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

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.

Experiential Engineering through iGEM--An Undergraduate Summer Competition in Synthetic Biology

ERIC Educational Resources Information Center

Mitchell, Rudolph; Dori, Yehudit Judy; Kuldell, Natalie H.

2011-01-01

Unlike students in other engineering disciplines, undergraduates in biological engineering typically have limited opportunity to develop design competencies, and even fewer chances to implement their designed projects. The international Genetically Engineered Machines (iGEM) competition is a student Synthetic Biology competition that, in 2009,…

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.

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

Modular projects and 'mean questions': best practices for advising an International Genetically Engineered Machines team.

PubMed

Tsui, Jennifer; Meyer, Anne S

2016-07-01

In the yearly Internationally Genetically Engineered Machines (iGEM) competition, teams of Bachelor's and Master's students design and build an engineered biological system using DNA technologies. Advising an iGEM team poses unique challenges due to the inherent difficulties of mounting and completing a new biological project from scratch over the course of a single academic year; the challenges in obtaining financial and structural resources for a project that will likely not be fully realized; and conflicts between educational and competition-based goals. This article shares tips and best practices for iGEM team advisors, from two team advisors with very different experiences with the iGEM competition. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

[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.

Girls in Engineering, Mathematics and Science, GEMS: A Science Outreach Program for Middle-School Female Students

ERIC Educational Resources Information Center

Dubetz, Terry A.; Wilson, Jo Ann

2013-01-01

Girls in Engineering, Mathematics and Science (GEMS) is a science and math outreach program for middle-school female students. The program was developed to encourage interest in math and science in female students at an early age. Increased scientific familiarity may encourage girls to consider careers in science and mathematics and will also help…

Environmental risk assessment of a genetically-engineered microorganism: Erwinia carotovora

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

Orvos, D.R.

1989-01-01

Environmental use of genetically-engineered microorganisms (GEMs) has raised concerns over potential ecological impact. Development of microcosm systems useful in preliminary testing for risk assessment will provide useful information for predicting potential structural, functional, and genetic effects of GEM release. This study was executed to develop techniques that may be useful in risk assessment and microbial ecology, to ascertain which parameters are useful in determining risk and to predict risk from releasing an engineered strain of Erwinia carotovora. A terrestrial microcosm system for use in GEM risk assessment studies was developed for use in assessing alterations of microbial structure and functionmore » that may be caused by introducing the engineered strain of E. carotovora. This strain is being developed for use as a biological control agent for plant soft rot. Parameters that were monitored included survival and intraspecific competition of E. carotovora, structural effects upon both total bacterial populations and numbers of selected bacterial genera, effects upon activities of dehydrogenase and alkaline phosphatase, effects upon soil nutrients, and potential for gene transfer into or out of the engineered strain.« less

PHYSICAL AND CHEMICAL CONTROL OF RELEASED MICROORGANISMS AT FIELD SITES

EPA Science Inventory

An important consideration in the environmental release of a genetically engineered microorganism (GEM) is the capability for reduction or elimination of GEM populations once their function is completed or if adverse environmental effects are observed. In this study the decontami...

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

Hattemer-Frey, H.A.; Brandt, E.J.; Travis, C.C.

Commercial genetic engineering is advancing into areas that require the small-scale introduction of genetically engineered microorganisms (GEMs) to better quantify variables that affect microorganism distribution and survival and to document potential long-term consequences. A recombinant DNA marker system, the lacZY marker, developed by the Monsanto Agricultural Co., enables the distribution and fate of marked fluorescent pseudomonad organisms to be monitored under actual field conditions. Critical evaluation of GEMs under field conditions is imperative if plant-beneficial effects are to be correlated with organism release. This paper evaluates the effectiveness of this marker system and its ability to facilitate the assessment ofmore » risks associated with deliberate environmental introductions of genetically engineered microorganisms. Results of prerelease contained growth chamber and field experiments demonstrated that: (1) the scientific risk assessment methodology adopted by Monsanto and approved by the U.S. Environmental Protection Agency was appropriate and comprehensive; (2) the deliberate introduction of a GEM did not pose unacceptable or unforeseen risks to human health or the environment; (3) the lacZY marker is an effective environmental tracking tool; and (4) regulatory oversight should reflect the expected risk and not be excessively burdensome for all GEMs.« less

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

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.

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

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

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

Promoting microbiology education through the iGEM synthetic biology competition.

PubMed

Kelwick, Richard; Bowater, Laura; Yeoman, Kay H; Bowater, Richard P

2015-08-01

Synthetic biology has developed rapidly in the 21st century. It covers a range of scientific disciplines that incorporate principles from engineering to take advantage of and improve biological systems, often applied to specific problems. Methods important in this subject area include the systematic design and testing of biological systems and, here, we describe how synthetic biology projects frequently develop microbiology skills and education. Synthetic biology research has huge potential in biotechnology and medicine, which brings important ethical and moral issues to address, offering learning opportunities about the wider impact of microbiological research. Synthetic biology projects have developed into wide-ranging training and educational experiences through iGEM, the International Genetically Engineered Machines competition. Elements of the competition are judged against specific criteria and teams can win medals and prizes across several categories. Collaboration is an important element of iGEM, and all DNA constructs synthesized by iGEM teams are made available to all researchers through the Registry for Standard Biological Parts. An overview of microbiological developments in the iGEM competition is provided. This review is targeted at educators that focus on microbiology and synthetic biology, but will also be of value to undergraduate and postgraduate students with an interest in this exciting subject area. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A Study of Corporate Entrepreneurship in a Department of Defense Organization

DTIC Science & Technology

2011-03-01

A STUDY OF CORPORATE ENTREPRENUERSHIP IN A DEPARTMENT OF DEFENSE ORGANIZATION THESIS Wade W. Brower, Civilian AFIT/GEM/ENV...CORPORATE ENTREPRENUERSHIP IN A DEPARTMENT OF DEFENSE ORGANIZATION THESIS Presented to the Faculty Department of Systems and Engineering...2011 APPROVED FOR PUBLIC RELEASE; DISTRIBUTION UNLIMITED AFIT/GEM/ENV/11-M01 A STUDY OF CORPORATE ENTREPRENUERSHIP IN A DEPARTMENT OF

An Historical Analysis of the Development of RED HORSE (Rapid Engineer Deployable, Heavy Operation Repair Squadron, Engineering)

DTIC Science & Technology

1987-09-01

BBiC FILE Copy- 00 ~OF AN HISTORICAL ANALYSIS OF THE DEVELOPMENT OF RED HORSE THESIS Jon A. Wheeler Captain, USAF AFIT/GEM/LSR/87S-26 T C Wrgh-atero...Air~ Forc BaEe, Ohi7 j~~pploved I ni8ie D~dmwdl AFIT/GEM/LSR/87S-26 AN HISTORICAL ANALYSIS OF THE DEVELOPMENT OF RED HORSE THESIS Jon A. Wheeler...DEVELOPMENT OF RED HORSE THESIS Presented to the Faculty of the School of Systems and Logistics of the Air Force Institute of Technology Air University

Dearth of American Engineering Graduate Students Concerns Academicians.

ERIC Educational Resources Information Center

Farrell, Charles S.

1989-01-01

A shortage of American engineering graduate students, particularly minorities and women, has resulted in the increasing award of research and graduate assistantships to foreign students. The National Consortium for Graduate Degrees for Minorities in Engineering (GEM) and the National Science Foundation (NSF) are offering financial encouragement…

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.

GEM1: First-year modeling and IT activities for the Global Earthquake Model

NASA Astrophysics Data System (ADS)

Anderson, G.; Giardini, D.; Wiemer, S.

2009-04-01

GEM is a public-private partnership initiated by the Organisation for Economic Cooperation and Development (OECD) to build an independent standard for modeling and communicating earthquake risk worldwide. GEM is aimed at providing authoritative, open information about seismic risk and decision tools to support mitigation. GEM will also raise risk awareness and help post-disaster economic development, with the ultimate goal of reducing the toll of future earthquakes. GEM will provide a unified set of seismic hazard, risk, and loss modeling tools based on a common global IT infrastructure and consensus standards. These tools, systems, and standards will be developed in partnership with organizations around the world, with coordination by the GEM Secretariat and its Secretary General. GEM partners will develop a variety of global components, including a unified earthquake catalog, fault database, and ground motion prediction equations. To ensure broad representation and community acceptance, GEM will include local knowledge in all modeling activities, incorporate existing detailed models where possible, and independently test all resulting tools and models. When completed in five years, GEM will have a versatile, penly accessible modeling environment that can be updated as necessary, and will provide the global standard for seismic hazard, risk, and loss models to government ministers, scientists and engineers, financial institutions, and the public worldwide. GEM is now underway with key support provided by private sponsors (Munich Reinsurance Company, Zurich Financial Services, AIR Worldwide Corporation, and Willis Group Holdings); countries including Belgium, Germany, Italy, Singapore, Switzerland, and Turkey; and groups such as the European Commission. The GEM Secretariat has been selected by the OECD and will be hosted at the Eucentre at the University of Pavia in Italy; the Secretariat is now formalizing the creation of the GEM Foundation. Some of GEM's global components are in the planning stages, such as the developments of a unified active fault database and earthquake catalog. The flagship activity of GEM's first year is GEM1, a focused pilot project to develop GEM's first hazard and risk modeling products and initial IT infrastructure, starting in January 2009 and ending in March 2010. GEM1 will provide core capabilities for the present and key knowledge for future development of the full GEM computing Environment and product set. We will build GEM1 largely using existing tools and datasets, connected through a unified IT infrastructure, in order to bring GEM's initial capabilities online as rapidly as possible. The Swiss Seismological Service at ETH-Zurich is leading the GEM1 effort in cooperation with partners around the world. We anticipate that GEM1's products will include: • A global compilation of regional seismic source zone models in one or more common representations • Global synthetic earthquake catalogs for use in hazard calculations • Initial set of regional and global catalogues for validation • Global hazard models in map and database forms • First compilation of global vulnerabilities and fragilities • Tools for exposure and loss assessment • Validation of results and software for existing risk assessment tools to be used in future GEM stages • Demonstration risk scenarios for target cities • First version of GEM IT infrastructure All these products will be made freely available to the greatest extent possible. For more information on GEM and GEM1, please visit http://www.globalquakemodel.org.

RGK protein-mediated impairment of slow depolarization- dependent Ca2+ entry into developing myotubes

PubMed Central

Romberg, Christin F; Beqollari, Donald; Meza, Ulises; Bannister, Roger A

2014-01-01

Three physiological functions have been described for the skeletal muscle 1,4-dihydropyridine receptor (CaV1.1): (1) voltage-sensor for excitation-contraction (EC) coupling, (2) L-type Ca2+ channel, and (3) voltage-sensor for slow depolarization-dependent Ca2+ entry. Members of the RGK (Rad, Rem, Rem2, Gem/Kir) family of monomeric GTP-binding proteins are potent inhibitors of the former two functions of CaV1.1. However, it is not known whether the latter function that has been attributed to CaV1.1 is subject to modulation by RGK proteins. Thus, the purpose of this study was to determine whether Rad, Gem and/or Rem inhibit the slowly developing, persistent Ca2+ entry that is dependent on the voltage-sensing capability of CaV1.1. As a means to investigate this question, Venus fluorescent protein-fused RGK proteins (V-Rad, V-Rem and V-Gem) were overexpressed in “normal” mouse myotubes. We observed that such overexpression of V-Rad, V-Rem or V-Gem in myotubes caused marked changes in morphology of the cells. As shown previously for YFP-Rem, both L-type current and EC coupling were also impaired greatly in myotubes expressing either V-Rad or V-Gem. The reductions in L-type current and EC coupling were paralleled by reductions in depolarization-induced Ca2+ entry. Our observations provide the first evidence of modulation of this enigmatic Ca2+ entry pathway peculiar to skeletal muscle. PMID:24476902

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

Engineering a Biological Revolution.

PubMed

Matheson, Susan

2017-01-26

The new field of synthetic biology promises to change health care, computer technology, the production of biofuels, and more. Students participating in the International Genetically Engineered Machine (iGEM) competition are on the front lines of this revolution. Copyright © 2017 Elsevier Inc. All rights reserved.

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

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

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.

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.

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.

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

Comparison of global brain gene expression profiles between inbred long-sleep and inbred short-sleep mice by high-density gene array hybridization.

PubMed

Xu, Y; Ehringer, M; Yang, F; Sikela, J M

2001-06-01

Inbred long-sleep (ILS) and short-sleep (ISS) mice show significant central nervous system-mediated differences in sleep time for sedative dose of ethanol and are frequently used as a rodent model for ethanol sensitivity. In this study, we have used complementary DNA (cDNA) array hybridization methodology to identify genes that are differentially expressed between the brains of ILS and ISS mice. To carry out this analysis, we used both the gene discovery array (GDA) and the Mouse GEM 1 Microarray. GDA consists of 18,378 nonredundant mouse cDNA clones on a single nylon filter. Complex probes were prepared from total brain mRNA of ILS or ISS mice by using reverse transcription and 33P labeling. The labeled probes were hybridized in parallel to the gene array filters. Data from GDA experiments were analyzed with SQL-Plus and Oracle 8. The GEM microarray includes 8,730 sequence-verified clones on a glass chip. Two fluorescently labeled probes were used to hybridize a microarray simultaneously. Data from GEM experiments were analyzed by using the GEMTools software package (Incyte). Differentially expressed genes identified from each method were confirmed by relative quantitative reverse transcription-polymerase chain reaction (RT-PCR). A total of 41 genes or expressed sequence tags (ESTs) display significant expression level differences between brains of ILS and ISS mice after GDA, GEM1 hybridization, and quantitative RT-PCR confirmation. Among them, 18 clones were expressed higher in ILS mice, and 23 clones were expressed higher in ISS mice. The individual gene or EST's function and mapping information have been analyzed. This study identified 41 genes that are differentially expressed between brains of ILS and ISS mice. Some of them may have biological relevance in mediation of phenotypic variation between ILS and ISS mice for ethanol sensitivity. This study also demonstrates that parallel gene expression comparison with high-density cDNA arrays is a rapid and efficient way to discover potential genes and pathways involved in alcoholism and alcohol-related physiologic processes.

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.

PERSISTENCE OF A SURROGATE FOR A GENETICALLY ENGINEERED CELLULOLYTIC MICROORGANISM AND EFFECTS ON AQUATIC COMMUNITY AND ECOSYSTEM PROPERTIES: MICROCOSM AND STREAM COMPARISONS

EPA Science Inventory

Our research objectives were to: (1) determine the persistence of an introduced surrogate (Cellulomonas sp NRC 2406) for a genetically engineered microorganism (GEM) in three streamlined habitats; sediments, growths of Cladophora (Chlorophyta), and leaf packs, (2) test ommunity a...

40 CFR 1037.810 - Incorporation by reference.

Code of Federal Regulations, 2014 CFR

2014-07-01

... must publish a notice of the change in the Federal Register and the material must be available to the.../climate/gem.htm. (2) [Reserved] (d) Society of Automotive Engineers, 400 Commonwealth Dr., Warrendale, PA...

Fuzzy simulation in concurrent engineering

NASA Technical Reports Server (NTRS)

Kraslawski, A.; Nystrom, L.

1992-01-01

Concurrent engineering is becoming a very important practice in manufacturing. A problem in concurrent engineering is the uncertainty associated with the values of the input variables and operating conditions. The problem discussed in this paper concerns the simulation of processes where the raw materials and the operational parameters possess fuzzy characteristics. The processing of fuzzy input information is performed by the vertex method and the commercial simulation packages POLYMATH and GEMS. The examples are presented to illustrate the usefulness of the method in the simulation of chemical engineering processes.

Erosion / Corrosion Resistant Coatings for Compressor Airfoils

DTIC Science & Technology

2012-08-29

Platforms in Evaluation / Qualification T56 for C-130 AE1107 for V-22 T700 for H-60 T55 for MH-47 GE38 for H-53K Gem for Lynx T58 for H-46... T56 Performance Summary Uncoated vs Coated Engine Uncoated Engine (April – May 2011) With “sand turbine” at San Antonio: Coated Engine (July...power retention 2-3% Corrected Fuel Flow 1-2% Specific Fuel Consumption decrease @ 95% shp Coated Engine T56 Sand Ingestion Test 10 Pressure

OSI-027 inhibits pancreatic ductal adenocarcinoma cell proliferation and enhances the therapeutic effect of gemcitabine both in vitro and in vivo.

PubMed

Zhi, Xiao; Chen, Wei; Xue, Fei; Liang, Chao; Chen, Bryan Wei; Zhou, Yue; Wen, Liang; Hu, Liqiang; Shen, Jian; Bai, Xueli; Liang, Tingbo

2015-09-22

Despite its relative rarity, pancreatic ductal adenocarcinoma (PDAC) accounts for a large percentage of cancer deaths. In this study, we investigated the in vitro efficacy of OSI-027, a selective inhibitor of mammalian target of rapamycin complex 1 (mTORC1) and mTORC2, to treat PDAC cell lines alone, and in combination with gemcitabine (GEM). Similarly, we tested the efficacy of these two compounds in a xenograft mouse model of PDAC. OSI-027 significantly arrested cell cycle in G0/G1 phase, inhibited the proliferation of Panc-1, BxPC-3, and CFPAC-1 cells, and downregulated mTORC1, mTORC2, phospho-Akt, phospho-p70S6K, phospho-4E-BP1, cyclin D1, and cyclin-dependent kinase 4 (CDK4) in these cells. Moreover, OSI-027 also downregulated multidrug resistance (MDR)-1, which has been implicated in chemotherapy resistance in PDAC cells and enhanced apoptosis induced by GEM in the three PDAC cell lines. When combined, OSI-027 with GEM showed synergistic cytotoxic effects both in vitro and in vivo. This is the first evidence of the efficacy of OSI-027 in PDAC and may provide the groundwork for a new clinical PDAC therapy.

OSI-027 inhibits pancreatic ductal adenocarcinoma cell proliferation and enhances the therapeutic effect of gemcitabine both in vitro and in vivo

PubMed Central

Xue, Fei; Liang, Chao; Chen, Bryan Wei; Zhou, Yue; Wen, Liang; Hu, Liqiang; Shen, Jian; Bai, Xueli; Liang, Tingbo

2015-01-01

Despite its relative rarity, pancreatic ductal adenocarcinoma (PDAC) accounts for a large percentage of cancer deaths. In this study, we investigated the in vitro efficacy of OSI-027, a selective inhibitor of mammalian target of rapamycin complex 1 (mTORC1) and mTORC2, to treat PDAC cell lines alone, and in combination with gemcitabine (GEM). Similarly, we tested the efficacy of these two compounds in a xenograft mouse model of PDAC. OSI-027 significantly arrested cell cycle in G0/G1 phase, inhibited the proliferation of Panc-1, BxPC-3, and CFPAC-1 cells, and downregulated mTORC1, mTORC2, phospho-Akt, phospho-p70S6K, phospho-4E-BP1, cyclin D1, and cyclin-dependent kinase 4 (CDK4) in these cells. Moreover, OSI-027 also downregulated multidrug resistance (MDR)-1, which has been implicated in chemotherapy resistance in PDAC cells and enhanced apoptosis induced by GEM in the three PDAC cell lines. When combined, OSI-027 with GEM showed synergistic cytotoxic effects both in vitro and in vivo. This is the first evidence of the efficacy of OSI-027 in PDAC and may provide the groundwork for a new clinical PDAC therapy. PMID:26213847

Synthetic biology approaches to biological containment: pre-emptively tackling potential risks

PubMed Central

Krüger, Antje; Csibra, Eszter; Gianni, Edoardo

2016-01-01

Biocontainment comprises any strategy applied to ensure that harmful organisms are confined to controlled laboratory conditions and not allowed to escape into the environment. Genetically engineered microorganisms (GEMs), regardless of the nature of the modification and how it was established, have potential human or ecological impact if accidentally leaked or voluntarily released into a natural setting. Although all evidence to date is that GEMs are unable to compete in the environment, the power of synthetic biology to rewrite life requires a pre-emptive strategy to tackle possible unknown risks. Physical containment barriers have proven effective but a number of strategies have been developed to further strengthen biocontainment. Research on complex genetic circuits, lethal genes, alternative nucleic acids, genome recoding and synthetic auxotrophies aim to design more effective routes towards biocontainment. Here, we describe recent advances in synthetic biology that contribute to the ongoing efforts to develop new and improved genetic, semantic, metabolic and mechanistic plans for the containment of GEMs. PMID:27903826

Synthetic biology approaches to biological containment: pre-emptively tackling potential risks.

PubMed

Torres, Leticia; Krüger, Antje; Csibra, Eszter; Gianni, Edoardo; Pinheiro, Vitor B

2016-11-30

Biocontainment comprises any strategy applied to ensure that harmful organisms are confined to controlled laboratory conditions and not allowed to escape into the environment. Genetically engineered microorganisms (GEMs), regardless of the nature of the modification and how it was established, have potential human or ecological impact if accidentally leaked or voluntarily released into a natural setting. Although all evidence to date is that GEMs are unable to compete in the environment, the power of synthetic biology to rewrite life requires a pre-emptive strategy to tackle possible unknown risks. Physical containment barriers have proven effective but a number of strategies have been developed to further strengthen biocontainment. Research on complex genetic circuits, lethal genes, alternative nucleic acids, genome recoding and synthetic auxotrophies aim to design more effective routes towards biocontainment. Here, we describe recent advances in synthetic biology that contribute to the ongoing efforts to develop new and improved genetic, semantic, metabolic and mechanistic plans for the containment of GEMs. © 2016 The Author(s).

The catalytic mechanism of mouse renin studied with QM/MM calculations.

PubMed

Brás, Natércia F; Ramos, Maria J; Fernandes, Pedro A

2012-09-28

Hypertension is a chronic condition that affects nearly 25% of adults worldwide. As the Renin-Angiotensin-Aldosterone System is implicated in the control of blood pressure and body fluid homeostasis, its combined blockage is an attractive therapeutic strategy currently in use for the treatment of several cardiovascular conditions. We have performed QM/MM calculations to study the mouse renin catalytic mechanism in atomistic detail, using the N-terminal His6-Asn14 segment of angiotensinogen as substrate. The enzymatic reaction (hydrolysis of the peptidic bond between residues in the 10th and 11th positions) occurs through a general acid/base mechanism and, surprisingly, it is characterized by three mechanistic steps: it begins with the creation of a first very stable tetrahedral gem-diol intermediate, followed by protonation of the peptidic bond nitrogen, giving rise to a second intermediate. In a final step the peptidic bond is completely cleaved and both gem-diol hydroxyl protons are transferred to the catalytic dyad (Asp32 and Asp215). The final reaction products are two separate peptides with carboxylic acid and amine extremities. The activation energy for the formation of the gem-diol intermediate was calculated as 23.68 kcal mol(-1), whereas for the other steps the values were 15.51 kcal mol(-1) and 14.40 kcal mol(-1), respectively. The rate limiting states were the reactants and the first transition state. The associated barrier (23.68 kcal mol(-1)) is close to the experimental values for the angiotensinogen substrate (19.6 kcal mol(-1)). We have also tested the influence of the density functional on the activation and reaction energies. All eight density functionals tested (B3LYP, B3LYP-D3, X3LYP, M06, B1B95, BMK, mPWB1K and B2PLYP) gave very similar results.

Customer Management Skills for Effective Air Force Civil Engineering Customer Service.

DTIC Science & Technology

1986-09-01

advertise --competence. (1) Craftsmen working closely with customer service -doing what is promised when it’s promised -if return to job site required, tell...RD-RI74 1 4 CUSTOMER MANAGEMENT SKILLS FOR EFFECTIVE AIR FORCE / I CIVIL ENGINEERING CUST (U) AIR FORCE INST OF TECH WRIGHT-PATTERSON RFS ON...I93 -A CUSTOMER MANAGEMENT SKILLS FOR EFFECTIVE AIR FORCE CIVIL ENGINEERING CUSTOMER SERVICE THESIS Danny S.- Long Captain, USAF AFIT/GEM/DEM/86S-1 7

78 FR 23231 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-18

...) Description and Quantity or Quantities of Articles or Services under Consideration for Purchase: 60 Active... equipment items, GEM-V GPS airborne receiver module, and communication security, software development... documents, U.S. Government and contract engineering and logistical personnel services, and other related...

Mining Hidden Gems Beneath the Surface: A Look At the Invisible Web.

ERIC Educational Resources Information Center

Carlson, Randal D.; Repman, Judi

2002-01-01

Describes resources for researchers called the Invisible Web that are hidden from the usual search engines and other tools and contrasts them with those resources available on the surface Web. Identifies specialized search tools, databases, and strategies that can be used to locate credible in-depth information. (Author/LRW)

With "Biobricks," Students Snap Together a New Science

ERIC Educational Resources Information Center

Trivedi, Bijal

2007-01-01

The underlying goal of the International Genetically Engineered Machine Competition, known as iGEM, is to figure out whether biological organisms and devices can be built from a collection of standard, off-the-shelf parts, just as someone might build a kit plane or car. For the undergraduates, it's an opportunity to construct whatever creature…

Mitochondria-associated ER Membranes (MAMs) and Glycosphingolipid Enriched Microdomains (GEMs): Isolation from Mouse Brain

PubMed Central

d'Azzo, Alessandra

2013-01-01

Intracellular organelles are highly dynamic structures with varying shape and composition, which are subjected to cell-specific intrinsic and extrinsic cues. Their membranes are often juxtaposed at defined contact sites, which become hubs for the exchange of signaling molecules and membrane components1,2,3,4. The inter-organellar membrane microdomains that are formed between the endoplasmic reticulum (ER) and the mitochondria at the opening of the IP3-sensitive Ca2+ channel are known as the mitochondria associated-ER membranes or MAMs4,5,6. The protein/lipid composition and biochemical properties of these membrane contact sites have been extensively studied particularly in relation to their role in regulating intracellular Ca2+ 4,5,6. The ER serves as the primary store of intracellular Ca2+, and in this capacity regulates a myriad of cellular processes downstream of Ca2+ signaling, including post-translational protein folding and protein maturation7. Mitochondria, on the other hand, maintain Ca2+ homeostasis, by buffering cytosolic Ca2+ concentration thereby preventing the initiation of apoptotic pathways downstream of Ca2+ unbalance4,8. The dynamic nature of the MAMs makes them ideal sites to dissect basic cellular mechanisms, including Ca2+ signaling and regulation of mitochondrial Ca2+ concentration, lipid biosynthesis and transport, energy metabolism and cell survival 4,9,10,11,12. Several protocols have been described for the purification of these microdomains from liver tissue and cultured cells13,14. Taking previously published methods into account, we have adapted a protocol for the isolation of mitochondria and MAMs from the adult mouse brain. To this procedure we have added an extra purification step, namely a Triton X100 extraction, which enables the isolation of the glycosphingolipid enriched microdomain (GEM) fraction of the MAMs. These GEM preparations share several protein components with caveolae and lipid rafts, derived from the plasma membrane or other intracellular membranes, and are proposed to function as gathering points for the clustering of receptor proteins and for protein–protein interactions4,15. PMID:23486347

Simulation of how a geo-engineering intervention to restore arctic sea ice might work in practice

NASA Astrophysics Data System (ADS)

Jackson, L. S.; Crook, J. A.; Forster, P.; Jarvis, A.; Leedal, D.; Ridgwell, A. J.; Vaughan, N.

2013-12-01

The declining trend in annual minimum Arctic sea ice coverage and years of more pronounced drops like 2007 and 2012 raise the prospect of an Arctic Ocean largely free of sea ice in late summer and the potential for a climate crisis or emergency. In a novel computer simulation, we treated one realisation of a climate model (HadGEM2) as the real world and tried to restore its Arctic sea ice by the rapid deployment of geo-engineering with emission of SO2 into the Arctic stratosphere. The objective was to restore the annual minimum Arctic sea ice coverage to levels seen in the late twentieth century using as little geo-engineering as possible. We took intervention decisions as one might do in the real world: by committee, using a limited set of uncertain 'observations' from our simulated world and using models and control theory to plan the best intervention strategy for the coming year - so learning as we went and being thrown off course by future volcanoes and technological breakdowns. Uncertainties in real world observations were simulated by applying noise to emerging results from the climate model. Volcanic forcing of twenty-first century climate was included with the timing and magnitude of the simulated eruptions unknown by the 'geo-engineers' until after the year of the eruption. Monitoring of Arctic sea ice with the option to intervene with SO2 emissions started from 2018 and continued to 2075. Simulated SO2 emissions were made in January-May each year at a latitude of 79o N and an altitude within the range of contemporary tanker aircraft. The magnitude of emissions was chosen annually using a model predictive control process calibrated using results from CMIP5 models (excluding HadGEM2), using the simplified climate model MAGICC and assimilation of emerging annual results from the HadGEM2 'real world'. We found that doubts in the minds of the 'geo-engineers' of the effectiveness and the side effects of their past intervention, and the veracity of the models used for planning intervention were a constant feature of the simulation. As a result, their assumptions and intervention approaches were considerably revised as the simulation progressed. Side effects of the geo-engineering were difficult to explicitly determine without a control experiment. Nevertheless, we found wide spread changes in precipitation that were believed to be due to the geo-engineering - a later control experiment confirmed this belief. On termination of the SO2 geo-engineering, northern hemisphere temperatures rose sharply and Arctic sea ice area dropped dramatically. These termination effects were so large that attribution to the geo-engineering cessation was unambiguous.

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.

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.

Development of the GEM-TPC X-ray Polarimeter with the Scalable Readout System

NASA Astrophysics Data System (ADS)

Kitaguchi, Takao; Hayato, Asami; Iwakiri, Wataru; Takeuchi, Yoko; Kubota, Megu; Nishida, Kazuki; Enoto, Teruaki; Tamagawa, Toru

2018-02-01

We have developed a gaseous Time Projection Chamber (TPC) containing a single-layered foil of a gas electron multiplier (GEM) to open up a new window on cosmic X-ray polarimetry in the 2-10 keV band. The micro-pattern TPC polarimeter in combination with the Scalable Readout System produced by the RD51 collaboration has been built as an engineering model to optimize detector parameters and improve polarimeter sensitivity. The polarimeter was characterized with unpolarized X-rays from an X-ray generator in a laboratory and polarized X-rays on the BL32B2 beamline at the SPring-8 synchrotron radiation facility. Preliminary results show that the polarimeter has a comparable modulation factor to a prototype of the flight one.

Engineering analyses of large precision cathode strip chambers for GEM

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

Horvath, J.A.; Belser, F.C.; Pratuch, S.M.

Structural analyses of large precision cathode strip chambers performed up to the date of this publication are documented. Mechanical property data for typical chamber materials are included. This information, originally intended to be an appendix to the {open_quotes}CSC Structural Design Bible,{close_quotes} is presented as a guide for future designers of large chambers.

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

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.

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.

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.

Computer-Aided System Needs for the Technical Design Section of the Base Level Civil Engineering Squadron.

DTIC Science & Technology

1986-09-01

iUADROi THESIS James P. ’Mi’tnik First Lieutenant, USAF AFIT/GEM/DEM/86S-1 9 Approved for public release; distribution unlimited DTIC F--I F CT ESDEC 16...9 COMPUTER-AIDED SYSTEM NEEDS FOR THE TECHNICAL DESIGN SECTION OF THE BASE LEVEL CIVIL ENGINEERING SQUADRON THESIS V :-. . Presented to the Faculty...directed his own thesis and then turned around as an AFIT instructor, and helped direct mine. His suggestions, talk and ability to calm me down

The military operator's experience of reliability and maintainability characteristics

NASA Astrophysics Data System (ADS)

Jones, R. Mcc.

An account is given of the British Army's approach to the achievement of high reliability and maintainability in rotorcraft during the procurement process. Attention is given to experience accumulated to date with the Gazelle, Scout, Agusta A109A, and Lynx helicopters; these offer lessons with respect to the Gem engine, fuel filtering, vibration, and an aircraft flight control system.

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.

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.

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

In-Memory Graph Databases for Web-Scale Data

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

Castellana, Vito G.; Morari, Alessandro; Weaver, Jesse R.

RDF databases have emerged as one of the most relevant way for organizing, integrating, and managing expo- nentially growing, often heterogeneous, and not rigidly structured data for a variety of scientific and commercial fields. In this paper we discuss the solutions integrated in GEMS (Graph database Engine for Multithreaded Systems), a software framework for implementing RDF databases on commodity, distributed-memory high-performance clusters. Unlike the majority of current RDF databases, GEMS has been designed from the ground up to primarily employ graph-based methods. This is reflected in all the layers of its stack. The GEMS framework is composed of: a SPARQL-to-C++more » compiler, a library of data structures and related methods to access and modify them, and a custom runtime providing lightweight software multithreading, network messages aggregation and a partitioned global address space. We provide an overview of the framework, detailing its component and how they have been closely designed and customized to address issues of graph methods applied to large-scale datasets on clusters. We discuss in details the principles that enable automatic translation of the queries (expressed in SPARQL, the query language of choice for RDF databases) to graph methods, and identify differences with respect to other RDF databases.« 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

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.

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

Digital Database of Selected Aggregate and Related Resources in Ada, Boise, Canyon, Elmore, Gem, and Owyhee Counties, Southwestern Idaho

USGS Publications Warehouse

Moyle, Phillip R.; Wallis, John C.; Bliss, James D.; Bolm, Karen D.

2004-01-01

The U.S. Geological Survey (USGS) compiled a database of aggregate sites and geotechnical sample data for six counties - Ada, Boise, Canyon, Elmore, Gem, and Owyhee - in southwest Idaho as part of a series of studies in support of the Bureau of Land Management (BLM) planning process. Emphasis is placed on sand and gravel sites in deposits of the Boise River, Snake River, and other fluvial systems and in Neogene lacustrine deposits. Data were collected primarily from unpublished Idaho Transportation Department (ITD) records and BLM site descriptions, published Army Corps of Engineers (ACE) records, and USGS sampling data. The results of this study provides important information needed by land-use planners and resource managers, particularly in the BLM, to anticipate and plan for demand and development of sand and gravel and other mineral material resources on public lands in response to the urban growth in southwestern Idaho.

An MDA Based Ontology Platform: AIR

NASA Astrophysics Data System (ADS)

Gaševic, Dragan; Djuric, Dragan; Devedžic, Vladan

In the past few years, software engineering has witnessed two major shifts: model-driven engineering has entered the mainstream, and some leading development tools have become open and extensible.1 AI has always been a spring of new ideas that have been adopted in software engineering, but most of its gems have stayed buried in laboratories, available only to a limited number of AI practitioners. Should AI tools be integrated into mainstream tools and could it be done? We think that it is feasible, and that both communities can benefit from this integration. In fact, some efforts in this direction have already been made, both by major industrial standardization bodies such as the OMG, and by academic laboratories.

GEM at 10: a decade's experience with the Guideline Elements Model.

PubMed

Hajizadeh, Negin; Kashyap, Nitu; Michel, George; Shiffman, Richard N

2011-01-01

The Guideline Elements Model (GEM) was developed in 2000 to organize the information contained in clinical practice guidelines using XML and to represent guideline content in a form that can be understood by human readers and processed by computers. In this work, we systematically reviewed the literature to better understand how GEM was being used, potential barriers to its use, and suggestions for improvement. Fifty external and twelve internally produced publications were identified and analyzed. GEM was used most commonly for modeling and ontology creation. Other investigators applied GEM for knowledge extraction and data mining, for clinical decision support for guideline generation. The GEM Cutter software-used to markup guidelines for translation into XML- has been downloaded 563 times since 2000. Although many investigators found GEM to be valuable, others critiqued its failure to clarify guideline semantics, difficulties in markup, and the fact that GEM files are not usually executable.

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.

The DcpS inhibitor RG3039 improves survival, function and motor unit pathologies in two SMA mouse models

PubMed Central

Gogliotti, Rocky G.; Cardona, Herminio; Singh, Jasbir; Bail, Sophie; Emery, Carina; Kuntz, Nancy; Jorgensen, Michael; Durens, Madel; Xia, Bing; Barlow, Courtenay; Heier, Christopher R.; Plasterer, Heather L.; Jacques, Vincent; Kiledjian, Megerditch; Jarecki, Jill; Rusche, James; DiDonato, Christine J.

2013-01-01

Spinal muscular atrophy (SMA) is caused by insufficient levels of the survival motor neuron (SMN) protein due to the functional loss of the SMN1 gene and the inability of its paralog, SMN2, to fully compensate due to reduced exon 7 splicing efficiency. Since SMA patients have at least one copy of SMN2, drug discovery campaigns have sought to identify SMN2 inducers. C5-substituted quinazolines increase SMN2 promoter activity in cell-based assays and a derivative, RG3039, has progressed to clinical testing. It is orally bioavailable, brain-penetrant and has been shown to be an inhibitor of the mRNA decapping enzyme, DcpS. Our pharmacological characterization of RG3039, reported here, demonstrates that RG3039 can extend survival and improve function in two SMA mouse models of varying disease severity (Taiwanese 5058 Hemi and 2B/− SMA mice), and positively impacts neuromuscular pathologies. In 2B/− SMA mice, RG3039 provided a >600% survival benefit (median 18 days to >112 days) when dosing began at P4, highlighting the importance of early intervention. We determined the minimum effective dose and the associated pharmacokinetic (PK) and exposure relationship of RG3039 and DcpS inhibition ex vivo. These data support the long PK half-life with extended pharmacodynamic outcome of RG3039 in 2B/− SMA mice. In motor neurons, RG3039 significantly increased both the average number of cells with gems and average number of gems per cell, which is used as an indirect measure of SMN levels. These studies contribute to dose selection and exposure estimates for the first studies with RG3039 in human subjects. PMID:23736298

Science, politics, and health in the brave new world of pharmaceutical carcinogenic risk assessment: Technical progress or cycle of regulatory capture?

PubMed Central

Abraham, John; Ballinger, Rachel

2012-01-01

The carcinogenicity (cancer-inducing potential) of pharmaceuticals is an important risk factor for health when considering whether thousands of patients on drug trials or millions/billions of consumers in the marketplace should be exposed to a new drug. Drawing on fieldwork involving over 50 interviews and documentary research spanning 2002–2010 in Europe and the US, and on regulatory capture theory, this article investigates how the techno-regulatory standards for carcinogenicity testing of pharmaceuticals have altered since 1998. It focuses on the replacement of long-term carcinogenicity tests in rodents (especially mice) with shorter-term tests involving genetically-engineered mice (GEM). Based on evidence regarding financial/organizational control, methodological design, and interpretation of the validation and application of these new GEM tests, it is argued that regulatory agencies permitted the drug industry to shape such validation and application in ways that prioritized commercial interests over the need to protect public health. Boundary-work enabling industry scientists to define some standards of public-health policy facilitated such capture. However, as the scientific credibility of GEM tests as tools to protect public health by screening out carcinogens became inescapably problematic, a regulatory resurgence, impelled by reputational concerns, exercised more control over industry’s construction and use of the tests, The extensive problems with GEM tests as public-health protective regulatory science raises the spectre that alterations to pharmaceutical carcinogenicity-testing standards since the 1990s may have been boundary-work in which the political project of decreasing the chance that companies’ products are defined as carcinogenic has masqueraded as techno-science. PMID:22784375

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.

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.

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.

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.

Genetically Engineered Mouse Models for Studying Inflammatory Bowel Disease

PubMed Central

Mizoguchi, Atsushi; Takeuchi, Takahito; Himuro, Hidetomo; Okada, Toshiyuki; Mizoguchi, Emiko

2015-01-01

Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition that is mediated by very complex mechanisms controlled by genetic, immune, and environmental factors. More than 74 kinds of genetically engineered mouse strains have been established since 1993 for studying IBD. Although mouse models cannot fully reflect human IBD, they have provided significant contributions for not only understanding the mechanism, but also developing new therapeutic means for IBD. Indeed, 20 kinds of genetically engineered mouse models carry the susceptibility genes identified in human IBD, and the functions of some other IBD susceptibility genes have also been dissected out using mouse models. Cutting-edge technologies such as cell-specific and inducible knockout systems, which were recently employed to mouse IBD models, have further enhanced the ability of investigators to provide important and unexpected rationales for developing new therapeutic strategies for IBD. In this review article, we briefly introduce 74 kinds of genetically engineered mouse models that spontaneously develop intestinal inflammation. PMID:26387641

The GEM-T2 gravitational model

NASA Technical Reports Server (NTRS)

Marsh, J. G.; Lerch, F. J.; Putney, B. H.; Felsentreger, T. L.; Sanchez, B. V.; Klosko, S. M.; Patel, G. B.; Robbins, J. W.; Williamson, R. G.; Engelis, T. E.

1989-01-01

The GEM-T2 is the latest in a series of Goddard Earth Models of the terrestrial field. It was designed to bring modeling capabilities one step closer towards ultimately determining the TOPEX/Poseidon satellite's radial position to an accuracy of 10-cm RMS (root mean square). It also improves models of the long wavelength geoid to support many oceanographic and geophysical applications. The GEM-T2 extends the spherical harmonic field to include more than 600 coefficients above degree 36 (which was the limit for its predecessor, GEM-T1). Like GEM-T1, it was produced entirely from satellite tracking data, but it now uses nearly twice as many satellites (31 vs. 17), contains four times the number of observations (2.4 million), has twice the number of data arcs (1132), and utilizes precise laser tracking from 11 satellites. The estimation technique for the solution has been augmented to include an optimum data weighting procedure with automatic error calibration for the gravitational parameters. Results for the GEM-T2 error calibration indicate significant improvement over previous satellite-only models. The error of commission in determining the geoid has been reduced from 155 cm in GEM-T1 to 105 cm for GEM-T2 for the 36 x 36 portion of the field, and 141 cm for the entire model. The orbital accuracies achieved using GEM-T2 are likewise improved. Also, the projected radial error on the TOPEX satellite orbit indicates 9.4 cm RMS for GEM-T2, compared to 24.1 cm for GEM-T1.

Reframed Genome-Scale Metabolic Model to Facilitate Genetic Design and Integration with Expression Data.

PubMed

Gu, Deqing; Jian, Xingxing; Zhang, Cheng; Hua, Qiang

2017-01-01

Genome-scale metabolic network models (GEMs) have played important roles in the design of genetically engineered strains and helped biologists to decipher metabolism. However, due to the complex gene-reaction relationships that exist in model systems, most algorithms have limited capabilities with respect to directly predicting accurate genetic design for metabolic engineering. In particular, methods that predict reaction knockout strategies leading to overproduction are often impractical in terms of gene manipulations. Recently, we proposed a method named logical transformation of model (LTM) to simplify the gene-reaction associations by introducing intermediate pseudo reactions, which makes it possible to generate genetic design. Here, we propose an alternative method to relieve researchers from deciphering complex gene-reactions by adding pseudo gene controlling reactions. In comparison to LTM, this new method introduces fewer pseudo reactions and generates a much smaller model system named as gModel. We showed that gModel allows two seldom reported applications: identification of minimal genomes and design of minimal cell factories within a modified OptKnock framework. In addition, gModel could be used to integrate expression data directly and improve the performance of the E-Fmin method for predicting fluxes. In conclusion, the model transformation procedure will facilitate genetic research based on GEMs, extending their applications.

A novel approach for monitoring genetically engineered microorganisms by using artificial, stable RNAs

NASA Technical Reports Server (NTRS)

Pitulle, C.; Hedenstierna, K. O.; Fox, G. E.

1995-01-01

Further improvements in technology for efficient monitoring of genetically engineered microorganisms (GEMs) in the environment are needed. Technology for monitoring rRNA is well established but has not generally been applicable to GEMs because of the lack of unique rRNA target sequences. In the work described herein, it is demonstrated that a deletion mutant of a plasmid-borne Vibrio proteolyticus 5S rRNA gene continues to accumulate to high levels in Escherichia coli although it is no longer incorporated into 70S ribosomes. This deletion construct was subsequently modified by mutagenesis to create a unique recognition site for the restriction endonuclease BstEII, into which new sequences could be readily inserted. Finally, a novel 17-nucleotide identifier sequence from Pennisetum purpureum was embedded into the construct to create an RNA identification cassette. The artificial identifier RNA, expressed from this cassette in vivo, accumulated in E. coli to levels comparable to those of wild-type 5S rRNA without being seriously detrimental to cell survival in laboratory experiments and without entering the ribosomes. These results demonstrate that artificial, stable RNAs containing sequence segments remarkably different from those present in any known rRNA can be designed and that neither the deleted sequence segment nor ribosome incorporation is essential for accumulation of an RNA product.

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.

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

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.

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.

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.

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.

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.

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.

Genetically engineered mouse models for studying inflammatory bowel disease.

PubMed

Mizoguchi, Atsushi; Takeuchi, Takahito; Himuro, Hidetomo; Okada, Toshiyuki; Mizoguchi, Emiko

2016-01-01

Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition that is mediated by very complex mechanisms controlled by genetic, immune, and environmental factors. More than 74 kinds of genetically engineered mouse strains have been established since 1993 for studying IBD. Although mouse models cannot fully reflect human IBD, they have provided significant contributions for not only understanding the mechanism, but also developing new therapeutic means for IBD. Indeed, 20 kinds of genetically engineered mouse models carry the susceptibility genes identified in human IBD, and the functions of some other IBD susceptibility genes have also been dissected out using mouse models. Cutting-edge technologies such as cell-specific and inducible knockout systems, which were recently employed to mouse IBD models, have further enhanced the ability of investigators to provide important and unexpected rationales for developing new therapeutic strategies for IBD. In this review article, we briefly introduce 74 kinds of genetically engineered mouse models that spontaneously develop intestinal inflammation. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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.

The determination of the orbit of the Japanese satellite Ajisai and the GEM-T1 and GEM-T2 gravity field models

NASA Technical Reports Server (NTRS)

Sanchez, Braulio V.

1990-01-01

The Japanese Experimental Geodetic Satellite Ajisai was launched on August 12, 1986. In response to the TOPEX-POSEIDON mission requirements, the GSFC Space Geodesy Branch and its associates are producing improved models of the Earth's gravitational field. With the launch of Ajisai, precise laser data is now available which can be used to test many current gravity models. The testing of the various gravity field models show improvements of more than 70 percent in the orbital fits when using GEM-T1 and GEM-T2 relative to results obtained with the earlier GEM-10B model. The GEM-T2 orbital fits are at the 13-cm level (RMS). The results of the tests with the various versions of the GEM-T1 model indicate that the addition of satellite altimetry and surface gravity anomalies as additional data types should improve future gravity field models.

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.

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.

A Genetically Engineered Mouse Model of Neuroblastoma Driven by Mutated ALK and MYCN

DTIC Science & Technology

2014-09-01

AWARD NUMBER: W81XWH-13-1-0220 TITLE: A Genetically Engineered Mouse Model of Neuroblastoma ...CONTRACT NUMBER A Genetically Engineered Mouse Model of Neuroblastoma Driven by Mutated ALK and MYCN 5b. GRANT NUMBER W81XWH-13-1-0220 5c...common ALK mutations in neuroblastoma , F1174L and R1275Q. We have determined that in tumors cells expressing mutated ALK, different downstream

Developing Novel Therapeutic Approaches in Small Cell Lung Carcinoma Using Genetically Engineered Mouse Models and Human Circulating Tumor Cells

DTIC Science & Technology

2014-10-01

AD_________________ Award Number: W81XWH-13-1-0325 TITLE: Developing Novel Therapeutic Approaches in Small Cell Lung Carcinoma Using ...Genetically Engineered Mouse Models and Human Circulating Tumor Cells PRINCIPAL INVESTIGATOR: Jeffrey Engelman MD PhD CONTRACTING ORGANIZATION ...Novel Therapeutic Approaches in Small Cell Lung 5a. CONTRACT NUMBER W81XWH-13-1-0325 Carcinoma Using Genetically Engineered Mouse Models and 5b

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.

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;

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.

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.

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

Development of a Screening Tool to Facilitate Technology Transfer of an Innovative Technology to Treat Perchlorate-Contaminated Water

DTIC Science & Technology

2008-03-01

foods such as fruits, vegetables, and beverages (U.S. FDA, 2004). If the U.S. EPA ultimately establishes a drinking water standard for perchlorate...TREAT PERCHLORATE-CONTAMINATED WATER THESIS Daniel A. Craig, Captain, USAF AFIT/GEM/ENV/08-M06 DEPARTMENT OF THE AIR FORCE AIR UNIVERSITY...OF AN INNOVATIVE TECHNOLOGY TO TREAT PERCHLORATE- CONTAMINATED WATER THESIS Presented to the Faculty Department of Systems and Engineering

Left to their own devices: Post-ELSI, ethical equipment and the International Genetically Engineered Machine (iGEM) Competition

PubMed Central

Balmer, Andrew S; Bulpin, Kate J

2013-01-01

In this article, we evaluate a novel method for post-ELSI (ethical, legal and social implications) collaboration, drawing on ‘human practices' (HP) to develop a form of reflexive ethical equipment that we termed ‘sociotechnical circuits'. We draw on a case study of working collaboratively in the International Genetically Engineered Machine Competition (iGEM) and relate this to the parts-based agenda of synthetic biology. We use qualitative methods to explore the experience of undergraduate students in the Competition, focussing on the 2010 University of Sheffield team. We examine how teams work collaboratively across disciplines to produce novel microorganisms. The Competition involves a HP component and we examine the way in which this has been narrowly defined within the ELSI framework. We argue that this is a much impoverished style of HP when compared with its original articulation as the development of ‘ethical equipment'. Inspired by this more theoretically rich HP framework, we explore the relations established between team members and how these were shaped by the norms, materials and practices of the Competition. We highlight the importance of care in the context of post-ELSI collaborations and report on the implications of our case study for such efforts and for the relation of the social sciences to the life sciences more generally. PMID:24159360

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Reproducibility of Fluorescent Expression from Engineered Biological Constructs in E. coli

PubMed Central

Beal, Jacob; Haddock-Angelli, Traci; Gershater, Markus; de Mora, Kim; Lizarazo, Meagan; Hollenhorst, Jim; Rettberg, Randy

2016-01-01

We present results of the first large-scale interlaboratory study carried out in synthetic biology, as part of the 2014 and 2015 International Genetically Engineered Machine (iGEM) competitions. Participants at 88 institutions around the world measured fluorescence from three engineered constitutive constructs in E. coli. Few participants were able to measure absolute fluorescence, so data was analyzed in terms of ratios. Precision was strongly related to fluorescent strength, ranging from 1.54-fold standard deviation for the ratio between strong promoters to 5.75-fold for the ratio between the strongest and weakest promoter, and while host strain did not affect expression ratios, choice of instrument did. This result shows that high quantitative precision and reproducibility of results is possible, while at the same time indicating areas needing improved laboratory practices. PMID:26937966

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.

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.

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.

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…

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.

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.

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.

Physical and chemical control of released microorganisms at field sites

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

Donegan, K.; Seidler, R.; Matyac, C.

1991-01-01

An important consideration in the environmental release of a genetically engineered microorganism (GEM) is the capability for reduction or elimination of GEM populations once their function is completed or if adverse environmental effects are observed. The decontamination treatments of burning and biocide application, alone and in combination with tilling, were evaluated for their ability to reduce populations of bacteria released on the phylloplane. Field plots of bush beans sprayed with the bacterium Erwinia herbicola, received the following treatments: (1) control, (2) control + till, (3) burn, (4) burn + till, (5) Kocide (cupric hydroxide), (6) Kocide + till, (7) Agri-strepmore » (streptomycin sulfate), and (8) Agri-strept + till. Leaves and soil from the plots were sampled -1, 1, 5, 8, 12, 15, 19, and 27 days after application of the decontamination treatments. Burning produced a significant and persistent reduction in the number of bacteria whereas tilling, alone or in combination with the biocide treatments, stimulated a significant and persistent reduction in the number of bacteria, whereas tilling, alone or in combination with the biocide treatments, stimulated a significant increase in bacterial populations that persisted for several weeks.« less

Modelling two-way interactions between atmospheric pollution and weather using high-resolution GEM-MACH

NASA Astrophysics Data System (ADS)

Makar, Paul; Gong, Wanmin; Pabla, Balbir; Cheung, Philip; Milbrandt, Jason; Gravel, Sylvie; Moran, Michael; Gilbert, Samuel; Zhang, Junhua; Zheng, Qiong

2013-04-01

The Global Environmental Multiscale (GEM) model is the source of the Canadian government's operational numerical weather forecast guidance, and GEM-MACH is the Canadian operational air-quality forecast model. GEM-MACH comprises GEM and the 'Modelling Air-quality and Chemistry' module, a gas-phase, aqueous-phase and aerosol chemistry and microphysics subroutine package called from within GEM's physics module. The present operational GEM-MACH model is "on-line" (both chemistry and meteorology are part of the same modelling structure) but is not fully coupled (weather variables are provided as inputs to the chemistry, but the chemical variables are not used to modify the weather). In this work, we describe modifications made to GEM-MACH as part of the 2nd phase of the Air Quality Model Evaluation International Initiative, in order to bring the model to a fully coupled status and present the results of initial tests comparing uncoupled and coupled versions of the model to observations for a high-resolution forecasting system. Changes to GEM's cloud microphysics and radiative transfer packages were carried out to allow two-way coupling. The cloud microphysics package used here is the Milbrandt-Yau 2-moment (MY2) bulk microphysics scheme, which solves prognostic equations for the total droplet number concentration and the mass mixing ratios of six hydrometeor categories. Here, we have replaced the original cloud condensation nucleation parameterization of MY2 (empirically relating supersaturation and CCN number) with the aerosol activation scheme of Abdul-Razzak and Ghan (2002). The latter scheme makes use of the particle size and speciation distribution of GEM-MACH's chemistry code as well as meteorological inputs to predict the number of aerosol particles activated to form cloud droplets, which is then used in the MY2 microphysics. The radiative transfer routines of GEM assume a default constant concentration aerosol profile between the surface and 1500m, and a single set of optical properties for extinction, single scattering albedo, and asymmetry factor. Ozone in GEM is taken from a default 2D (latitude-height) monthly climatology. We have replaced the ozone below the model top with the ozone calculated from GEM-MACH's chemistry, and the default optical parameters associated with particulate matter have been replaced by those calculated with a Mie scattering algorithm. These changes were found to have a significant local impact on both weather and air-quality predictions for short-term test runs of 24 hours duration. In that particular case, the maximum number concentration of cloud droplets decreased by an order of magnitude, while the number of raindrops increased by an order of magnitude and changed in spatial distribution, but surface rainfall was found to decrease. The differences in meteorology had a profound effect on local pollutant plume concentrations at specific locations and times. We compare results over a longer time period, using two parallel forecast systems, one with feedbacks between meteorology and chemistry, one without. Both nest GEM-MACH from a North American domain (10 km horizontal grid spacing) to a 1535 x 1360 km, 2.5 km domain. These systems will be evaluated against monitoring networks within the high resolution domain.

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.

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

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.

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

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.

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.

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.

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.

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.

Signals that regulate the oncogenic fate of neural stem cells and progenitors

PubMed Central

Swartling, Fredrik J.; Bolin, Sara; Phillips, Joanna J.; Persson, Anders I.

2013-01-01

Brain tumors have frequently been associated with a neural stem cell (NSC) origin and contain stem-like tumor cells, so-called brain tumor stem cells (BTSCs) that share many features with normal NSCs. A stem cell state of BTSCs confers resistance to radiotherapy and treatment with alkylating agents. It is also a hallmark of aggressive brain tumors and is maintained by transcriptional networks that are also active in embryonic stem cells. Advances in reprogramming of somatic cells into induced pluripotent stem (iPS) cells have further identified genes that drive stemness. In this review, we will highlight the possible drivers of stemness in medulloblastoma and glioma, the most frequent types of primary malignant brain cancer in children and adults, respectively. Signals that drive expansion of developmentally defined neural precursor cells are also active in corresponding brain tumors. Transcriptomal subgroups of human medulloblastoma and glioma match features of NSCs but also more restricted progenitors. Lessons from genetically-engineered mouse (GEM) models show that temporally and regionally defined NSCs can give rise to distinct subgroups of medulloblastoma and glioma. We will further discuss how acquisition of stem cell features may drive brain tumorigenesis from a non-NSC origin. Genetic alterations, signaling pathways, and therapy-induced changes in the tumor microenvironment can drive reprogramming networks and induce stemness in brain tumors. Finally, we propose a model where dysregulation of microRNAs (miRNAs) that normally provide barriers against reprogramming plays an integral role in promoting stemness in brain tumors. PMID:23376224

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...

AN IMPROVEMENT TO THE MOUSE COMPUTERIZED UNCERTAINTY ANALYSIS SYSTEM

EPA Science Inventory

The original MOUSE (Modular Oriented Uncertainty System) system was designed to deal with the problem of uncertainties in Environmental engineering calculations, such as a set of engineering cast or risk analysis equations. It was especially intended for use by individuals with l...

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.

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.

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.

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

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.

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.

Application of the GEM Inventory Data Capture Tools for Dynamic Vulnerability Assessment and Recovery Modelling

NASA Astrophysics Data System (ADS)

Verrucci, Enrica; Bevington, John; Vicini, Alessandro

2014-05-01

A set of open-source tools to create building exposure datasets for seismic risk assessment was developed from 2010-13 by the Inventory Data Capture Tools (IDCT) Risk Global Component of the Global Earthquake Model (GEM). The tools were designed to integrate data derived from remotely-sensed imagery, statistically-sampled in-situ field data of buildings to generate per-building and regional exposure data. A number of software tools were created to aid the development of these data, including mobile data capture tools for in-field structural assessment, and the Spatial Inventory Data Developer (SIDD) for creating "mapping schemes" - statistically-inferred distributions of building stock applied to areas of homogeneous urban land use. These tools were made publically available in January 2014. Exemplar implementations in Europe and Central Asia during the IDCT project highlighted several potential application areas beyond the original scope of the project. These are investigated here. We describe and demonstrate how the GEM-IDCT suite can be used extensively within the framework proposed by the EC-FP7 project SENSUM (Framework to integrate Space-based and in-situ sENSing for dynamic vUlnerability and recovery Monitoring). Specifically, applications in the areas of 1) dynamic vulnerability assessment (pre-event), and 2) recovery monitoring and evaluation (post-event) are discussed. Strategies for using the IDC Tools for these purposes are discussed. The results demonstrate the benefits of using advanced technology tools for data capture, especially in a systematic fashion using the taxonomic standards set by GEM. Originally designed for seismic risk assessment, it is clear the IDCT tools have relevance for multi-hazard risk assessment. When combined with a suitable sampling framework and applied to multi-temporal recovery monitoring, data generated from the tools can reveal spatio-temporal patterns in the quality of recovery activities and resilience trends can be inferred. Lastly, this work draws attention to the use of the IDCT suite as an education resource for inspiring and training new students and engineers in the field of disaster risk reduction.

Overexpression of survival motor neuron improves neuromuscular function and motor neuron survival in mutant SOD1 mice.

PubMed

Turner, Bradley J; Alfazema, Neza; Sheean, Rebecca K; Sleigh, James N; Davies, Kay E; Horne, Malcolm K; Talbot, Kevin

2014-04-01

Spinal muscular atrophy results from diminished levels of survival motor neuron (SMN) protein in spinal motor neurons. Low levels of SMN also occur in models of amyotrophic lateral sclerosis (ALS) caused by mutant superoxide dismutase 1 (SOD1) and genetic reduction of SMN levels exacerbates the phenotype of transgenic SOD1(G93A) mice. Here, we demonstrate that SMN protein is significantly reduced in the spinal cords of patients with sporadic ALS. To test the potential of SMN as a modifier of ALS, we overexpressed SMN in 2 different strains of SOD1(G93A) mice. Neuronal overexpression of SMN significantly preserved locomotor function, rescued motor neurons, and attenuated astrogliosis in spinal cords of SOD1(G93A) mice. Despite this, survival was not prolonged, most likely resulting from SMN mislocalization and depletion of gems in motor neurons of symptomatic mice. Our results reveal that SMN upregulation slows locomotor deficit onset and motor neuron loss in this mouse model of ALS. However, disruption of SMN nuclear complexes by high levels of mutant SOD1, even in the presence of SMN overexpression, might limit its survival promoting effects in this specific mouse model. Studies in emerging mouse models of ALS are therefore warranted to further explore the potential of SMN as a modifier of ALS. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

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.

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.

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.

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.

Overview of genetically engineered mouse models of colorectal carcinoma to enable translational biology and drug development.

PubMed

Roper, Jatin; Martin, Eric S; Hung, Kenneth E

2014-06-16

Preclinical models for colorectal cancer (CRC) are critical for translational biology and drug development studies to characterize and treat this condition. Mouse models of human cancer are particularly popular because of their relatively low cost, short life span, and ease of use. Genetically engineered mouse models (GEMMs) of CRC are engineered from germline or somatic modification of critical tumor suppressor genes and/or oncogenes that drive mutations in human disease. Detailed in this overview are the salient features of several useful colorectal cancer GEMMs and their value as tools for translational biology and preclinical drug development. Copyright © 2014 John Wiley & Sons, Inc.

Physiological significance of ghrelin revealed by studies using genetically engineered mouse models with modifications in the ghrelin system.

PubMed

Ariyasu, Hiroyuki; Akamizu, Takashi

2015-01-01

Ghrelin, an endogenous ligand for the growth hormone (GH) secretagogue receptor (GHS-R or ghrelin receptor), is a 28-amino acid acylated peptide mainly produced in the stomach. The pharmacological administration of ghrelin is known to exert diverse effects, such as stimulating GH secretion, promoting food intake, and increasing adiposity. In recent years, genetically engineered mouse models have provided important insights into the physiology of various hormones. In this review, we discuss current knowledge regarding the physiological significance of ghrelin on the basis of studies using genetically engineered mouse models with modifications in the ghrelin system.

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.

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.

Evaluation of aquatic sediment microcosms and their use in assessing possible effects of introduced microorganisms on ecosystem parameters.

PubMed Central

Wagner-Döbler, I; Pipke, R; Timmis, K N; Dwyer, D F

1992-01-01

In this paper we describe a sediment microcosm system consisting of 20 undisturbed, layered sediment cores with overlying site water which are incubated under identical conditions of temperature, light, stirring rate of overlying water, and water exchange rate. Ecosystem parameters (nutrient level, photosynthetic potential, community structure of heterotrophic bacteria, thymidine incorporation rate, and oxygen microgradients) of the laboratory microcosms and the source ecosystem were compared and shown to be indistinguishable for the first 2 weeks. In weeks 3 and 4, small differences were detectable in the nutrient level, community structure of heterotrophic bacteria, and thymidine incorporation rate. However, the photosynthetic potential, depth profiles of heterotrophic bacterial community structure, and oxygen microgradients were maintained throughout the incubation period and did not differ between laboratory microcosms and the source ecosystem. The microcosm system described here would thus appear to be a valid model of aquatic sediments for up to 4 weeks; the actual period would depend on the sediment source and incubation temperature. The validated systems were used with Rhine river sediment to assess possible effects on ecosystem parameters of Pseudomonas sp. strain B13 FR1(pFRC20P), a genetically engineered microorganism (GEM) that had been constructed to degrade mixtures of halo- and alkylbenzoates and -phenols. The GEM survived in the surface sediment at densities of 5 x 10(4) to 5 x 10(5)/g (dry weight) for 4 weeks and degraded added chloro- and methylaromatics. The GEM did not measurably influence ecosystem parameters such as photosynthesis, densities of selected heterotrophic bacteria, thymidine incorporation rate, and oxygen microgradients. Thus, the microcosm system described here would seem to be useful for the study of the ecology of biodegradation and the fate and effect of microorganisms introduced into the environment. PMID:1599244

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.

Evaluation of a GEM and CAT-based detector for radiation therapy beam monitoring

NASA Astrophysics Data System (ADS)

Brahme, A.; Danielsson, M.; Iacobaeus, C.; Ostling, J.; Peskov, V.; Wallmark, M.

2000-11-01

We are developing a radiation therapy beam monitor for the Karolinska Institute. This monitor will consist of two consecutive detectors confined in one gas chamber: a "keV-photon detector", which will allow diagnostic quality visualization of the patient, and a "MeV-photon detector", that will measure the absolute intensity of the therapy beam and its position with respect to the patient. Both detectors are based on highly radiation resistant gas and solid photon to electron converters, combined with GEMs and a CAT as amplification structures. We have performed systematic studies of the high-rate characteristics of the GEM and the CAT, as well as tested the electron transfer through these electron multipliers and various types of converters. The tests show that the GEM and the CAT satisfy all requirements for the beam monitoring system. As a result of these studies we successfully developed and tested a full section of the beam monitor equipped with a MeV-photon converter placed between the GEM and the CAT.

MeerLICHT and BlackGEM: custom-built telescopes to detect faint optical transients

NASA Astrophysics Data System (ADS)

Bloemen, Steven; Groot, Paul; Woudt, Patrick; Klein Wolt, Marc; McBride, Vanessa; Nelemans, Gijs; Körding, Elmar; Pretorius, Margaretha L.; Roelfsema, Ronald; Bettonvil, Felix; Balster, Harry; Bakker, Roy; Dolron, Peter; van Elteren, Arjen; Elswijk, Eddy; Engels, Arno; Fender, Rob; Fokker, Marc; de Haan, Menno; Hagoort, Klaas; de Hoog, Jasper; ter Horst, Rik; van der Kevie, Giel; Kozłowski, Stanisław; Kragt, Jan; Lech, Grzegorz; Le Poole, Rudolf; Lesman, Dirk; Morren, Johan; Navarro, Ramon; Paalberends, Willem-Jelle; Paterson, Kerry; Pawłaszek, Rafal; Pessemier, Wim; Raskin, Gert; Rutten, Harrie; Scheers, Bart; Schuil, Menno; Sybilski, Piotr W.

2016-07-01

We present the MeerLICHT and BlackGEM telescopes, which are wide-field optical telescopes that are currently being built to study transient phenomena, gravitational wave counterparts and variable stars. The telescopes have 65 cm primary mirrors and a 2.7 square degree field-of-view. The MeerLICHT and BlackGEM projects have different science goals, but will use identical telescopes. The first telescope, MeerLICHT, will be commissioned at Sutherland (South Africa) in the first quarter of 2017. It will co-point with MeerKAT to collect optical data commensurate with the radio observations. After careful analysis of MeerLICHT's performance, three telescopes of the same type will be commissioned in La Silla (Chile) in 2018 to form phase I of the BlackGEM array. BlackGEM aims at detecting and characterizing optical counterparts of gravitational wave events detected by Advanced LIGO and Virgo. In this contribution we present an overview of the science goals, the design and the status of the two projects.

Implementation of the P barANDA Planar-GEM tracking detector in Monte Carlo simulations

NASA Astrophysics Data System (ADS)

Divani Veis, Nazila; Ehret, Andre; Firoozabadi, Mohammad M.; Karabowicz, Radoslaw; Maas, Frank; Saito, Nami; Saito, Takehiko R.; Voss, Bernd; PANDA Gem-Tracker Subgroup

2018-02-01

The P barANDA experiment at FAIR will be performed to investigate different aspects of hadron physics using anti-proton beams interacting with a fixed nuclear target. The experimental setup consists of a complex series of detector components covering a large solid angle. A detector with a gaseous active media equipped with gas electron multiplier (GEM) technique will be employed to measure tracks of charged particles at forward direction in order to achieve a high momentum resolution. In this work, a full setup of the GEM tracking detector has been implemented in the P barANDA Monte Carlo simulation package (PandaRoot) based on the current technical and conceptual design, and the expected performance of the P barANDA GEM-tracking detector has been investigated. Furthermore, material-budget studies in terms of the radiation length of the P barANDA GEM-tracking detector have been made in order to investigate the effect of the detector materials and its associated structures to particle measurements.

Genetically Engineered Humanized Mouse Models for Preclinical Antibody Studies

PubMed Central

Proetzel, Gabriele; Wiles, Michael V.; Roopenian, Derry C.

2015-01-01

The use of genetic engineering has vastly improved our capabilities to create animal models relevant in preclinical research. With the recent advances in gene-editing technologies, it is now possible to very rapidly create highly tunable mouse models as needs arise. Here, we provide an overview of genetic engineering methods, as well as the development of humanized neonatal Fc receptor (FcRn) models and their use for monoclonal antibody in vivo studies. PMID:24150980

Identifying the Source of Gem Diamonds: Requirements for a Certification System

NASA Astrophysics Data System (ADS)

Shigley, J. E.

2002-05-01

Recent civil conflicts in several countries, in which profits from the sales of gem diamonds have supported the rival factions, have forced the jewelry industry to confront the need to certify the geographic sources of gem diamonds. The goals of this program are to prohibit the sale of so-called "conflict diamonds", and to prevent the loss of consumer confidence. Efforts to identify unique characteristics of gem diamonds have been hampered so far by the absence of chemical or physical features that are diagnostic of particular sources, and the lack of a representative collection of diamonds from major producing areas that would be required for a rigorous scientific study. The jewelry industry has therefore adopted plans to track gem diamonds from the mine through the manufacturing process to the consumer. Practical requirements for implementation of such a certification system will be summarized. Any proposed solutions for determining the sources of gem diamonds by some analytical technique, or for following diamonds from the mine, must take into account the annual production of several tens of millions of carats of rough diamonds, which are transformed during manufacturing into several hundreds of millions of polished gemstones (with an average weight of only about 0.03 carat, or 0.006 gram).

Electrochemical DNA biosensor based on poly(2,6-pyridinedicarboxylic acid) modified glassy carbon electrode for the determination of anticancer drug gemcitabine.

PubMed

Tığ, Gözde Aydoğdu; Zeybek, Bülent; Pekyardımcı, Şule

2016-07-01

In this study, a simple methodology was used to develop a new electrochemical DNA biosensor based on poly(2,6-pyridinedicarboxylic acid) (P(PDCA)) modified glassy carbon electrode (GCE). This modified electrode was used to monitor for the electrochemical interaction between the dsDNA and gemcitabine (GEM) for the first time. A decrease in oxidation signals of guanine after the interaction of the dsDNA with the GEM was used as an indicator for the selective determination of the GEM via differential pulse voltammetry (DPV). The guanine oxidation peak currents were linearly proportional to the concentrations of the GEM in the range of 1-30mgL(‒1). Limit of detection (LOD) and limit of quantification (LOQ) were found to be 0.276mgL(‒1) and 0.922mgL(‒1), respectively. The reproducibility, repeatability, and applicability of the analysis to pharmaceutical dosage forms and human serum samples were also examined. In addition to DPV method, UV-vis and viscosity measurements were utilized to propose the interaction mechanism between the GEM and the dsDNA. The novel DNA biosensor could serve for sensitive, accurate and rapid determination of the GEM. Copyright © 2016 Elsevier B.V. All rights reserved.

The fibrate drug gemfibrozil disrupts lipoprotein metabolism in rainbow trout

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

Prindiville, John S., E-mail: jprin041@uottawa.ca; Mennigen, Jan A.; Zamora, Jake M.

2011-03-15

Gemfibrozil (GEM) is a fibrate drug consistently found in effluents from sewage treatment plants. This study characterizes the pharmacological effects of GEM on the plasma lipoproteins of rainbow trout (Oncorhynchus mykiss). Our goals were to quantify the impact of the drug on: 1) lipid constituents of lipoproteins (phospholipids (PL), triacylglycerol (TAG), and cholesterol), 2) lipoprotein classes (high, low and very low density lipoproteins), and 3) fatty acid composition of lipoproteins. Potential mechanisms of GEM action were investigated by measuring lipoprotein lipase activity (LPL) and the hepatic gene expression of LPL and of the peroxisome proliferator-activated receptor (PPAR) {alpha}, {beta}, andmore » {gamma} isoforms. GEM treatment resulted in decreased plasma lipoprotein levels (- 29%) and a reduced size of all lipoprotein classes (lower PL:TAG ratios). However, the increase in HDL-cholesterol elicited by GEM in humans failed to be observed in trout. Therefore, HDL-cholesterol cannot be used to assess the impact of the drug on fish. GEM also modified lipoprotein composition by reducing the abundance of long-chain n-3 fatty acids, thereby potentially reducing the nutritional quality of exposed fish. The relative gene expression of LPL was increased, but the activity of the enzyme was not, and we found no evidence for the activation of PPAR pathways. The depressing effects of GEM on fish lipoproteins demonstrated here may be a concern in view of the widespread presence of fibrates in aquatic environments. Work is needed to test whether exposure to environmental concentrations of these drugs jeopardizes the capacity of fish for reproduction, temperature acclimation or migratory behaviors.« less

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.

A comparison of speciated atmospheric mercury at an urban center and an upwind rural location

USGS Publications Warehouse

Rutter, A.P.; Schauer, J.J.; Lough, G.C.; Snyder, D.C.; Kolb, C.J.; Von Klooster, S.; Rudolf, T.; Manolopoulos, H.; Olson, M.L.

2008-01-01

Gaseous elemental mercury (GEM), particulate mercury (PHg) and reactive gaseous mercury (RGM) were measured every other hour at a rural location in south central Wisconsin (Devil's Lake State Park, WI, USA) between April 2003 and March 2004, and at a predominantly downwind urban site in southeastern Wisconsin (Milwaukee, WI, USA) between June 2004 and May 2005. Annual averages of GEM, PHg, and RGM at the urban site were statistically higher than those measured at the rural site. Pollution roses of GEM and reactive mercury (RM; sum of PHg and RGM) at the rural and urban sites revealed the influences of point source emissions in surrounding counties that were consistent with the US EPA 1999 National Emission Inventory and the 2003-2005 US EPA Toxics Release Inventory. Source-receptor relationships at both sites were studied by quantifying the impacts of point sources on mercury concentrations. Time series of GEM, PHg, and RGM concentrations were sorted into two categories; time periods dominated by impacts from point sources, and time periods dominated by mercury from non-point sources. The analysis revealed average point source contributions to GEM, PHg, and RGM concentration measurements to be significant over the year long studies. At the rural site, contributions to annual average concentrations were: GEM (2%; 0.04 ng m-3); and, RM (48%; 5.7 pg m-3). At the urban site, contributions to annual average concentrations were: GEM (33%; 0.81 ng m-3); and, RM (64%; 13.8 pg m-3). ?? The Royal Society of Chemistry.

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

A Genetically Engineered Mouse Model of Sporadic Colorectal Cancer.

PubMed

Betzler, Alexander M; Kochall, Susan; Blickensdörfer, Linda; Garcia, Sebastian A; Thepkaysone, May-Linn; Nanduri, Lahiri K; Muders, Michael H; Weitz, Jürgen; Reissfelder, Christoph; Schölch, Sebastian

2017-07-06

Despite the advantages of easy applicability and cost-effectiveness, colorectal cancer mouse models based on tumor cell injection have severe limitations and do not accurately simulate tumor biology and tumor cell dissemination. Genetically engineered mouse models have been introduced to overcome these limitations; however, such models are technically demanding, especially in large organs such as the colon in which only a single tumor is desired. As a result, an immunocompetent, genetically engineered mouse model of colorectal cancer was developed which develops highly uniform tumors and can be used for tumor biology studies as well as therapeutic trials. Tumor development is initiated by surgical, segmental infection of the distal colon with adeno-cre virus in compound conditionally mutant mice. The tumors can be easily detected and monitored via colonoscopy. We here describe the surgical technique of segmental adeno-cre infection of the colon, the surveillance of the tumor via high-resolution colonoscopy and present the resulting colorectal tumors.

Gemstones

USGS Publications Warehouse

Olson, D.W.

2003-01-01

Part of the 2002 industrial minerals review. Statistics on gemstone production, processing, consumption, prices, and trade are provided. The outlook for gem diamonds and other precious gems is considered.

Depletion of pro-oncogenic RUNX2 enhances gemcitabine (GEM) sensitivity of p53-mutated pancreatic cancer Panc-1 cells through the induction of pro-apoptotic TAp63.

PubMed

Ozaki, Toshinori; Nakamura, Mizuyo; Ogata, Takehiro; Sang, Meijie; Yoda, Hiroyuki; Hiraoka, Kiriko; Sang, Meixiang; Shimozato, Osamu

2016-11-01

Recently, we have described that siRNA-mediated silencing of runt-related transcription factor 2 (RUNX2) improves anti-cancer drug gemcitabine (GEM) sensitivity of p53-deficient human pancreatic cancer AsPC-1 cells through the augmentation of p53 family TAp63-dependent cell death pathway. In this manuscript, we have extended our study to p53-mutated human pancreatic cancer Panc-1 cells. According to our present results, knockdown of mutant p53 alone had a marginal effect on GEM-mediated cell death of Panc-1 cells. We then sought to deplete RUNX2 using siRNA in Panc-1 cells and examined its effect on GEM sensitivity. Under our experimental conditions, RUNX2 knockdown caused a significant enhancement of GEM sensitivity of Panc-1 cells. Notably, GEM-mediated induction of TAp63 but not of TAp73 was further stimulated in RUNX2-depleted Panc-1 cells, indicating that, like AsPC-1 cells, TAp63 might play a pivotal role in the regulation of GEM sensitivity of Panc-1 cells. Consistent with this notion, forced expression of TAp63α in Panc-1 cells promoted cell cycle arrest and/or cell death, and massively increased luciferase activities driven by TAp63-target gene promoters such as p21WAF1 and NOXA. In addition, immunoprecipitation experiments indicated that RUNX2 forms a complex with TAp63 in Panc-1 cells. Taken together, our current observations strongly suggest that depletion of RUNX2 enhances the cytotoxic effect of GEM on p53-mutated Panc-1 cells through the stimulation of TAp63-dependent cell death pathway even in the presence of a large amount of pro-oncogenic mutant p53, and might provide an attractive strategy to treat pancreatic cancer patients with p53 mutations.

Depletion of pro-oncogenic RUNX2 enhances gemcitabine (GEM) sensitivity of p53-mutated pancreatic cancer Panc-1 cells through the induction of pro-apoptotic TAp63

PubMed Central

Ozaki, Toshinori; Nakamura, Mizuyo; Ogata, Takehiro; Sang, Meijie; Yoda, Hiroyuki; Hiraoka, Kiriko; Sang, Meixiang; Shimozato, Osamu

2016-01-01

Recently, we have described that siRNA-mediated silencing of runt-related transcription factor 2 (RUNX2) improves anti-cancer drug gemcitabine (GEM) sensitivity of p53-deficient human pancreatic cancer AsPC-1 cells through the augmentation of p53 family TAp63-dependent cell death pathway. In this manuscript, we have extended our study to p53-mutated human pancreatic cancer Panc-1 cells. According to our present results, knockdown of mutant p53 alone had a marginal effect on GEM-mediated cell death of Panc-1 cells. We then sought to deplete RUNX2 using siRNA in Panc-1 cells and examined its effect on GEM sensitivity. Under our experimental conditions, RUNX2 knockdown caused a significant enhancement of GEM sensitivity of Panc-1 cells. Notably, GEM-mediated induction of TAp63 but not of TAp73 was further stimulated in RUNX2-depleted Panc-1 cells, indicating that, like AsPC-1 cells, TAp63 might play a pivotal role in the regulation of GEM sensitivity of Panc-1 cells. Consistent with this notion, forced expression of TAp63α in Panc-1 cells promoted cell cycle arrest and/or cell death, and massively increased luciferase activities driven by TAp63-target gene promoters such as p21WAF1 and NOXA. In addition, immunoprecipitation experiments indicated that RUNX2 forms a complex with TAp63 in Panc-1 cells. Taken together, our current observations strongly suggest that depletion of RUNX2 enhances the cytotoxic effect of GEM on p53-mutated Panc-1 cells through the stimulation of TAp63-dependent cell death pathway even in the presence of a large amount of pro-oncogenic mutant p53, and might provide an attractive strategy to treat pancreatic cancer patients with p53 mutations. PMID:27713122

GEM-loaded magnetic albumin nanospheres modified with cetuximab for simultaneous targeting, magnetic resonance imaging, and double-targeted thermochemotherapy of pancreatic cancer cells.

PubMed

Wang, Ling; An, Yanli; Yuan, Chenyan; Zhang, Hao; Liang, Chen; Ding, Fengan; Gao, Qi; Zhang, Dongsheng

2015-01-01

Targeted delivery is a promising strategy to improve the diagnostic imaging and therapeutic effect of cancers. In this paper, novel cetuximab (C225)-conjugated, gemcitabine (GEM)-containing magnetic albumin nanospheres (C225-GEM/MANs) were fabricated and applied as a theranostic nanocarrier to conduct simultaneous targeting, magnetic resonance imaging (MRI), and double-targeted thermochemotherapy against pancreatic cancer cells. Fe3O4 nanoparticles (NPs) and GEM co-loaded albumin nanospheres (GEM/MANs) were prepared, and then C225 was further conjugated to synthesize C225-GEM/MANs. Their morphology, mean particle size, GEM encapsulation ratio, specific cell-binding ability, and thermal dynamic profiles were characterized. The effects of discriminating different EGFR-expressing pancreatic cancer cells (AsPC-1 and MIA PaCa-2) and monitoring cellular targeting effects were assessed by targeted MRI. Lastly, the antitumor efficiency of double/C225/magnetic-targeted and nontargeted thermochemotherapy was compared with chemotherapy alone using 3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and flow cytometry (FCM) assay. When treated with targeted nanospheres, AsPC-1 cells showed a significantly less intense MRI T2 signal than MIA PaCa-2 cells, while both cells had similar signal strength when incubated with nontargeted nanospheres. T2 signal intensity was significantly lower when magnetic and C225 targeting were combined, rather than used alone. The inhibitory and apoptotic rates of each thermochemotherapy group were significantly higher than those of the chemotherapy-alone groups. Additionally, both MTT and FCM analysis verified that double-targeted thermochemotherapy had the highest targeted killing efficiency among all groups. The C225-GEM/MANs can distinguish various EGFR-expressing live pancreatic cancer cells, monitor diverse cellular targeting effects using targeted MRI imaging, and efficiently mediate double-targeted thermochemotherapy against pancreatic cancer cells.

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.

Low-dose gemcitabine induces major histocompatibility complex class I-related chain A/B expression and enhances an antitumor innate immune response in pancreatic cancer.

PubMed

Miyashita, Tomoharu; Miki, Kenji; Kamigaki, Takashi; Makino, Isamu; Nakagawara, Hisatoshi; Tajima, Hidehiro; Takamura, Hiroyuki; Kitagawa, Hirohisa; Fushida, Sachio; Ahmed, Ali K; Duncan, Mark D; Harmon, John W; Ohta, Tetsuo

2017-02-01

We investigated the effect of gemcitabine (GEM), a key drug for pancreatic cancer treatment, on the expression of cell surface MICA/B in pancreatic cancer cells and resulting cytotoxicity of γδ T cells. We assessed the effect of GEM on the upregulation of cell surface MICA/B expression by flow cytometry, utilizing six pancreatic cancer cell lines. MICA and CD16 expressions from resected pancreatic cancer patient specimens, which received neoadjuvant chemotherapy (NAC) with GEM, were analyzed by immunohistochemistry. GEM could increase MICA/B expression on cell surface in pancreatic cancer cell lines (in 2 of 6 cell lines). This effect was most effectively at concentration not affecting cell growth of GEM (0.001 μM), because MICA/B negative population was appeared at concentration at cytostatic and cytotoxic effect to cell growth (0.1 and 10 μM). The cytotoxic activity of γδ T cells against PANC-1 was detected and functions through interactions between NKG2D and MICA/B. However, the enhancement of NKG2D-dependent cytotoxicity with increased MICA/B expression, by GEM treatment, was not observed. In addition, soluble MIC molecules were released from pancreatic cancer cell lines in culture supernatant with GEM treatment. Immunohistochemical staining demonstrated that MICA expression in tumor cells and CD16 positive cells surrounding tumors were significantly higher in the NAC group compared to that of the control group. There was a significant correlation between NAC and MICA expression, as well as NAC and CD16 positive cell expression. The present results indicate that low-dose GEM-induced MICA/B expression enhances innate immune function rather than cytotoxicity in pancreatic cancer. In addition, our result suggests that the inhibition of cleavage and release of MIC molecules from the tumor surface could potentially improve NKG2D-dependent cytotoxicity.

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.

Building a Brainier Mouse.

ERIC Educational Resources Information Center

Tsien, Joe Z.

2000-01-01

Describes a genetic engineering project to build an intelligent mouse. Cites understanding the molecular basis of learning and memory as a very important step. Concludes that while science will never create a genius mouse that plays the stock market, it can turn a mouse into a quick learner with a better memory. (YDS)

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.

Gains in the Education of Mathematics and Science GEMS: Teaching Robotics to High School Students

DTIC Science & Technology

2013-01-01

find amusing but that we find of less educational value, like having the robots say comical things. Those who have more teaching time would doubtless...Gains in the Education of Mathematics and Science GEMS: Teaching Robotics to High School Students by Edward M. Measure and Edward Creegan...TR-6220 January 2013 Gains in the Education of Mathematics and Science (GEMS): Teaching Robotics to High School Students Edward M

Python based integration of GEM detector electronics with JET data acquisition system

NASA Astrophysics Data System (ADS)

Zabołotny, Wojciech M.; Byszuk, Adrian; Chernyshova, Maryna; Cieszewski, Radosław; Czarski, Tomasz; Dalley, Simon; Hogben, Colin; Jakubowska, Katarzyna L.; Kasprowicz, Grzegorz; Poźniak, Krzysztof; Rzadkiewicz, Jacek; Scholz, Marek; Shumack, Amy

2014-11-01

This paper presents the system integrating the dedicated measurement and control electronic systems for Gas Electron Multiplier (GEM) detectors with the Control and Data Acquisition system (CODAS) in the JET facility in Culham, England. The presented system performs the high level procedures necessary to calibrate the GEM detector and to protect it against possible malfunctions or dangerous changes in operating conditions. The system also allows control of the GEM detectors from CODAS, setting of their parameters, checking their state, starting the plasma measurement and to reading the results. The system has been implemented using the Python language, using the advanced libraries for implementation of network communication protocols, for object based hardware management and for data processing.

Tissue-engineered skin preserving the potential of epithelial cells to differentiate into hair after grafting.

PubMed

Larouche, Danielle; Cuffley, Kristine; Paquet, Claudie; Germain, Lucie

2011-03-01

The aim of this study was to evaluate whether tissue-engineered skin produced in vitro was able to sustain growth of hair follicles in vitro and after grafting. Different tissues were designed. Dissociated newborn mouse keratinocytes or newborn mouse hair buds (HBs) were added onto dermal constructs consisting of a tissue-engineered cell-derived matrix elaborated from either newborn mouse or adult human fibroblasts cultured with ascorbic acid. After 7-21 days of maturation at the air-liquid interface, no hair was noticed in vitro. Epidermal differentiation was observed in all tissue-engineered skin. However, human fibroblast-derived tissue-engineered dermis (hD) promoted a thicker epidermis than mouse fibroblast-derived tissue-engineered dermis (mD). In association with mD, HBs developed epithelial cyst-like inclusions presenting outer root sheath-like attributes. In contrast, epidermoid cyst-like inclusions lined by a stratified squamous epithelium were present in tissues composed of HBs and hD. After grafting, pilo-sebaceous units formed and hair grew in skin elaborated from HBs cultured 10-26 days submerged in culture medium in association with mD. However, the number of normal hair follicles decreased with longer culture time. This hair-forming capacity after grafting was not observed in tissues composed of hD overlaid with HBs. These results demonstrate that epithelial stem cells can be kept in vitro in a permissive tissue-engineered dermal environment without losing their potential to induce hair growth after grafting.

FPGA-based GEM detector signal acquisition for SXR spectroscopy system

NASA Astrophysics Data System (ADS)

Wojenski, A.; Pozniak, K. T.; Kasprowicz, G.; Kolasinski, P.; Krawczyk, R.; Zabolotny, W.; Chernyshova, M.; Czarski, T.; Malinowski, K.

2016-11-01

The presented work is related to the Gas Electron Multiplier (GEM) detector soft X-ray spectroscopy system for tokamak applications. The used GEM detector has one-dimensional, 128 channel readout structure. The channels are connected to the radiation-hard electronics with configurable analog stage and fast ADCs, supporting speeds of 125 MSPS for each channel. The digitalized data is sent directly to the FPGAs using fast serial links. The preprocessing algorithms are implemented in the FPGAs, with the data buffering made in the on-board 2Gb DDR3 memory chips. After the algorithmic stage, the data is sent to the Intel Xeon-based PC for further postprocessing using PCI-Express link Gen 2. For connection of multiple FPGAs, PCI-Express switch 8-to-1 was designed. The whole system can support up to 2048 analog channels. The scope of the work is an FPGA-based implementation of the recorder of the raw signal from GEM detector. Since the system will work in a very challenging environment (neutron radiation, intense electro-magnetic fields), the registered signals from the GEM detector can be corrupted. In the case of the very intense hot plasma radiation (e.g. laser generated plasma), the registered signals can overlap. Therefore, it is valuable to register the raw signals from the GEM detector with high number of events during soft X-ray radiation. The signal analysis will have the direct impact on the implementation of photon energy computation algorithms. As the result, the system will produce energy spectra and topological distribution of soft X-ray radiation. The advanced software was developed in order to perform complex system startup and monitoring of hardware units. Using the array of two one-dimensional GEM detectors it will be possible to perform tomographic reconstruction of plasma impurities radiation in the SXR region.

High levels of reactive gaseous mercury observed at a high elevation research laboratory in the Rocky Mountains

NASA Astrophysics Data System (ADS)

Faïn, X.; Obrist, D.; Hallar, A. G.; McCubbin, I.; Rahn, T.

2009-07-01

The chemical cycling and spatiotemporal distribution of mercury in the troposphere is poorly understood. We measured gaseous elemental mercury (GEM), reactive gaseous mercury (RGM) and particulate mercury (HgP) along with CO, ozone, aerosols, and meteorological variables at Storm Peak Laboratory at an elevation of 3200 m a.s.l., in Colorado, from 28 April to 1 July 2008. The mean mercury concentrations were 1.6 ng m-3 (GEM), 20 pg m-3 (RGM) and 9 pg m-3 (HgP). We observed eight events of strongly enhanced atmospheric RGM levels with maximum concentrations up to 135 pg m-3. RGM enhancement events were unrelated to daytime/nighttime patterns and lasted for long time periods of 2 to 6 days. During seven of these events, RGM was inversely correlated to GEM (RGM/GEM regression slope ~ -0.1), but did not exhibit correlations with ozone, carbon monoxide, or aerosol concentrations. Relative humidity was the dominant factor affecting RGM levels with high RGM levels always present whenever relative humidity was below 40 to 50%. We conclude that RGM enhancements observed at Storm Peak Laboratory were not induced by pollution events and were related to oxidation of tropospheric GEM, but the mechanism remain unclear. Based on backtrajectory analysis and a lack of mass balance between RGM and GEM, we propose that in situ production of RGM may have occurred in some distance allowing for scavenging and/or deposition of some RGM prior to reaching the laboratory, and that GEM oxidation is an important tropospheric Hg sink. Our observations provide evidence that the tropospheric pool of mercury is frequently enriched in divalent mercury and that high RGM levels are not limited to the upper troposphere.

Preparation, Optimization and Toxicity Evaluation of (SPION-PLGA) ±PEG Nanoparticles Loaded with Gemcitabine as a Multifunctional Nanoparticle for Therapeutic and Diagnostic Applications.

PubMed

Hamzian, Nima; Hashemi, Maryam; Ghorbani, Mahdi; Bahreyni Toosi, Mohammad Hossein; Ramezani, Mohammad

2017-01-01

The aim of this study was to develop a novel multifunctional nanoparticle, which encapsulates SPION and Gemcitabine in PLGA ± PEG to form multifunctional drug delivery system. For this aim, super paramagnetic iron oxide nanoparticles (SPIONs) were simultaneously synthesized and encapsulated with Gemcitabine (Gem) in PLGA ± PEG copolymers via W/O/W double emulsification method. Optimum size and encapsulation efficiency for radiosensitization, hyperthermia and diagnostic applications were considered and the preparation parameters systematically were investigated and physicochemical characteristics of optimized nanoparticle were studied. Then SPION-PLGA and PLGA-Gem nanoparticles were prepared with the same optimized parameters and the toxicity of these nanoparticles was compared with Gemcitabine in human breast cancer cell line (MCF-7). The optimum preparation parameters were obtained with Gem/polymer equal to 0.04, SPION/polymer equal to 0.8 and 1% sucrose per 20 mg of polymer. The hydrodynamic diameters of all nanoparticles were under 200 nm. Encapsulation efficiency was adjusted between 13.2% to 16.1% for Gemcitabine and 48.2% to 50.1% for SPION. In-vitro Gemcitabine release kinetics had controlled behavior. Enhancement ratios for PLGA-Gem and SPION-PLGA-Gem at concentration of nanoparticles equal to IC50 of Gemcitabine were 1.53 and 1.89 respectively. The statistical difference was significant ( p -value = 0.006 for SPION-PLGA-Gem and p -value = 0.015 for PLGA-Gem compared with Gemcitabine). In conclusion, we have successfully developed a Gemcitabine loaded super paramagnetic PLGA-Iron Oxide multifunctional drag delivery system. Future work includes in-vitro and in-vivo investigation of radiosensitization and other application of these nanoparticles.

Gaseous Electron Multiplier (GEM) Detectors

NASA Astrophysics Data System (ADS)

Gnanvo, Kondo

2017-09-01

Gaseous detectors have played a pivotal role as tracking devices in the field of particle physics experiments for the last fifty years. Recent advances in photolithography and micro processing techniques have enabled the transition from Multi Wire Proportional Chambers (MWPCs) and Drift Chambers to a new family of gaseous detectors refer to as Micro Pattern Gaseous Detectors (MPGDs). MPGDs combine the basic gas amplification principle with micro-structure printed circuits to provide detectors with excellent spatial and time resolution, high rate capability, low material budget and high radiation tolerance. Gas Electron Multiplier (GEMs) is a well-established MPGD technology invented by F. Sauli at CERN in 1997 and deployed various high energy physics (HEP) and nuclear NP experiment for tracking systems of current and future NP experiments. GEM detector combines an exceptional high rate capability (1 MHz / mm2) and robustness against harsh radiation environment with excellent position and timing resolution performances. Recent breakthroughs over the past decade have allowed the possibility for large area GEMs, making them cost effective and high-performance detector candidates to play pivotal role in current and future particle physics experiments. After a brief introduction of the basic principle of GEM technology, I will give a brief overview of the GEM detectors used in particle physics experiments over the past decades and especially in the NP community at Thomas Jefferson National Laboratory (JLab) and Brookhaven National Laboratory (BNL). I will follow by a review of state of the art of the new GEM development for the next generation of colliders such as Electron Ion Collider (EIC) or High Luminosity LHC and future Nuclear Physics experiments. I will conclude with a presentation of the CERN-based RD51 collaboration established in 2008 and its major achievements regarding technological developments and applications of MPGDs.

Fluoropyrimidines plus cisplatin versus gemcitabine/gemcitabine plus cisplatin in locally advanced and metastatic biliary tract carcinoma - a retrospective study.

PubMed

Croitoru, Adina; Gramaticu, Iulia; Dinu, Ioana; Gheorghe, Liana; Alexandrescu, Sorin; Buica, Florina; Luca, Ioana; Becheanu, Gabriel; Herlea, Vlad; Simionov, Iulia; Hrehoret, Doina; Lupescu, Ioana; Popescu, Irinel; Diculescu, Mircea

2012-09-01

This is a retrospective study of patients with advanced biliary tract carcinoma (BTC), who were treated with different regimens of chemotherapy. We studied patients with advanced BTC registered at the Department of Oncology at the Fundeni Clinical Institute between 2004 and 2008. The following data were analyzed: rate of response, progression free survival (PFS) to first and second line of chemotherapy, overall survival (OS) and drug toxicity. Ninety-six patients were eligible having either advanced intra or extrahepatic cholangiocarcinoma, or gallbladder cancer with no prior chemotherapy. Out of 96 patients, 57 (59.4%) received fluoropyrimidines (FP)+cisplatin and 39 (40.6%) gemcitabine (Gem)+/-cisplatin. The median PFS for FP+cisplatin was 5.9 months (95%CI 5-6.9) and for Gem+/-cisplatin 6.3 months (95%CI 5.4-7.1), p=0.661. Median OS for FP+cisplatin was 10.3 months (95%CI 7.5-13.1) and for Gem+/-cisplatin 9.1 months (95%CI 7.0-11.2), p=0.098. On disease progression, 46 patients received second line CT (Gem or FP+/-platinum compounds). Median OS for patients with FP based first line and Gem+/-cisplatin in second line was 19 months (95%CI 8.9-29) higher than for the reverse sequence: 13.2 months (95%CI 12-14.4), but not statistically significant (p=0.830). All patients were evaluated for toxicities. Most patients (75.5%) reported at least one adverse event. Our results through direct comparison of FP+cisplatin with Gem+/-cisplatin as first line treatment did not show any statistical differences in terms of rate of response, PFS and OS. However, our study showed that FP+cisplatin as first line and Gem based second line therapy gave a better OS rate.

The properties and applications of nanodiamonds.

PubMed

Mochalin, Vadym N; Shenderova, Olga; Ho, Dean; Gogotsi, Yury

2011-12-18

Nanodiamonds have excellent mechanical and optical properties, high surface areas and tunable surface structures. They are also non-toxic, which makes them well suited to biomedical applications. Here we review the synthesis, structure, properties, surface chemistry and phase transformations of individual nanodiamonds and clusters of nanodiamonds. In particular we discuss the rational control of the mechanical, chemical, electronic and optical properties of nanodiamonds through surface doping, interior doping and the introduction of functional groups. These little gems have a wide range of potential applications in tribology, drug delivery, bioimaging and tissue engineering, and also as protein mimics and a filler material for nanocomposites.

Genetically engineered mouse models of craniopharyngioma: an opportunity for therapy development and understanding of tumor biology

PubMed Central

Martinez‐Barbera, Juan Pedro

2017-01-01

Abstract Adamantinomatous craniopharyngioma (ACP) is the commonest tumor of the sellar region in childhood. Two genetically engineered mouse models have been developed and are giving valuable insights into ACP biology. These models have identified novel pathways activated in tumors, revealed an important function of paracrine signalling and extended conventional theories about the role of organ‐specific stem cells in tumorigenesis. In this review, we summarize these mouse models, what has been learnt, their limitations and open questions for future research. We then discussed how these mouse models may be used to test novel therapeutics against potentially targetable pathways recently identified in human ACP. PMID:28414891

The application of a monolithic triphenylphosphine reagent for conducting Ramirez gem-dibromoolefination reactions in flow.

PubMed

Roper, Kimberley A; Berry, Malcolm B; Ley, Steven V

2013-01-01

The application of a monolithic form of triphenylphosphine to the Ramirez gem-dibromoolefination reaction using flow chemistry techniques is reported. A variety of gem-dibromides were synthesised in high purity and excellent yield following only removal of solvent and no further off-line purification. It is also possible to perform the Appel reaction using the same monolith and the relationship between the mechanisms of the two reactions is discussed.

The application of a monolithic triphenylphosphine reagent for conducting Ramirez gem-dibromoolefination reactions in flow

PubMed Central

Roper, Kimberley A; Berry, Malcolm B

2013-01-01

Summary The application of a monolithic form of triphenylphosphine to the Ramirez gem-dibromoolefination reaction using flow chemistry techniques is reported. A variety of gem-dibromides were synthesised in high purity and excellent yield following only removal of solvent and no further off-line purification. It is also possible to perform the Appel reaction using the same monolith and the relationship between the mechanisms of the two reactions is discussed. PMID:24062843

Design and Pilot Study of a Gait Enhancing Mobile Shoe.

PubMed

Handzic, Ismet; Barno, Eileen M; Vasudevan, Erin V; Reed, Kyle B

2011-12-01

Hemiparesis is a frequent and disabling consequence of stroke and can lead to asymmetric and inefficient walking patterns. Training on a split-belt treadmill, which has two separate treads driving each leg at a different speed, can correct such asymmetries post-stroke. However, the effects of split-belt treadmill training only partially transfer to everyday walking over ground and extended training sessions are required to achieve long-lasting effects. Our aim is to develop an alternative device, the Gait Enhancing Mobile Shoe (GEMS), that mimics the actions of the split-belt treadmill, but can be used during overground walking and in one's own home, thus enabling long-term training. The GEMS does not require any external power and is completely passive; all necessary forces are redirected from the natural forces present during walking. Three healthy subjects walked on the shoes for twenty minutes during which one GEMS generated a backward motion and the other GEMS generated a forward motion. Our preliminary experiments suggest that wearing the GEMS did cause subjects to modify coordination between the legs and these changes persisted when subjects returned to normal over-ground walking. The largest effects were observed in measures of temporal coordination (e.g., duration of double-support). These results suggest that the GEMS is capable of altering overground walking coordination in healthy controls and could potentially be used to correct gait asymmetries post-stroke.

Combined Gemcitabine and Metronidazole Is a Promising Therapeutic Strategy for Cancer Stem-like Cholangiocarcinoma.

PubMed

Kawamoto, Makoto; Umebayashi, Masayo; Tanaka, Hiroto; Koya, Norihiro; Nakagawa, Sinichiro; Kawabe, Ken; Onishi, Hideya; Nakamura, Masafumi; Morisaki, Takashi

2018-05-01

Metronidazole (MNZ) is a common antibiotic that exerts disulfiram-like effects when taken together with alcohol. However, the relationship between MNZ and aldehyde dehydrogenase (ALDH) activity remains unclear. This study investigated whether MNZ reduces cancer stemness by suppressing ALDH activity and accordingly reducing the malignancy of cholangiocarcinoma (CCA). We developed gemcitabine (GEM)-resistant TFK-1 cells and originally established CCA cell line from a patient with GEM-resistant CCA. Using these cell lines, we analyzed the impacts of MNZ for cancer stem cell markers, invasiveness, and chemosensitivity. MNZ reduced ALDH activity in GEM-resistant CCA cells, leading to decreased invasiveness and enhanced chemosensitivity. MNZ diminished the invasiveness by inducing mesenchymal-epithelial transition and enhancing chemosensitivity by increasing ENT1 (equilibrative nucleoside transporter 1) and reducing RRM1 (ribonucleotide reductase M1). MNZ reduced cancer stemness in GEM-resistant CCA cells. Combined GEM and MNZ would be a promising therapeutic strategy for cancer stem-like CAA. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Gem1 and ERMES Do Not Directly Affect Phosphatidylserine Transport from ER to Mitochondria or Mitochondrial Inheritance

PubMed Central

Nguyen, Tammy T; Lewandowska, Agnieszka; Choi, Jae-Yeon; Markgraf, Daniel F; Junker, Mirco; Bilgin, Mesut; Ejsing, Christer S; Voelker, Dennis R; Rapoport, Tom A; Shaw, Janet M

2012-01-01

In yeast, a protein complex termed the ER-Mitochondria Encounter Structure (ERMES) tethers mitochondria to the endoplasmic reticulum. ERMES proteins are implicated in a variety of cellular functions including phospholipid synthesis, mitochondrial protein import, mitochondrial attachment to actin, polarized mitochondrial movement into daughter cells during division, and maintenance of mitochondrial DNA (mtDNA). The mitochondrial-anchored Gem1 GTPase has been proposed to regulate ERMES functions. Here, we show that ERMES and Gem1 have no direct role in the transport of phosphatidylserine (PS) from the ER to mitochondria during the synthesis of phosphatidylethanolamine (PE), as PS to PE conversion is not affected in ERMES or gem1 mutants. In addition, we report that mitochondrial inheritance defects in ERMES mutants are a secondary consequence of mitochondrial morphology defects, arguing against a primary role for ERMES in mitochondrial association with actin and mitochondrial movement. Finally, we show that ERMES complexes are long-lived, and do not depend on the presence of Gem1. Our findings suggest that the ERMES complex may have primarily a structural role in maintaining mitochondrial morphology. PMID:22409400

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.

Differential role of glycolipid-enriched membrane domains in glycoprotein VI- and integrin-mediated phospholipase Cgamma2 regulation in platelets.

PubMed Central

Wonerow, Peter; Obergfell, Achim; Wilde, Jonathan I; Bobe, Régis; Asazuma, Naoki; Brdicka, Tomás; Leo, Albrecht; Schraven, Burkhart; Horejsí, Václav; Shattil, Sanford J; Watson, Steve P

2002-01-01

The platelet collagen receptor glycoprotein VI (GPVI) and the fibrinogen receptor integrin alphaIIbbeta3 trigger intracellular signalling cascades involving the tyrosine kinase Syk, the adapter SLP-76 and phospholipase Cgamma2 (PLCgamma2). Similar pathways are activated downstream of immune receptors in lymphocytes, where they have been localized in part to glycolipid-enriched membrane domains (GEMs). Here we provide several lines of evidence that GPVI-mediated tyrosine phosphorylation of PLCgamma2 in platelets is dependent on GEM-organized signalling and utilizes the GEM resident adapter protein LAT (linker for activation of T cells). In sharp contrast, although fibrinogen binding to platelets stimulates alphaIIbbeta3-dependent activation of Syk and tyrosine phosphorylation of SLP-76 and PLCgamma2, it does not utilize GEMs to promote these responses or to support platelet aggregation. These results establish that GPVI and alphaIIbbeta3 trigger distinct patterns of receptor signalling in platelets, leading to tyrosine phosphorylation of PLCgamma2, and they highlight the role of GEMs in compartmentalizing signalling reactions involved in haemostasis. PMID:12049640

Engineering control of bacterial cellulose production using a genetic toolkit and a new cellulose-producing strain

PubMed Central

Florea, Michael; Hagemann, Henrik; Santosa, Gabriella; Micklem, Chris N.; Spencer-Milnes, Xenia; de Arroyo Garcia, Laura; Paschou, Despoina; Lazenbatt, Christopher; Kong, Deze; Chughtai, Haroon; Jensen, Kirsten; Freemont, Paul S.; Kitney, Richard; Reeve, Benjamin; Ellis, Tom

2016-01-01

Bacterial cellulose is a strong and ultrapure form of cellulose produced naturally by several species of the Acetobacteraceae. Its high strength, purity, and biocompatibility make it of great interest to materials science; however, precise control of its biosynthesis has remained a challenge for biotechnology. Here we isolate a strain of Komagataeibacter rhaeticus (K. rhaeticus iGEM) that can produce cellulose at high yields, grow in low-nitrogen conditions, and is highly resistant to toxic chemicals. We achieved external control over its bacterial cellulose production through development of a modular genetic toolkit that enables rational reprogramming of the cell. To further its use as an organism for biotechnology, we sequenced its genome and demonstrate genetic circuits that enable functionalization and patterning of heterologous gene expression within the cellulose matrix. This work lays the foundations for using genetic engineering to produce cellulose-based materials, with numerous applications in basic science, materials engineering, and biotechnology. PMID:27247386

Engineering control of bacterial cellulose production using a genetic toolkit and a new cellulose-producing strain.

PubMed

Florea, Michael; Hagemann, Henrik; Santosa, Gabriella; Abbott, James; Micklem, Chris N; Spencer-Milnes, Xenia; de Arroyo Garcia, Laura; Paschou, Despoina; Lazenbatt, Christopher; Kong, Deze; Chughtai, Haroon; Jensen, Kirsten; Freemont, Paul S; Kitney, Richard; Reeve, Benjamin; Ellis, Tom

2016-06-14

Bacterial cellulose is a strong and ultrapure form of cellulose produced naturally by several species of the Acetobacteraceae Its high strength, purity, and biocompatibility make it of great interest to materials science; however, precise control of its biosynthesis has remained a challenge for biotechnology. Here we isolate a strain of Komagataeibacter rhaeticus (K. rhaeticus iGEM) that can produce cellulose at high yields, grow in low-nitrogen conditions, and is highly resistant to toxic chemicals. We achieved external control over its bacterial cellulose production through development of a modular genetic toolkit that enables rational reprogramming of the cell. To further its use as an organism for biotechnology, we sequenced its genome and demonstrate genetic circuits that enable functionalization and patterning of heterologous gene expression within the cellulose matrix. This work lays the foundations for using genetic engineering to produce cellulose-based materials, with numerous applications in basic science, materials engineering, and biotechnology.

Applications of Raman spectroscopy to gemology.

PubMed

Bersani, Danilo; Lottici, Pier Paolo

2010-08-01

Being nondestructive and requiring short measurement times, a low amount of material, and no sample preparation, Raman spectroscopy is used for routine investigation in the study of gemstone inclusions and treatments and for the characterization of mounted gems. In this work, a review of the use of laboratory Raman and micro-Raman spectrometers and of portable Raman systems in the gemology field is given, focusing on gem identification and on the evaluation of the composition, provenance, and genesis of gems. Many examples are shown of the use of Raman spectroscopy as a tool for the identification of imitations, synthetic gems, and enhancement treatments in natural gemstones. Some recent developments are described, with particular attention being given to the semiprecious stone jade and to two important organic materials used in jewelry, i.e., pearls and corals.

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.

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)

Readout electronics for the GEM detector

NASA Astrophysics Data System (ADS)

Kasprowicz, G.; Czarski, T.; Chernyshova, M.; Czyrkowski, H.; Dabrowski, R.; Dominik, W.; Jakubowska, K.; Karpinski, L.; Kierzkowski, K.; Kudla, I. M.; Pozniak, K.; Rzadkiewicz, J.; Salapa, Z.; Scholz, M.; Zabolotny, W.

2011-10-01

A novel approach to the Gas Electron Multiplier (GEM) detector readout is presented. Unlike commonly used methods, based on discriminators[2],[3] and analogue FIFOs[1], the method developed uses simultaneously sampling high speed ADCs and advanced FPGA-based processing logic to estimate the energy of every single photon. Such method is applied to every GEM strip signal. It is especially useful in case of crystal-based spectrometers for soft X-rays, where higher order reflections need to be identified and rejected[5].

FPGA based charge fast histogramming for GEM detector

NASA Astrophysics Data System (ADS)

Poźniak, Krzysztof T.; Byszuk, A.; Chernyshova, M.; Cieszewski, R.; Czarski, T.; Dominik, W.; Jakubowska, K.; Kasprowicz, G.; Rzadkiewicz, J.; Scholz, M.; Zabolotny, W.

2013-10-01

This article presents a fast charge histogramming method for the position sensitive X-ray GEM detector. The energy resolved measurements are carried out simultaneously for 256 channels of the GEM detector. The whole process of histogramming is performed in 21 FPGA chips (Spartan-6 series from Xilinx) . The results of the histogramming process are stored in an external DDR3 memory. The structure of an electronic measuring equipment and a firmware functionality implemented in the FPGAs is described. Examples of test measurements are presented.

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...

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.

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

The GEM-Mars general circulation model for Mars: Description and evaluation

NASA Astrophysics Data System (ADS)

Neary, L.; Daerden, F.

2018-01-01

GEM-Mars is a gridpoint-based three-dimensional general circulation model (GCM) of the Mars atmosphere extending from the surface to approximately 150 km based on the GEM (Global Environmental Multiscale) model, part of the operational weather forecasting and data assimilation system for Canada. After the initial modification for Mars, the model has undergone considerable changes. GEM-Mars is now based on GEM 4.2.0 and many physical parameterizations have been added for Mars-specific atmospheric processes and surface-atmosphere exchange. The model simulates interactive carbon dioxide-, dust-, water- and atmospheric chemistry cycles. Dust and water ice clouds are radiatively active. Size distributed dust is lifted by saltation and dust devils. The model includes 16 chemical species (CO2, Argon, N2, O2, CO, H2O, CH4, O3, O(1D), O, H, H2, OH, HO2, H2O2 and O2(a1Δg)) and has fully interactive photochemistry (15 reactions) and gas-phase chemistry (31 reactions). GEM-Mars provides a good simulation of the water and ozone cycles. A variety of other passive tracers can be included for dedicated studies, such as the emission of methane. The model has both a hydrostatic and non-hydrostatic formulation, and together with a flexible grid definition provides a single platform for simulations on a variety of horizontal scales. The model code is fully parallelized using OMP and MPI. Model results are evaluated by comparison to a selection of observations from instruments on the surface and in orbit, relating to atmosphere and surface temperature and pressure, dust and ice content, polar ice mass, polar argon, and global water and ozone vertical columns. GEM-Mars will play an integral part in the analysis and interpretation of data that is received by the NOMAD spectrometer on the ESA-Roskosmos ExoMars Trace Gas Orbiter. The present paper provides an overview of the current status and capabilities of the GEM-Mars model and lays the foundations for more in-depth studies in support of the NOMAD mission.

Measurements of Atmospheric Mercury at a High Elevation Site (Lulin Atmospheric Background Station, LABS) in Taiwan

NASA Astrophysics Data System (ADS)

Sheu, G.; Lee, C.; Lin, N.

2007-12-01

Taiwan is located on the edge of the west Pacific Ocean and to the downwind side of East Asia, which is the largest anthropogenic mercury (Hg) emitting region globally. It has been demonstrated that the environmental quality of Taiwan can be influenced by regional Asian atmospheric pollution events, such as acid deposition, dust storm, and biomass burning. Therefore, Taiwan could also be under the influence of the East Asian Hg emissions. As a result, continuous atmospheric Hg measurements have been conducted at Lulin Atmospheric Background Station (LABS, 2862 m a.s.l.) since April 13, 2006 to study the long-range transport and transformation of atmospheric Hg. Three types of atmospheric Hg, including gaseous elemental Hg (GEM), reactive gaseous Hg (RGM), and particulate Hg (PHg), are measured using the Tekran 2537A/1130/1135 speciation system. Here we report the atmospheric Hg data collected between April, 2006 and April, 2007. The average GEM, RGM, and PHg concentrations were 1.83(±0.65) ng m-3, 17.85(±18.70) pg m- 3, and 6.12(±7.36) pg m-3, respectively. Seasonal variability in GEM concentration was evident with higher GEM concentrations between fall and spring. The highest monthly GEM average of 2.43 ng m-3 was observed in October, 2006. GEM concentrations were usually low in summer months with the lowest monthly average of 1.10 ng m-3 in July, 2006. Backward trajectory analysis indicated change in air mass origins among seasons. In summer (May ~ July), air masses were mainly from the Pacific Ocean with minimal land influence. On the other hand, between fall and spring, air masses were more or less under the influence of East Asia continent. These results suggested that Taiwan could be impacted by East Asia Hg emissions between fall and spring. Also, spikes of RGM were frequently detected between midnight and early morning with concurrent decreases in GEM and relative humidity and increases in ozone concentrations, suggesting the oxidation of GEM and formation of RGM in free troposphere.

Influence of the erineum strain of Colomerus vitis (Acari: Eriophyidae) on grape (Vitis vinifera) defense mechanisms.

PubMed

Javadi Khederi, Saeid; Khanjani, Mohammad; Gholami, Mansur; Panzarino, Onofrio; de Lillo, Enrico

2018-05-01

Grape (Vitis vinifera) is commonly affected by the erineum strain of Colomerus vitis (GEM) in Iran and the susceptibility of grape cultivars to GEM is poorly understood. In order to evaluate the impact of GEM on grape and its defense mechanisms against the mite, an exploratory study was carried out on 19 cultivars (18 Iranian and the non-native Muscat Gordo). The differential susceptibility of cultivars to GEM was compared on the basis of the area of leaf damage induced by GEM. The cultivars White Thompson seedless of Bovanat, Atabaki Zarghan, Koladari Ghoochan and Sahebi Uroomie were less susceptible to GEM, whereas Ghalati Dodaj, Rishbaba, Muscat Gordo and Neyshaboori Birjand appeared to be the most affected by the mite. In a no-choice setup, plants of selected cultivars of these two groups were infested by GEM and assayed for 10 biomarkers usually related to plant stress mechanisms against plant feeders: the activity of defense enzymes-peroxidase (POX), polyphenol oxidase (PPO), superoxide dismutase (SOD), phenylalanine ammonia-lyase (PAL), catalase (CAT), the amount of total polyphenolics, total flavonoids, total soluble carbohydrates, hydrogen peroxide (H 2 O 2 ), and malondialdehyde (MDA) expressing lipid peroxidation. The biomarkers were assessed in grape leaves 7 days before releasing the mites, as well as 7, 14 and 28 days after infestation (DAI). The activity of the enzymes and the amount of the compounds usually increased in percentage after mite infestation. A significant negative correlation was found between the area of leaf damage and PPO, POX, SOD, MDA and H 2 O 2 for all sampling dates. The area of leaf damage showed a significant positive correlation with total soluble carbohydrates at 28 DAI, and significant negative correlations with CAT (at 14 and 28 DAI), PAL and total flavonoids (at 7 DAI). No correlation was observed between area of leaf damage and total polyphenolics. The biomarkers PPO, SOD, CAT activity and H 2 O 2 provided the best explanation for the response of grape cultivars to GEM infestation.

Rational Design of Mouse Models for Cancer Research.

PubMed

Landgraf, Marietta; McGovern, Jacqui A; Friedl, Peter; Hutmacher, Dietmar W

2018-03-01

The laboratory mouse is widely considered as a valid and affordable model organism to study human disease. Attempts to improve the relevance of murine models for the investigation of human pathologies led to the development of various genetically engineered, xenograft and humanized mouse models. Nevertheless, most preclinical studies in mice suffer from insufficient predictive value when compared with cancer biology and therapy response of human patients. We propose an innovative strategy to improve the predictive power of preclinical cancer models. Combining (i) genomic, tissue engineering and regenerative medicine approaches for rational design of mouse models with (ii) rapid prototyping and computational benchmarking against human clinical data will enable fast and nonbiased validation of newly generated models. Copyright © 2017 Elsevier Ltd. All rights reserved.

Generation of a Knockout Mouse Embryonic Stem Cell Line Using a Paired CRISPR/Cas9 Genome Engineering Tool.

PubMed

Wettstein, Rahel; Bodak, Maxime; Ciaudo, Constance

2016-01-01

CRISPR/Cas9, originally discovered as a bacterial immune system, has recently been engineered into the latest tool to successfully introduce site-specific mutations in a variety of different organisms. Composed only of the Cas9 protein as well as one engineered guide RNA for its functionality, this system is much less complex in its setup and easier to handle than other guided nucleases such as Zinc-finger nucleases or TALENs.Here, we describe the simultaneous transfection of two paired CRISPR sgRNAs-Cas9 plasmids, in mouse embryonic stem cells (mESCs), resulting in the knockout of the selected target gene. Together with a four primer-evaluation system, it poses an efficient way to generate new independent knockout mouse embryonic stem cell lines.

OSG-GEM: Gene Expression Matrix Construction Using the Open Science Grid.

PubMed

Poehlman, William L; Rynge, Mats; Branton, Chris; Balamurugan, D; Feltus, Frank A

2016-01-01

High-throughput DNA sequencing technology has revolutionized the study of gene expression while introducing significant computational challenges for biologists. These computational challenges include access to sufficient computer hardware and functional data processing workflows. Both these challenges are addressed with our scalable, open-source Pegasus workflow for processing high-throughput DNA sequence datasets into a gene expression matrix (GEM) using computational resources available to U.S.-based researchers on the Open Science Grid (OSG). We describe the usage of the workflow (OSG-GEM), discuss workflow design, inspect performance data, and assess accuracy in mapping paired-end sequencing reads to a reference genome. A target OSG-GEM user is proficient with the Linux command line and possesses basic bioinformatics experience. The user may run this workflow directly on the OSG or adapt it to novel computing environments.

OSG-GEM: Gene Expression Matrix Construction Using the Open Science Grid

PubMed Central

Poehlman, William L.; Rynge, Mats; Branton, Chris; Balamurugan, D.; Feltus, Frank A.

2016-01-01

High-throughput DNA sequencing technology has revolutionized the study of gene expression while introducing significant computational challenges for biologists. These computational challenges include access to sufficient computer hardware and functional data processing workflows. Both these challenges are addressed with our scalable, open-source Pegasus workflow for processing high-throughput DNA sequence datasets into a gene expression matrix (GEM) using computational resources available to U.S.-based researchers on the Open Science Grid (OSG). We describe the usage of the workflow (OSG-GEM), discuss workflow design, inspect performance data, and assess accuracy in mapping paired-end sequencing reads to a reference genome. A target OSG-GEM user is proficient with the Linux command line and possesses basic bioinformatics experience. The user may run this workflow directly on the OSG or adapt it to novel computing environments. PMID:27499617

Operating range of a gas electron multiplier for portal imaging

NASA Astrophysics Data System (ADS)

Wallmark, M.; Brahme, A.; Danielsson, M.; Fonte, P.; Iacobaeus, C.; Peskov, V.; Östling, J.

2001-09-01

At the Karolinska Institute in Stockholm, Sweden a new detector for portal imaging is under development, which could greatly improve the alignment of the radiation beam with respect to the tumor during radiation treatment. The detector is based on solid converters combined with gas electron multipliers (GEMs) as an amplification structure. The detector has a large area and will be operated in a very high rate environment in the presence of heavy ionizing particles. As was discovered recently high rates and alpha particles could cause discharges in GEM and discharge propagation from GEM to GEM and to the readout electronics. Since reliability is one of the main requirements for the portal imaging device, we performed systematic studies to find a safe operating range of the device, free from typical high rate problems, such as discharges.

The cylindrical GEM detector of the KLOE-2 experiment

NASA Astrophysics Data System (ADS)

Bencivenni, G.; Branchini, P.; Ciambrone, P.; Czerwinski, E.; De Lucia, E.; Di Cicco, A.; Domenici, D.; Felici, G.; Fermani, P.; Morello, G.

2017-07-01

The KLOE-2 experiment started its data taking campaign in November 2014 with an upgraded tracking system at the DAΦNE electron-positron collider at the Frascati National Laboratory of INFN. The new tracking device, the Inner Tracker, operated together with the KLOE-2 Drift Chamber, has been installed to improve track and vertex reconstruction capabilities of the experimental apparatus. The Inner Tracker is a cylindrical GEM detector composed of four cylindrical triple-GEM detectors, each provided with an X-V strips-pads stereo readout. Although GEM detectors are already used in high energy physics experiments, this device is considered a frontier detector due to its fully-cylindrical geometry: KLOE-2 is the first experiment benefiting of this novel detector technology. Alignment and calibration of this detector will be presented together with its operating performance and reconstruction capabilities.

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.

Clinical evaluation of GEM 21S® and a collagen membrane with a coronally advanced flap as a root coverage procedure in the treatment of gingival recession defects: A comparative study

PubMed Central

Singh, Preetinder; Suresh, D. K.

2012-01-01

Aim: Clinical evaluation of efficacy of rhPDGF-BB plus beta tricalcium phosphate (GEM 21S®) along with a collagen membrane in root coverage using a coronally advanced flap. Materials and Methods: This human case series evaluated the clinical outcome of rhPDGF-BB with beta-tricalcium phosphate (GEM 21S®) and a collagen membrane in the treatment of recession defects using a coronally advanced flap. Patients were followed postoperatively, and healing was evaluated at 1, 3, and 6 months, with recession depth as the primary outcome measure. Results: This pioneer case series revealed a favorable tissue response to GEM 21S® and collagen membrane from both clinical and esthetic point of view in regenerative periodontal surgery. PMID:23493720

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.

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.

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.

How Genetically Engineered Mouse Tumor Models Provide Insights Into Human Cancers

PubMed Central

Politi, Katerina; Pao, William

2011-01-01

Genetically engineered mouse models (GEMMs) of human cancer were first created nearly 30 years ago. These early transgenic models demonstrated that mouse cells could be transformed in vivo by expression of an oncogene. A new field emerged, dedicated to generating and using mouse models of human cancer to address a wide variety of questions in cancer biology. The aim of this review is to highlight the contributions of mouse models to the diagnosis and treatment of human cancers. Because of the breadth of the topic, we have selected representative examples of how GEMMs are clinically relevant rather than provided an exhaustive list of experiments. Today, as detailed here, sophisticated mouse models are being created to study many aspects of cancer biology, including but not limited to mechanisms of sensitivity and resistance to drug treatment, oncogene cooperation, early detection, and metastasis. Alternatives to GEMMs, such as chemically induced or spontaneous tumor models, are not discussed in this review. PMID:21263096

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.

IUE observations of two late-type stars Bx Mon (M + pec) and TV Gem (M1 Iab)

NASA Technical Reports Server (NTRS)

Michalitsianos, A. G.; Hobbs, R. W.; Kafatos, M.

1981-01-01

The IUE observations of two late type stars BX Mon and TV Gem that reveal the emission properties in the ultraviolet of subluminous companions are discussed. Analysis of the continuum emission observed from BX Mon suggests the companion, is a middle A III star. High excitation emission lines observed between 1200 A and 2000 A that generally do not typify emission observed in either late M type variables or A type stars are also detected. It is suggested that these strong high excitation lines arise in a large volume of gas heated by nonradiation processes that could be the result of tidal interaction and mass exchange in the binary system. In contrast to stars such as BX Mon, the luminous M1 supergiant TV Gem shows unexpected intense UV continuum throughout the sensitivity range of IUE. The UV spectrum of TV Gem is characterized by intense continuum with broad absorption features detected in the short wavelength range. The analysis shows that the companion could be a B9 or A1 III-IV star. Alternate suggestions are presented for explaining the UV continuum in terms of an accretion disk in association with TV Gem.

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

Simulation and Digitization of a Gas Electron Multiplier Detector Using Geant4 and an Object-Oriented Digitization Program

NASA Astrophysics Data System (ADS)

McMullen, Timothy; Liyanage, Nilanga; Xiong, Weizhi; Zhao, Zhiwen

2017-01-01

Our research has focused on simulating the response of a Gas Electron Multiplier (GEM) detector using computational methods. GEM detectors provide a cost effective solution for radiation detection in high rate environments. A detailed simulation of GEM detector response to radiation is essential for the successful adaption of these detectors to different applications. Using Geant4 Monte Carlo (GEMC), a wrapper around Geant4 which has been successfully used to simulate the Solenoidal Large Intensity Device (SoLID) at Jefferson Lab, we are developing a simulation of a GEM chamber similar to the detectors currently used in our lab. We are also refining an object-oriented digitization program, which translates energy deposition information from GEMC into electronic readout which resembles the readout from our physical detectors. We have run the simulation with beta particles produced by the simulated decay of a 90Sr source, as well as with a simulated bremsstrahlung spectrum. Comparing the simulation data with real GEM data taken under similar conditions is used to refine the simulation parameters. Comparisons between results from the simulations and results from detector tests will be presented.

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.

GEM detector performance and efficiency in Proton Charge Radius (PRad) Experiment

NASA Astrophysics Data System (ADS)

Bai, Xinzhan; PRad Collaboration

2017-09-01

The PRad experiment (E12-11-106) was performed in 2016 at Jefferson Lab in Hall B. It aims to investigate the proton charge radius puzzle through electron proton elastic scattering process. The experiment used a non-magnetic spectrometer method, and reached a very small ep scattering angle and thus an unprecedented small four-momentum transfer squared region, Q2 from 2 ×10-4 to 0.06(GeV / c) 2 . PRad experiment was designed to measure the proton charge radius within a sub-percent precision. Gas Electron Multiplier (GEM) detectors have contributed to reach the experimental goal. A pair of large area GEM detectors, and a large acceptance, high resolution calorimeter(HyCal) were utilized in the experiment to detect the scattered electrons. The precision requirements of the experiment demands a highly accurate understanding of efficiency and stability of GEM detectors. In this talk, we will present the preliminary results on the performance and efficiency of GEM detectors. This work is supported in part by NSF MRI award PHY-1229153, the U.S. Department of Energy under Contract No. DE-FG02-07ER41528, No. DE-FG02-03ER41240 and Thomas Jefferson National Laboratory.

Data Quality Monitoring System for New GEM Muon Detectors for the CMS Experiment Upgrade

NASA Astrophysics Data System (ADS)

King, Robert; CMS Muon Group Team

2017-01-01

The Gas Electron Multiplier (GEM) detectors are novel detectors designed to improve the muon trigger and tracking performance in CMS experiment for the high luminosity upgrade of the LHC. Partial installation of GEM detectors is planned during the 2016-2017 technical stop. Before the GEM system is installed underground, its data acquisition (DAQ) electronics must be thoroughly tested. The DAQ system includes several commercial and custom-built electronic boards running custom firmware. The front-end electronics are radiation-hard and communicate via optical fibers. The data quality monitoring (DQM) software framework has been designed to provide online verification of the integrity of the data produced by the detector electronics, and to promptly identify potential hardware or firmware malfunctions in the system. Local hits reconstruction and clustering algorithms allow quality control of the data produced by each GEM chamber. Once the new detectors are installed, the DQM will monitor the stability and performance of the system during normal data-taking operations. We discuss the design of the DQM system, the software being developed to read out and process the detector data, and the methods used to identify and report hardware and firmware malfunctions of the system.

GenomeGems: evaluation of genetic variability from deep sequencing data

PubMed Central

2012-01-01

Background Detection of disease-causing mutations using Deep Sequencing technologies possesses great challenges. In particular, organizing the great amount of sequences generated so that mutations, which might possibly be biologically relevant, are easily identified is a difficult task. Yet, for this assignment only limited automatic accessible tools exist. Findings We developed GenomeGems to gap this need by enabling the user to view and compare Single Nucleotide Polymorphisms (SNPs) from multiple datasets and to load the data onto the UCSC Genome Browser for an expanded and familiar visualization. As such, via automatic, clear and accessible presentation of processed Deep Sequencing data, our tool aims to facilitate ranking of genomic SNP calling. GenomeGems runs on a local Personal Computer (PC) and is freely available at http://www.tau.ac.il/~nshomron/GenomeGems. Conclusions GenomeGems enables researchers to identify potential disease-causing SNPs in an efficient manner. This enables rapid turnover of information and leads to further experimental SNP validation. The tool allows the user to compare and visualize SNPs from multiple experiments and to easily load SNP data onto the UCSC Genome browser for further detailed information. PMID:22748151

Evolution in boron-based GEM detectors for diffraction measurements: from planar to 3D converters

NASA Astrophysics Data System (ADS)

Albani, Giorgia; Perelli Cippo, Enrico; Croci, Gabriele; Muraro, Andrea; Schooneveld, Erik; Scherillo, Antonella; Hall-Wilton, Richard; Kanaki, Kalliopi; Höglund, Carina; Hultman, Lars; Birch, Jens; Claps, Gerardo; Murtas, Fabrizio; Rebai, Marica; Tardocchi, Marco; Gorini, Giuseppe

2016-11-01

The so-called ‘3He-crisis’ has motivated the neutron detector community to undertake an intense R&D programme in order to develop technologies alternative to standard 3He tubes and suitable for neutron detection systems in future spallation sources such as the European spallation source (ESS). Boron-based GEM (gas electron multiplier) detectors are a promising ‘3He-free’ technology for thermal neutron detection in neutron scattering experiments. In this paper the evolution of boron-based GEM detectors from planar to 3D converters with an application in diffraction measurements is presented. The use of 3D converters coupled with GEMs allows for an optimization of the detector performances. Three different detectors were used for diffraction measurements on the INES instrument at the ISIS spallation source. The performances of the GEM-detectors are compared with those of conventional 3He tubes installed on the INES instrument. The conceptual detector with the 3D converter used in this paper reached a count rate per unit area of about 25% relative to the currently installed 3He tube. Its timing resolution is similar and the signal-to-background ratio (S/B) is 2 times lower.

Cosmic Ray Tests of Gas Electron Multipliers

NASA Astrophysics Data System (ADS)

Harris, Letrell; Kohl, Michael; Super Bigbite Spectrometer Collaboration; MUSE Collaboration; Hampton University Collaboration; DarkLight Collaboration

2017-09-01

The Super Bigbite Spectrometer (SBS) collaboration at Jefferson Laboratory (Jlab) is conducting an experimental program to measure the elastic form factors of nucleons. In association with Jlab, SBS Gas Electron Multipliers (GEMs) have been constructed by the University of Virginia (back trackers) and INFN in Italy (front trackers). The SBS GEMs measuring 40 × 150 cm2 (front trackers) and 60 × 200 cm2 (back trackers) in surface area are in the process of being conditioned and analyzed for tracking efficiency using cosmic rays in a clean room test lab before further assembly in the fall. These GEMs will be used to track the path of particles scattered off nuclear targets. Scintillators are placed both above and below GEM stacks to trigger a readout. In addition, Hampton University has also constructed a set of 10 × 10 cm2 GEMs originally for the OLYMPUS experiment at DESY in Germany, which are now being used for both the MUSE experiment at Paul Scherrer Institute (PSI) in Switzerland and the DarkLight experiment at Jlab's Low Energy Recirculatory Facility (LERF), where they are in the process of being characterized with cosmic rays. Jefferson Laboratory. This work has been supported by Jefferson Laboratory.

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.

Summertime elemental mercury exchange of temperate grasslands on an ecosystem-scale

PubMed Central

Fritsche, J.; Wohlfahrt, G.; Ammann, C.; Zeeman, M.; Hammerle, A.; Obrist, D.; Alewell, C.

2013-01-01

In order to estimate the air-surface mercury exchange of grasslands in temperate climate regions, fluxes of gaseous elemental mercury (GEM) were measured at two sites in Switzerland and one in Austria during summer 2006. Two classic micrometeorological methods (aerodynamic and modified Bowen ratio) have been applied to estimate net GEM exchange rates and to determine the response of the GEM flux to changes in environmental conditions (e.g. heavy rain, summer ozone) on an ecosystem-scale. Both methods proved to be appropriate to estimate fluxes on time scales of a few hours and longer. Average dry deposition rates up to 4.3 ng m−2 h−1 and mean deposition velocities up to 0.10 cm s−1 were measured, which indicates that during the active vegetation period temperate grasslands are a small net sink for atmospheric mercury. With increasing ozone concentrations depletion of GEM was observed, but could not be quantified from the flux signal. Night-time deposition fluxes of GEM were measured and seem to be the result of mercury co-deposition with condensing water. Effects of grass cuts could also be observed, but were of minor magnitude. PMID:24348525

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.

Design of T-GEM detectors for X-ray diagnostics on JET

NASA Astrophysics Data System (ADS)

Rzadkiewicz, J.; Dominik, W.; Scholz, M.; Chernyshova, M.; Czarski, T.; Czyrkowski, H.; Dabrowski, R.; Jakubowska, K.; Karpinski, L.; Kasprowicz, G.; Kierzkowski, K.; Pozniak, K.; Salapa, Z.; Zabolotny, W.; Blanchard, P.; Tyrrell, S.; Zastrow, K.-D.; JET EFDA Contributors

2013-08-01

Upgraded high-resolution X-ray diagnostics on JET is expected to monitor the plasma radiation emitted by W46+ and Ni26+ ions at 2.4 keV and 7.8 keV photon energies, respectively. Both X-ray lines will be monitored by new generation energy-resolved micropattern gas detectors with 1-D position reconstruction capability. The detection structure is based on triple GEM (T-GEM) amplification structure followed by the strip readout electrode. This article presents a design of new detectors and prototype detector tests.

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.

Construction of the TH-GEM detector components for metrology of low energy ionizing radiation

NASA Astrophysics Data System (ADS)

Silva, N. F.; Silva, T. F.; Castro, M. C.; Natal da Luz, H.; Caldas, L. V. E.

2018-03-01

The Gas Electron Multiplier (GEM) detector was originally proposed as a position sensitive detector to determine trajectories of particles prevenient from high-energy collisions. In order to study the potential of TH-GEM type detectors in dosimetric applications for low energy X-rays, specifically for the mammography standard qualities, it was proposed to construct a prototype with characteristics suitable for such use. In this work the general, structural and material parameters applicable to the necessary conditions were defined, establishing the process of construction of the components of a prototype.

High Performance, Mission Critical Applications for the War-fighter: Solutions to Network Challenges and Today’s Fluid Combat Environment

DTIC Science & Technology

2010-04-01

ADDRESS(ES) GemStone ,1260 NW Waterhouse Ave., Suite 200,Beaverton,OR,97006 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY...rates as needed, in massively distributed environments. Such a type of software, a “Data Fabric” is available today from GemStone Systems. It is...Plaza, 23rd Floor New York, NY 10001 | Phone: 646.530.8458 Washington D.C. | Phone: 301.564.0550 Copyright© 2008 by GemStone Systems, Inc. All rights

Tunable Cascade Reaction of Aryl Diazonium Salts and Trialkylamine: Synthesis of Monofluorinated Arylhydrazones and gem-Difluorinated Azo Compounds.

PubMed

Guo, Rui; Zhang, Zhengjuan; Shi, Feng; Tang, Pingping

2016-03-04

The first example of a mild and tunable cascade reaction of aryl diazonium salts and trialkylamine in the presence of Selectfluor to prepare monofluorinated arylhydrazones and gem-difluorinated azo compounds without metal has been explored. In the presence of H2O, the monofluorinated arylhydrazones were observed in moderate to good yield. In the absence of H2O, the gem-difluorinated azo compounds were obtained. The fluorinated arylhydrazones were utilized to synthesize fluorinated pyrazoles and other nitrogen-containing compounds.

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.

UTMD-Promoted Co-Delivery of Gemcitabine and miR-21 Inhibitor by Dendrimer-Entrapped Gold Nanoparticles for Pancreatic Cancer Therapy

PubMed Central

Lin, Lizhou; Fan, Yu; Gao, Feng; Jin, Lifang; Li, Dan; Sun, Wenjie; Li, Fan; Qin, Peng; Shi, Qiusheng; Shi, Xiangyang; Du, Lianfang

2018-01-01

Conventional chemotherapy of pancreatic cancer (PaCa) suffers the problems of low drug permeability and inherent or acquired drug resistance. Development of new strategies for enhanced therapy still remains a great challenge. Herein, we report a new ultrasound-targeted microbubble destruction (UTMD)-promoted delivery system based on dendrimer-entrapped gold nanoparticles (Au DENPs) for co-delivery of gemcitabine (Gem) and miR-21 inhibitor (miR-21i). Methods: In this study, Gem-Au DENPs/miR-21i was designed and synthesized. The designed polyplexes were characterized via transmission electron microscopy (TEM), Gel retardation assay and dynamic light scattering (DLS). Then, the optimum exposure parameters were examined by an ultrasound exposure platform. The cellular uptake, cytotoxicity and anticancer effects in vitro were analyzed by confocal laser microscopy, spectra microplate reader, flow cytometry and a chemiluminescence imaging system. Lastly, the anticancer effects in vivo were evaluated by contrast-enhanced ultrasound (CEUS), hematoxylin and eosin (H&E) staining, TUNEL staining and comparison of tumor volume. Results: The results showed that the Gem-Au DENPs/miR-21i can be uptake by cancer cells and the cellular uptake was further facilitated by UTMD with an ultrasound power of 0.4 W/cm2 to enhance the cell permeability. Further, the co-delivery of Gem and miR-21i with or without UTMD treatment displayed 82-fold and 13-fold lower IC50 values than the free Gem, respectively. The UTMD-promoted co-delivery of Gem and miR-21i was further validated by in vivo treatment and showed a significant tumor volume reduction and an increase in blood perfusion of xenografted pancreatic tumors. Conclusion: The co-delivery of Gem and miR-21i using Au DENPs can be significantly promoted by UTMD technology, hence providing a promising strategy for effective pancreatic cancer treatments. PMID:29556365

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.

Secondary scintillation yield from GEM and THGEM gaseous electron multipliers for direct dark matter search

NASA Astrophysics Data System (ADS)

Monteiro, C. M. B.; Fernandes, L. M. P.; Veloso, J. F. C. A.; Oliveira, C. A. B.; dos Santos, J. M. F.

2012-07-01

The search for alternatives to PMTs as photosensors in optical TPCs for rare event detection has significantly increased in the last few years. In particular, in view of the next generation large volume detectors, the use of photosensors with lower natural radioactivity, such as large area APDs or GM-APDs, with the additional possibility of sparse surface coverage, triggered the intense study of secondary scintillation production in micropattern electron multipliers, such as GEMs and THGEMs, as alternatives to the commonly used uniform electric field region between two parallel meshes. The much higher scintillation output obtained from the electron avalanches in such microstructures presents an advantage in those situations. The accurate knowledge of the amount of such scintillation is important for correct detector simulation and optimization. It will also serve as a benchmark for software tools developed and/or under development for the calculation of the amount of such scintillation.The secondary scintillation yield, or electroluminescence yield, in the electron avalanches of GEMs and THGEMs operating in gaseous xenon and argon has been determined for different gas pressures. At 1 bar, THGEMs deliver electroluminescence yields that are more than one order of magnitude higher when compared to those achieved in GEMs and two orders of magnitude when compared to those achieved in a uniform field gap. The THGEM electroluminescence yield presents a faster decrease with pressure when comparing to the GEM electroluminescence yield, reaching similar values to what is achieved in GEMs for xenon pressures of 2.5 bar, but still one order of magnitude higher than that produced in a uniform field gap. Another exception is the GEM operating in argon, which presents an electroluminescence yield similar to that produced in a uniform electric field gap, while the THGEM achieves yields that are more than one order of magnitude higher.

Efficacy and Factors Affecting Outcome of Gemcitabine Concurrent Chemoradiotherapy in Patients With Locally Advanced Pancreatic Cancer

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

Huang, P.-I.; National Yang-Ming University School of Medicine, Taipei, Taiwan; Chao, Yee

Purpose: To evaluate the efficacy and prognostic factors of gemcitabine (GEM) concurrent chemoradiotherapy (CCRT) in patients with locally advanced pancreatic cancer. Methods and Materials: Between January 2002 and December 2005, 55 patients with locally advanced pancreatic cancer treated with GEM (400 mg/m{sup 2}/wk) concurrently with radiotherapy (median dose, 50.4 Gy; range, 26-61.2) at Taipei Veterans General Hospital were enrolled. GEM (1,000 mg/m{sup 2}) was continued after CCRT as maintenance therapy once weekly for 3 weeks and repeated every 4 weeks. The response, survival, toxicity, and prognostic factors were evaluated. Results: With a median follow-up of 10.8 months, the 1- andmore » 2-year survival rate was 52% and 19%, respectively. The median overall survival (OS) and median time to progression (TTP) was 12.4 and 5.9 months, respectively. The response rate was 42% (2 complete responses and 21 partial responses). The major Grade 3-4 toxicities were neutropenia (22%) and anorexia (19%). The median OS and TTP was 15.8 and 9.5 months in the GEM CCRT responders compared with 7.5 and 3.5 months in the nonresponders, respectively (both p < 0.001). The responders had a better Karnofsky performance status (KPS) (86 {+-} 2 vs. 77 {+-} 2, p = 0.002) and had received a greater GEM dose intensity (347 {+-} 13 mg/m{sup 2}/wk vs. 296 {+-} 15 mg/m{sup 2}/wk, p = 0.02) than the nonresponders. KPS and serum carbohydrate antigen 19-9 were the most significant prognostic factors of OS and TTP. Conclusion: The results of our study have shown that GEM CCRT is effective and tolerable for patients with locally advanced pancreatic cancer. The KPS and GEM dose correlated with response. Also, the KPS and CA 19-9 level were the most important factors affecting OS and TTP.« less

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.

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.

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.

Experimental and Theoretical Progress on the GEM Theory

NASA Astrophysics Data System (ADS)

Brandenburg, J. E.

This paper reports experimental and theoretical progress on the GEM unification theory. In theoretical progress, the derivation of the GEM theory using it in a fully covariant form is achieved based on the principle of self-cancellation of the ZPF EM stress-momentum tensor. This derivation reveals that the final Gravity-EM system obeys a Helmholtz-like equation resembling that governing sound propagation. Finally an improved derivation of the formula for the Newton Gravitation constant is shown, qresulting in the formula G = e2/(4πɛ0 me mp) α exp (-2 (α-.86/σ2…) = 6.673443 x10-11 N-m2 kg-2 that agrees with experimental values to 3 parts per 100,000. Experiments have found parity violating weight reductions in gyroscopes driven by rotating EM fields. These experiments appear to confirm gravity modification using electromagnetism predicted by the GEM theory through the Vacuum Bernoulli Equation.

Optical characterization of synthetic faceted gem materials grown from hydrothermal solutions

NASA Astrophysics Data System (ADS)

Lu, Taijin; Shigley, James E.

1998-10-01

Various non-destructive optical characterization techniques have been used to characterize and identify synthetic gem materials grown from hydrothermal solutions, to include ruby, sapphire, emerald, amethyst and ametrine (amethyst-citrine), from their natural counterparts. The ability to observe internal features, such as inclusions, dislocations, twins, color bands, and growth zoning in gem materials is strongly dependent on the observation techniques and conditions, since faceted gemstones have many polished surfaces which can reflect and scatter light in various directions which can make observation difficult. However, diagnostic gemological properties of these faceted synthetic gem materials can be obtained by choosing effective optical characterization methods, and by modifying optical instruments. Examples of some of the distinctive features of synthetic amethyst, ametrine, pink quartz, ruby and emerald are presented to illustrate means of optical characterization of gemstones. The ability to observe defects by light scattering techniques is discussed.

A new design using GEM-based technology for the CMS experiment

NASA Astrophysics Data System (ADS)

Ressegotti, M.

2017-07-01

The muon system of the Compact Muon Solenoid (CMS) experiment at the LHC is currently not instrumented for pseudorapidity higher than |η|> 2.4. The main challenges to the installation of a detector in that position are the high particle flux to be sustained, a high level of radiation, and the ability to accomodate a multilevel detector into the small available space (less than 30 cm). A new back-to-back configuration of a Gas Electron Multiplier (GEM) detector is presented with the aim of developing a compact, multi-layer GEM detector. It is composed of two independent stacked triple-GEM detectors, positioned with the anodes toward the outside and sharing the same cathode plane, which is located at the center of the chamber, to reduce the total detector's thickness. A first prototype has been produced and tested with an X-Ray source and muon beam. First results on its performance are presented.

COMPARATIVE TUMOR-INITIATING ACTIVITY OF COMPLEX MIXTURES FROM ENVIRONMENTAL PARTICULATE EMISSIONS ON SENCAR MOUSE SKIN

EPA Science Inventory

The value of the SENCAR mouse for testing tumorigenic properties of complex mixtures on mouse skin was studied. Seven complex mixtures were obtained as dichloromethane extracts of collected particulate emissions from three diesel-fueled automobiles, a heavy-duty diesel engine, a ...

Genetically engineered mouse models of craniopharyngioma: an opportunity for therapy development and understanding of tumor biology.

PubMed

Apps, John Richard; Martinez-Barbera, Juan Pedro

2017-05-01

Adamantinomatous craniopharyngioma (ACP) is the commonest tumor of the sellar region in childhood. Two genetically engineered mouse models have been developed and are giving valuable insights into ACP biology. These models have identified novel pathways activated in tumors, revealed an important function of paracrine signalling and extended conventional theories about the role of organ-specific stem cells in tumorigenesis. In this review, we summarize these mouse models, what has been learnt, their limitations and open questions for future research. We then discussed how these mouse models may be used to test novel therapeutics against potentially targetable pathways recently identified in human ACP. © 2017 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.

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

Short-time variation of mercury speciation in the urban of Göteborg during GÖTE-2005

NASA Astrophysics Data System (ADS)

Li, Jing; Sommar, Jonas; Wängberg, Ingvar; Lindqvist, Oliver; Wei, Shi-qiang

Mercury species samples for gaseous elemental mercury (GEM) with a temporal resolution of 5 min, 5 h and 20 min integrated measurements of reactive gaseous mercury (RGM), and 24-h sampling of particulate mercury (HgP) at urban Femman and total gaseous mercury (TGM) at rural Rörvik were conducted during the measurement campaign GÖTE-2005 in Göteborg, Sweden. Results showed that average concentrations for GEM, RGM, HgP and TGM were 1.96 ± 0.38 ng m -3, 2.53 ± 4.09 pg m -3, 12.50 ± 5.88 pg m -3 and 1.63 ± 0.19 ng m -3, respectively. A reverse diurnal distribution pattern between GEM and RGM was observed, and early morning GEM concentration was elevated compared to daytime values which was likely due to activation of fossil fuel combustion, electric utilities, etc., by the formation of a nighttime inversion layer, less activity of GEM and reduced mixing. The subsequent decline and afternoon minimum were likely related to increase vertical mixing, photochemical reaction, and coupling with the coal combustion. However, the photochemical conversion from GEM during daytime and nocturnal behavior of "sticky" gases under higher relative humidity may result in strong diurnal cycles for RGM. Sampling site was heavily affected by anthropogenic sources from two distinguished wind sectors. One was ESE-SSW sector which was likely impacted by long distance transport from south highly industrialized region; the other was likely tied with local sources from N-NE sector.

Impacts of large-scale circulation on urban ambient concentrations of gaseous elemental mercury in New York, USA

NASA Astrophysics Data System (ADS)

Mao, Huiting; Hall, Dolly; Ye, Zhuyun; Zhou, Ying; Felton, Dirk; Zhang, Leiming

2017-09-01

The impact of large-scale circulation on urban gaseous elemental mercury (GEM) was investigated through analysis of 2008-2015 measurement data from an urban site in New York City (NYC), New York, USA. Distinct annual cycles were observed in 2009-2010 with mixing ratios in warm seasons (i.e., spring-summer) 10-20 ppqv ( ˜ 10-25 %) higher than in cool seasons (i.e., fall-winter). This annual cycle was disrupted in 2011 by an anomalously strong influence of the US East Coast trough in that warm season and was reproduced in 2014 associated with a particularly strong Bermuda High. The US East Coast trough axis index (TAI) and intensity index (TII) were used to characterize the effect of the US East Coast trough on NYC GEM, especially in winter and summer. The intensity and position of the Bermuda High appeared to have a significant impact on GEM in warm seasons. Regional influence on NYC GEM was supported by the GEM-carbon monoxide (CO) correlation with r of 0.17-0.69 (p ˜ 0) in most seasons. Simulated regional and local anthropogenic contributions to wintertime NYC anthropogenically induced GEM concentrations were averaged at ˜ 75 % and 25 %, with interannual variation ranging over 67 %-83 % and 17 %-33 %, respectively. Results from this study suggest the possibility that the increasingly strong Bermuda High over the past decades could dominate over anthropogenic mercury emission control in affecting ambient concentrations of mercury via regional buildup and possibly enhancing natural and legacy emissions.

The Properties and Applications of Nanodiamonds.

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

Mochalin, Vadym N.; Shenderova, Olga; Ho, Dean

Nanodiamonds have excellent mechanical and optical properties, high surface areas and tunable surface structures. They are also non-toxic, which makes them well suited to biomedical applications. Here we review the synthesis, structure, properties, surface chemistry and phase transformations of individual nanodiamonds and clusters of nanodiamonds. In particular we discuss the rational control of the mechanical, chemical, electronic and optical properties of nanodiamonds through surface doping, interior doping and the introduction of functional groups. These little gems have a wide range of potential applications in tribology, drug delivery, bioimaging and tissue engineering, and also as protein mimics and a filler materialmore » for nanocomposites.« less

The properties and applications of nanodiamonds.

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

Mochalin, Vadym; Shenderova, Olga; Ho, Dean

Nanodiamonds have excellent mechanical and optical properties, high surface areas and tunable surface structures. They are also non-toxic, which makes them well suited to biomedical applications. Here we review the synthesis, structure, properties, surface chemistry and phase transformations of individual nanodiamonds and clusters of nanodiamonds. In particular we discuss the rational control of the mechanical, chemical, electronic and optical properties of nanodiamonds through surface doping, interior doping and the introduction of functional groups. These little gems have a wide range of potential applications in tribology, drug delivery, bioimaging and tissue engineering, and also as protein mimics and a filler materialmore » for nanocomposites.« less

New Gem-Dicyanocyclobutane-Containing Hydroxyesters

DTIC Science & Technology

1989-04-01

polar saponification conditions, the cyclobutanes underwent ring opening to unidentified products. When in one case we obtained a carboxylic acid, it...polar saponification conditions also favored ionization of the cyclobutane back to the tetramethylenes. We conclude that the proposed route to gem

How incense and joss paper burning during the worship activities influences ambient mercury concentrations in indoor and outdoor environments of an Asian temple?

PubMed

Shen, Huazhen; Tsai, Cheng-Mou; Yuan, Chung-Shin; Jen, Yi-Hsiu; Ie, Iau-Ren

2017-01-01

This study firstly investigated the species, concentration variation, and emission factors of mercury emitted from the burning of incenses and joss papers in an Asian temple. Both indoor and outdoor speciated mercury (GEM, GOM, and PHg) were sampled by manual samplers, while ambient GEM at an indoor site was in-situ monitored by a continuous GEM monitor. Field measurement results showed that the total atmospheric mercury (TAM) concentrations in indoor and outdoor environments were in the range of 8.03-35.72 and 6.03-31.35 ng/m 3 , respectively. The indoor and outdoor ratios (I/O) of TAM in the daytime and at nighttime were in the range of 0.64-0.90 and 1.50-2.04, respectively. The concentrations of GEM, GOM, and PHg during the holiday periods were approximately 1-4 times higher than those during the non-holiday periods. GEM was the dominant mercury species in the indoor and outdoor environments and accounted for 63-81% of TAM, while the oxidized mercury accounted for 19-37% of TAM. Burning incenses and joss papers in a combustion chamber showed that the concentration of GEM from joss paper burning ranged from 4.07 to 11.62 μg/m 3 , or about 13.97 times higher than that of incense burning, while the concentration of PHg from incense burning ranged from 95.91 to 135.07 ng/m 3 , or about 3.29 times higher than that of joss paper burning. The emission factors of incense burning were 10.39 ng/g of GEM and 1.40 ng/g of PHg, while those of joss paper burning were 12.65 ng/g of GEM and 1.27 ng/g of PHg, respectively. This study revealed that speciated mercury emitted from worship activities had significant influence on the indoor and outdoor mercury concentrations in an Asian temple. Higher intensity of worship activities during holidays resulted in a higher concentration of speciated mercury in indoor and outdoor air, which might cause health threats to worshipers, staffs, and surrounding inhabitants through long-term exposure. Copyright © 2016 Elsevier Ltd. All rights reserved.

Theranostic reduction-sensitive gemcitabine prodrug micelles for near-infrared imaging and pancreatic cancer therapy

NASA Astrophysics Data System (ADS)

Han, Haijie; Wang, Haibo; Chen, Yangjun; Li, Zuhong; Wang, Yin; Jin, Qiao; Ji, Jian

2015-12-01

A biodegradable and reduction-cleavable gemcitabine (GEM) polymeric prodrug with in vivo near-infrared (NIR) imaging ability was reported. This theranostic GEM prodrug PEG-b-[PLA-co-PMAC-graft-(IR820-co-GEM)] was synthesized by ring-opening polymerization and ``click'' reaction. The as-prepared reduction-sensitive prodrug could self-assemble into prodrug micelles in aqueous solution confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). In vitro drug release studies showed that these prodrug micelles were able to release GEM in an intracellular-mimicking reductive environment. These prodrug micelles could be effectively internalized by BxPC-3 pancreatic cancer cells, which were observed by confocal laser scanning microscopy (CLSM). Meanwhile, a methyl thiazolyl tetrazolium (MTT) assay demonstrated that this prodrug exhibited high cytotoxicity against BxPC-3 cells. The in vivo whole-animal near-infrared (NIR) imaging results showed that these prodrug micelles could be effectively accumulated in tumor tissue and had a longer blood circulation time than IR820-COOH. The endogenous reduction-sensitive gemcitabine prodrug micelles with the in vivo NIR imaging ability might have great potential in image-guided pancreatic cancer therapy.A biodegradable and reduction-cleavable gemcitabine (GEM) polymeric prodrug with in vivo near-infrared (NIR) imaging ability was reported. This theranostic GEM prodrug PEG-b-[PLA-co-PMAC-graft-(IR820-co-GEM)] was synthesized by ring-opening polymerization and ``click'' reaction. The as-prepared reduction-sensitive prodrug could self-assemble into prodrug micelles in aqueous solution confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). In vitro drug release studies showed that these prodrug micelles were able to release GEM in an intracellular-mimicking reductive environment. These prodrug micelles could be effectively internalized by BxPC-3 pancreatic cancer cells, which were observed by confocal laser scanning microscopy (CLSM). Meanwhile, a methyl thiazolyl tetrazolium (MTT) assay demonstrated that this prodrug exhibited high cytotoxicity against BxPC-3 cells. The in vivo whole-animal near-infrared (NIR) imaging results showed that these prodrug micelles could be effectively accumulated in tumor tissue and had a longer blood circulation time than IR820-COOH. The endogenous reduction-sensitive gemcitabine prodrug micelles with the in vivo NIR imaging ability might have great potential in image-guided pancreatic cancer therapy. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06734k

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.

CHOP versus GEM-P in previously untreated patients with peripheral T-cell lymphoma (CHEMO-T): a phase 2, multicentre, randomised, open-label trial.

PubMed

Gleeson, Mary; Peckitt, Clare; To, Ye Mong; Edwards, Laurice; Oates, Jacqueline; Wotherspoon, Andrew; Attygalle, Ayoma D; Zerizer, Imene; Sharma, Bhupinder; Chua, Sue; Begum, Ruwaida; Chau, Ian; Johnson, Peter; Ardeshna, Kirit M; Hawkes, Eliza A; Macheta, Marian P; Collins, Graham P; Radford, John; Forbes, Adam; Hart, Alistair; Montoto, Silvia; McKay, Pamela; Benstead, Kim; Morley, Nicholas; Kalakonda, Nagesh; Hasan, Yasmin; Turner, Deborah; Cunningham, David

2018-05-01

Outcomes with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) or CHOP-like chemotherapy in peripheral T-cell lymphoma are poor. We investigated whether the regimen of gemcitabine, cisplatin, and methylprednisolone (GEM-P) was superior to CHOP as front-line therapy in previously untreated patients. We did a phase 2, parallel-group, multicentre, open-label randomised trial in 47 hospitals: 46 in the UK and one in Australia. Participants were patients aged 18 years and older with bulky (tumour mass diameter >10 cm) stage I to stage IV disease (WHO performance status 0-3), previously untreated peripheral T-cell lymphoma not otherwise specified, angioimmunoblastic T-cell lymphoma, anaplastic lymphoma kinase-negative anaplastic large cell lymphoma, enteropathy-associated T-cell lymphoma, or hepatosplenic γδ T-cell lymphoma. We randomly assigned patients (1:1) stratified by subtype of peripheral T-cell lymphoma and international prognostic index to either CHOP (intravenous cyclophosphamide 750 mg/m 2 , doxorubicin 50 mg/m 2 , and vincristine 1·4 mg/m 2 [maximum 2 mg] on day 1, and oral prednisolone 100 mg on days 1-5) every 21 days for six cycles; or GEM-P (intravenous gemcitabine 1000 mg/m 2 on days 1, 8, and 15, cisplatin 100 mg/m 2 on day 15, and oral or intravenous methylprednisolone 1000 mg on days 1-5) every 28 days for four cycles. The primary endpoint was the proportion of patients with a CT-based complete response or unconfirmed complete response on completion of study chemotherapy, to detect a 20% superiority of GEM-P compared with CHOP, assessed in all patients who received at least one cycle of treatment and had an end-of-treatment CT scan or reported clinical progression as the reason for stopping trial treatment. Safety was assessed in all patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov (NCT01719835) and the European Clinical Trials Database (EudraCT 2011-004146-18). Between June 18, 2012, and Nov 16, 2016, we randomly assigned 87 patients to treatment, 43 to CHOP and 44 to GEM-P. A planned unmasked review of efficacy data by the independent data monitoring committee in November, 2016, showed that the number of patients with a confirmed or unconfirmed complete response with GEM-P was non-significantly inferior compared with CHOP and the trial was closed early. At a median follow-up of 27·4 months (IQR 16·6-38·4), 23 patients (62%) of 37 assessable patients assigned to CHOP had achieved a complete response or unconfirmed complete response compared with 17 (46%) of 37 assigned to GEM-P (odds ratio 0·52, 95% CI 0·21-1·31; p=0·164). The most common adverse events of grade 3 or worse in both groups were neutropenia (17 [40%] with CHOP and nine [20%] with GEM-P), thrombocytopenia (4 [10%] with CHOP and 13 [30%] with GEM-P, and febrile neutropenia (12 [29%] with CHOP and 3 [7%] with GEM-P). Two patients (5%) died during the study, both in the GEM-P group, from lung infections. The number of patients with a complete response or unconfirmed complete response did not differ between the groups, indicating that GEM-P was not superior for this outcome. CHOP should therefore remain the reference regimen for previously untreated peripheral T-cell lymphoma. Bloodwise and the UK National Institute of Health Research. Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Fast ADC based multichannel acquisition system for the GEM detector

NASA Astrophysics Data System (ADS)

Kasprowicz, G.; Czarski, T.; Chernyshova, M.; Dominik, W.; Jakubowska, K.; Karpinski, L.; Kierzkowski, K.; Pozniak, K.; Rzadkiewicz, J.; Scholz, M.; Zabolotny, W.

2012-05-01

A novel approach to the Gas Electron Multiplier1 (GEM) detector readout is presented. Unlike commonly used methods, based on discriminators, and analogue FIFOs,[ the method developed uses simultaneously sampling high speed ADCs and advanced FPGA-based processing logic to estimate the energy of every single photon. Such method is applied to every GEM strip signal. It is especially useful in case of crystal-based spectrometers for soft X-rays, where higher order reflections need to be identified and rejected. For the purpose of the detector readout, a novel conception of the measurement platform was developed.

GEM detectors for WEST and potential application for heavy impurity transport studies

NASA Astrophysics Data System (ADS)

Mazon, D.; Jardin, A.; Coston, C.; Faisse, F.; Chernyshova, M.; Czarski, T.; Kasprowicz, G.; Wojenski, A.

2016-08-01

In tokamaks equipped with metallic walls and in particular tungsten, the interplay between particle transport and MagnetoHydroDynamic (MHD) activity might lead to impurities accumulation and finally to sudden plasma termination called disruption. Studying such transport phenomena is thus essential if stationary discharges are to be achieved. On WEST a new SXR diagnostic is developed in collaboration with IPPLM (Poland) and the Warsaw University of Technology, based on a triple Gas Electron Multiplier (GEM) detector. Potential application of the WEST GEM detectors for tomographic reconstruction and subsequent transport analysis is presented.

NGS2: a focal plane array upgrade for the GeMS multiple tip-tilt wavefront sensor

NASA Astrophysics Data System (ADS)

Rigaut, François; Price, Ian; d'Orgeville, Céline; Bennet, Francis; Herrald, Nick; Paulin, Nicolas; Uhlendorf, Kristina; Garrel, Vincent; Sivo, Gaetano; Montes, Vanessa; Trujillo, Chad

2016-07-01

NGS2 is an upgrade for the multi-natural guide star tip-tilt & plate scale wavefront sensor for GeMS (Gemini Multi-Conjugate Adaptive Optics system). It uses a single Nüvü HNü-512 Electron-Multiplied CCD array that spans the entire GeMS wavefront sensor focal plane. Multiple small regions-of-interest are used to enable frame rates up to 800Hz. This set up will improve the optical throughput with respect to the current wavefront sensor, as well as streamline acquisition and allow for distortion compensation.

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.

PlasmoGEM, a database supporting a community resource for large-scale experimental genetics in malaria parasites.

PubMed

Schwach, Frank; Bushell, Ellen; Gomes, Ana Rita; Anar, Burcu; Girling, Gareth; Herd, Colin; Rayner, Julian C; Billker, Oliver

2015-01-01

The Plasmodium Genetic Modification (PlasmoGEM) database (http://plasmogem.sanger.ac.uk) provides access to a resource of modular, versatile and adaptable vectors for genome modification of Plasmodium spp. parasites. PlasmoGEM currently consists of >2000 plasmids designed to modify the genome of Plasmodium berghei, a malaria parasite of rodents, which can be requested by non-profit research organisations free of charge. PlasmoGEM vectors are designed with long homology arms for efficient genome integration and carry gene specific barcodes to identify individual mutants. They can be used for a wide array of applications, including protein localisation, gene interaction studies and high-throughput genetic screens. The vector production pipeline is supported by a custom software suite that automates both the vector design process and quality control by full-length sequencing of the finished vectors. The PlasmoGEM web interface allows users to search a database of finished knock-out and gene tagging vectors, view details of their designs, download vector sequence in different formats and view available quality control data as well as suggested genotyping strategies. We also make gDNA library clones and intermediate vectors available for researchers to produce vectors for themselves. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Glycemic load, exercise, and monitoring blood glucose (GEM): A paradigm shift in the treatment of type 2 diabetes mellitus.

PubMed

Cox, Daniel J; Taylor, Ann G; Singh, Harsimran; Moncrief, Matthew; Diamond, Anne; Yancy, William S; Hegde, Shefali; McCall, Anthony L

2016-01-01

This preliminary RCT investigated whether an integrated lifestyle modification program that focuses on reducing postprandial blood glucose through replacing high with low glycemic load foods and increasing routine physical activities guided by systematic self-monitoring of blood glucose (GEM) could improve metabolic control of adults with type 2 diabetes mellitus, without compromising other physiological parameters. Forty-seven adults (mean age 55.3 years) who were diagnosed with type 2 diabetes mellitus for less than 5 years (mean 2.1 years), had HbA1c ≥ 7% (mean 8.4%) and were not taking blood glucose lowering medications, were randomized to routine care or five 1-h instructional sessions of GEM. Assessments at baseline and 6 months included a physical exam, metabolic and lipid panels, and psychological questionnaires. The GEM intervention led to significant improvements in HbA1c (decreasing from 8.4 to 7.4% [69-57 mmol/mol] compared with 8.3 to 8.3% [68-68 mmol/mol] for routine care; Interaction p<.01) and psychological functioning without compromising other physiological parameters. Consistent with a patient-centered approach, GEM appears to be an effective lifestyle modification option for adults recently diagnosed with type 2 diabetes mellitus. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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.

Label-free Raman spectroscopy for accessing intracellular anticancer drug release on gold nanoparticles.

PubMed

Ock, Kwang-Su; Ganbold, Erdene Ochir; Park, Jin; Cho, Keunchang; Joo, Sang-Woo; Lee, So Yeong

2012-06-21

We investigated glutathione (GSH)-induced purine or pyrimidine anticancer drug release on gold nanoparticle (AuNP) surfaces by means of label-free Raman spectroscopy. GSH-triggered releases of 6-thioguanine (6TG), gemcitabine (GEM), acycloguanosine (ACY), and fadrozole (FAD) were examined in a comparative way by means of surface-enhanced Raman scattering (SERS). The GSH-induced dissociation constant of GEM (or ACY/FAD) from AuNPs was estimated to be larger by more than 38 times than that of 6TG from the kinetic relationship. Tripeptide control experiments were presented to check the turn-off Raman signalling mechanism. Dark-field microscopy (DFM) and transmission electron microscopy (TEM) indicated the intracellular AuNP loads. After their cellular uptake, GEM, ACY, and FAD would not show SERS intensities as strong as 6TG. This may be due to easier release of GEM, ACY, and FAD than 6TG by intracellular reducing species including GSH. We observed fairly strong SERS signals of GEM and 6TG in cell culture media solution. Our CCK-8 cytotoxicity assay data support that 6TG-AuNPs did not exhibit a substantial decrease in cell viability presumably due to strong binding. Label-free confocal Raman spectroscopy can be utilized as an effective tool to access intracellular anticancer drug release.

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.

Evaluation of gemfibrozil effects on a marine fish (Sparus aurata) combining gene expression with conventional endocrine and biochemical endpoints.

PubMed

Teles, M; Fierro-Castro, C; Na-Phatthalung, P; Tvarijonaviciute, A; Soares, A M V M; Tort, L; Oliveira, M

2016-11-15

The information on the potential hazardous effects of gemfibrozil (GEM) on marine fish is extremely scarce. In the current study, molecular, endocrine and biochemical parameters were assessed in Sparus aurata after 96h waterborne exposure to a GEM concentration range. Hepatic mRNA levels of target genes known to be regulated via peroxisome proliferator-activated receptor α (pparα) in mammals, such as apolipoprotein AI (apoa1) and lipoprotein (lpl) were significantly increased, without a concomitant activation of the ppar pathways. GEM (15μgL(-1)) induced an upregulation in mRNA levels of interleukin 1β (il1β), tumour necrosis factor-α (tnfα) and caspase 3 (casp3), suggesting an activation of proinflammatory processes in S. aurata liver. However, mRNA levels of genes related with the antioxidant defence system and cell-tissue repair were unaltered under the tested experimental conditions. Higher levels of GEM induced a cortisol rise, an indication that it is recognized as a stressor by S. aurata. Cortisol levels and the mRNA levels of il1β, tnfα and casp3 may be suggested as potential biomarkers of GEM effects in marine fish. Copyright © 2016 Elsevier B.V. All rights reserved.

Mathematical model of rhamnolipid production using E.coli bacteria

NASA Astrophysics Data System (ADS)

Adham, Muhammad Fariduddin; Apri, Mochamad; Moeis, Maelita Ramdani

2018-03-01

Rhamnolipid is one of biosurfactants that is widely used in many industries. Despite its wide use, production of rhamnolipid usually involves a pathogen that may endanger our health. To tackle this issue, in iGEM (International Genetically Engineered Machine) competition 2015, our team engineered Escherichia coli (E.coli) to produce rhamnolipid. The bacteria were then put into medium containing glucose and lactose. It turned out that bacteria E. coli produced lower rhamnolipid than that by pseudomonas, therefore a good strategy is required to improve their productivity. We present a mathematical model to describe the production of rhamnolipid by the engineered E coli. Using bifurcation analysis, the equilibrium points of the model and their stabilities were analyzed as the amount of lactose was varied. We show that the system produces bistability behavior for some interval values of lactose. From this analysis we found that to guarantee a high production of rhamnolipid, a high level of lactose is required. To maintain the productivity, however, it is sufficient to maintain the lactose level above a certain threshold value.

CtGEM typing: Discrimination of Chlamydia trachomatis ocular and urogenital strains and major evolutionary lineages by high resolution melting analysis of two amplified DNA fragments.

PubMed

Giffard, Philip M; Andersson, Patiyan; Wilson, Judith; Buckley, Cameron; Lilliebridge, Rachael; Harris, Tegan M; Kleinecke, Mariana; O'Grady, Kerry-Ann F; Huston, Wilhelmina M; Lambert, Stephen B; Whiley, David M; Holt, Deborah C

2018-01-01

Chlamydia trachomatis infects the urogenital tract (UGT) and eyes. Anatomical tropism is correlated with variation in the major outer membrane protein encoded by ompA. Strains possessing the ocular ompA variants A, B, Ba and C are typically found within the phylogenetically coherent "classical ocular lineage". However, variants B, Ba and C have also been found within three distinct strains in Australia, all associated with ocular disease in children and outside the classical ocular lineage. CtGEM genotyping is a method for detecting and discriminating ocular strains and also the major phylogenetic lineages. The rationale was facilitation of surveillance to inform responses to C. trachomatis detection in UGT specimens from young children. CtGEM typing is based on high resolution melting analysis (HRMA) of two PCR amplified fragments with high combinatorial resolving power, as defined by computerised comparison of 65 whole genomes. One fragment is from the hypothetical gene defined by Jali-1891 in the C. trachomatis B_Jali20 genome, while the other is from ompA. Twenty combinatorial CtGEM types have been shown to exist, and these encompass unique genotypes for all known ocular strains, and also delineate the TI and T2 major phylogenetic lineages, identify LGV strains and provide additional resolution beyond this. CtGEM typing and Sanger sequencing were compared with 42 C. trachomatis positive clinical specimens, and there were no disjunctions. CtGEM typing is a highly efficient method designed and tested using large scale comparative genomics. It divides C. trachomatis into clinically and biologically meaningful groups, and may have broad application in surveillance.

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.

Multiple generations of grain aggregation in different environments preceded solar system body formation.

PubMed

Ishii, Hope A; Bradley, John P; Bechtel, Hans A; Brownlee, Donald E; Bustillo, Karen C; Ciston, James; Cuzzi, Jeffrey N; Floss, Christine; Joswiak, David J

2018-06-26

The solar system formed from interstellar dust and gas in a molecular cloud. Astronomical observations show that typical interstellar dust consists of amorphous ( a -) silicate and organic carbon. Bona fide physical samples for laboratory studies would yield unprecedented insight about solar system formation, but they were largely destroyed. The most likely repositories of surviving presolar dust are the least altered extraterrestrial materials, interplanetary dust particles (IDPs) with probable cometary origins. Cometary IDPs contain abundant submicron a- silicate grains called GEMS (glass with embedded metal and sulfides), believed to be carbon-free. Some have detectable isotopically anomalous a- silicate components from other stars, proving they are preserved dust inherited from the interstellar medium. However, it is debated whether the majority of GEMS predate the solar system or formed in the solar nebula by condensation of high-temperature (>1,300 K) gas. Here, we map IDP compositions with single nanometer-scale resolution and find that GEMS contain organic carbon. Mapping reveals two generations of grain aggregation, the key process in growth from dust grains to planetesimals, mediated by carbon. GEMS grains, some with a- silicate subgrains mantled by organic carbon, comprise the earliest generation of aggregates. These aggregates (and other grains) are encapsulated in lower-density organic carbon matrix, indicating a second generation of aggregation. Since this organic carbon thermally decomposes above ∼450 K, GEMS cannot have accreted in the hot solar nebula, and formed, instead, in the cold presolar molecular cloud and/or outer protoplanetary disk. We suggest that GEMS are consistent with surviving interstellar dust, condensed in situ, and cycled through multiple molecular clouds. Copyright © 2018 the Author(s). Published by PNAS.

Scaling properties of observed and simulated satellite visible radiances

NASA Astrophysics Data System (ADS)

Barker, Howard W.; Qu, Zhipeng; Bélair, Stéphane; Leroyer, Sylvie; Milbrandt, Jason A.; Vaillancourt, Paul A.

2017-09-01

Structure functions Sq, which are related to power spectra and used to study turbulence, were computed for GOES-13 visible radiances measured on 16 May 2015 over French Guiana and adjacent Atlantic Ocean. The nested Global Environmental Multiscale (GEM) numerical weather prediction (NWP) model was run for the same time and area. Cloud data generated by GEM over (300 km)2 domains, with one-way nesting ending at horizontal grid-spacing of 0.25 km, were operated on by a 3-D solar radiative transfer model with resulting radiances degraded to GOES-13 resolution ( 1 km) and Sq computed for them, too. For GOES-13 radiances, scaling exponents ζ(2) associated with S2, for separation distances between 5 km and 25 km, were typically >0.6 for deep convective and marine boundary layer clouds and <0.4 for shallow cumuli over land. ζ(2) for GEM agreed well with GOES-13 for deep convective clouds. This suggests that the self-organizing properties of deep convection in GEM exhibit realistic geometric features, a potentially important point given the link between cloud structure and precipitation, with the latter being much more difficult to measure and assess than visible radiances. Regarding radiances for GEM's marine boundary layer clouds, their Sq differed markedly from GOES-13's; better resembling fair-weather cumulus. Likewise, GEM's shallow cumuli over land appear to have bypassed the "scattered" fair-weather stage and went straight into more organized convection. Thus, it appears that comparing time series of Sq for geostationary satellite data and corresponding modeled radiances has the potential to benefit assessment of cloud system-resolving models.

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

Formation of Glass with Embedded Metal and Sulfides from Shock-accelerated Crystalline Dust in Superbubbles

NASA Astrophysics Data System (ADS)

Westphal, A. J.; Bradley, J. P.

2004-12-01

Interplanetary dust particles (IDPs) contain enigmatic submicron components called GEMS (glass with embedded metal and sulfides). The compositions and structures of GEMS indicate that they have been processed by exposure to ionizing radiation, but details of the actual irradiation environment(s) have remained elusive. Here we propose a mechanism and astrophysical site for GEMS formation that explains for the first time the following key properties of GEMS: they are stoichiometrically enriched in oxygen and systematically depleted in S, Mg, Ca, and Fe (relative to solar abundances); most have normal (solar) oxygen isotopic compositions; they exhibit a strikingly narrow size distribution (0.1-0.5 μm diameter); and some of them contain ``relict'' crystals within their silicate glass matrices. We show that the compositions, size distribution, and survival of relict crystals are inconsistent with amorphization by particles accelerated by diffusive shock acceleration. Instead, we propose that GEMS are formed from crystalline grains that condense in stellar outflows from massive stars in OB associations, are accelerated in encounters with frequent supernova shocks inside the associated superbubble (SB), and are implanted with atoms from the hot gas in the SB interior. We thus reverse the usual roles of target and projectile. Rather than being bombarded at rest by energetic ions, grains are accelerated and bombarded by a nearly monovelocity beam of atoms as viewed in their rest frame. Meyer, Drury, and Ellison have proposed that Galactic cosmic rays (GCRs) originate from ions sputtered from such accelerated dust grains. We suggest that GEMS are surviving members of a population of fast grains that constitute the long-sought source material for GCRs. Thus, representatives of the GCR source material may have been awaiting discovery in cosmic dust labs for the last 30 yr.

Seasonal variations of ambient air mercury species nearby an airport

NASA Astrophysics Data System (ADS)

Fang, Guor-Cheng; Tsai, Kai-Hsiang; Huang, Chao-Yang; Yang, Kuang-Pu Ou; Xiao, You-Fu; Huang, Wen-Chuan; Zhuang, Yuan-Jie

2018-04-01

This study focuses on the collection of ambient air mercury species (total gaseous mercury (TGM), reactive gaseous mercury (RGM), gaseous element mercury (GEM) and particulate bound mercury (PBM) pollutants at airport nearby sampling site during the year of Apr. 2016 to Mar. 2017 by using Four-stage gold amalgamation and denuder. The results indicated that the average TGM, RGM and GEM concentrations were 5.04 ± 2.43 ng/m3, 29.58 ± 80.54 pg/m3, 4.70 ± 2.63 ng/m3, respectively during the year of Apr. 2016 to Mar. 2017 (n = 49) period at this airport sampling site nearby. In addition, the results also indicated that the average PBM concentrations in TSP and PM2.5 were 0.35 ± 0.08 ng/m3 and 0.09 ± 0.03 ng/m3, respectively. And the average PBM in TSP concentrations order follows as summer > autumn > spring > winter, while the average PBM in PM2.5 concentrations order follows as spring > summer > winter > autumn. Moreover, the average TGM, RGM and GEM concentrations order follow as spring > summer > autumn > winter. Finally, the Asian continent has the highest average mercury species concentrations (TGM, RGM, GEM and PBM) when compared with the American and European continents, and the average mercury species concentrations (TGM, RGM, GEM and PBM) displayed declined trends for North America (United States and Canada) and Europe (Spain, Sweden and Southern Baltic) during the years of 2004-2014. Also noteworthy is that the average mercury species concentrations (TGM, RGM, GEM) displayed increasing trends in China and Taiwan during the years of 2008-2016. Japan and Korea are the only two exceptions. Those above two countries mercury species concentrations displayed decreasing trends during years of 2008-2015.

Factors Controlling the Distribution of Atmospheric Mercury in the East Asian Free Troposphere

NASA Astrophysics Data System (ADS)

Sheu, G.; Lee, C.; Lin, N.; Wang, J.; Ouyang, C.

2008-12-01

Taiwan is located to the downwind side of both East and Southeast Asia, which are the major anthropogenic mercury (Hg) source region worldwide. Also, it has been suggested that mountain-top monitoring sites, which are frequently in the free troposphere, are essential to the understanding of the global Hg transport. Accordingly, continuous measurements of atmospheric Hg have been conducting at Lulin Atmospheric Background Station (LABS, 2862 m a.s.l.) in Taiwan since April 13, 2006 to study the trans-boundary transport and transformation of Hg in the free troposphere. Three types of atmospheric Hg, including gaseous elemental Hg (GEM), reactive gaseous Hg (RGM), and particulate Hg (PHg), are measured using the Tekran 2537A/1130/1135 speciation system. Diurnal variations in the concentrations of GEM, RGM, ozone, and water vapor (WV) mixing ratio indicated the influence of boundary layer air in daytime and the subsidence of free tropospheric air masses from higher altitudes at night. Seasonal variation in GEM concentrations was evident with elevated concentrations usually observed between fall and spring when air masses were more or less under the influence of Asian continent. Low summer GEM values were associated with marine air masses. Spikes of RGM were frequently detected between midnight and early morning with concurrent decreases in GEM and WV mixing ratio and increases in ozone concentrations, suggesting the oxidation of GEM and formation of RGM in free troposphere. Concentrations of PHg were usually low; however, elevated concentrations were detected in spring when the Southeast Asian biomass burning plumes affected the LABS. Analysis of the collected data indicate that at LABS the distribution of atmospheric Hg is dynamically controlled by background atmosphere, exchange and mixing of free troposphere/boundary layer air, chemical transformation, and long-range transport from East and Southeast Asia.

A novel application of Fiber Bragg Grating (FBG) sensors in MPGD

NASA Astrophysics Data System (ADS)

Abbaneo, D.; Abbas, M.; Abbrescia, M.; Abi Akl, M.; Aboamer, O.; Acosta, D.; Ahmad, A.; Ahmed, W.; Aleksandrov, A.; Altieri, P.; Asawatangtrakuldee, C.; Aspell, P.; Assran, Y.; Awan, I.; Bally, S.; Ban, Y.; Banerjee, S.; Barashko, V.; Barria, P.; Bencze, G.; Beni, N.; Benussi, L.; Bhopatkar, V.; Bianco, S.; Bos, J.; Bouhali, O.; Braghieri, A.; Braibant, S.; Buontempo, S.; Calabria, C.; Caponero, M.; Caputo, C.; Cassese, F.; Castaneda, A.; Cauwenbergh, S.; Cavallo, F. R.; Celik, A.; Choi, M.; Choi, S.; Christiansen, J.; Cimmino, A.; Colafranceschi, S.; Colaleo, A.; Conde Garcia, A.; Czellar, S.; Dabrowski, M. M.; De Lentdecker, G.; De Oliveira, R.; de Robertis, G.; Dildick, S.; Dorney, B.; Endroczi, G.; Errico, F.; Fenyvesi, A.; Ferrini, M.; Ferry, S.; Furic, I.; Giacomelli, P.; Gilmore, J.; Golovtsov, V.; Guiducci, L.; Guilloux, F.; Gutierrez, A.; Hadjiiska, R. M.; Hauser, J.; Hoepfner, K.; Hohlmann, M.; Hoorani, H.; Iaydjiev, P.; Jeng, Y. G.; Kamon, T.; Karchin, P.; Korytov, A.; Krutelyov, S.; Kumar, A.; Kim, H.; Lalli, A.; Lee, J.; Lenzi, T.; Litov, L.; Loddo, F.; Madorsky, A.; Maerschalk, T.; Maggi, M.; Magnani, A.; Mal, P. K.; Mandal, K.; Marchioro, A.; Marinov, A.; Majumdar, N.; Merlin, J. A.; Mitselmakher, G.; Mohanty, A. K.; Mohapatra, A.; Molnar, J.; Muhammad, S.; Mukhopadhyay, S.; Naimuddin, M.; Nuzzo, S.; Oliveri, E.; Pant, L. M.; Paolucci, P.; Park, I.; Passamonti, L.; Passeggio, G.; Pavlov, B.; Philipps, B.; Piccolo, D.; Pierluigi, D.; Postema, H.; Primavera, F.; Puig Baranac, A.; Radi, A.; Radogna, R.; Raffone, G.; Ranieri, A.; Rashevski, G.; Riccardi, C.; Rodozov, M.; Rodrigues, A.; Ropelewski, L.; RoyChowdhury, S.; Russo, A.; Ryu, G.; Ryu, M. S.; Safonov, A.; Salva, S.; Saviano, G.; Sharma, A.; Sharma, A.; Sharma, R.; Shah, A. H.; Shopova, M.; Sturdy, J.; Sultanov, G.; Swain, S. K.; Szillasi, Z.; Talvitie, J.; Tatarinov, A.; Tuuva, T.; Tytgat, M.; Valente, M.; Vai, I.; Van Stenis, M.; Venditti, R.; Verhagen, E.; Verwilligen, P.; Vitulo, P.; Volkov, S.; Vorobyev, A.; Wang, D.; Wang, M.; Yang, U.; Yang, Y.; Yonamine, R.; Zaganidis, N.; Zenoni, F.; Zhang, A.

2018-02-01

We present a novel application of Fiber Bragg Grating (FBG) sensors in the construction and characterisation of Micro Pattern Gaseous Detector (MPGD), with particular attention to the realisation of the largest triple (Gas electron Multiplier) GEM chambers so far operated, the GE1/1 chambers of the CMS experiment at LHC. The GE1/1 CMS project consists of 144 GEM chambers of about 0.5 m2 active area each, employing three GEM foils per chamber, to be installed in the forward region of the CMS endcap during the long shutdown of LHC in 2108-2019. The large active area of each GE1/1 chamber consists of GEM foils that are mechanically stretched in order to secure their flatness and the consequent uniform performance of the GE1/1 chamber across its whole active surface. So far FBGs have been used in high energy physics mainly as high precision positioning and re-positioning sensors and as low cost, easy to mount, low space consuming temperature sensors. FBGs are also commonly used for very precise strain measurements in material studies. In this work we present a novel use of FBGs as flatness and mechanical tensioning sensors applied to the wide GEM foils of the GE1/1 chambers. A network of FBG sensors have been used to determine the optimal mechanical tension applied and to characterise the mechanical tension that should be applied to the foils. We discuss the results of the test done on a full-sized GE1/1 final prototype, the studies done to fully characterise the GEM material, how this information was used to define a standard assembly procedure and possible future developments.

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.

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.

Combined readout of a triple-GEM detector

NASA Astrophysics Data System (ADS)

Antochi, V. C.; Baracchini, E.; Cavoto, G.; Di Marco, E.; Marafini, M.; Mazzitelli, G.; Pinci, D.; Renga, F.; Tomassini, S.; Voena, C.

2018-05-01

Optical readout of GEM based devices by means of high granularity and low noise CMOS sensors allows to obtain very interesting tracking performance. Space resolution of the order of tens of μm were measured on the GEM plane along with an energy resolution of 20%÷30%. The main limitation of CMOS sensors is represented by their poor information about time structure of the event. In this paper, the use of a concurrent light readout by means of a suitable photomultiplier and the acquisition of the electric signal induced on the GEM electrode are exploited to provide the necessary timing informations. The analysis of the PMT waveform allows a 3D reconstruction of each single clusters with a resolution on z of 100 μm. Moreover, from the PMT signals it is possible to obtain a fast reconstruction of the energy released within the detector with a resolution of the order of 25% even in the tens of keV range useful, for example, for triggering purpose.

Remote Sensing of Air Pollution from Geo with GEMS and TEMPO

NASA Astrophysics Data System (ADS)

Lasnik, J.; Nicks, D. K., Jr.; Baker, B.; Canova, B.; Chance, K.; Liu, X.; Suleiman, R. M.; Pennington, W. F.; Flittner, D. E.; Al-Saadi, J. A.; Rosenbaum, D. M.

2017-12-01

The Geostationary Environmental Monitoring System (GEMS) and Tropospheric Emissions: Monitoring of Pollution (TEMPO) instruments will provide a new capability for the understanding of air quality and pollution. Ball Aerospace is the instrument developer. The GEMS and TEMPO instruments use well-proven remote sensing techniques and take advantage of a geostationary orbit to take hourly measurements of the same geographical area. The high spatial and temporal resolution of these instruments will allow for measurements of the complex diurnal cycle of pollution driven by the combination of photochemistry, chemical composition and the dynamic nature of the atmosphere. Status of the manufacturing, test and calibration efforts will be presented.The GEMS instrument is being built for the Korea Aerospace Research Institute and their customer the National Institute of Environmental Research (NIER). The TEMPO instrument is being built for NASA under the Earth Venture Instrument EVI Program. NASA Langley Research Center (LaRC) is the managing center and the Principle Investigator (PI) is Kelly Chance of the Smithsonian Astrophysical Observatory (SAO).

Understanding of diagnosis and medications among non-English-speaking older patients.

PubMed

Teo, Ken Gw; Tacey, Mark; Holbeach, Edwina

2018-01-28

To determine whether non-English-speaking background (NESB) patients had a poorer understanding of diagnosis and medications compared to English-speaking background (ESB) patients. English-speaking background and NESB patients admitted to inpatient geriatric evaluation and management (GEM) unit were asked standardised questions about their admission diagnosis, reason for GEM admission and medications. Accuracy of answers, as compared to medical notes, ranked as 'full credit', 'partial credit' or 'no credit'. Of the 66 patients recruited (30 NESB), understanding of diagnosis and purpose of GEM admission was good. There was no difference between ESB and NESB patients. Understanding of medications taken prior to admission was poor, with 67% of overall patients scoring 'no credit'. NESB patients were more likely to score 'no credit' compared to ESB (80% vs 56%, P = 0.036). Reassuringly, patients had a reasonable understanding of diagnosis and purpose of GEM admission. Lack of understanding of medications, especially among NESB patients, should be improved. © 2018 AJA Inc.

Quality control for the first large areas of triple-GEM chambers for the CMS endcaps

NASA Astrophysics Data System (ADS)

Abbaneo, D.; Abbas, M.; Abbrescia, M.; Abi Akl, M.; Aboamer, O.; Acosta, D.; Ahmad, A.; Ahmed, W.; Aleksandrov, A.; Altieri, P.; Asawatangtrakuldee, C.; Aspell, P.; Assran, Y.; Awan, I.; Bally, S.; Ban, Y.; Banerjee, S.; Barashko, V.; Barria, P.; Bencze, G.; Beni, N.; Benussi, L.; Bhopatkar, V.; Bianco, S.; Bos, J.; Bouhali, O.; Braghieri, A.; Braibant, S.; Buontempo, S.; Calabria, C.; Caponero, M.; Caputo, C.; Cassese, F.; Castaneda, A.; Cauwenbergh, S.; Cavallo, F. R.; Celik, A.; Choi, M.; Choi, S.; Christiansen, J.; Cimmino, A.; Colafranceschi, S.; Colaleo, A.; Conde Garcia, A.; Czellar, S.; Dabrowski, M. M.; De Lentdecker, G.; De Oliveira, R.; de Robertis, G.; Dildick, S.; Dorney, B.; Endroczi, G.; Errico, F.; Fenyvesi, A.; Ferry, S.; Furic, I.; Giacomelli, P.; Gilmore, J.; Golovtsov, V.; Guiducci, L.; Guilloux, F.; Gutierrez, A.; Hadjiiska, R. M.; Hauser, J.; Hoepfner, K.; Hohlmann, M.; Hoorani, H.; Iaydjiev, P.; Jeng, Y. G.; Kamon, T.; Karchin, P.; Korytov, A.; Krutelyov, S.; Kumar, A.; Kim, H.; Lee, J.; Lenzi, T.; Litov, L.; Loddo, F.; Madorsky, A.; Maerschalk, T.; Maggi, M.; Magnani, A.; Mal, P. K.; Mandal, K.; Marchioro, A.; Marinov, A.; Majumdar, N.; Merlin, J. A.; Mitselmakher, G.; Mohanty, A. K.; Mohapatra, A.; Molnar, J.; Muhammad, S.; Mukhopadhyay, S.; Naimuddin, M.; Nuzzo, S.; Oliveri, E.; Pant, L. M.; Paolucci, P.; Park, I.; Passeggio, G.; Pavlov, B.; Philipps, B.; Piccolo, D.; Postema, H.; Puig Baranac, A.; Radi, A.; Radogna, R.; Raffone, G.; Ranieri, A.; Rashevski, G.; Riccardi, C.; Rodozov, M.; Rodrigues, A.; Ropelewski, L.; RoyChowdhury, S.; Ryu, G.; Ryu, M. S.; Safonov, A.; Salva, S.; Saviano, G.; Sharma, A.; Sharma, A.; Sharma, R.; Shah, A. H.; Shopova, M.; Sturdy, J.; Sultanov, G.; Swain, S. K.; Szillasi, Z.; Talvitie, J.; Tatarinov, A.; Tuuva, T.; Tytgat, M.; Vai, I.; Van Stenis, M.; Venditti, R.; Verhagen, E.; Verwilligen, P.; Vitulo, P.; Volkov, S.; Vorobyev, A.; Wang, D.; Wang, M.; Yang, U.; Yang, Y.; Yonamine, R.; Zaganidis, N.; Zenoni, F.; Zhang, A.

2018-02-01

The CMS Collaboration plans to equip the very forward muon system with triple-GEM detectors that can withstand the environment of the High-Luminosity LHC. This project is at the final stages of R&D and moving to production. An unprecedented large area of several 100 m2 are to be instrumented with GEM detectors which will be produced in six different sites around the world. A common construction and quality control procedure is required to ensure the performance of each detector. The quality control steps will include optical inspection, cleaning and baking of all materials and parts used to build the detector, leakage current tests of the GEM foils, high voltage tests, gas leak tests of the chambers and monitoring pressure drop vs. time, gain calibration to know the optimal operation region of the detector, gain uniformity tests, and studying the efficiency, noise and tracking performance of the detectors in a cosmic stand using scintillators.

Generalized extracellular molecule sensor platform for programming cellular behavior.

PubMed

Scheller, Leo; Strittmatter, Tobias; Fuchs, David; Bojar, Daniel; Fussenegger, Martin

2018-04-23

Strategies for expanding the sensor space of designer receptors are urgently needed to tailor cell-based therapies to respond to any type of medically relevant molecules. Here, we describe a universal approach to designing receptor scaffolds that enables antibody-specific molecular input to activate JAK/STAT, MAPK, PLCG or PI3K/Akt signaling rewired to transgene expression driven by synthetic promoters. To demonstrate its scope, we equipped the GEMS (generalized extracellular molecule sensor) platform with antibody fragments targeting a synthetic azo dye, nicotine, a peptide tag and the PSA (prostate-specific antigen) biomarker, thereby covering inputs ranging from small molecules to proteins. These four GEMS devices provided robust signaling and transgene expression with high signal-to-noise ratios in response to their specific ligands. The sensitivity of the nicotine- and PSA-specific GEMS devices matched the clinically relevant concentration ranges, and PSA-specific GEMS were able to detect pathological PSA levels in the serum of patients diagnosed with prostate cancer.

Gem and mineral identification using GL Gem Raman and comparison with other portable instruments

NASA Astrophysics Data System (ADS)

Culka, Adam; Hyršl, Jaroslav; Jehlička, Jan

2016-11-01

Several mainly silicate minerals in their gemstone varieties have been analysed by the Gem Raman portable system by Gemlab R&T, Vancouver, Canada, in order to ascertain the general performance of this relatively non-expensive tool developed exactly for the purpose of gemstone identification. The Raman spectra of gemstones acquired by this system have been subsequently critically compared with the data obtained by several other portable or handheld Raman instruments. The Raman spectra acquired with the Gem Raman instrument were typically of lesser quality when compared with the spectra taken by other instruments. Characteristic features such as steep baseline probably due to the fluorescence of the minerals, Raman bands much broader and therefore less resolved closely located Raman bands, and generally greater shifts of the band positions from the reference values were encountered. Some gemstone groups such as rubies did not provide useful Raman spectra at all. Nevertheless, general identification of gemstones was possible for a selection of gemstones.

Numerical Investigation on Electron and Ion Transmission of GEM-based Detectors

NASA Astrophysics Data System (ADS)

Bhattacharya, Purba; Sahoo, Sumanya Sekhar; Biswas, Saikat; Mohanty, Bedangadas; Majumdar, Nayana; Mukhopadhyay, Supratik

2018-02-01

ALICE at the LHC is planning a major upgrade of its detector systems, including the TPC, to cope with an increase of the LHC luminosity after 2018. Different R&D activities are currently concentrated on the adoption of the Gas Electron Multiplier (GEM) as the gas amplification stage of the ALICE-TPC upgrade version. The major challenge is to have low ion feedback in the drift volume as well as to ensure a collection of good percentage of primary electrons in the signal generation process. In the present work, Garfield simulation framework has been adopted to numerically estimate the electron transparency and ion backflow fraction of GEM-based detectors. In this process, extensive simulations have been carried out to enrich our understanding of the complex physical processes occurring within single, triple and quadruple GEM detectors. A detailed study has been performed to observe the effect of detector geometry, field configuration and magnetic field on the above mentioned characteristics.

gem-Difluoroolefination of Diazo Compounds with TMSCF3 or TMSCF2Br: Transition-Metal-Free Cross-Coupling of Two Carbene Precursors.

PubMed

Hu, Mingyou; Ni, Chuanfa; Li, Lingchun; Han, Yongxin; Hu, Jinbo

2015-11-18

A new olefination protocol for transition-metal-free cross-coupling of two carbene fragments arising from two different sources, namely, a nonfluorinated carbene fragment resulting from a diazo compound and a difluorocarbene fragment derived from Ruppert-Prakash reagent (TMSCF3) or TMSCF2Br, has been developed. This gem-difluoroolefination proceeds through the direct nucleophilic addition of diazo compounds to difluorocarbene followed by elimination of N2. Compared to previously reported Cu-catalyzed gem-difluoroolefination of diazo compounds with TMSCF3, which possesses a narrow substrate scope due to a demanding requirement on the reactivity of diazo compounds and in-situ-generated CuCF3, this transition-metal-free protocol affords a general and efficient approach to various disubstituted 1,1-difluoroalkenes, including difluoroacrylates, diaryldifluoroolefins, as well as arylalkyldifluoroolefins. In view of the ready availability of diazo compounds and difluorocarbene reagents and versatile transformations of 1,1-difluoroalkenes, this new gem-difluoroolefination method is expected to find wide applications in organic synthesis.

Development of near infrared spectrometer for gem materials study

NASA Astrophysics Data System (ADS)

Jindata, W.; Meesiri, W.; Wongkokua, W.

2015-07-01

Most of gem materials can be characterized by infrared absorption spectroscopy. Normally, mid infrared absorption technique has been applied for investigating fundamental vibrational modes. However, for some gem materials, such as tourmaline, NIR is a better choice due to differentiation. Most commercial NIR spectrometers employ complicated dispersive grating or Fourier transform techniques. In this work, we developed a filter type NIR spectrometer with the availability of high efficiency and low-cost narrow bandpass NIR interference filters to be taught in a physics laboratory. The instrument was designed for transmission-mode configuration. A 50W halogen lamp was used as NIR source. There were fourteen NIR filters mounted on a rotatory wheel for wavelength selection ranging from 1000-1650 nm with steps of 50 nm. A 1.0 mm diameter of InGaAs photodiode was used as the detector for the spectrometer. Hence, transparent gem materials can be used as samples for experiment. Student can learn vibrational absorption spectroscopy as well as Beer-Lambert law from the development of this instrument.

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.

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.

Lifetime Estimation of a Time Projection Chamber X-ray Polarimeter

NASA Technical Reports Server (NTRS)

Hill, Joanne E.; Black, J. Kevin; Brieda, Lubos; Dickens, Patsy L.; deGarcia, Kristina Montt; Hawk, Douglas L.; Hayato, Asami; Jahoda, Keith; Mohammed, Jelila

2013-01-01

The Gravity and Extreme Magnetism Small Explorer (GEMS) X-ray polarimeter Instrument (XPI) was designed to measure the polarization of 23 sources over the course of its 9 month mission. The XPI design consists of two telescopes each with a polarimeter assembly at the focus of a grazing incidence mirror. To make sensitive polarization measurements the GEMS Polarimeter Assembly (PA) employed a gas detection system based on a Time Projection Chamber (TPC) technique. Gas detectors are inherently at risk of degraded performance arising from contamination from outgassing of internal detector components or due to loss of gas. This paper describes the design and the materials used to build a prototype of the flight polarimeter with the required GEMS lifetime. We report the results from outgassing measurements of the polarimeter subassemblies and assemblies, enclosure seal tests, life tests, and performance tests that demonstrate that the GEMS lifetime is achievable. Finally we report performance measurements and the lifetime enhancement from the use of a getter.

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.

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.

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.

Phase I dose-escalation study of copanlisib in combination with gemcitabine or cisplatin plus gemcitabine in patients with advanced cancer.

PubMed

Kim, R D; Alberts, S R; Peña, C; Genvresse, I; Ajavon-Hartmann, A; Xia, C; Kelly, A; Grilley-Olson, J E

2018-02-20

Copanlisib is a pan-class I phosphatidylinositol 3-kinase (PI3K) inhibitor with predominant PI3K-α/δ activity that has demonstrated clinical activity and manageable safety when administered as monotherapy in a phase II study. Combination therapy may overcome compensatory signalling that could occur with PI3K pathway inhibition, resulting in enhanced inhibitory activity, and preclinical studies of copanlisib with gemcitabine have demonstrated potent anti-tumour activity in vivo. A phase I, open-label, dose-escalation study to evaluate the safety, tolerability and recommended phase II dose (RP2D) of copanlisib with gemcitabine or with cisplatin plus gemcitabine (CisGem) in patients with advanced malignancies, including an expansion cohort in patients with biliary tract cancer (BTC) at the RP2D of copanlisib plus CisGem. Copanlisib and gemcitabine were administered on days 1, 8 and 15 of a 28-day cycle; maximum tolerated dose (MTD) and RP2D of copanlisib were determined. Copanlisib plus CisGem was administered on days 1 and 8 of a 21-day cycle; pharmacokinetics and biomarkers were assessed. Fifty patients received treatment as follows: dose-escalation cohorts, n=16; copanlisib plus CisGem cohort, n=14; and BTC expansion cohort, n=20. Copanlisib 0.8 mg kg -1 plus gemcitabine was the MTD and RP2D for both combinations. Common treatment-emergent adverse events included nausea (86%), hyperglycaemia (80%) and decreased platelet count (80%). Copanlisib exposure displayed a dose-proportional increase. No differences were observed upon co-administration of CisGem. Response rates were as follows: copanlisib plus gemcitabine, 6.3% (one partial response in a patient with peritoneal carcinoma); copanlisib plus CisGem, 12% (one complete response and three partial responses all in patients with BTC (response rate 17.4% in patients with BTC)). Mutations were detected in PIK3CA (1 out of 43), KRAS (10 out of 43) and BRAF (2 out of 22), with phosphate and tensin homologue protein loss in 41% (12 out of 29). Copanlisib plus CisGem demonstrated a manageable safety profile, favourable pharmacokinetics, and potentially promising clinical response.

[Nab-Paclitaxel plus Gemcitabine Hydrochloride in Patients with Metastatic or Recurrent Pancreatic Cancer - A Single Institution Experience].

PubMed

Takeda, Yutaka; Katsura, Yoshiteru; Ohmura, Yoshiaki; Sakamoto, Takuya; Akiyama, Yasuki; Kuwahara, Ryuichi; Morimoto, Yoshihiro; Ishida, Tomo; Oneda, Yasuo; Murakami, Kouhei; Naito, Atsushi; Kagawa, Yoshinori; Takeno, Atsushi; Kato, Takeshi; Tamura, Shigeyuki

2016-11-01

Pancreatic adenocarcinoma is one of the leading causes of cancer deaths in Japan.Albumin -bound paclitaxel (nab-paclitaxel)plus gemcitabine hydrochloride(GEM)combination chemotherapy provided significant improvements in the overall and progression-free survival in a phase III trial in Europe and America and a phase II trial in Japan.As a result, this combination therapy was approved for use in Japan. We evaluated the efficacy of nab-paclitaxel plus GEM with metastatic or recurrent pancreatic cancer.Between December 2014 and March 2016, 11 patients received nab-paclitaxel plus GEM as follows: nab-paclitaxel(125mg/m2 of body-surface area)followed by GEM(1,000mg/m2)on days 1, 8, and 15 every 4 weeks.The treatment was continued until disease progression, unacceptable adverse events, discontinuation as decided by the investigators, or patient refusal. The mean age was 65.6 years(range, 48-75 years), and 8 out of 11 patients were men.Ten patients had an Eastern Cooperative Oncology Group(ECOG)performance status(PS)of 0.Ten patients had metastatic disease.Only 4 patients had no prior therapy.The mean duration of treatment was 10.2 weeks(range, 2-41 weeks).The relative dose intensities of nab-paclitaxel and GEM were 90.6%(66.7-100%)and 87.5%(62.9-100%), respectively.The major Grade 3 or 4 hematological toxicities were leucopenia(54.5%), neutropenia(36.4%), anemia (27.3%), and thrombocytopenia(18.2%).The major grade 2 or 3 non-hematological toxicities were fatigue(45.6%), skin rash(27.3%), peripheral sensory neuropathy(9.1%), anorexia(9.1%), and stomatitis(9.1%).There were no treatmentrelated deaths.Interstitial lung disease was not observed.The 6 month progression-free and overall survival rate were 25.7% and 66.7%, respectively. The disease control rate was 90.9%(complete response, n=0; partial response, n=1; stable disease, n=9; progressive disease, n=1). Nab-paclitaxel plus GEM is well tolerated and associated with efficacy and improved survival outcomes.Nab -paclitaxel plus GEM can be the standard treatment for patients with metastatic pancreatic adenocarcinoma.

Eddy covariance flux measurements of gaseous elemental mercury using cavity ring-down spectroscopy.

PubMed

Pierce, Ashley M; Moore, Christopher W; Wohlfahrt, Georg; Hörtnagl, Lukas; Kljun, Natascha; Obrist, Daniel

2015-02-03

A newly developed pulsed cavity ring-down spectroscopy (CRDS) system for measuring atmospheric gaseous elemental mercury (GEM) concentrations at high temporal resolution (25 Hz) was used to successfully conduct the first eddy covariance (EC) flux measurements of GEM. GEM is the main gaseous atmospheric form, and quantification of bidirectional exchange between the Earth's surface and the atmosphere is important because gas exchange is important on a global scale. For example, surface GEM emissions from natural sources, legacy emissions, and re-emission of previously deposited anthropogenic pollution may exceed direct primary anthropogenic emissions. Using the EC technique for flux measurements requires subsecond measurements, which so far has not been feasible because of the slow time response of available instrumentation. The CRDS system measured GEM fluxes, which were compared to fluxes measured with the modified Bowen ratio (MBR) and a dynamic flux chamber (DFC). Measurements took place near Reno, NV, in September and October 2012 encompassing natural, low-mercury (Hg) background soils and Hg-enriched soils. During nine days of measurements with deployment of Hg-enriched soil in boxes within 60 m upwind of the EC tower, the covariance of GEM concentration and vertical wind speed was measured, showing that EC fluxes over an Hg-enriched area were detectable. During three separate days of flux measurements over background soils (without Hg-enriched soils), no covariance was detected, indicating fluxes below the detection limit. When fluxes were measurable, they strongly correlated with wind direction; the highest fluxes occurred when winds originated from the Hg-enriched area. Comparisons among the three methods showed good agreement in direction (e.g., emission or deposition) and magnitude, especially when measured fluxes originated within the Hg-enriched soil area. EC fluxes averaged 849 ng m(-2) h(-1), compared to DFC fluxes of 1105 ng m(-2) h(-1) and MBR fluxes of 1309 ng m(-2) h(-1). This study demonstrated that a CRDS system can be used to measure GEM fluxes over Hg-enriched areas, with a conservative detection limit estimate of 32 ng m(-2) h(-1).

Illuminating Cancer Systems With Genetically-Engineered Mouse Models and Coupled Luciferase Reporters In Vivo

PubMed Central

Kocher, Brandon; Piwnica-Worms, David

2013-01-01

Bioluminescent imaging (BLI) is a powerful non-invasive tool that has dramatically accelerated the in vivo interrogation of cancer systems and longitudinal analysis of mouse models of cancer over the past decade. Various luciferase enzymes have been genetically engineered into mouse models (GEMMs) of cancer which permit investigation of cellular and molecular events associated with oncogenic transcription, post-transcriptional processing, protein-protein interactions, transformation and oncogene addiction in live cells and animals. Luciferase-coupled GEMMs ultimately serve as a non-invasive, repetitive, longitudinal, and physiological means by which cancer systems and therapeutic responses can be investigated accurately within the autochthonous context of a living animal. PMID:23585416

X-Ray Polarimetry with GEMS

NASA Technical Reports Server (NTRS)

Strohmayer, Tod

2011-01-01

The polarization properties of cosmic X-ray sources are still largely unexplored. The Gravity and Extreme Magnetism SMEX (GEMS) will carry out the first sensitive X-ray polarization survey of a wide range of sources including; accreting compact objects (black holes and neutron stars), AGN, supernova remnants, magnetars and rotation-powered pulsars. GEMS employs grazing-incidence foil mirrors and novel time-projection chamber (TPC) polarimeters leveraging the photoelectric effect to achieve high polarization sensitivity in the 2 - 10 keV band. I will provide an update of the project status, illustrate the expected performance with several science examples, and provide a brief overview of the data analysis challenges

VizieR Online Data Catalog: Algol-type binaries. VIII. DI Peg & AF Gem (Yang+, 2014)

NASA Astrophysics Data System (ADS)

Yang, Y.-G.; Yang, Y.; Li, S.-Z.

2014-10-01

In the 2012-2013 observing season, DI Peg and AF Gem were observed using the 60cm telescope and the 85cm telescope at Xinglong station (XLs) of National Astronomical Observatories of Chinese (NAOC). The standard Johnson-Cousins UBVRcIc photometric systems were mounted upon two small telescopes. On five consecutive nights from 2012 October 9 to 13, the multi-color photometry of DI Peg was made with the 60cm telescope. The other variable star, AF Gem, was observed using the 85cm telescope on 7 nights from 2013 January 1 to 7. (5 data files).

The BoNuS GEM-Based Radial Time-Projection Chamber

NASA Astrophysics Data System (ADS)

Fenker, Howard

2006-10-01

A special-purpose detector for measuring low-momentum spectator protons from e-d collisions has been developed. It is a radial time-projection chamber in which the gas-amplification elements are GEM foils formed into cylinders. This is believed to be the first application of curved GEMs. In a 4T magnetic field, this low-mass detector allows tracking of spectator protons with momentum as low as 70 MeV/c while covering a large solid angle. Physics data were taken using the system in late 2005. We report on the development of the detector, experience with operating it, and the data coming out of it.

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.

Dust lifting in GEM-Mars using a roughness length map

NASA Astrophysics Data System (ADS)

Daerden, F.; Neary, L.; Whiteway, J. A.; Hébrard, E.

2013-09-01

Lifting of size distributed dust due to surface wind stress and dust devils has been implemented in the GEM-Mars 3D-GCM. It turned out that a detailed surface roughness length map was necessary to bring the simulated dust opacities in accordance with observations.

Highly effective copper-mediated gem-difluoromethylenation of arylboronic acids.

PubMed

Ma, Guobin; Wan, Wen; Hu, Qingyang; Jiang, Haizhen; Wang, Jing; Zhu, Shizheng; Hao, Jian

2014-07-18

A copper-mediated gem-difluoromethylenation of aryl, heteroaryl and vinyl boronic acids with bromodifluoromethylated oxazole or thiazole derivatives has been developed. This novel reaction showed an excellent functional group tolerance and wide substrate scope, providing facile access to practical application in drug discovery and development.

A Hidden GEM

ERIC Educational Resources Information Center

Khan, Samia

2012-01-01

The internet abounds with free science education applications. But, on their own, these applications have limited capacity to teach students curricular concepts or skills. The author integrated several free web-based applications into a broader pedagogical approach called T-GEM, in which the teacher guides student investigations. In this article,…

The Greenhouse Gases. UNEP/GEMS Environment Library No. 1.

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 including urban air pollution, climate modification,…

Trace elements in Gem-Quality Diamonds - Origin and evolution of diamond-forming fluid inclusions

NASA Astrophysics Data System (ADS)

Pearson, Graham; Krebs, Mandy; Stachel, Thomas; Woodland, Sarah; Chinn, Ingrid; Kong, Julie

2017-04-01

In the same way that melt inclusions in phenocrysts have expanded our idea of melt formation and evolution in basalts, studying fluids trapped in diamonds is providing important new constraints on the nature of diamond-forming fluids. Fibrous and cloudy diamonds trap a high but variable density of fluid inclusions and so have been extensively studied using major and trace element compositions. In contrast, constraining the nature of the diamond-forming fluid for high purity gem-quality diamonds has been restricted by the rarity of available high quality trace element data. This is due to the extremely low concentrations of impurities that gem diamonds contain - often in the ppt range. The recent discovery of fluids in gem diamonds showing similar major element chemistry to fluid-rich diamonds suggest that many diamonds may share a common spectrum of parental fluids. Here we test this idea further. Recent advances in analytical techniques, in particular the development of the "off-line" laser ablation pre-concentration approach, have allowed fully quantitative trace element data to be recovered from "fluid-poor", high quality gem diamonds. We present trace element data for gem diamonds from a variety of locations from Canada, S. Africa and Russia, containing either silicate or sulphide inclusions to examine possible paragenetic or genetic differences between fluids. REE abundance in the "gem" diamonds vary from 0.1 to 0.0001 x chondrite. To a first order, we observe the same spectrum of trace element compositions in the gem diamonds as that seen in fluid-rich "fibrous" diamonds, supporting a common origin for the fluids. REE patterns range from extremely flat (Ce/Yb)n 2.5 to 5 (commonly in sulphide-bearing diamonds) to >70, the latter having significantly greater inter-element HFSE/LILE fractionation. In general, the fluids from the sulphide-bearing diamonds are less REE-enriched than the silicate-bearing diamonds, but the ranges overlap significantly. The very large range in REE fractionation mimics very closely that produced in high pressure (5-6 GPa) experimental melts of CO2-H2O fluxed peridotite. Hence, the elemental characteristics of the fluids could be reconciled by the diamonds growing from such melts over a range of T and hence F, with the sulphide-bearing diamonds generally being produced by larger fraction (higher T) melts that have reacted less with their wall rocks. It is also possible that the less REE enriched fluids are consistent with derivation from more reduced CH4-bearing fluids that have lower solute capacity than oxidised fluids. This option is being evaluated.

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.

GEnomes Management Application (GEM.app): a new software tool for large-scale collaborative genome analysis.

PubMed

Gonzalez, Michael A; Lebrigio, Rafael F Acosta; Van Booven, Derek; Ulloa, Rick H; Powell, Eric; Speziani, Fiorella; Tekin, Mustafa; Schüle, Rebecca; Züchner, Stephan

2013-06-01

Novel genes are now identified at a rapid pace for many Mendelian disorders, and increasingly, for genetically complex phenotypes. However, new challenges have also become evident: (1) effectively managing larger exome and/or genome datasets, especially for smaller labs; (2) direct hands-on analysis and contextual interpretation of variant data in large genomic datasets; and (3) many small and medium-sized clinical and research-based investigative teams around the world are generating data that, if combined and shared, will significantly increase the opportunities for the entire community to identify new genes. To address these challenges, we have developed GEnomes Management Application (GEM.app), a software tool to annotate, manage, visualize, and analyze large genomic datasets (https://genomics.med.miami.edu/). GEM.app currently contains ∼1,600 whole exomes from 50 different phenotypes studied by 40 principal investigators from 15 different countries. The focus of GEM.app is on user-friendly analysis for nonbioinformaticians to make next-generation sequencing data directly accessible. Yet, GEM.app provides powerful and flexible filter options, including single family filtering, across family/phenotype queries, nested filtering, and evaluation of segregation in families. In addition, the system is fast, obtaining results within 4 sec across ∼1,200 exomes. We believe that this system will further enhance identification of genetic causes of human disease. © 2013 Wiley Periodicals, Inc.

Psychometric validation of the Growth and Empowerment Measure (GEM) applied with Indigenous Australians.

PubMed

Haswell, Melissa R; Kavanagh, David; Tsey, Komla; Reilly, Lyndon; Cadet-James, Yvonne; Laliberte, Arlene; Wilson, Andrew; Doran, Chris

2010-09-01

Empowerment is a complex process of psychological, social, organizational and structural change. It allows individuals and groups to achieve positive growth and effectively address the social and psychological impacts of historical oppression, marginalization and disadvantage. The Growth and Empowerment Measure (GEM) was developed to measure change in dimensions of empowerment as defined and described by Aboriginal Australians who participated in the Family Well Being programme. The GEM has two components: a 14-item Emotional Empowerment Scale (EES14) and 12 Scenarios (12S). It is accompanied by the Kessler 6 Psychological Distress Scale (K6), supplemented by two questions assessing frequency of happy and angry feelings. For validation, the measure was applied with 184 Indigenous Australian participants involved in personal and/or organizational social health activities. Psychometric analyses of the new instruments support their validity and reliability and indicate two-component structures for both the EES (Self-capacity; Inner peace) and the 12S (Healing and enabling growth, Connection and purpose). Strong correlations were observed across the scales and subscales. Participants who scored higher on the newly developed scales showed lower distress on the K6, particularly when the two additional questions were included. However, exploratory factor analyses demonstrated that GEM subscales are separable from the Kessler distress measure. The GEM shows promise in enabling measurement and enhancing understanding of both process and outcome of psychological and social empowerment within an Australian Indigenous context.

Development of a Walking-Safety Scale for Older Adults, Part II: Interrater and Test–Retest Agreement of the GEM Scale

PubMed Central

Rousseau, Jacqueline; Kaegi, Christine; Boudreault, Renée; Nadeau, Sylvie

2008-01-01

Purpose: The GEM scale is an objective assessment tool, specifically developed for older adults, to evaluate walking safety using standardized tasks. The purpose of this study was to estimate the interrater and test–retest agreement of the GEM scale. Method: Participants (n = 41; ≥ 65 years) were recruited from geriatric units and assessed independently and simultaneously by three raters on two occasions using the GEM scale. Kappa coefficients and percentage agreement were calculated for each item of the scale. Results: A majority of walking items (n = 22) showed fair to substantial interrater agreement (κ ≥ 0.25) and substantial to almost perfect test–retest agreement (κ ≥ 0.60). Mean percentage agreement was high for both interrater and test–retest agreement (79% ± 15% and 83% ± 16% respectively). Moreover, detailed analyses demonstrated that the relatively low agreement of some items resulted from changes in the performance of some participants and the low variability of scores. Although some walking items showed less agreement, the final decision regarding the participants’ ability to walk safely resulted in moderate to substantial interrater and test–retest agreement. Conclusion: The GEM scale is a new assessment tool that can now be used with estimated interrater and test–retest properties to allow therapists to objectively evaluate walking safety among the elderly. PMID:20145760

The SMN Protein is a Key Regulator of Nuclear Architecture in Differentiating Neuroblastoma Cells

PubMed Central

Clelland, Allyson K; Kinnear, Nicholas P; Oram, Lisa; Burza, Julie; Sleeman, Judith E

2009-01-01

The cell nucleus contains two closely related structures, Cajal bodies (CBs) and gems. CBs are the first site of accumulation of newly assembled splicing snRNPs (small nuclear ribonucleoproteins) following their import into the nucleus, before they form their steady-state localization in nuclear splicing speckles. Gems are the nuclear site of accumulation of survival motor neurons (SMNs), an insufficiency of which leads to the inherited neurodegenerative condition, spinal muscular atrophy (SMA). SMN is required in the cytoplasm for the addition of core, Sm, proteins to new snRNPs and is believed to accompany snRNPs to the CB. In most cell lines, gems are indistinguishable from CBs, although the structures are often separate in vivo. The relationship between CBs and gems is not fully understood, but there is evidence that symmetrical dimethylation of arginine residues in the CB protein coilin brings them together in HeLa cells. During neuronal differentiation of the human neuroblastoma cell line SH-SY5Y, CBs and gems increase their colocalization, mimicking changes seen during foetal development. This does not result from alterations in the methylation of coilin, but from increased levels of SMN. Expression of exogenous SMN results in an increased efficiency of snRNP transport to nuclear speckles. This suggests different mechanisms are present in different cell types and in vivo that may be significant for the tissue-specific pathology of SMA. PMID:19735367

Priceless GEMMs: genetically engineered mouse models for colorectal cancer drug development.

PubMed

Roper, Jatin; Hung, Kenneth E

2012-08-01

To establish effective drug development for colorectal cancer (CRC), preclinical models that are robust surrogates for human disease are crucial. Mouse models are an attractive platform because of their relatively low cost, short life span, and ease of use. There are two main categories of mouse CRC models: xenografts derived from implantation of CRC cells or tumors in immunodeficient mice; and genetically engineered mouse models (GEMMs) derived from modification of human cancer predisposition genes, resulting in spontaneous tumor formation. Here, we review xenografts and GEMMs and focus on their potential application in translational research. Furthermore, we describe newer GEMMs for sporadic CRC that are particularly suitable for drug testing. Finally, we discuss recent advances in small-animal imaging, such as optical colonoscopy, which allow in vivo assessment of tumors. With the increasing sophistication of GEMMs, our preclinical armamentarium provides new hope for the ongoing war against CRC. Copyright © 2012. Published by Elsevier Ltd.

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.

Only One Ocean: Marine Science Activities for Grades 5-8. Teacher's Guide.

ERIC Educational Resources Information Center

Halversen, Catherine; Strang, Craig

This guide was designed by the Marine Activities, Resources & Education (MARE) Program through the Great Explorations in Math and Science (GEMS) ongoing curriculum development program for middle school students. This GEMS guide addresses the concepts of the interconnectedness of the ocean basins, respect for organisms, oceanography, physical…

Fluorination of thiocarbonyl compounds with Bis(2-methoxyethyl)aminosulfur trifluoride (Deoxo-fluor reagent): A facile synthesis of gem-difluorides

PubMed

Lal; Lobach; Evans

2000-08-11

A variety of thiocarbonyl derivatives (thioketone, thioester, thioamide, dithioester, and dithiocarbamate) were converted to the corresponding gem-difluorides in excellent yields on reaction with the fluorinating agent, bis(2-methoxyethyl)aminosulfur trifluoride, in the presence of SbCl(3).

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

Genomic landscapes of endogenous retroviruses unveil intricate genetics of conventional and genetically-engineered laboratory mouse strains.

PubMed

Lee, Kang-Hoon; Lim, Debora; Chiu, Sophia; Greenhalgh, David; Cho, Kiho

2016-04-01

Laboratory strains of mice, both conventional and genetically engineered, have been introduced as critical components of a broad range of studies investigating normal and disease biology. Currently, the genetic identity of laboratory mice is primarily confirmed by surveying polymorphisms in selected sets of "conventional" genes and/or microsatellites in the absence of a single completely sequenced mouse genome. First, we examined variations in the genomic landscapes of transposable repetitive elements, named the TREome, in conventional and genetically engineered mouse strains using murine leukemia virus-type endogenous retroviruses (MLV-ERVs) as a probe. A survey of the genomes from 56 conventional strains revealed strain-specific TREome landscapes, and certain families (e.g., C57BL) of strains were discernible with defined patterns. Interestingly, the TREome landscapes of C3H/HeJ (toll-like receptor-4 [TLR4] mutant) inbred mice were different from its control C3H/HeOuJ (TLR4 wild-type) strain. In addition, a CD14 knock-out strain had a distinct TREome landscape compared to its control/backcross C57BL/6J strain. Second, an examination of superantigen (SAg, a "TREome gene") coding sequences of mouse mammary tumor virus-type ERVs in the genomes of the 46 conventional strains revealed a high diversity, suggesting a potential role of SAgs in strain-specific immune phenotypes. The findings from this study indicate that unexplored and intricate genomic variations exist in laboratory mouse strains, both conventional and genetically engineered. The TREome-based high-resolution genetics surveillance system for laboratory mice would contribute to efficient study design with quality control and accurate data interpretation. This genetics system can be easily adapted to other species ranging from plants to humans. Copyright © 2016 Elsevier Inc. All rights reserved.

Developing Novel Therapeutic Approaches in Small Cell Lung Carcinoma Using Genetically Engineered Mouse Models and Human Circulating Tumor Cells

DTIC Science & Technology

2015-10-01

xenograft models . 12-36 Dr. Engelman Subtask 3: Analyze CTCs for P-4EBP1, P-S6, BIM , Bcl-2, Bcl-xL, and Mcl-1 using ISH and IHC We propose...Using Genetically Engineered Mouse Models and Human Circulating Tumor Cells PRINCIPAL INVESTIGATOR: Jeffrey Engelman MD PhD CONTRACTING...reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions

Murine tissue-engineered stomach demonstrates epithelial differentiation.

PubMed

Speer, Allison L; Sala, Frederic G; Matthews, Jamil A; Grikscheit, Tracy C

2011-11-01

Gastric cancer remains the second largest cause of cancer-related mortality worldwide. Postgastrectomy morbidity is considerable and quality of life is poor. Tissue-engineered stomach is a potential replacement solution to restore adequate food reservoir and gastric physiology. In this study, we performed a detailed investigation of the development of tissue-engineered stomach in a mouse model, specifically evaluating epithelial differentiation, proliferation, and the presence of putative stem cell markers. Organoid units were isolated from <3 wk-old mouse glandular stomach and seeded onto biodegradable scaffolds. The constructs were implanted into the omentum of adult mice. Implants were harvested at designated time points and analyzed with histology and immunohistochemistry. Tissue-engineered stomach grows as an expanding sphere with a simple columnar epithelium organized into gastric glands and an adjacent muscularis. The regenerated gastric epithelium demonstrates differentiation of all four cell types: mucous, enteroendocrine, chief, and parietal cells. Tissue-engineered stomach epithelium proliferates at a rate comparable to native glandular stomach and expresses two putative stem cell markers: DCAMKL-1 and Lgr5. This study demonstrates the successful generation of tissue-engineered stomach in a mouse model for the first time. Regenerated gastric epithelium is able to appropriately proliferate and differentiate. The generation of murine tissue-engineered stomach is a necessary advance as it provides the transgenic tools required to investigate the molecular and cellular mechanisms of this regenerative process. Delineating the mechanism of how tissue-engineered stomach develops in vivo is an important precursor to its use as a human stomach replacement therapy. Copyright © 2011 Elsevier Inc. All rights reserved.

Reduction of Defects in Jewelry Manufacturing

NASA Astrophysics Data System (ADS)

Ayudhya, Phitchaya Phanomwan na; Tangjitsitcharoen, Somkiat

2017-06-01

The aim of this research was to reduce the defects of gem bracelet found during manufacturing process at a jewelry company. It was found that gem bracelet product has the highest rejects compared to the rejects found in ring, earring, and pendant products. Types of defect were classified by using Pareto Diagram consisting of gem falling, seam, unclean casting, impinge, and deformation. The causes of defect were analyzed by Cause and Effect Diagram and applied Failure Mode and Effects Analysis (FMEA) was applied during manufacturing processes. This research found that the improvement of manufacturing process could reduce the Risk Priority Number (RPN) and total of all defects by 48.70% and 48.89%, respectively.

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.

Galium Electromagnetic (GEM) Thruster Concept and Design

NASA Technical Reports Server (NTRS)

Polzin, Kurt A.; Markusic, Thomas E.

2005-01-01

We describe the design of a new type of two-stage pulsed electromagnetic accelerator, the gallium electromagnetic (GEM) thruster. A schematic illustration of the GEM thruster concept is given. In this concept, liquid gallium propellant is pumped into the first stage through a porous metal electrode using an electromagnetic pump. At a designated time, a pulsed discharge (approx. 10-50 J) is initiated in the first stage, ablating the liquid gallium from the porous electrode surface and ejecting a dense thermal gallium plasma into the second state. The presence of the gallium plasma in the second stage serves to trigger the high-energy (approx. 500 J), second-stage pulse which provides the primary electromagnetic (j x B) acceleration.

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.

40 CFR 1037.810 - Incorporation by reference.

Code of Federal Regulations, 2013 CFR

2013-07-01

... must publish a notice of the change in the Federal Register and the material must be available to the... software is also available for download at http://www.epa.gov/otaq/climate/gem.htm. (2) [Reserved] (d... working version of this software is also available for download at http://www.epa.gov/otaq/climate/gem.htm. ...

The Germplasm Enhancement of Maize (GEM) project: A Public-Private Partnership (PPP) to increase genetic diversity in US maize

USDA-ARS?s Scientific Manuscript database

The Germplasm Enhancement of Maize (GEM) Project is a mission-oriented, cooperative research effort of the United States Department of Agriculture – Agricultural Research Service (USDA-ARS), land grant universities, private industry, and international agricultural research centers to broaden the ger...

77 FR 68881 - DIAS Holding, Inc., EarthBlock Technologies, Inc., Ensurapet, Inc., FIIC Holdings, Inc., GeM...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-16

... SECURITIES AND EXCHANGE COMMISSION [File No. 500-1] DIAS Holding, Inc., EarthBlock Technologies, Inc., Ensurapet, Inc., FIIC Holdings, Inc., GeM Solutions, Inc., Gold Star Tutoring Services Inc., and... accurate information concerning the securities of EarthBlock Technologies, Inc. because it has not filed...

Stages of Psychometric Measure Development: The Example of the Generalized Expertise Measure (GEM)

ERIC Educational Resources Information Center

Germain, Marie-Line

2006-01-01

This paper chronicles the steps, methods, and presents hypothetical results of quantitative and qualitative studies being conducted to develop a Generalized Expertise Measure (GEM). Per Hinkin (1995), the stages of scale development are domain and item generation, content expert validation, and pilot test. Content/face validity and internal…

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.

A Muon Tomography Station with GEM Detectors for Nuclear Threat Detection

NASA Astrophysics Data System (ADS)

Staib, Michael; Gnanvo, Kondo; Grasso, Leonard; Hohlmann, Marcus; Locke, Judson; Costa, Filippo; Martoiu, Sorin; Muller, Hans

2011-10-01

Muon tomography for homeland security aims at detecting well-shielded nuclear contraband in cargo and imaging it in 3D. The technique exploits multiple scattering of atmospheric cosmic ray muons, which is stronger in dense, high-Z nuclear materials, e.g. enriched uranium, than in low-Z and medium-Z shielding materials. We have constructed and operated a compact Muon Tomography Station (MTS) that tracks muons with six to ten 30 cm x 30 cm Triple Gas Electron Multiplier (GEM) detectors placed on the sides of a 27-liter cubic imaging volume. The 2D strip readouts of the GEMs achieve a spatial resolution of ˜130 μm in both dimensions and the station is operated at a muon trigger rate of ˜20 Hz. The 1,536 strips per GEM detector are read out with the first medium-size implementation of the Scalable Readout System (SRS) developed specifically for Micro-Pattern Gas Detectors by the RD51 collaboration at CERN. We discuss the performance of this MTS prototype and present experimental results on tomographic imaging of high-Z objects with and without shielding.

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

Measurement of basic characteristics and gain uniformity of a triple GEM detector

NASA Astrophysics Data System (ADS)

Patra, Rajendra Nath; Singaraju, Rama N.; Biswas, Saikat; Ahammed, Zubayer; Nayak, Tapan K.; Viyogi, Yogendra P.

2017-08-01

Large area Gas Electron Multiplier (GEM) detectors have been the preferred choice for tracking devices in major nuclear and particle physics experiments. Uniformity over surface of the detector in terms of gain, energy resolution and efficiency is crucial for the optimum performance of these detectors. In the present work, detailed performance study of a 10×10 cm2 triple GEM detector operated using Ar and CO2 gas mixtures in proportions of 70:30 and 90:10, has been made by making a voltage scan of the efficiency with 106Ru-Rh β-source and cosmic rays. The gain and energy resolution of the detector were studied using the X-ray spectrum of 55Fe source. The uniformity of the detector has been investigated by dividing the detector in 7×7 zones and measuring the gain and energy resolution at the centre of each zone. The variations of the gain and energy resolution have been found to be 8.8% and 6.7%, respectively. These studies are essential to characterise GEM detectors before their final use in the experiments.

A GEM readout with radial zigzag strips and linear charge-sharing response

DOE PAGES

Zhang, Aiwu; Hohlmann, Marcus; Azmoun, Babak; ...

2018-01-10

Here, we study the position sensitivity of radial zigzag strips intended to read out large GEM detectors for tracking at future experiments. Zigzag strips can cover a readout area with fewer strips than regular straight strips while maintaining good spatial resolution. Consequently, they can reduce the number of required electronic channels and related cost for large-area GEM detector systems. A non-linear relation between incident particle position and hit position measured from charge sharing among zigzag strips was observed in a previous study. We significantly reduce this non-linearity by improving the interleaving of adjacent physical zigzag strips. Zigzag readout structures aremore » implemented on PCBs and on a flexible foil and are tested using a 10 cm × 10 cm triple-GEM detector scanned with a strongly collimated X-ray gun on a 2D motorized stage. Lastly, angular resolutions of 60–84 μrad are achieved with a 1.37 mrad angular strip pitch at a radius of 784 mm. On a linear scale this corresponds to resolutions below 100 μm.« less

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.

A GEM readout with radial zigzag strips and linear charge-sharing response

NASA Astrophysics Data System (ADS)

Zhang, Aiwu; Hohlmann, Marcus; Azmoun, Babak; Purschke, Martin L.; Woody, Craig

2018-04-01

We study the position sensitivity of radial zigzag strips intended to read out large GEM detectors for tracking at future experiments. Zigzag strips can cover a readout area with fewer strips than regular straight strips while maintaining good spatial resolution. Consequently, they can reduce the number of required electronic channels and related cost for large-area GEM detector systems. A non-linear relation between incident particle position and hit position measured from charge sharing among zigzag strips was observed in a previous study. We significantly reduce this non-linearity by improving the interleaving of adjacent physical zigzag strips. Zigzag readout structures are implemented on PCBs and on a flexible foil and are tested using a 10 cm × 10 cm triple-GEM detector scanned with a strongly collimated X-ray gun on a 2D motorized stage. Angular resolutions of 60-84 μrad are achieved with a 1.37 mrad angular strip pitch at a radius of 784 mm. On a linear scale this corresponds to resolutions below 100 μm.

Status of the KLOE-2 Inner Tracker

NASA Astrophysics Data System (ADS)

De Lucia, Erika

2018-01-01

KLOE-2 at the DAΦNE Φ-factory is the main experiment of the INFN Laboratori Nazionali di Frascati (LNF) and is the first high-energy experiment using the GEM technology with a cylindrical geometry, a novel idea developed at LNF. Four concentric cylindrical triple-GEM detectors compose the Inner Tracker, inserted around the interaction region and before the inner wall of the pre-existing KLOE Drift Chamber to improve the resolution on decay vertices close to the interaction point. State-of-the-art solutions have been expressly developed or tuned for this project: single-mask GEM etching, multi-layer XV patterned readout, PEEK spacer grid, GASTONE front-end board, a custom 64-channel ASIC with digital output, and the Global Interface Board for data collection, with a configurable FPGA architecture and Gigabit Ethernet. Alignment and calibration of a cylindrical GEM detector was never done before and represents one of the challenging activities of the experiment. The Inner Tracker detector construction, operation, calibration and performance obtained with cosmic-ray muons and Bhabha scattering events will be reported.

Characterization of multilayer Thick-GEM geometries as 10B converters aiming thermal neutron detection

NASA Astrophysics Data System (ADS)

Natal da Luz, H.; Souza, F. A.; Moralles, M.; Carlin, N.; Oliveira, R. A. N.; Bregant, M.; Suaide, A. A. P.; Chubaci, J. F. D.; Matsuoka, M.; Silva, T. F.; Moro, M. V.; Rodrigues, C. L.; Munhoz, M. G.

2018-02-01

Boron-based thermal neutron detectors have recently regained some attention from the instrumentation community as a strong alternative to helium-3 detectors. From the existing concepts exploiting boron layers in position sensitive detectors, the Cascade [1] is the one that takes full advantage of the 2D capabilities of gaseous detectors, with the position resolution not limited by the architecture of the detector. In this work, a proposal for the Cascade detector, based on Thick-GEMs is presented, together with some preliminary studies of the suitable pitch that optimizes the neutron conversion efficiency, while keeping the collection efficiency intact. The characterization of Thick-GEM prototypes produced in Brazil with hole pitch from 0.75 to 3 mm shows that these devices already present a stable performance at low gains, also resulting in fair energy resolution, when cascaded with a standard KaptonTM 50 µm GEM. Results of the first attempts of boron film depositions with Ion Beam Assisted Deposition and characterization by Ion Beam Analysis are also presented.

MOST-visualization: software for producing automated textbook-style maps of genome-scale metabolic networks.

PubMed

Kelley, James J; Maor, Shay; Kim, Min Kyung; Lane, Anatoliy; Lun, Desmond S

2017-08-15

Visualization of metabolites, reactions and pathways in genome-scale metabolic networks (GEMs) can assist in understanding cellular metabolism. Three attributes are desirable in software used for visualizing GEMs: (i) automation, since GEMs can be quite large; (ii) production of understandable maps that provide ease in identification of pathways, reactions and metabolites; and (iii) visualization of the entire network to show how pathways are interconnected. No software currently exists for visualizing GEMs that satisfies all three characteristics, but MOST-Visualization, an extension of the software package MOST (Metabolic Optimization and Simulation Tool), satisfies (i), and by using a pre-drawn overview map of metabolism based on the Roche map satisfies (ii) and comes close to satisfying (iii). MOST is distributed for free on the GNU General Public License. The software and full documentation are available at http://most.ccib.rutgers.edu/. dslun@rutgers.edu. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

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

LASP-01: Distribution of Mouse Embryonic Stem Cells Expressing MicroRNAs | Frederick National Laboratory for Cancer Research

Cancer.gov

The Laboratory Animal Sciences Program manages the expansion, processing, and distribution of1,501 genetically engineered mouse embryonic stem cell (mESC) linesharboring conditional microRNA transgenes. The Laboratory Animal Sciences Prog

Indoor and outdoor elemental mercury: a comparison of three different cases.

PubMed

Loupa, G; Polyzou, C; Zarogianni, A M; Ouzounis, K; Rapsomanikis, S

2017-02-01

Gaseous elemental mercury (GEM) concentrations were determined in three different indoor environments: an office in a building with no indoor sources of mercury (Bldg. I), an office affected by indoor mercury emissions from an adjacent laboratory (Bldg. II), and finally, an office where an outdoor mercury spill occurred accidentally (Bldg. III). The maximum recorded indoor GEM concentrations, with the largest variation in time, were observed in Bldg. II, with a continuous indoor mercury source (lower to upper quartile 15 to 62 ng m -3 ). The lowest values were recorded in Bldg. I (lower to upper quartile 3 to 5 ng m -3 ), where indoor GEM levels were affected mainly by the exhaust of vehicles in the parking lot of the building. The monitoring of GEM indoors (lower to upper quartile 15 to 42 ng m -3 ), and outdoors (in several heights) of the Bldg. III, revealed that the cleaning up procedure that followed the spill was not adequate. Auxiliary measurements in the first two cases were the indoor microclimatic conditions, as well as the indoor CO 2 concentrations, and in the third case the outdoor meteorological data. The exhaust of vehicles, the chemical reagents, and an outdoor mercury spill were found to mainly affect the observed indoor GEM levels. People in Bldg. II and people walking through the area, where Hg 0 was spilled, were found to be exposed to concentrations above some guide values.

From First Line to Sequential Treatment in the Management of Metastatic Pancreatic Cancer

PubMed Central

Martín, Andrés Muñoz; Hidalgo, Manuel; Alvarez, Rafael; Arrazubi, Virginia; Martínez-Galán, Joaquina; Salgado, Mercedes; Macarulla, Teresa; Carrato, Alfredo

2018-01-01

The current management of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) is based on systemic chemotherapy. The results of the MPACT and PRODIGE clinical trials have demonstrated that the combination of nab-paclitaxel and gemcitabine (GEM) as well as FOLFIRINOX regimen result in improvement in overall survival when compared to GEM alone. Treatment guidelines now recommend either one of these two regimens as first line treatment for fit patients with mPDAC. Because no head-to-head comparison between the two regimens exists, the selection of one versus the other is based on clinical criteria. The design and eligibility criteria of these two clinical trials are dissimilar, making the results of the MPACT trial more applicable to the general population of patients with mPDAC. In addition, the combination of nab-paclitaxel and GEM is better tolerated and easier to administer in clinical practice than FOLFIRINOX. Furthermore, when the regimens are studied in comparable patient populations the efficacy results are very similar. Nanoliposomal irinotecan plus 5FU has recently demonstrated a significant increase in efficacy rates after a GEM-based treatment. Importantly, treatment of mPDAC should now be considered as a continuum care for patients who are fit, with second and even third line treatments. Different sequential treatment algorithms are proposed based on available data. In retrospective studies, patients who were managed with GEM-based regimens followed by fluoropyrimidine-based regimens appear to have the most favorable outcome. PMID:29896283

Monitoring Period and Amplitude Changes in Classical Cepheids

NASA Astrophysics Data System (ADS)

Erickson, Mary; Engle, Scott; Guinan, Edward; Wells, Mark

2018-01-01

Classical Cepheids are a specific class of radially pulsating variable stars and are fundamentally important to Astronomy and Cosmology. Their pulsations can be used to determine accurate distances, both inside the Milky Way and to other galaxies throughout the Universe, via the well-studied Period-Luminosity Relationship (the Leavitt Law). This makes Cepheids “standard candles,” and they are helping Astronomers refine the expansion rate and age of the Universe.Though Cepheid pulsations were long-theorized to be completely stable, we now know that they undergo small but observable changes in their pulsation periods. The rates of the period change give us invaluable information on the Cepheids themselves, and the advent of reliable all-sky photometry surveys has allowed Cepheid pulsations to be monitored more easily than ever before.Five Cepheids were analyzed for this study – AA Gem, BB Gem, RZ Gem, AD Gem, and DX Gem. Photometric data were obtained from two sources: ASAS (the All-Sky Automated Survey) and the RCT (Robotically Controlled Telescope) at Kitt Peak National Observatory in Arizona, whose consortium Villanova is a member of. This photometry is combined with available data from the literature. The two instruments combined give a longer time span, and increased precision, from which period variations can be monitored. This gives us an excellent look at how the pulsations of these 5 Cepheids are evolving over time. The pulsation behavior of the 5 Cepheids studies will be presented, along with their calculated stellar parameters.

PHOTOMETRIC PROPERTIES OF SELECTED ALGOL-TYPE BINARIES. III. AL GEMINORUM AND BM MONOCEROTIS WITH POSSIBLE LIGHT-TIME ORBITS

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

Yang, Y.-G.; Dai, H.-F.; Li, H.-L., E-mail: yygcn@163.com

We present the CCD photometry of two Algol-type binaries, AL Gem and BM Mon, observed from 2008 November to 2011 January. With the updated Wilson-Devinney program, photometric solutions were deduced from their EA-type light curves. The mass ratios and fill-out factors of the primaries are found to be q{sub ph} = 0.090({+-} 0.005) and f{sub 1} = 47.3%({+-} 0.3%) for AL Gem, and q{sub ph} = 0.275({+-} 0.007) and f{sub 1} = 55.4%({+-} 0.5%) for BM Mon, respectively. By analyzing the O-C curves, we discovered that the periods of AL Gem and BM Mon change in a quasi-sinusoidal mode, whichmore » may possibly result from the light-time effect via the presence of a third body. Periods, amplitudes, and eccentricities of light-time orbits are 78.83({+-} 1.17) yr, 0fd0204({+-}0fd0007), and 0.28({+-} 0.02) for AL Gem and 97.78({+-} 2.67) yr, 0fd0175({+-}0fd0006), and 0.29({+-} 0.02) for BM Mon, respectively. Assumed to be in a coplanar orbit with the binary, the masses of the third bodies would be 0.29 M{sub Sun} for AL Gem and 0.26 M{sub Sun} for BM Mon. This kind of additional companion can extract angular momentum from the close binary orbit, and such processes may play an important role in multiple star evolution.« less

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.

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).

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.

Outcomes with two different schedules of bortezomib, melphalan, and prednisone (VMP) for previously untreated multiple myeloma: matched pair analysis using long-term follow-up data from the phase 3 VISTA and PETHEMA/GEM05 trials.

PubMed

Mateos, Maria-Victoria; Oriol, Albert; Martínez-López, Joaquín; Teruel, Ana-Isabel; Bengoechea, Enrique; Palomera, Luis; de Arriba, Felipe; Esseltine, Dixie-Lee; Cakana, Andrew; Pei, Lixia; van de Velde, Helgi; Miguel, Jesus San

2016-12-01

Bortezomib-melphalan-prednisone (VMP) is a standard-of-care for previously untreated, transplant-ineligible multiple myeloma (MM). Here, we compared outcomes between VMP regimens in the VISTA trial (9-cycle VMP schedule, including 4 cycles of twice weekly bortezomib) and the PETHEMA/GEM05 trial (less intensive 6-cycle VMP schedule with 1 cycle of twice weekly and 5 cycles of weekly bortezomib, then bortezomib-based maintenance). A total of 113 patient pairs matched by propensity score (estimated using logistic regression and incorporating eight exposure/outcome-related parameters) were included in this retrospective analysis. Median cumulative bortezomib dose was higher in PETHEMA/GEM05 than VISTA (49.6 vs 37.0 mg/m 2 ); median dose intensity was lower (2.0 vs 5.1 mg/m 2 /month). Median progression-free survival (PFS) and time-to-progression (TTP) were significantly longer in PETHEMA/GEM05 than VISTA (PFS, 30.5 vs 20.0 months, p = 0.0265; TTP, 33.8 vs 24.2 months, p = 0.0049) after a median follow-up of 77.2 and 26.0 months, respectively. Median overall survival (OS) was similar (61.3 vs 61.0 months, p = 0.6528; median follow-up, 77.6 vs 60.1 months). Post-induction complete response rate was lower in PETHEMA/GEM05 than VISTA (19 vs 31 %; p = 0.03318); on-study (including maintenance) rate was similar (30 vs 31 %; p = 0.89437). This analysis suggests that the less-intensive PETHEMA/GEM05 VMP regimen plus maintenance may improve PFS and TTP, but not OS, compared with the VISTA VMP regimen. NCT00111319, NCT00443235.

Effect of the lipid regulator Gemfibrozil in the Cladocera Daphnia magna at different temperatures.

PubMed

Salesa, Beatriz; Ferrando, María D; Villarroel, María J; Sancho, Encarna

2017-02-23

In the present study, an ecotoxicological approach to the evaluation of Gemfibrozil (GEM) as an emerging organic pollutant was done. In order to assess its toxicity, tests were conducted using the cladocera Daphnia magna. Experiments were carried out at 22°C and 28°C. EC 50 , feeding behavior, and chronic toxicity tests (21 days) were evaluated in D. magna exposed to GEM as well as cholesterol levels at 21-day chronic exposure. D. magna GEM EC 50 values (24 h) in our experimental conditions were 148.75 and 116.24 mg L -1 at 22°C and 28°C, respectively. Test concentrations of 0.1, 0.5, 1.0, 5.0 and 7.5 mg L -1 were selected for subacute and chronic experiments. Subacute short-term test (feeding study) was assessed after exposure to the toxicant. Filtration and ingestion rates of D. magna exposed animals did not show any significant difference (P > 0.05) with respect to control daphniids neither at 22°C nor at 28°C. Therefore, GEM test concentrations used in the present study did not reduce feeding behavior in D. magna. Temperature increased from 22°C to 28°C, which resulted in a decrease of the daphniids reproductive parameters such as brood size and number of young per female. Other parameters as longevity were not affected. The GEM concentrations used in the chronic test with D. magna did not affect daphniids longevity but some reproductive parameters as number of young per female or brood size were affected. Finally, a significant decreased in cholesterol levels was found in those animals exposed to the highest toxicant concentrations. More studies must be done to determine the possible implications of GEM in aquatic fauna and to derive its possible effects on the environment.

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.

Palatogenesis

PubMed Central

Levi, Benjamin; Brugman, Samantha; Wong, Victor W; Grova, Monica; Longaker, Michael T

2011-01-01

Cleft palate represents the second most common birth defect and carries substantial physiologic and social challenges for affected patients, as they often require multiple surgical interventions during their lifetime. A number of genes have been identified to be associated with the cleft palate phenotype, but etiology in the majority of cases remains elusive. In order to better understand cleft palate and both surgical and potential tissue engineering approaches for repair, we have performed an in-depth literature review into cleft palate development in humans and mice, as well as into molecular pathways underlying these pathologic developments. We summarize the multitude of pathways underlying cleft palate development, with the transforming growth factor β superfamily being the most commonly studied. Furthermore, while the majority of cleft palate studies are performed using a mouse model, studies focusing on tissue engineering have also focused heavily on mouse models. A paucity of human randomized controlled studies exists for cleft palate repair, and so far, tissue engineering approaches are limited. In this review, we discuss the development of the palate, explain the basic science behind normal and pathologic palate development in humans as well as mouse models and elaborate on how these studies may lead to future advances in palatal tissue engineering and cleft palate treatments. PMID:21964245

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.

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.

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.

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.

A tissue-engineered subcutaneous pancreatic cancer model for antitumor drug evaluation.

PubMed

He, Qingyi; Wang, Xiaohui; Zhang, Xing; Han, Huifang; Han, Baosan; Xu, Jianzhong; Tang, Kanglai; Fu, Zhiren; Yin, Hao

2013-01-01

The traditional xenograft subcutaneous pancreatic cancer model is notorious for its low incidence of tumor formation, inconsistent results for the chemotherapeutic effects of drug molecules of interest, and a poor predictive capability for the clinical efficacy of novel drugs. These drawbacks are attributed to a variety of factors, including inoculation of heterogeneous tumor cells from patients with different pathological histories, and use of poorly defined Matrigel(®). In this study, we aimed to tissue-engineer a pancreatic cancer model that could readily cultivate a pancreatic tumor derived from highly homogenous CD24(+)CD44(+) pancreatic cancer stem cells delivered by a well defined electrospun scaffold of poly(glycolide-co-trimethylene carbonate) and gelatin. The scaffold supported in vitro tumorigenesis from CD24(+)CD44(+) cancer stem cells for up to 7 days without inducing apoptosis. Moreover, CD24(+)CD44(+) cancer stem cells delivered by the scaffold grew into a native-like mature pancreatic tumor within 8 weeks in vivo and exhibited accelerated tumorigenesis as well as a higher incidence of tumor formation than the traditional model. In the scaffold model, we discovered that oxaliplatin-gemcitabine (OXA-GEM), a chemotherapeutic regimen, induced tumor regression whereas gemcitabine alone only capped tumor growth. The mechanistic study attributed the superior antitumorigenic performance of OXA-GEM to its ability to induce apoptosis of CD24(+)CD44(+) cancer stem cells. Compared with the traditional model, the scaffold model demonstrated a higher incidence of tumor formation and accelerated tumor growth. Use of a tiny population of highly homogenous CD24(+)CD44(+) cancer stem cells delivered by a well defined scaffold greatly reduces the variability associated with the traditional model, which uses a heterogeneous tumor cell population and poorly defined Matrigel. The scaffold model is a robust platform for investigating the antitumorigenesis mechanism of novel chemotherapeutic drugs with a special focus on cancer stem cells.

Introducing parallelism to histogramming functions for GEM systems

NASA Astrophysics Data System (ADS)

Krawczyk, Rafał D.; Czarski, Tomasz; Kolasinski, Piotr; Pozniak, Krzysztof T.; Linczuk, Maciej; Byszuk, Adrian; Chernyshova, Maryna; Juszczyk, Bartlomiej; Kasprowicz, Grzegorz; Wojenski, Andrzej; Zabolotny, Wojciech

2015-09-01

This article is an assessment of potential parallelization of histogramming algorithms in GEM detector system. Histogramming and preprocessing algorithms in MATLAB were analyzed with regard to adding parallelism. Preliminary implementation of parallel strip histogramming resulted in speedup. Analysis of algorithms parallelizability is presented. Overview of potential hardware and software support to implement parallel algorithm is discussed.

On algorithmic optimization of histogramming functions for GEM systems

NASA Astrophysics Data System (ADS)

Krawczyk, Rafał D.; Czarski, Tomasz; Kolasinski, Piotr; Poźniak, Krzysztof T.; Linczuk, Maciej; Byszuk, Adrian; Chernyshova, Maryna; Juszczyk, Bartlomiej; Kasprowicz, Grzegorz; Wojenski, Andrzej; Zabolotny, Wojciech

2015-09-01

This article concerns optimization methods for data analysis for the X-ray GEM detector system. The offline analysis of collected samples was optimized for MATLAB computations. Compiled functions in C language were used with MEX library. Significant speedup was received for both ordering-preprocessing and for histogramming of samples. Utilized techniques with obtained results are presented.

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…

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)…

Difluoromethyl 2-pyridyl sulfone: a new gem-difluoroolefination reagent for aldehydes and ketones.

PubMed

Zhao, Yanchuan; Huang, Weizhou; Zhu, Lingui; Hu, Jinbo

2010-04-02

Difluoromethyl 2-pyridyl sulfone, a previously unknown compound, was found to act as a novel and efficient gem-difluoroolefination reagent for both aldehydes and ketones. It was found that the fluorinated sulfinate intermediate in the reaction is relatively stable, which can be observed by (19)F NMR and trapped with CH(3)I.

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.

Gallium Electromagnetic (GEM) Thrustor Concept and Design

NASA Technical Reports Server (NTRS)

Polzin, Kurt A.; Markusic, Thomas E.

2006-01-01

We describe the design of a new type of two-stage pulsed electromagnetic accelerator, the gallium electromagnetic (GEM) thruster. A schematic illustration of the GEM thruster concept is given in Fig. 1. In this concept, liquid gallium propellant is pumped into the first stage through a porous metal electrode using an electromagneticpump[l]. At a designated time, a pulsed discharge (approx.10-50 J) is initiated in the first stage, ablating the liquid gallium from the porous electrode surface and ejecting a dense thermal gallium plasma into the second state. The presence of the gallium plasma in the second stage serves to trigger the high-energy (approx.500 I), send-stage puke which provides the primary electromagnetic (j x B) acceleration.

Revisiting the case for genetically engineered mouse models in human myelodysplastic syndrome research.

PubMed

Zhou, Ting; Kinney, Marsha C; Scott, Linda M; Zinkel, Sandra S; Rebel, Vivienne I

2015-08-27

Much-needed attention has been given of late to diseases specifically associated with an expanding elderly population. Myelodysplastic syndrome (MDS), a hematopoietic stem cell-based blood disease, is one of these. The lack of clear understanding of the molecular mechanisms underlying the pathogenesis of this disease has hampered the development of efficacious therapies, especially in the presence of comorbidities. Mouse models could potentially provide new insights into this disease, although primary human MDS cells grow poorly in xenografted mice. This makes genetically engineered murine models a more attractive proposition, although this approach is not without complications. In particular, it is unclear if or how myelodysplasia (abnormal blood cell morphology), a key MDS feature in humans, presents in murine cells. Here, we evaluate the histopathologic features of wild-type mice and 23 mouse models with verified myelodysplasia. We find that certain features indicative of myelodysplasia in humans, such as Howell-Jolly bodies and low neutrophilic granularity, are commonplace in healthy mice, whereas other features are similarly abnormal in humans and mice. Quantitative hematopoietic parameters, such as blood cell counts, are required to distinguish between MDS and related diseases. We provide data that mouse models of MDS can be genetically engineered and faithfully recapitulate human disease. © 2015 by The American Society of Hematology.

Sequences in Influenza A Virus PB2 Protein That Determine Productive Infection for an Avian Influenza Virus in Mouse and Human Cell Lines

PubMed Central

Yao, Yongxiu; Mingay, Louise J.; McCauley, John W.; Barclay, Wendy S.

2001-01-01

Reverse genetics was used to analyze the host range of two avian influenza viruses which differ in their ability to replicate in mouse and human cells in culture. Engineered viruses carrying sequences encoding amino acids 362 to 581 of PB2 from a host range variant productively infect mouse and human cells. PMID:11333926

Genetically Engineered Mouse Models of Pituitary Tumors

PubMed Central

Cano, David A.; Soto-Moreno, Alfonso; Leal-Cerro, Alfonso

2014-01-01

Animal models constitute valuable tools for investigating the pathogenesis of cancer as well as for preclinical testing of novel therapeutics approaches. However, the pathogenic mechanisms of pituitary-tumor formation remain poorly understood, particularly in sporadic adenomas, thus, making it a challenge to model pituitary tumors in mice. Nevertheless, genetically engineered mouse models (GEMMs) of pituitary tumors have provided important insight into pituitary tumor biology. In this paper, we review various GEMMs of pituitary tumors, highlighting their contributions and limitations, and discuss opportunities for research in the field. PMID:25136513

The GEM Global Active Faults Database: The growth and synthesis of a worldwide database of active structures for PSHA, research, and education

NASA Astrophysics Data System (ADS)

Styron, R. H.; Garcia, J.; Pagani, M.

2017-12-01

A global catalog of active faults is a resource of value to a wide swath of the geoscience, earthquake engineering, and hazards risk communities. Though construction of such a dataset has been attempted now and again through the past few decades, success has been elusive. The Global Earthquake Model (GEM) Foundation has been working on this problem, as a fundamental step in its goal of making a global seismic hazard model. Progress on the assembly of the database is rapid, with the concatenation of many national—, orogen—, and continental—scale datasets produced by different research groups throughout the years. However, substantial data gaps exist throughout much of the deforming world, requiring new mapping based on existing publications as well as consideration of seismicity, geodesy and remote sensing data. Thus far, new fault datasets have been created for the Caribbean and Central America, North Africa, and northeastern Asia, with Madagascar, Canada and a few other regions in the queue. The second major task, as formidable as the initial data concatenation, is the 'harmonization' of data. This entails the removal or recombination of duplicated structures, reconciliation of contrastinginterpretations in areas of overlap, and the synthesis of many different types of attributes or metadata into a consistent whole. In a project of this scale, the methods used in the database construction are as critical to project success as the data themselves. After some experimentation, we have settled on an iterative methodology that involves rapid accumulation of data followed by successive episodes of data revision, and a computer-scripted data assembly using GIS file formats that is flexible, reproducible, and as able as possible to cope with updates to the constituent datasets. We find that this approach of initially maximizing coverage and then increasing resolution is the most robust to regional data problems and the most amenable to continued updates and refinement. Combined with the public, open-source nature of this project, GEM is producing a resource that can continue to evolve with the changing knowledge and needs of the community.

100+ years of instrumental seismology: the example of the ISC-GEM Global Earthquake Instrumental Catalogue

NASA Astrophysics Data System (ADS)

Storchak, Dmitry; Di Giacomo, Domenico

2015-04-01

Systematic seismological observations of earthquakes using seismic instruments on a global scale began more than 100 years ago. Since then seismologists made many discoveries about the Earth interior and the physics of the earthquakes, also thanks to major developments in the seismic instrumentation deployed around the world. Besides, since the establishment of the first global networks (Milne and Jesuit networks), seismologists around the world stored and exchanged the results of routine observations (e.g., picking of arrival times, amplitude-period measurements, etc.) or more sophisticated analyses (e.g., moment tensor inversion) in seismological bulletins/catalogues. With a project funded by the GEM Foundation (www.globalquakemodel.org), the ISC and the Team of International Experts released a new global earthquake catalogue, the ISC-GEM Global Instrumental Earthquake Catalogue (1900 2009) (www.isc.ac.uk/iscgem/index.php), which, differently from previous global seismic catalogues, has the unique feature of covering the entire period of instrumental seismology with locations and magnitude re-assessed using modern approaches for the global earthquakes selected for processing (in the current version approximately 21,000). During the 110 years covered by the ISC-GEM catalogue many seismological developments occurred in terms of instrumentation, seismological practice and knowledge of the physics of the earthquakes. In this contribution we give a brief overview of the major milestones characterizing the last 100+ years of instrumental seismology that were relevant for the production of the ISC-GEM catalogue and the major challenges we faced to obtain a catalogue as homogenous as possible.

Study of the spatial resolution of low-material GEM tracking detectors

NASA Astrophysics Data System (ADS)

Kudryavtsev, V. N.; Maltsev, T. V.; Shekhtman, L. I.

2018-02-01

The spatial resolution of GEM based tracking detectors has been simulated and measured. The simulation includes the GEANT4 based transport of high energy electrons with careful accounting for atomic relaxation processes including emission of fluorescent photons and Auger electrons and custom post-processing, including accounting for diffusion, gas amplification fluctuations, the distribution of signals on readout electrodes, electronics noise and a particular algorithm of the final coordinate calculation (center of gravity). The simulation demonstrates that a minimum of the spatial resolution of about 10 μm can be achieved with strip pitches from 250 μm to 300 μm. For larger pitches the resolution is quickly degrading reaching 80-100 μm at a pitch of 500 μm. The spatial resolution of low-material triple-GEM detectors for the DEUTRON facility at the VEPP-3 storage ring is measured at the extracted beam facility of the VEPP-4M collider. The amount of material in these detectors is reduced by etching the copper of the GEMs electrodes and using a readout structure on a thin kapton foil rather than on a glass fibre plate. The exact amount of material in one DEUTRON detector is measured by studying multiple scattering of 100 MeV electrons in it. The result of these measurements is X/X0 = 2.4×10-3 corresponding to a thickness of the copper layers of the GEM foils of 3 μm. The spatial resolution of one DEUTRON detector is measured with 500 MeV electrons and the measured value is equal to 35 ± 1 μm for orthogonal tracks.

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.

Variation in concentrations of three mercury (Hg) forms at a rural and a suburban site in New York State.

PubMed

Choi, Hyun-Deok; Huang, Jiaoyan; Mondal, Sumona; Holsen, Thomas M

2013-03-15

Tekran® Hg speciation systems were used at a rural site (Huntington Forest, NY; HF) and a suburban site (Rochester, NY; ROC) to measure gaseous elemental mercury (GEM), gaseous oxidized mercury (GOM), and fine particulate-bound mercury (PBM2.5) concentrations for two years (December 2007 to November 2009). Ancillary data were also available from the New York State Department of Environmental Conservation and the United States Environmental Protection Agency Clean Air Status and Trends Network. Seasonal GEM concentrations were similar at both sites and influenced by factors such as the planet boundary layer (PBL) height and mercury emissions from snow, soil, and point sources. In some seasons, O3 was negatively correlated with GEM at ROC and positively correlated with GEM at HF. At HF, O3 was correlated with GOM and was typically higher in the afternoon. The cause of this pattern may be photochemical reactions during the day, and the GOM diel pattern may also be due to deposition which is enhanced by dew formation during the night and early morning. PBM2.5 concentrations were higher in winter at both sites. This is indicative of local wood combustion for space heating in winter, increased sorption to particles at lower temperatures, and lower PBL in the winter. At the suburban site, 2 of 12 events with enhanced GEM/CO ratios were poorly correlated with SO2/GOM, implying that these two events were due either to long range transport or regional metallurgical industries in Canada. Copyright © 2012 Elsevier B.V. All rights reserved.

New Mouse Model May Aid in Developing Effective Therapies for Ovarian Cancer | Poster

Cancer.gov

By Frank Blanchard, Staff Writer A new genetically engineered mouse model appears promising as an effective tool for preclinical testing of novel therapies for ovarian cancer, which tends to be diagnosed in late stage. There are few effective treatments for the disease.

MYST: a comprehensive high-level AO control tool for GeMS

NASA Astrophysics Data System (ADS)

Rigaut, F.; Neichel, B.; Bec, M.; Garcia-Rissman, A.

2010-07-01

Myst is the Gemini MCAO System (GeMS) high level control GUI. It is written in yorick, python and C. In this paper, we review the software architecture of Myst and its primary purposes, which are many: Real-time display, high level diagnostics, calibrations, and executor/sequencer of high level actions (closing the loop, coordinating dithers, etc).

High School Students' Experience with Near-Peer Mentorship and Laboratory-Based Learning: In Their Own Words

ERIC Educational Resources Information Center

Tenenbaum, Laura S.; Anderson, Margery; Ramadorai, Swati B.; Yourick, Debra L.

2017-01-01

The Walter Reed Army Institute of Research established the Gains in the Education of Mathematics and Science (GEMS) program to serve communities in the National Capitol Area (Anderson, Tenenbaum, Ramadorai, & Yourick, 2015). The GEMS program was founded on four key elements to provide opportunities to primarily middle and high school students…

Ultrasound-enhanced nanotherapy of pancreatic cancer

NASA Astrophysics Data System (ADS)

Rapoport, N.; Nam, K.-H.; Christensen, D. A.; Kennedy, A. M.; Shea, J. E.; Scaife, C. L.

2010-03-01

The paper reports in vivo results of ultrasonic nanotherapy of orthotopically grown pancreatic cancer. Phase-shift paclitaxel (PTX) loaded perfluoropentane (PFP) nanoemusions combined with tumor-directed ultrasound have been used with a considerable success for tumor-targeted chemotherapy of gemcitabin (GEM)-refractory pancreatic cancer (PC). The GEM-resistant pancreatic cancer proved sensitive to treatment by a micellar PTX formulation Genexol PM (GEN) andor nanodroplet PTX formulation ndGEN. Due to increased permeability of tumor blood vessels, drug-loaded nanodroplets accumulated in the tumor via passive targeting, which was confirmed by ultrasound imaging. Nanodroplets converted into microbubbles in situ under the action of tumor-directed 1-MHz therapeutic ultrasound. The strongest therapeutic effect was observed for the combination therapy by PTX-loaded nanodroplets, GEM and ultrasound (ndGEN+GEM+ultrasound). This combination therapy resulted in a spectacular tumor regression and in some cases complete tumor resolution. Moreover, formation of metastases was dramatically decreased and ascitis generation was completely suppressed. However for all animal groups, local tumor recurrence was observed after the completion of the treatment indicating that some cancer cells survived the treatment. The recurrent tumors proved more resistant to the repeated therapy than initial tumors.

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.

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

A GEM-TPC in twin configuration for the Super-FRS tracking of heavy ions at FAIR

NASA Astrophysics Data System (ADS)

García, F.; Grahn, T.; Hoffmann, J.; Jokinen, A.; Kaya, C.; Kunkel, J.; Rinta-Antila, S.; Risch, H.; Rusanov, I.; Schmidt, C. J.; Simon, H.; Simons, C.; Turpeinen, R.; Voss, B.; Äystö, J.; Winkler, M.

2018-03-01

The GEM-TPC described herein will be part of the standard beam-diagnostics equipment of the Super-FRS. This chamber will provide tracking information for particle identification at rates up to 1 MHz on an event-by-event basis. The key requirements of operation for these chambers are: close to 100% tracking efficiency under conditions of high counting rate, spatial resolution below 1 mm and a superb large dynamic range covering projectiles from Z = 1 up to Z = 92. The current prototype consists of two GEM-TPCs inside a single vessel, which are operating independently and have electrical drift fields in opposite directions. The twin configuration is done by flipping one of the GEM-TPCs on the middle plane with respect to the second one. In order to put this development in context, the evolution of previous prototypes will be described and its performances discussed. Finally, this chamber was tested at the University of Jyväskylä accelerator with proton projectiles and at GSI with Uranium, Xenon, fragments and Carbon beams. The results obtained have shown a position resolution between 120 to 300 μm at moderate counting rate under conditions of full tracking efficiency.

Variation of mineralogy and organic material during the early stages of aqueous activity recorded in Antarctic micrometeorites

NASA Astrophysics Data System (ADS)

Noguchi, T.; Yabuta, H.; Itoh, S.; Sakamoto, N.; Mitsunari, T.; Okubo, A.; Okazaki, R.; Nakamura, T.; Tachibana, S.; Terada, K.; Ebihara, M.; Imae, N.; Kimura, M.; Nagahara, H.

2017-07-01

Micrometeorites (MMs) recovered from surface snow near the Dome Fuji Station, Antarctica are almost free from terrestrial weathering and contain very primitive materials, and are suitable for investigation of the evolution and interaction of inorganic and organic materials in the early solar system. We carried out a comprehensive study on seven porous and fluffy MMs [four Chondritic porous (CP) MMs and three fluffy fine-grained (Fluffy Fg) MMs] and one fine-grained type 1 (Fg C1) MM for comparison with scanning electron microscope, transmission electron microscope, X-ray absorption near-edge structure analysis, and secondary ion mass spectrometer. They show a variety of early aqueous activities. Four out of the seven CP MMs contain glass with embedded metal and sulfide (GEMS) and enstatite whiskers/platelets and do not have hydrated minerals. Despite the same mineralogy, organic chemistry of the CP MMs shows diversity. Two of them contain considerable amounts of organic materials with high carboxyl functionality, and one of them contains nitrile (Ctbnd N) and/or nitrogen heterocyclic groups with D and 15N enrichments, suggesting formation in the molecular cloud or a very low temperature region of the outer solar system. Another two CP MMs are poorer in organic materials than the above-mentioned MMs. Organic material in one of them is richer in aromatic C than the CP MMs mentioned above, being indistinguishable from those of hydrated carbonaceous chondrites. In addition, bulk chemical compositions of GEMS in the latter organic poor CP MMs are more homogeneous and have higher Fe/(Si + Mg + Fe) ratios than those of GEMS in the former organic-rich CP MMs. Functional group of the organic materials and amorphous silicate in GEMS in the organic-poor CP MMs may have transformed in the earliest stage of aqueous alteration, which did not form hydrated minerals. Three Fluffy Fg MMs contain abundant phyllosilicates, showing a clear evidence of aqueous alteration. Phyllosilicates in thee MMs are richer in Fe than those in hydrated IDPs, typical fine-grained hydrated (Fg C1) MMs, and hydrated carbonaceous chondrites. One of the Fluffy Fg MMs contains amorphous silicate, which is richer in Fe than GEMS and contains little or no nanophase Fe metal but contains Fe sulfide. Because the chemical compositions of the amorphous silicate are within the compositional field of GEMS in CP IDPs, the amorphous silicate may be alteration products of GEMS. The entire compositional field of GEMS in the CP MMs and the amorphous silicate in the Fluffy Fg MM matches that of the previously reported total compositional range of GEMS in IDPs. One Fluffy Fg MM contains Mg-rich phyllosilicate along with Fe-rich phyllosilicate and Mg-Fe carbonate. Mg-rich phyllosilicate and Mg-Fe carbonate may have been formed through the reaction of Fe-rich phyllosilicate, Mg-rich olivine and pyroxene, and water with C-bearing chemical species. These data indicate that CP MMs and Fluffy Fg MMs recovered from Antarctic surface snow contain materials that throw a light on the earliest stages of aqueous alteration on very primitive solar system bodies. Because mineralogy and isotopic and structural features of organic materials in D10IB009 are comparable with isotopically primitive IDPs, its parent body could be comets or icy asteroids showing mass ejection (active asteroids). By contrast, organic-poor CP MMs may have experienced the earliest stage of aqueous alteration and Fluffy Fg MMs experienced weak aqueous alteration. The precursor materials of the parent bodies of Fluffy Fg MMs probably contained abundant GEMS or GEMS-like materials like CP IDPs, which is common to fine-grained matrices of very primitive carbonaceous chondrites such as CR3s. However, highly porous nature of organic-poor CP MMs and Fluffy Fg MMs suggests that parent bodies of these MMs must have been much more porous than the parent bodies of primitive carbonaceous chondrites. Given no phyllosilicate among the returned samples of 81P/Wild 2 comet, the MMs may have been derived from porous icy asteroids such as active asteroids as well as P- and D-type asteroids rather than comets.

TRAF4 and Castration Resistant Prostate Cancer

DTIC Science & Technology

2016-10-01

Generation of TRAF4 mouse This minigene was then inserted into the Rosa 26 locus in the mouse embryonic stem cells. After embryo injection, we...were delayed in the Major Task 3 subtask 2 and 3. The problem was we did not get germline transmission after embryo injection. The embryo injection...was performed in the Genetically Engineered Mouse Core at Baylor College of Medicine. Similar problem was also reported with other PIs’ embryo

Fast modular data acquisition system for GEM-2D detector

NASA Astrophysics Data System (ADS)

Kasprowicz, G.; Byszuk, Adrian; Wojeński, A.; Zienkiewicz, P.; Czarski, T.; Chernyshova, M.; Poźniak, K.; Rzadkiewicz, J.; Zabolotny, W.; Juszczyk, B.

2014-11-01

A novel approach to two dimensional Gas Electron Multiplier (GEM) detector readout is presented. Unlike commonly used methods, based on discriminators and analogue FIFOs, the method developed uses simulta- neously sampling high speed ADCs with fast hybrid integrator and advanced FPGA-based processing logic to estimate the energy of every single photon. Such a method is applied to every GEM strip / pixel signal. It is especially useful in case of crystal-based spectrometers for soft X-rays, 2D imaging for plasma tomography and all these applications where energy resolution of every single photon is required. For the purpose of the detector readout, a novel, highly modular and extendable conception of the measurement platform was developed. It is evolution of already deployed measurement system for JET Spectrometer.

GEM detector development for tokamak plasma radiation diagnostics: SXR poloidal tomography

NASA Astrophysics Data System (ADS)

Chernyshova, Maryna; Malinowski, Karol; Ziółkowski, Adam; Kowalska-Strzeciwilk, Ewa; Czarski, Tomasz; Poźniak, Krzysztof T.; Kasprowicz, Grzegorz; Zabołotny, Wojciech; Wojeński, Andrzej; Kolasiński, Piotr; Krawczyk, Rafał D.

2015-09-01

An increased attention to tungsten material is related to a fact that it became a main candidate for the plasma facing material in ITER and future fusion reactor. The proposed work refers to the studies of W influence on the plasma performances by developing new detectors based on Gas Electron Multiplier GEM) technology for tomographic studies of tungsten transport in ITER-oriented tokamaks, e.g. WEST project. It presents current stage of design and developing of cylindrically bent SXR GEM detector construction for horizontal port implementation. Concept to overcome an influence of constraints on vertical port has been also presented. It is expected that the detecting unit under development, when implemented, will add to the safe operation of tokamak bringing creation of sustainable nuclear fusion reactors a step closer.

The KLOE-2 Inner Tracker: Detector commissioning and operation

NASA Astrophysics Data System (ADS)

Balla, A.; Bencivenni, G.; Branchini, P.; Ciambrone, P.; Czerwinski, E.; De Lucia, E.; Cicco, A.; Di Domenici, D.; Felici, G.; Morello, G.

2017-02-01

The KLOE-2 experiment started its data taking campaign in November 2014 with an upgraded tracking system including an Inner Tracker built with the cylindrical GEM technology, to operate together with the Drift Chamber improving the apparatus tracking performance. The Inner Tracker is composed of four cylindrical triple-GEM, each provided with an X-V strips-pads stereo readout and equipped with the GASTONE ASIC developed inside the KLOE-2 collaboration. Although GEM detectors are already used in high energy physics experiment, this device is considered a frontier detector due to its cylindrical geometry: KLOE-2 is the first experiment to use this novel solution. The results of the detector commissioning, detection efficiency evaluation, calibration studies and alignment, both with dedicated cosmic-ray muon and Bhabha scattering events, will be reported.

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.

Setting the Stage for Harmonized Risk Assessment by Seismic Hazard Harmonization in Europe (SHARE)

NASA Astrophysics Data System (ADS)

Woessner, Jochen; Giardini, Domenico; SHARE Consortium

2010-05-01

Probabilistic seismic hazard assessment (PSHA) is arguably one of the most useful products that seismology can offer to society. PSHA characterizes the best available knowledge on the seismic hazard of a study area, ideally taking into account all sources of uncertainty. Results form the baseline for informed decision making, such as building codes or insurance rates and provide essential input to each risk assessment application. Several large scale national and international projects have recently been launched aimed at improving and harmonizing PSHA standards around the globe. SHARE (www.share-eu.org) is the European Commission funded project in the Framework Programme 7 (FP-7) that will create an updated, living seismic hazard model for the Euro-Mediterranean region. SHARE is a regional component of the Global Earthquake Model (GEM, www.globalquakemodel.org), a public/private partnership initiated and approved by the Global Science Forum of the OECD-GSF. GEM aims to be the uniform, independent and open access standard to calculate and communicate earthquake hazard and risk worldwide. SHARE itself will deliver measurable progress in all steps leading to a harmonized assessment of seismic hazard - in the definition of engineering requirements, in the collection of input data, in procedures for hazard assessment, and in engineering applications. SHARE scientists will create a unified framework and computational infrastructure for seismic hazard assessment and produce an integrated European probabilistic seismic hazard assessment (PSHA) model and specific scenario based modeling tools. The results will deliver long-lasting structural impact in areas of societal and economic relevance, they will serve as reference for the Eurocode 8 (EC8) application, and will provide homogeneous input for the correct seismic safety assessment for critical industry, such as the energy infrastructures and the re-insurance sector. SHARE will cover the whole European territory, the Maghreb countries in the Southern Mediterranean and Turkey in the Eastern Mediterranean. By strongly including the seismic engineering community, the project maintains a direct connection to the Eurocode 8 applications and the definition of the Nationally Determined Parameters, through the participation of the CEN/TC250/SC8 committee in the definition of the output specification requirements and in the hazard validation. SHARE will thus produce direct outputs for risk assessment. With this contribution, we focus on providing an overview of the goals and current achievement of the project.

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.

The Impact of Vodcast Utilisation upon Student Learning of Physiology by First Year Graduate to Entry Medicine Students

ERIC Educational Resources Information Center

Rae, Mark G.; McCarthy, Marion

2017-01-01

The current study sought to determine the effectiveness of video-on-demand podcasts (vodcasts) as a tool for facilitating the understanding of Physiology by first year undergraduate Graduate Entry to Medicine (GEM 1) students. Seventy-three GEM 1 students were provided with full length vodcasts of lecture material in advance of each of nine…

Einstein observations of three classical Cepheids

NASA Technical Reports Server (NTRS)

Bohm-Vitense, E.; Parsons, S. B.

1983-01-01

We have looked for X-ray emission from the classical Cepheids delta Cep, beta Dor, and zeta Gem during phases when the latter two stars show emission in low excitation chromospheric lines. No X-ray flux was detected except possibly from zeta Gem at phase 0.26. Derived upper limits are in line with emission flux or upper limits obtained for other F and G supergiants.

Early Action on the Global Environmental Monitoring System. A Report of the International Environmental Programs Committee.

ERIC Educational Resources Information Center

National Academy of Sciences - National Research Council, Washington, DC. Environmental Studies Board.

The Global Environmental Monitoring System (GEMS) is one of four components of Earthwatch, a part of the United Nations Environment Program (UNEP). The purpose of GEMS is to provide early warning of impending natural or man-induced environmental changes or trends that threaten direct or indirect harm to human health or well-being. In 1975, the…

A large ungated TPC with GEM amplification

NASA Astrophysics Data System (ADS)

Berger, M.; Ball, M.; Fabbietti, L.; Ketzer, B.; Arora, R.; Beck, R.; Böhmer, F. V.; Chen, J.-C.; Cusanno, F.; Dørheim, S.; García, F.; Hehner, J.; Herrmann, N.; Höppner, C.; Kaiser, D.; Kis̆, M.; Kleipa, V.; Konorov, I.; Kunkel, J.; Kurz, N.; Leifels, Y.; Müllner, P.; Münzer, R.; Neubert, S.; Rauch, J.; Schmidt, C. J.; Schmitz, R.; Soyk, D.; Vandenbroucke, M.; Voss, B.; Walther, D.; Zmeskal, J.

2017-10-01

A Time Projection Chamber (TPC) is an ideal device for the detection of charged particle tracks in a large volume covering a solid angle of almost 4 π. The high density of hits on a given particle track facilitates the task of pattern recognition in a high-occupancy environment and in addition provides particle identification by measuring the specific energy loss for each track. For these reasons, TPCs with Multiwire Proportional Chamber (MWPC) amplification have been and are widely used in experiments recording heavy-ion collisions. A significant drawback, however, is the large dead time of the order of 1 ms per event generated by the use of a gating grid, which is mandatory to prevent ions created in the amplification region from drifting back into the drift volume, where they would severely distort the drift path of subsequent tracks. For experiments with higher event rates this concept of a conventional TPC operating with a triggered gating grid can therefore not be applied without a significant loss of data. A continuous readout of the signals is the more appropriate way of operation. This, however, constitutes a change of paradigm with considerable challenges to be met concerning the amplification region, the design and bandwidth of the readout electronics, and the data handling. A mandatory prerequisite for such an operation is a sufficiently good suppression of the ion backflow from the avalanche region, which otherwise limits the tracking and particle identification capabilities of such a detector. Gas Electron Multipliers (GEM) are a promising candidate to combine excellent spatial resolution with an intrinsic suppression of ions. In this paper we describe the design, construction and the commissioning of a large TPC with GEM amplification and without gating grid (GEM-TPC). The design requirements have driven innovations in the construction of a light-weight field-cage, a supporting media flange, the GEM amplification and the readout system, which are presented in this paper. We further describe the support infrastructure such as gas, cooling and slow control. Finally, we report on the operation of the GEM-TPC in the FOPI experiment, and describe the calibration procedures which are applied to achieve the design performance of the device.

High levels of reactive gaseous mercury observed at a high elevation research laboratory in the Rocky Mountains

NASA Astrophysics Data System (ADS)

Faïn, X.; Obrist, D.; Hallar, A. G.; McCubbin, I.; Rahn, T.

2009-10-01

The chemical cycling and spatiotemporal distribution of mercury in the troposphere is poorly understood. We measured gaseous elemental mercury (GEM), reactive gaseous mercury (RGM) and particulate mercury (HgP) along with carbon monoxide (CO), ozone (O3), aerosols, and meteorological variables at Storm Peak Laboratory at an elevation of 3200 m a.s.l., in Colorado, from 28 April to 1 July 2008. The mean mercury concentrations were 1.6 ng m-3 (GEM), 20 pg m-3 (RGM) and 9 pg m-3 (HgP). We observed eight events of strongly enhanced atmospheric RGM levels with maximum concentrations up to 137 pg m-3. RGM enhancement events lasted for long time periods of 2 to 6 days showing both enriched level during daytime and nighttime when other tracers (e.g., aerosols) showed different representations of boundary layer air and free tropospheric air. During seven of these events, RGM was inversely correlated to GEM (RGM/GEM regression slope ~-0.1), but did not exhibit correlations with ozone, carbon monoxide, or aerosol concentrations. Relative humidity was the dominant factor affecting RGM levels with high RGM levels always present whenever relative humidity was below 40 to 50%. We conclude that RGM enhancements observed at Storm Peak Laboratory were not induced by pollution events and were related to oxidation of tropospheric GEM. High RGM levels were not limited to upper tropospheric or stratospherically influenced air masses, indicating that entrainment processes and deep vertical mixing of free tropospheric air enriched in RGM may lead to high RGM levels throughout the troposphere and into the boundary layer over the Western United States. Based on backtrajectory analysis and a lack of mass balance between RGM and GEM, atmospheric production of RGM may also have occurred in some distance allowing for scavenging and/or deposition of RGM prior to reaching the laboratory. Our observations provide evidence that the tropospheric pool of mercury is frequently enriched in divalent mercury, that high RGM levels are not limited to upper tropospheric air masses, but that the build-up of high RGM in the troposphere is limited to the presence of dry air.

Logistics of air medical transport: When and where does helicopter transport reduce prehospital time for trauma?

PubMed

Chen, Xilin; Gestring, Mark L; Rosengart, Matthew R; Peitzman, Andrew B; Billiar, Timothy R; Sperry, Jason L; Brown, Joshua B

2018-05-04

Trauma is a time sensitive disease. Helicopter emergency medical services (HEMS) have shown benefit over ground EMS (GEMS), which may be related to reduced prehospital time. The distance at which this time benefit emerges depends on many factors that can vary across regions. Our objective was to determine the threshold distance at which HEMS has shorter prehospital time than GEMS under different conditions. Patients in the PA trauma registry 2000-2013 were included. Distance between zip centroid and trauma center was calculated using straight-line distance for HEMS and driving distance from GIS network analysis for GEMS. Contrast margins from linear regression identified the threshold distance at which HEMS had a significantly lower prehospital time than GEMS, indicated by non-overlapping 95% confidence intervals. The effect of peak traffic times and adverse weather on the threshold distance was evaluated. Geographic effects across EMS regions were also evaluated. A total of 144,741 patients were included with 19% transported by HEMS. Overall, HEMS became faster than GEMS at 7.7miles from the trauma center (p=0.043). HEMS became faster at 6.5miles during peak traffic (p=0.025) compared to 7.9miles during off-peak traffic (p=0.048). Adverse weather increased the distance at which HEMS was faster to 17.1miles (p=0.046) from 7.3miles in clear weather (p=0.036). Significant variation occurred across EMS regions, with threshold distances ranging from 5.4miles to 35.3miles. There was an inverse but non-significant relationship between urban population and threshold distance across EMS regions (ρ -0.351, p=0.28). This is the first study to demonstrate that traffic, weather, and geographic region significantly impact the threshold distance at which HEMS is faster than GEMS. HEMS was faster at shorter distances during peak traffic while adverse weather increased this distance. The threshold distance varied widely across geographic region. These factors must be considered to guide appropriate HEMS triage protocols. III, Therapeutic.

The Bear River's history and diversion: Constraints, unsolved problems, and implications for the Lake Bonneville record: Chapter 2

USGS Publications Warehouse

Pederson, Joel L.; Janecke, Susanne U.; Reheis, Marith; Kaufmann, Darrell S.; Oaks, R. Q.

2016-01-01

The shifting course of the Bear River has influenced the hydrologic balance of the Bonneville basin through time, including the magnitude of Lake Bonneville. This was first recognized by G.K. Gilbert and addressed in the early work of Robert Bright, who focused on the southeastern Idaho region of Gem Valley and Oneida Narrows. In this chapter, we summarize and evaluate existing knowledge from this region, present updated and new chronostratigraphic evidence for the Bear River's drainage history, and discuss implications for the Bonneville record as well as future research needs.The Bear River in Plio-Pleistocene time joined the Snake River to the north by following the present-day Portneuf or Blackfoot drainages, with it likely joining the Portneuf River by middle Pleistocene time. An episode of volcanism in the Blackfoot-Gem Valley volcanic field, sparsely dated to ~ 100–50 ka, diverted the Bear River southward from where the Alexander shield volcano obstructed the river's path into Gem Valley. Previous chronostratigraphic and isotopic work on the Main Canyon Formation in southern Gem Valley indicates internal-basin sedimentation during the Quaternary, with a possible brief incursion of the Bear River ~ 140 ka. New evidence confirms that the Bear River's final diversion at 60–50 ka led to its integration into the Bonneville basin by spillover at a paleo-divide above present-day Oneida Narrows. This drove rapid incision before the rise of Lake Bonneville into the canyon and southern Gem Valley.Bear River diversion at 60–50 ka coincides with the end of the Cutler Dam lake cycle, at the onset of marine isotope stage 3. The Bear River subsequently contributed to the rise of Lake Bonneville, the highest pluvial lake known in the basin, culminating in the Bonneville flood. Key research questions include the prior path of the upper Bear River, dating and understanding the complex geologic relations within the Gem Valley-Blackfoot volcanic field, resolving evidence for possible earlier incursions of Bear River water into the Bonneville basin, and interpreting the sedimentology of the Main Canyon Formation.

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.

Effects of the lipid regulator drug gemfibrozil: A toxicological and behavioral perspective.

PubMed

Henriques, Jorge F; Almeida, Ana Rita; Andrade, Thayres; Koba, Olga; Golovko, Oksana; Soares, Amadeu M V M; Oliveira, Miguel; Domingues, Inês

2016-01-01

Pharmaceuticals are emerging contaminants as their worldwide consumption increases. Fibrates such as gemfibrozil (GEM) are used in human medicine to reduce blood concentrations of cholesterol and triacylglycerol and also are some of the most frequently reported pharmaceuticals in waste waters and surface waters. Despite some studies have already demonstrated the negative impact in physiological and/or reproductive endpoints in adult fish, data on survival and behavioral effects in fish larvae are lacking. This study aimed to assess the effects of GEM on zebrafish eleutheroembryo development and locomotor behavior. A fish embryo toxicity (FET) test was undertaken to evaluate GEM acute toxicity by exposing embryos to 0, 6.58, 9.87, 14.81, 22.22, 33.33 and 50mg/L. Developmental endpoints such as hatching success, edemas and malformations were recorded. A second test was undertaken by exposing embryos to 0, 1.5, 3 and 6mg/L in order to evaluate the effects of GEM on 120 and 144h post fertilization (hpf) larvae locomotor activity by video tracking, using a Zebrabox(®) (Viewpoint, France) device. From the data recorded, several parameters such as total swimming distance (TSD) and total swimming time (TST) in each 120s integration time were calculated. Data showed that this compound has a moderate toxic effect on fish embryo development, affecting both survival and hatching success with a calculated 96h LC50 of 11.01mg/L and no effects at the developmental level at 6mg/L. GEM seems to impair locomotor activity, even at concentrations where developmental abnormalities were unperceived, at concentrations as low as 1.5mg/L. Both TSD and TST were sensitive to GEM exposure. These effects do not seem to be independent of the developmental stage as 120hpf larvae seem to present a development bias with repercussions in locomotor behavior. This study highlights the need to include behavioral endpoints in ecotoxicological assays as this seems to be a more sensitive endpoint often disregarded. Copyright © 2015 Elsevier B.V. All rights reserved.

The impact of a physician-staffed helicopter on outcome in patients admitted to a stroke unit: a prospective observational study.

PubMed

Funder, Kamilia S; Rasmussen, Lars S; Lohse, Nicolai; Hesselfeldt, Rasmus; Siersma, Volkert; Gyllenborg, Jesper; Wulffeld, Sandra; Hendriksen, Ole M; Lippert, Freddy K; Steinmetz, Jacob

2017-02-23

Transportation by helicopter may reduce time to hospital admission and improve outcome. We aimed to investigate the effect of transport mode on mortality, disability, and labour market affiliation in patients admitted to the stroke unit. Prospective, observational study with 5.5 years of follow-up. We included patients admitted to the stroke unit the first three years after implementation of a helicopter emergency medical services (HEMS) from a geographical area covered by both the HEMS and the ground emergency medical services (GEMS). HEMS patients were compared with GEMS patients. Primary outcome was long-term mortality after admission to the stroke unit. Of the 1679 patients admitted to the stroke unit, 1068 were eligible for inclusion. Mortality rates were 9.04 per 100 person-years at risk (PYR) in GEMS patients and 9.71 per 100 PYR in HEMS patients (IRR = 1.09, 95% CI 0.79-1.49; p = 0.60). The 30-day mortality was 7.4% with GEMS and 7.9% with HEMS (OR = 1.02, CI 0.53-1.96; p = 0.96). Incidence rate of involuntary early retirement was 6.97 per 100 PYR and 7.58 per 100 PYR in GEMS and HEMS patients, respectively (IRR = 1.19, CI 0.27-5.26; p = 0.81). Work ability after 2 years and time on social transfer payments did not differ between groups. We found no significant difference in mean modified Rankin Scale score after 3 months (2.21 GEMS vs. 2.09 HEMS; adjusted mean difference = -0.20, CI -0.74-0.33; p = 0.46). The possible benefit of HEMS for neurological outcome is probably difficult to detect by considering mortality, but for the secondary analyses we had less statistical power as illustrated by the wide confidence intervals. Helicopter transport of stroke patients was not associated with reduced mortality or disability, nor improved labour market affiliation compared to patients transported by a ground unit. The study was registered at ClinicalTrials.gov ( NCT02576379 ).

Generation of Knock-in Mouse by Genome Editing.

PubMed

Fujii, Wataru

2017-01-01

Knock-in mice are useful for evaluating endogenous gene expressions and functions in vivo. Instead of the conventional gene-targeting method using embryonic stem cells, an exogenous DNA sequence can be inserted into the target locus in the zygote using genome editing technology. In this chapter, I describe the generation of epitope-tagged mice using engineered endonuclease and single-stranded oligodeoxynucleotide through the mouse zygote as an example of how to generate a knock-in mouse by genome editing.

Dual role of SLP-76 in mediating T cell receptor-induced activation of phospholipase C-gamma1.

PubMed

Beach, Dvora; Gonen, Ronnie; Bogin, Yaron; Reischl, Ilona G; Yablonski, Deborah

2007-02-02

Phospholipase C-gamma1 (PLC-gamma1) activation depends on a heterotrimeric complex of adaptor proteins composed of LAT, Gads, and SLP-76. Upon T cell receptor stimulation, a portion of PLC-gamma1 is recruited to a detergent-resistant membrane fraction known as the glycosphingolipid-enriched membrane microdomains (GEMs), or lipid rafts, to which LAT is constitutively localized. In addition to LAT, PLC-gamma1 GEM recruitment depended on SLP-76, and, in particular, required the Gads-binding domain of SLP-76. The N-terminal tyrosine phosphorylation sites and P-I region of SLP-76 were not required for PLC-gamma1 GEM recruitment, but were required for PLC-gamma1 phosphorylation at Tyr(783). Thus, GEM recruitment can be insufficient for full activation of PLC-gamma1 in the absence of a second SLP-76-mediated event. Indeed, a GEM-targeted derivative of PLC-gamma1 depended on SLP-76 for T cell receptor-induced phosphorylation at Tyr783 and subsequent NFAT activation. On a biochemical level, SLP-76 inducibly associated with both Vav and catalytically active ITK, which efficiently phosphorylated a PLC-gamma1 fragment at Tyr783 in vitro. Both associations were disrupted upon mutation of the N-terminal tyrosine phosphorylation sites of SLP-76. The P-I region deletion disrupted Vav association and reduced SLP-76-associated kinase activity. A smaller deletion within the P-I region, which does not impair PLC-gamma1 activation, did not impair the association with Vav, but reduced SLP-76-associated kinase activity. These results provide new insight into the multiple roles of SLP-76 and the functional importance of its interactions with other signaling proteins.

GEM detector performance with innovative micro-TPC readout in high magnetic field

NASA Astrophysics Data System (ADS)

Garzia, I.; Alexeev, M.; Amoroso, A.; Baldini Ferroli, R.; Bertani, M.; Bettoni, D.; Bianchi, F.; Calcaterra, A.; Canale, N.; Capodiferro, M.; Cassariti, V.; Cerioni, S.; Chai, J. Y.; Chiozzi, S.; Cibinetto, G.; Cossio, F.; Cotta Ramusino, A.; De Mori, F.; Destefanis, M.; Dong, J.; Evangelisti, F.; Evangelisti, F.; Farinelli, R.; Fava, L.; Felici, G.; Fioravanti, E.; Gatta, M.; Greco, M.; Lavezzi, L.; Leng, C. Y.; Li, H.; Maggiora, M.; Malaguti, R.; Marcello, S.; Melchiorri, M.; Mezzadri, G.; Mignone, M.; Morello, G.; Pacetti, S.; Patteri, P.; Pellegrino, J.; Pelosi, A.; Rivetti, A.; Rolo, M. D.; Savrié, M.; Scodeggio, M.; Soldani, E.; Sosio, S.; Spataro, S.; Tskhadadze, E.; Verma, S.; Wheadon, R.; Yan, L.

2018-01-01

Gas detector development is one of the pillars of the research in fundamental physics. Since several years, a new concept of detectors, called Micro Pattern Gas Detector (MPGD), allowed to overcome several problems related to other types of commonly used detectors, like drift chamber and micro strips detectors, reducing the rate of discharges and providing better radiation tolerance. Among the most used MPGDs are the Gas Electron Multipliers (GEMs). Invented by Sauli in 1997, nowadays GEMs have become an important reality for particle detectors in high energy physics. Commonly deployed as fast timing detectors and triggers, their fast response, high rate capability and high radiation hardness make them also suitable as tracking detectors. The readout scheme is one of the most important features in tracking technology. Analog readout based on the calculation of the center of gravity technique allows to overcome the limit imposed by digital pads, whose spatial resolution is limited by the pitch dimensions. However, the presence of high external magnetic fields can distort the electronic cloud and affect the performance. The development of the micro-TPC reconstruction method brings GEM detectors into a new prospective, improving significantly the spatial resolutionin presence of high magnetic fields. This innovative technique allows to reconstruct the 3-dimensional particle position, as Time Projection Chamber, but within a drift gap of a few millimeters. In these report, the charge centroid and micro-TPC methods are described in details. We discuss the results of several test beams performed with planar chambers in magnetic field. These results are one of the first developments of micro-TPC technique for GEM detectors, which allows to reach unprecedented performance in a high magnetic field of 1 T.

Tumor-targeted polymeric nanostructured lipid carriers with precise ratiometric control over dual-drug loading for combination therapy in non-small-cell lung cancer.

PubMed

Liang, Yan; Tian, Baocheng; Zhang, Jing; Li, Keke; Wang, Lele; Han, Jingtian; Wu, Zimei

2017-01-01

Gemcitabine (GEM) and paclitaxel (PTX) are effective combination anticancer agents against non-small-cell lung cancer (NSCLC). At the present time, a main challenge of combination treatment is the precision of control that will maximize the combined effects. Here, we report a novel method to load GEM (hydrophilic) and PTX (hydrophobic) into simplex tumor-targeted nanostructured lipid carriers (NLCs) for accurate control of the ratio of the two drugs. We covalently preconjugated the dual drugs through a hydrolyzable ester linker to form drug conjugates. N -acetyl-d-glucosamine (NAG) is a glucose receptor-targeting ligand. We added NAG to the formation of NAG-NLCs. In general, synthesis of poly(6- O -methacryloyl-d-galactopyranose)-GEM/PTX (PMAGP-GEM/PTX) conjugates was demonstrated, and NAG-NLCs were prepared using emulsification and solvent evaporation. NAG-NLCs displayed sphericity with an average diameter of 120.3±1.3 nm, a low polydispersity index of 0.233±0.04, and accurate ratiometric control over the two drugs. A cytotoxicity assay showed that the NAG-NLCs had better antitumor activity on NSCLC cells than normal cells. There was an optimal ratio of the two drugs, exhibiting the best cytotoxicity and combinatorial effects among all the formulations we tested. In comparison with both the free-drug combinations and separately nanopackaged drug conjugates, PMAGP-GEM/PTX NAG-NLCs (3:1) exhibited superior synergism. Flow cytometry and confocal laser scanning microscopy showed that NAG-NLCs exhibited higher uptake efficiency in A549 cells via glucose receptor-mediated endocytosis. This combinatorial delivery system settles problems with ratiometric coloading of hydrophilic and hydrophobic drugs for tumor-targeted combination therapy to achieve maximal anticancer efficacy in NSCLC.

An empowerment intervention for Indigenous communities: an outcome assessment.

PubMed

Kinchin, Irina; Jacups, Susan; Tsey, Komla; Lines, Katrina

2015-08-21

Empowerment programs have been shown to contribute to increased empowerment of individuals and build capacity within the community or workplace. To-date, the impact of empowerment programs has yet to be quantified in the published literature in this field. This study assessed the Indigenous-developed Family Wellbeing (FWB) program as an empowerment intervention for a child safety workforce in remote Indigenous communities by measuring effect sizes. The study also assessed the value of measurement tools for future impact evaluations. A three-day FWB workshop designed to promote empowerment and workplace engagement among child protection staff was held across five remote north Queensland Indigenous communities. The FWB assessment tool comprised a set of validated surveys including the Growth and Empowerment Measure (GEM), Australian Unity Wellbeing Index, Kessler psychological distress scale (K10) and Workforce engagement survey. The assessment was conducted pre-intervention and three months post-intervention. The analysis of pre-and post-surveys revealed that the GEM appeared to be the most tangible measure for detecting positive changes in communication, conflict resolution, decision making and life skill development. The GEM indicated a 17 % positive change compared to 9 % for the Australian Unity Wellbeing Index, 5 % for the workforce engagement survey and less than 1 % for K10. This study extended qualitative research and identified the best measurement tool for detecting the outcomes of empowerment programs. The GEM was found the most sensitive and the most tangible measure that captures improvements in communication, conflict resolution, decision making and life skill development. The GEM and Australian Unity Wellbeing Index could be recommended as routine measures for empowerment programs assessment among similar remote area workforce.

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.

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.

Lorentz violation, gravitoelectromagnetism and Bhabha scattering at finite temperature

NASA Astrophysics Data System (ADS)

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

2018-04-01

Gravitoelectromagnetism (GEM) is an approach for the gravitation field that is described using the formulation and terminology similar to that of electromagnetism. The Lorentz violation is considered in the formulation of GEM that is covariant in its form. In practice, such a small violation of the Lorentz symmetry may be expected in a unified theory at very high energy. In this paper, a non-minimal coupling term, which exhibits Lorentz violation, is added as a new term in the covariant form. The differential cross-section for Bhabha scattering in the GEM framework at finite temperature is calculated that includes Lorentz violation. The Thermo Field Dynamics (TFD) formalism is used to calculate the total differential cross-section at finite temperature. The contribution due to Lorentz violation is isolated from the total cross-section. It is found to be small in magnitude.

Multi-GEM Detectors in High Particle Fluxes

NASA Astrophysics Data System (ADS)

Thuiner, P.; Resnati, F.; Franchino, S.; Gonzalez Diaz, D.; Hall-Wilton, R.; Müller, H.; Oliveri, E.; Pfeiffer, D.; Ropelewski, L.; Van Stenis, M.; Streli, C.; Veenhof, R.

2018-02-01

Gaseous Electron Multipliers (GEM) are well known for stable operation at high particle fluxes. We present a study of the intrinsic limits of GEMdetectors when exposed to very high particle fluxes of the order of MHz/mm2. We give an interpretation to the variations of the effective gain, which, as a function of the particle flux, first increases and then decreases. We also discuss the reduction of the ion back-flow with increasing flux. We present measurements and simulations of a triple GEM detector, describing its behaviour in terms of accumulation of positive ions that results in changes of the transfer fields and the amplification fields. The behaviour is expected to be common to all multi-stage amplification devices where the efficiency of transferring the electrons from one stage to the next one is not 100%.

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 development of algorithms for the deployment of new version of GEM-detector-based acquisition system

NASA Astrophysics Data System (ADS)

Krawczyk, Rafał D.; Czarski, Tomasz; Kolasiński, Piotr; Linczuk, Paweł; Poźniak, Krzysztof T.; Chernyshova, Maryna; Kasprowicz, Grzegorz; Wojeński, Andrzej; Zabolotny, Wojciech; Zienkiewicz, Paweł

2016-09-01

This article is an overview of what has been implemented in the process of development and testing the GEM detector based acquisition system in terms of post-processing algorithms. Information is given on mex functions for extended statistics collection, unified hex topology and optimized S-DAQ algorithm for splitting overlapped signals. Additional discussion on bottlenecks and major factors concerning optimization is presented.

Data processing for soft X-ray diagnostics based on GEM detector measurements for fusion plasma imaging

NASA Astrophysics Data System (ADS)

Czarski, T.; Chernyshova, M.; Pozniak, K. T.; Kasprowicz, G.; Byszuk, A.; Juszczyk, B.; Wojenski, A.; Zabolotny, W.; Zienkiewicz, P.

2015-12-01

The measurement system based on GEM - Gas Electron Multiplier detector is developed for X-ray diagnostics of magnetic confinement fusion plasmas. The Triple Gas Electron Multiplier (T-GEM) is presented as soft X-ray (SXR) energy and position sensitive detector. The paper is focused on the measurement subject and describes the fundamental data processing to obtain reliable characteristics (histograms) useful for physicists. So, it is the software part of the project between the electronic hardware and physics applications. The project is original and it was developed by the paper authors. Multi-channel measurement system and essential data processing for X-ray energy and position recognition are considered. Several modes of data acquisition determined by hardware and software processing are introduced. Typical measuring issues are deliberated for the enhancement of data quality. The primary version based on 1-D GEM detector was applied for the high-resolution X-ray crystal spectrometer KX1 in the JET tokamak. The current version considers 2-D detector structures initially for the investigation purpose. Two detector structures with single-pixel sensors and multi-pixel (directional) sensors are considered for two-dimensional X-ray imaging. Fundamental output characteristics are presented for one and two dimensional detector structure. Representative results for reference source and tokamak plasma are demonstrated.

Technological aspects of GEM detector design and assembling for soft x-ray application

NASA Astrophysics Data System (ADS)

Kowalska-Strzeciwilk, E.; Chernyshova, M.

2016-09-01

Various types of Micro Pattern Gas Detectors (MPGDs) found applications as tracking detectors in high energy particle physics experiments and as well as imaging detectors, especially for soft X-rays. These detectors offer several advantages like high count rate capability, good spatial and energy resolution, low cost and possibility of constructing large area detectors with very small dead area. Construction, like the triple Gas Electron Multiplier (GEM) detector has become a standard detector, which is widely used for different imaging applications. Some examples of such applications are: monitoring the impurity in plasma, imaging system for mapping of some parameters like pigment distributions using X-ray fluorescence technique[1], proton range radiography system for quality assurance in hadron therapy. Measuring of the Soft X-Ray (SXR) radiation of magnetic fusion plasma is a standard way of accessing valuable information, for example, about particle transport and MHD. The paper is focused on the design of GEM based soft Xray radiation detecting system which is under development. It is dedicated to study soft X-ray emission of plasma radiation with focus on tungsten emission lines energy region. The paper presents the designing, construction and assembling of a prototype of two triple-GEM detectors for soft-X ray application on the WEST device.

On a gas electron multiplier based synthetic diagnostic for soft x-ray tomography on WEST with focus on impurity transport studies

NASA Astrophysics Data System (ADS)

Jardin, A.; Mazon, D.; Malard, P.; O'Mullane, M.; Chernyshova, M.; Czarski, T.; Malinowski, K.; Kasprowicz, G.; Wojenski, A.; Pozniak, K.

2017-08-01

The tokamak WEST aims at testing ITER divertor high heat flux component technology in long pulse operation. Unfortunately, heavy impurities like tungsten (W) sputtered from the plasma facing components can pollute the plasma core by radiation cooling in the soft x-ray (SXR) range, which is detrimental for the energy confinement and plasma stability. SXR diagnostics give valuable information to monitor impurities and study their transport. The WEST SXR diagnostic is composed of two new cameras based on the Gas Electron Multiplier (GEM) technology. The WEST GEM cameras will be used for impurity transport studies by performing 2D tomographic reconstructions with spectral resolution in tunable energy bands. In this paper, we characterize the GEM spectral response and investigate W density reconstruction thanks to a synthetic diagnostic recently developed and coupled with a tomography algorithm based on the minimum Fisher information (MFI) inversion method. The synthetic diagnostic includes the SXR source from a given plasma scenario, the photoionization, electron cloud transport and avalanche in the detection volume using Magboltz, and tomographic reconstruction of the radiation from the GEM signal. Preliminary studies of the effect of transport on the W ionization equilibrium and on the reconstruction capabilities are also presented.

Polar firn air reveals large-scale impact of anthropogenic mercury emissions during the 1970s.

PubMed

Faïn, Xavier; Ferrari, Christophe P; Dommergue, Aurélien; Albert, Mary R; Battle, Mark; Severinghaus, Jeff; Arnaud, Laurent; Barnola, Jean-Marc; Cairns, Warren; Barbante, Carlo; Boutron, Claude

2009-09-22

Mercury (Hg) is an extremely toxic pollutant, and its biogeochemical cycle has been perturbed by anthropogenic emissions during recent centuries. In the atmosphere, gaseous elemental mercury (GEM; Hg degrees ) is the predominant form of mercury (up to 95%). Here we report the evolution of atmospheric levels of GEM in mid- to high-northern latitudes inferred from the interstitial air of firn (perennial snowpack) at Summit, Greenland. GEM concentrations increased rapidly after World War II from approximately 1.5 ng m(-3) reaching a maximum of approximately 3 ng m(-3) around 1970 and decreased until stabilizing at approximately 1.7 ng m(-3) around 1995. This reconstruction reproduces real-time measurements available from the Arctic since 1995 and exhibits the same general trend observed in Europe since 1990. Anthropogenic emissions caused a two-fold rise in boreal atmospheric GEM concentrations before the 1970s, which likely contributed to higher deposition of mercury in both industrialized and remotes areas. Once deposited, this toxin becomes available for methylation and, subsequently, the contamination of ecosystems. Implementation of air pollution regulations, however, enabled a large-scale decline in atmospheric mercury levels during the 1980s. The results shown here suggest that potential increases in emissions in the coming decades could have a similar large-scale impact on atmospheric Hg levels.

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.

Atmospheric mercury (Hg) in the Adirondacks: Concentrations and sources

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

Hyun-Deok Choi; Thomas M. Holsen; Philip K. Hopke

2008-08-15

Hourly averaged gaseous elemental Hg (GEM) concentrations and hourly integrated reactive gaseous Hg (RGM), and particulate Hg (HgP) concentrations in the ambient air were measured at Huntington Forest in the Adirondacks, New York from June 2006 to May 2007. The average concentrations of GEM, RGM, and HgP were 1.4 {+-} 0.4 ng m{sup -3}, 1.8 {+-} 2.2 pg m{sup -3}, and 3.2 {+-} 3.7 pg m{sup -3}, respectively. RGM represents <3.5% of total atmospheric Hg or total gaseous Hg (TGM: GEM + RGM) and HgP represents <3.0% of the total atmospheric Hg. The highest mean concentrations of GEM, RGM, andmore » HgP were measured during winter and summer whereas the lowest mean concentrations were measured during spring and fall. Significant diurnal patterns were apparent in warm seasons for all species whereas diurnal patterns were weak in cold seasons. RGM was better correlated with ozone concentration and temperature in both warm than the other species. Potential source contribution function (PSCF) analysis was applied to identify possible Hg sources. This method identified areas in Pennsylvania, West Virginia, Ohio, Kentucky, Texas, Indiana, and Missouri, which coincided well with sources reported in a 2002 U.S. mercury emissions inventory. 51 refs., 7 figs., 1 tab.« less

Performance of a large size triple GEM detector at high particle rate for the CBM Experiment at FAIR

NASA Astrophysics Data System (ADS)

Adak, Rama Prasad; Kumar, Ajit; Dubey, Anand Kumar; Chattopadhyay, Subhasis; Das, Supriya; Raha, Sibaji; Samanta, Subhasis; Saini, Jogender

2017-02-01

In CBM Experiment at FAIR, dimuons will be detected by a Muon Chamber (MUCH) consisting of segmented absorbers of varying widths and tracking chambers sandwiched between the absorber-pairs. In this fixed target heavy-ion collision experiment, operating at highest interaction rate of 10 MHz for Au+Au collision, the inner region of the 1st detector will face a particle rate of 1 MHz/cm2. To operate at such a high particle density, GEM technology based detectors have been selected for the first two stations of MUCH. We have reported earlier the performance of several small-size GEM detector prototypes built at VECC for use in MUCH. In this work, we report on a large GEM prototype tested with proton beam of momentum 2.36 GeV/c at COSY-Jülich Germany. The detector was read out using nXYTER operated in self-triggering mode. An efficiency higher than 96% at ΔVGEM = 375.2 V was achieved. The variation of efficiency with the rate of incoming protons has been found to vary within 2% when tested up to a maximum rate of 2.8 MHz/cm2. The gain was found to be stable at high particle rate with a maximum variation of ∼9%.

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.

Genome Editing in Mice Using TALE Nucleases.

PubMed

Wefers, Benedikt; Brandl, Christina; Ortiz, Oskar; Wurst, Wolfgang; Kühn, Ralf

2016-01-01

Gene engineering for generating targeted mouse mutants is a key technology for biomedical research. Using TALENs as sequence-specific nucleases to induce targeted double-strand breaks, the mouse genome can be directly modified in zygotes in a single step without the need for embryonic stem cells. By embryo microinjection of TALEN mRNAs and targeting vectors, knockout and knock-in alleles can be generated fast and efficiently. In this chapter we provide protocols for the application of TALENs in mouse zygotes.

The Oncogenic Role of RhoGAPs in Basal-Like Breast Cancer

DTIC Science & Technology

2015-02-01

cell lines, and mouse models . c) In vivo tumorigenesis and metastasis assays. Milestones: Identify whether ArhGAP11A and RacGAP1 can promote tumor growth...also upregulated in basal (C3(I)-Tag) but not luminal (MMTV-Neu) genetically- engineered mouse models (Fig. 1B). At the protein level, RacGAP1 was...hypothesis that these RhoGAPs are indeed playing an oncogenic role in these cells. Human Tumors Mouse Model Tumors Normal Luminal A Basal-like Normal

Postdoctoral Fellow | Center for Cancer Research

Cancer.gov

Dr. St. Croix’s laboratory at the Mouse Cancer Genetics Program (MCGP), National Cancer Institute, USA has an open postdoctoral position. We seek a highly motivated, creative and bright individual to participate in a collaborative project that involves the targeting of tumor-associated stroma using T-cells engineered to express chimeric antigen receptors (CARs). The laboratory focuses on the characterization and exploitation of molecules associated with tumor angiogenesis. The successful candidate would be involved in developing, producing and characterizing new therapeutic antibodies and CARs that recognize cancer cells or its associated stroma, and preclinical testing of these agents using mouse tumor models. The tumor angiogenesis lab is located at the National Cancer Institute in Frederick with access to state-of-the-art facilities for antibody engineering, genomic analysis, pathology, and small animal imaging, among others. Detailed information about Dr. St. Croix’s research and publications can be accessed at https://ccr.cancer.gov/Mouse-Cancer-Genetics-Program/brad-st-croix.

Visualizing the enteric nervous system using genetically engineered double reporter mice: Comparison with immunofluorescence.

PubMed

Jiang, Yanfen; Dong, Hui; Eckmann, Lars; Hanson, Elaine M; Ihn, Katherine C; Mittal, Ravinder K

2017-01-01

The enteric nervous system (ENS) plays a crucial role in the control of gastrointestinal motility, secretion and absorption functions. Immunohistochemistry has been widely used to visualize neurons of the ENS for more than two decades. Genetically engineered mice that report specific proteins can also be used to visualize neurons of the ENS. The goal of our study was to develop a mouse that expresses fluorescent neuronal nitric oxide synthase (nNOS) and choline acetyltransferase (ChAT), the two proteins expressed in 95% of the ENS neurons. We compared ENS neurons visualized in the reporter mouse with the wild type mouse stained using classical immunostaining techniques. Mice hemizygous for ChAT-ChR2-YFP BAC transgene with expression of the mhChR2:YFP fusion protein directed by ChAT promoter/enhancer regions on the BAC transgene were purchased commercially. The Cre/LoxP technique of somatic recombination was used to construct mice with nNOS positive neurons. The two mice were crossbred and tissues were harvested and examined using fluorescent microscopy. Immunostaining was performed in the wild type mice, using antibodies to nNOS, ChAT, Hu and PGP 9.5. Greater than 95% of the ENS neurons were positive for either nNOS or ChAT or both. The nNOS and ChAT neurons and their processes in the ENS were well visualized in all the regions of the GI tract, i.e., esophagus, small intestine and colon. The number of nNOS and ChAT neurons was approximately same in the reporter mouse and immunostaining method in the wild type mouse. The nNOS fluorescence in the reporter mouse was seen in both cytoplasm as well as nucleus but in the immunostained specimens it was seen only in the cytoplasm. We propose that the genetically engineered double reporter mouse for ChAT and nNOS proteins is a powerful tool to study of the effects of various diseases on the ENS without the need for immunostaining.

Hows, Whats, and (Don't Forget) Whos: The Future of Inquiry in Communication, Teaching, and Learning. Forum: The Future of Instructional Communication

ERIC Educational Resources Information Center

Dannels, Deanna P.

2017-01-01

Reading through the articles in this issue of "Communication Education" took incoming editor, Deanna Dannels, back in time to reflect on a camping trip in North Carolina where she and her daughter went gem mining. She reflects on the the one piece of advice from the employee who taught them how to gem mine: "If you want to find…

A Survey of Object-Oriented Database Technology

DTIC Science & Technology

1990-05-01

now mention briefly the various security and autho- rization schemes provided by GEMSTONE. 1. Login Authorization. There are two ways to login to...GemStone- through the OPAL programming environment or through the GemStone C interface. A user ID and password is required in both cases to login . 2. Name...lIlj A. Black. Object structure in the Emerald system. Proc. Ist Intl. Conf. on Objcct- Oriented Programming Systems, Languages and Applications, pp

Formation of benzo[f]-1-indanone frameworks by regulable intramolecular annulations of gem-dialkylthio trienynes.

PubMed

Fang, Zhongxue; Liu, Ying; Barry, Badru-Deen; Liao, Peiqiu; Bi, Xihe

2015-02-20

An atom-economic route to benzo[f]-1-indanone frameworks has been developed starting from the readily available gem-dialkylthio trienynes by intramolecular annulations. The chemoselectivity of the intramolecular cyclizations can be regulated by both the base and the type of gas atmosphere used in the reaction, thus allowing the divergent synthesis of the corresponding functionalized benzo[f]-1-indanones in good to excellent yields.

Polyborylated reagents for modern organic synthesis

PubMed Central

SHIMIZU, Masaki; HIYAMA, Tamejiro

2008-01-01

Diverse kinds of gem- and vic-diborylated compounds are now readily available thanks to advances in gem-diborylation of lithium carbenoids as well as vic-diborylation of carbon–carbon multiple bonds with diboron compounds. These diborylated reagents lead to invention of polyborylated reagents and many novel and useful synthetic methods for supreme stereocontrol. This review summarizes preparative methods and synthetic reactions of di- and polyborylated reagents with the emphasis on multiple bond formation. PMID:18941288

Mild and efficient strontium chloride hexahydrate-catalyzed conversion of ketones and aldehydes into corresponding gem-dihydroperoxides by aqueous H2O2.

PubMed

Azarifar, Davood; Khosravi, Kaveh; Soleimanei, Fatemeh

2010-03-08

SrCl2 x 6 H2O has been shown to act as an efficient catalyst for the conversion of aldehydes or ketones into the corresponding gem-dihydroperoxides (DHPs) by treatment with aqueous H2O2 (30%) in acetonitrile. The reactions proceed under mild and neutral conditions at room temperature to afford good to excellent yields of product.

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.

Asthenopia (eyestrain) in working children of gem-polishing industries.

PubMed

Tiwari, Rajnarayan R; Saha, Asim; Parikh, Jagdish R

2011-04-01

Working children of gem-polishing units are exposed to poor illumination and improper workstations. Also processes require lot of visual and mental concentration for precision. This may result in eyestrain. The study included 432 exposed and 569 comparison group subjects. Self-reported eyestrain was recorded through personal interview. Eyestrain included symptoms like itching, burning, or irritated eyes; tired or heavy eyes; difficulty seeing clearly (including blurred or double vision); and headache. The study variables included age, gender, daily working hours, and duration of exposure. The prevalence of eyestrain in child labourers was 32.2%, which was significantly more than the comparison group subjects. Also, the working children of gem-polishing units were at 1.4 times higher risk of developing eyestrain. Age (3)14 years and female gender were significantly associated with the eyestrain. The prevalence of eyestrain in child labourers was 32.2% and was associated with age (3)14 years and female gender.

High granularity tracker based on a Triple-GEM optically read by a CMOS-based camera

NASA Astrophysics Data System (ADS)

Marafini, M.; Patera, V.; Pinci, D.; Sarti, A.; Sciubba, A.; Spiriti, E.

2015-12-01

The detection of photons produced during the avalanche development in gas chambers has been the subject of detailed studies in the past. The great progresses achieved in last years in the performance of micro-pattern gas detectors on one side and of photo-sensors on the other provide the possibility of making high granularity and very sensitive particle trackers. In this paper, the results obtained with a triple-GEM structure read-out by a CMOS based sensor are described. The use of an He/CF4 (60/40) gas mixture and a detailed optimization of the electric fields made possible to obtain a very high GEM light yield. About 80 photons per primary electron were detected by the sensor resulting in a very good capability of tracking both muons from cosmic rays and electrons from natural radioactivity.