CP IDPs. However, it is premature to draw firm conclusions about the mineralogy of comet Wild-2 because only approx. 1% of the sample has been examined. The most abundant silicates in CP IDPs are GEMS (glass with embedded metal and sulfides). Nonsolar O isotopic compositions confirm that at least some GEMS in IDPs are presolar amorphous silicates. The presence or absence of GEMS in the Wild-2 sample is important because it addresses, (a) the relationship between CP IDPs and comets, and (b) the hypothesis that other GEMS in IDPs formed in the solar nebula. Here we show that most of the GEMSlike materials so far identified in Stardust aerogel were likely impact generated during collection. At the nanometer scale, they are compositionally and crystallographically distinct from GEMS in IDPs.

A review of current challenges for the identification of gemstones

NASA Astrophysics Data System (ADS)

Shigley, James E.

2008-01-01

A variety of treated and synthetic gem materials are encountered today in the jewelry marketplace in increasing quantities. Although normally entering into the market with correct information, in some cases these materials are sold with incorrect or inaccurate information on their identity. In some cases, they exhibit appearances that correspond closely to those of valuable untreated, natural gemstones. Although they can display certain distinctive gemological characteristics, some treated and synthetic gem materials can be difficult for jewelers to recognize, especially when these individuals lack gemological training and access to standard gem-testing methods and equipment. In such instances, testing by a professional gemological laboratory may be required. Accurate gem identification and complete information disclosure are essential in the jewelry trade to maintain both the commercial value of natural gemstones and the confidence among consumers who are considering gemstone purchases. The goal of most current gemological research is to provide practical means of gem identification for jewelers and gemologists to help insure integrity in the international gemstone trade. To support this goal, research on gem materials increasingly relies upon characterization with modern analytical tools such as chemical analysis, various spectroscopy methods, and other scientific techniques.

A review of predictive nonlinear theories for multiscale modeling of heterogeneous materials

NASA Astrophysics Data System (ADS)

Matouš, Karel; Geers, Marc G. D.; Kouznetsova, Varvara G.; Gillman, Andrew

2017-02-01

Since the beginning of the industrial age, material performance and design have been in the midst of innovation of many disruptive technologies. Today's electronics, space, medical, transportation, and other industries are enriched by development, design and deployment of composite, heterogeneous and multifunctional materials. As a result, materials innovation is now considerably outpaced by other aspects from component design to product cycle. In this article, we review predictive nonlinear theories for multiscale modeling of heterogeneous materials. Deeper attention is given to multiscale modeling in space and to computational homogenization in addressing challenging materials science questions. Moreover, we discuss a state-of-the-art platform in predictive image-based, multiscale modeling with co-designed simulations and experiments that executes on the world's largest supercomputers. Such a modeling framework consists of experimental tools, computational methods, and digital data strategies. Once fully completed, this collaborative and interdisciplinary framework can be the basis of Virtual Materials Testing standards and aids in the development of new material formulations. Moreover, it will decrease the time to market of innovative products.

A review of predictive nonlinear theories for multiscale modeling of heterogeneous materials

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

Matouš, Karel, E-mail: kmatous@nd.edu; Geers, Marc G.D.; Kouznetsova, Varvara G.

2017-02-01

Since the beginning of the industrial age, material performance and design have been in the midst of innovation of many disruptive technologies. Today's electronics, space, medical, transportation, and other industries are enriched by development, design and deployment of composite, heterogeneous and multifunctional materials. As a result, materials innovation is now considerably outpaced by other aspects from component design to product cycle. In this article, we review predictive nonlinear theories for multiscale modeling of heterogeneous materials. Deeper attention is given to multiscale modeling in space and to computational homogenization in addressing challenging materials science questions. Moreover, we discuss a state-of-the-art platformmore » in predictive image-based, multiscale modeling with co-designed simulations and experiments that executes on the world's largest supercomputers. Such a modeling framework consists of experimental tools, computational methods, and digital data strategies. Once fully completed, this collaborative and interdisciplinary framework can be the basis of Virtual Materials Testing standards and aids in the development of new material formulations. Moreover, it will decrease the time to market of innovative products.« less

Integrated Farm System Model Version 4.3 and Dairy Gas Emissions Model Version 3.3 Software development and distribution

USDA-ARS?s Scientific Manuscript database

Modeling routines of the Integrated Farm System Model (IFSM version 4.2) and Dairy Gas Emission Model (DairyGEM version 3.2), two whole-farm simulation models developed and maintained by USDA-ARS, were revised with new components for: (1) simulation of ammonia (NH3) and greenhouse gas emissions gene...

Beyond Low Rank + Sparse: Multi-scale Low Rank Matrix Decomposition

PubMed Central

Ong, Frank; Lustig, Michael

2016-01-01

We present a natural generalization of the recent low rank + sparse matrix decomposition and consider the decomposition of matrices into components of multiple scales. Such decomposition is well motivated in practice as data matrices often exhibit local correlations in multiple scales. Concretely, we propose a multi-scale low rank modeling that represents a data matrix as a sum of block-wise low rank matrices with increasing scales of block sizes. We then consider the inverse problem of decomposing the data matrix into its multi-scale low rank components and approach the problem via a convex formulation. Theoretically, we show that under various incoherence conditions, the convex program recovers the multi-scale low rank components either exactly or approximately. Practically, we provide guidance on selecting the regularization parameters and incorporate cycle spinning to reduce blocking artifacts. Experimentally, we show that the multi-scale low rank decomposition provides a more intuitive decomposition than conventional low rank methods and demonstrate its effectiveness in four applications, including illumination normalization for face images, motion separation for surveillance videos, multi-scale modeling of the dynamic contrast enhanced magnetic resonance imaging and collaborative filtering exploiting age information. PMID:28450978

A Study of Spatio-Temporal Variability in Future Wind Energy over the Korean Peninsula Using Regional Climate Model Ensemble Projections

NASA Astrophysics Data System (ADS)

KIM, Y.; Lim, Y. J.; Kim, Y. H.; Kim, B. J.

2015-12-01

The impacts of climate change on wind speed, wind energy density (WED), and potential electronic production (PEP) over the Korean peninsula have been investigated by using five regional climate models (HadGEM3-RA, RegCM, WRF, GRIMs and MM5) ensemble projection data. HadGEM2-AO based two RCP scenarios (RCP4.5/8.5) data have been used for initial and boundary condition to all RCMs. Wind energy density and its annual and seasonal variability have been estimated based on monthly near-surface wind speeds, and the potential electronic production and its change have been also analyzed. As a result of comparison ensemble models based annual mean wind speed for 25-yr historical period (1981-2005) to the ERA-interim, it is shown that all RCMs overestimate near-surface wind speed compared to the reanalysis data but the results of HadGEM3-RA are most comparable. The changes annual and seasonal mean of WED and PEP for the historical period and comparison results to future projection (2021-2050) will be presented in this poster session. We also scrutinize the changes in mean sea level pressure and mean sea level pressure gradient in driving GCM/RCM as a factor inducing the variations. Our results can be used as a background data for devising a plan to develop and operate wind farm over the Korean Peninsula.

Coordinated X-ray, ultraviolet and optical observations of AM Herculis, U Geminorum, and SS Cygni

NASA Technical Reports Server (NTRS)

Fabbiano, G.; Hartmann, L.; Raymond, J.; Branduardi-Raymont, G.; Matilsky, T.; Steiner, J.

1981-01-01

Simultaneous and quasi-simultaneous optical, UV and X-ray observations of the accreting degenerate dwarf stars AM Herculis, U Geminorum and SS Cygni are reported. The observations were obtained in March 1979, by instruments on board the Einstein Observatory and the IUE satellite, and optical properties were monitored on the ground. AM Her was found to be in a high state at the time of the observations, while SS Cyg and U Gem appeared to be in the optical low state. The presence of a strong UV excess is found in SS Cyg, U Gem and AM Her, which most likely originates from the boundary of the accretion disk in U Gem. The observed excess, with a blackbody component greater than 10 eV, is noted to be inconsistent with standard accretion disk and column models. It is suggested that nuclear burning at the surface of the white dwarf may be responsible for the excess UV flux in the three systems, with differences in spectral distributions resulting from different levels of magnetic field intensity and accretion rate.

Transition between inverse and direct energy cascades in multiscale optical turbulence.

PubMed

Malkin, V M; Fisch, N J

2018-03-01

Multiscale turbulence naturally develops and plays an important role in many fluid, gas, and plasma phenomena. Statistical models of multiscale turbulence usually employ Kolmogorov hypotheses of spectral locality of interactions (meaning that interactions primarily occur between pulsations of comparable scales) and scale-invariance of turbulent pulsations. However, optical turbulence described by the nonlinear Schrodinger equation exhibits breaking of both the Kolmogorov locality and scale-invariance. A weaker form of spectral locality that holds for multi-scale optical turbulence enables a derivation of simplified evolution equations that reduce the problem to a single scale modeling. We present the derivation of these equations for Kerr media with random inhomogeneities. Then, we find the analytical solution that exhibits a transition between inverse and direct energy cascades in optical turbulence.

Transition between inverse and direct energy cascades in multiscale optical turbulence

NASA Astrophysics Data System (ADS)

Malkin, V. M.; Fisch, N. J.

2018-03-01

Multiscale turbulence naturally develops and plays an important role in many fluid, gas, and plasma phenomena. Statistical models of multiscale turbulence usually employ Kolmogorov hypotheses of spectral locality of interactions (meaning that interactions primarily occur between pulsations of comparable scales) and scale-invariance of turbulent pulsations. However, optical turbulence described by the nonlinear Schrodinger equation exhibits breaking of both the Kolmogorov locality and scale-invariance. A weaker form of spectral locality that holds for multi-scale optical turbulence enables a derivation of simplified evolution equations that reduce the problem to a single scale modeling. We present the derivation of these equations for Kerr media with random inhomogeneities. Then, we find the analytical solution that exhibits a transition between inverse and direct energy cascades in optical turbulence.

Hybrid multiscale modeling and prediction of cancer cell behavior

PubMed Central

Habibi, Jafar

2017-01-01

Background Understanding cancer development crossing several spatial-temporal scales is of great practical significance to better understand and treat cancers. It is difficult to tackle this challenge with pure biological means. Moreover, hybrid modeling techniques have been proposed that combine the advantages of the continuum and the discrete methods to model multiscale problems. Methods In light of these problems, we have proposed a new hybrid vascular model to facilitate the multiscale modeling and simulation of cancer development with respect to the agent-based, cellular automata and machine learning methods. The purpose of this simulation is to create a dataset that can be used for prediction of cell phenotypes. By using a proposed Q-learning based on SVR-NSGA-II method, the cells have the capability to predict their phenotypes autonomously that is, to act on its own without external direction in response to situations it encounters. Results Computational simulations of the model were performed in order to analyze its performance. The most striking feature of our results is that each cell can select its phenotype at each time step according to its condition. We provide evidence that the prediction of cell phenotypes is reliable. Conclusion Our proposed model, which we term a hybrid multiscale modeling of cancer cell behavior, has the potential to combine the best features of both continuum and discrete models. The in silico results indicate that the 3D model can represent key features of cancer growth, angiogenesis, and its related micro-environment and show that the findings are in good agreement with biological tumor behavior. To the best of our knowledge, this paper is the first hybrid vascular multiscale modeling of cancer cell behavior that has the capability to predict cell phenotypes individually by a self-generated dataset. PMID:28846712

Hybrid multiscale modeling and prediction of cancer cell behavior.

PubMed

Zangooei, Mohammad Hossein; Habibi, Jafar

2017-01-01

Understanding cancer development crossing several spatial-temporal scales is of great practical significance to better understand and treat cancers. It is difficult to tackle this challenge with pure biological means. Moreover, hybrid modeling techniques have been proposed that combine the advantages of the continuum and the discrete methods to model multiscale problems. In light of these problems, we have proposed a new hybrid vascular model to facilitate the multiscale modeling and simulation of cancer development with respect to the agent-based, cellular automata and machine learning methods. The purpose of this simulation is to create a dataset that can be used for prediction of cell phenotypes. By using a proposed Q-learning based on SVR-NSGA-II method, the cells have the capability to predict their phenotypes autonomously that is, to act on its own without external direction in response to situations it encounters. Computational simulations of the model were performed in order to analyze its performance. The most striking feature of our results is that each cell can select its phenotype at each time step according to its condition. We provide evidence that the prediction of cell phenotypes is reliable. Our proposed model, which we term a hybrid multiscale modeling of cancer cell behavior, has the potential to combine the best features of both continuum and discrete models. The in silico results indicate that the 3D model can represent key features of cancer growth, angiogenesis, and its related micro-environment and show that the findings are in good agreement with biological tumor behavior. To the best of our knowledge, this paper is the first hybrid vascular multiscale modeling of cancer cell behavior that has the capability to predict cell phenotypes individually by a self-generated dataset.

New Approach to Monitor Transboundary Particulate Pollution over Northeast Asia

NASA Technical Reports Server (NTRS)

Park, M. E.; Song, C. H.; Park, R. S.; Lee, Jaehwa; Kim, J.; Lee, S.; Woo, J. H.; Carmichael, G. R.; Eck, Thomas F.; Holben, Brent N.;

New approach to monitor transboundary particulate pollution over Northeast Asia

NASA Astrophysics Data System (ADS)

Park, M. E.; Song, C. H.; Park, R. S.; Lee, J.; Kim, J.; Lee, S.; Woo, J.-H.; Carmichael, G. R.; Eck, T. F.; Holben, B. N.; Lee, S.-S.; Song, C. K.; Hong, Y. D.

2014-01-01

A new approach to more accurately monitor and evaluate transboundary particulate matter (PM) pollution is introduced based on aerosol optical products from Korea's Geostationary Ocean Color Imager (GOCI). The area studied is Northeast Asia (including eastern parts of China, the Korean peninsula and Japan), where GOCI has been monitoring since June 2010. The hourly multi-spectral aerosol optical data that were retrieved from GOCI sensor onboard geostationary satellite COMS (Communication, Ocean, and Meteorology Satellite) through the Yonsei aerosol retrieval algorithm were first presented and used in this study. The GOCI-retrieved aerosol optical data are integrated with estimated aerosol distributions from US EPA Models-3/CMAQ (Community Multi-scale Air Quality) v4.5.1 model simulations via data assimilation technique, thereby making the aerosol data spatially continuous and available even for cloud contamination cells. The assimilated aerosol optical data are utilized to provide quantitative estimates of transboundary PM pollution from China to the Korean peninsula and Japan. For the period of 1 April to 31 May, 2011 this analysis yields estimates that AOD as a proxy for PM2.5 or PM10 during long-range transport events increased by 117-265% compared to background average AOD (aerosol optical depth) at the four AERONET sites in Korea, and average AOD increases of 121% were found when averaged over the entire Korean peninsula. This paper demonstrates that the use of multi-spectral AOD retrievals from geostationary satellites can improve estimates of transboundary PM pollution. Such data will become more widely available later this decade when new sensors such as the GEMS (Geostationary Environment Monitoring Spectrometer) and GOCI-2 are scheduled to be launched.

Precision GPS ephemerides and baselines

NASA Technical Reports Server (NTRS)

1992-01-01

The required knowledge of the Global Positioning System (GPS) satellite position accuracy can vary depending on a particular application. Application to relative positioning of receiver locations on the ground to infer Earth's tectonic plate motion requires the most accurate knowledge of the GPS satellite orbits. Research directed towards improving and evaluating the accuracy of GPS satellite orbits was conducted at the University of Texas Center for Space Research (CSR). Understanding and modeling the forces acting on the satellites was a major focus of the research. Other aspects of orbit determination, such as the reference frame, time system, measurement modeling, and parameterization, were also investigated. Gravitational forces were modeled by truncated versions of extant gravity fields such as, Goddard Earth Model (GEM-L2), GEM-T1, TEG-2, and third body perturbations due to the Sun and Moon. Nongravitational forces considered were the solar radiation pressure, and perturbations due to thermal venting and thermal imbalance. At the GPS satellite orbit accuracy level required for crustal dynamic applications, models for the nongravitational perturbation play a critical role, since the gravitational forces are well understood and are modeled adequately for GPS satellite orbits.

WW Geminorum: An early B-type eclipsing binary evolving into the contact phase

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

Yang, Y.-G.; Dai, H.-F.; Yin, X.-G.

2014-11-01

WW Gem is a B-type eclipsing binary with a period of 1.2378 days. The CCD photometry of this binary was performed in 2013 December using the 85 cm telescope at the Xinglong Stations of the National Astronomical Observatories of China. Using the updated W-D program, the photometric model was deduced from the VRI light curves. The results imply that WW Gem is a near-contact eclipsing binary whose primary component almost fills its Roche lobe. The photometric mass ratio is q {sub ph} = 0.48(± 0.05). All collected times of minimum light, including two new ones, were used for the periodmore » studies. The orbital period changes of WW Gem could be described by an upward parabola, possibly overlaid by a light-time orbit with a period of P {sub mod} = 7.41(± 0.04) yr and a semi-amplitude of A = 0.0079 days(± 0.0005 days), respectively. This kind of cyclic oscillation may be attributed to the light-travel time effect via the third body. The long-term period increases at a rate of dP/dt = +3.47(±0.04) × 10{sup –8} day yr{sup –1}, which may be explained by the conserved mass transfer from the less massive component to the more massive one. With mass transfer, the massive binary WW Gem may be evolving into a contact binary.« less

ULTRAVIOLET SPECTROSCOPY OF PQ Gem AND V405 Aur FROM THE HST AND IUE SATELLITES

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

Sanad, M. R., E-mail: mrsanad1@yahoo.com

Ultraviolet spectra of two intermediate polars (IPs), PQ Gem and V405 Aur, observed with Hubble Space Telescope (HST) Space Telescope Imaging Spectrograph and Faint Object Spectrograph and International Ultraviolet Explorer (IUE) satellites were analyzed during the period between 1994–2000. We estimated the reddening of the two systems from the 2200 Å feature. Six spectra of the two systems revealing modulations of line fluxes at different times are presented. PQ Gem and V405 Aur are featured by spectral lines in different ionization states. This paper focuses on the third ionized carbon emission line at 1550 Å and the first ionized heliummore » emission line at 1640 Å produced in the optically thin outer region of the accretion curtain for the two systems by calculating spectral line fluxes. From HST and IUE data, we deduced ultraviolet luminosities and ultraviolet accretion rates for the two binary stars. The average temperature of the accretion streams for PQ Gem and V405 Aur are ∼4500 K and 4100 K, respectively. The results reveal that there are modulations in fluxes of spectral lines, ultraviolet luminosities, and ultraviolet accretion rates with time for both systems. These modulations are referred to the changes of both density and temperature as a result of the variations of mass transfer rate from the secondary star to the primary star. The current results are consistent with an accretion curtain model for IPs.« less

SHORT RANGE ENSEMBLE Products

Science.gov Websites

- CONUS Double Resolution (Lambert Conformal - 40km) NEMS Non-hydrostatic Multiscale Model on the B grid AWIPS grid 212 Regional - CONUS Double Resolution (Lambert Conformal - 40km) NEMS Non-hydrostatic 132 - Double Resolution (Lambert Conformal - 16km) NEMS Non-hydrostatic Multiscale Model on the B grid

Extending the Applicability of the Community Multiscale Air Quality Model to Hemispheric Scales: Motivation, Challenges, and Progress

EPA Science Inventory

The adaptation of the Community Multiscale Air Quality (CMAQ) modeling system to simulate O₃, particulate matter, and related precursor distributions over the northern hemisphere is presented. Hemispheric simulations with CMAQ and the Weather Research and Forecasting (...

Inherited genetic variants associated with occurrence of multiple primary melanoma.

PubMed

Gibbs, David C; Orlow, Irene; Kanetsky, Peter A; Luo, Li; Kricker, Anne; Armstrong, Bruce K; Anton-Culver, Hoda; Gruber, Stephen B; Marrett, Loraine D; Gallagher, Richard P; Zanetti, Roberto; Rosso, Stefano; Dwyer, Terence; Sharma, Ajay; La Pilla, Emily; From, Lynn; Busam, Klaus J; Cust, Anne E; Ollila, David W; Begg, Colin B; Berwick, Marianne; Thomas, Nancy E

2015-06-01

Recent studies, including genome-wide association studies, have identified several putative low-penetrance susceptibility loci for melanoma. We sought to determine their generalizability to genetic predisposition for multiple primary melanoma in the international population-based Genes, Environment, and Melanoma (GEM) Study. GEM is a case-control study of 1,206 incident cases of multiple primary melanoma and 2,469 incident first primary melanoma participants as the control group. We investigated the odds of developing multiple primary melanoma for 47 SNPs from 21 distinct genetic regions previously reported to be associated with melanoma. ORs and 95% confidence intervals were determined using logistic regression models adjusted for baseline features (age, sex, age by sex interaction, and study center). We investigated univariable models and built multivariable models to assess independent effects of SNPs. Eleven SNPs in 6 gene neighborhoods (TERT/CLPTM1L, TYRP1, MTAP, TYR, NCOA6, and MX2) and a PARP1 haplotype were associated with multiple primary melanoma. In a multivariable model that included only the most statistically significant findings from univariable modeling and adjusted for pigmentary phenotype, back nevi, and baseline features, we found TERT/CLPTM1L rs401681 (P = 0.004), TYRP1 rs2733832 (P = 0.006), MTAP rs1335510 (P = 0.0005), TYR rs10830253 (P = 0.003), and MX2 rs45430 (P = 0.008) to be significantly associated with multiple primary melanoma, while NCOA6 rs4911442 approached significance (P = 0.06). The GEM Study provides additional evidence for the relevance of these genetic regions to melanoma risk and estimates the magnitude of the observed genetic effect on development of subsequent primary melanoma. ©2015 American Association for Cancer Research.

Inherited genetic variants associated with occurrence of multiple primary melanoma

PubMed Central

Gibbs, David C.; Orlow, Irene; Kanetsky, Peter A.; Luo, Li; Kricker, Anne; Armstrong, Bruce K.; Anton-Culver, Hoda; Gruber, Stephen B.; Marrett, Loraine D.; Gallagher, Richard P.; Zanetti, Roberto; Rosso, Stefano; Dwyer, Terence; Sharma, Ajay; La Pilla, Emily; From, Lynn; Busam, Klaus J.; Cust, Anne E.; Ollila, David W.; Begg, Colin B.; Berwick, Marianne; Thomas, Nancy E.

2015-01-01

Recent studies including genome-wide association studies have identified several putative low-penetrance susceptibility loci for melanoma. We sought to determine their generalizability to genetic predisposition for multiple primary melanoma in the international population-based Genes, Environment, and Melanoma (GEM) Study. GEM is a case-control study of 1,206 incident cases of multiple primary melanoma and 2,469 incident first primary melanoma participants as the control group. We investigated the odds of developing multiple primary melanoma for 47 single nucleotide polymorphisms (SNP) from 21 distinct genetic regions previously reported to be associated with melanoma. ORs and 95% CIs were determined using logistic regression models adjusted for baseline features (age, sex, age by sex interaction, and study center). We investigated univariable models and built multivariable models to assess independent effects of SNPs. Eleven SNPs in 6 gene neighborhoods (TERT/CLPTM1L, TYRP1, MTAP, TYR, NCOA6, and MX2) and a PARP1 haplotype were associated with multiple primary melanoma. In a multivariable model that included only the most statistically significant findings from univariable modeling and adjusted for pigmentary phenotype, back nevi, and baseline features, we found TERT/CLPTM1L rs401681 (P = 0.004), TYRP1 rs2733832 (P = 0.006), MTAP rs1335510 (P = 0.0005), TYR rs10830253 (P = 0.003), and MX2 rs45430 (P = 0.008) to be significantly associated with multiple primary melanoma while NCOA6 rs4911442 approached significance (P = 0.06). The GEM study provides additional evidence for the relevance of these genetic regions to melanoma risk and estimates the magnitude of the observed genetic effect on development of subsequent primary melanoma. PMID:25837821

HEAVY-DUTY GREENHOUSE GAS EMISSIONS MODEL (GEM)

EPA Science Inventory

Class 2b-8 vocational truck manufacturers and Class 7/8 tractor manufacturers would be subject to vehicle-based fuel economy and emission standards that would use a truck simulation model to evaluate the impact of the truck tires and/or tractor cab design on vehicle compliance wi...

Integrated Farm System Model Version 4.1 and Dairy Gas Emissions Model Version 3.1 software release and distribution

USDA-ARS?s Scientific Manuscript database

Animal facilities are significant contributors of gaseous emissions including ammonia (NH3) and nitrous oxide (N2O). Previous versions of the Integrated Farm System Model (IFSM version 4.0) and Dairy Gas Emissions Model (DairyGEM version 3.0), two whole-farm simulation models developed by USDA-ARS, ...

16 CFR 23.25 - Misuse of the word “gem.”

Code of Federal Regulations, 2010 CFR

2010-01-01

... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Misuse of the word âgem.â 23.25 Section 23... JEWELRY, PRECIOUS METALS, AND PEWTER INDUSTRIES § 23.25 Misuse of the word “gem.” (a) It is unfair or deceptive to use the word “gem” to describe, identify, or refer to a ruby, sapphire, emerald, topaz, or...

Comparison of the accuracy of hemoglobin point of care testing using HemoCue and GEM Premier 3000 with automated hematology analyzer in emergency room.

PubMed

Zatloukal, Jan; Pouska, Jiri; Kletecka, Jakub; Pradl, Richard; Benes, Jan

2016-12-01

The laboratory analysis provides accurate, but time consuming hemoglobin level estimation especially in the emergency setting. The reliability of time-sparing point of care devices (POCT) remains uncertain. We tested two POCT devices accuracy (HemoCue ® 201 + and Gem ® Premier™3000) in routine emergency department workflow. Blood samples taken from patients admitted to the emergency department were analyzed for hemoglobin concentration using a laboratory reference Beckman Coulter LH 750 (HB LAB ), the HemoCue (HB HC ) and the Gem Premier 3000 (HB GEM ). Pairwise comparison for each device and Hb LAB was performed using correlation and the Bland-Altman methods. The reliability of transfusion decision was assessed using three-zone error grid. A total of 292 measurements were performed in 99 patients. Mean hemoglobin level were 115 ± 33, 110 ± 28 and 111 ± 30 g/l for Hb HC , Hb GEM and Hb LAB respectively. A significant correlation was observed for both devices: Hb HC versus Hb LAB (r 2  = 0.93, p < 0.001) and HB GEM versus HB LAB (r 2  = 0.86, p < 0.001). The Bland-Altman method revealed bias of -3.7 g/l (limits of agreement -20.9 to 13.5) for HB HC and HB LAB and 2.5 g/l (-18.6 to 23.5) for HB GEM and HB LAB , which significantly differed between POCT devices (p < 0.001). Using the error grid methodology: 94 or 91 % of values (Hb HC and Hb GEM ) fell in the zone of acceptable difference (A), whereas 0 and 1 % (Hb HC and Hb GEM ) were unacceptable (zone C). The absolute accuracy of tested POCT devices was low though reaching a high level of correlation with laboratory measurement. The results of the Morey´s error grid were unfavorable for both POCT devices.

A Goddard Multi-Scale Modeling System with Unified Physics

NASA Technical Reports Server (NTRS)

Tao, W.K.; Anderson, D.; Atlas, R.; Chern, J.; Houser, P.; Hou, A.; Lang, S.; Lau, W.; Peters-Lidard, C.; Kakar, R.;

Towards multiscale modeling of influenza infection

PubMed Central

Murillo, Lisa N.; Murillo, Michael S.; Perelson, Alan S.

2013-01-01

Aided by recent advances in computational power, algorithms, and higher fidelity data, increasingly detailed theoretical models of infection with influenza A virus are being developed. We review single scale models as they describe influenza infection from intracellular to global scales, and, in particular, we consider those models that capture details specific to influenza and can be used to link different scales. We discuss the few multiscale models of influenza infection that have been developed in this emerging field. In addition to discussing modeling approaches, we also survey biological data on influenza infection and transmission that is relevant for constructing influenza infection models. We envision that, in the future, multiscale models that capitalize on technical advances in experimental biology and high performance computing could be used to describe the large spatial scale epidemiology of influenza infection, evolution of the virus, and transmission between hosts more accurately. PMID:23608630

Hybrid methods for simulating hydrodynamics and heat transfer in multiscale (1D-3D) models

NASA Astrophysics Data System (ADS)

Filimonov, S. A.; Mikhienkova, E. I.; Dekterev, A. A.; Boykov, D. V.

2017-09-01

The work is devoted to application of different-scale models in the simulation of hydrodynamics and heat transfer of large and/or complex systems, which can be considered as a combination of extended and “compact” elements. The model consisting of simultaneously existing three-dimensional and network (one-dimensional) elements is called multiscale. The paper examines the relevance of building such models and considers three main options for their implementation: the spatial and the network parts of the model are calculated separately; spatial and network parts are calculated simultaneously (hydraulically unified model); network elements “penetrate” the spatial part and are connected through the integral characteristics at the tube/channel walls (hydraulically disconnected model). Each proposed method is analyzed in terms of advantages and disadvantages. The paper presents a number of practical examples demonstrating the application of multiscale models.

Versatile Micromechanics Model for Multiscale Analysis of Composite Structures

NASA Astrophysics Data System (ADS)

Kwon, Y. W.; Park, M. S.

2013-08-01

A general-purpose micromechanics model was developed so that the model could be applied to various composite materials such as reinforced by particles, long fibers and short fibers as well as those containing micro voids. Additionally, the model can be used with hierarchical composite materials. The micromechanics model can be used to compute effective material properties like elastic moduli, shear moduli, Poisson's ratios, and coefficients of thermal expansion for the various composite materials. The model can also calculate the strains and stresses at the constituent material level such as fibers, particles, and whiskers from the composite level stresses and strains. The model was implemented into ABAQUS using the UMAT option for multiscale analysis. An extensive set of examples are presented to demonstrate the reliability and accuracy of the developed micromechanics model for different kinds of composite materials. Another set of examples is provided to study the multiscale analysis of composite structures.

Zooming in on star formation in the brightest galaxies of the early Universe discovered with the Planck and Herschel satellites

NASA Astrophysics Data System (ADS)

Canameras, Raoul

2016-09-01

Strongly gravitationally lensed galaxies offer an outstanding opportunity to characterize the most intensely star-forming galaxies in the high-redshift universe. In the most extreme cases, one can probe the mechanisms that underlie the intense star formation on the scales of individual star-forming regions. This requires very fortuitous gravitational lensing configurations offering magnification factors >>10, which are particularly rare toward the high-redshift dusty star-forming galaxies. The Planck's Dusty GEMS (Gravitationally Enhanced subMillimeter Sources) sample contains eleven of the brightest high-redshift galaxies discovered with the Planck submillimeter all-sky survey, with flux densities between 300 and 1000 mJy at 350 microns, factors of a few brighter than the majority of lensed sources previously discovered with other surveys. Six of them are above the 90% completeness limit of the Planck Catalog of Compact Sources (PCCS), suggesting that they are among the brightest high-redshift sources on the sky selected by their active star formation. This thesis comes within the framework of the extensive multi-wavelength follow-up programme designed to determine the overall properties of the high-redshift sources and to probe the lensing configurations. Firstly, to characterize the intervening lensing structures and calculate lensing models, I use optical and near/mid-infrared imaging and spectroscopy. I deduce that our eleven GEMS are aligned with intervening matter overdensities at intermediate redshift, either massive isolated galaxies or galaxy groups and clusters. The foreground sources exhibit evolved stellar populations of a few giga years, characteristic of early-type galaxies. Moreover, the first detailed models of the light deflection toward the GEMS suggest magnification factors systematically >10, and >20 for some lines-of-sight. Secondly, we observe the GEMS in the far-infrared and sub-millimeter domains in order to characterize the background sources. The sub-arcsec resolution IRAM and SMA interferometry shows distorded morphologies which definitively confirm that the eleven sources are strongly lensed. I obtain dust temperatures between 33 and 50 K, and outstanding far-infrared luminosities of up to 2x1014 solar luminosities before correcting for the gravitational magnification. The relationship between dust temperatures and far-infrared luminosities also confirms that the GEMS are brighter than field galaxies at a given dust temperature. I conclude that dust heating seems to be strongly dominated by the star formation activity with an AGN contamination systematically below 30%. We find secure spectroscopic redshifts between 2.2 and 3.6 for the eleven targets thanks to the detection of at least two CO emission lines per source. Finally, I focus on the three gravitationally lensed sources showing the most remarkable properties including the brightest GEMS, a maximal starburst with star formation surface densities near the Eddington limit.

Multiscale Modeling of Multiphase Fluid Flow

DTIC Science & Technology

2016-08-01

the disparate time and length scales involved in modeling fluid flow and heat transfer. Molecular dynamics simulations were carried out to provide a...fluid dynamics methods were used to investigate the heat transfer process in open-cell micro-foam with phase change material; enhancement of natural...Computational fluid dynamics, Heat transfer, Phase change material in Micro-foam, Molecular Dynamics, Multiphase flow, Multiscale modeling, Natural

Multi-Scale Characterization of Orthotropic Microstructures

DTIC Science & Technology

2008-04-01

D. Valiveti, S. J. Harris, J. Boileau, A domain partitioning based pre-processor for multi-scale modelling of cast aluminium alloys , Modelling and...SUPPLEMENTARY NOTES Journal article submitted to Modeling and Simulation in Materials Science and Engineering. PAO Case Number: WPAFB 08-3362...element for charac- terization or simulation to avoid misleading predictions of macroscopic defor- mation, fracture, or transport behavior. Likewise

Simulations of Tornadoes, Tropical Cyclones, MJOs, and QBOs, using GFDL's multi-scale global climate modeling system

NASA Astrophysics Data System (ADS)

Lin, Shian-Jiann; Harris, Lucas; Chen, Jan-Huey; Zhao, Ming

2014-05-01

A multi-scale High-Resolution Atmosphere Model (HiRAM) is being developed at NOAA/Geophysical Fluid Dynamics Laboratory. The model's dynamical framework is the non-hydrostatic extension of the vertically Lagrangian finite-volume dynamical core (Lin 2004, Monthly Wea. Rev.) constructed on a stretchable (via Schmidt transformation) cubed-sphere grid. Physical parametrizations originally designed for IPCC-type climate predictions are in the process of being modified and made more "scale-aware", in an effort to make the model suitable for multi-scale weather-climate applications, with horizontal resolution ranging from 1 km (near the target high-resolution region) to as low as 400 km (near the antipodal point). One of the main goals of this development is to enable simulation of high impact weather phenomena (such as tornadoes, thunderstorms, category-5 hurricanes) within an IPCC-class climate modeling system previously thought impossible. We will present preliminary results, covering a very wide spectrum of temporal-spatial scales, ranging from simulation of tornado genesis (hours), Madden-Julian Oscillations (intra-seasonal), topical cyclones (seasonal), to Quasi Biennial Oscillations (intra-decadal), using the same global multi-scale modeling system.

Bayesian inference on multiscale models for poisson intensity estimation: applications to photon-limited image denoising.

PubMed

Lefkimmiatis, Stamatios; Maragos, Petros; Papandreou, George

2009-08-01

We present an improved statistical model for analyzing Poisson processes, with applications to photon-limited imaging. We build on previous work, adopting a multiscale representation of the Poisson process in which the ratios of the underlying Poisson intensities (rates) in adjacent scales are modeled as mixtures of conjugate parametric distributions. Our main contributions include: 1) a rigorous and robust regularized expectation-maximization (EM) algorithm for maximum-likelihood estimation of the rate-ratio density parameters directly from the noisy observed Poisson data (counts); 2) extension of the method to work under a multiscale hidden Markov tree model (HMT) which couples the mixture label assignments in consecutive scales, thus modeling interscale coefficient dependencies in the vicinity of image edges; 3) exploration of a 2-D recursive quad-tree image representation, involving Dirichlet-mixture rate-ratio densities, instead of the conventional separable binary-tree image representation involving beta-mixture rate-ratio densities; and 4) a novel multiscale image representation, which we term Poisson-Haar decomposition, that better models the image edge structure, thus yielding improved performance. Experimental results on standard images with artificially simulated Poisson noise and on real photon-limited images demonstrate the effectiveness of the proposed techniques.

Voluntary EMG-to-force estimation with a multi-scale physiological muscle model

PubMed Central

2013-01-01

Background EMG-to-force estimation based on muscle models, for voluntary contraction has many applications in human motion analysis. The so-called Hill model is recognized as a standard model for this practical use. However, it is a phenomenological model whereby muscle activation, force-length and force-velocity properties are considered independently. Perreault reported Hill modeling errors were large for different firing frequencies, level of activation and speed of contraction. It may be due to the lack of coupling between activation and force-velocity properties. In this paper, we discuss EMG-force estimation with a multi-scale physiology based model, which has a link to underlying crossbridge dynamics. Differently from the Hill model, the proposed method provides dual dynamics of recruitment and calcium activation. Methods The ankle torque was measured for the plantar flexion along with EMG measurements of the medial gastrocnemius (GAS) and soleus (SOL). In addition to Hill representation of the passive elements, three models of the contractile parts have been compared. Using common EMG signals during isometric contraction in four able-bodied subjects, torque was estimated by the linear Hill model, the nonlinear Hill model and the multi-scale physiological model that refers to Huxley theory. The comparison was made in normalized scale versus the case in maximum voluntary contraction. Results The estimation results obtained with the multi-scale model showed the best performances both in fast-short and slow-long term contraction in randomized tests for all the four subjects. The RMS errors were improved with the nonlinear Hill model compared to linear Hill, however it showed limitations to account for the different speed of contractions. Average error was 16.9% with the linear Hill model, 9.3% with the modified Hill model. In contrast, the error in the multi-scale model was 6.1% while maintaining a uniform estimation performance in both fast and slow contractions schemes. Conclusions We introduced a novel approach that allows EMG-force estimation based on a multi-scale physiology model integrating Hill approach for the passive elements and microscopic cross-bridge representations for the contractile element. The experimental evaluation highlights estimation improvements especially a larger range of contraction conditions with integration of the neural activation frequency property and force-velocity relationship through cross-bridge dynamics consideration. PMID:24007560

JPL Developments in Retrieval Algorithms for Geostationary Observations - Applications to H2CO

NASA Technical Reports Server (NTRS)

Kurosu, Thomas P.; Kulawik, Susan; Natraj, Vijay

2012-01-01

JPL has strong expertise in atmospheric retrievals from UV and thermal IR, and a wide range of tools to apply to observations and instrument characterization. Radiative Transfer, AMF, Inversion, Fitting, Assimilation. Tools were applied for a preliminary study of H2CO sensitivities from GEO. Results show promise for moderate/strong H2CO lading but also that low background conditions will prove a challenge. H2CO DOF are not too strongly dependent on FWHM. GEMS (Geostationary Environmental Monitoring Spectrometer) choice of 0.6 nm FWHM (?) spectral resolution is adequate for H2CO retrievals. Case study can easily be adapted to GEMS observations/instrument model for more in-depth sensitivity characterization.

Statistical Field Estimation for Complex Coastal Regions and Archipelagos (PREPRINT)

DTIC Science & Technology

2011-04-09

and study the computational properties of these schemes. Specifically, we extend a multiscale Objective Analysis (OA) approach to complex coastal...computational properties of these schemes. Specifically, we extend a multiscale Objective Analysis (OA) approach to complex coastal regions and... multiscale free-surface code builds on the primitive-equation model of the Harvard Ocean Predic- tion System (HOPS, Haley et al. (2009)). Additionally

Multi-scale Computational Electromagnetics for Phenomenology and Saliency Characterization in Remote Sensing

DTIC Science & Technology

2016-07-15

AFRL-AFOSR-JP-TR-2016-0068 Multi-scale Computational Electromagnetics for Phenomenology and Saliency Characterization in Remote Sensing Hean-Teik...SUBTITLE Multi-scale Computational Electromagnetics for Phenomenology and Saliency Characterization in Remote Sensing 5a.  CONTRACT NUMBER 5b.  GRANT NUMBER... electromagnetics to the application in microwave remote sensing as well as extension of modelling capability with computational flexibility to study

Multi-scale Computational Electromagnetics for Phenomenology and Saliency Characterization in Remote Sensing

DTIC Science & Technology

2016-07-15

AFRL-AFOSR-JP-TR-2016-0068 Multi-scale Computational Electromagnetics for Phenomenology and Saliency Characterization in Remote Sensing Hean-Teik...SUBTITLE Multi-scale Computational Electromagnetics for Phenomenology and Saliency Characterization in Remote Sensing 5a.  CONTRACT NUMBER 5b.  GRANT NUMBER...electromagnetics to the application in microwave remote sensing as well as extension of modelling capability with computational flexibility to study

Prediction of Exploration Target Areas for GEM Deposits in Mogok Stone Tract, Northern Myanmar by Integrating Remote Sensing and Geoscience Data

NASA Astrophysics Data System (ADS)

Oo, Tin Ko

2011-07-01

The Mogok Stone Tract area has long been known for world famous finest ruby since 1597. The Mogok area lies in northern Myanmar and is located at about 205.99km northeast from Mandalay, the second largest city of Myanmar. The Mogok Group of metasedimentary rocks is divided into four units: (1) Wabyudaung Marble, (2) Ayenyeinchantha Calc-silicate, (3) Gwebin Quartzite, and (4) Kabe Gneiss. Igneous rocks in the Mogok area are classified into two units: (1) Kabaing Granite and (2) Pingutaung Leucogranite. The Mogok area has a complex structure involving several folds and faults. Using marbles and calc-silicates as marker horizons, a series of anticline and syncline can be identified such as Mogok syncline, Ongaing anticline, Bawpadan syncline, and Kyatpyin anticline. All the foldings show a low-angle plunge to the south. The main precious stones of the Mogok area are ruby and sapphire; and the other important semi-precious stones are spinel, topaz, peridot, garnet, apatite, beryl, tourmaline (rubellite), quartz, diopside, fluorite, and enstatite. Geological and remote sensing data are processed to extract the indicative features of gem mineralized areas: lithology, structure, and hydrothermal alteration. Density slice version of Landsat ETM band ratios 5/7 is used to map clay alterations. Filtering Landsat ETM band 5 by using edge detection filter is applied for lineament mapping. Spatial integration of various geoscience and remote sensing data sets such as geological maps, Landsat ETM images, and the location map of gem mines show the distribution of alteration zones associated with the gem mineralization in the study area. Geographic Information System (GIS) model has been designed and implemented by ARCVIEW software package based on the overlay of lithologic, lineament, and alteration vector maps. This process has resulted in delineation of most promising areas of probable gem mineralized zones as on the output map.

Changes in Nutritional and Functional Status in Longer Stay Patients Admitted to a Geriatric Evaluation and Management Unit.

PubMed

Whitley, A; Skliros, E; Graven, C; McIntosh, R; Lasry, C; Newsome, C; Bowie, A

2017-01-01

Malnutrition and functional decline are common in older inpatients admitted to subacute care settings. However the association between changes in nutritional status and relevant functional outcomes remains under-researched. This study examined changes in nutritional status, function and mobility in patients admitted to a Geriatric Evaluation and Management (GEM) unit who had a length of stay (LOS) longer than 21 days. A prospective, observational study. Two GEM units at St Vincent's Hospital Melbourne, Australia. Patients admitted to the GEM units who stayed longer than 21 days were included in the study. Patients were assessed on admission and prior to discharge using the Subjective Global Assessment (SGA), Functional Independence Measure (FIM) motor domain and the Modified Elderly Mobility Scale (MEMS). Fifty-nine patients (Mean age 84.0 ± 7 years) met the required length of stay and were included in the study. Fifty-four per cent (n=32) were malnourished on admission (SGA B/C) and 44% (n=26) were malnourished on discharge. Twenty-two per cent (n=13) improved SGA category, 75% remained stable (n=44) and 3% deteriorated (n=2) from admission to discharge. Total Motor FIM scores significantly increased from admission to discharge in both the improved (p<0.001) and stable or deteriorated (p<0.001) nutritional status groups. Subjects who improved in nutritional status had a significantly higher MEMS score at discharge (p<0.001). On admission to the GEM unit, just over half the included patients were rated as malnourished defined by SGA category. Nearly one quarter of the sample had improved their nutritional status at the time of discharge. Improvement in nutritional status was associated with greater improvement in mobility scores. Further studies are required to investigate the effectiveness of nutrition interventions, which will inform models of care aiming to optimise nutritional, functional, and associated clinical outcomes in patients admitted to GEM units.