Sample records for evangelos gr avdikos

  1. Gr/gr deletions on Y-chromosome correlate with male infertility: an original study, meta-analyses, and trial sequential analyses

    NASA Astrophysics Data System (ADS)

    Bansal, Sandeep Kumar; Jaiswal, Deepika; Gupta, Nishi; Singh, Kiran; Dada, Rima; Sankhwar, Satya Narayan; Gupta, Gopal; Rajender, Singh

    2016-02-01

    We analyzed the AZFc region of the Y-chromosome for complete (b2/b4) and distinct partial deletions (gr/gr, b1/b3, b2/b3) in 822 infertile and 225 proven fertile men. We observed complete AZFc deletions in 0.97% and partial deletions in 6.20% of the cases. Among partial deletions, the frequency of gr/gr deletions was the highest (5.84%). The comparison of partial deletion data between cases and controls suggested a significant association of the gr/gr deletions with infertility (P = 0.0004); however, the other partial deletions did not correlate with infertility. In cohort analysis, men with gr/gr deletions had a relatively poor sperm count (54.20 ± 57.45 million/ml) in comparison to those without deletions (72.49 ± 60.06), though the difference was not statistically significant (p = 0.071). Meta-analysis also suggested that gr/gr deletions are significantly associated with male infertility risk (OR = 1.821, 95% CI = 1.39-2.37, p = 0.000). We also performed trial sequential analyses that strengthened the evidence for an overall significant association of gr/gr deletions with the risk of male infertility. Another meta-analysis suggested a significant association of the gr/gr deletions with low sperm count. In conclusion, the gr/gr deletions show a strong correlation with male infertility risk and low sperm count, particularly in the Caucasian populations.

  2. Studies of Second Layer Hydrogens on Graphite: Hydrogen/hd/gr and Hd/hd/gr.

    NASA Astrophysics Data System (ADS)

    Liu, Yuanming

    Quasi-adiabatic heat capacity and volumetric vapor pressure isotherm techniques were used to study the thermodynamic properties of monolayer H_2 adsorbed on HD plated graphite (H_2/HD/Gr) and bilayer HD on bare graphite (HD/HD/Gr). Quasielastic neutron scattering (QENS) measurements were performed at the Laboratoire Leon Brillouin (LLB) in Saclay, France, to study the mobility of the bilayer HD films. The three techniques complemented each other. Three types of graphite were used: graphite foam for the heat capacity measurements, more loose and homogeneous graphite 'worms' for the isotherm measurements, and Papyex (similar to Grafoil) with a high surface-to-volume ratio for the QENS measurements. The heat capacity study on the mixture system H_2/HD/Gr is a continuation of the previous study on H_2/D _2/Gr by F. C. Liu et al. The results show three peculiar features which have not been seen in the pure bilayer hydrogen films: a tilted triple line, a distorted liquid(L)-vapor(V) coexistence region, and weak heat capacity anomalies at 10.1K. The triple line tilts backwards, from 6.58K to 6.25K as the H2 coverage increases. The lowest triple point temperature (6.25K) is still higher than both 5.96K of H_2/H _2/Gr (Wiechert et al.) and 5.74K of H_2/D_2/Gr (F. C. Liu et al.). The behavior of the triple line can be semi-quantitatively explained by a model of interlayer mixing which is based on the consideration that interlayer mixing lowers the system's free energy. The distortion of the L-V region and appearance of weak heat capacity anomalies are also believed to be due to interlayer mixing. The heat capacity measurements on HD/HD/Gr show a phase diagram similar to those of H_2 /H_2/MgO, H_2 /H_2/Gr, and 3D van der Waals systems, with the 2D triple and critical points at T _{t} = 8.44K and T_ {c} = 11.45K. The entropy change and heat of fusion at the triple point melting in HD/HD/Gr are comparable with those of H_2/H _2/Gr and D_2/D _2/Gr, but are considerably less

  3. Comparison of Notch Strength between Gr/PEEK (APC-1 and APC-2) and Gr/Epoxy Composite Materials at Elevated Temperature.

    DTIC Science & Technology

    1985-12-01

    J ub. we Jr. Captain, USARt Z712 AFIT/GAE/AA/85D- 12 Iv COMPARISON OF NOTCH STRENGTH BETWEEN GR/PEEK (APC-1 AND APC-2) AND GR/EPOXY COMPOSITE ...85D-12 COMPARISON OF NOTCH STRENGTH BETWEEN GR/PEEK _ (APC-1 AND APC-2) AND GR/EPOXY COMPOSITE MATERIAL AT ELEVATED TEMPERATURE THESIS Presented to the...unlimited Preface In this experimental investigation, the reduction of strength for notched composite laminates of Aromatic Polymer Composite , APC-2

  4. CRTC2 Is a Coactivator of GR and Couples GR and CREB in the Regulation of Hepatic Gluconeogenesis.

    PubMed

    Hill, Micah J; Suzuki, Shigeru; Segars, James H; Kino, Tomoshige

    2016-01-01

    Glucocorticoid hormones play essential roles in the regulation of gluconeogenesis in the liver, an adaptive response that is required for the maintenance of circulating glucose levels during fasting. Glucocorticoids do this by cooperating with glucagon, which is secreted from pancreatic islets to activate the cAMP-signaling pathway in hepatocytes. The cAMP-response element-binding protein (CREB)-regulated transcription coactivator 2 (CRTC2) is a coactivator known to be specific to CREB and plays a central role in the glucagon-mediated activation of gluconeogenesis in the early phase of fasting. We show here that CRTC2 also functions as a coactivator for the glucocorticoid receptor (GR). CRTC2 strongly enhances GR-induced transcriptional activity of glucocorticoid-responsive genes. CRTC2 physically interacts with the ligand-binding domain of the GR through a region spanning amino acids 561-693. Further, CRTC2 is required for the glucocorticoid-associated cooperative mRNA expression of the glucose-6-phosphatase, a rate-limiting enzyme for hepatic gluconeogenesis, by facilitating the attraction of GR and itself to its promoter region already occupied by CREB. CRTC2 is required for the maintenance of blood glucose levels during fasting in mice by enhancing the GR transcriptional activity on both the G6p and phosphoenolpyruvate carboxykinase (Pepck) genes. Finally, CRTC2 modulates the transcriptional activity of the progesterone receptor, indicating that it may influence the transcriptional activity of other steroid/nuclear receptors. Taken together, these results reveal that CRTC2 plays an essential role in the regulation of hepatic gluconeogenesis through coordinated regulation of the glucocorticoid/GR- and glucagon/CREB-signaling pathways on the key genes G6P and PEPCK.

  5. A Study on Gröbner Basis with Inexact Input

    NASA Astrophysics Data System (ADS)

    Nagasaka, Kosaku

    Gröbner basis is one of the most important tools in recent symbolic algebraic computations. However, computing a Gröbner basis for the given polynomial ideal is not easy and it is not numerically stable if polynomials have inexact coefficients. In this paper, we study what we should get for computing a Gröbner basis with inexact coefficients and introduce a naive method to compute a Gröbner basis by reduced row echelon form, for the ideal generated by the given polynomial set having a priori errors on their coefficients.

  6. On the Computation of Comprehensive Boolean Gröbner Bases

    NASA Astrophysics Data System (ADS)

    Inoue, Shutaro

    We show that a comprehensive Boolean Gröbner basis of an ideal I in a Boolean polynomial ring B (bar A,bar X) with main variables bar X and parameters bar A can be obtained by simply computing a usual Boolean Gröbner basis of I regarding both bar X and bar A as variables with a certain block term order such that bar X ≫ bar A. The result together with a fact that a finite Boolean ring is isomorphic to a direct product of the Galois field mathbb{GF}_2 enables us to compute a comprehensive Boolean Gröbner basis by only computing corresponding Gröbner bases in a polynomial ring over mathbb{GF}_2. Our implementation in a computer algebra system Risa/Asir shows that our method is extremely efficient comparing with existing computation algorithms of comprehensive Boolean Gröbner bases.

  7. Optimization of the production of thermostable endo-beta-1,4 mannanases from a newly isolated Aspergillus niger gr and Aspergillus flavus gr.

    PubMed

    Kote, Naganagouda V; Patil, Aravind Goud G; Mulimani, V H

    2009-02-01

    The aim of this work was to establish optimal conditions for the maximum production of endo-beta-1,4 mannanases using cheaper sources. Eight thermotolerant fungal strains were isolated from garden soil and compost samples collected in and around the Gulbarga University campus, India. Two strains were selected based on their ability to produce considerable endo-beta-1,4 mannanases activity while growing in liquid medium at 37 degrees C with locust bean gum (LBG) as the only carbon source. They were identified as Aspergillus niger gr and Aspergillus flavus gr. The experiment to evaluate the effect of different carbon sources, nitrogen sources, temperatures and initial pH of the medium on maximal enzyme production was studied. Enzyme productivity was influenced by the type of polysaccharide used as the carbon source. Copra meal defatted with n-hexane showed to be a better substrate than LBG and guar gum for endo-beta-1,4 mannanases production by A. niger gr (40.011 U/ml), but for A. flavus gr (33.532 U/ml), the difference was not significant. Endo-beta-1,4 mannanases produced from A. niger gr and A. flavus gr have high optimum temperature (65 and 60 degrees C) and good thermostability in the absence of any stabilizers (maintaining 50% of residual activity for 8 and 6 h, respectively, at 60 degrees C) and are stable over in a wide pH range. These new strains offer an attractive alternative source of enzymes for the food and feed processing industries.

  8. Complete Genome Sequence of the Alfalfa Symbiont Sinorhizobium/Ensifer meliloti Strain GR4

    PubMed Central

    Martínez-Abarca, Francisco; Martínez-Rodríguez, Laura; López-Contreras, José Antonio; Jiménez-Zurdo, José Ignacio

    2013-01-01

    We present the complete nucleotide sequence of the multipartite genome of Sinorhizobium/Ensifer meliloti GR4, a predominant rhizobial strain in an agricultural field site. The genome (total size, 7.14 Mb) consists of five replicons: one chromosome, two expected symbiotic megaplasmids (pRmeGR4c and pRmeGR4d), and two accessory plasmids (pRmeGR4a and pRmeGR4b). PMID:23409262

  9. Complete Genome Sequence of the Alfalfa Symbiont Sinorhizobium/Ensifer meliloti Strain GR4.

    PubMed

    Martínez-Abarca, Francisco; Martínez-Rodríguez, Laura; López-Contreras, José Antonio; Jiménez-Zurdo, José Ignacio; Toro, Nicolás

    2013-01-01

    We present the complete nucleotide sequence of the multipartite genome of Sinorhizobium/Ensifer meliloti GR4, a predominant rhizobial strain in an agricultural field site. The genome (total size, 7.14 Mb) consists of five replicons: one chromosome, two expected symbiotic megaplasmids (pRmeGR4c and pRmeGR4d), and two accessory plasmids (pRmeGR4a and pRmeGR4b).

  10. Recruitment of Gr-1+ monocytes is essential for control of acute toxoplasmosis

    PubMed Central

    Robben, Paul M.; LaRegina, Marie; Kuziel, William A.; Sibley, L. David

    2005-01-01

    Circulating murine monocytes comprise two largely exclusive subpopulations that are responsible for seeding normal tissues (Gr-1−/CCR2−/CX3CR1high) or responding to sites of inflammation (Gr-1+/CCR2+/CX3CR1lo). Gr-1+ monocytes are recruited to the site of infection during the early stages of immune response to the intracellular pathogen Toxoplasma gondii. A murine model of toxoplasmosis was thus used to examine the importance of Gr-1+ monocytes in the control of disseminated parasitic infection in vivo. The recruitment of Gr-1+ monocytes was intimately associated with the ability to suppress early parasite replication at the site of inoculation. Infection of CCR2−/− and MCP-1−/− mice with typically nonlethal, low doses of T. gondii resulted in the abrogated recruitment of Gr-1+ monocytes. The failure to recruit Gr-1+ monocytes resulted in greatly enhanced mortality despite the induction of normal Th1 cell responses leading to high levels of IL-12, TNF-α, and IFN-γ. The profound susceptibility of CCR2−/− mice establishes Gr-1+ monocytes as necessary effector cells in the resistance to acute toxoplasmosis and suggests that the CCR2-dependent recruitment of Gr-1+ monocytes may be an important general mechanism for resistance to intracellular pathogens. PMID:15928200

  11. Melanin production by Rhizobium meliloti GR4 is linked to nonsymbiotic plasmid pRmeGR4b: cloning, sequencing, and expression of the tyrosinase gene mepA.

    PubMed Central

    Mercado-Blanco, J; García, F; Fernández-López, M; Olivares, J

    1993-01-01

    Melanin production by Rhizobium meliloti GR4 is linked to nonsymbiotic plasmid pRmeGR4b (140 MDa). Transfer of this plasmid to GR4-cured derivatives or to Agrobacterium tumefaciens enables these bacteria to produce melanin. Sequence analysis of a 3.5-kb PstI fragment of plasmid pRmeGR4b has revealed the presence of a open reading frame 1,481-bp that codes for a protein whose sequence shows strong homology to two conserved regions involved in copper binding in tyrosinases and hemocyanins. In vitro-coupled transcription-translation experiments showed that this open reading frame codes for a 55-kDa polypeptide. Melanin production in GR4 is not under the control of the RpoN-NifA regulatory system, unlike that in R. leguminosarum bv. phaseoli 8002. The GR4 tyrosinase gene could be expressed in Escherichia coli under the control of the lacZ promoter. For avoiding confusion with mel genes (for melibiose), a change of the name of the previously reported mel genes of R. leguminosarum bv. phaseoli and other organisms to mep genes (for melanin production) is proposed. Images PMID:8366027

  12. Computing Gröbner Bases within Linear Algebra

    NASA Astrophysics Data System (ADS)

    Suzuki, Akira

    In this paper, we present an alternative algorithm to compute Gröbner bases, which is based on computations on sparse linear algebra. Both of S-polynomial computations and monomial reductions are computed in linear algebra simultaneously in this algorithm. So it can be implemented to any computational system which can handle linear algebra. For a given ideal in a polynomial ring, it calculates a Gröbner basis along with the corresponding term order appropriately.

  13. Single Nucleotide Variations of the Human GR Gene Manifested as Pathologic Mutations or Polymorphisms.

    PubMed

    Kino, Tomoshige

    2018-05-11

    The human genome contains numerous single nucleotide variations (SNVs), and the human GR gene harbors ∼450 of these genetic changes. Among them, extremely rare non-synonymous variants known as pathologic GR gene mutations develop a characteristic pathologic condition, familial/sporadic generalized glucocorticoid resistance syndrome, by replacing the amino acids critical for GR protein structure and functions, whereas others known as pathologic polymorphisms develop mild manifestations recognized mainly at population bases by changing the GR activities slightly. Recent progress on the structural analysis to the GR protein and subsequent computer-based structural simulation revealed details of the molecular defects caused by such pathologic GR gene mutations, including their impact on the receptor interaction to ligands, nuclear receptor coactivators (NCoAs) or DNA glucocorticoid response elements (GREs). Indeed, those found in the GR ligand-binding domain significantly damage protein structure of the ligand-binding pocket and/or the activation function-2 transactivation domain and change their molecular interaction to glucocorticoids or the LxxLL signature motif of NCoAs. Two mutations found in GR DBD also affect interaction of the mutant receptors to GRE DNA by affecting the critical amino acid for the interaction or changing local hydrophobic circumstance. In this review, we discuss recent findings on the structural simulation of the pathologic GR mutants in connection to their functional and clinical impacts along with brief explanation to recent research achievement on the GR polymorphisms.

  14. Extending Clause Learning of SAT Solvers with Boolean Gröbner Bases

    NASA Astrophysics Data System (ADS)

    Zengler, Christoph; Küchlin, Wolfgang

    We extend clause learning as performed by most modern SAT Solvers by integrating the computation of Boolean Gröbner bases into the conflict learning process. Instead of learning only one clause per conflict, we compute and learn additional binary clauses from a Gröbner basis of the current conflict. We used the Gröbner basis engine of the logic package Redlog contained in the computer algebra system Reduce to extend the SAT solver MiniSAT with Gröbner basis learning. Our approach shows a significant reduction of conflicts and a reduction of restarts and computation time on many hard problems from the SAT 2009 competition.

  15. Application of Gr/PMR-15 to commercial aircraft

    NASA Technical Reports Server (NTRS)

    Postlewaite, J.; Porter, K.; Mclaren, D.

    1985-01-01

    Following from early experience with polyimides on the SST program and Shuttle aft flap studies the Boeing Company is now working on collaborative programs with its principal nacelle suppliers to pursue the development of Gr/PMR-15 nacelle components. Two programs are currently in effect. The first program is directed specifically towards the flight test and service evaluation at the earliest possible date of a 747 nacelle core cowl structure. The second program seeks to firmly establish the producibility and cost of a 757 thrust reverser C duct in a production environment. The near term objectives of these programs include: (1) the comparison of estimated cost and weight of Gr/PMR-15 versus metal structure, (2) the engine test of representative composite structure, (3) the preliminary design and analysis of the C duct structure, and (4) the preparation of cost data and time schedules for the development and producibility program. In addition to powerplant structure, the propulsion ducting system has shown to be a strong candidate for Gr/PMR-15 application. Currently, the Boeing 747 Organization is evaluating the use of PMR-15 matrix composites to replace nearly 800 lbs of titanium ducting per airplane.

  16. Octopamine Neuromodulation Regulates Gr32a-Linked Aggression and Courtship Pathways in Drosophila Males

    PubMed Central

    Andrews, Jonathan C.; Fernández, María Paz; Yu, Qin; Leary, Greg P.; Leung, Adelaine K. W.; Kavanaugh, Michael P.; Kravitz, Edward A.; Certel, Sarah J.

    2014-01-01

    Chemosensory pheromonal information regulates aggression and reproduction in many species, but how pheromonal signals are transduced to reliably produce behavior is not well understood. Here we demonstrate that the pheromonal signals detected by Gr32a-expressing chemosensory neurons to enhance male aggression are filtered through octopamine (OA, invertebrate equivalent of norepinephrine) neurons. Using behavioral assays, we find males lacking both octopamine and Gr32a gustatory receptors exhibit parallel delays in the onset of aggression and reductions in aggression. Physiological and anatomical experiments identify Gr32a to octopamine neuron synaptic and functional connections in the suboesophageal ganglion. Refining the Gr32a-expressing population indicates that mouth Gr32a neurons promote male aggression and form synaptic contacts with OA neurons. By restricting the monoamine neuron target population, we show that three previously identified OA-FruM neurons involved in behavioral choice are among the Gr32a-OA connections. Our findings demonstrate that octopaminergic neuromodulatory neurons function as early as a second-order step in this chemosensory-driven male social behavior pathway. PMID:24852170

  17. Biomass Burning and the 2012 Greenland Ice Sheet (GrIS) melt

    NASA Astrophysics Data System (ADS)

    Choi, H. D.; Soja, A. J.; Polashenski, C.; Fairlie, T. D.; Winker, D. M.; Trepte, C. R.

    2017-12-01

    This study is the part of the Sunlight Absorption on the Greenland ice sheet Experiment (SAGE) project investigating the impact of light absorbing impurities (e.g., aerosols) on the Greenland Ice Sheet (GrIS). Satellite observations, [e.g. Oceansat-2 (OS2) and the Moderate-resolution Imaging Spectroradionmeter (MODIS)] discovered an unusually large melt event in July 2012. NASA sensors showed that nearly 98.6% of the GrIS experienced melting at or near surface [Nghiem et al., 2012]. In this study, we question the extent to which biomass burning derived aerosols enhanced melting across the GrIS. Random points [59 total, 13 coincident with snow pit sites and 46 gridded] are selected across the entire extent of the GrIS from April 1st to August 31st 2012, and then the NASA Langley Trajectory Model (LaTM) is used to simulate the transport of potentially smoke-filled air parcels backwards for 5 days form these points, evaluation the back trajectory for coincidence with active fire detections. The trajectory model is initialized for 24-hour sustained injection from each site, and air parcels are released from the surface to 2 km at 200m intervals. With the trajectory model outputs, we are able to identify trajectories that have coincidences with fires. We focus on events in April through July when the GrIS albedo was dramatically decreased. We also utilize Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) data to verify smoke-aerosol signatures in boreal regions based on the NASA LaTM results. The results of this study will help us better understand the transport of biomass burning plumes and black carbon deposition that could lead to enhanced GrIS melting.

  18. Some Applications of Gröbner Bases in Robotics and Engineering

    NASA Astrophysics Data System (ADS)

    Abłamowicz, Rafał

    Gröbner bases in polynomial rings have numerous applications in geometry, applied mathematics, and engineering. We show a few applications of Gröbner bases in robotics, formulated in the language of Clifford algebras, and in engineering to the theory of curves, including Fermat and Bézier cubics, and interpolation functions used in finite element theory.

  19. Converging shock flows for a Mie-Grüneisen equation of state

    NASA Astrophysics Data System (ADS)

    Ramsey, Scott D.; Schmidt, Emma M.; Boyd, Zachary M.; Lilieholm, Jennifer F.; Baty, Roy S.

    2018-04-01

    Previous work has shown that the one-dimensional (1D) inviscid compressible flow (Euler) equations admit a wide variety of scale-invariant solutions (including the famous Noh, Sedov, and Guderley shock solutions) when the included equation of state (EOS) closure model assumes a certain scale-invariant form. However, this scale-invariant EOS class does not include even simple models used for shock compression of crystalline solids, including many broadly applicable representations of Mie-Grüneisen EOS. Intuitively, this incompatibility naturally arises from the presence of multiple dimensional scales in the Mie-Grüneisen EOS, which are otherwise absent from scale-invariant models that feature only dimensionless parameters (such as the adiabatic index in the ideal gas EOS). The current work extends previous efforts intended to rectify this inconsistency, by using a scale-invariant EOS model to approximate a Mie-Grüneisen EOS form. To this end, the adiabatic bulk modulus for the Mie-Grüneisen EOS is constructed, and its key features are used to motivate the selection of a scale-invariant approximation form. The remaining surrogate model parameters are selected through enforcement of the Rankine-Hugoniot jump conditions for an infinitely strong shock in a Mie-Grüneisen material. Finally, the approximate EOS is used in conjunction with the 1D inviscid Euler equations to calculate a semi-analytical Guderley-like imploding shock solution in a metal sphere and to determine if and when the solution may be valid for the underlying Mie-Grüneisen EOS.

  20. Constructing the quantum Hall system on the Grassmannians Gr2(CN)

    NASA Astrophysics Data System (ADS)

    Ballı, F.; Behtash, A.; Kürkçüoğlu, S.; Ünal, G.

    2015-04-01

    In this talk, we give the formulation of Quantum Hall Effects (QHEs) on the complex Grassmann manifolds Gr2(CN). We set up the Landau problem in Gr2(CN), solve it using group theoretical techniques and provide the energy spectrum and the eigenstates in terms of the SU(N) Wigner D-functions for charged particles on Gr2(CN) under the influence of abelian and non-abelian background magnetic monopoles or a combination of these thereof. For the simplest case of Gr2(C4) we provide explicit constructions of the single and many- particle wavefunctions by introducing the Plucker coordinates and show by calculating the two-point correlation function that the lowest Landau level (LLL) at filling factor v = 1 forms an incompressible fluid. Finally, we heuristically identify a relation between the U(1) Hall effect on Gr2(C4) and the Hall effect on the odd sphere S5, which is yet to be investigated in detail, by appealing to the already known analogous relations between the Hall effects on CP3 and CP7 and those on the spheres S4 and S8, respectively. The talk is given by S. Kürkçüoğlu at the Group 30 meeting at Ghent University, Ghent, Belgium in July 2014 and based on the article by F.Ballı, A.Behtash, S. Kürkçüoğlu, G.Ünal [1].

  1. Iceland's Grímsvötn volcano erupts

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    2011-05-01

    About 13 months after Iceland's Eyjafjallajökull volcano began erupting on 14 April 2010, which led to extensive air traffic closures over Europe, Grímsvötn volcano in southeastern took its turn. Iceland's most active volcano, which last erupted in 2004 and lies largely beneath the Vatnajökull ice cap, began its eruption activity on 21 May, with the ash plume initially reaching about 20 kilometers in altitude, according to the Icelandic Meteorological Office. Volcanic ash from Grímsvötn has cancelled hundreds of airplane flights and prompted U.S. president Barack Obama to cut short his visit to Ireland. As Eos went to press, activity at the volcano was beginning to subside.

  2. The Grid Analysis and Display System (GrADS)

    NASA Technical Reports Server (NTRS)

    Kinter, James L., III

    1994-01-01

    During the period 1 September 1993 - 31 August 1994, further development of the Grid Analysis and Display System (GrADS) was conducted at the Center for Ocean-Land-Atmosphere Studies (COLA) of the Institute of Global Environment and Society, Inc. (IGES) under subcontract 5555-31 from the University Space Research Association (USRA) administered by The Center of Excellence in Space Data and Information Sciences (CESDIS). This final report documents progress made under this subcontract and provides directions on how to access the software and documentation developed therein. A short description of GrADS is provided followed by summary of progress completed and a summary of the distribution of the software to date and the establishment of research collaborations.

  3. Iceland: Grímsvötn Volcano

    Atmospheric Science Data Center

    2013-04-17

    article title:  Grímsvötn Volcano Injects Ash into the Stratosphere     ... p.m. local time (1730 UTC) on Saturday, May 21, 2011. The volcano, located approximately 140 miles (220 kilometers) east of the capital ...

  4. GR712RC- Dual-Core Processor- Product Status

    NASA Astrophysics Data System (ADS)

    Sturesson, Fredrik; Habinc, Sandi; Gaisler, Jiri

    2012-08-01

    The GR712RC System-on-Chip (SoC) is a dual core LEON3FT system suitable for advanced high reliability space avionics. Fault tolerance features from Aeroflex Gaisler’s GRLIB IP library and an implementation using Ramon Chips RadSafe cell library enables superior radiation hardness.The GR712RC device has been designed to provide high processing power by including two LEON3FT 32- bit SPARC V8 processors, each with its own high- performance IEEE754 compliant floating-point-unit and SPARC reference memory management unit.This high processing power is combined with a large number of serial interfaces, ranging from high-speed links for data transfers to low-speed control buses for commanding and status acquisition.

  5. SiglecF+Gr1hi eosinophils are a distinct subpopulation within the lungs of allergen-challenged mice

    PubMed Central

    Percopo, Caroline M.; Brenner, Todd A.; Ma, Michelle; Kraemer, Laura S.; Hakeem, Reem M. A.; Lee, James J.; Rosenberg, Helene F.

    2017-01-01

    Although eosinophils as a group are readily identified by their unique morphology and staining properties, flow cytometry provides an important means for identification of subgroups based on differential expression of distinct surface Ags. Here, we characterize an eosinophil subpopulation defined by high levels of expression of the neutrophil Ag Gr1 (CD45+CD11c−SiglecF+Gr1hi). SiglecF+Gr1hi eosinophils, distinct from the canonical SiglecF+Gr1− eosinophil population, were detected in allergen-challenged wild-type and granule protein-deficient (EPX−/− and MBP-1−/−) mice, but not in the eosinophil-deficient ΔdblGATA strain. In contrast to Gr1+ neutrophils, which express both cross-reacting Ags Ly6C and Ly6G, SiglecF+Gr1hi eosinophils from allergen-challenged lung tissue are uniquely Ly6G+. Although indistinguishable from the more-numerous SiglecF+Gr1− eosinophils under light microscopy, FACS-isolated populations revealed prominent differences in cytokine contents. The lymphocyte-targeting cytokines CXCL13 and IL-27 were identified only in the SiglecF+Gr1hi eosinophil population (at 3.9 and 4.8 pg/106 cells, respectively), as was the prominent proinflammatory mediator IL-13 (72 pg/106 cells). Interestingly, bone marrow-derived (SiglecF+), cultured eosinophils include a more substantial Gr1+ subpopulation (∼50%); Gr1+ bmEos includes primarily a single Ly6C+ and a smaller, double-positive (Ly6C+Ly6G+) population. Taken together, our findings characterize a distinct SiglecF+Gr1hi eosinophil subset in lungs of allergen-challenged, wild-type and granule protein-deficient mice. SiglecF+Gr1hi eosinophils from wild-type mice maintain a distinct subset of cytokines, including those active on B and T lymphocytes. These cytokines may facilitate eosinophil-mediated immunomodulatory responses in the allergen-challenged lung as well as in other distinct microenvironments. PMID:27531929

  6. SiglecF+Gr1hi eosinophils are a distinct subpopulation within the lungs of allergen-challenged mice.

    PubMed

    Percopo, Caroline M; Brenner, Todd A; Ma, Michelle; Kraemer, Laura S; Hakeem, Reem M A; Lee, James J; Rosenberg, Helene F

    2017-01-01

    Although eosinophils as a group are readily identified by their unique morphology and staining properties, flow cytometry provides an important means for identification of subgroups based on differential expression of distinct surface Ags. Here, we characterize an eosinophil subpopulation defined by high levels of expression of the neutrophil Ag Gr1 (CD45 + CD11c - SiglecF + Gr1 hi ). SiglecF + Gr1 hi eosinophils, distinct from the canonical SiglecF + Gr1 - eosinophil population, were detected in allergen-challenged wild-type and granule protein-deficient (EPX -/- and MBP-1 -/- ) mice, but not in the eosinophil-deficient ΔdblGATA strain. In contrast to Gr1 + neutrophils, which express both cross-reacting Ags Ly6C and Ly6G, SiglecF + Gr1 hi eosinophils from allergen-challenged lung tissue are uniquely Ly6G + Although indistinguishable from the more-numerous SiglecF + Gr1 - eosinophils under light microscopy, FACS-isolated populations revealed prominent differences in cytokine contents. The lymphocyte-targeting cytokines CXCL13 and IL-27 were identified only in the SiglecF + Gr1 hi eosinophil population (at 3.9 and 4.8 pg/10 6 cells, respectively), as was the prominent proinflammatory mediator IL-13 (72 pg/10 6 cells). Interestingly, bone marrow-derived (SiglecF + ), cultured eosinophils include a more substantial Gr1 + subpopulation (∼50%); Gr1 + bmEos includes primarily a single Ly6C + and a smaller, double-positive (Ly6C + Ly6G + ) population. Taken together, our findings characterize a distinct SiglecF + Gr1 hi eosinophil subset in lungs of allergen-challenged, wild-type and granule protein-deficient mice. SiglecF + Gr1 hi eosinophils from wild-type mice maintain a distinct subset of cytokines, including those active on B and T lymphocytes. These cytokines may facilitate eosinophil-mediated immunomodulatory responses in the allergen-challenged lung as well as in other distinct microenvironments. © Society for Leukocyte Biology.

  7. Targeting the FKBP51/GR/Hsp90 Complex to Identify Functionally Relevant Treatments for Depression and PTSD.

    PubMed

    Sabbagh, Jonathan J; Cordova, Ricardo A; Zheng, Dali; Criado-Marrero, Marangelie; Lemus, Andrea; Li, Pengfei; Baker, Jeremy D; Nordhues, Bryce A; Darling, April L; Martinez-Licha, Carlos; Rutz, Daniel A; Patel, Shreya; Buchner, Johannes; Leahy, James W; Koren, John; Dickey, Chad A; Blair, Laura J

    2018-06-19

    Genetic and epigenetic alterations in FK506-binding protein 5 ( FKBP5) have been associated with increased risk for psychiatric disorders, including post-traumatic stress disorder (PTSD). Some of these common variants can increase the expression of FKBP5, the gene that encodes FKBP51. Excess FKBP51 promotes hypothalamic-pituitary-adrenal (HPA) axis dysregulation through altered glucocorticoid receptor (GR) signaling. Thus, we hypothesized that GR activity could be restored by perturbing FKBP51. Here, we screened 1280 pharmacologically active compounds and identified three compounds that rescued FKBP51-mediated suppression of GR activity without directly activating GR. One of the three compounds, benztropine mesylate, disrupted the association of FKBP51 with the GR/Hsp90 complex in vitro. Moreover, we show that removal of FKBP51 from this complex by benztropine restored GR localization in ex vivo brain slices and primary neurons from mice. In conclusion, we have identified a novel disruptor of the FKBP51/GR/Hsp90 complex. Targeting this complex may be a viable approach to developing treatments for disorders related to aberrant FKBP51 expression.

  8. NRIP enhances HPV gene expression via interaction with either GR or E2

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

    Chang, Szu-Wei; Lu, Pei-Yu; Guo, Jih-Huong

    We previously identified a gene, nuclear receptor-interaction protein (NRIP), which functions as a transcription cofactor in glucocorticoid receptor (GR) and human papillomavirus E2 (HPV E2)-driven gene expression. Here, we comprehensively evaluated the role of NRIP in HPV-16 gene expression. NRIP acts as a transcription cofactor to enhance GR-regulated HPV-16 gene expression in the presence of hormone. NRIP also can form complex with E2 that caused NRIP-induced HPV gene expression via E2-binding sites in a hormone-independent manner. Furthermore, NRIP can associate with GR and E2 to form tri-protein complex to activate HPV gene expression via GRE, not the E2-binding site, inmore » a hormone-dependent manner. These results indicate that NRIP and GR are viral E2-binding proteins and that NRIP regulates HPV gene expression via GRE and/or E2 binding site in the HPV promoter in a hormone-dependent or independent manner, respectively.« less

  9. 77 FR 40511 - Safety Zone; GR Symphony Fireworks Display, Kalamazoo Lake, Saugatuck, MI

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-10

    ...-AA00 Safety Zone; GR Symphony Fireworks Display, Kalamazoo Lake, Saugatuck, MI AGENCY: Coast Guard, DHS... Kalamazoo Lake during the GR Symphony Fireworks display. This temporary safety zone is necessary to protect spectators and vessels from the hazards associated with a fireworks display. DATES: This rule will be...

  10. Variable stars in the dwarf galaxy GR 8 (DDO 155)

    NASA Technical Reports Server (NTRS)

    Tolstoy, Eline; Saha, A.; Hoessel, John G.; Danielson, G. Edward

    1995-01-01

    Observations of the resolved stars in dwarf galaxy GR 8, obtained over the period 1980 February to 1994 March, are presented. Thirty-four separate epochs were searched for variable stars, and a total of six were found, of which one has Cepheid characteristics. After correction for Galactic extinction this single Cepheid yields a distance modulus of m - M = 26.75 +/- 0.35. This corresponds to a distance of 2.24 Mpc, placing GR 8 near the Local Group (LG) zero-velocity surface. The other five variable stars are very red, and possibly have long periods of order 100 days or more.

  11. Gr-GDHP: A New Architecture for Globalized Dual Heuristic Dynamic Programming.

    PubMed

    Zhong, Xiangnan; Ni, Zhen; He, Haibo

    2017-10-01

    Goal representation globalized dual heuristic dynamic programming (Gr-GDHP) method is proposed in this paper. A goal neural network is integrated into the traditional GDHP method providing an internal reinforcement signal and its derivatives to help the control and learning process. From the proposed architecture, it is shown that the obtained internal reinforcement signal and its derivatives can be able to adjust themselves online over time rather than a fixed or predefined function in literature. Furthermore, the obtained derivatives can directly contribute to the objective function of the critic network, whose learning process is thus simplified. Numerical simulation studies are applied to show the performance of the proposed Gr-GDHP method and compare the results with other existing adaptive dynamic programming designs. We also investigate this method on a ball-and-beam balancing system. The statistical simulation results are presented for both the Gr-GDHP and the GDHP methods to demonstrate the improved learning and controlling performance.

  12. Maternal betaine supplementation during gestation modifies hippocampal expression of GR and its regulatory miRNAs in neonatal piglets

    PubMed Central

    SUN, Qinwei; LI, Xi; JIA, Yimin; PAN, Shifeng; LI, Runsheng; YANG, Xiaojing; ZHAO, Ruqian

    2016-01-01

    Methyl donor nutrients are critical for embryonic development of brain. Hippocampus is the most susceptible brain region to various factors including prenatal supply of methyl donors. Glucocorticoid receptor (GR) expressed in hippocampus is involved in the regulation of energy homeostasis and stress sensitivity. Hippocampal GR expression is highly susceptible to epigenetic regulation, yet the effect of maternal methyl donor supplementation on epigenetic regulation of GR transcription in offspring hippocampus remains unclear. In this study, we fed sows with betaine (3 g/kg) throughout the gestation and analyzed the hippocampal expression of GR mRNA and its variants, as well as the CpG methylation status of the promoter and the microRNAs predicted to target 3’ UTR of porcine GR gene in neonatal piglets. Total GR mRNA (P<0.01) and its variants GR 1-4 (P<0.05) and 1-9,10 (P<0.01), were significantly higher in the hippocampus of betaine-treated piglets, while the content of GR protein was not significantly changed. The CpGs located in the –1650 ~ –1515 segment of GR gene were hypermethylated (P<0.05). The hippocampal expression of miR-130b (P<0.05), miR-181a (P<0.05) and miR-181d (P<0.01) was significantly up-regulated. The targeting efficacy of miR-130b and miR-181d was validated in vitro using dual-luciferase reporter assay system. Our results demonstrate that maternal betaine supplementation during gestation enhances GR mRNA expression in offspring hippocampus, which involves alterations in miRNAs expression. PMID:26875838

  13. The novel GrCEP12 peptide from the plant-parasitic nematode Globodera rostochiensis suppresses flg22-mediated PTI.

    PubMed

    Chen, Shiyan; Chronis, Demosthenis; Wang, Xiaohong

    2013-09-01

    The potato cyst nematode Globodera rostochiensis is a biotrophic pathogen that secretes effector proteins into host root cells to promote successful plant parasitism. In addition to the role in generating within root tissue the feeding cells essential for nematode development, (1) nematode secreted effectors are becoming recognized as suppressors of plant immunity. (2)(-) (4) Recently we reported that the effector ubiquitin carboxyl extension protein (GrUBCEP12) from G. rostochiensis is processed into free ubiquitin and a 12-amino acid GrCEP12 peptide in planta. Transgenic potato lines overexpressing the derived GrCEP12 peptide showed increased susceptibility to G. rostochiensis and to an unrelated bacterial pathogen Streptomyces scabies, suggesting that GrCEP12 has a role in suppressing host basal defense or possibly pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) during the parasitic interaction. (3) To determine if GrCEP12 functions as a PTI suppressor we evaluated whether GrCEP12 suppresses flg22-induced PTI responses in Nicotiana benthamiana. Interestingly, we found that transient expression of GrCEP12 in N. benthamiana leaves suppressed reactive oxygen species (ROS) production and the induction of two PTI marker genes triggered by the bacterial PAMP flg22, providing direct evidence that GrCEP12 indeed has an activity in PTI suppression.

  14. HPA axis dysregulation and behavioral analysis of mouse mutants with altered GR or MR function

    PubMed Central

    Kolber, Benedict J.; Wieczorek, Lindsay; Muglia, Louis J.

    2009-01-01

    Corticosteroid receptors are critical for the maintenance of homeostasis after both psychological and physiological stress. To properly understand the different roles and interactions of the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) during stress, it is necessary to dissect the role of corticosteroid signaling at both the system and sub-system level. A variety of GR transgenic mouse lines have recently been used to characterize the role of GR in the CNS as a whole and particularly in the forebrain. We will describe both the behavioral and cellular/molecular implications of disrupting GR function in these animal models and describe the implications of this data for our understanding of normal endocrine function and stress adaptation. MRs in tight epithelia have a long established role in sodium homeostasis. Recently however, evidence has suggested that limbic MRs also play an important role in psychological stress. Just as with GR, targeted mutations in MR induce a variety of behavioral changes associated with stress adaptation. In this review, we will discuss the implications of this work on MR. Finally, we will discuss the possible interaction between MR and GR and how future work using double mutants (through conventional means or virus based gene alteration) will be needed to fully understand how signaling through these two steroid receptors provides the adaptive mechanisms to deal with a variety of stressors. PMID:18609295

  15. The pharmacology of GR203040, a novel, potent and selective non-peptide tachykinin NK1 receptor antagonist.

    PubMed Central

    Beattie, D. T.; Beresford, I. J.; Connor, H. E.; Marshall, F. H.; Hawcock, A. B.; Hagan, R. M.; Bowers, J.; Birch, P. J.; Ward, P.

    1995-01-01

    1. The in vitro and in vivo pharmacology of GR203040 ((2S, 3S)-2-methoxy-5-tetrazol-1-yl-benzyl-(2-phenyl-piperidin-3-y l)-amine), a novel, highly potent and selective non-peptide tachykinin NK1 receptor antagonist, was investigated in the present study. 2. GR203040 potently inhibited [3H]-substance P binding to human NK1 receptors expressed in Chinese hamster ovary (CHO) and U373 MG astrocytoma cells, and NK1 receptors in ferret and gerbil cortex (pKi values of 10.3, 10.5, 10.1 and 10.1 respectively). GR203040 had lower affinity at rat NK1 receptors (pKi = 8.6) and little affinity for human NK2 receptors (pKi < 5.0) in CHO cells and NK3 receptors in guinea-pig cortex (pKi < 6.0). With the exception of the histamine H1 receptor (pIC50 = 7.5). GR203040 had little affinity (pIC50 < 6.0) at all non-NK1 receptors and ion channels examined. Furthermore, GR203040 produced only weak inhibition of Na+ currents in SH-SY5Y neuroblastoma and superior cervical ganglion cells (pIC50 values < 4.0). GR203040 produced only weak antagonism of Ca(2+)-evoked contractions of rat isolated portal vein (pKn = 4.1). The enantiomer of GR203040, GR205608 (2R, 3R)-2-methoxy-5-tetrazol-1-yl-benzyl-(2-phenyl-piperidin-3-y l)-amine), had 10,000 fold lower affinity at the human NK1 receptor expressed in CHO cells (pKi = 6.3). 3. In gerbil ex vivo binding experiments, GR203040 produced a dose-dependent inhibition of the binding of [3H]-substance P to cerebral cortical membranes (ED50 = 15 micrograms kg-1 s.c. and 0.42 mg kg-1 p.o.). At 10 micrograms kg-1 s.c., the inhibition of [3H]-substance P binding was maintained for > 6 h. In the rat, GR203040 was less potent (ED50 = 15.4 mg kg-1 s.c.) probably reflecting, at least in part, its lower affinity at the rat NK1 receptor. 4. In guinea-pig isolated ileum and dog isolated middle cerebral and basilar arteries, GR203040 produced a rightward displacement of the concentration-effect curves to substance P methyl ester (SPOMe) with suppression of the

  16. Multi-band photometric study of the short-period eclipsing binary GR Boo

    NASA Astrophysics Data System (ADS)

    Wang, Daimei; Zhang, Liyun; Han, Xianming L.; Lu, Hongpeng

    2017-05-01

    We present BVRI light curves with complete phase coverage for the short-period (p = 0.377day) eclipsing binary star GR Boo. We carried out the observations using the SARA 90 cm telescope located at Kitt Peak National Observatory. We obtained six new light curve minimum times. By fitting all of the available O-C minimum times, we obtained an updated ephemeris that shows the orbital period of GR Boo is decreasing at a rate of P˙ = - 2.36 ×10-7 days/year. This decrease in its period can be explained by either mass transfer from the more massive component to the less massive one, or angular momentum exchange due to magnetic activities. We also obtained a set of revised orbital parameters using the Wilson & Devinney program. And finally, we concluded that GR Boo is a contact binary with a dark spot.

  17. [125I]-GR231118: a high affinity radioligand to investigate neuropeptide Y Y1 and Y4 receptors

    PubMed Central

    Dumont, Yvan; Quirion, Rémi

    2000-01-01

    GR231118 (also known as 1229U91 and GW1229), a purported Y1 antagonist and Y4 agonist was radiolabelled using the chloramine T method. [125I]-GR231118 binding reached equilibrium within 10 min at room temperature and remained stable for at least 4 h. Saturation binding experiments showed that [125I]-GR231118 binds with very high affinity (Kd of 0.09–0.24 nM) in transfected HEK293 cells with the rat Y1 and Y4 receptor cDNA and in rat brain membrane homogenates. No specific binding sites could be detected in HEK293 cells transfected with the rat Y2 or Y5 receptor cDNA demonstrating the absence of significant affinity of GR231118 for these two receptor classes. Competition binding experiments revealed that specific [125I]-GR231118 binding in rat brain homogenates is most similar to that observed in HEK293 cells transfected with the rat Y1, but not rat Y4, receptor cDNA. Autoradiographic studies demonstrated that [125I]-GR231118 binding sites were fully inhibited by the Y1 antagonist BIBO3304 in most areas of the rat brain. Interestingly, high percentage of [125I]-GR231118/BIBO3304-insensitive binding sites were detected in few areas. These [125I]-GR231118/BIBO3304-insensitive binding sites likely represent labelling to the Y4 receptor subtype. In summary, [125I]-GR231118 is a new radiolabelled probe to investigate the Y1 and Y4 receptors; its major advantage being its high affinity. Using highly selective Y1 antagonists such as BIBO3304 or BIBP3226 it is possible to block the binding of [125I]-GR231118 to the Y1 receptor allowing for the characterization and visualization of the purported Y4 subtype. PMID:10694200

  18. Interplay between gravity and quintessence: a set of new GR solutions

    NASA Astrophysics Data System (ADS)

    Chernin, Arthur D.; Santiago, David I.; Silbergleit, Alexander S.

    2002-02-01

    A set of new exact analytical general relativity (GR) solutions with time-dependent and spatially inhomogeneous quintessence demonstrate (1) a static non-empty space-time with a horizon-type singular surface; (2) time-dependent spatially homogeneous `spheres' which are completely different in geometry from the Friedmann isotropic models; (3) infinitely strong anti-gravity at a `true' singularity where the density is infinitely large. It is also found that (4) the GR solutions allow for an extreme `density-free' form of energy that can generate regular space-time geometries.

  19. The Response of the Root Proteome to the Synthetic Strigolactone GR24 in Arabidopsis*

    PubMed Central

    Walton, Alan; Stes, Elisabeth; Goeminne, Geert; Braem, Lukas; Vuylsteke, Marnik; Matthys, Cedrick; De Cuyper, Carolien; Staes, An; Vandenbussche, Jonathan; Boyer, François-Didier; Vanholme, Ruben; Fromentin, Justine; Boerjan, Wout; Gevaert, Kris; Goormachtig, Sofie

    2016-01-01

    Strigolactones are plant metabolites that act as phytohormones and rhizosphere signals. Whereas most research on unraveling the action mechanisms of strigolactones is focused on plant shoots, we investigated proteome adaptation during strigolactone signaling in the roots of Arabidopsis thaliana. Through large-scale, time-resolved, and quantitative proteomics, the impact of the strigolactone analog rac-GR24 was elucidated on the root proteome of the wild type and the signaling mutant more axillary growth 2 (max2). Our study revealed a clear MAX2-dependent rac-GR24 response: an increase in abundance of enzymes involved in flavonol biosynthesis, which was reduced in the max2–1 mutant. Mass spectrometry-driven metabolite profiling and thin-layer chromatography experiments demonstrated that these changes in protein expression lead to the accumulation of specific flavonols. Moreover, quantitative RT-PCR revealed that the flavonol-related protein expression profile was caused by rac-GR24-induced changes in transcript levels of the corresponding genes. This induction of flavonol production was shown to be activated by the two pure enantiomers that together make up rac-GR24. Finally, our data provide much needed clues concerning the multiple roles played by MAX2 in the roots and a comprehensive view of the rac-GR24-induced response in the root proteome. PMID:27317401

  20. SDSS (g--r) colors of isolated galaxies

    NASA Astrophysics Data System (ADS)

    Fernández Lorenzo, M.; Sulentic, J.; Verdes-Montenegro, L.; Ruiz, J. E.; Sabater, J.; Sánchez-Expósito, S.

    2013-05-01

    Several processes can affect a galaxy over its lifetime. If effects of interaction with companions are minimized, it is possible to focus on secular evolutionary processes. We present a study of the SDSS (g--r) colors of isolated galaxies in the AMIGA project (Analysis of the interstellar Medium of Isolated GAlaxies; http://www.amiga.iaa.es). Assuming that color is an indicator of the star formation history, this work better records the signature of passive star formation via pure secular evolution. We focused on median values for the main morphological subtypes found in the AMIGA sample (66% Sb--Sc and 14% E/S0) and compared them with equivalent measures of galaxies in denser environments. The main results of this study include: 1) a tendency for AMIGA spiral galaxies to be redder than similar type galaxies in close pairs, but 2) no clear difference when we compare with galaxies in other (e.g. group) environments; 3) a Gaussian distribution of the (g--r) color of isolated galaxies, as might be expected in the case of pure secular evolution; and 4) a smaller median absolute deviation in colors for isolated galaxies compared to both wide and close pairs.

  1. Validation of the German revised version of the program in palliative care education and practice questionnaire (PCEP-GR).

    PubMed

    Fetz, Katharina; Wenzel-Meyburg, Ursula; Schulz-Quach, Christian

    2017-12-28

    The evaluation of the effectiveness of undergraduate palliative care education (UPCE) programs is an essential foundation to providing high-quality UPCE programs. Therefore, the implementation of valid evaluation tools is indispensable. Until today, there has been no general consensus regarding concrete outcome parameters and their accurate measurement. The Program in Palliative Care Education and Practice Questionnaire (German Revised Version; PCEP-GR) is a promising assessment tool for UPCE. The aim of the current study was to evaluate the psychometric properties of PCEP-GR and to demonstrate its feasibility for the evaluation of UPCE programs. The practical feasibility of the PCEP-GR and its acceptance in medical students were investigated in a pilot study with 24 undergraduate medical students at Heinrich Heine University Dusseldorf, Germany. Subsequently, the PCEP-GR was surveyed in a representative sample (N = 680) of medical students in order to investigate its psychometric properties. Factorial validity was investigated by means of principal component analysis (PCA). Reliability was examined by means of split-half-reliability analysis and analysis of internal consistency. After taking into consideration the PCA and distribution analysis results, an evaluation instruction for the PCEP-GR was developed. The PCEP-GR proved to be feasible and well-accepted in medical students. PCA revealed a four-factorial solution indicating four PCEP-GR subscales: preparation to provide palliative care, attitudes towards palliative care, self-estimation of competence in communication with dying patients and their relatives and self-estimation of knowledge and skills in palliative care. The PCEP-GR showed good split-half-reliability and acceptable to good internal consistency of subscales. Attitudes towards palliative care slightly missed the criterion of acceptable internal consistency. The evaluation instruction suggests a global PCEP-GR index and four subscales. The

  2. Convergence of glycogen synthase kinase 3β and GR signaling in response to fluoxetine treatment in chronically stressed female and male rats.

    PubMed

    Mitic, Milos; Brkic, Zeljka; Lukic, Iva; Adzic, Miroslav

    2017-08-30

    Accumulating evidence strongly suggest that impaired glucocorticoid receptor (GR) signaling is involved in stress-related mood disorders, and nominate GR as a potential target for antidepressants (ADs). It is known that different classes of ADs affects the GR action via modifying its phosphorylation, while the mechanism through which ADs alter GR phosphorylation targeted by GSK3β, a kinase modulated via serotonin neurotransmission, are unclear. On this basis, we investigated whether GSK3β-GR signaling could be a convergence point of fluoxetine action on brain function and behavior, by examining its effect on GSK3β targeted-GR phosphorylation on threonine 171 (pGR171), and expression of GR-regulated genes in the hippocampus of female and male rats exposed to chronic isolation stress. Stress induced sex-specific GSK3β-targeted phosphorylation of pGR171 in the nucleus of the hippocampus of stressed animals. Namely, while in females stress triggered coupled action of GSK3β-pGR171 signaling, in males changes in pGR171 levels did not correspond to GSK3β activity. On the other hand, fluoxetine managed to up-regulate this pathway in sex-unbiased manner. Furthermore, fluoxetine reverted stress-induced changes in most of the analyzed genes in males, CRH, 5-HT1a and p11, while in females its effect was limited to CRH. These data further suggest that pGR171 signaling affects cellular localization of GR in response to chronic stress and fluoxetine in both sexes. Collectively, our results describe a novel convergence point between GR signaling and GSK3β pathway in rat hippocampus in response to stress and fluoxetine in both sexes and its involvement in fluoxetine-regulated brain function in males. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Functional characterization of PhGR and PhGRL1 during flower senescence in the petunia.

    PubMed

    Yang, Weiyuan; Liu, Juanxu; Tan, Yinyan; Zhong, Shan; Tang, Na; Chen, Guoju; Yu, Yixun

    2015-09-01

    Petunia PhGRL1 suppression accelerated flower senescence and increased the expression of the genes downstream of ethylene signaling, whereas PhGR suppression did not. Ethylene plays an important role in flowers senescence. Homologous proteins Green-Ripe and Reversion to Ethylene sensitivity1 are positive regulators of ethylene responses in tomato and Arabidopsis, respectively. The petunia flower has served as a model for the study of ethylene response during senescence. In this study, petunia PhGR and PhGRL1 expression was analyzed in different organs, throughout floral senescence, and after exogenous ethylene treatment; and the roles of PhGR and PhGRL1 during petunia flower senescence were investigated. PhGRL1 suppression mediated by virus-induced gene silencing accelerated flower senescence and increased ethylene production; however, the suppression of PhGR did not. Taken together, these data suggest that PhGRL1 is involved in negative regulation of flower senescence, possibly via ethylene production inhibition and consequently reduced ethylene signaling activation.

  4. GR 290 (ROMANO’S STAR). II. LIGHT HISTORY AND EVOLUTIONARY STATE

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

    Polcaro, V. F.; Nesci, R.; Chieffi, A.

    We have investigated the past light history of the luminous variable star GR 290 (M33/V532, Romano’s Star) in the M33 galaxy, and collected new spectrophotometric observations in order to analyze links between this object, the LBV category, and the Wolf–Rayet stars of the nitrogen sequence. We have built the historical light curve of GR 290 back to 1901, from old observations of the star found in several archival plates of M33. These old recordings together with published and new data on the star allowed us to infer that for at least half a century the star was in a lowmore » luminosity state, with B ≃ 18–19, most likely without brighter luminosity phases. After 1960, five large variability cycles of visual luminosity were recorded. The amplitude of the oscillations was seen increasing toward the 1992–1994 maximum, then decreasing during the last maxima. The recent light curve indicates that the photometric variations have been quite similar in all the bands and that the B – V color index has been constant within ±0.1{sup m} despite the 1.5{sup m} change of the visual luminosity. The spectrum of GR 290 at the large maximum of 1992–94 was equivalent to late-B-type, while, during 2002–2014, it varied between WN10h-11h near the visual maxima to WN8h-9h at the luminosity minima. We have detected, during this same period, a clear anti-correlation between the visual luminosity, the strength of the He ii 4686 Å emission line, the strength of the 4600–4700 Å lines’ blend, and the spectral type. From a model analysis of the spectra collected during the whole 2002–2014 period, we find that the Rosseland radius R {sub 2/3}, changed between the minimum and maximum luminosity phases by a factor of three while T {sub eff} varied between about 33,000 and 23,000 K. We confirm that the bolometric luminosity of the star has not been constant, but has increased by a factor of ∼1.5 between minimum and maximum luminosity, in phase with the apparent

  5. GrDHP: a general utility function representation for dual heuristic dynamic programming.

    PubMed

    Ni, Zhen; He, Haibo; Zhao, Dongbin; Xu, Xin; Prokhorov, Danil V

    2015-03-01

    A general utility function representation is proposed to provide the required derivable and adjustable utility function for the dual heuristic dynamic programming (DHP) design. Goal representation DHP (GrDHP) is presented with a goal network being on top of the traditional DHP design. This goal network provides a general mapping between the system states and the derivatives of the utility function. With this proposed architecture, we can obtain the required derivatives of the utility function directly from the goal network. In addition, instead of a fixed predefined utility function in literature, we conduct an online learning process for the goal network so that the derivatives of the utility function can be adaptively tuned over time. We provide the control performance of both the proposed GrDHP and the traditional DHP approaches under the same environment and parameter settings. The statistical simulation results and the snapshot of the system variables are presented to demonstrate the improved learning and controlling performance. We also apply both approaches to a power system example to further demonstrate the control capabilities of the GrDHP approach.

  6. Development of glyphosate-resistant alfalfa (Medicago sativa L.) upon transformation with the GR79Ms gene encoding 5-enolpyruvylshikimate-3-phosphate synthase.

    PubMed

    Yi, Dengxia; Ma, Lin; Lin, Min; Li, Cong

    2018-07-01

    The glyphosate-resistant gene, GR79Ms, was successfully introduced into the genome of alfalfa. The transgenic events may serve as novel germplasm resources in alfalfa breeding. Weed competition can reduce the alfalfa yield, generating new alfalfa germplasm with herbicide resistance is essential. To obtain transgenic alfalfa lines with glyphosate resistance, a new synthetic glyphosate-resistant gene GR79Ms encoding 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) was introduced into alfalfa germplasm by Agrobacterium tumefaciens-mediated transformation. In total, 67 transformants were obtained. PCR and Southern blot analyses confirmed that GR79Ms was successfully inserted into the genome of alfalfa. Reverse transcription-PCR and western blot analyses further demonstrated the expression of GR79Ms and its product, GR79Ms EPSPS. Moreover, two homozygous transgenic lines were developed in the T 2 generation by means of molecular-assisted selection. Herbicide tolerance spray tests showed that the transgenic plants T 0 -GR1, T 0 -GR2, T 0 -GR3 and two homozygous lines were able to tolerate fourfold higher commercial usage of glyphosate than non-transgenic plants.

  7. Bacillus amyloliquefaciens subsp. plantarum GR53, a potent biocontrol agent resists Rhizoctonia disease on Chinese cabbage through hormonal and antioxidants regulation.

    PubMed

    Kang, Sang-Mo; Radhakrishnan, Ramalingam; Lee, In-Jung

    2015-10-01

    The fungus Rhizoctonia solani is one of the causal agents of numerous diseases that affect crop growth and yield. The aim of this present investigation was to identify a biocontrol agent that acts against R. solani and to determine the agent's protective effect through phytohormones and antioxidant regulation in experimentally infected Chinese cabbage plants. Four rhizospheric soil bacterial isolates GR53, GR169, GR786, and GR320 were tested for their antagonistic activity against R. solani. Among these isolates, GR53 significantly suppressed fungal growth. GR53 was identified as Bacillus amyloliquefaciens subsp. plantarum by phylogenetic analysis of the 16S rDNA sequence. The biocontrol activity of B. amyloliquefaciens subsp. plantarum GR53 was tested in Chinese cabbage plants under controlled conditions. Results showed that R. solani inhibited plant growth (length, width, fresh and dry weight of leaves) by reducing chlorophyll and total phenolic content, as well as by increasing the levels of salicylic acid, jasmonic acid, abscisic acid, and DPPH scavenging activity. By regulating the levels of these compounds, the co-inoculation of B. amyloliquefaciens subsp. plantarum GR53 heightened induced systemic resistance in infected Chinese cabbage, effectively mitigating R. solani-induced damaging effects and improving plant growth. The results obtained from this study suggest that B. amyloliquefaciens subsp. plantarum GR53 is an effective biocontrol agent to prevent the damage caused by R. solani in Chinese cabbage plants.

  8. Master curve characterization of the fracture toughness behavior in SA508 Gr.4N low alloy steels

    NASA Astrophysics Data System (ADS)

    Lee, Ki-Hyoung; Kim, Min-Chul; Lee, Bong-Sang; Wee, Dang-Moon

    2010-08-01

    The fracture toughness properties of the tempered martensitic SA508 Gr.4N Ni-Mo-Cr low alloy steel for reactor pressure vessels were investigated by using the master curve concept. These results were compared to those of the bainitic SA508 Gr.3 Mn-Mo-Ni low alloy steel, which is a commercial RPV material. The fracture toughness tests were conducted by 3-point bending with pre-cracked charpy (PCVN) specimens according to the ASTM E1921-09c standard method. The temperature dependency of the fracture toughness was steeper than those predicted by the standard master curve, while the bainitic SA508 Gr.3 steel fitted well with the standard prediction. In order to properly evaluate the fracture toughness of the Gr.4N steels, the exponential coefficient of the master curve equation was changed and the modified curve was applied to the fracture toughness test results of model alloys that have various chemical compositions. It was found that the modified curve provided a better description for the overall fracture toughness behavior and adequate T0 determination for the tempered martensitic SA508 Gr.4N steels.

  9. Expression of AmGR10 of the Gustatory Receptor Family in Honey Bee Is Correlated with Nursing Behavior.

    PubMed

    Paerhati, Yisilahaiti; Ishiguro, Shinichi; Ueda-Matsuo, Risa; Yang, Ping; Yamashita, Tetsuro; Ito, Kikukatsu; Maekawa, Hideaki; Tani, Hiroko; Suzuki, Koichi

    2015-01-01

    We investigated the association between the expression of a gene encoding gustatory receptor (G10) and division of labor in the honey bee, Apis mellifera. Among 10 GR genes encoding proteins 15% ~ 99% amino acid identity in the honey bee, we found that AmGR10 with 99% identity is involved in nursing or brood care. Expression of AmGR10 was restricted to organs of the hypopharyngeal gland, brain, and ovary in the nurse bee phase. Members of an extended nursing caste under natural conditions continued to express this gene. RNAi knockdown of AmGR10 accelerated the transition to foraging. Our findings demonstrate that this one gene has profound effects on the division of labor associated with the development and physiology of honeybee society.

  10. Propagation of Flexural Mode AE Signals in GR/EP Composite Plates

    NASA Technical Reports Server (NTRS)

    Prosser, W. H.; Gorman, M. R.

    1992-01-01

    It has been documented that AE signals propagate in thin plates as extensional and flexural plate modes. This was demonstrated using simulated AE sources (pencil lead breaks) by Gorman on thin aluminum and gr/ep composite plates and by Gorman and Prosser on thin aluminum plates. A typical signal from a pencil lead break source which identifies these two modes is shown. AE signals from transverse matrix cracking sources in gr/ep composite plates were also shown to propagate as plate modes by Gorman and Ziola. Smith showed that crack growth events in thin aluminum plates under spectrum fatigue loading produced signals that propagated as plate modes. Additionally, Prosser et al. showed that AE signals propagated as plate modes in a thin walled composite tube.

  11. Generalized Clifford Algebras as Algebras in Suitable Symmetric Linear Gr-Categories

    NASA Astrophysics Data System (ADS)

    Cheng, Tao; Huang, Hua-Lin; Yang, Yuping

    2016-01-01

    By viewing Clifford algebras as algebras in some suitable symmetric Gr-categories, Albuquerque and Majid were able to give a new derivation of some well known results about Clifford algebras and to generalize them. Along the same line, Bulacu observed that Clifford algebras are weak Hopf algebras in the aforementioned categories and obtained other interesting properties. The aim of this paper is to study generalized Clifford algebras in a similar manner and extend the results of Albuquerque, Majid and Bulacu to the generalized setting. In particular, by taking full advantage of the gauge transformations in symmetric linear Gr-categories, we derive the decomposition theorem and provide categorical weak Hopf structures for generalized Clifford algebras in a conceptual and simpler manner.

  12. A Glycine-Rich RNA-Binding Protein, CsGR-RBP3, Is Involved in Defense Responses Against Cold Stress in Harvested Cucumber (Cucumis sativus L.) Fruit

    PubMed Central

    Wang, Bin; Wang, Guang; Shen, Fei; Zhu, Shijiang

    2018-01-01

    Plant glycine-rich RNA-binding proteins (GR-RBPs) have been shown to play important roles in response to abiotic stresses in actively proliferating organs such as young plants, root tips, and flowers, but their roles in chilling responses of harvested fruit remains largely unknown. Here, we investigated the role of CsGR-RBP3 in the chilling response of cucumber fruit. Pre-storage cold acclimation at 10°C (PsCA) for 3 days significantly enhanced chilling tolerance of cucumber fruit compared with the control fruit that were stored at 5°C. In the control fruit, only one of the six cucumber CsGR-RBP genes, CsGR-RBP2, was enhanced whereas the other five, i.e., CsGR-RBP3, CsGR-RBP4, CsGR-RBP5, CsGR-RBP-blt801, and CsGR-RBP-RZ1A were not. However, in the fruit exposed to PsCA before storage at 5°C, CsGR-RBP2 transcript levels were not obviously different from those in the controls, whereas the other five were highly upregulated, with CsGR-RBP3 the most significantly induced. Treatment with endogenous ABA and NO biosynthesis inhibitors, tungstate and L-nitro-arginine methyl ester, respectively, prior to PsCA treatment, clearly downregulated CsGR-RBP3 expression and significantly aggravated chilling injury. These results suggest a strong connection between CsGR-RBP3 expression and chilling tolerance in cucumber fruit. Transient expression in tobacco suggests CsGR-RBP3 was located in the mitochondria, implying a role for CsGR-RBP3 in maintaining mitochondria-related functions under low temperature. Arabidopsis lines overexpressing CsGR-RBP3 displayed faster growth at 23°C, lower electrolyte leakage and higher Fv/Fm ratio at 0°C, and higher survival rate at -20°C, than wild-type plants. Under cold stress conditions, Arabidopsis plants overexpressing CsGR-RBP3 displayed lower reactive oxygen species levels, and higher catalase and superoxide dismutase expression and activities, compared with the wild-type plants. In addition, overexpression of CsGR-RBP3 significantly

  13. GR-891: a novel 5-fluorouracil acyclonucleoside prodrug for differentiation therapy in rhabdomyosarcoma cells

    PubMed Central

    Marchal, J A; Prados, J; Melguizo, C; Gómez, J A; Campos, J; Gallo, M A; Espinosa, A; Arena, N; Aránega, A

    1999-01-01

    Differentiation therapy provides an alternative treatment of cancer that overcomes the undesirable effects of classical chemotherapy, i.e. cytotoxicity and resistance to drugs. This new approach to cancer therapy focuses on the development of specific agents designed to selectively engage the process of terminal differentiation, leading to the elimination of tumorigenic cells and recovery of normal cell homeostasis. A series of new anti-cancer pyrimidine acyclonucleoside-like compounds were designed and synthesized by structural modifications of 5-fluorouracil, a drug which causes considerable cell toxicity and morbidity, and we evaluated their applicability for differentiation therapy in human rhabdomyosarcoma cells. We tested the pyrimidine derivative GR-891, (RS)-1-{[3-(2-hydroxyethoxy)-1-isopropoxy]propyl}-5-fluorouracil, an active drug which shows low toxicity in vivo and releases acrolein which is an aldehyde with anti-tumour activity. Both GR-891 and 5-fluorouracil caused time- and dose-dependent growth inhibition in vitro; however, GR-891 showed no cytotoxicity at low doses (22.5 μmol l−1 and 45 μmol l−1) and induced terminal myogenic differentiation in RD cells (a rhabdomyosarcoma cell line) treated for 6 days. Changes in morphological features and in protein organization indicated re-entry in the pathway of muscular maturation. Moreover, GR-891 increased adhesion capability mediated by the expression of fibronectin, and did not induce overexpression of P-glycoprotein, the mdr1 gene product, implicated in multidrug resistance. New acyclonucleoside-like compounds such as GR-891 have important potential advantages over 5-fluorouracil because of their lower toxicity and their ability to induce myogenic differentiation in rhabdomyosarcoma cells. Our results suggest that this drug may be useful for differentiation therapy in this type of tumour. 1999 Cancer Research Campaign PMID:10070873

  14. airGR: a suite of lumped hydrological models in an R-package

    NASA Astrophysics Data System (ADS)

    Coron, Laurent; Perrin, Charles; Delaigue, Olivier; Andréassian, Vazken; Thirel, Guillaume

    2016-04-01

    Lumped hydrological models are useful and convenient tools for research, engineering and educational purposes. They propose catchment-scale representations of the precipitation-discharge relationship. Thanks to their limited data requirements, they can be easily implemented and run. With such models, it is possible to simulate a number of hydrological key processes over the catchment with limited structural and parametric complexity, typically evapotranspiration, runoff, underground losses, etc. The Hydrology Group at Irstea (Antony) has been developing a suite of rainfall-runoff models over the past 30 years with the main objectives of designing models as efficient as possible in terms of streamflow simulation, applicable to a wide range of catchments and having low data requirements. This resulted in a suite of models running at different time steps (from hourly to annual) applicable for various issues including water balance estimation, forecasting, simulation of impacts and scenario testing. Recently, Irstea has developed an easy-to-use R-package (R Core Team, 2015), called airGR, to make these models widely available. It includes: - the water balance annual GR1A (Mouehli et al., 2006), - the monthly GR2M (Mouehli, 2003) models, - three versions of the daily model, namely GR4J (Perrin et al., 2003), GR5J (Le Moine, 2008) and GR6J (Pushpalatha et al., 2011), - the hourly GR4H model (Mathevet, 2005), - a degree-day snow module CemaNeige (Valéry et al., 2014). The airGR package has been designed to facilitate the use by non-expert users and allow the addition of evaluation criteria, models or calibration algorithms selected by the end-user. Each model core is coded in FORTRAN to ensure low computational time. The other package functions (i.e. mainly the calibration algorithm and the efficiency criteria) are coded in R. The package is already used for educational purposes. The presentation will detail the main functionalities of the package and present a case

  15. Balloon Angioplasty – The Legacy of Andreas Grüntzig, M.D. (1939–1985)

    PubMed Central

    Barton, Matthias; Grüntzig, Johannes; Husmann, Marc; Rösch, Josef

    2014-01-01

    In 1974, at the Medical Policlinic of the University of Zürich, German-born physician-scientist Andreas Grüntzig (1939–1985) for the first time applied a balloon-tipped catheter to re-open a severely stenosed femoral artery, a procedure, which he initially called “percutaneous transluminal dilatation”. Balloon angioplasty as a therapy of atherosclerotic vascular disease, for which Grüntzig and Charles T. Dotter (1920–1985) received a nomination for the Nobel Prize in Physiology or Medicine in 1978, became one of the most successful examples of translational medicine in the twentieth century. Known today as percutaneous transluminal angioplasty (PTA) in peripheral arteries or percutaneous transluminal coronary angioplasty (PTCA) or percutaneous coronary intervention (PCI) in coronary arteries, balloon angioplasty has become the method of choice to treat patients with acute myocardial infarction or occluded leg arteries. On the occasion of the 40th anniversary of balloon angioplasty, we summarize Grüntzig’s life and career in Germany, Switzerland, and the United States and also review the developments in vascular medicine from the 1890s to the 1980s, including Dotter’s first accidental angioplasty in 1963. The work of pioneers of catheterization, including Pedro L. Fariñas in Cuba, André F. Cournand in France, Werner Forssmann, Werner Porstmann and Eberhard Zeitler in Germany, António Egas Moniz and Reynaldo dos Santos in Portugal, Sven-Ivar Seldinger in Sweden, and Barney Brooks, Thomas J. Fogarty, Melvin P. Judkins, Richard K. Myler, Dickinson W. Richards, and F. Mason Sones in the United States, is discussed. We also present quotes by Grüntzig and excerpts from his unfinished autobiography, statements of Grüntzig’s former colleagues and contemporary witnesses, and have included hitherto unpublished historic photographs and links to archive recordings and historic materials. This year, on June 25, 2014, Andreas Grüntzig would have celebrated

  16. Economic Analysis of the Greenland Inland Traverse (GrIT)

    DTIC Science & Technology

    2016-06-01

    Weale of CRREL and that Randy Olsen, Gary Eells, Jen Mer- cer, and Scot Arnold provided on behalf of NSF-PLR. COL Bryan S. Green was Commander of ERDC...pontoons as lightweight, compliant suspensions be- tween HMW-PE sheets and wood -framed cargo decks. In 2012, GrIT de- ployed several tube-in-pouch ARCS

  17. Reanalysis of the orbital period variations of two DLMR overcontact binaries: FG Hya and GR Vir

    NASA Astrophysics Data System (ADS)

    Zhang, Xu-Dong; Yu, Yun-Xia; Xiang, Fu-Yuan; Hu, Ke

    2017-12-01

    We investigate orbital period changes of two deep, low mass ratio (DLMR) overcontact W UMa-type binaries, FG Hya and GR Vir. It is found that the orbital period of FG Hya shows a cyclic change with a period of {P}{mod}=54.44 {yr}. The cyclic oscillation may be due to a third body in an eccentric orbit, while the orbital period of GR Vir shows a periodic variation with a period of {P}{mod}=28.56 {yr} and an amplitude of A = 0.0352 d. The periodic variation of GR Vir can be interpreted as a result of either the light-time effect of an unseen third body or the magnetic activity cycle.

  18. CD11b+Gr-1dim Tolerogenic Dendritic Cell-Like Cells Are Expanded in Interstitial Lung Disease in SKG Mice.

    PubMed

    Sendo, Sho; Saegusa, Jun; Okano, Takaichi; Takahashi, Soshi; Akashi, Kengo; Morinobu, Akio

    2017-12-01

    SKG mice develop interstitial lung disease (ILD) resembling rheumatoid arthritis-associated ILD in humans. The aim of this study was to clarify the mechanism underlying the lung pathology by analyzing lung-infiltrating cells in SKG mice with ILD. We assessed the severity of zymosan A (ZyA)-induced ILD in SKG mice histologically, and we examined lung-infiltrating cells by flow cytometry. Total lung cells and isolated monocytic myeloid-derived suppressor cells (MDSCs) were cultured in vitro with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4. The proliferation of 5,6-carboxyfluorescein diacetate N-succinimidyl ester-labeled naive T cells cocultured with isolated CD11b+Gr-1 dim cells and MDSCs was evaluated by flow cytometry. CD11b+Gr-1 dim cells were adoptively transferred to ZyA-treated SKG mice. MDSCs, Th17 cells, and group 1 and 3 innate lymphoid cells (ILC1s and ILC3s) were increased in the lungs; the proportion of these cells varied with ILD severity. In this process, we found that a unique cell population, CD11b+Gr-1 dim cells, was expanded in the severely inflamed lungs. Approximately half of the CD11b+Gr-1 dim cells expressed CD11c. CD11b+Gr-1 dim cells were induced from monocytic MDSCs with GM-CSF in vitro and were considered tolerogenic because they suppressed T cell proliferation. These CD11b+Gr-1 dim cells have never been described previously, and we termed them CD11b+Gr-1 dim tolerogenic dendritic cell (DC)-like cells. Th17 cells, ILC1s, and ILC3s in the inflamed lung produced GM-CSF, which may have expanded CD11b+Gr-1 dim tolerogenic DC-like cells in vivo. Furthermore, adoptive transfer of CD11b+Gr-1 dim tolerogenic DC-like cells significantly suppressed progression of ILD in SKG mice. We identified unique suppressive myeloid cells that were differentiated from monocytic MDSCs in SKG mice with ILD, and we termed them CD11b+Gr-1 dim tolerogenic DC-like cells. © 2017, American College of Rheumatology.

  19. Origin, distribution and 3D-modeling of Gr-EXPB1, an expansin from the potato cyst nematode Globodera rostochiensis.

    PubMed

    Kudla, Urszula; Qin, Ling; Milac, Adina; Kielak, Anna; Maissen, Cyril; Overmars, Hein; Popeijus, Herman; Roze, Erwin; Petrescu, Andrei; Smant, Geert; Bakker, Jaap; Helder, Johannes

    2005-04-25

    Southern analysis showed that Gr-EXPB1, a functional expansin from the potato cyst nematode Globodera rostochiensis, is member of a multigene family, and EST data suggest expansins to be present in other plant parasitic nematodes as well. Homology modeling predicted that Gr-EXPB1 domain 1 (D1) has a flat beta-barrel structure with surface-exposed aromatic rings, whereas the 3D structure of Gr-EXPB1-D2 was remarkably similar to plant expansins. Gr-EXPB1 shows highest sequence similarity to two extracellular proteins from saprophytic soil-inhabiting Actinobacteria, and includes a bacterial type II carbohydrate-binding module. These results support the hypothesis that a number of pathogenicity factors of cyst nematodes is of procaryotic origin and were acquired by horizontal gene transfer.

  20. Long-term orbital period behaviour of low mass ratio contact binaries GR Vir and FP Boo

    NASA Astrophysics Data System (ADS)

    Ćetinkaya, Halil; Soydugan, Faruk

    2017-02-01

    In this study, we investigated orbital period variations of two low mass ratio contact binaries GR Vir and FP Boo based on published minima times. From the O-C analysis, it was found that FP Boo indicates orbital period decrease while the period of GR Vir is increasing. Mass transfer process was used to explain increase and decrease in the orbital periods. In the O-C diagrams of both systems periodic variations also exist. Cyclic changes can be explained as being the result of a light-travel time effect via a third component around the eclipsing binaries. In order to interpret of cyclic orbital period changes for GR Vir, which has late-type components, possible magnetic activity cycles of the components have been also considered.

  1. Cisplatin-Induced Conditioned Taste Aversion: Attenuation by Dexamethasone but not Zacopride or GR38032F

    DTIC Science & Technology

    1992-01-01

    SR2-1 Cisplatin-induced conditioned taste aversion: ateuto by dexamethasone but not zacopride or GR38032F Nm I- Paul C Mele, John R. McDonough, David...to 5-H1’, receptor blockade. 5-HT., receptor antagonists; Zacopridc: GR38032F; Desamethasone: Cisplatin: Taste aversion (conditioned) I. Introductlon...intake) was used as the area known as the chemoreceptor trigger zone (Borri- index of the CTA. son, 1974). Moreover. the findings that rats, ferrets

  2. CCR2-dependent Gr1high monocytes promote kidney injury in shiga toxin-induced hemolytic uremic syndrome in mice.

    PubMed

    Pohl, Judith-Mira; Volke, Julia K; Thiebes, Stephanie; Brenzel, Alexandra; Fuchs, Kerstin; Beziere, Nicolas; Ehrlichmann, Walter; Pichler, Bernd J; Squire, Anthony; Gueler, Faikah; Engel, Daniel R

    2018-06-01

    The hemolytic uremic syndrome (HUS) is a life-threatening disease of the kidney that is induced by shiga toxin-producing E.coli. Major changes in the monocytic compartment and in CCR2-binding chemokines have been observed. However, the specific contribution of CCR2-dependent Gr1 high monocytes is unknown. To investigate the impact of these monocytes during HUS, we injected a combination of LPS and shiga toxin into mice. We observed an impaired kidney function and elevated levels of the CCR2-binding chemokine CCL2 after shiga toxin/LPS- injection, thus suggesting Gr1 high monocyte infiltration into the kidney. Indeed, the number of Gr1 high monocytes was strongly increased one day after HUS induction. Moreover, these cells expressed high levels of CD11b suggesting activation after tissue entry. Non-invasive PET-MR imaging revealed kidney injury mainly in the kidney cortex and this damage coincided with the detection of Gr1 high monocytes. Lack of Gr1 high monocytes in Ccr2-deficient animals reduced neutrophil gelatinase-associated lipocalin and blood urea nitrogen levels. Moreover, the survival of Ccr2-deficient animals was significantly improved. Conclusively, this study demonstrates that CCR2-dependent Gr1 high monocytes contribute to the kidney injury during HUS and targeting these cells is beneficial during this disease. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Quantification of sensitivity and resistance of breast cancer cell lines to anti-cancer drugs using GR metrics

    PubMed Central

    Hafner, Marc; Heiser, Laura M.; Williams, Elizabeth H.; Niepel, Mario; Wang, Nicholas J.; Korkola, James E.; Gray, Joe W.; Sorger, Peter K.

    2017-01-01

    Traditional means for scoring the effects of anti-cancer drugs on the growth and survival of cell lines is based on relative cell number in drug-treated and control samples and is seriously confounded by unequal division rates arising from natural biological variation and differences in culture conditions. This problem can be overcome by computing drug sensitivity on a per-division basis. The normalized growth rate inhibition (GR) approach yields per-division metrics for drug potency (GR50) and efficacy (GRmax) that are analogous to the more familiar IC50 and Emax values. In this work, we report GR-based, proliferation-corrected, drug sensitivity metrics for ~4,700 pairs of breast cancer cell lines and perturbagens. Such data are broadly useful in understanding the molecular basis of therapeutic response and resistance. Here, we use them to investigate the relationship between different measures of drug sensitivity and conclude that drug potency and efficacy exhibit high variation that is only weakly correlated. To facilitate further use of these data, computed GR curves and metrics can be browsed interactively at http://www.GRbrowser.org/. PMID:29112189

  4. Activation of Antigen-Specific CD8(+) T Cells by Poly-DL-Lactide/Glycolide (PLGA) Nanoparticle-Primed Gr-1(high) Cells.

    PubMed

    Luo, Wen-Hui; Yang, Ya-Wun

    2016-04-01

    The aim of this study was to investigate the induction of antigen-specific T cell activation and cell cycle modulation by a poly-DL-lactide/glycolide (PLGA) nanoparticle (NP)-primed CD11b(+)Gr-1(high) subset isolated from mouse bone marrow. PLGA NPs containing the ovalbumin (OVA) antigen were prepared using the double emulsion and solvent evaporation method, and protein release rate and cell viability were determined. The Lin2(¯)CD11b(+)Gr-1(high)Ly6c(low) (Gr-1(high)) subset was sorted from the bone marrow of C57BL/6 J mice by fluorescence-activated cell sorting (FACS) and co-cultured with OT-I CD8(+) splenic T cells. Proliferation of OT-I CD8(+) T cells was monitored, and cell cycles were determined by 5-bromo-2'-deoxyuridine (BrdU) labeling. Treatment of Gr-1(high) cells with PLGA/OVA NPs upregulated expression of the SIINFEKL-H2K(b) complex in the context of MHC I. Co-cultures of OT-I CD8(+) T cells with the PLGA/OVA NP-primed Gr-1(high) cells induced the proliferation of T cells in vitro and modulated cell division and morphology. Treatment of Gr-1(high) cells with PLGA/OVA NPs also induced cell apoptosis and necrosis. This study demonstrated the function of PLGA/OVA NPs in the activation of OT-I CD8(+) T cells and the capability of cross-presentation via the Gr-1(high) polymorphonuclear subset from mouse bone marrow.

  5. Tumor cell-released TLR4 ligands stimulate Gr-1+CD11b+F4/80+ cells to induce apoptosis of activated T cells.

    PubMed

    Liu, Yan-Yan; Sun, Ling-Cong; Wei, Jing-Jing; Li, Dong; Yuan, Ye; Yan, Bin; Liang, Zhi-Hui; Zhu, Hui-Fen; Xu, Yong; Li, Bo; Song, Chuan-Wang; Liao, Sheng-Jun; Lei, Zhang; Zhang, Gui-Mei; Feng, Zuo-Hua

    2010-09-01

    Gr-1(+)CD11b(+)F4/80(+) cells play important roles in tumor development and have a negative effect on tumor immunotherapy. So far, the mechanisms underlying the regulation of their immunosuppressive phenotype by classical and alternative macrophage activation stimuli are not well elucidated. In this study, we found that molecules from necrotic tumor cells (NTC-Ms) stimulated Gr-1(+)CD11b(+)F4/80(+) cells to induce apoptosis of activated T cells but not nonstimulated T cells. The apoptosis-inducing capacity was determined by higher expression levels of arginase I and IL-10 relative to those of NO synthase 2 and IL-12 in Gr-1(+)CD11b(+)F4/80(+) cells, which were induced by NTC-Ms through TLR4 signaling. The apoptosis-inducing capacity of NTC-Ms-stimulated Gr-1(+)CD11b(+)F4/80(+) cells could be enhanced by IL-10. IFN-gamma may reduce the apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells only if their response to IFN-gamma was not attenuated. However, the potential of Gr-1(+)CD11b(+)F4/80(+) cells to express IL-12 in response to IFN-gamma could be attenuated by tumor, partially due to the existence of active STAT3 in Gr-1(+)CD11b(+)F4/80(+) cells and NTC-Ms from tumor. In this situation, IFN-gamma could not effectively reduce the apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells. Tumor immunotherapy with 4-1BBL/soluble programmed death-1 may significantly reduce, but not abolish the apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells in local microenvironment. Blockade of TLR4 signaling could further reduce the apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells and enhance the suppressive effect of 4-1BBL/soluble form of programmed death-1 on tumor growth. These findings indicate the relationship of distinct signaling pathways with apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells and emphasize the importance of blocking TLR4 signaling to prevent the induction of T cell apoptosis by Gr-1(+)CD11b(+)F4/80(+) cells.

  6. Recruitment of bone marrow CD11b+Gr-1+ cells by polymeric nanoparticles for antigen cross-presentation

    NASA Astrophysics Data System (ADS)

    Yang, Ya-Wun; Luo, Wen-Hui

    2017-03-01

    The objective of this study was to investigate the function of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) on the activation of antigen-specific CD8+ T cell responses via the CD11b+Gr-1+ myeloid subpopulations in murine bone marrow (BM). PLGA NPs containing ovalbumin (OVA) were fabricated by the double-emulsion method. The CD11b+Gr-1lowLy-6Chigh and CD11b+Gr-1highLy-6Clow subsets from mice bone marrow were sorted and treated with the PLGA/OVA NPs, followed by co-culture with the carboxyfluorescein succinimidyl ester (CFSE)-labelled OT-I CD8+ cells. Co-culture of OT-I CD8+ T cells with PLGA/OVA NPs-primed CD11b+Gr-1+ subsets upregulated the expression of IL-2, TNF-α, INF-γ, granzyme B, and perforin, resulting in proliferation of CD8+ T cells and differentiation into effector cytotoxic T lymphocytes (CTLs). In vivo proliferation of CFSE-labelled OT-I CD8+ cells in response to OVA was also obtained in the animals immunized with PLGA/OVA NPs. The results presented in this study demonstrate the ability of polymeric NPs to recruit two CD11b+Gr-1+ myeloid subsets for effective presentation of exogenous antigen to OT-I CD8+ T cells in the context of major histocompatibility complex (MHC) class I, leading to an induction of antigen-specific cell proliferation and differentiation into effector cells.

  7. Conservation of Animal Genetic Resources (AnGR): the Next Decade

    USDA-ARS?s Scientific Manuscript database

    After 20 years, progress has been made in conserving AnGR; but how it will be in ten years? Viewing gene banks and in situ conservation in the context of food security, climate change, and product demand suggest a more efficient use of these practices to support sustainable production. Gene banks sh...

  8. Grímsvötn Volcano Injects Ash into the Stratosphere

    NASA Image and Video Library

    2011-05-24

    NASA Terra spacecraft captured this image of Grímsvötn, the most active of Iceland volcanoes, which began erupting around 5:30 p.m. local time 1730 UTC on Saturday, May 21, 2011, east of the capital city of Reykjavik.

  9. HIV-1 Vpr Induces Adipose Dysfunction in Vivo Through Reciprocal Effects on PPAR/GR Co-Regulation

    PubMed Central

    Agarwal, Neeti; Iyer, Dinakar; Patel, Sanjeet G.; Sekhar, Rajagopal V.; Phillips, Terry M.; Schubert, Ulrich; Oplt, Toni; Buras, Eric D.; Samson, Susan L.; Couturier, Jacob; Lewis, Dorothy E.; Rodriguez-Barradas, Maria C.; Jahoor, Farook; Kino, Tomoshige; Kopp, Jeffrey B.; Balasubramanyam, Ashok

    2014-01-01

    Viral infections, such as HIV, have been linked to obesity, but mechanistic evidence that they cause adipose dysfunction in vivo is lacking. We investigated a pathogenic role for the HIV-1 accessory protein viral protein R (Vpr), which can coactivate the glucocorticoid receptor (GR) and co-repress peroxisome proliferator–activated receptor γ (PPARγ) in vitro, in HIV-associated adipose dysfunction. Vpr circulated in the blood of most HIV-infected patients tested, including those on antiretroviral therapy (ART) with undetectable viral load. Vpr-mediated mechanisms were dissected in vivo using mouse models expressing the Vpr transgene in adipose tissues and liver (Vpr-Tg) or infused with synthetic Vpr. Both models demonstrated accelerated whole-body lipolysis, hyperglycemia and hypertriglyceridemia, and tissue-specific findings. Fat depots in these mice had diminished mass, macrophage infiltration, and blunted PPARγ target gene expression but increased GR target gene expression. In liver, we observed blunted PPARα target gene expression, steatosis with decreased adenosine monophosphate– activated protein kinase activity, and insulin resistance. Similar to human HIV-infected patients, Vpr circulated in the serum of Vpr-Tg mice. Vpr blocked differentiation in preadipocytes through cell cycle arrest, whereas in mature adipocytes, it increased lipolysis with reciprocally altered association of PPARγ and GR with their target promoters. These results delineate a distinct pathogenic sequence: Vpr, released from HIV-1 in tissue reservoirs after ART, can disrupt PPAR/GR co-regulation and cell cycle control to produce adipose dysfunction and hepatosteatosis. Confirmation of these mechanisms in HIV patients could lead to targeted treatment of the metabolic complications with Vpr inhibitors, GR antagonists, or PPARγ/PPARα agonists. PMID:24285483

  10. Anharmonic interatomic force constants and thermal conductivity from Grüneisen parameters: An application to graphene

    NASA Astrophysics Data System (ADS)

    Lee, Ching Hua; Gan, Chee Kwan

    2017-07-01

    Phonon-mediated thermal conductivity, which is of great technological relevance, arises due fundamentally to anharmonic scattering from interatomic potentials. Despite its prevalence, accurate first-principles calculations of thermal conductivity remain challenging, primarily due to the high computational cost of anharmonic interatomic force constant (IFC) calculations. Meanwhile, the related anharmonic phenomenon of thermal expansion is much more tractable, being computable from the Grüneisen parameters associated with phonon frequency shifts due to crystal deformations. In this work, we propose an approach for computing the largest cubic IFCs from the Grüneisen parameter data. This allows an approximate determination of the thermal conductivity via a much less expensive route. The key insight is that although the Grüneisen parameters cannot possibly contain all the information on the cubic IFCs, being derivable from spatially uniform deformations, they can still unambiguously and accurately determine the largest and most physically relevant ones. By fitting the anisotropic Grüneisen parameter data along judiciously designed deformations, we can deduce (i.e., reverse-engineer) the dominant cubic IFCs and estimate three-phonon scattering amplitudes. We illustrate our approach by explicitly computing the largest cubic IFCs and thermal conductivity of graphene, especially for its out-of-plane (flexural) modes that exhibit anomalously large anharmonic shifts and thermal conductivity contributions. Our calculations on graphene not only exhibit reasonable agreement with established density-functional theory results, but they also present a pedagogical opportunity for introducing an elegant analytic treatment of the Grüneisen parameters of generic two-band models. Our approach can be readily extended to more complicated crystalline materials with nontrivial anharmonic lattice effects.

  11. UV light B-mediated inhibition of skin catalase activity promotes Gr-1+ CD11b+ myeloid cell expansion.

    PubMed

    Sullivan, Nicholas J; Tober, Kathleen L; Burns, Erin M; Schick, Jonathan S; Riggenbach, Judith A; Mace, Thomas A; Bill, Matthew A; Young, Gregory S; Oberyszyn, Tatiana M; Lesinski, Gregory B

    2012-03-01

    Skin cancer incidence and mortality are higher in men compared with women, but the causes of this sex discrepancy remain largely unknown. UV light exposure induces cutaneous inflammation and neutralizes cutaneous antioxidants. Gr-1(+)CD11b(+) myeloid cells are heterogeneous bone marrow-derived cells that promote inflammation-associated carcinogenesis. Reduced activity of catalase, an antioxidant present in the skin, has been associated with skin carcinogenesis. We used the outbred, immune-competent Skh-1 hairless mouse model of UVB-induced inflammation and non-melanoma skin cancer to further define sex discrepancies in UVB-induced inflammation. Our results demonstrated that male skin had relatively lower baseline catalase activity, which was inhibited following acute UVB exposure in both sexes. Further analysis revealed that skin catalase activity inversely correlated with splenic Gr-1(+)CD11b(+) myeloid cell percentage. Acute UVB exposure induced Gr-1(+)CD11b(+) myeloid cell skin infiltration, which was inhibited to a greater extent in male mice by topical catalase treatment. In chronic UVB studies, we demonstrated that the percentage of splenic Gr-1(+)CD11b(+) myeloid cells was 55% higher in male tumor-bearing mice compared with their female counterparts. Together, our findings indicate that lower skin catalase activity in male mice may at least in part contribute to increased UVB-induced generation of Gr-1(+)CD11b(+) myeloid cells and subsequent skin carcinogenesis.

  12. Evolution of radiation defect and radiation hardening in heat treated SA508 Gr3 steel

    NASA Astrophysics Data System (ADS)

    Jin, Hyung-Ha; Kwon, Junhyun; Shin, Chansun

    2014-01-01

    The formation of radiation defects and corresponding radiation hardening in heat-treated SA508 Gr3 steel after Fe ion irradiation were investigated by means of transmission electron microscopy and a nano-indentation technique. As the residual dislocation density is increased in the matrix, the formation of radiation defects is considerably weakened. Comparison between the characteristics of the radiation defect and an evaluation of radiation hardening indicates that a large dislocation loop contributes little to the radiation hardening in the heat-treated SA508 Gr3 steel.

  13. Bone marrow-derived Gr1+ cells can generate a metastasis-resistant microenvironment via induced secretion of thrombospondin-1

    PubMed Central

    Catena, Raúl; Bhattacharya, Nandita; Rayes, Tina El; Wang, Suming; Choi, Hyejin; Gao, Dingcheng; Ryu, Seongho; Joshi, Natasha; Bielenberg, Diane; Lee, Sharrell B.; Haukaas, Svein A.; Gravdal, Karsten; Halvorsen, Ole J.; Akslen, Lars A.; Watnick, Randolph S.; Mittal, Vivek

    2013-01-01

    Metastatic tumors have been shown to establish permissive microenvironments for metastases via recruitment of bone marrow (BM)- derived cells. Here, we show that metastasis-incompetent tumors are also capable of generating such microenvironments. However, in these situations the otherwise pro-metastatic Gr1+ myeloid cells create a metastasis-refractory microenvironment via the induction of thrombospondin-1 (Tsp-1) by tumor-secreted prosaposin. (BM)-specific genetic deletion of Tsp-1 abolished the inhibition of metastasis, which was restored by BM transplant from Tsp-1+ donors. We also developed a 5-amino acid peptide from prosaposin as a pharmacological inducer of Tsp-1 in Gr1+ BM cells, which dramatically suppresses metastasis. These results provide mechanistic insights into why certain tumors are deficient in metastatic potential and implicate recruited Gr1+ myeloid cells as the main source of Tsp-1. The results underscore the plasticity of Gr1+ cells, which, depending on the context, promote or inhibit metastasis, and suggest that the peptide could be a potential therapeutic agent against metastatic cancer. PMID:23633432

  14. Transcriptional regulation of human paraoxonase 1 by PXR and GR in human hepatoma cells.

    PubMed

    Ponce-Ruiz, N; Rojas-García, A E; Barrón-Vivanco, B S; Elizondo, G; Bernal-Hernández, Y Y; Mejía-García, A; Medina-Díaz, I M

    2015-12-25

    Human paraoxonase 1 (PON1) is A-esterase synthesized in the liver and secreted into the plasma, where it associates with HDL. PON1 acts as an antioxidant preventing lipid oxidation and detoxifies a wide range of substrates, including organophosphate compounds. The variability of PON1 (enzyme activity/serum levels) has been attributed to internal and external factors. However, the molecular mechanisms involved in the transcriptional regulation of PON1 have not been well-studied. The aim of this study was to evaluate and characterize the transcriptional activation of PON1 by nuclear receptors (NR) in human hepatoma cells. In silico analysis was performed on the promoter region of PON1 to determine the response elements of NR. Real-time PCR was used to evaluate the effect of specific NR ligands on the mRNA levels of genes regulated by NR and PON1. The results indicated that NR response elements had 95% homology to pregnenolone (PXR), glucocorticoids (GR), retinoic acid (RXR) and peroxisomes proliferator-activated receptor alpha (PPARα). Treatments with Dexamethasone (GR ligand), Rifampicin (PXR ligand) and TCDD (AhR ligand) increased the mRNA levels of PON1 at 24 and 48 h. We showed that the activation of GR by Dexamethasone results in PON1 gene induction accompanied by an increase in activity levels. In conclusion, these results demonstrate that GR regulates PON1 gene transcription through directly binding to NR response elements at -95 to -628 bp of the PON1 promoter. This study suggests new molecular mechanisms for the transcriptional regulation of PON1 through a process involving the activation of PXR. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Elevated utero/placental GR/NR3C1 is not required for the induction of parturition in the dog.

    PubMed

    Gram, Aykut; Trachsel, Alexandra; Boos, Alois; Kowalewski, Mariusz P

    2016-10-01

    The endocrine mechanisms that lead to initiation of parturition in dogs are still not fully understood. The prepartum luteolysis is associated with increased prostaglandin (PG) F2α secretion; however, there is no pregnancy- or parturition-related increase in estrogens. Moreover, unlike in other mammalian species, in the dog, increased peripartum levels of cortisol measured sporadically in maternal peripheral blood are not mandatory for normal parturition. Nevertheless, auto/paracrine effects of cortisol at the placental feto-maternal level cannot be excluded. Therefore, the aim of this study was to investigate the expression and localization of glucocorticoid receptor (GR/NR3C1) in canine utero/placental (Ut/Pl) units and uterine interplacental sites at selected time points during pregnancy (pre-implantation, post-implantation and mid-gestation), and at normal and antigestagen-induced parturition. The Ut/Pl expression of GR/NR3C1 did not change significantly from pre-implantation until mid-gestation; however, it was strongly induced during the prepartum luteolysis. Within the interplacental samples, expression of GR/NR3C1-mRNA was greater post-implantation than pre-implantation and did not change afterward, i.e. toward mid-gestation. Compartmentalization studies within the Ut/Pl units, involving placenta, endometrium and myometrium separately, performed at the prepartum luteolysis revealed the highest GR/NR3C1-mRNA levels in placenta compared with endometrium and myometrium. Interestingly, in antigestagen-treated mid-pregnancy dogs, Ut/Pl and interplacental GR/NR3C1-mRNA expression remained unaffected. At the cellular level, placental GR/NR3C1 was clearly detectable in placenta fetalis, i.e. in trophoblast cells. In conclusion, increased expression of GR/NR3C1 during normal parturition, but not following antigestagen-treatment, suggest that it is not required for initiating the signaling cascade of PG synthesis leading to the induction of parturition in the dog.

  16. Glucocorticoid-induced tethered transrepression requires SUMOylation of GR and formation of a SUMO-SMRT/NCoR1-HDAC3 repressing complex

    PubMed Central

    Hua, Guoqiang; Ganti, Krishna Priya; Chambon, Pierre

    2016-01-01

    Upon binding of a glucocorticoid (GC), the GC receptor (GR) can exert one of three transcriptional regulatory functions. We recently reported that SUMOylation of the GR at position K293 in humans (K310 in mice) within the N-terminal domain is indispensable for GC-induced evolutionary conserved inverted repeated negative GC response element (IR nGRE)-mediated direct transrepression. We now demonstrate that the integrity of this GR SUMOylation site is mandatory for the formation of a GR-small ubiquitin-related modifiers (SUMOs)-SMRT/NCoR1-HDAC3 repressing complex, which is indispensable for NF-κB/AP1-mediated GC-induced tethered indirect transrepression in vitro. Using GR K310R mutant mice or mice containing the N-terminal truncated GR isoform GRα-D3 lacking the K310 SUMOylation site, revealed a more severe skin inflammation than in WT mice. Importantly, cotreatment with dexamethasone (Dex) could not efficiently suppress a 12-O-tetradecanoylphorbol-13-acetate (TPA)–induced skin inflammation in these mutant mice, whereas it was clearly decreased in WT mice. In addition, in mice selectively ablated in skin keratinocytes for either nuclear receptor corepressor 1 (NCoR1)/silencing mediator for retinoid or thyroid-hormone receptors (SMRT) corepressors or histone deacetylase 3 (HDAC3), Dex-induced tethered transrepression and the formation of a repressing complex on DNA-bound NF-κB/AP1 were impaired. We previously suggested that GR ligands that would lack both (+)GRE-mediated transactivation and IR nGRE-mediated direct transrepression activities of GCs may preferentially exert the therapeutically beneficial GC antiinflammatory properties. Interestingly, we now identified a nonsteroidal antiinflammatory selective GR agonist (SEGRA) that selectively lacks both Dex-induced (+)GRE-mediated transactivation and IR nGRE-mediated direct transrepression functions, while still exerting a tethered indirect transrepression activity and could therefore be clinically lesser

  17. Common data model for natural language processing based on two existing standard information models: CDA+GrAF.

    PubMed

    Meystre, Stéphane M; Lee, Sanghoon; Jung, Chai Young; Chevrier, Raphaël D

    2012-08-01

    An increasing need for collaboration and resources sharing in the Natural Language Processing (NLP) research and development community motivates efforts to create and share a common data model and a common terminology for all information annotated and extracted from clinical text. We have combined two existing standards: the HL7 Clinical Document Architecture (CDA), and the ISO Graph Annotation Format (GrAF; in development), to develop such a data model entitled "CDA+GrAF". We experimented with several methods to combine these existing standards, and eventually selected a method wrapping separate CDA and GrAF parts in a common standoff annotation (i.e., separate from the annotated text) XML document. Two use cases, clinical document sections, and the 2010 i2b2/VA NLP Challenge (i.e., problems, tests, and treatments, with their assertions and relations), were used to create examples of such standoff annotation documents, and were successfully validated with the XML schemata provided with both standards. We developed a tool to automatically translate annotation documents from the 2010 i2b2/VA NLP Challenge format to GrAF, and automatically generated 50 annotation documents using this tool, all successfully validated. Finally, we adapted the XSL stylesheet provided with HL7 CDA to allow viewing annotation XML documents in a web browser, and plan to adapt existing tools for translating annotation documents between CDA+GrAF and the UIMA and GATE frameworks. This common data model may ease directly comparing NLP tools and applications, combining their output, transforming and "translating" annotations between different NLP applications, and eventually "plug-and-play" of different modules in NLP applications. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Modeling the Mechanism of GR/c-Jun/Erg Crosstalk in Apoptosis of Acute Lymphoblastic Leukemia

    PubMed Central

    Chen, Daphne Wei-Chen; Krstic-Demonacos, Marija; Schwartz, Jean-Marc

    2012-01-01

    Acute lymphoblastic leukemia (ALL) is one of the most common forms of malignancy that occurs in lymphoid progenitor cells, particularly in children. Synthetic steroid hormones glucocorticoids (GCs) are widely used as part of the ALL treatment regimens due to their apoptotic function, but their use also brings about various side effects and drug resistance. The identification of the molecular differences between the GCs responsive and resistant cells therefore are essential to decipher such complexity and can be used to improve therapy. However, the emerging picture is complicated as the activities of genes and proteins involved are controlled by multiple factors. By adopting the systems biology framework to address this issue, we here integrated the available knowledge together with experimental data by building a series of mathematical models. This rationale enabled us to unravel molecular interactions involving c-Jun in GC induced apoptosis and identify Ets-related gene (Erg) as potential biomarker of GC resistance. The results revealed an alternative possible mechanism where c-Jun may be an indirect GR target that is controlled via an upstream repressor protein. The models also highlight the importance of Erg for GR function, particularly in GC sensitive C7 cells where Erg directly regulates GR in agreement with our previous experimental results. Our models describe potential GR-controlled molecular mechanisms of c-Jun/Bim and Erg regulation. We also demonstrate the importance of using a systematic approach to translate human disease processes into computational models in order to derive information-driven new hypotheses. PMID:23181019

  19. Modeling the Mechanism of GR/c-Jun/Erg Crosstalk in Apoptosis of Acute Lymphoblastic Leukemia.

    PubMed

    Chen, Daphne Wei-Chen; Krstic-Demonacos, Marija; Schwartz, Jean-Marc

    2012-01-01

    Acute lymphoblastic leukemia (ALL) is one of the most common forms of malignancy that occurs in lymphoid progenitor cells, particularly in children. Synthetic steroid hormones glucocorticoids (GCs) are widely used as part of the ALL treatment regimens due to their apoptotic function, but their use also brings about various side effects and drug resistance. The identification of the molecular differences between the GCs responsive and resistant cells therefore are essential to decipher such complexity and can be used to improve therapy. However, the emerging picture is complicated as the activities of genes and proteins involved are controlled by multiple factors. By adopting the systems biology framework to address this issue, we here integrated the available knowledge together with experimental data by building a series of mathematical models. This rationale enabled us to unravel molecular interactions involving c-Jun in GC induced apoptosis and identify Ets-related gene (Erg) as potential biomarker of GC resistance. The results revealed an alternative possible mechanism where c-Jun may be an indirect GR target that is controlled via an upstream repressor protein. The models also highlight the importance of Erg for GR function, particularly in GC sensitive C7 cells where Erg directly regulates GR in agreement with our previous experimental results. Our models describe potential GR-controlled molecular mechanisms of c-Jun/Bim and Erg regulation. We also demonstrate the importance of using a systematic approach to translate human disease processes into computational models in order to derive information-driven new hypotheses.

  20. A topological extension of GR: Black holes induce dark energy

    NASA Astrophysics Data System (ADS)

    Spaans, M.

    2013-02-01

    A topological extension of general relativity is presented. The superposition principle of quantum mechanics, as formulated by the Feynman path integral, is taken as a starting point. It is argued that the trajectories that enter this path integral are distinct and thus that space-time topology is multiply connected. Specifically, space-time at the Planck scale consists of a lattice of three-tori that facilitates many distinct paths for particles to travel along. To add gravity, mini black holes are attached to this lattice. These mini black holes represent Wheeler's quantum foam and result from the fact that GR is not conformally invariant. The number of such mini black holes in any time-slice through four-space is found to be equal to the number of macroscopic (so long-lived) black holes in the entire universe. This connection, by which macroscopic black holes induce mini black holes, is a topological expression of Mach's principle. The proposed topological extension of GR can be tested because, if correct, the dark energy density of the universe should be proportional the total number of macroscopic black holes in the universe at any time. This prediction, although strange, agrees with current astrophysical observations.

  1. GR718- Radiation-Tolerant 18x SpaceWire Router

    NASA Astrophysics Data System (ADS)

    Ekergaren, Jonas; Habinc, Sandi; Johansson, Fredrik; Sturesson, Fredrik; Simlastik, Martin; Hernandez, Francisco; Redant, Steven; Stinkens, Kurt; Thys, Geert; Das Arul Mahesh, Jagadeesa; Suess, Martin

    2015-09-01

    GR718 is a radiation tolerant 18 port standalone SpaceWire router component that has been developed by Cobham Gaisler together with IMEC (BE), in an activity initiated by the European Space Agency under ESTEC contract 4000105402/12/NL/Cbi. Out of the 18 SpaceWire ports, 16 use on-chip LVDS transceivers, and two use LVTTL signaling. Included also is the mandatory configuration port, as well as an internal port for system level testing. All ports are capable of operating in 200 Mbit/s. UART and JTAG interfaces, that gives access to the on-chip AMBA AHB bus, are provided for configuration and debugging. SPI and GPIO interfaces are accessible through the configuration port, which allows SPI devices to be accessed and general purpose signaling to be performed through RMAP commands. In addition to the mandatory features in the current ECSS SpaceWire standard, GR718 supports group adaptive routing for path addresses, and packet distribution. It also includes support for the incoming SpaceWire standard revision 1 (ECSS-E-ST-50-12C Rev.1), the SpaceWire-D protocol, and the SpaceWire Plug-and-Play protocol currently being developed for ECSS. The technology used is UMC 180 nm, using the DARE library from IMEC, and the package is a 256 pin CQFP. A development board for evaluation and software development has been manufactured as well.

  2. Friction Stir Welding of GR-Cop 84 for Combustion Chamber Liners

    NASA Technical Reports Server (NTRS)

    Russell, Carolyn K.; Carter, Robert; Ellis, David L.; Goudy, Richard

    2004-01-01

    GRCop-84 is a copper-chromium-niobium alloy developed by the Glenn Research Center for liquid rocket engine combustion chamber liners. GRCop-84 exhibits superior properties over conventional copper-base alloys in a liquid hydrogen-oxygen operating environment. The Next Generation Launch Technology program has funded a program to demonstrate scale-up production capabilities of GR-Cop 84 to levels suitable for main combustion chamber production for the prototype rocket engine. This paper describes a novel method of manufacturing the main combustion chamber liner. The process consists of several steps: extrude the GR-Cop 84 powder into billets, roll the billets into plates, bump form the plates into cylinder halves and friction stir weld the halves into a cylinder. The cylinder is then metal spun formed to near net liner dimensions followed by finish machining to the final configuration. This paper describes the friction stir weld process development including tooling and non-destructive inspection techniques, culminating in the successful production of a liner preform completed through spin forming.

  3. Dexamethasone-Mediated Changes in Adipose Triacylglycerol Metabolism Are Exaggerated, Not Diminished, in the Absence of a Functional GR Dimerization Domain

    PubMed Central

    Roohk, Donald J.; Mascharak, Smita; Khambatta, Cyrus; Leung, Ho; Hellerstein, Marc

    2013-01-01

    The glucocorticoid (GC) receptor (GR) has multiple effector mechanisms, including dimerization-mediated transactivation of target genes via DNA binding and transcriptional repression mediated by protein-protein interactions. Much attention has been focused on developing selective GR modulators that would dissociate adverse effects from therapeutic anti-inflammatory effects. The GRdim/dim mouse has a mutation in the dimerization domain of GR and has been shown to have attenuated transactivation with intact repression. To understand the role of GR dimerization-dependent targets in multiple tissues, we measured metabolic fluxes through several disease-relevant GC target pathways using heavy water labeling and mass spectrometry in wild-type and GRdim/dim mice administered the potent GC dexamethasone (DEX). Absolute triglyceride synthesis was increased in both wild-type and GRdim/dim mice by DEX in the inguinal and epididymal fat depots. GRdim/dim mice showed an exaggerated response to DEX in both depots. De novo lipogenesis was also greatly increased in both depots in response to DEX in GRdim/dim, but not wild-type mice. In contrast, the inhibitory effect of DEX on bone and skin collagen synthesis rates was greater in wild-type compared with GRdim/dim mice. Wild-type mice were more sensitive to DEX-dependent decreases in insulin sensitivity than GRdim/dim mice. Wild-type and GRdim/dim mice were equally sensitive to DEX-dependent decreases in muscle protein synthesis. Chronic elevation of GCs in GRdim/dim mice results in severe runting and lethality. In conclusion, some metabolic effects of GC treatment are exaggerated in adipose tissue of GRdim/dim mice, suggesting that selective GR modulators based on dissociating GR transactivation from repression should be evaluated carefully. PMID:23493372

  4. Chromatin recruitment of activated AMPK drives fasting response genes co-controlled by GR and PPARα.

    PubMed

    Ratman, Dariusz; Mylka, Viacheslav; Bougarne, Nadia; Pawlak, Michal; Caron, Sandrine; Hennuyer, Nathalie; Paumelle, Réjane; De Cauwer, Lode; Thommis, Jonathan; Rider, Mark H; Libert, Claude; Lievens, Sam; Tavernier, Jan; Staels, Bart; De Bosscher, Karolien

    2016-12-15

    Adaptation to fasting involves both Glucocorticoid Receptor (GRα) and Peroxisome Proliferator-Activated Receptor α (PPARα) activation. Given both receptors can physically interact we investigated the possibility of a genome-wide cross-talk between activated GR and PPARα, using ChIP- and RNA-seq in primary hepatocytes. Our data reveal extensive chromatin co-localization of both factors with cooperative induction of genes controlling lipid/glucose metabolism. Key GR/PPAR co-controlled genes switched from transcriptional antagonism to cooperativity when moving from short to prolonged hepatocyte fasting, a phenomenon coinciding with gene promoter recruitment of phosphorylated AMP-activated protein kinase (AMPK) and blocked by its pharmacological inhibition. In vitro interaction studies support trimeric complex formation between GR, PPARα and phospho-AMPK. Long-term fasting in mice showed enhanced phosphorylation of liver AMPK and GRα Ser211. Phospho-AMPK chromatin recruitment at liver target genes, observed upon prolonged fasting in mice, is dampened by refeeding. Taken together, our results identify phospho-AMPK as a molecular switch able to cooperate with nuclear receptors at the chromatin level and reveal a novel adaptation mechanism to prolonged fasting. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  5. On computation of Gröbner bases for linear difference systems

    NASA Astrophysics Data System (ADS)

    Gerdt, Vladimir P.

    2006-04-01

    In this paper, we present an algorithm for computing Gröbner bases of linear ideals in a difference polynomial ring over a ground difference field. The input difference polynomials generating the ideal are also assumed to be linear. The algorithm is an adaptation to difference ideals of our polynomial algorithm based on Janet-like reductions.

  6. The C.A.M.S. 54 G.R. transatlantic seaplane (French)

    NASA Technical Reports Server (NTRS)

    Ide, John Jay

    1928-01-01

    Tested at the end of March, 1928, the C.A.M.S. 54 G.R. was built for the purpose of crossing the Atlantic from Europe by way of the azores. It has a biplane construction with wings mounted above the hull. It is powered by two new series 500 HP. geared Hispano Suiza V type engines.

  7. Gröbner bases for finite-temperature quantum computing and their complexity

    NASA Astrophysics Data System (ADS)

    Crompton, P. R.

    2011-11-01

    Following the recent approach of using order domains to construct Gröbner bases from general projective varieties, we examine the parity and time-reversal arguments relating to the Wightman axioms of quantum field theory and propose that the definition of associativity in these axioms should be introduced a posteriori to the cluster property in order to generalize the anyon conjecture for quantum computing to indefinite metrics. We then show that this modification, which we define via ideal quotients, does not admit a faithful representation of the Braid group, because the generalized twisted inner automorphisms that we use to reintroduce associativity are only parity invariant for the prime spectra of the exterior algebra. We then use a coordinate prescription for the quantum deformations of toric varieties to show how a faithful representation of the Braid group can be reconstructed and argue that for a degree reverse lexicographic (monomial) ordered Gröbner basis, the complexity class of this problem is bounded quantum polynomial.

  8. Higher curvature gravities, unlike GR, cannot be bootstrapped from their (usual) linearizations

    NASA Astrophysics Data System (ADS)

    Deser, S.

    2017-12-01

    We show that higher curvature order gravities, in particular the propagating quadratic curvature models, cannot be derived by self-coupling from their linear, flat space, forms, except through an unphysical version of linearization; only GR can. Separately, we comment on an early version of the self-coupling bootstrap.

  9. ΛGR Centennial: Cosmic Web in Dark Energy Background

    NASA Astrophysics Data System (ADS)

    Chernin, A. D.

    The basic building blocks of the Cosmic Web are groups and clusters of galaxies, super-clusters (pancakes) and filaments embedded in the universal dark energy background. The background produces antigravity, and the antigravity effect is strong in groups, clusters and superclusters. Antigravity is very weak in filaments where matter (dark matter and baryons) produces gravity dominating in the filament internal dynamics. Gravity-antigravity interplay on the large scales is a grandiose phenomenon predicted by ΛGR theory and seen in modern observations of the Cosmic Web.

  10. Term Cancellations in Computing Floating-Point Gröbner Bases

    NASA Astrophysics Data System (ADS)

    Sasaki, Tateaki; Kako, Fujio

    We discuss the term cancellation which makes the floating-point Gröbner basis computation unstable, and show that error accumulation is never negligible in our previous method. Then, we present a new method, which removes accumulated errors as far as possible by reducing matrices constructed from coefficient vectors by the Gaussian elimination. The method manifests amounts of term cancellations caused by the existence of approximate linearly dependent relations among input polynomials.

  11. GrB TWEAK: A Potential Novel Biologic for NSCLC Therapy

    DTIC Science & Technology

    2017-07-01

    saline (control) or GrB-Fc-IT4 at 20 mg...intravenously   treated  with   saline  or  MRT-­‐101  construct  (Qod  X  5).  On  average,  tumors  from   saline -­‐treated...also   demonstrated   >50%   tumor   suppression   vs   saline   controls.   Overall,   treatment  with  MRT-­‐101

  12. [Knowledge of the "Gräfenberg zone" and female ejaculation in ancient Indian sexual science. A medical history contribution].

    PubMed

    Syed, R

    1999-01-01

    Ancient Indian texts in sexology (kamaśastra) from the 11th century onwards prove that their authors knew about the area later termed the "Gräfenberg zone" in Europe, as well as about the female ejaculation connected with the stimulation of this area. The Gräfenberg zone is a sexually arousable zone in the front part of the vagina, stimulation of which can lead to the discharge of liquid from the urethra, a phenomenon which is described as female ejaculation. The german gynaecologist Ernst Gräfenberg, who worked in America, described this zone, situated beneath the clitoris, for the first time (at least in this century) in Western medicine in an article published in 1950. (There are, however, evidences, that the 17th-century anatomist Regnier de Graaf had knowledge about the mentioned erogenous zone as well as female ejaculation.) Since the 1980s the so-called Gräfenberg zone, popularly termed "G-spot", and female ejaculation have been controversially discussed medically as well as in popular science, first in the United States, then in Europe; both phenomena have meanwhile been accepted as facts in medical manuals and reference books (e.g. the "Pschyrembel"). Whereas the oldest and most well-known sexological-erotological work of Ancient India, the Kamasutra, dating probably from the third century A.D., apparently did not know the Gräfenberg zone and female ejaculation, texts such as the Pañcasayaka (11th century), Jayamangala (Yaśodhara's commentary on the Kamasutra from the 13th century), the Ratirahasya (13th century), as well as the late kamaśastra-works Smaradipika and Anangaranga (16th century?) demonstrably describe both, the Gräfenberg zone and female ejaculation, in great detail. The female ejaculation is described already in the 7th century in a non-kamaśastra-text, in a work of the poet Amaru called the Amaruśataka.

  13. Purification and characterization of thermostable alpha-galactosidase from Aspergillus terreus (GR).

    PubMed

    Shankar, S K; Dhananjay, S K; Mulimani, V H

    2009-02-01

    An extracellular thermostable alpha-galactosidase producing Aspergillus terreus (GR) strain was isolated from soil sample using guar gum as sole source of carbon. It was purified to apparent homogeneity by acetone precipitation, gel filtration followed by DEAE-Sephacel chromatographic step. The purified enzyme showed a single band after sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The molecular weight of the purified enzyme after SDS-PAGE was 108 kDa. The enzyme showed optimum pH and temperature of 5.0 and 65 degrees C, respectively, for artificial substrate pNPalphaGal. alpha-Galactosidase from A. terreus (GR) is found to be thermostable, as it was not inactivated after heating at 65 degrees C for 40 min. The K (m) for pNPalphaGal, oNPalphaGal, raffinose, and stachyose are 0.1, 0.28, 0.42, and 0.33 mM, respectively. Inhibitors such as 1,10-phenanthroline, phenylmethylsulfonyl fluoride, ethylenediaminetetraacetic acid, mercaptoethanol, and urea have no effect, whereas N-bromosuccinamide inhibited enzyme activity by 100%. Among metal ions tested, Mg(2+), Ni(2+), Ca(2+), Co(2+), and Mn(2+) had no effect on enzyme activity, but Ag(+), Hg(2+), and Cu(2+) have inhibited complete activity.

  14. Hamiltonian approach to GR - Part 1: covariant theory of classical gravity

    NASA Astrophysics Data System (ADS)

    Cremaschini, Claudio; Tessarotto, Massimo

    2017-05-01

    A challenging issue in General Relativity concerns the determination of the manifestly covariant continuum Hamiltonian structure underlying the Einstein field equations and the related formulation of the corresponding covariant Hamilton-Jacobi theory. The task is achieved by adopting a synchronous variational principle requiring distinction between the prescribed deterministic metric tensor \\widehat{g}(r)≡ { \\widehat{g}_{μ ν }(r)} solution of the Einstein field equations which determines the geometry of the background space-time and suitable variational fields x≡ { g,π } obeying an appropriate set of continuum Hamilton equations, referred to here as GR-Hamilton equations. It is shown that a prerequisite for reaching such a goal is that of casting the same equations in evolutionary form by means of a Lagrangian parametrization for a suitably reduced canonical state. As a result, the corresponding Hamilton-Jacobi theory is established in manifestly covariant form. Physical implications of the theory are discussed. These include the investigation of the structural stability of the GR-Hamilton equations with respect to vacuum solutions of the Einstein equations, assuming that wave-like perturbations are governed by the canonical evolution equations.

  15. Expression of the fructose receptor BmGr9 and its involvement in the promotion of feeding, suggested by its co-expression with neuropeptide F1 in Bombyx mori.

    PubMed

    Mang, Dingze; Shu, Min; Tanaka, Shiho; Nagata, Shinji; Takada, Tomoyuki; Endo, Haruka; Kikuta, Shingo; Tabunoki, Hiroko; Iwabuchi, Kikuo; Sato, Ryoichi

    2016-08-01

    Insect gustatory receptors (Grs) are members of a large family of proteins with seven transmembrane domains that provide insects with the ability to detect chemical signals critical for feeding, mating, and oviposition. To date, 69 Bombyx mori Grs (BmGrs) genes have been identified via genome studies. BmGr9 has been shown to respond specifically to fructose and to function as a ligand-gated ion channel selectively activated by fructose. However, the sites where this Gr are expressed remain unclear. We demonstrated using reverse transcription (RT)-PCR that BmGr9 is widely expressed in the central nervous system (CNS), as well as oral sensory organs. Additionally, immunohistochemistry was performed using anti-BmGr9 antiserum to show that BmGr9 is expressed in cells of the oral sensory organs, including the maxillary galea, maxillary palps, labrum, and labium, as well as in putative neurosecretory cells of the CNS. Furthermore, double immunohistochemical analysis showed that most BmGr9-expressing cells co-localized with putative neuropeptide F1-expressing cells in the brain, suggesting that BmGr9 is involved in the promotion of feeding behaviors. In addition, a portion of BmGr9-expressing cells in the brain co-localized with cells expressing BmGr6, a molecule of the sugar receptor clade, suggesting that sugars other than fructose are involved in the regulation of feeding behaviors in B. mori larvae. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. In vitro effect of adenosine agonist GR79236 on the insulin sensitivity of glucose utilisation in rat soleus and human rectus abdominus muscle.

    PubMed

    Webster, J M; Heseltine, L; Taylor, R

    1996-06-07

    The dose-response effects of a new adenosine agonist, GR79236, were examined in isolated rat soleus muscle strips and human rectus abdominus muscle strips. Effects on the insulin sensitivity of carbohydrate metabolism were examined, in particular upon insulin stimulated glycogen synthesis and glycolytic flux. In the presence of adenosine deaminase (ADA), GR79236 increased insulin sensitivity of pyruvate release from rat soleus muscle strips by 24% from 82.5 +/- 10.0 to 102.5 +/- 10.0 (P < 0.01), by 27% to 105.0 +/- 12.5 (P < 0.01) and by 24% to 102.5 +/- 10.0 (P < 0.01) nmol/25 mg per h at 0.1 and 10 microM GR79236, respectively. Rates of lactate release followed a similar but non-significant trend. Addition of GR79236 in the presence of ADA had no effect on rates of glycogen synthesis. Insulin stimulated rates of pyruvate or lactate release or of glycogen synthesis were unaffected by the addition of adenosine deaminase or GR79236 in human rectus abdominus muscle strips. Adenosine agonists may act indirectly to modulate insulin sensitivity of carbohydrate metabolism.

  17. Field redefinitions and Plebanski formalism for GR

    NASA Astrophysics Data System (ADS)

    Krasnov, Kirill

    2018-07-01

    We point out that there exists a family of transformations acting on BF-type Lagrangians of gravity, with Lagrangians related by such a transformation corresponding to classically equivalent theories. A transformation of this type corresponds to a particular field redefinition. We discuss both the chiral and non-chiral cases. In the chiral case there is a one-parameter, and in the non-chiral case a two-parameter family of such transformations. In the chiral setup, we use these transformations to give an alternative derivation of the chiral BF plus potential formulation of general relativity that was proposed recently. In the non-chiral case, we show that there is a new BF plus potential type formulation of GR. We also make some remarks on the non-chiral pure connection formulation.

  18. MyD88-dependent expansion of an immature GR-1+CD11b+ population induces T cell suppression and Th2 polarization in sepsis

    PubMed Central

    Delano, Matthew J.; Scumpia, Philip O.; Weinstein, Jason S.; Coco, Dominique; Nagaraj, Srinivas; Kelly-Scumpia, Kindra M.; O'Malley, Kerri A.; Wynn, James L.; Antonenko, Svetlana; Al-Quran, Samer Z.; Swan, Ryan; Chung, Chun-Shiang; Atkinson, Mark A.; Ramphal, Reuben; Gabrilovich, Dmitry I.; Reeves, Wesley H.; Ayala, Alfred; Phillips, Joseph; LaFace, Drake; Heyworth, Paul G.; Clare-Salzler, Michael; Moldawer, Lyle L.

    2007-01-01

    Polymicrobial sepsis alters the adaptive immune response and induces T cell suppression and Th2 immune polarization. We identify a GR-1+CD11b+ population whose numbers dramatically increase and remain elevated in the spleen, lymph nodes, and bone marrow during polymicrobial sepsis. Phenotypically, these cells are heterogeneous, immature, predominantly myeloid progenitors that express interleukin 10 and several other cytokines and chemokines. Splenic GR-1+ cells effectively suppress antigen-specific CD8+ T cell interferon (IFN) γ production but only modestly suppress antigen-specific and nonspecific CD4+ T cell proliferation. GR-1+ cell depletion in vivo prevents both the sepsis-induced augmentation of Th2 cell–dependent and depression of Th1 cell–dependent antibody production. Signaling through MyD88, but not Toll-like receptor 4, TIR domain–containing adaptor-inducing IFN-β, or the IFN-α/β receptor, is required for complete GR-1+CD11b+ expansion. GR-1+CD11b+ cells contribute to sepsis-induced T cell suppression and preferential Th2 polarization. PMID:17548519

  19. User Manual for the Data-Series Interface of the Gr Application Software

    USGS Publications Warehouse

    Donovan, John M.

    2009-01-01

    This manual describes the data-series interface for the Gr Application software. Basic tasks such as plotting, editing, manipulating, and printing data series are presented. The properties of the various types of data objects and graphical objects used within the application, and the relationships between them also are presented. Descriptions of compatible data-series file formats are provided.

  20. Poly(GR) in C9ORF72-Related ALS/FTD Compromises Mitochondrial Function and Increases Oxidative Stress and DNA Damage in iPSC-Derived Motor Neurons.

    PubMed

    Lopez-Gonzalez, Rodrigo; Lu, Yubing; Gendron, Tania F; Karydas, Anna; Tran, Helene; Yang, Dejun; Petrucelli, Leonard; Miller, Bruce L; Almeida, Sandra; Gao, Fen-Biao

    2016-10-19

    GGGGCC repeat expansions in C9ORF72 are the most common genetic cause of both ALS and FTD. To uncover underlying pathogenic mechanisms, we found that DNA damage was greater, in an age-dependent manner, in motor neurons differentiated from iPSCs of multiple C9ORF72 patients than control neurons. Ectopic expression of the dipeptide repeat (DPR) protein (GR) 80 in iPSC-derived control neurons increased DNA damage, suggesting poly(GR) contributes to DNA damage in aged C9ORF72 neurons. Oxidative stress was also increased in C9ORF72 neurons in an age-dependent manner. Pharmacological or genetic reduction of oxidative stress partially rescued DNA damage in C9ORF72 neurons and control neurons expressing (GR) 80 or (GR) 80 -induced cellular toxicity in flies. Moreover, interactome analysis revealed that (GR) 80 preferentially bound to mitochondrial ribosomal proteins and caused mitochondrial dysfunction. Thus, poly(GR) in C9ORF72 neurons compromises mitochondrial function and causes DNA damage in part by increasing oxidative stress, revealing another pathogenic mechanism in C9ORF72-related ALS and FTD. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Photometric study of the eclipsing binary GR Bootis

    NASA Astrophysics Data System (ADS)

    Zhang, Z. L.; Zhang, Y. P.; Fu, J. N.; Xue, H. F.

    2016-07-01

    We present CCD photometry and low-resolution spectra of the eclipsing binary GR Boo. A new ephemeris is determined based on all the available times of the minimum light. The period analysis reveals that the orbital period is decreasing with a rate of dP / dt = - 2.05 ×10-10 d yr-1 . A photometric analysis for the obtained light curves is performed with the Wilson-Devinney Differential Correction program for the first time. The photometric solutions confirm the W UMa-type nature of the binary system. The mass ratio turns out to be q = 0.985 ± 0.001 . The evolutionary status and physical nature of the binary system are briefly discussed.

  2. Nonlinear Elastic Effects on the Energy Flux Deviation of Ultrasonic Waves in GR/EP Composites

    NASA Technical Reports Server (NTRS)

    Prosser, William H.; Kriz, R. D.; Fitting, Dale W.

    1992-01-01

    In isotropic materials, the direction of the energy flux (energy per unit time per unit area) of an ultrasonic plane wave is always along the same direction as the normal to the wave front. In anisotropic materials, however, this is true only along symmetry directions. Along other directions, the energy flux of the wave deviates from the intended direction of propagation. This phenomenon is known as energy flux deviation and is illustrated. The direction of the energy flux is dependent on the elastic coefficients of the material. This effect has been demonstrated in many anisotropic crystalline materials. In transparent quartz crystals, Schlieren photographs have been obtained which allow visualization of the ultrasonic waves and the energy flux deviation. The energy flux deviation in graphite/epoxy (gr/ep) composite materials can be quite large because of their high anisotropy. The flux deviation angle has been calculated for unidirectional gr/ep composites as a function of both fiber orientation and fiber volume content. Experimental measurements have also been made in unidirectional composites. It has been further demonstrated that changes in composite materials which alter the elastic properties such as moisture absorption by the matrix or fiber degradation, can be detected nondestructively by measurements of the energy flux shift. In this research, the effects of nonlinear elasticity on energy flux deviation in unidirectional gr/ep composites were studied. Because of elastic nonlinearity, the angle of the energy flux deviation was shown to be a function of applied stress. This shift in flux deviation was modeled using acoustoelastic theory and the previously measured second and third order elastic stiffness coefficients for T300/5208 gr/ep. Two conditions of applied uniaxial stress were considered. In the first case, the direction of applied uniaxial stress was along the fiber axis (x3) while in the second case it was perpendicular to the fiber axis along the

  3. Recruitment of Gr1(+)CD11b (+)F4/80 (+) population in the bone marrow and spleen by irradiation-induced pulmonary damage.

    PubMed

    Thanasegaran, Suganya; Ito, Sachiko; Nishio, Naomi; Uddin, Mohammad Nizam; Sun, Yang; Isobe, Ken-ichi

    2015-04-01

    Radiation-induced lung injury is a kind of sterile inflammation, which may lead to morbidity and mortality. The mechanism by which ionizing radiation activate the immune system is not well understood. In the present study, we have investigated the immunological responses induced by local irradiation-induced damage in mouse lung. The left lungs of C57BL/6 mice were irradiated at a high dose of 100 Gy. The histology of the lungs and spleen showed evidences of alveolar inflammation and congestion at 2 weeks after X-ray treatment. Also, prominent increase in cells expressing the cell surface markers, Gr(+)CD11b(+)F4/80(+) and Ly6C(+) Ly6G(+) were observed 2 weeks after X-ray treatment (100 Gy). Gr1(+)CD11b(+)F4/80(+) cell depletion by clodronate treatment reversed the histological effects and also failed to recruit Gr(+)CD11b(+) cells or F4/80(+) cells caused by irradiation. The origin of recruited Gr1(+)CD11b(+) cells was found to be a mixed resident and recruited phenotype.

  4. Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis | Center for Cancer Research

    Cancer.gov

    We demonstrate a novel tumor-promoting role of myeloid immune suppressor Gr+CD11b+ cells, which are evident in cancer patients and tumor-bearing animals. These cells constitute approximately 5% of total cells in tumors. Tumors coinjected with Gr+CD11b+ cells exhibited increased vascular density, vascular maturation, and decreased necrosis. These immune cells produce high

  5. gr-MRI: A software package for magnetic resonance imaging using software defined radios

    NASA Astrophysics Data System (ADS)

    Hasselwander, Christopher J.; Cao, Zhipeng; Grissom, William A.

    2016-09-01

    The goal of this work is to develop software that enables the rapid implementation of custom MRI spectrometers using commercially-available software defined radios (SDRs). The developed gr-MRI software package comprises a set of Python scripts, flowgraphs, and signal generation and recording blocks for GNU Radio, an open-source SDR software package that is widely used in communications research. gr-MRI implements basic event sequencing functionality, and tools for system calibrations, multi-radio synchronization, and MR signal processing and image reconstruction. It includes four pulse sequences: a single-pulse sequence to record free induction signals, a gradient-recalled echo imaging sequence, a spin echo imaging sequence, and an inversion recovery spin echo imaging sequence. The sequences were used to perform phantom imaging scans with a 0.5 Tesla tabletop MRI scanner and two commercially-available SDRs. One SDR was used for RF excitation and reception, and the other for gradient pulse generation. The total SDR hardware cost was approximately 2000. The frequency of radio desynchronization events and the frequency with which the software recovered from those events was also measured, and the SDR's ability to generate frequency-swept RF waveforms was validated and compared to the scanner's commercial spectrometer. The spin echo images geometrically matched those acquired using the commercial spectrometer, with no unexpected distortions. Desynchronization events were more likely to occur at the very beginning of an imaging scan, but were nearly eliminated if the user invoked the sequence for a short period before beginning data recording. The SDR produced a 500 kHz bandwidth frequency-swept pulse with high fidelity, while the commercial spectrometer produced a waveform with large frequency spike errors. In conclusion, the developed gr-MRI software can be used to develop high-fidelity, low-cost custom MRI spectrometers using commercially-available SDRs.

  6. gr-MRI: A software package for magnetic resonance imaging using software defined radios.

    PubMed

    Hasselwander, Christopher J; Cao, Zhipeng; Grissom, William A

    2016-09-01

    The goal of this work is to develop software that enables the rapid implementation of custom MRI spectrometers using commercially-available software defined radios (SDRs). The developed gr-MRI software package comprises a set of Python scripts, flowgraphs, and signal generation and recording blocks for GNU Radio, an open-source SDR software package that is widely used in communications research. gr-MRI implements basic event sequencing functionality, and tools for system calibrations, multi-radio synchronization, and MR signal processing and image reconstruction. It includes four pulse sequences: a single-pulse sequence to record free induction signals, a gradient-recalled echo imaging sequence, a spin echo imaging sequence, and an inversion recovery spin echo imaging sequence. The sequences were used to perform phantom imaging scans with a 0.5Tesla tabletop MRI scanner and two commercially-available SDRs. One SDR was used for RF excitation and reception, and the other for gradient pulse generation. The total SDR hardware cost was approximately $2000. The frequency of radio desynchronization events and the frequency with which the software recovered from those events was also measured, and the SDR's ability to generate frequency-swept RF waveforms was validated and compared to the scanner's commercial spectrometer. The spin echo images geometrically matched those acquired using the commercial spectrometer, with no unexpected distortions. Desynchronization events were more likely to occur at the very beginning of an imaging scan, but were nearly eliminated if the user invoked the sequence for a short period before beginning data recording. The SDR produced a 500kHz bandwidth frequency-swept pulse with high fidelity, while the commercial spectrometer produced a waveform with large frequency spike errors. In conclusion, the developed gr-MRI software can be used to develop high-fidelity, low-cost custom MRI spectrometers using commercially-available SDRs. Copyright

  7. Incomplete Gröbner basis as a preconditioner for polynomial systems

    NASA Astrophysics Data System (ADS)

    Sun, Yang; Tao, Yu-Hui; Bai, Feng-Shan

    2009-04-01

    Precondition plays a critical role in the numerical methods for large and sparse linear systems. It is also true for nonlinear algebraic systems. In this paper incomplete Gröbner basis (IGB) is proposed as a preconditioner of homotopy methods for polynomial systems of equations, which transforms a deficient system into a system with the same finite solutions, but smaller degree. The reduced system can thus be solved faster. Numerical results show the efficiency of the preconditioner.

  8. CD11b+ Gr1+ Bone Marrow Cells Ameliorate Liver Fibrosis by Producing Interleukin-10 in Mice

    PubMed Central

    Suh, Yang-Gun; Kim, Ja Kyung; Byun, Jin-Seok; Yi, Hyon-Seung; Lee, Young-Sun; Eun, Hyuk Soo; Kim, So Yeon; Han, Kwang-Hyub; Lee, Kwan Sik; Duester, Gregg; Friedman, Scott L.; Jeong, Won-Il

    2012-01-01

    Clinical trials and animal models suggest that infusion of bone marrow cells (BMC) is effective therapy for liver fibrosis, but the underlying mechanisms are obscure, especially those associated with early effects of BMC. Here, we analyzed the early impact of BMC infusion and identified the subsets of BMC showing antifibrotic effects in mice with carbon tetrachloride-induced liver fibrosis. An interaction between BMC and activated hepatic stellate cells (HSCs) was investigated using in vitro co-culturing system. Within 24 hours, infused BMC were in close contact with activated HSCs, which was associated with reduced liver fibrosis, enhanced hepatic expression of interleukin (IL)-10, expanded regulatory T cells but decreased macrophage infiltration in the liver at 24 hours after BMC infusion. In contrast, IL-10-deficient (IL-10−/−) BMC failed to reproduce these effects in the fibrotic livers. Intriguingly, in isolated cells, CD11b+Gr1highF4/80− and CD11b+Gr1+F4/80+ BMC expressed more IL-10 after co-culturing with activated HSCs, leading to suppressed expression of collagen and α-smooth muscle actin in HSCs. Moreover, these effects were either enhanced or abrogated, respectively, when BMC were co-cultured with IL-6−/− and retinaldehyde dehydrogenase 1−/− HSCs. Similar to murine data, human BMC expressed more IL-10 after co-culturing with human HSC lines (LX-2 or hTERT), and serum IL-10 levels were significantly elevated in patients with liver cirrhosis after autologous BMC infusion. Conclusion Activated HSCs increase IL-10 expression in BMC (CD11b+Gr1highF4/80− and CD11b+Gr1+F4/80+ cells), which in turn ameliorates liver fibrosis. Our findings could enhance the design of BMC therapy for liver fibrosis. PMID:22544759

  9. Integrated proteomics identified novel activation of dynein IC2-GR-COX-1 signaling in neurofibromatosis type I (NF1) disease model cells.

    PubMed

    Hirayama, Mio; Kobayashi, Daiki; Mizuguchi, Souhei; Morikawa, Takashi; Nagayama, Megumi; Midorikawa, Uichi; Wilson, Masayo M; Nambu, Akiko N; Yoshizawa, Akiyasu C; Kawano, Shin; Araki, Norie

    2013-05-01

    Neurofibromatosis type 1 (NF1) tumor suppressor gene product, neurofibromin, functions in part as a Ras-GAP, and though its loss is implicated in the neuronal abnormality of NF1 patients, its precise cellular function remains unclear. To study the molecular mechanism of NF1 pathogenesis, we prepared NF1 gene knockdown (KD) PC12 cells, as a NF1 disease model, and analyzed their molecular (gene and protein) expression profiles with a unique integrated proteomics approach, comprising iTRAQ, 2D-DIGE, and DNA microarrays, using an integrated protein and gene expression analysis chart (iPEACH). In NF1-KD PC12 cells showing abnormal neuronal differentiation after NGF treatment, of 3198 molecules quantitatively identified and listed in iPEACH, 97 molecules continuously up- or down-regulated over time were extracted. Pathway and network analysis further revealed overrepresentation of calcium signaling and transcriptional regulation by glucocorticoid receptor (GR) in the up-regulated protein set, whereas nerve system development was overrepresented in the down-regulated protein set. The novel up-regulated network we discovered, "dynein IC2-GR-COX-1 signaling," was then examined in NF1-KD cells. Validation studies confirmed that NF1 knockdown induces altered splicing and phosphorylation patterns of dynein IC2 isomers, up-regulation and accumulation of nuclear GR, and increased COX-1 expression in NGF-treated cells. Moreover, the neurite retraction phenotype observed in NF1-KD cells was significantly recovered by knockdown of the dynein IC2-C isoform and COX-1. In addition, dynein IC2 siRNA significantly inhibited nuclear translocation and accumulation of GR and up-regulation of COX-1 expression. These results suggest that dynein IC2 up-regulates GR nuclear translocation and accumulation, and subsequently causes increased COX-1 expression, in this NF1 disease model. Our integrated proteomics strategy, which combines multiple approaches, demonstrates that NF1-related neural

  10. Computing Gröbner and Involutive Bases for Linear Systems of Difference Equations

    NASA Astrophysics Data System (ADS)

    Yanovich, Denis

    2018-02-01

    The computation of involutive bases and Gröbner bases for linear systems of difference equations is solved and its importance for physical and mathematical problems is discussed. The algorithm and issues concerning its implementation in C are presented and calculation times are compared with the competing programs. The paper ends with consideration on the parallel version of this implementation and its scalability.

  11. Substances released from probiotic Lactobacillus rhamnosus GR-1 potentiate NF-κB activity in Escherichia coli-stimulated urinary bladder cells.

    PubMed

    Karlsson, Mattias; Scherbak, Nikolai; Khalaf, Hazem; Olsson, Per-Erik; Jass, Jana

    2012-11-01

    Lactobacillus rhamnosus GR-1 is a probiotic bacterium used to maintain urogenital health. The putative mechanism for its probiotic effect is by modulating the host immunity. Urinary tract infections (UTI) are often caused by uropathogenic Escherichia coli that frequently evade or suppress immune responses in the bladder and can target pathways, including nuclear factor-kappaB (NF-κB). We evaluated the role of L. rhamnosus GR-1 on NF-κB activation in E. coli-stimulated bladder cells. Viable L. rhamnosus GR-1 was found to potentiate NF-κB activity in E. coli-stimulated T24 bladder cells, whereas heat-killed lactobacilli demonstrated a marginal increase in NF-κB activity. Surface components released by trypsin- or LiCl treatment, or the resultant heat-killed shaved lactobacilli, had no effect on NF-κB activity. Isolation of released products from L. rhamnosus GR-1 demonstrated that the induction of NF-κB activity was owing to released product(s) with a relatively large native size. Several putative immunomodulatory proteins were identified, namely GroEL, elongation factor Tu and NLP/P60. GroEL and elongation factor Tu have previously been shown to elicit immune responses from human cells. Isolating and using immune-augmenting substances produced by lactobacilli is a novel strategy for the prevention or treatment of UTI caused by immune-evading E. coli. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  12. Gröbner Bases and Generation of Difference Schemes for Partial Differential Equations

    NASA Astrophysics Data System (ADS)

    Gerdt, Vladimir P.; Blinkov, Yuri A.; Mozzhilkin, Vladimir V.

    2006-05-01

    In this paper we present an algorithmic approach to the generation of fully conservative difference schemes for linear partial differential equations. The approach is based on enlargement of the equations in their integral conservation law form by extra integral relations between unknown functions and their derivatives, and on discretization of the obtained system. The structure of the discrete system depends on numerical approximation methods for the integrals occurring in the enlarged system. As a result of the discretization, a system of linear polynomial difference equations is derived for the unknown functions and their partial derivatives. A difference scheme is constructed by elimination of all the partial derivatives. The elimination can be achieved by selecting a proper elimination ranking and by computing a Gröbner basis of the linear difference ideal generated by the polynomials in the discrete system. For these purposes we use the difference form of Janet-like Gröbner bases and their implementation in Maple. As illustration of the described methods and algorithms, we construct a number of difference schemes for Burgers and Falkowich-Karman equations and discuss their numerical properties.

  13. Increased total DNA damage and oxidative stress in brain are associated with decreased longevity in high sucrose diet fed WNIN/Gr-Ob obese rats.

    PubMed

    Potukuchi, Aruna; Addepally, Uma; Sindhu, Kirankumar; Manchala, Raghunath

    2017-06-01

    Obesity and Type 2 Diabetes (T2D) are chronic nutrient-related disorders that occur together and pose a grave burden to society. They are among the most common causes of ageing and death. Obesity and T2D per se accelerate ageing albeit the underlying mechanisms are unclear yet. Also, it is not clear whether or not superimposing T2D on obesity accelerates ageing. Present study validated the hypothesis, 'super-imposing T2D on obesity accelerates ageing' in WNIN/Gr-Ob, the impaired glucose tolerant, obese rat as the model and evaluated probable underlying mechanisms. To estimate the survival analysis of WNIN/Gr-Ob rats induced with T2D. To determine the extent of DNA damage and oxidative stress in the brain, the master controller of the body, in WNIN/Gr-Ob rats with/without high sucrose induced T2D/aggravation of insulin resistance (IR) after 3 and 6 months of feeding. T2D was induced/IR was aggravated by feeding high sucrose diet (HSD) to 9-10 weeks old, male WNIN/Gr-Ob rats. Survival percentage was determined statistically by Kaplan-Meier estimator. Neuronal DNA damage was quantified by the Comet assay while the oxidative stress and antioxidant status were evaluated from the levels of malonaldialdehyde, reduced glutathione, and superoxide dismutase (SOD) activity. HSD feeding decreased longevity of WNIN/Gr-Ob rats and was associated with significantly higher total neuronal DNA damage after three months of feeding but not later. In line with this was the increased neuronal oxidative stress (lipid peroxidation) and decreased antioxidant status (reduced glutathione and SOD activity) in HSD than Starch-based diet (SBD) fed rats. The results suggest that HSD feeding decreased the longevity of WNIN/Gr-Ob obese rats probably by increasing oxidative stress and aggravating IR, a condition that precedes T2D.

  14. Mapping soil erosion risk in Serra de Grândola (Portugal)

    NASA Astrophysics Data System (ADS)

    Neto Paixão, H. M.; Granja Martins, F. M.; Zavala, L. M.; Jordán, A.; Bellinfante, N.

    2012-04-01

    Geomorphological processes can pose environmental risks to people and economical activities. Information and a better knowledge of the genesis of these processes is important for environmental planning, since it allows to model, quantify and classify risks, what can mitigate the threats. The objective of this research is to assess the soil erosion risk in Serra de Grândola, which is a north-south oriented mountain ridge with an altitude of 383 m, located in southwest of Alentejo (southern Portugal). The study area is 675 km2, including the councils of Grândola, Santiago do Cacém and Sines. The process for mapping of erosive status was based on the guidelines for measuring and mapping the processes of erosion of coastal areas of the Mediterranean proposed by PAP/RAC (1997), developed and later modified by other authors in different areas. This method is based on the application of a geographic information system that integrates different types of spatial information inserted into a digital terrain model and in their derivative models. Erosive status are classified using information from soil erodibility, slope, land use and vegetation cover. The rainfall erosivity map was obtained using the modified Fournier index, calculated from the mean monthly rainfall, as recorded in 30 meteorological stations with influence in the study area. Finally, the soil erosion risk map was designed by ovelaying the erosive status map and the rainfall erosivity map.

  15. Clarithromycin expands CD11b+Gr-1+ cells via the STAT3/Bv8 axis to ameliorate lethal endotoxic shock and post-influenza bacterial pneumonia

    PubMed Central

    Fujii, Hideki; Yagi, Kazuma; Suzuki, Shoji; Hegab, Ahmed E.; Tasaka, Sadatomo; Nakamoto, Nobuhiro; Iwata, Satoshi; Honda, Kenya; Kanai, Takanori; Hasegawa, Naoki; Betsuyaku, Tomoko

    2018-01-01

    Macrolides are used to treat various inflammatory diseases owing to their immunomodulatory properties; however, little is known about their precise mechanism of action. In this study, we investigated the functional significance of the expansion of myeloid-derived suppressor cell (MDSC)-like CD11b+Gr-1+ cells in response to the macrolide antibiotic clarithromycin (CAM) in mouse models of shock and post-influenza pneumococcal pneumonia as well as in humans. Intraperitoneal administration of CAM markedly expanded splenic and lung CD11b+Gr-1+ cell populations in naïve mice. Notably, CAM pretreatment enhanced survival in a mouse model of lipopolysaccharide (LPS)-induced shock. In addition, adoptive transfer of CAM-treated CD11b+Gr-1+ cells protected mice against LPS-induced lethality via increased IL-10 expression. CAM also improved survival in post-influenza, CAM-resistant pneumococcal pneumonia, with improved lung pathology as well as decreased interferon (IFN)-γ and increased IL-10 levels. Adoptive transfer of CAM-treated CD11b+Gr-1+ cells protected mice from post-influenza pneumococcal pneumonia. Further analysis revealed that the CAM-induced CD11b+Gr-1+ cell expansion was dependent on STAT3-mediated Bv8 production and may be facilitated by the presence of gut commensal microbiota. Lastly, an analysis of peripheral blood obtained from healthy volunteers following oral CAM administration showed a trend toward the expansion of human MDSC-like cells (Lineage−HLA-DR−CD11b+CD33+) with increased arginase 1 mRNA expression. Thus, CAM promoted the expansion of a unique population of immunosuppressive CD11b+Gr-1+ cells essential for the immunomodulatory properties of macrolides. PMID:29621339

  16. Closed form solution for a double quantum well using Gröbner basis

    NASA Astrophysics Data System (ADS)

    Acus, A.; Dargys, A.

    2011-07-01

    Analytical expressions for the spectrum, eigenfunctions and dipole matrix elements of a square double quantum well (DQW) are presented for a general case when the potential in different regions of the DQW has different heights and the effective masses are different. This was achieved by using a Gröbner basis algorithm that allowed us to disentangle the resulting coupled polynomials without explicitly solving the transcendental eigenvalue equation.

  17. VizieR Online Data Catalog: BVRI light curves of GR Boo (Wang+, 2017)

    NASA Astrophysics Data System (ADS)

    Wang, D.; Zhang, L.; Han, X. L.; Lu, H.

    2017-11-01

    We observed the eclipsing binary GR Boo on May 12, 22 and 24 in 2015 using the SARA 90-cm telescope located at Kitt Peak National Observatory, Arizona, USA. This telescope was equipped with an ARC CCD camera with a resolution of 2048x2048pixels but used at 2x2 binning, resulting in 1024x1024pixels. We used the Bessel BVRI filters. (1 data file).

  18. Measurements of Sound Speed and Grüneisen Parameter in Polystyrene Shocked to 8.5 Mbar

    NASA Astrophysics Data System (ADS)

    Boehly, T. R.; Rygg, J. R.; Zaghoo, M.; Hu, S. X.; Collins, G. W.; Fratanduono, D. E.; Celliers, P. M.; McCoy, C. A.

    2017-10-01

    The high-pressure behavior of polymers is important to fundamental high-energy-density studies and inertial confinement fusion experiments. The sound speed affects shock timing and determines the amplitude of modulations in unstable shocks. The Grüneisen parameter provides a means to model off-Hugoniot behavior, especially release physics. We use laser-driven shocks and a nonsteady wave analysis to infer sound speed in shocked material from the arrival times of drive-pressure perturbations at the shock front. Data are presented for CH shocked to 8.5 Mbar and compared to models. The Grüneisen parameter is observed to drop significantly near the insulator-conductor transition-a behavior not predicted by tabular models but is observed in quantum molecular dynamic simulations. This material is based upon work supported by the Department of Energy National Nuclear Security Administration under Award Number DE-NA0001944.

  19. Effects of artificial sweeteners on the AhR- and GR-dependent CYP1A1 expression in primary human hepatocytes and human cancer cells.

    PubMed

    Kamenickova, Alzbeta; Pecova, Michaela; Bachleda, Petr; Dvorak, Zdenek

    2013-12-01

    Food constituents may cause a phenomenon of food-drug interactions. In the current study, we examined the effects of artificial sweeteners (aspartame, acesulfame, cyclamate, saccharin) on the aryl hydrocarbon receptor (AhR) and glucocorticoid receptor (GR)-dependent expression of CYP1A1 in human hepatocytes, hepatic HepG2 and intestinal LS174T cancer cell lines. Sweeteners were tested in concentrations up to those occurring in non-alcoholic beverages. Basal and ligand-inducible AhR- and GR-dependent reporter gene activation in stably transfected HepG2 and HeLa cells, respectively, were not affected by either of the sweeteners tested after 24h of incubation. The expression of CYP1A1 mRNA and protein in primary cultures of human hepatocytes and in LS174T and HepG2 cells was not induced by any of the tested sweeteners. Overall, aspartame, acesulfame, saccharin and cyclamate had no effects on CYP1A1 expression and transcriptional activities of AhR and GR. These data imply the safety of artificial sweeteners in terms of interference with AhR, GR and CYP1A1. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Key algorithms used in GR02: A computer simulation model for predicting tree and stand growth

    Treesearch

    Garrett A. Hughes; Paul E. Sendak; Paul E. Sendak

    1985-01-01

    GR02 is an individual tree, distance-independent simulation model for predicting tree and stand growth over time. It performs five major functions during each run: (1) updates diameter at breast height, (2) updates total height, (3) estimates mortality, (4) determines regeneration, and (5) updates crown class.

  1. A Maple package for computing Gröbner bases for linear recurrence relations

    NASA Astrophysics Data System (ADS)

    Gerdt, Vladimir P.; Robertz, Daniel

    2006-04-01

    A Maple package for computing Gröbner bases of linear difference ideals is described. The underlying algorithm is based on Janet and Janet-like monomial divisions associated with finite difference operators. The package can be used, for example, for automatic generation of difference schemes for linear partial differential equations and for reduction of multiloop Feynman integrals. These two possible applications are illustrated by simple examples of the Laplace equation and a one-loop scalar integral of propagator type.

  2. An Application of Gröbner Basis in Differential Equations of Physics

    NASA Astrophysics Data System (ADS)

    Chaharbashloo, Mohammad Saleh; Basiri, Abdolali; Rahmany, Sajjad; Zarrinkamar, Saber

    2013-11-01

    We apply the Gröbner basis to the ansatz method in quantum mechanics to obtain the energy eigenvalues and the wave functions in a very simple manner. There are important physical potentials such as the Cornell interaction which play significant roles in particle physics and can be treated via this technique. As a typical example, the algorithm is applied to the semi-relativistic spinless Salpeter equation under the Cornell interaction. Many other applications of the idea in a wide range of physical fields are listed as well.

  3. Application of Neural Networks to Predict UH-60L Electrical Generator Condition using (IMD-HUMS) Data

    DTIC Science & Technology

    2006-12-01

    Data transfer unit ( DTU ) • Remote data concentrator (RDC) • Main processor unit (MPU) • 2 junction boxes (JB1/JB2) • 20 drive train and...NETWORKS TO PREDICT UH-60L ELECTRICAL GENERATOR CONDITION USING (IMD-HUMS) DATA by Evangelos Tourvalis December 2006 Thesis Advisor...including the time for reviewing instruction, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the

  4. Local mechanical properties of Alloy 82/182 dissimilar weld joint between SA508 Gr.1a and F316 SS at RT and 320C

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

    Byun, Thak Sang; Kim, Jin Weon

    2009-01-01

    This paper presents the variations of local mechanical and microstructural properties in dissimilar metal weld joints consisting of the SA508 Gr.1a ferritic steel, Alloy 82/182 filler metal, and F316 austenitic stainless steel. Flat or round tensile specimens and transmission electron microscopy disks were taken from the base metals, welds, and heat-affected zones (HAZ) of the joints and tested at room temperature (RT) and/or at 320 C. The tensile test results indicated that the mechanical property was relatively uniform within each material zone, but varied considerably between different zones. Further, significant variations were observed both in the austenitic HAZ of F316more » SS and in the ferritic HAZ of SA508 Gr.1a. The yield stress (YS) of the weld metal was under-matched with respect to the HAZs of SA508 Gr.1a and F316 SS by 0.78 to 0.92, although the YS was over-matched with respect to both base metals. The minimum ductility occurred in the HAZ of SA508 Gr.1 at both test temperatures. The plastic instability stress also varied considerably in the weld joints, with minimum values occurring in the SA508 Gr.1a base metal at RT and in the HAZ of F316 SS at 320 C, suggesting that the probability of ductile failure caused by a unstable deformation at the Alloy 82/182 buttering layer is low. Within the HAZ of SA508 Gr.1a, the gradient of the YS and ultimate tensile strength (UTS) was significant, primarily because of the different microstructures produced by the phase transformation during the welding process. The increment of YS was unexpectedly high in the HAZ of F316 SS, which was explained by the strain hardening induced by a strain mismatch between the weldment and the base metal. This was confirmed by the transmission electron micrographs showing high dislocation density in the HAZ.« less

  5. Jet Launching in Resistive GR-MHD Black Hole–Accretion Disk Systems

    NASA Astrophysics Data System (ADS)

    Qian, Qian; Fendt, Christian; Vourellis, Christos

    2018-05-01

    We investigate the launching mechanism of relativistic jets from black hole sources, in particular the strong winds from the surrounding accretion disk. Numerical investigations of the disk wind launching—the simulation of the accretion–ejection transition—have so far almost only been done for nonrelativistic systems. From these simulations we know that resistivity, or magnetic diffusivity, plays an important role for the launching process. Here we extend this treatment to general relativistic magnetohydrodynamics (GR-MHD), applying the resistive GR-MHD code rHARM. Our model setup considers a thin accretion disk threaded by a large-scale open magnetic field. We run a series of simulations with different Kerr parameter, field strength, and diffusivity level. Indeed, we find strong disk winds with, however, mildly relativistic speed, the latter most probably due to our limited computational domain. Further, we find that magnetic diffusivity lowers the efficiency of accretion and ejection, as it weakens the efficiency of the magnetic lever arm of the disk wind. As a major driving force of the disk wind we disentangle the toroidal magnetic field pressure gradient; however, magnetocentrifugal driving may also contribute. Black hole rotation in our simulations suppresses the accretion rate owing to an enhanced toroidal magnetic field pressure that seems to be induced by frame dragging. Comparing the energy fluxes from the Blandford–Znajek-driven central spine and the surrounding disk wind, we find that the total electromagnetic energy flux is dominated by the total matter energy flux of the disk wind (by a factor of 20). The kinetic energy flux of the matter outflow is comparatively small and comparable to the Blandford–Znajek electromagnetic energy flux.

  6. Nonlinear elastic effects on the energy flux deviation of ultrasonic waves in gr/ep composites

    NASA Technical Reports Server (NTRS)

    Prosser, William H.; Kriz, R. D.; Fitting, Dale W.

    1992-01-01

    The effects of nonlinear elasticity on energy flux deviation in undirectional gr/ep composites are examined. The shift in the flux deviation is modeled using acoustoelasticity theory and the second- and third-order elastic stiffness coefficients for T300/5208 gr/ep. Two conditions of applied uniaxial stress are considered. In the first case, the direction of applied uniaxial stress was along the fiber axis (x3), while in the second case it was perpendicular to the fiber axis along the laminate stacking direction (x1). For both conditions, the change in the energy flux deviation angle from the condition of zero applied stress is computed over the range of propagation directions of 0 to 60 deg from the fiber axis at two-degree intervals. A positive flux deviation angle implies the energy deviates away from the fiber direction toward the x1 axis, while a negative deviation means that the energy deviates toward the fibers. Over this range of fiber orientation angles, the energy of the quasi-longitudinal and pure mode transverse waves deviates toward the fibers, while that of the quasi-transverse mode deviates away from the fibers.

  7. CD40 dependent exacerbation of immune mediated hepatitis by hepatic CD11b+ Gr-1+ myeloid derived suppressor cells in tumor bearing mice

    PubMed Central

    Kapanadze, Tamar; Medina-Echeverz, José; Gamrekelashvili, Jaba; Weiss, Jonathan M.; Wiltrout, Robert H.; Kapoor, Veena; Hawk, Nga; Terabe, Masaki; Berzofsky, Jay A.; Manns, Michael P.; Wang, Ena; Marincola, Francesco M.; Korangy, Firouzeh; Greten, Tim F.

    2015-01-01

    Immunosuppressive CD11b+Gr-1+ myeloid-derived suppressor cells (MDSC) accumulate in the livers of tumor-bearing mice. We studied hepatic MDSC in two murine models of immune mediated hepatitis. Unexpectedly, treatment of tumor bearing mice with Concanavalin A or α-Galactosylceramide resulted in increased ALT and AST serum levels in comparison to tumor free mice. Adoptive transfer of hepatic MDSC into naïve mice exacerbated Concanavalin A induced liver damage. Hepatic CD11b+Gr-1+ cells revealed a polarized pro-inflammatory gene signature after Concanavalin A treatment. An interferon gamma- dependent up-regulation of CD40 on hepatic CD11b+Gr-1+ cells along with an up-regulation of CD80, CD86, and CD1d after Concanavalin A treatment was observed. Concanavalin A treatment resulted in a loss of suppressor function by tumor-induced CD11b+Gr-1+ MDSC as well as enhanced reactive oxygen species-mediated hepatotoxicity. CD40 knockdown in hepatic MDSC led to increased arginase activity upon Concanavalin A treatment and lower ALT/AST serum levels. Finally, blockade of arginase activity in Cd40−/− tumor-induced myeloid cells resulted in exacerbation of hepatitis and increased reactive oxygen species production in vivo. Our findings indicate that in a setting of acute hepatitis, tumor-induced hepatic MDSC act as pro-inflammatory immune effector cells capable of killing hepatocytes in a CD40-dependent manner. PMID:25616156

  8. Implications for future activity of Grímsvötn volcano, Iceland, from compositional time series of historical tephra

    NASA Astrophysics Data System (ADS)

    Carpentier, Marion; Sigmarsson, Olgeir; Larsen, Gudrun

    2014-05-01

    The nature of future eruptions of active volcanoes is hard to predict. Improved understanding of the past volcanic activity is probably the best way to infer future eruptive scenarios. The most active volcano in Iceland, Grímsvötn, last erupted in 2011 with consequences for habitants living close to the volcano and aviation in the North-Atlantic. In an effort to better understand the magmatic system of the volcano, we have investigated the compositions of 23 selected tephra layers representing the last 8 centuries of volcanic activity at Grímsvötn. The tephra was collected in the ablation area of outlet glaciers from Vatnajökull ice cap. The ice-conserved tephra are less prone to alteration than those exposed in soil sections. Major element analyses are indistinguishable and of quartz-normative tholeiite composition, and Sr and Nd isotope ratios are constant. In contrast, both trace element concentrations (Th range from 0.875 ppm to 1.37 ppm and Ni from 28.5 ppm to 56.6 ppm) in the basalts and Pb isotopes show small but significant variations. The high-precision analyses of Pb isotope ratios allow the identification of tephra samples (3 in total) with more radiogenic ratios than the bulk of the samples. The tephra of constant isotope ratios show linear increase in incompatible element concentrations with time. The rate of increasing concentrations permits exploring possible future scenarios assuming that the magmatic system beneath the volcano follows the established historical evolution. Assuming similar future behaviour of the magma system beneath Grímsvötn volcano, the linear increase in e.g. Th concentration suggests that the volcano is likely to principally produce basalts for the next 500-1000 years. Evolution of water concentration will most likely follow those of incompatible elements with consequent increases in explosiveness of future Grímsvötn eruptions.

  9. Chronic corticosterone administration facilitates aversive memory retrieval and increases GR/NOS immunoreactivity.

    PubMed

    Santos, Thays B; Céspedes, Isabel C; Viana, Milena B

    2014-07-01

    Glucocorticoids are stress hormones that mediate the organism's reaction to stress. It has been previously proposed that the facilitation of emotional aversive conditioning induced by these hormones may involve nitric oxide-pathways. The purpose of the present study was to address this question. For that, male Wistar rats were surgically implanted with slow-release corticosterone (CORT) pellets (21 days) and tested in a step-down inhibitory avoidance task. Additional groups of animals were also submitted to the same treatment conditions and on the 21st day of treatment assayed for GR (glucocorticoid receptors)-nNOS (neuronal nitric oxide synthase) immunoreactivity (GRi-nNOSi) or measurements of plasma CORT. Results showed that CORT treatment induced facilitation of step-down inhibitory avoidance. This same treatment also significantly increased CORT plasma levels and GRi in the medial, basolateral and basomedial amygdala, in the paraventricular hypothalamic nucleus (PVN), in the ventral and dorsal dentate gyrus, in the ventral CA1 region and in the dorsal CA1 and CA3 regions. Furthermore, nNOSi and GRi-nNOSi were significantly increased by CORT treatment in the medial amygdala and basolateral amygdaloid complex, in the PVN, subiculum, in the dorsal CA3 region and in the ventral CA1 and CA3 regions. These results indicate that the facilitation of aversive conditioning induced by CORT involves GR-nNOS pathways activation, what may be of relevance for a better understanding of stress-related psychiatric conditions. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Sense-encoded poly-GR dipeptide repeat proteins correlate to neurodegeneration and uniquely co-localize with TDP-43 in dendrites of repeat-expanded C9orf72 amyotrophic lateral sclerosis.

    PubMed

    Saberi, Shahram; Stauffer, Jennifer E; Jiang, Jie; Garcia, Sandra Diaz; Taylor, Amy E; Schulte, Derek; Ohkubo, Takuya; Schloffman, Cheyenne L; Maldonado, Marcus; Baughn, Michael; Rodriguez, Maria J; Pizzo, Don; Cleveland, Don; Ravits, John

    2018-03-01

    Hexanucleotide repeat expansions in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (C9 ALS). The main hypothesized pathogenic mechanisms are C9orf72 haploinsufficiency and/or toxicity from one or more of bi-directionally transcribed repeat RNAs and their dipeptide repeat proteins (DPRs) poly-GP, poly-GA, poly-GR, poly-PR and poly-PA. Recently, nuclear import and/or export defects especially caused by arginine-containing poly-GR or poly-PR have been proposed as significant contributors to pathogenesis based on disease models. We quantitatively studied and compared DPRs, nuclear pore proteins and C9orf72 protein in clinically related and clinically unrelated regions of the central nervous system, and compared them to phosphorylated TDP-43 (pTDP-43), the hallmark protein of ALS. Of the five DPRs, only poly-GR was significantly abundant in clinically related areas compared to unrelated areas (p < 0.001), and formed dendritic-like aggregates in the motor cortex that co-localized with pTDP-43 (p < 0.0001). While most poly-GR dendritic inclusions were pTDP-43 positive, only 4% of pTDP-43 dendritic inclusions were poly-GR positive. Staining for arginine-containing poly-GR and poly-PR in nuclei of neurons produced signals that were not specific to C9 ALS. We could not detect significant differences of nuclear markers RanGap, Lamin B1, and Importin β1 in C9 ALS, although we observed subtle nuclear changes in ALS, both C9 and non-C9, compared to control. The C9orf72 protein itself was diffusely expressed in cytoplasm of large neurons and glia, and nearly 50% reduced, in both clinically related frontal cortex and unrelated occipital cortex, but not in cerebellum. In summary, sense-encoded poly-GR DPR was unique, and localized to dendrites and pTDP43 in motor regions of C9 ALS CNS. This is consistent with new emerging ideas about TDP-43 functions in dendrites.

  11. Sense-encoded poly-GR dipeptide repeat proteins correlate to neurodegeneration and uniquely co-localize with TDP-43 in dendrites of repeat expanded C9orf72 amyotrophic lateral sclerosis

    PubMed Central

    Saberi, Shahram; Stauffer, Jennifer E.; Jiang, Jie; Garcia, Sandra Diaz; Taylor, Amy E; Schulte, Derek; Ohkubo, Takuya; Schloffman, Cheyenne L.; Maldonado, Marcus; Baughn, Michael; Rodriguez, Maria J; Pizzo, Don; Cleveland, Don; Ravits, John

    2018-01-01

    Hexanucleotide repeat expansions in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (C9 ALS). The main hypothesized pathogenic mechanisms are C9orf72 haploinsufficiency and/or toxicity from one or more of bi-directionally transcribed repeat RNAs and their dipeptide repeat proteins (DPRs) poly-GP, poly-GA, poly-GR, poly-PR and poly-PA. Recently, nuclear import and/or export defects especially caused by arginine-containing poly-GR or poly-PR have been proposed as significant contributors to pathogenesis based on disease models. We quantitatively studied and compared DPRs, nuclear pore proteins and C9orf72 protein in clinically-related and clinically-unrelated regions of the central nervous system, and compared them to phosphorylated TDP-43 (pTDP-43), the hallmark protein of ALS. Of the five DPRs, only poly-GR was significantly abundant in clinically-related areas compared to unrelated areas (p<0.001), and formed dendritic-like aggregates in the motor cortex that co-localized with pTDP-43 (p<0.0001). While most poly-GR dendritic inclusions were pTDP-43-positive, only 4% of pTDP-43 dendritic inclusions were poly-GR-positive. Staining for arginine-containing poly-GR and poly-PR in nuclei of neurons produced signals that were not specific to C9 ALS. We could not detect significant differences of nuclear markers RanGap, Lamin B1, and Importin β1 in C9 ALS, although we observed subtle nuclear changes in ALS, both C9 and non-C9, compared to control. The C9orf72 protein itself was diffusely expressed in cytoplasm of large neurons and glia, and nearly 50% reduced, in both clinically-related frontal cortex and unrelated occipital cortex, but not in cerebellum. In summary, sense-encoded poly-GR DPR was unique, and localized to neurites and pTDP43 in motor regions of C9 ALS CNS. This is consistent with new emerging ideas about TDP-43 functions in dendrites. PMID:29196813

  12. Long-term creep characterization of Gr. 91 steel by modified creep constitutive equations

    NASA Astrophysics Data System (ADS)

    Kim, Woo-Gon; Kim, Sung-Ho; Lee, Chan-Bock

    2011-06-01

    This paper focuses on the long-term creep characterization of Gr. 91 steel using creep constitutive equations. The models of three such equations, a combination of power-law form and omega model (CPO), a combination of exponential form and omega model (CEO), and a combination of logarithmic form and omega model (CLO), which are described as sum decaying primary creep and accelerating tertiary creep, are proposed. A series of creep rupture data was obtained through creep tests with various applied loads at 600 °C. On the basis of the creep data, a nonlinear least-square fitting (NLSF) analysis was carried out to provide the best fit with the experimental data in optimizing the parameter constants of an individual equation. The results of the NLSF analysis showed that in the lower stress regions of 160 MPa (σ/σys <0.65), the CEO model showed a match with the experimental creep data comparable to those of the CPO and CLO models; however, in the higher stress regions of 160 MPa (σ/σy > 0.65), the CPO model showed better agreement than the other two models. It was found that the CEO model was superior to the CPO and CLO models in the modeling of long-term creep curves. Using the CEO model, the long-term creep curves of Gr. 91 steel were numerically characterized, and its creep life was predicted accurately.

  13. Hydrogen Sulfide Attenuates the Recruitment of CD11b+Gr-1+ Myeloid Cells and Regulates Bax/Bcl-2 Signaling in Myocardial Ischemia Injury

    PubMed Central

    Zhang, Youen; Li, Hua; Zhao, Gang; Sun, Aijun; Zong, Nobel C.; Li, Zhaofeng; Zhu, Hongming; Zou, Yunzeng; Yang, Xiangdong; Ge, Junbo

    2014-01-01

    Hydrogen sulfide, an endogenous signaling molecule, plays an important role in the physiology and pathophysiology of the cardiovascular system. Using a mouse model of myocardial infarction, we investigated the anti-inflammatory and anti-apoptotic effects of the H2S donor sodium hydrosulfide (NaHS). The results demonstrated that the administration of NaHS improved survival, preserved left ventricular function, limited infarct size, and improved H2S levels in cardiac tissue to attenuate the recruitment of CD11b+Gr-1+ myeloid cells and to regulate the Bax/Bcl-2 pathway. Furthermore, the cardioprotective effects of NaHS were enhanced by inhibiting the migration of CD11b+Gr-1+ myeloid cells from the spleen into the blood and by attenuating post-infarction inflammation. These observations suggest that the novel mechanism underlying the cardioprotective function of H2S is secondary to a combination of attenuation the recruitment of CD11b+Gr-1+ myeloid cells and regulation of the Bax/Bcl-2 apoptotic signaling. PMID:24758901

  14. Polymorphisms of the GR and HSD11B1 genes influence body mass index and weight gain during hormone replacement treatment in patients with Addison's disease.

    PubMed

    Molnár, Ágnes; Kövesdi, Annamária; Szücs, Nikolette; Tóth, Miklós; Igaz, Péter; Rácz, Károly; Patócs, Attila

    2016-08-01

    Glucocorticoid substitution is essential in patients with chronic primary adrenocortical insufficiency (Addison's disease) and both over-treatment and inadequate dosage have deleterious effects. Individual sensitivity to glucocorticoids is partly genetically determined. To test the hypothesis whether the well-characterized SNPs of the GR and HSD11B1 genes may modulate the individual sensitivity to exogenous glucocorticoids and may influence clinical and/or laboratory parameters and the glucocorticoid substitution dosage in patients with Addison's disease. 68 patients with primary adrenocortical insufficiency were involved. Clinical and laboratory data, as well as the dosage of the hormone replacement therapy were collected. Peripheral blood DNA was isolated, and the GR and HSD11B1 SNPs were examined using allele-specific PCR or Taqman assay on Real Time PCR. The allele frequency of the GR N363S polymorphism was higher in patients compared to the control group and the disease appeared significantly earlier in patients harbouring the GR A3669G compared to noncarriers. These patients had higher ACTH level measured at the time of diagnosis. Homozygous BclI carriers had higher body mass index (BMI) and lower total hydrocortisone equivalent supplementation dose needed than heterozygous or noncarriers. The BMI and weight gain during hormone replacement therapy were also higher in carriers of the HSD11B1 rs4844880 treated with glucocorticoids other than dexamethasone. The BclI polymorphism of the GR gene and the rs4844880 of the HSD11B1 gene may contribute to weight gain and may affect the individual need of glucocorticoid substitution dose in these patients. © 2016 John Wiley & Sons Ltd.

  15. Local mechanical properties of Alloy 82/182 dissimilar weld joint between SA508 Gr.1a and F316 SS at RT and 320 °C

    NASA Astrophysics Data System (ADS)

    Kim, Jin Weon; Lee, Kyoungsoo; Kim, Jong Sung; Byun, Thak Sang

    2009-02-01

    The distributions of mechanical and microstructural properties were investigated for the dissimilar metal weld joints between SA508 Gr.1a ferritic steel and F316 austenitic stainless steel with Alloy 82/182 filler metal using small-size tensile specimens. The material properties varied significantly in different zones while those were relatively uniform within each material. In particular, significant gradient of the mechanical properties were observed near the both heat-affected zones (HAZs) of F316 SS and SA508 Gr.1a. Thus, the yield stress (YS) was under-matched with respect to the both HAZs, although, the YS of the weld metal was over-matched with respect to both base metals. The minimum ductility occurred in the HAZ of SA508 Gr.1a at both test temperatures. The plastic instability stress also varied considerably across the weld joints, with minimum values occurring in the SA508 Gr.1a base metal at RT and in the HAZ of F316 SS at 320 °C. The transmission electron micrographs showed that the strengthening in the HAZ of F316 SS was attributed to the strain hardening, induced by a strain mismatch between the weldment and the base metal, which was evidenced by high dislocation density in the HAZ of F316 SS.

  16. Persistence of Lactobacillus fermentum RC-14 and Lactobacillus rhamnosus GR-1 but Not L. rhamnosus GG in the Human Vagina as Demonstrated by Randomly Amplified Polymorphic DNA

    PubMed Central

    Gardiner, Gillian E.; Heinemann, Christine; Bruce, Andrew W.; Beuerman, Dee; Reid, Gregor

    2002-01-01

    Lactobacillus rhamnosus GR-1 and L. fermentum RC-14 are well-characterized probiotic strains with efficacy in the prevention and treatment of urogenital infections in women. The aim of the present study was to apply a molecular biology-based methodology for the detection of these strains and L. rhamnosus GG (a commercially available intestinal probiotic) in the human vagina in order to assess probiotic persistence at this site. Ten healthy women inserted vaginally a capsule containing either a combination of strains GR-1 and RC-14 or the GG strain for 3 consecutive nights. Vaginal swabs taken before and at various time points after probiotic insertion were analyzed, and the Lactobacillus flora was assessed by randomly amplified polymorphic DNA (RAPD) analysis. This method generated discrete DNA fingerprints for GR-1, RC-14, and GG and enabled successful detection of these strains in the vagina. Strain GR-1 and/or strain RC-14 was found to persist in the vaginal tract for up to 19 days after vaginal instillation, while L. rhamnosus GG was detectable for up to 5 days postadministration. In conclusion, the fates of probiotic L. rhamnosus and L. fermentum strains were successfully monitored in the human vagina by RAPD analysis. This technique provides molecular biology-based evidence that RC-14 and GR-1, strains selected as urogenital probiotics, persist in the human vagina and may be more suited to vaginal colonization than L. rhamnosus GG. This highlights the importance of proper selection of strains for urogenital probiotic applications. PMID:11777835

  17. Biomimetic Trehalose Biosensor Using Gustatory Receptor (Gr5a) Expressed in Drosophila Cells and Ion-Sensitive Field-Effect Transistor

    NASA Astrophysics Data System (ADS)

    Lau, Hui-Chong; Bae, Tae-Eon; Jang, Hyun-June; Kwon, Jae-Young; Cho, Won-Ju; Lim, Jeong-Ok

    2013-04-01

    The development of potential applications of biosensors using the sensory systems of vertebrates and invertebrates has progressed rapidly, especially in clinical diagnosis. The biosensor developed here involves the use of Drosophila cells expressing the gustatory receptor Gr5a and an ion-sensitive field-effect transistor (ISFET) sensor device. Gustatory receptor Gr5a is expressed abundantly in gustatory neurons and acts as a primary marker for tastants, especially sugar, in Drosophila. As a result, it could potentially serve as a good candidate for potential biomarkers of diseases in which the current knowledge of the cause and treatment is limited. The developed ISFET was based on the outstanding electrical characteristics of the metal-oxide-semiconductor field-effect transistor (MOSFET) with a subthreshold swing of 85 mV/dec, low leakage current of <10-12 and high on/off current ratio of 7.3×106. The SiO2 sensing membrane with a pH sensitivity of 34.9 mV/pH and drift rate 1.17 mV/h was sufficient for biosensing applications. In addition, the sensor device also showed significant compatibility with the Drosophila cells expressing Gr5a and their response to sugar, particularly trehalose. Moreover, the interactions between the transfected Drosophila cells and trehalose were consistent and reliable. This suggests that the developed ISFET sensor device could have potential use in the future as a screening device in diagnosis.

  18. Tumor-induced CD11b(+) Gr-1(+) myeloid-derived suppressor cells exacerbate immune-mediated hepatitis in mice in a CD40-dependent manner.

    PubMed

    Kapanadze, Tamar; Medina-Echeverz, José; Gamrekelashvili, Jaba; Weiss, Jonathan M; Wiltrout, Robert H; Kapoor, Veena; Hawk, Nga; Terabe, Masaki; Berzofsky, Jay A; Manns, Michael P; Wang, Ena; Marincola, Francesco M; Korangy, Firouzeh; Greten, Tim F

    2015-04-01

    Immunosuppressive CD11b(+) Gr-1(+) myeloid-derived suppressor cells (MDSCs) accumulate in the livers of tumor-bearing (TB) mice. We studied hepatic MDSCs in two murine models of immune-mediated hepatitis. Unexpectedly, treatment of TB mice with Concanavalin A (Con A) or α-galactosylceramide resulted in increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) serum levels in comparison to tumor-free mice. Adoptive transfer of hepatic MDSCs into naïve mice exacerbated Con A induced liver damage. Hepatic CD11b(+) Gr-1(+) cells revealed a polarized proinflammatory gene signature after Con A treatment. An IFN-γ-dependent upregulation of CD40 on hepatic CD11b(+) Gr-1(+) cells along with an upregulation of CD80, CD86, and CD1d after Con A treatment was observed. Con A treatment resulted in a loss of suppressor function by tumor-induced CD11b(+) Gr-1(+) MDSCs as well as enhanced reactive oxygen species (ROS)-mediated hepatotoxicity. CD40 knockdown in hepatic MDSCs led to increased arginase activity upon Con A treatment and lower ALT/AST serum levels. Finally, blockade of arginase activity in Cd40(-/-) tumor-induced myeloid cells resulted in exacerbation of hepatitis and increased ROS production in vivo. Our findings indicate that in a setting of acute hepatitis, tumor-induced hepatic MDSCs act as proinflammatory immune effector cells capable of killing hepatocytes in a CD40-dependent manner. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

  19. Wear and friction behavior of Al-TiB2-nano-Gr hybrid composites fabricated through ultrasonic cavitation assisted stir casting

    NASA Astrophysics Data System (ADS)

    Poria, Suswagata; Sutradhar, Goutam; Sahoo, Prasanta

    2018-05-01

    The present study reports the role of nano-graphite particles in determining wear and friction behavior of Al-TiB2-nano-Gr hybrid composites. Ultrasonic cavitation assisted stir casting method has been used for fabrication of composites. Al-Si5Cu3 alloy is used as base alloy along with micro sized TiB2 hard ceramic particles (2.5 and 5.5 wt%) as reinforcement and nano-Gr particles (2 and 4 wt%) as solid lubricant additives. SEM micrographs, EDAX spectrum and optical images are considered to observe uniform dispersion of reinforcing phases. Micro-hardness is evaluated using Vicker’s microhardness tester. Hardness is seen to increase with incorporation of TiB2 while the same decreases with incorporation of graphite. Wear and friction of composites are tested for varying load (10 to 40 N) and sliding speed (0.2 to 0.4 m s‑1) using a pin-on-disk tribometer. Worn surfaces are characterized using SEM and EDAX analysis. Wear resistance of composites increases with incorporation of reinforcing phases together. Nano-Gr particles are easily sheared out from the sub-surface and provide a layer over the tribo-surface of composite that enhances friction and wear behavior. Wear mechanism in composites is predominantly adhesion while abrasion and ploughing is prominent in base alloy.

  20. GrTEdb: the first web-based database of transposable elements in cotton (Gossypium raimondii).

    PubMed

    Xu, Zhenzhen; Liu, Jing; Ni, Wanchao; Peng, Zhen; Guo, Yue; Ye, Wuwei; Huang, Fang; Zhang, Xianggui; Xu, Peng; Guo, Qi; Shen, Xinlian; Du, Jianchang

    2017-01-01

    Although several diploid and tetroploid Gossypium species genomes have been sequenced, the well annotated web-based transposable elements (TEs) database is lacking. To better understand the roles of TEs in structural, functional and evolutionary dynamics of the cotton genome, a comprehensive, specific, and user-friendly web-based database, Gossypium raimondii transposable elements database (GrTEdb), was constructed. A total of 14 332 TEs were structurally annotated and clearly categorized in G. raimondii genome, and these elements have been classified into seven distinct superfamilies based on the order of protein-coding domains, structures and/or sequence similarity, including 2929 Copia-like elements, 10 368 Gypsy-like elements, 299 L1 , 12 Mutators , 435 PIF-Harbingers , 275 CACTAs and 14 Helitrons . Meanwhile, the web-based sequence browsing, searching, downloading and blast tool were implemented to help users easily and effectively to annotate the TEs or TE fragments in genomic sequences from G. raimondii and other closely related Gossypium species. GrTEdb provides resources and information related with TEs in G. raimondii , and will facilitate gene and genome analyses within or across Gossypium species, evaluating the impact of TEs on their host genomes, and investigating the potential interaction between TEs and protein-coding genes in Gossypium species. http://www.grtedb.org/. © The Author(s) 2017. Published by Oxford University Press.

  1. Ghrelin accelerates wound healing through GHS-R1a-mediated MAPK-NF-κB/GR signaling pathways in combined radiation and burn injury in rats.

    PubMed

    Liu, Cong; Huang, Jiawei; Li, Hong; Yang, Zhangyou; Zeng, Yiping; Liu, Jing; Hao, Yuhui; Li, Rong

    2016-06-07

    The therapeutic effect of ghrelin on wound healing was assessed using a rat model of combined radiation and burn injury (CRBI). Rat ghrelin, anti-rat tumor necrosis factor (TNF) α polyclonal antibody (PcAb), or selective antagonists of p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), and growth hormone secretagogue receptor (GHS-R) 1a (SB203580, SP600125, and [D-Lys3]-GHRP-6, respectively), were administered for seven consecutive days. Levels of various signaling molecules were assessed in isolated rat peritoneal macrophages. The results showed that serum ghrelin levels and levels of macrophage glucocorticoid receptor (GR) decreased, while phosphorylation of p38MAPK, JNK, and p65 nuclear factor (NF) κB increased. Ghrelin inhibited the serum induction of proinflammatory mediators, especially TNF-α, and promoted wound healing in a dose-dependent manner. Ghrelin treatment decreased phosphorylation of p38MAPK, JNK, and p65NF-κB, and increased GR levels in the presence of GHS-R1a. SB203580 or co-administration of SB203580 and SP600125 decreased TNF-α level, which may have contributed to the inactivation of p65NF-κB and increase in GR expression, as confirmed by western blotting. In conclusion, ghrelin enhances wound recovery in CRBI rats, possibly by decreasing the induction of TNF-α or other proinflammatory mediators that are involved in the regulation of GHS-R1a-mediated MAPK-NF-κB/GR signaling pathways.

  2. An Algebraic Approach to Guarantee Harmonic Balance Method Using Gröbner Base

    NASA Astrophysics Data System (ADS)

    Yagi, Masakazu; Hisakado, Takashi; Okumura, Kohshi

    Harmonic balance (HB) method is well known principle for analyzing periodic oscillations on nonlinear networks and systems. Because the HB method has a truncation error, approximated solutions have been guaranteed by error bounds. However, its numerical computation is very time-consuming compared with solving the HB equation. This paper proposes an algebraic representation of the error bound using Gröbner base. The algebraic representation enables to decrease the computational cost of the error bound considerably. Moreover, using singular points of the algebraic representation, we can obtain accurate break points of the error bound by collisions.

  3. EDITORIAL: 19th International Conference on General Relativity and Gravitation (GR19), México, 4-9 July 2010 19th International Conference on General Relativity and Gravitation (GR19), México City, México, 4-9 July 2010

    NASA Astrophysics Data System (ADS)

    Marolf, Don; Sudarsky, Daniel

    2011-06-01

    The GR19 meeting was held in México City from 6-9 July 2010. The decision to have the meeting in México was taken during the GR18 meeting in Sydney, Australia in 2007, and represented a great milestone for the scientific community working in the fields related to gravitation in México. This fact was evidenced by the commitment of the most important institutions in México where the field is developed, by the support the meeting received at various governmental levels, and also by a promotional campaign dedicated to educate the public about our subject, which was undertaken by important segments of the gravitational physics community in Mexico. This campaign was named 'El Mes de Einstein' or 'The Einsteinian Month', and consisted of a series of presentations, talks and movies about topics related to General Relativity which culminated with the public talk of the GR19 meeting (now a traditional aspect of the GR events). This talk was given by George Smoot, Nobel laureate in physics 2006, on the amazing developments around the detailed studies of the Cosmic Microwave Background, and was held at the Nezahualc'oyotl Hall in the main campus of the National Autonomous University of México, which was filled to capacity by enthusiastic crowds of lay people fascinated with the subject. The meeting itself was a very successful one with participants from dozens of countries spanning the five continents, with a rich, varied and informative plenary program. Highlights, featured in this issue, were perhaps the talk by Veronika Hubeny on the fluid/gravity correspondence, a subject that has grown dramatically during the last few years, the lecture by Tarun Souradeep on the enormous potential for discovery offered by the ever increasing accuracy of cosmological observations, the presentation by Jeffrey McClintock, about accreting black holes and the exciting possibility of measuring their spins, the informative review about Loop Quantum Gravity from one of the pioneers of the

  4. Goneis.gr: Training Greek Parents on ICT and Safer Internet

    NASA Astrophysics Data System (ADS)

    Manouselis, Nikos; Riviou, Katerina; Palavitsinis, Nikos; Giannikopoulou, Vasiliki; Tsanakas, Panayotis

    Children's use of the Internet has significantly risen in the last decade. Nevertheless, children spend a lot of time online which makes them susceptible to various threats (such as inappropriate material, offensive language, etc). Parents are the last frontier to this menace but they also need to be educated and trained in order to protect their children. Goneis.gr is an initiative launched by the Greek government that aims to educate parents on safer Internet and the use of parental control software. Parents are also entitled to distance learning courses covering basic computer skills. This paper presents the results of two separate surveys that took place in the last few months (December 2008-January 2009). The first survey targeted the parents that have completed the programme and the second one the educational providers that participate in the programme and offer the training to the beneficiaries.

  5. Cannabinoids and traumatic stress modulation of contextual fear extinction and GR expression in the amygdala-hippocampal-prefrontal circuit.

    PubMed

    Ganon-Elazar, Eti; Akirav, Irit

    2013-09-01

    Considerable evidence suggests that cannabinoids modulate the behavioral and physiological response to stressful events. We have recently shown that activating the cannabinoid system using the CB1/CB2 receptor agonist WIN55,212-2 (WIN) in proximity to exposure to single-prolonged stress (SPS), a rat model of emotional trauma, prevented the stress-induced enhancement of acoustic startle response, the impairment in avoidance extinction and the enhanced negative feedback on the hypothalamic-pituitary-adrenal (HPA) axis (Ganon-Elazar and Akirav, 2012). Some of the effects were found to be mediated by CB1 receptors in the basolateral amygdala (BLA). Here we examined whether cannabinoid receptor activation in a putative brain circuit that includes the BLA, hippocampus and prefrontal cortex (PFC), could prevent the effects of traumatic stress on contextual fear extinction and alterations in glucocorticoid receptor (GR) protein levels. We found that: (i) SPS impaired contextual fear extinction tested one week after trauma exposure and that WIN prevented the stress-induced impairment of extinction when microinjected immediately after trauma exposure into the BLA or hippocampus (5 μg), but not when microinjected into the PFC, (ii) the ameliorating effects of WIN on contextual extinction were prevented by blocking GRs in the BLA and hippocampus, and (iii) SPS up regulated GRs in the BLA, PFC and hippocampus and systemic WIN administration (0.5 mg/kg) after trauma exposure normalized GR levels in the BLA and hippocampus, but not in the PFC. Cannabinoid receptor activation in the aftermath of trauma exposure may regulate the emotional response to the trauma and prevent stress-induced impairment of extinction and GR up regulation through the mediation of CB1 receptors in the BLA and hippocampus. Taken together, the findings suggest that the interaction between the cannabinoid and glucocorticoid systems is crucial in the modulation of emotional trauma. Copyright © 2013 Elsevier

  6. Comparison of Abbott RealTime genotype II, GeneMatrix restriction fragment mass polymorphism and Sysmex HISCL HCV Gr assays for hepatitis C virus genotyping.

    PubMed

    Han, Mi-Soon; Park, Yongjung; Kim, Hyon-Suk

    2017-07-26

    Hepatitis C virus (HCV) genotype is a predictive marker for treatment response. We sequentially evaluated the performances of two nucleic acid amplification tests (NAATs) and one serology assay for HCV genotype: Abbott RealTime genotype II (RealTime II), GeneMatrix restriction fragment mass polymorphism (RFMP), and Sysmex HISCL HCV Gr (HISCL Gr). We examined 281 clinical samples with three assays. The accuracy was assessed using the HCV Genotype Performance Panel PHW204 (SeraCare Life Sciences) for two NAATs. Discrepant cases were re-genotyped by the Versant HCV v.2.0 (line probe 2.0) assay. With the RealTime II assay, clinic samples were analyzed as follows: genotypes 1b (43.1%), 2 (40.2%), 1 subtypes other than 1a and 1b (12.5%), 3 (1.8%), 4 (1.4%), 1a (0.7%), 6 (0.4%), and mixed (1.1%). The RealTime II and RFMP assays showed a type concordance rate of 97.5% (274/281) (κ=0.80) and no significant discordance (p=0.25). Both assays accurately genotyped all samples in the Performance Panel by the subtype level. The HISCL Gr assay showed concordance rates of about 91% (κ<0.40) and statistically significant discordances with two NAATs (p<0.05). In confirmation tests, the results of RFMP assay were the most consistent with those of Versant 2.0 assay. The three HCV assays provided genotyping and serotyping results with good concordance rates. The two NAATs (RealTime II and RFMP) showed comparable performance and good agreement. However, the results of the HISCL Gr assay showed statistically significant differences with those of the NAATs.

  7. Electrochemical treatment of 2, 4-dichlorophenol using a nanostructured 3D-porous Ti/Sb-SnO2-Gr anode: Reaction kinetics, mechanism, and continuous operation.

    PubMed

    Asim, Sumreen; Zhu, Yunqing; Batool, Aisha; Hailili, Reshalaiti; Luo, Jianmin; Wang, Yuanhao; Wang, Chuanyi

    2017-10-01

    2, 4-dichlorophenol (2, 4-DCP) is considered to be a highly toxic, mutagenic, and possibly carcinogenic pollutant. This study is focused on the electrochemical oxidation of 2, 4-DCP on nanostructured 3D-porous Ti/Sb-SnO 2 -Gr anodes, with the aim of presenting a comprehensive elucidation of mineralization process through the investigation of influential kinetics, the reactivity of hydroxyl radical's and analysis of intermediates. High efficiency was achieved at pH of 3 using Na 2 SO 4 electrolytes at a current density of 30 mA cm -2 . Under the optimized conditions, a maximum removal of 2, 4-DCP of up to 99.9% was reached, whereas a TOC removal of 81% was recorded with the lowest EC TOC (0.49 kW h g -1 ) within 40 min of electrolysis. To explore the stability of the 3D-Ti/Sb-SnO 2 -Gr electrodes, a continuous electrochemical operation was established, and the consistent mineralization results indicated the effectiveness of the 3D-Ti/Sb-SnO 2 -Gr system concerning its durability and practical utilization. EPR studies demonstrated the abundant generation of OH radicals on 3D-Ti/Sb-SnO 2 -Gr, resulting in fast recalcitrant pollutant incineration. From dechlorination and the reactivity of the OH radicals, several intermediates including six cyclic byproducts and three aliphatic carboxylic acids were detected, and two possible degradation pathways were proposed that justify the complete mineralization of 2, 4-DCP. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Developing an Optimum Protocol for Thermoluminescence Dosimetry with GR-200 Chips using Taguchi Method.

    PubMed

    Sadeghi, Maryam; Faghihi, Reza; Sina, Sedigheh

    2017-06-15

    Thermoluminescence dosimetry (TLD) is a powerful technique with wide applications in personal, environmental and clinical dosimetry. The optimum annealing, storage and reading protocols are very effective in accuracy of TLD response. The purpose of this study is to obtain an optimum protocol for GR-200; LiF: Mg, Cu, P, by optimizing the effective parameters, to increase the reliability of the TLD response using Taguchi method. Taguchi method has been used in this study for optimization of annealing, storage and reading protocols of the TLDs. A number of 108 GR-200 chips were divided into 27 groups, each containing four chips. The TLDs were exposed to three different doses, and stored, annealed and read out by different procedures as suggested by Taguchi Method. By comparing the signal-to-noise ratios the optimum dosimetry procedure was obtained. According to the results, the optimum values for annealing temperature (°C), Annealing Time (s), Annealing to Exposure time (d), Exposure to Readout time (d), Pre-heat Temperature (°C), Pre-heat Time (s), Heating Rate (°C/s), Maximum Temperature of Readout (°C), readout time (s) and Storage Temperature (°C) are 240, 90, 1, 2, 50, 0, 15, 240, 13 and -20, respectively. Using the optimum protocol, an efficient glow curve with low residual signals can be achieved. Using optimum protocol obtained by Taguchi method, the dosimetry can be effectively performed with great accuracy. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Effects of static tensile load on the thermal expansion of Gr/PI composite material

    NASA Technical Reports Server (NTRS)

    Farley, G. L.

    1981-01-01

    The effect of static tensile load on the thermal expansion of Gr/PI composite material was measured for seven different laminate configurations. A computer program was developed which implements laminate theory in a piecewise linear fashion to predict the coupled nonlinear thermomechanical behavior. Static tensile load significantly affected the thermal expansion characteristics of the laminates tested. This effect is attributed to a fiber instability micromechanical behavior of the constituent materials. Analytical results correlated reasonably well with free thermal expansion tests (no load applied to the specimen). However, correlation was poor for tests with an applied load.

  10. Presence of S100A8/Gr1-Positive Myeloid-Derived Suppressor Cells in Primary Tumors and Visceral Organs Invaded by Breast Carcinoma Cells.

    PubMed

    Tanriover, Gamze; Eyinc, Mehmet Berk; Aliyev, Elnur; Dilmac, Sayra; Erin, Nuray

    2018-04-26

    Increased S100A8/A9 expression in Gr1-positive cells has been shown in myeloid-derived suppressor cells and may play a role in the formation of a metastatic milieu. We aimed to determine S100A8/A9 expression alone and with coexpression of Gr1 (a myeloid marker) in primary tumor and visceral tissues invaded by metastatic breast carcinoma. Female BALB/c mice were injected with 4TLM, 4THM, and 67NR orthotopically. Confluent cells (75%-80%) were used. Primary tumor, lung, liver, and spleen tissue samples were removed 26 days after injection. Peripheral blood smears and metastasis assay were performed, as was immunohistochemistry and staining. S100A8/A9 immunoreactivity alone or coexpressed with Gr1 was found in primary tumors formed by 4TLM and 4THM cells, which was markedly higher than in primary tumors formed by nonmetastatic 67NR cells. Similarly, liver and lung tissues obtained from mice injected with 4TLM or 4THM cells were invaded by S100A8/A9-positive and Gr1-positive cells. Double-positive cells were markedly fewer in liver and lung tissues of animals injected with 67NR cells. S100A8/A9-positive cells were mostly localized in red pulp of spleens. We observed an increased number of neutrophils in the peripheral blood of mice injected with metastatic breast carcinoma cells. Tumor-derived factors may increase S100A8/A9-positive cells locally and systemically, and S100A8/A9-positive cells may provide an appropriate milieu for the formation of metastasis. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. The disruption of two salt bridges of the cold-active xylanase XynGR40 results in an increase in activity, but a decrease in thermostability.

    PubMed

    Wang, Guozeng; Wu, Jingjing; Lin, Juan; Ye, Xiuyun; Yao, Bin

    2016-12-02

    Cold-active xylanases are of great interest due to their large potential for application in the food industry. In this study, salt bridges of the eight glycoside hydrolase (GH) family 10 cold-active xylanases reported to date were predicted and the salt bridges specific to the cold-active xylanase XynGR40 were identified. Seven mutants were constructed to disrupt salt bridges specific to XynGR40. The results suggested that five mutants lost their xylanase activity, while the other two mutants, D30N and D83N, displayed different properties when compared with the wild-type XynGR40. First, both mutations showed an obvious decrease in thermostability, with the T 1/2 of D30N and D83N at 50 °C being about one half and one sixth of the wild-type, respectively. Second, both D30N and D83N had a higher specific activity than the wild-type, with activities about 13 and 163% higher, respectively. Third, both D30N and D83N had high k cat and K m values, which resulted in a higher catalytic efficiency of the mutant D83N, but a lower catalytic efficiency of the mutant D30N compared to the wild-type. Our results suggested that salt bridges play important roles in both the activity and thermostability of the cold-active xylanase XynGR40. The mutant D83N had a higher k cat and higher relative activity at low temperatures than the wild-type, and is a good candidate for application in the food industry. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Positivity bound on the imaginary part of the right-chiral tensor coupling gR in polarized top quark decay

    NASA Astrophysics Data System (ADS)

    Groote, S.; Körner, J. G.

    2017-12-01

    We derive a positivity bound on the right-chiral tensor coupling Im gR in polarized top quark decay by analyzing the angular decay distribution of the three-body polarized top quark decay t (↑)→b +ℓ++νℓ in next-to-leading order QCD. We obtain the bound -0.0420 ≤Im gR≤0.0420 .

  13. Plinian vs. phreatomagmatic eruptions at Grímsvötn volcano, Iceland

    NASA Astrophysics Data System (ADS)

    Haddadi, Baptiste; Sigmarsson, Olgeir; Larsen, Guðrún

    2016-04-01

    Grímsvötn is a subglacial central volcano located under the Vatnajökull ice cap, above the assumed centre of the Iceland mantle plume. Historical explosive eruptions are mostly of phreatomagmatic character whereas pure magmatic behaviour may characterize the largest eruptions. What causes this different eruption behaviour is uncertain. Here, we report petrological estimates of crystallization depth and volatile degassing as recorded by sulfur concentrations in melt inclusions (MI) hosted by ferromagnesian minerals and the groundmass glass. Tephra from four eruptions, AD 1823, 1873, 2004 and 2011, were selected. The 2011 and 1873 are the largest known historical eruptions, whereas the 2004 eruption is probably amongst the smallest. The repose time preceding those eruptions is surprisingly similar, or 6 to 7 years, and the major-element compositions are uniform. Plagioclase, clinopyroxene (cpx) and olivine are the three coexisting phases at the liquidus in the quartz-tholeiites of Grímsvötn. The cpx-melt geothermobarometer (Putirka 2008) applied to the 2011 tephra reveals that cpx crystallized over a large range of P from 60 to 640 MPa (depth range: 1.7-18km) and T between 1060 and 1175°C before the Plinian eruption, therefore mobilizing the entire crustal magma system. In contrast, the phreatomagmatic tephra do not record the shallowest crystallization but interestingly all four tephra have identical median entrapment pressure of approximately 400 MPa. Therefore, the depth from which the magma bodies are derived, does not explain the difference in explosivity between those eruptions nor the variable magma volume (V) produced. Sulfur concentrations in MI are only slightly higher in the Plinian products, the difference (10%) being insufficient to explain the different eruption regimes. The ΔS, the difference between the maximum S concentrations in MI and the mean of the groundmass glass for a given eruption, is higher in the Plinian tephra. Based on literature

  14. Bloch-Grüneisen nonlinearity of electron transport in GaAs/AlGaAs heterostructures

    DOE PAGES

    Raichev, O. E.; Hatke, A. T.; Zudov, M. A.; ...

    2017-08-22

    We report on nonlinear transport measurements in a two-dimensional electron gas hosted in GaAs/AlGaAs heterostructures. Upon application of direct current, the low-temperature differential resistivity acquires a positive correction, which exhibits a pronounced maximum followed by a plateau. With increasing temperature, the nonlinearity diminishes and disappears. These observations can be understood in terms of a crossover from the Bloch-Gr¨uneisen regime to the quasielastic scattering regime as the electrons are heated by direct current. Calculations considering interaction of electrons with acoustic phonons provide reasonable description of our experimental findings.

  15. [Technical recommendations and best practice guidelines for May-Grünwald-Giemsa staining: literature review and insights from the quality assurance].

    PubMed

    Piaton, Eric; Fabre, Monique; Goubin-Versini, Isabelle; Bretz-Grenier, Marie-Françoise; Courtade-Saïdi, Monique; Vincent, Serge; Belleannée, Geneviève; Thivolet, Françoise; Boutonnat, Jean; Debaque, Hervé; Fleury-Feith, Jocelyne; Vielh, Philippe; Cochand-Priollet, Béatrix; Egelé, Caroline; Bellocq, Jean-Pierre; Michiels, Jean-François

    2015-08-01

    May-Grünwald-Giemsa (MGG) stain is a Romanowsky-type, polychromatic stain as those of Giemsa, Leishman and Wright. Apart being the reference method of haematology, it has become a routine stain of diagnostic cytopathology for the study of air-dried preparations (lymph node imprints, centrifuged body fluids and fine needle aspirations). In the context of their actions of promoting the principles of quality assurance in cytopathology, the French Association for Quality Assurance in Anatomic and Cytologic Pathology (AFAQAP) and the French Society of Clinical Cytology (SFCC) conducted a proficiency test on MGG stain in 2013. Results from the test, together with the review of literature data allow pre-analytical and analytical steps of MGG stain to be updated. Recommendations include rapid air-drying of cell preparations/imprints, fixation using either methanol or May-Grünwald alone for 3-10minutes, two-step staining: 50% May-Grünwald in buffer pH 6.8 v/v for 3-5minutes, followed by 10% buffered Giemsa solution for 10-30minutes, and running water for 1-3minutes. Quality evaluation must be performed on red blood cells (RBCs) and leukocytes, not on tumour cells. Under correct pH conditions, RBCs must appear pink-orange (acidophilic) or buff-coloured, neither green nor blue. Leukocyte cytoplasm must be almost transparent, with clearly delineated granules. However, staining may vary somewhat and testing is recommended for automated methods (slide stainers) which remain the standard for reproducibility. Though MGG stain remains the reference stain, Diff-Quik(®) stain can be used for the rapid evaluation of cell samples. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  16. Theoretical prediction of Grüneisen parameter for SiO{sub 2}.TiO{sub 2} bulk metallic glasses

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

    Singh, Chandra K.; Pandey, Brijesh K., E-mail: bkpmmmec11@gmail.com; Pandey, Anjani K.

    2016-05-23

    The Grüneisen parameter (γ) is very important to decide the limitations for the prediction of thermoelastic properties of bulk metallic glasses. It can be defined in terms of microscopic and macroscopic parameters of the material in which former is based on vibrational frequencies of atoms in the material while later is closely related to its thermodynamic properties. Different formulation and equation of states are used by the pioneer researchers of this field to predict the true sense of Gruneisen parameter for BMG but for SiO{sub 2}.TiO{sub 2} very few and insufficient information is available till now. In the present workmore » we have tested the validity of two different isothermal EOS viz. Poirrior-Tarantola EOS and Usual-Tait EOS to predict the true value of Gruneisen parameter for SiO{sub 2}.TiO{sub 2} as a function of compression. Using different thermodynamic limitations related to the material constraints and analyzing obtained result it is concluded that the Poirrior-Tarantola EOS gives better numeric values of Grüneisen parameter (γ) for SiO{sub 2}.TiO{sub 2} BMG.« less

  17. Discovery of a novel non-steroidal GR antagonist with in vivo efficacy in the olanzapine-induced weight gain model in the rat.

    PubMed

    Hunt, Hazel J; Ray, Nicholas C; Hynd, George; Sutton, Jon; Sajad, Mohammed; O'Connor, Elizabeth; Ahmed, Shahadat; Lockey, Peter; Daly, Steve; Buckley, Gerry; Clark, Robin D; Roe, Robert; Blasey, Christine; Belanoff, Joe

    2012-12-15

    We report the optimization of a series of non-steroidal GR antagonists that led to the identification of compound 7. This compound is efficacious when dosed orally in an olanzapine-induced weight gain model in rats. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Time constraints on the origin of large volume basalts derived from O-isotope and trace element mineral zoning and U-series disequilibria in the Laki and Grímsvötn volcanic system

    NASA Astrophysics Data System (ADS)

    Bindeman, Ilya N.; Sigmarsson, Olgeir; Eiler, John

    2006-05-01

    The 1783-1784 AD fissure eruption of Laki (Iceland) produced 15 km 3 of homogeneous basaltic lavas and tephra that are characterized by extreme (3‰) 18O-depletion relative to normal mantle. Basaltic tephra erupted over the last 8 centuries and as late as in November 2004 from the Grímsvötn central volcano, which together with Laki are a part of a single volcanic system, is indistinguishable in δ18O from Laki glass. This suggests that all tap a homogeneous and long-lived low- δ18O magma reservoir. In contrast, we observe extreme oxygen isotope heterogeneity (2.2-5.2‰) in olivine and plagioclase contained within these lavas and tephra, and disequilibrium mineral-glass oxygen-isotope fractionations. Such low- δ18O glass values, and extreme 3‰ range in δ18O olivine have not been described in any other unaltered basalt. The energy constrained mass balance calculation involving oxygen isotopes and major element composition calls for an origin of the Laki-Grímsvötn quartz tholeiitic basaltic melts with δ18O = 3.1‰ by bulk digestion of low- δ18O hydrated basaltic crust with δ18O = - 4‰ to + 1‰, rather than magma mixing with ultra-low- δ18O silicic melt. The abundant Pleistocene hyaloclastites, which were altered by synglacial meltwaters, can serve as a likely assimilant material for the Grímsvötn magmas. The ( 226Ra / 230Th) activity ratio in Laki lavas and 20th century Grímsvötn tephras is 13% in-excess of secular equilibrium, but products of the 20th century Grímsvötn eruptions have equilibrium ( 210Pb / 226Ra). Modeling of oxygen isotope exchange between disequilibrium phenocrysts and magmas, and these short-lived U-series nuclides yields a coherent age for the Laki-Grímsvötn magma reservoir between 100 and 1000 yrs. We propose the existence of uniquely fingerprinted, low- δ18O, homogeneous, large volume, and long-lived basaltic reservoir beneath the Laki-Grímsvötn volcanic system that has been kept alive in its position above the

  19. Specific labelling of serotonin 5-HT(1B) receptors in rat frontal cortex with the novel, phenylpiperazine derivative, [3H]GR125,743. A pharmacological characterization.

    PubMed

    Millan, M J; Newman-Tancredi, A; Lochon, S; Touzard, M; Aubry, S; Audinot, V

    2002-04-01

    Although several tritiated agonists have been used for radiolabelling serotonin (5-hydroxytryptamine, 5-HT)(1B) receptors in rats, data with a selective, radiolabelled antagonist have not been presented. Inasmuch as [3H]GR125,743 specifically labels cloned, human and native guinea pig 5-HT(1B) receptors and has been employed for characterization of cerebral 5-HT(1B) receptor in the latter species [Eur. J. Pharmacol. 327 (1997) 247.], the present study evaluated its utility for characterization of native, cerebral 5-HT(1B) sites in the rat. In homogenates of frontal cortex, [3H]GR125,743 (0.8 nM) showed rapid association (t(1/2)=3.4 min), >90% specific binding and high affinity (K(d)=0.6 nM) for a homogeneous population of receptors with a density (B(max)) of 160 fmol/mg protein. In competition binding studies, affinities were determined for 15 chemically diverse 5-HT(1B) agonists, including 2-[5-[3-(4-methylsulphonylamino)benzyl-1,2,4-oxadiazol-5-yl]-1H-indole-3-yl]ethylamine (L694,247; pK(i), 10.4), 5-carboxamidotryptamine (5-CT; 9.7), 3-[3-(2-dimethylamino-ethyl)-1H-indol-6-yl]-N-(4-methoxybenzyl)acrylamide (GR46,611; 9.6), 5-methoxy-3-(1,2,5,6-tetrahydro-4-pyridinyl)-1H-indole (RU24,969; 9.5), dihydroergotamine (DHE; 8.6), 5-H-pyrrolo[3,2-b]pyridin-5-one,1,4-dihydro-3-(1,2,3,6-tetrahydro-4-pyridinyl (CP93,129; 8.4), anpirtoline (7.9), sumatriptan (7.4), 1-[2-(3-fluorophenyl)ethyl]-4-[3-[5-(1,2,4-triazol-4-yl)-1H-indol-3-yl]propyl]piperazine (L775,606; 6.4) and (minus sign)-1(S)-[2-[4-(4-methoxyphenyl)piperazin-1-yl]ethyl]-N-methyl-3,4-dihydro-1H-2-benzopyran-6-carboxamide (PNU109,291; <5.0). Similarly, affinities were established for 13 chemically diverse antagonists, including N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-3-methyl-4-(4-pyridyl)benzamide (GR125,743; pK(i), 9.1), (-)cyanopindolol (9.0), (-)-tertatolol (8.2), N-(4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiozol-3-yl)biphenyl-4-carboxamide (GR127,935; 8.2), N-[3

  20. Report on the Results of Site Testing to Determine National Register Eligibility for Sites 39GR32, 39GR53, 39LM33 and 39LM39, in the Lake Francis Case Area, South Dakota. Volume 2. Appendices

    DTIC Science & Technology

    1987-06-01

    WESTERN STUDIES AUGUSTANA COLLEGE, SIOUX FALLS, SOUTH DAKOTA 57105 ARCHEOLOGICAL CONTRACT SERIES NUMBER 29 VOLUME 2 APPENDICES 1. Location of Sites...Specialist Report - Report on the Soils at Sites 39GR53 and 39LM33, by Dr. Frederick Westin APPENDIX I Location of Sites on UGSG 7.5’ Quadrangle Maps...QUADANGL LOCTIO / (r\\\\ 2~0 SCALE 12000 0~ 1 0IL QUDANL OATO 1PPROXLOMETERA 51ONOU INTRVA 10LNAIN FEET DAU 1S MEILEALEE Location of site 39LM39. J~27 . ~ FIt

  1. WNIN/GR-Ob - an insulin-resistant obese rat model from inbred WNIN strain.

    PubMed

    Harishankar, N; Vajreswari, A; Giridharan, N V

    2011-09-01

    WNIN/GR-Ob is a mutant obese rat strain with impaired glucose tolerance (IGT) developed at the National Institute of Nutrition (NIN), Hyderabad, India, from the existing 80 year old Wistar rat (WNIN) stock colony. The data presented here pertain to its obese nature along with IGT trait as evidenced by physical, physiological and biochemical parameters. The study also explains its existence, in three phenotypes: homozygous lean (+/+), heterozygous carrier (+/-) and homozygous obese (-/-). Thirty animals (15 males and 15 females) from each phenotype (+/+, +/-, -/-) and 24 lean and obese (6 males and 6 females) rats were taken for growth and food intake studies respectively. Twelve adult rats from each phenotype were taken for body composition measurement by total body electrical conductivity (TOBEC); 12 rats of both genders from each phenotype at different ages were taken for clinical chemistry parameters. Physiological indices of insulin resistance were calculated according to the homeostasis model assessment for insulin resistance (HOMA-IR) and also by studying U¹⁴C 2-deoxy glucose uptake (2DG). WNINGR-Ob mutants had high growth, hyperphagia, polydipsia, polyurea, glycosuria, and significantly lower lean body mass, higher fat mass as compared with carrier and lean rats. These mutants, at 50 days of age displayed abnormal response to glucose load (IGT), hyperinsulinaemia, hypertriglyceridaemia, hypercholesterolaemia and hyperleptinaemia. Basal and insulin-stimulated glucose uptakes by diaphragm were significantly decreased in obese rats as compared with lean rats. Obese rats of the designated WNIN/GR-Ob strain showed obesity with IGT, as adjudged by physical, physiological and biochemical indices. These indices varied among the three phenotypes, being lowest in lean, highest in obese and intermediate in carrier phenotypes thereby suggesting that obesity is inherited as autosomal incomplete dominant trait in this strain. This mutant obese rat model is easy to

  2. Metformin extended release: metformin gastric retention, metformin GR, metformin XR.

    PubMed

    2005-01-01

    Metformin extended release [Glumetza, metformin hydrochloride, metformin gastric retention, metformin GR] is a proprietary once-a-day formulation of metformin hydrochloride under development with Depomed for the treatment of diabetes mellitus. In May 2002, Depomed licensed manufacturing and marketing rights for its proprietary formulation of metformin extended release (500mg dose) to Biovail Corporation for the US (including Puerto Rico) and Canada. Under the terms of the agreement, Biovail will pay DepoMed a 25 million dollars milestone fee upon approval of the 500mg dosage and also customary royalties on the net sales in the US and Canada. Biovail also agreed to acquire approximately 2.4 million of additionally issued Depomed shares for 12.3 million dollars. Biovail has subsequently developed a 1000mg dose of metformin extended release [metformin XR] using its proprietary Smartcoat delivery technology allowing a graduated release of the active drug from the tablet. In April 2004, Depomed and Biovail amended their original license agreement of May 2002. Under the terms of the amended agreement, Depomed will receive royalties on sales of Biovail's 1000mg tablet in the US and Canada. In turn, Biovail acquired access to Depomed's clinical data for the metformin 500mg tablet that will be used to accelerate regulatory filings for Biovail's 1000mg tablet and establish equivalence between the two dosages. Biovail is seeking marketing partners for metformin extended release (Glumetza) in the US. The company anticipates signing an agreement for the US during the second half of 2005. In Canada, Biovail Corporation will market Glumetzatrade mark through its Canadian division, Bioval Pharmaceuticals Canada. Depomed has an agreement with LG Life Sciences for the commercialisation and distribution of metformin extended release in Korea. Metformin GR is available for partnership in Europe and Asia. Biovail Corporation and Depomed announced in June 2005 that the US FDA has

  3. Volcanic ash leaching as a means of tracing the environmental impact of the 2011 Grímsvötn eruption, Iceland.

    PubMed

    Cabré, J; Aulinas, M; Rejas, M; Fernandez-Turiel, J L

    2016-07-01

    The Grímsvötn volcanic eruption, from 21 to 28 May, 2011, was the largest eruption of the Grímsvötn Volcanic System since 1873, with a Volcanic Explosivity Index (VEI) of magnitude 4. The main geochemical features of the potential environmental impact of the volcanic ash-water interaction were determined using two different leaching methods as proxies (batch and vertical flow-through column experiments). Ash consists of glass with minor amounts of plagioclase, clinopyroxene, diopside, olivine and iron sulphide; this latter mineral phase is very rare in juvenile ash. Ash grain morphology and size reflect the intense interaction of magma and water during eruption. Batch and column leaching tests in deionised water indicate that Na, K, Ca, Mg, Si, Cl, S and F had the highest potential geochemical fluxes to the environment. Release of various elements from volcanic ash took place immediately through dissolution of soluble salts from the ash surface. Element solubilities of Grímsvötn ash regarding bulk ash composition were <1 %. Combining the element solubilities and the total estimated mass of tephra (7.29 × 10(14) g), the total inputs of environmentally important elements were estimated to be 8.91 × 10(9) g Ca, 7.02 × 10(9) g S, 1.10 × 10(9) g Cl, 9.91 × 10(8) g Mg, 9.91 × 10(8) g Fe and 1.45 × 10(8) g P The potential environmental problems were mainly associated with the release of F (5.19 × 10(9) g).

  4. Test Characteristics of Acridine Orange, Gram, and May-Grünwald-Giemsa Stains for Enumeration of Intracellular Organisms in Bronchoalveolar Lavage Fluid

    PubMed Central

    De Brauwer, Els; Jacobs, Jan; Nieman, Fred; Bruggeman, Cathrien; Drent, Marjolein

    1999-01-01

    For enumeration of intracellular organisms (ICO) in bronchoalveolar lavage fluid samples, the May-Grünwald-Giemsa (MGG) stain displayed higher interobserver agreement than the acridine orange and Gram stains. The MGG stain offered a reliable enumeration of ICO when 200 cells were counted by one observer. PMID:9889233

  5. Study of the Phototransference in GR-200 Dosimetric Material and its Convenience for Dose Re-estimation

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

    Baly, L.; Otazo, M. R.; Molina, D.

    2006-09-08

    A study of the phototransference of charges from deep to dosimetric traps in GR-200 material is presented and its convenience for dose re-estimation in the dose range between 2 and 100mSv is also analyzed. The recovering coefficient (RC) defined as the ratio between the phototransferred thermoluminescence (PTTL) and the original thermoluminescence (TL) of the dosimetric trap was used to evaluate the ratio of phototransferred charges from deep traps and the original charges in the dosimetric traps. The results show the convenience of this method for dose re-estimation for this material in the selected range of doses.

  6. Position Extrema in Keplerian Relative Motion: A Gröbner Basis Approach

    NASA Astrophysics Data System (ADS)

    Allgeier, Shawn E.; Fitz-Coy, Norman G.; Erwin, R. Scott

    2012-12-01

    This paper analyzes the relative motion between two spacecraft in orbit. Specifically, the paper provides bounds for relative spacecraft position-based measures which impact spacecraft formation-flight mission design and analysis. Previous efforts have provided bounds for the separation distance between two spacecraft. This paper presents a methodology for bounding the local vertical, horizontal, and cross track components of the relative position vector in a spacecraft centered, rotating reference frame. Three metrics are derived and a methodology for bounding them is presented. The solution of the extremal equations for the metrics is formulated as an affine variety and obtained using a Gröbner basis reduction. No approximations are utilized and the only assumption is that the two spacecraft are in bound Keplerian orbits. Numerical examples are included to demonstrate the efficacy of the method. The metrics have utility to the mission designer of formation flight architectures, with relevance to Earth observation constellations.

  7. Testing the Gräfenberg Ring in Interwar Britain: Norman Haire, Helena Wright, and the Debate over Statistical Evidence, Side Effects, and Intra-uterine Contraception.

    PubMed

    Rusterholz, Caroline

    2017-10-01

    This paper examines the introduction to Britain of the Gräfenberg ring, an early version of what later became known as an intrauterine device (IUD). The struggle during the interwar years to establish the value of the ring provides an opportunity for a case study of the evaluation and acceptance of a new medical device. With the professionalization of the birth control movement and the expansion of birth control clinics in interwar Britain, efforts to develop better scientific means for contraception grew rapidly. At the end of the nineteenth century, methods for controlling fertility ranged from coitus interruptus and abstinence, to diverse substances ingested or placed into the vagina, to barrier methods. The first decades of the twentieth century brought early work on chemical contraceptives as well as a number of new intrauterine devices, among them the Gräfenberg ring. Developing a cheap, reliable, and widely acceptable contraceptive became a pressing goal for activists in the voluntary birth control movement in Britain between the wars. Yet, tensions developed over the best form of contraception to prescribe. By situating the Gräfenberg ring within the context of the debates and competition among British medical and birth control professionals, this paper reveals broader issues of power relationships and expertise in the assessment of a new medical technology. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. Tumor development in murine ulcerative colitis depends on MyD88 signaling of colonic F4/80+CD11bhighGr1low macrophages

    PubMed Central

    Schiechl, Gabriela; Bauer, Bernhard; Fuss, Ivan; Lang, Sven A.; Moser, Christian; Ruemmele, Petra; Rose-John, Stefan; Neurath, Markus F.; Geissler, Edward K.; Schlitt, Hans-Jürgen; Strober, Warren; Fichtner-Feigl, Stefan

    2011-01-01

    Patients with prolonged ulcerative colitis (UC) frequently develop colorectal adenocarcinoma for reasons that are not fully clear. To analyze inflammation-associated colonic tumorigenesis, we developed a chronic form of oxazolone-induced colitis in mice that, similar to UC, was distinguished by the presence of IL-13–producing NKT cells. In this model, the induction of tumors using azoxymethane was accompanied by the coappearance of F4/80+CD11bhighGr1low M2 macrophages, cells that undergo polarization by IL-13 and are absent in tumors that lack high level IL-13 production. Importantly, this subset of macrophages was a source of tumor-promoting factors, including IL-6. Similar to dextran sodium sulfate–induced colitis, F4/80+CD11bhighGr1intermediate macrophages were present in the mouse model of chronic oxazolone-induced colitis and may influence tumor development through production of TGF-β1, a cytokine that inhibits tumor immunosurveillance. Finally, while robust chronic oxazolone-induced colitis developed in myeloid differentiation primary response gene 88–deficient (Myd88–/–) mice, these mice did not support tumor development. The inhibition of tumor development in Myd88–/– mice correlated with cessation of IL-6 and TGF-β1 production by M2 and F4/80+CD11bhighGr1intermediate macrophages, respectively, and was reversed by exogenous IL-6. These data show that an UC-like inflammation may facilitate tumor development by providing a milieu favoring development of MyD88-dependent tumor-supporting macrophages. PMID:21519141

  9. Dopamine inhibits the function of Gr-1+CD115+ myeloid-derived suppressor cells through D1-like receptors and enhances anti-tumor immunity.

    PubMed

    Wu, Jin; Zhang, Ruihua; Tang, Ning; Gong, Zizhen; Zhou, Jiefei; Chen, Yingwei; Chen, Kang; Cai, Wei

    2015-01-01

    MDSCs accumulate in tumor-bearing animals and cancer patients and are a major factor responsible for cancer-induced immunosuppression that limits effective cancer immunotherapy. Strategies aimed at effectively inhibiting the function of MDSCs are expected to enhance host anti-tumor immunity and improve cancer immunotherapy significantly. The neurotransmitter DA has been found to have anti-cancer activity, but the underlying mechanism is poorly understood. In this study, we sought to investigate the therapeutic mechanism and efficacy of DA on the inhibition of cancer development via the regulation of MDSC functions. The regulation of the suppressive function of Gr-1(+)CD115(+) MDSCs by DA was determined by use of murine syngeneic LLC and B16 graft models treated with DA in vivo, as well as Gr-1(+)CD115(+) MDSCs isolated from these model treated with DA ex vivo. Here, we show that Gr-1(+)CD115(+) monocytic MDSCs express D1-like DA receptors. DA dramatically attenuated the inhibitory function of tumor-induced monocytic MDSCs on T cell proliferation and IFN-γ production via D1-like DA receptors and retarded tumor growth. DA and other D1 receptor agonists inhibited IFN-γ-induced NO production by MDSCs from tumor-bearing mice and cancer patients. Decreased NO production was, in part, mediated via the suppression of p-ERK and p-JNK. In conclusion, the neurotransmitter DA potently inhibits the suppressive function of MDSC and enhances anti-tumor immunity. Our finding provides a mechanistic basis for the use of DA or D1-like receptor agonists to overcome tumor-induced immunosuppression in cancer immunotherapy. © Society for Leukocyte Biology.

  10. Quantitative Voronovskaya and Grüss-Voronovskaya type theorems for Jain-Durrmeyer operators of blending type

    NASA Astrophysics Data System (ADS)

    Kajla, Arun; Deshwal, Sheetal; Agrawal, P. N.

    2018-05-01

    In the present paper we introduce a Durrmeyer variant of Jain operators based on a function ρ (x) where ρ is a continuously differentiable function on [0,∞), ρ (0)=0 and \\inf ρ '(x)≥ a, a >0, x \\in [0,∞) . For these new operators, some indispensable auxiliary results are established first. Then, the degree of approximation with the aid of Ditzian-Totik modulus of smoothness and the rate of convergence for functions whose derivatives are of bounded variation, is obtained. Further, we focus on the study of a Voronovskaja type asymptotic theorem, quantitative Voronovskaya and Grüss-Voronovskaya type theorems.

  11. An exon 53 frameshift mutation in CUBN abrogates cubam function and causes Imerslund-Gräsbeck syndrome in dogs

    PubMed Central

    Fyfe, John C.; Hemker, Shelby L.; Venta, Patrick J.; Fitzgerald, Caitlin A.; Outerbridge, Catherine A.; Myers, Sherry L.; Giger, Urs

    2013-01-01

    Cobalamin malabsorption accompanied by selective proteinuria is an autosomal recessive disorder known as Imerslund-Gräsbeck syndrome in humans and was previously described in dogs due to amnionless (AMN) mutations. The resultant vitamin B12 deficiency causes dyshematopoiesis, lethargy, failure to thrive, and life-threatening metabolic disruption in the juvenile period. We studied 3 kindreds of border collies with cobalamin malabsorption and mapped the disease locus in affected dogs to a 2.9 Mb region of homozygosity on canine chromosome 2. The region included CUBN, the locus encoding cubilin, a peripheral membrane protein that in concert with AMN forms the functional intrinsic factor-cobalamin receptor expressed in ileum and a multi-ligand receptor in renal proximal tubules. Cobalamin malabsorption and proteinuria comprising CUBN ligands were demonstrated by radiolabeled cobalamin uptake studies and SDS-PAGE, respectively. CUBN mRNA and protein expression were reduced ~10 fold and ~20 fold, respectively, in both ileum and kidney of affected dogs. DNA sequencing demonstrated a single base deletion in exon 53 predicting a translational frameshift and early termination codon likely triggering nonsense mediated mRNA decay. The mutant allele segregated with disease in the border collie kindred. The border collie disorder indicates that a CUBN mutation far C-terminal from the intrinsic factor-cobalamin binding site can abrogate receptor expression and cause Imerslund-Gräsbeck syndrome. PMID:23746554

  12. Distinct CCR2(+) Gr1(+) cells control growth of the Yersinia pestis ΔyopM mutant in liver and spleen during systemic plague.

    PubMed

    Ye, Zhan; Uittenbogaard, Annette M; Cohen, Donald A; Kaplan, Alan M; Ambati, Jayakrishna; Straley, Susan C

    2011-02-01

    We are using a systemic plague model to identify the cells and pathways that are undermined by the virulence protein YopM of the plague bacterium Yersinia pestis. In this study, we pursued previous findings that Gr1(+) cells are required to selectively limit growth of ΔyopM Y. pestis and that CD11b(+) cells other than polymorphonuclear leukocytes (PMNs) are selectively lost in spleens infected with parent Y. pestis. When PMNs were ablated from mice, ΔyopM Y. pestis grew as well as the parent strain in liver but not in spleen, showing that these cells are critical for controlling growth of the mutant in liver but not spleen. In mice lacking expression of the chemokine receptor CCR2, wild-type growth was restored to ΔyopM Y. pestis in both organs. In spleen, the Gr1(+) cells differentially recruited by parent and ΔyopM Y. pestis infections were CCR2(+) Gr1(+) CD11b(+) CD11c(Lo-Int) MAC3(+) iNOS(+) (inducible nitric oxide synthase-positive) inflammatory dendritic cells (iDCs), and their recruitment to spleen from blood was blocked when YopM was present in the infecting strain. Consistent with influx of iDCs being affected by YopM in spleen, the growth defect of the ΔyopM mutant was relieved by the parent Y. pestis strain in a coinfection assay in which the parent strain could affect the fate of the mutant in trans. In a mouse model of bubonic plague, CCR2 also was shown to be required for ΔyopM Y. pestis to show wild-type growth in skin. The data imply that YopM's pathogenic effect indirectly undermines signaling through CCR2. We propose a model for how YopM exerts its different effects in liver and spleen.

  13. The genetics of domestication of yardlong bean, Vigna unguiculata (L.) Walp. ssp. unguiculata cv.-gr. sesquipedalis

    PubMed Central

    Kongjaimun, Alisa; Kaga, Akito; Tomooka, Norihiko; Somta, Prakit; Vaughan, Duncan A.; Srinives, Peerasak

    2012-01-01

    Background and Aims The genetics of domestication of yardlong bean [Vigna unguiculata (L.) Walp. ssp. unguiculata cv.-gr. sesquipedalis] is of particular interest because the genome of this legume has experienced divergent domestication. Initially, cowpea was domesticated from wild cowpea in Africa; in Asia a vegetable form of cowpea, yardlong bean, subsequently evolved from cowpea. Information on the genetics of domestication-related traits would be useful for yardlong bean and cowpea breeding programmes, as well as comparative genome study among members of the genus Vigna. The objectives of this study were to identify quantitative trait loci (QTLs) for domestication-related traits in yardlong bean and compare them with previously reported QTLs in closely related Vigna. Methods Two linkage maps were developed from BC1F1 and F2 populations from the cross between yardlong bean (V. unguiculata ssp. unguiculata cv.-gr. sesquipedalis) accession JP81610 and wild cowpea (V. unguiculata ssp. unguiculata var. spontanea) accession TVnu457. Using these linkage maps, QTLs for 24 domestication-related traits were analysed and mapped. QTLs were detected for traits related to seed, pod, stem and leaf. Key Results Most traits were controlled by between one and 11 QTLs. QTLs for domestication-related traits show co-location on several narrow genomic regions on almost all linkage groups (LGs), but especially on LGs 3, 7, 8 and 11. Major QTLs for sizes of seed, pod, stem and leaf were principally located on LG7. Pleiotropy or close linkage of genes for the traits is suggested in these chromosome regions. Conclusions This is the first report of QTLs for domestication-related traits in yardlong bean. The results provide a foundation for marker-assisted selection of domestication-related QTLs in yardlong bean and enhance understanding of domestication in the genus Vigna. PMID:22419763

  14. Tamoxifen inhibits macrophage FABP4 expression through the combined effects of the GR and PPARγ pathways.

    PubMed

    Jiang, Meixiu; Zhang, Ling; Ma, Xingzhe; Hu, Wenquan; Chen, Yuanli; Yu, Miao; Wang, Qixue; Li, Xiaoju; Yin, Zhinan; Zhu, Yan; Gao, Xiumei; Hajjar, David P; Duan, Yajun; Han, Jihong

    2013-09-15

    Macrophage adipocyte fatty acid-binding protein (FABP4) plays an important role in foam cell formation and development of atherosclerosis. Tamoxifen inhibits this disease process. In the present study, we determined whether the anti-atherogenic property of tamoxifen was related to its inhibition of macrophage FABP4 expression. We initially observed that tamoxifen inhibited macrophage/foam cell formation, but the inhibition was attenuated when FABP4 expression was selectively inhibited by siRNA.We then observed that tamoxifen and 4-hydroxytamoxifen inhibited FABP4 protein expression in primary macrophages isolated from both the male and female wild-type mice, suggesting that the inhibition is sex-independent. Tamoxifen and 4-hydroxytamoxifen inhibited macrophage FABP4 protein expression induced either by activation of GR (glucocorticoid receptor) or PPARγ (peroxisome-proliferator-activated receptor γ). Associated with the decreased protein expression, Fabp4 mRNA expression and promoter activity were also inhibited by tamoxifen and 4-hydroxytamoxifen, indicating transcriptional regulation. Analysis of promoter activity and EMSA/ChIP assays indicated that tamoxifen and 4-hydroxytamoxifen activated the nGRE (negative glucocorticoid regulatory element), but inhibited the PPRE (PPARγ regulatory element) in the Fabp4 gene. In vivo, administration of tamoxifen to ApoE (apolipoprotein E)-deficient (apoE-/-) mice on a high-fat diet decreased FABP4 expression in macrophages and adipose tissues as well as circulating FABP4 levels. Tamoxifen also inhibited FABP4 protein expression by human blood monocyte-derived macrophages. Taken together, the results of the present study show that tamoxifen inhibited FABP4 expression through the combined effects of GR and PPARγ signalling pathways. Our findings suggest that the inhibition of macrophage FABP4 expression can be attributed to the antiatherogenic properties of tamoxifen.

  15. The Centennial of GR: Looking forward to Black Hole Mergers at Cosmic Dawn

    NASA Astrophysics Data System (ADS)

    Cornish, Neil J.

    2015-01-01

    Einstein's theory of gravity has fundamentally altered mankind's conception of the Universe and its contents. Once outlandish notions such as the Universe expanding from a mere speck to its current vast size, or stars collapsing to form black holes are now well supported pillars of modern astronomy. Gravity is the dominant force that shapes the Universe, and gravity is behind all extremely energetic astrophysical phenomena. However, we are currently blind to the most powerful events in nature - bursts of pure gravitational wave energy from the collision of two black holes. A Laser Interferometer Space Antenna (LISA) will be able to record these collisions throughout the Universe, and provide unique insights into the co-evolution of galaxies and massive black holes. Motivated by the GR centennial, I'll take a look back at the rich and turbulent history of the LISA mission, and a look forward to the incredible science potential of its current incarnation as the European L3 eLISA mission.

  16. Exact period-four solutions of a family of n-dimensional quadratic maps via harmonic balance and Gröbner bases.

    PubMed

    D'Amico, María Belén; Calandrini, Guillermo L

    2015-11-01

    Analytical solutions of the period-four orbits exhibited by a classical family of n-dimensional quadratic maps are presented. Exact expressions are obtained by applying harmonic balance and Gröbner bases to a single-input single-output representation of the system. A detailed study of a generalized scalar quadratic map and a well-known delayed logistic model is included for illustration. In the former example, conditions for the existence of bistability phenomenon are also introduced.

  17. Exact period-four solutions of a family of n-dimensional quadratic maps via harmonic balance and Gröbner bases

    NASA Astrophysics Data System (ADS)

    D'Amico, María Belén; Calandrini, Guillermo L.

    2015-11-01

    Analytical solutions of the period-four orbits exhibited by a classical family of n-dimensional quadratic maps are presented. Exact expressions are obtained by applying harmonic balance and Gröbner bases to a single-input single-output representation of the system. A detailed study of a generalized scalar quadratic map and a well-known delayed logistic model is included for illustration. In the former example, conditions for the existence of bistability phenomenon are also introduced.

  18. The Type Ic SN 2007gr: a census of the ejecta from late-time optical-infrared spectra

    NASA Astrophysics Data System (ADS)

    Mazzali, Paolo A.; Maurer, I.; Valenti, S.; Kotak, R.; Hunter, D.

    2010-10-01

    Nebular spectra of supernovae (SNe) offer an unimpeded view of the inner region of the ejecta, where most nucleosynthesis takes place. Optical spectra cover most, but not all, of the emitting elements and therefore offer only a partial view of the products of the explosion. Simultaneous optical-infrared spectra, on the other hand, contain emission lines of all important elements, from C and O through to the intermediate mass elements (IME) Mg, Si, S, Ca and to Fe and Ni. In particular, Si and S are best seen in the IR. The availability of IR data makes it possible to explore in greater detail the results of the explosion. SN2007gr is the first Type Ic SN for which such data are available. Modelling the spectra with a non-local thermodynamic equilibrium (NLTE) code reveals that the inner ejecta contain ~1Msolar of material within a velocity of ~4500kms-1. The same mass of 56Ni derived from the light-curve peak (0.076Msolar) was used to power the spectrum, yielding consistent results. Oxygen is the dominant element, contributing ~0.8Msolar. The C/O ratio is <0.2. IME account for ~0.1Msolar. This confirms that SN2007gr was the explosion of a low-mass CO core, probably the result of a star of main-sequence mass ~15Msolar. The ratios of the CaII lines, and those of FeII, are sensitive to the assumed degree of clumping. In particular, the optical lines of [FeII] become stronger, relative to the IR lines, for higher degrees of clumping.

  19. An exon 53 frameshift mutation in CUBN abrogates cubam function and causes Imerslund-Gräsbeck syndrome in dogs.

    PubMed

    Fyfe, John C; Hemker, Shelby L; Venta, Patrick J; Fitzgerald, Caitlin A; Outerbridge, Catherine A; Myers, Sherry L; Giger, Urs

    2013-08-01

    Cobalamin malabsorption accompanied by selective proteinuria is an autosomal recessive disorder known as Imerslund-Gräsbeck syndrome in humans and was previously described in dogs due to amnionless (AMN) mutations. The resultant vitamin B12 deficiency causes dyshematopoiesis, lethargy, failure to thrive, and life-threatening metabolic disruption in the juvenile period. We studied 3 kindreds of border collies with cobalamin malabsorption and mapped the disease locus in affected dogs to a 2.9Mb region of homozygosity on canine chromosome 2. The region included CUBN, the locus encoding cubilin, a peripheral membrane protein that in concert with AMN forms the functional intrinsic factor-cobalamin receptor expressed in ileum and a multi-ligand receptor in renal proximal tubules. Cobalamin malabsorption and proteinuria comprising CUBN ligands were demonstrated by radiolabeled cobalamin uptake studies and SDS-PAGE, respectively. CUBN mRNA and protein expression were reduced ~10 fold and ~20 fold, respectively, in both ileum and kidney of affected dogs. DNA sequencing demonstrated a single base deletion in exon 53 predicting a translational frameshift and early termination codon likely triggering nonsense mediated mRNA decay. The mutant allele segregated with the disease in the border collie kindred. The border collie disorder indicates that a CUBN mutation far C-terminal from the intrinsic factor-cobalamin binding site can abrogate receptor expression and cause Imerslund-Gräsbeck syndrome. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Réalisation de circuits intégrés I^2L à base de transistors bipolaires a double hétérojonction GaAlAs/GaAs

    NASA Astrophysics Data System (ADS)

    Vannel, J. P.; Camps, T.; Ferreira, A. S.; Tasselh, J.; Cazarré, A.; Marty, A.; Bailbé, J. P.

    1991-04-01

    GaAlAs/GaAs double heterojunction bipolar transistors (DHBT's) have a number of advantages for I^2L (integrated injection logic) high speed integrated circuits concerning the interchangeability between the emitter and the collector and a high design flexibility due to the use of two heterojunctions. We present the fabrication process of an I^2L integrated circuit including a frequency divider-by-two and a ring oscillator which presents a propagation delay time of 1.2 ns for a power consumption of 8 mW. Les transistors bipolaires à double hétérojonction GaAlAs/GaAs (TBDH) présentent de nombreux avantages pour leur application dans des circuits intégrés de logique I^2L (logique à injection intégrée), dont en particulier l'interchangeabilité entre émetteur et collecteur, et la liberté de conception résultant de l'utilisation de deux hétérojonctions. Dans ce cadre nous décrivons les principales étapes technologiques de fabrication d'un circuit intégré I^2L comportant un diviseur de fréquence par 2 et un oscillateur en anneau. Ce demier présente un temps de propagation de 1,2 ns pour une puissance dissipée de 8 mW.

  1. Influence of the thermodynamic parameters on the temper embrittlement of SA508 Gr.4N Ni-Cr-Mo low alloy steel with variation of Ni, Cr and Mn contents

    NASA Astrophysics Data System (ADS)

    Park, Sang-Gyu; Lee, Ki-Hyoung; Min, Ki-Deuk; Kim, Min-Chul; Lee, Bong-Sang

    2012-07-01

    It is well known that SA508 Gr.4N low alloy steel offers improved fracture toughness and strength compared to commercial low alloy steels such as SA508 Gr.3 Mn-Mo-Ni low alloy steel. In this study, the effects of Cr, Mn, and Ni on temper embrittlement in SA508 Gr.4N low alloy steel were evaluated from the viewpoint of thermodynamic parameters such as P diffusivity and C activity. The changes of the ductile-brittle transition temperatures before and after aging were correlated with varying alloying element content, and the diffusivity of P and the activity of C were calculated and correlated with the transition behaviors. The addition of Ni, Cr, and Mn reduce the resistance to temper embrittlement, showing increased Transition-Temperature Shift (TTS) and an increased fraction of intergranular fracture. Although the diffusivity of P is changed by the addition of alloying elements, it does not considerably affect the temper embrittlement. The Mn and Cr content in the matrix significantly reduce the C activity, with showing an inversely proportional relationship to TTS. The change of susceptibility to temper embrittlement caused by Cr and Mn addition could be explained by the variation of C activity. Unlike Cr and Mn, Ni has little effect on the temper embrittlement and C activity.

  2. Bond compressibility and bond Grüneisen parameters of CdTe

    NASA Astrophysics Data System (ADS)

    Fornasini, P.; Grisenti, R.; Irifune, T.; Shinmei, T.; Mathon, O.; Pascarelli, S.; Rosa, A. D.

    2018-06-01

    Extended x-ray absorption fine structure (EXAFS) at the Cd K edge and diffraction patterns have been measured on CdTe as a function of pressure from 100 kPa (1 bar) to 5 GPa using a cell with nano-polycrystalline diamond anvils and an x-ray focussing scanning spectrometer. Three phases—zincblende (ZB), mixed cinnabar-ZB and rocksalt (RS)—are well distinguished in different pressure intervals. The bond compressibility measured by EXAFS in the ZB phase is slightly smaller than the one measured by diffraction and decreases significantly faster when the pressure increases; the difference is attributed to the effect of relative vibrations perpendicular to the Cd–Te bond. The parallel mean square relative displacement (MSRD) decreases, the perpendicular MSRD increases when the pressure increases, leading to an increasing anisotropy of relative atomic vibrations. A constant-temperature bond Grüneisen parameter (GP) has been evaluated for the ZB phase and compared with the constant-pressure bond GP measured in a previous experiment; an attempt is made to connect the bond GPs measured by EXAFS and the more familiar thermodynamic GP and mode GPs; the comparisons suggest the inadequacy of the quasi-harmonic approximation to deal with the local vibrational properties sampled by EXAFS.

  3. [The apothecaries of the Saint-Honoré district of Paris in the 17th century. The apothecaries Antoine and Jacques Grégoire and Louis XIII’s first painter, Simon Vouet].

    PubMed

    Warolin, Christian

    2016-12-01

    This article presents the biographies of the apothecaries who lived in the Rue Saint-Honoré in Paris in the 17th century. Two major facts emerge from this study. The first concerns the formation of a family network involving the apothecaries and the royal artists. The apothecaries Antoine and Jacques Grégoire became allied with Simon Vouet, the first painter of Louis XIII . Links were also made between Antoine Grégoire and Jacques Sarazin, the King’s sculptor, and then with Michel Corneille, painter to the King. The famous painting by Simon Vouet hanging in the assembly hall of the Faculty of Pharmacy in Paris is probably the fruit of his collaboration with Jacques Grégoire, his brother-in-law and an erudite botanist. The other notable fact concerns the relations between Anne de Furnes, widow of Antoine Brulon, the rich apothecary to the King Antoine Brulon, and Molière, both in Paris and in the village of Auteuil. The other notable fact concerns the relations between Anne de Furnes, widow of Antoine Brulon, the rich apothecary to the King Antoine Brulon, and Molière, both in Paris and in the village of Auteuil.

  4. Physicochemical and toxicological profiling of ash from the 2010 and 2011 eruptions of Eyjafjallajökull and Grímsvötn volcanoes, Iceland using a rapid respiratory hazard assessment protocol.

    PubMed

    Horwell, C J; Baxter, P J; Hillman, S E; Calkins, J A; Damby, D E; Delmelle, P; Donaldson, K; Dunster, C; Fubini, B; Kelly, F J; Le Blond, J S; Livi, K J T; Murphy, F; Nattrass, C; Sweeney, S; Tetley, T D; Thordarson, T; Tomatis, M

    2013-11-01

    The six week eruption of Eyjafjallajökull volcano in 2010 produced heavy ash fall in a sparsely populated area of southern and south eastern Iceland and disrupted European commercial flights for at least 6 days. We adopted a protocol for the rapid analysis of volcanic ash particles, for the purpose of informing respiratory health risk assessments. Ash collected from deposits underwent a multi-laboratory physicochemical and toxicological investigation of their mineralogical parameters associated with bio-reactivity, and selected in vitro toxicology assays related to pulmonary inflammatory responses. Ash from the eruption of Grímsvötn, Iceland, in 2011 was also studied. The results were benchmarked against ash from Soufrière Hills volcano, Montserrat, which has been extensively studied since the onset of eruptive activity in 1995. For Eyjafjallajökull, the grain size distributions were variable: 2-13 vol% of the bulk samples were <4 µm, with the most explosive phases of the eruption generating abundant respirable particulate matter. In contrast, the Grímsvötn ash was almost uniformly coarse (<3.5 vol%<4 µm material). Surface area ranged from 0.3 to 7.7 m2 g(-1) for Eyjafjallajökull but was very low for Grímsvötn (<0.6 m2 g(-1)). There were few fibre-like particles (which were unrelated to asbestos) and the crystalline silica content was negligible in both eruptions, whereas Soufrière Hills ash was cristobalite-rich with a known potential to cause silicosis. All samples displayed a low ability to deplete lung antioxidant defences, showed little haemolysis and low acute cytotoxicity in human alveolar type-1 like epithelial cells (TT1). However, cell-free tests showed substantial hydroxyl radical generation in the presence of hydrogen peroxide for Grímsvötn samples, as expected for basaltic, Fe-rich ash. Cellular mediators MCP-1, IL-6, and IL-8 showed chronic pro-inflammatory responses in Eyjafjallajökull, Grímsvötn and Soufrière Hills samples

  5. Gabapentin Extended-Release - Depomed: Gabapentin ER, Gabapentin Gastric Retention, Gabapentin GR.

    PubMed

    2007-01-01

    Depomed is developing an extended-release (ER) oral formulation of gabapentin, a GABA receptor agonist commonly used for the treatment of epilepsy and seizures, neuropathic pain and hot flushes. Gabapentin ER is based on the company's proprietary AcuForm drug delivery technology, which is part of the Gastric Retention (GR) family of technologies; this offers improved drug absorption and bioavailability compared with the existing immediate-release formulation of gabapentin (Neurontin), making gabapentin ER suitable for twice-daily dosing. The product is in clinical development for the treatment of postherpetic neuralgia and diabetic neuropathies in the US. Additionally, Depomed has commenced a phase II trial of gabapentin ER in postmenopausal patients with hot flushes. Depomed's AcuForm platform is based on polymer technology that provides targeted drug delivery for a variety of compounds. Following ingestion, AcuForm tablets swell and are retained for 6-8 hours in the stomach, enabling controlled and prolonged release of gabapentin to the upper intestinal tract; this extends the time of drug delivery to the small intestine for complete and safe elimination via the lower intestinal track. Gabapentin ER is available for licensing. Depomed acquired exclusive development and commercialisation rights to gabapentin ER in September 2003 via its subsidiary, Depomed Development Ltd (DDL). Depomed is not required to pay upfront license fees, but will make royalty and milestone payments to DDL upon successful commercialisation of gabapentin ER. Gabapentin ER was originally developed by DDL, a joint venture between Depomed and Elan established in January 2000 to design products using the GR family of technologies. However, in efforts to restructure joint venture relationships, Elan withdrew from operational involvement of DDL in September 2003, and Depomed has gained full ownership of DDL. Depomed sublicensed exclusive rights to a US patent (held by the University of Rochester

  6. A novel sandwich-type electrochemical aptasensor based on GR-3D Au and aptamer-AuNPs-HRP for sensitive detection of oxytetracycline.

    PubMed

    Liu, Su; Wang, Yu; Xu, Wei; Leng, Xueqi; Wang, Hongzhi; Guo, Yuna; Huang, Jiadong

    2017-02-15

    In this paper, a novel sandwich-type electrochemical aptasensor has been fabricated and applied for sensitive and selective detection of antibiotic oxytetracycline (OTC). This sensor was based on graphene-three dimensional nanostructure gold nanocomposite (GR-3D Au) and aptamer-AuNPs-horseradish peroxidase (aptamer-AuNPs-HRP) nanoprobes as signal amplification. Firstly, GR-3D Au film was modified on glassy carbon electrode only by one-step electrochemical coreduction with graphite oxide (GO) and HAuCl 4 at cathodic potentials, which enhanced the electron transfer and loading capacity of biomolecules. Then the aptamer and HRP modified Au nanoparticles provide high affinity and ultrasensitive electrochemical probe with excellent specificity for OTC. Under the optimized conditions, the peak current was linearly proportional to the concentration of OTC in the range of 5×10 -10 -2×10 -3 gL -1 , with a detection limit of 4.98×10 -10 gL -1 . Additionally, this aptasensor had the advantages in high sensitivity, superb specificity and showed good recovery in synthetic samples. Hence, the developed sandwich-type electrochemical aptasensor might provide a useful and practical tool for OTC determination and related food safety analysis and clinical diagnosis. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Dry sliding wear behavior of Al 2219/SiCp-Gr hybrid metal matrix composites

    NASA Astrophysics Data System (ADS)

    Basavarajappa, S.; Chandramohan, G.; Mukund, K.; Ashwin, M.; Prabu, M.

    2006-12-01

    The dry sliding wear behavior of Al 2219 alloy and Al 2219/SiCp/Gr hybrid composites are investigated under similar conditions. The composites are fabricated using the liquid metallurgy technique. The dry sliding wear test is carried out for sliding speeds up to 6 m/s and for normal loads up to 60 N using a pin on disc apparatus. It is found that the addition of SiCp and graphite reinforcements increases the wear resistance of the composites. The wear rate decreases with the increase in SiCp reinforcement content. As speed increases, the wear rate decreases initially and then increases. The wear rate increases with the increase in load. Scanning electron microscopy micrographs of the worn surface are used to predict the nature of the wear mechanism. Abrasion is the principle wear mechanism for the composites at low sliding speeds and loads. At higher loads, the wear mechanism changes to delamination.

  8. Transcriptome analysis of Phelipanche aegyptiaca seed germination mechanisms stimulated by fluridone, TIS108, and GR24

    PubMed Central

    Bao, Ya Zhou; Yao, Zhao Qun; Cao, Xiao Lei; Peng, Jin Feng; Xu, Ying; Chen, Mei Xiu

    2017-01-01

    P. aegyptiaca is one of the most destructive root parasitic plants worldwide, causing serious damage to many crop species. Under natural conditions P. aegyptiaca seeds must be conditioned and then stimulated by host root exudates before germinating. However, preliminary experiments indicated that TIS108 (a triazole-type inhibitor of strigolactone) and fluridone (FL, an inhibitor of carotenoid-biosynthesis) both stimulated the germination of P. aegyptiaca seeds without a water preconditioning step (i.e. unconditioned seeds). The objective of this study was to use deep RNA sequencing to learn more about the mechanisms by which TIS108 and FL stimulate the germination of unconditioned P. aegyptiaca seeds. Deep RNA sequencing was performed to compare the mechanisms of germination in the following treatments: (i) unconditioned P. aegyptiaca seeds with no other treatment, (ii) unconditioned seeds treated with 100 mg/L TIS108, (iii) unconditioned seeds treated with 100 mg/L FL + 100 mg/L GA3, (iv) conditioned seeds treated with sterile water, and (v) conditioned seeds treated with 0.03 mg/L GR24. The de novo assembled transcriptome was used to analyze transcriptional dynamics during seed germination. The key gene categories involved in germination were also identified. The results showed that only 119 differentially expressed genes were identified in the conditioned treatment vs TIS108 treatment. This indicated that the vast majority of conditions for germination were met during the conditioning stage. Abscisic acid (ABA) and gibberellic acid (GA) played important roles during P. aegyptiaca germination. The common pathway of TIS108, FL+GA3, and GR24 in stimulating P. aegyptiaca germination was the simultaneous reduction in ABA concentrations and increase GA concentrations. These results could potentially aid the identification of more compounds that are capable of stimulating P. aegyptiaca germination. Some potential target sites of TIS108 were also identified in our

  9. Transcriptome analysis of Phelipanche aegyptiaca seed germination mechanisms stimulated by fluridone, TIS108, and GR24.

    PubMed

    Bao, Ya Zhou; Yao, Zhao Qun; Cao, Xiao Lei; Peng, Jin Feng; Xu, Ying; Chen, Mei Xiu; Zhao, Si Feng

    2017-01-01

    P. aegyptiaca is one of the most destructive root parasitic plants worldwide, causing serious damage to many crop species. Under natural conditions P. aegyptiaca seeds must be conditioned and then stimulated by host root exudates before germinating. However, preliminary experiments indicated that TIS108 (a triazole-type inhibitor of strigolactone) and fluridone (FL, an inhibitor of carotenoid-biosynthesis) both stimulated the germination of P. aegyptiaca seeds without a water preconditioning step (i.e. unconditioned seeds). The objective of this study was to use deep RNA sequencing to learn more about the mechanisms by which TIS108 and FL stimulate the germination of unconditioned P. aegyptiaca seeds. Deep RNA sequencing was performed to compare the mechanisms of germination in the following treatments: (i) unconditioned P. aegyptiaca seeds with no other treatment, (ii) unconditioned seeds treated with 100 mg/L TIS108, (iii) unconditioned seeds treated with 100 mg/L FL + 100 mg/L GA3, (iv) conditioned seeds treated with sterile water, and (v) conditioned seeds treated with 0.03 mg/L GR24. The de novo assembled transcriptome was used to analyze transcriptional dynamics during seed germination. The key gene categories involved in germination were also identified. The results showed that only 119 differentially expressed genes were identified in the conditioned treatment vs TIS108 treatment. This indicated that the vast majority of conditions for germination were met during the conditioning stage. Abscisic acid (ABA) and gibberellic acid (GA) played important roles during P. aegyptiaca germination. The common pathway of TIS108, FL+GA3, and GR24 in stimulating P. aegyptiaca germination was the simultaneous reduction in ABA concentrations and increase GA concentrations. These results could potentially aid the identification of more compounds that are capable of stimulating P. aegyptiaca germination. Some potential target sites of TIS108 were also identified in our

  10. Reflection seismic characterization of the Grängesberg iron deposit and its mining-induced structures, central Sweden

    NASA Astrophysics Data System (ADS)

    Place, Joachim; Malehmir, Alireza; Högdahl, Karin; Juhlin, Christopher; Persson Nilsson, Katarina

    2014-05-01

    Reflection seismic investigation has been conducted on the Grängesberg apatite iron deposit where over 150 Mt of iron ore were produced until the mine closed in 1989. The mine infrastructure with shafts and tunnels extend down to ca. 650 m below the surface. Both natural and mine induced fracture and fault systems are today water-filled (some of them extending to the surface). The disputed ore genesis of the apatite-iron ores and its exploration potential due to large remaining quantities once again attracts both scientific and commercial interests. A good understanding of the geometry of mineral deposits and their hostrock structures at depth is essential for optimizing their exploration and exploitation. In addition, deep understanding of the fracture system is vital if mining activity is resumed as these may impact the terrain stability and seismicity, which may put at risk new populated and industrial areas. To address some of these challenging issues related to the past mining and also to obtain information about the depth continuation of the existing deposit, two E-W oriented reflection lines with a total length of 3.5 km were acquired in May 2013 by Uppsala University. A weight drop mounted on an hydraulic bobcat truck (traditionally used for concrete breaking in demolition sector) was used to generate seismic signal. In order to increase the signal-to-noise ratio, several impacts were generated at each shot point and stacked together. The seismic lines intersect at high angle the Grängesberg ore body and open pit, as well as several mining-induced faults. A combination of cabled and wireless receivers placed at every 10 m was used for the data recording. Use of wireless receivers was necessary as deploying cabled sensors was not possible due to city infrastructures, roads and houses. A careful analysis of the data suggested that several field-related issues such as (1) the crooked geometry of the lines (due to the available path and road network), (2

  11. Magma plumbing in the Grímsvötn volcanic system, Iceland: an overview

    NASA Astrophysics Data System (ADS)

    Thordarson, T.

    2016-12-01

    The basaltic Grímsvötn volcanic system (GVS) consists of Grímsvötn central volcano (GCV) and an immature fissure swarm extending 70 km to the southwest from GCV. The GCV has the highest eruption frequency of all central volcanos in Iceland, or 7 events per 100 years. In contrast, the GVS fissure swarm has only featured two events in postglacial times, the 1783-4 Laki and the prehistoric Lambavatnsgígar fissure eruptions. These two events account for 25% of the total Holocene magma output from the GVS and 80% of the output in historic time (i.e. last 1100 years). Although GVS magma plumbing has been a topic of research for four decades, its general structure, extent and geometry is still deliberated. Is mantle-derived magma delivered straight up beneath the GCV to an upper crustal magma chamber and then vertically to eruptions at the GCV and laterally to eruption on the GVS fissure swarm? Or does the system feature two levels of crustal storage, one in the upper crust beneath GCV and another at mid-crustal depth? Or is the structure of the GVS plumbing more complex? The data that we have so far and is pertinent to GVS magma plumbing is summarised below: Geophysical measurements imply that shallowest magma storage beneath GCV is at 3-4 km. The Zr and Nb concentrations in the tephra from the 1998 and 2004 GCV plus Laki eruptions show that the parent magmas for each was produced by different degrees of partial melting of a similar mantle source. It also demonstrates transport to the surface via separate pathways and that neither magma can be derived by fractional crystallization from a Laki-like magma. Detailed petrological studies on the Laki tephra and lava indicate polybaric magma evolution within the mid-crust (at 6 to 15 km depth), with further evolution at shallower depths induced either by disequilibrium crystal growth during ascent of magma from the mid-crust storage or a brief residence at 3-6 km depths. The Laki magma contains significant abundances of

  12. Role of CD11b+Gr-1+ myeloid cells in AGEs-induced myocardial injury in a mice model of acute myocardial infarction.

    PubMed

    Yao, Tongqing; Lu, Wenbin; Zhu, Jian; Jin, Xian; Ma, Genshan; Wang, Yuepeng; Meng, Shu; Zhang, Yachen; Li, Yigang; Shen, Chengxing

    2015-01-01

    Polymorph neutrophils are the predominant inflammatory cells and play a crucial role on the pathogenesis of myocardial injury at the early stage of acute myocardial infarction (AMI). However, the precursors and the differentiation of neutrophils are not fully understood. Here we explored the role of CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs) on myocardial injury in the absence and presence of advanced glycation end-products (AGEs) in a mice model of AMI. Male C57BL/6J mice were selected. Fluorescent actived cell sortor (FACS) data demonstrated significantly increased CD11b+Gr-1+ MDSCs both in peripheral blood circulation and in the ischemic myocardium at 24 hours post AMI. Quantitative-real-time PCR results also revealed significantly upregulated CD11b and Ly6G mRNA expression in the ischemic myocardium. AGEs treatment further aggravated these changes in AMI mice but not in sham mice. Moreover, AGEs treatment also significantly increased infarction size and enhanced cardiomyocyte apoptosis. The mRNA expression of pro-inflammatory cytokine IL-6 and iNOS2 was also significantly increased in AMI + AGEs group compared to AMI group. These data suggest enhanced infiltration of MDSCs by AGEs contributes to aggravated myocardial injury in AMI mice, which might be one of the mechanisms responsible for severer myocardial injury in AMI patients complicating diabetes.

  13. Icaritin opposes the development of social aversion after defeat stress via increases of GR mRNA and BDNF mRNA in mice.

    PubMed

    Wu, Xiao; Wu, Jinfeng; Xia, Shijin; Li, Bei; Dong, Jingcheng

    2013-11-01

    Icariin is a major constituent of flavonoids isolated from Herba Epimedii. Several previous studies have demonstrated the antidepressant-like effects of icariin. After oral administration of icariin, 19 metabolites of icariin were detected in rat plasma. Icaritin is one such of metabolite of icariin. In this study, a chronic social defeat protocol is used as a mouse model for depression, and the effects of icaritin administration on social avoidance are investigated. The data indicates that icaritin (5mg/kg and 10mg/kg) oral administration opposes the development of social aversion after defeat stress. In vitro corticosterone sensitivity assay demonstrated that icaritin partially restored social defeat-induced impairment of glucocorticoid sensitivity. The expressions of GR mRNA and BDNFmRNA in the hippocampus were increased after icaritin treatment. Meanwhile, the social defeat-induced increases in CRH mRNA in hypothalamus were restored by icaritin administration. Our data also suggests that icaritin administration remarkably attenuated the increases in serum IL-6 and TNF-α level that occur following exposure to social defeat. In conclusion, icaritin is a novel antidepressant. It partially restored social defeat-induced impairment of glucocorticoid sensitivity, HPA axis hyperactivity. These effects are at least partially attributed to normalization of the GR function and increases in BDNF expression. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. High pressure behavior of complex phosphate K2Ce[PO4]2: Grüneisen parameter and anharmonicity properties

    NASA Astrophysics Data System (ADS)

    Mishra, Karuna Kara; Bevara, Samatha; Ravindran, T. R.; Patwe, S. J.; Gupta, Mayanak K.; Mittal, Ranjan; Krishnan, R. Venkata; Achary, S. N.; Tyagi, A. K.

    2018-02-01

    Herein we reported structural stability, vibrational and thermal properties of K2Ce[PO4]2, a relatively underexplored complex phosphate of tetravalent Ce4+ from in situ high-pressure Raman spectroscopic investigations up to 28 GPa using a diamond anvil cell. The studies identified the soft phonons that lead to a reversible phase transformation above 8 GPa, and a phase coexistence of ambient (PI) and high pressure (PII) phases in a wider pressure region 6-11 GPa. From a visual representation of the computed eigen vector displacements, the Ag soft mode at 82 cm-1 is assigned as a lattice mode of K+ cation. Pressure-induced positional disorder is apparent from the substantial broadening of internal modes and the disappearance of low frequency lattice and external modes in phase PII above 18 GPa. Isothermal mode Grüneisen parameters γi of the various phonon modes are calculated and compared for several modes. Using these values, thermal properties such as average Grüneisen parameter, and thermal expansion coefficient are estimated as 0.47, and 2.5 × 10-6 K-1, respectively. The specific heat value was estimated from all optical modes obtained from DFT calculations as 314 J-mol-1 K-1. Our earlier reported temperature dependence of phonon frequencies is used to decouple the "true anharmonic" (explicit contribution at constant volume) and "quasi harmonic" (implicit contribution brought out by volume change) contributions from the total anharmonicity. In addition to the 81 cm-1 Ag lattice mode, several other lattice and external modes of PO43- ions are found to be strongly anharmonic.

  15. Efficient computation of the Grünwald-Letnikov fractional diffusion derivative using adaptive time step memory

    NASA Astrophysics Data System (ADS)

    MacDonald, Christopher L.; Bhattacharya, Nirupama; Sprouse, Brian P.; Silva, Gabriel A.

    2015-09-01

    Computing numerical solutions to fractional differential equations can be computationally intensive due to the effect of non-local derivatives in which all previous time points contribute to the current iteration. In general, numerical approaches that depend on truncating part of the system history while efficient, can suffer from high degrees of error and inaccuracy. Here we present an adaptive time step memory method for smooth functions applied to the Grünwald-Letnikov fractional diffusion derivative. This method is computationally efficient and results in smaller errors during numerical simulations. Sampled points along the system's history at progressively longer intervals are assumed to reflect the values of neighboring time points. By including progressively fewer points backward in time, a temporally 'weighted' history is computed that includes contributions from the entire past of the system, maintaining accuracy, but with fewer points actually calculated, greatly improving computational efficiency.

  16. Probiotics [LGG-BB12 or RC14-GR1] versus placebo as prophylaxis for urinary tract infection in persons with spinal cord injury [ProSCIUTTU]: a study protocol for a randomised controlled trial.

    PubMed

    Lee, Bonsan Bonne; Toh, Swee-Ling; Ryan, Suzanne; Simpson, Judy M; Clezy, Kate; Bossa, Laetitia; Rice, Scott A; Marial, Obaydullah; Weber, Gerard; Kaur, Jasbeer; Boswell-Ruys, Claire; Goodall, Stephen; Middleton, James; Tudehope, Mark; Kotsiou, George

    2016-04-16

    Urinary tract infections [UTIs] are very common in people with Spinal Cord Injury [SCI]. UTIs are increasingly difficult and expensive to treat as the organisms that cause them become more antibiotic resistant. Among the SCI population, there is a high rate of multi-resistant organism [MRO] colonisation. Non-antibiotic prevention strategies are needed to prevent UTI without increasing resistance. Probiotics have been reported to be beneficial in preventing UTIs in post-menopausal women in several in vivo and in vitro studies. The main aim of this study is to determine whether probiotic therapy with combinations of Lactobacillus reuteri RC-14 + Lactobacillus rhamnosus GR-1 [RC14-GR1] and/or Lactobacillus rhamnosus GG + Bifidobacterium BB-12 [LGG-BB12] are effective in preventing UTI in people with SCI compared to placebo. This is a multi-site randomised double-blind double-dummy placebo-controlled factorial design study conducted in New South Wales, Australia. All participants have a neurogenic bladder as a result of spinal injury. Recruitment started in April 2011. Participants are randomised to one of four arms, designed for factorial analysis of LGG-BB12 and/or RC14-GR1 v Placebo. This involves 24 weeks of daily oral treatment with RC14-GR1 + LGG-BB12, RC14-GR1 + placebo, LGG-BB12 + placebo or two placebo capsules. Randomisation is stratified by bladder management type and inpatient status. Participants are assessed at baseline, three months and six months for Short Form Health Survey [SF-36], microbiological swabs of rectum, nose and groin; urine culture and urinary catheters for subjects with indwelling catheters. A bowel questionnaire is administered at baseline and three months to assess effect of probiotics on bowel function. The primary outcome is time from randomisation to occurrence of symptomatic UTI. The secondary outcomes are change of MRO status and bowel function, quality of life and cost-effectiveness of probiotics in persons

  17. Triboelectric charging of volcanic ash from the 2011 Grímsvötn eruption.

    PubMed

    Houghton, Isobel M P; Aplin, Karen L; Nicoll, Keri A

    2013-09-13

    The plume from the 2011 eruption of Grímsvötn was highly electrically charged, as shown by the considerable lightning activity measured by the United Kingdom Met Office's low-frequency lightning detection network. Previous measurements of volcanic plumes have shown that ash particles are electrically charged up to hundreds of kilometers away from the vent, which indicates that the ash continues to charge in the plume [R. G. Harrison, K. A. Nicoll, Z. Ulanowski, and T. A. Mather, Environ. Res. Lett. 5, 024004 (2010); H. Hatakeyama J. Meteorol. Soc. Jpn. 27, 372 (1949)]. In this Letter, we study triboelectric charging of different size fractions of a sample of volcanic ash experimentally. Consistently with previous work, we find that the particle size distribution is a determining factor in the charging. Specifically, our laboratory experiments demonstrate that the normalized span of the particle size distribution plays an important role in the magnitude of charging generated. The influence of the normalized span on plume charging suggests that all ash plumes are likely to be charged, with implications for remote sensing and plume lifetime through scavenging effects.

  18. Triboelectric Charging of Volcanic Ash from the 2011 Grímsvötn Eruption

    NASA Astrophysics Data System (ADS)

    Houghton, Isobel M. P.; Aplin, Karen L.; Nicoll, Keri A.

    2013-09-01

    The plume from the 2011 eruption of Grímsvötn was highly electrically charged, as shown by the considerable lightning activity measured by the United Kingdom Met Office’s low-frequency lightning detection network. Previous measurements of volcanic plumes have shown that ash particles are electrically charged up to hundreds of kilometers away from the vent, which indicates that the ash continues to charge in the plume [R. G. Harrison, K. A. Nicoll, Z. Ulanowski, and T. A. Mather, Environ. Res. Lett. 5, 024004 (2010)1748-932610.1088/1748-9326/5/2/024004; H. Hatakeyama J. Meteorol. Soc. Jpn. 27, 372 (1949)JMSJAU0026-1165]. In this Letter, we study triboelectric charging of different size fractions of a sample of volcanic ash experimentally. Consistently with previous work, we find that the particle size distribution is a determining factor in the charging. Specifically, our laboratory experiments demonstrate that the normalized span of the particle size distribution plays an important role in the magnitude of charging generated. The influence of the normalized span on plume charging suggests that all ash plumes are likely to be charged, with implications for remote sensing and plume lifetime through scavenging effects.

  19. Uptake of algal carbon and the synthesis of an "essential" fatty acid by Uvigerina ex. gr. semiornata (Foraminifera) within the Pakistan margin oxygen minimum zone: evidence from fatty acid biomarker and 13C tracer experiments

    NASA Astrophysics Data System (ADS)

    Larkin, K. E.; Gooday, A. J.; Woulds, C.; Jeffreys, R.; Schwartz, M.; Cowie, G.; Whitcraft, C.; Levin, L.; Dick, J. R.; Pond, D. W.

    2014-01-01

    Foraminifera are an important component of benthic communities in oxygen depleted settings, where they potentially play a~significant role in the processing of organic matter. We tracked the uptake of a 13C-labeled algal food source into individual fatty acids in the benthic foraminiferal species, Uvigerina ex. gr. semiornata, from the Arabian Sea oxygen minimum zone (OMZ). The tracer experiments were conducted on the Pakistan Margin during the late/post monsoon period (August-October 2003). A monoculture of the diatom Thalassiosira weisflogii was 13C-labeled and used to simulate a pulse of phytoplankton in two complementary experiments. A lander system was used for in situ incubations at 140 m and for 2.5 days duration, whilst a laboratory incubation used an oxystat system to maintain ambient dissolved oxygen concentrations. These shipboard experiments were terminated after 5 days. Uptake of diatoms was rapid, with high incorporation of diatom fatty acids into foraminifera after ~2 days in both experiments. Ingestion of the diatom food source was indicated by the increase over time in the quantity of diatom biomarker fatty acids in the foraminifera and by the high percentage of 13C in many of the fatty acids present at the endpoint of both in~situ and laboratory-based experiments. These results indicate that U. ex. gr. semiornata rapidly ingested the diatom food source and that this foraminifera will play an important role in the short-term cycling of organic matter within this OMZ environment. The experiments also suggested that U. ex. gr. semiornata consumed non-labeled bacterial food items, particularly bacteria, and synthesised the polyunsaturated fatty acid 20:4(n-6) de novo. 20:4(n-6) is often abundant in benthic fauna yet its origins and function have remained unclear. This study demonstrates that U. ex. gr. semiornata is capable of de novo synthesis of this "essential fatty acid" and is potentially a major source of this dietary nutrient in benthic food

  20. IL-33 expands suppressive CD11b+ Gr-1int and regulatory T cells (Treg), including ST2L+ Foxp3+ cells, and mediates Treg-dependent promotion of cardiac allograft survival

    PubMed Central

    Turnquist, Hēth R.; Zhao, Zhenlin; Rosborough, Brian R.; Liu, Quan; Castellaneta, Antonino; Isse, Kumiko; Wang, Zhiliang; Lang, Megan; Stolz, Donna Beer; Zheng, Xin Xiao; Demetris, A. Jake; Liew, Foo Y.; Wood, Kathryn J.; Thomson, Angus W.

    2011-01-01

    IL-33 administration is associated with facilitation of Th type-2 (Th2) responses and cardioprotective properties in rodent models. However, in heart transplantation, the mechanism by which IL-33, signaling through ST2L, the membrane-bound form of ST2, promotes transplant survival is unclear. We report that IL-33 administration, while facilitating Th2 responses, also increases immunoregulatory myeloid cells and CD4+ Foxp3+ regulatory T cells (Treg) in mice. IL-33 expands functional myeloid-derived suppressor cells (MDSC), -CD11b+ cells that exhibit intermediate (int) levels of Gr-1 and potent T cell suppressive function. Furthermore, IL-33 administration causes a St2-dependent expansion of suppressive CD4+ Foxp3+ Treg, including a ST2L+ population. IL-33 monotherapy following fully allogeneic mouse heart transplantation resulted in significant graft prolongation, associated with increased Th2-type responses and decreased systemic CD8+ IFN-γ+ cells. Also, despite reducing overall CD3+ cell infiltration of the graft, IL-33 administration markedly increased intragraft Foxp3+ cells. Whereas control graft recipients displayed increases in systemic CD11b+ Gr-1hi cells, IL-33-treated recipients exhibited increased CD11b+ Gr-1int cells. Enhanced ST2 expression was observed in the myocardium and endothelium of rejecting allografts, however the therapeutic effect of IL-33 required recipient St2 expression and was dependent on Treg. These findings reveal a new immunoregulatory property of IL-33. Specifically, in addition to supporting Th2 responses, IL-33 facilitates regulatory cells, particularly functional CD4+ Foxp3+ Treg that underlie IL-33-mediated cardiac allograft survival. PMID:21949025

  1. Continuous state-space representation of a bucket-type rainfall-runoff model: a case study with the GR4 model using state-space GR4 (version 1.0)

    NASA Astrophysics Data System (ADS)

    Santos, Léonard; Thirel, Guillaume; Perrin, Charles

    2018-04-01

    In many conceptual rainfall-runoff models, the water balance differential equations are not explicitly formulated. These differential equations are solved sequentially by splitting the equations into terms that can be solved analytically with a technique called operator splitting. As a result, only the solutions of the split equations are used to present the different models. This article provides a methodology to make the governing water balance equations of a bucket-type rainfall-runoff model explicit and to solve them continuously. This is done by setting up a comprehensive state-space representation of the model. By representing it in this way, the operator splitting, which makes the structural analysis of the model more complex, could be removed. In this state-space representation, the lag functions (unit hydrographs), which are frequent in rainfall-runoff models and make the resolution of the representation difficult, are first replaced by a so-called Nash cascade and then solved with a robust numerical integration technique. To illustrate this methodology, the GR4J model is taken as an example. The substitution of the unit hydrographs with a Nash cascade, even if it modifies the model behaviour when solved using operator splitting, does not modify it when the state-space representation is solved using an implicit integration technique. Indeed, the flow time series simulated by the new representation of the model are very similar to those simulated by the classic model. The use of a robust numerical technique that approximates a continuous-time model also improves the lag parameter consistency across time steps and provides a more time-consistent model with time-independent parameters.

  2. Purification and Characterization of (Per)Chlorate Reductase from the Chlorate-Respiring Strain GR-1

    PubMed Central

    Kengen, Servé W. M.; Rikken, Geoffrey B.; Hagen, Wilfred R.; van Ginkel, Cees G.; Stams, Alfons J. M.

    1999-01-01

    Strain GR-1 is one of several recently isolated bacterial species that are able to respire by using chlorate or perchlorate as the terminal electron acceptor. The organism performs a complete reduction of chlorate or perchlorate to chloride and oxygen, with the intermediate formation of chlorite. This study describes the purification and characterization of the key enzyme of the reductive pathway, the chlorate and perchlorate reductase. A single enzyme was found to catalyze both the chlorate- and perchlorate-reducing activity. The oxygen-sensitive enzyme was located in the periplasm and had an apparent molecular mass of 420 kDa, with subunits of 95 and 40 kDa in an α3β3 composition. Metal analysis showed the presence of 11 mol of iron, 1 mol of molybdenum, and 1 mol of selenium per mol of heterodimer. In accordance, quantitative electron paramagnetic resonance spectroscopy showed the presence of one [3Fe-4S] cluster and two [4Fe-4S] clusters. Furthermore, two different signals were ascribed to Mo(V). The Kmvalues for perchlorate and chlorate were 27 and <5 μM, respectively. Besides perchlorate and chlorate, nitrate, iodate, and bromate were also reduced at considerable rates. The resemblance of the enzyme to nitrate reductases, formate dehydrogenases, and selenate reductase is discussed. PMID:10542172

  3. Water/magma mass fractions in phreatomagmatic eruption plumes - constraints from the Grímsvötn 2011 eruption

    NASA Astrophysics Data System (ADS)

    Gudmundsson, M. T.; Pálsson, F.; Thordarson, T.; Hoskuldsson, A.; Larsen, G.; Hognadottir, T.; Oddsson, B.; Oladottir, B. A.; Gudnason, J.

    2014-12-01

    Explosive interaction of magma and water leads to vaporization and introduces external water vapor to volcanic plumes. Theoretical considerations on the effect of external water magma ratio on volcanic plumes indicate that plume buoyancy should be enhanced by external water fractions up to at least 30%, while fractions reaching 40% should lead to plume collapse. The basaltic VEI 4 eruption of Grímsvötn in May 2011 produced a 15-20 km high eruption plume and over 100 km wide umbrella cloud. External water interacted with the magma and entered the plume from the melting out of a 100-150 m deep ice cauldron that had acquired a volume of 0.1 km3 at the end of the eruption. About 0.7 km3 of tephra was produced in the eruption whereof about half was erupted in phreatomagmatic phases and the other half in magmatic phases. During the dry, magmatic phases melting was apparently not fast enough to supply sufficient external water to the vents to control the style of activity. The only source of external water was the melting out of the ice cauldron since no changes took place in the level of the larger, subglacial lake in the center of the Grímsvötn caldera, and no meltwater was drained from the caldera. The eruption site therefore had little or no hydrological connection with the adjacent subglacial lake. Water remaining at the eruption site at the end of the eruption was miniscule compared to the amount of ice melted. Hence, most of the meltwater was vaporized and carried away as a part of the eruption plume. About one third of the thermal energy of the magma erupted was used to melt, heat up and vaporize water. A large part of this water was released from the plume through condensation and re-freezing, manifested in hail-rich tephra deposited out to several kilometers from the vent. The data indicate that the external water/tephra mass ratio in the phreatomagmatic phases was 20-25%, but similar to 5% for the predominantly magmatic phases.

  4. A study of planar Richtmyer-Meshkov instability in fluids with Mie-Grüneisen equations of state

    NASA Astrophysics Data System (ADS)

    Ward, G. M.; Pullin, D. I.

    2011-07-01

    We present a numerical comparison study of planar Richtmyer-Meshkov instability with the intention of exposing the role of the equation of state. Results for Richtmyer-Meshkov instability in fluids with Mie-Grüneisen equations of state derived from a linear shock-particle speed Hugoniot relationship (Jeanloz, J. Geophys. Res. 94, 5873, 1989; McQueen et al., High Velocity Impact Phenomena (1970), pp. 294-417; Menikoff and Plohr, Rev. Mod. Phys. 61(1), 75 1989) are compared to those from perfect gases under nondimensionally matched initial conditions at room temperature and pressure. The study was performed using Caltech's Adaptive Mesh Refinement, Object-oriented C++ (AMROC) (Deiterding, Adaptive Mesh Refinement: Theory and Applications (2005), Vol. 41, pp. 361-372; Deiterding, "Parallel adaptive simulation of multi-dimensional detonation structures," Ph.D. thesis (Brandenburgische Technische Universität Cottbus, September 2003)) framework with a low-dissipation, hybrid, center-difference, limiter patch solver (Ward and Pullin, J. Comput. Phys. 229, 2999 (2010)). Results for single and triple mode planar Richtmyer-Meshkov instability when a reflected shock wave occurs are first examined for mid-ocean ridge basalt (MORB) and molybdenum modeled by Mie-Grüneisen equations of state. The single mode case is examined for incident shock Mach numbers of 1.5 and 2.5. The planar triple mode case is studied using a single incident Mach number of 2.5 with initial corrugation wavenumbers related by k1=k2+k3. Comparison is then drawn to Richtmyer-Meshkov instability in perfect gases with matched nondimensional pressure jump across the incident shock, post-shock Atwood ratio, post-shock amplitude-to-wavelength ratio, and time nondimensionalized by Richtmyer's linear growth time constant prediction. Differences in start-up time and growth rate oscillations are observed across equations of state. Growth rate oscillation frequency is seen to correlate directly to the oscillation

  5. Uptake of algal carbon and the likely synthesis of an "essential" fatty acid by Uvigerina ex. gr. semiornata (Foraminifera) within the Pakistan margin oxygen minimum zone: evidence from fatty acid biomarker and 13C tracer experiments

    NASA Astrophysics Data System (ADS)

    Larkin, K. E.; Gooday, A. J.; Woulds, C.; Jeffreys, R. M.; Schwartz, M.; Cowie, G.; Whitcraft, C.; Levin, L.; Dick, J. R.; Pond, D. W.

    2014-07-01

    Foraminifera are an important component of benthic communities in oxygen-depleted settings, where they potentially play a significant role in the processing of organic matter. We tracked the uptake of a 13C-labelled algal food source into individual fatty acids in the benthic foraminiferal species Uvigerina ex. gr. semiornata from the Arabian Sea oxygen minimum zone (OMZ). The tracer experiments were conducted on the Pakistan margin during the late/post monsoon period (August-October 2003). A monoculture of the diatom Thalassiosira weisflogii was 13C-labelled and used to simulate a pulse of phytoplankton in two complementary experiments. A lander system was used for in situ incubations at 140 m water depth and for 2.5 days in duration. Shipboard laboratory incubations of cores collected at 140 m incorporated an oxystat system to maintain ambient dissolved oxygen concentrations and were terminated after 5 days. Uptake of diatoms was rapid, with a high incorporation of diatom fatty acids into foraminifera after ~ 2 days in both experiments. Ingestion of the diatom food source was indicated by the increase over time in the quantity of diatom biomarker fatty acids in the foraminifera and by the high percentage of 13C in many of the fatty acids present at the endpoint of both in situ and laboratory-based experiments. These results indicate that gr. semiornata rapidly ingested the diatom food source and that these foraminifera will play an important role in the short-term cycling of organic matter within this OMZ environment. The presence of 18:1(n-7) in the experimental foraminifera suggested that U. ex. gr. semiornata also consumed non-labelled bacterial food items. In addition, levels of 20:4(n-6), a PUFA only present in low amounts in the diatom food, increased dramatically in the foraminifera during both the in situ and shipboard experiments, possibly because it was synthesised de novo. This "essential fatty acid" is often abundant in benthic fauna, yet

  6. Impact of Chronic Stress on the Spatial Learning and GR-PKAc-NF-κB Signaling in the Hippocampus and Cortex in Rats Following Cholinergic Depletion.

    PubMed

    Lee, Sun-Young; Cho, Woo-Hyun; Lee, Yo-Seob; Han, Jung-Soo

    2018-05-01

    Studies have shown that the removal of the cholinergic innervation to the hippocampus induces dysfunction of the hypothalamic-pituitary-adrenocortical axis and decreases the number of glucocorticoid receptors (GRs). Subsequent studies have revealed that the loss of cholinergic input to the hippocampus reduces the expression of GRs and activates nuclear factor-kappa B (NF-κB) signaling through interactions with the cytoplasmic catalytic subunit of protein kinase A (PKAc). We examined the effects of chronic stress on cognitive status and GR-PKAc-NF-κB signaling in rats with a loss of cholinergic input to the hippocampus and cortex. Male Sprague-Dawley rats received 192 IgG-saporin injections to selectively eliminate cholinergic neurons in their basal forebrain. Two weeks later, rats were subjected to 1 h of restraint stress per day for 14 days. Rats subjected to both chronic stress and cholinergic depletion showed more severe memory impairments compared to those that received either treatment alone. The reduction in nuclear GR levels induced by cholinergic depletion was unaffected by chronic stress. The activation of NF-κB signaling in the hippocampus and the cerebral cortex induced by cholinergic depletion was augmented by chronic stress, resulting in the increased expression of pro-inflammatory markers, such as inducible nitric oxide synthase and cyclooxygenase-2. The activation of NF-κB induced by cholinergic depletion appears to be aggravated by chronic stress, and this might explain the increased susceptibility of patients with Alzheimer's disease to stress since activation of NF-κB is associated with stress.

  7. The acute and post-discontinuation effects of a glucocorticoid receptor (GR) antagonist probe on sleep and the HPA axis in chronic insomnia: a pilot study.

    PubMed

    Buckley, Theresa; Duggal, Vandana; Schatzberg, Alan F

    2008-06-15

    Hypothalamic-pituitary-adrenal axis (HPA) hyperactivity has been reported in patients with chronic insomnia without depression. Aglucocorticoid receptor (GR) antagonist may re-regulate HPA axis activity even after discontinuation and may have clinical benefit. Ten subjects with chronic insomnia participated in a placebo controlled double-blinded prospective 30-day pilot study of the acute and post-discontinuation effects of a 5-day course of 600 mg of the glucocorticoid antagonist, mifepristone. Sleep outcome measures were polysomnogram and Insomnia Severity Index. Hormonal outcome measures were mean overnight cortisol and ACTH (23:00-07:00). We predicted sleep would improve and that overnight cortisol and ACTH would decrease at 2 weeks post-treatment discontinuation. At 2 weeks post-discontinuation, Insomnia Severity Index (ISI) decreased by 4.0 points (effect size = 0.97). Polysomnogram findings were limited. Mean cortisol (0.84 microg/dL, effect size = 0.91) and ACTH (5.50 pg/mL, effect size = 0.96) were still mildly increased (23:00 to 07:00). Post hoc analysis revealed that, the ratio of cortisol/ ACTH decreased (-0.21, effect size = 1.15) as did mean cortisol from 18:00 to 23:00 (-0.47 microg/dL, effect size = 0.56). This is the first study of a GR antagonist in chronic insomnia. Sleep improvement manifests in terms of decreased ISI post-treatment discontinuation. The decrease in cortisol in the early evening (18:00 to 23:00) in combination with the decrease in cortisol/ ACTH ratio may be an indicator of the longer-term biological mode of action of the drug.

  8. Characteristic of retained austenite decomposition during tempering and its effect on impact toughness in SA508 Gr.3 steel

    NASA Astrophysics Data System (ADS)

    Yan, Guanghua; Han, Lizhan; Li, Chuanwei; Luo, Xiaomeng; Gu, Jianfeng

    2017-01-01

    Retained austenite(RA) usually presents in the quenched Nuclear Pressure-Vessel SA508 Gr.3 steel. In the present work, the characteristic of RA decomposition and its effect on the impact toughness were investigated by microstructure observation, dilatometric experiments and Charpy impact tests. The results show that the RA transformed into martensite and bainite during tempering at 230 °C and 400 °C respectively, while mixture of long rod carbides and ferrite formed at 650 °C. The long rod carbides formed from RA decomposition decrease the critical cleavage stress for initiation of micro-cracks, and deteriorate the impact toughness of the steel. Pre-tempering at a low temperature such as 230 °C or 400 °C leading to the decomposition of RA into martensite or baintie can eliminate the deterioration of the toughness caused by direct decomposition into long rod carbides. The absorbed energy indicate that pre-tempering at 400 °C can drive dramatically improvement in the toughness of the steel.

  9. Teleseismic P-wave polarization analysis at the Gräfenberg array

    NASA Astrophysics Data System (ADS)

    Cristiano, L.; Meier, T.; Krüger, F.; Keers, H.; Weidle, C.

    2016-12-01

    P-wave polarization at the Gräfenberg array (GRF) in southern Germany is analysed in terms of azimuthal deviations and deviations in the vertical polarization using 20 yr of broad-band recordings. An automated procedure for estimating P-wave polarization parameters is suggested, based on the definition of a characteristic function, which evaluates the polarization angles and their time variability as well as the amplitude, linearity and the signal-to-noise ratio of the P wave. P-wave polarization at the GRF array is shown to depend mainly on frequency and backazimuth and only slightly on epicentral distance indicating depth-dependent local anisotropy and lateral heterogeneity. A harmonic analysis is applied to the azimuthal anomalies to analyse their periodicity as a function of backazimuth. The dominant periods are 180° and 360°. At low frequencies, between 0.03 and 0.1 Hz, the observed fast directions of azimuthal anisotropy inferred from the 180° periodicity are similar across the array. The average fast direction of azimuthal anisotropy at these frequencies is N20°E with an uncertainty of about 8° and is consistent with fast directions of Pn-wave propagation. Lateral velocity gradients determined for the low-frequency band are compatible with the Moho topography of the area. A more complex pattern in the horizontal fast axis orientation beneath the GRF array is observed in the high-frequency band between 0.1 and 0.5 Hz, and is attributed to anisotropy in the upper crust. A remarkable rotation of the horizontal fast axis orientation across the suture between the geological units Moldanubicum and Saxothuringicum is observed. In contrast, the 360° periodicity at high frequencies is rather consistent across the array and may either point to lower velocities in the upper crust towards the Bohemian Massif and/or to anisotropy dipping predominantly in the NE-SW direction. Altogether, P-wave polarization analysis indicates the presence of layered lithospheric

  10. S100a8/a9 released by CD11b+Gr1+ neutrophils activates cardiac fibroblasts to initiate angiotensin II-Induced cardiac inflammation and injury.

    PubMed

    Wu, Yina; Li, Yulin; Zhang, Congcong; A, Xi; Wang, Yueli; Cui, Wei; Li, Huihua; Du, Jie

    2014-06-01

    Angiotensin II induces cardiovascular injury, in part, by activating inflammatory response; however, the initial factors that trigger the inflammatory cascade remain unclear. Microarray analysis of cardiac tissue exposed to systemic angiotensin II infusion revealed that extracellular heterodimeric proteins S100a8/a9 were highly upregulated. The increase in S100a8/a9 mRNA of CD11b(+)Gr1(+) neutrophils isolated from both the peripheral blood and heart was highest on day 1 of angiotensin II infusion and decreased to baseline at day 7. Immunostaining showed that S100a8/a9 was primarily present in infiltrating CD11b(+)Gr1(+) neutrophils in the heart. The receptor for advanced glycation end products, an S100a8/a9 receptor, was expressed in cardiac fibroblasts (CFs). Microarray analysis and Bio-Plex protein array showed that treatment of CFs with recombinant S100a8/a9 activated multiple chemokine and cytokines released. Luciferase reporter assay indicated S100a8/a9-activated nuclear factor-κ B pathway in CFs. Consequently, recombinant S100a8/a9-treated CFs promoted migration of monocytes and CFs, whereas neutralizing S100a9 antibody blocked S100a9 or receptor for advanced glycation end products-suppressed cellular migration. Finally, administration of a neutralizing S100a9 antibody prevented angiotensin II infusion-induced nuclear factor-κ B activation, inflammatory cell infiltration, cytokine production, subsequent perivascular and interstitial fibrosis, and hypertrophy in heart. Our findings identify neutrophil-produced S100a8/a9 as an initial proinflammatory factor needed to trigger inflammation and cardiac injury during acute hypertension.

  11. Purification and characterization of endo-beta-1,4 mannanase from Aspergillus niger gr for application in food processing industry.

    PubMed

    Naganagouda, K; Salimath, P V; Mulimani, V H

    2009-10-01

    A thermostable extracellular beta-mannanase from the culture supernatant of a fungus Aspergillus niger gr was purified to homogeneity. SDS-PAGE of the purified enzyme showed a single protein band of molecular mass 66 kDa. The beta- mannanase exhibited optimum catalytic activity at pH 5.5 and 55 degrees C. It was thermostable at 55 degrees C, and retained 50% activity after 6 h at 55 degrees C. The enzyme was stable at a pH range of 3.0 to 7.0. The metal ions Hg(2+), Cu(2+), and Ag(2+) inhibited complete enzyme activity. The inhibitors tested, EDTA, PMSF, and 1,10-phenanthroline, did not inhibit the enzyme activity. N-Bromosuccinimide completely inhibited enzyme activity. The relative substrate specificity of enzyme towards the various mannans is in the order of locust bean gum>guar gum>copra mannan, with K(m) of 0.11, 0.28, and 0.33 mg/ml, respectively. Since the enzyme is active over a wide range of pH and temperature, it could find potential use in the food-processing industry.

  12. Grüneisen Parameter and Thermal Expansion by the Self-Consistent Renormalization Theory of Spin Fluctuations

    NASA Astrophysics Data System (ADS)

    Watanabe, Shinji; Miyake, Kazumasa

    2018-03-01

    The thermal expansion coefficient α and the Grüneisen parameter Γ near the magnetic quantum critical point (QCP) are derived on the basis of the self-consistent renormalization (SCR) theory of spin fluctuations. From the SCR entropy, the specific heat CV, α, and Γ are shown to be expressed in a simple form as CV = Ca - Cb, α = αa + αb, and Γ = Γa + Γb, respectively, where Ci, αi, and Γi (i = a, b) are related with each other. As the temperature T decreases, Ca, αb, and Γb become dominant in CV, α, and Γ, respectively. The inverse susceptibility of spin fluctuation coupled to the volume V in Γb is found to give rise to the divergence of Γ at the QCP for each class of ferromagnetism and antiferromagnetism (AFM) in spatial dimensions d = 3 and 2. This V-dependent inverse susceptibility in αb and Γb contributes to the T dependences of α and Γ, and even affects their criticality in the case of the AFM QCP in d = 2. Γa is expressed as Γ a(T = 0) = - V/T0( {partial T0}/{partial V} )T = 0 with T0 being the characteristic temperature of spin fluctuation, which has an enhanced value in heavy electron systems.

  13. Gr and hp-1 tomato mutants unveil unprecedented interactions between arbuscular mycorrhizal symbiosis and fruit ripening.

    PubMed

    Chialva, Matteo; Zouari, Inès; Salvioli, Alessandra; Novero, Mara; Vrebalov, Julia; Giovannoni, James J; Bonfante, Paola

    2016-07-01

    Systemic responses to an arbuscular mycorrhizal fungus reveal opposite phenological patterns in two tomato ripening mutants depending whether ethylene or light reception is involved. The availability of tomato ripening mutants has revealed many aspects of the genetics behind fleshy fruit ripening, plant hormones and light signal reception. Since previous analyses revealed that arbuscular mycorrhizal symbiosis influences tomato berry ripening, we wanted to test the hypothesis that an interplay might occur between root symbiosis and fruit ripening. With this aim, we screened seven tomato mutants affected in the ripening process for their responsiveness to the arbuscular mycorrhizal fungus Funneliformis mosseae. Following their phenological responses we selected two mutants for a deeper analysis: Green ripe (Gr), deficient in fruit ethylene perception and high-pigment-1 (hp-1), displaying enhanced light signal perception throughout the plant. We investigated the putative interactions between ripening processes, mycorrhizal establishment and systemic effects using biochemical and gene expression tools. Our experiments showed that both mutants, notwithstanding a normal mycorrhizal phenotype at root level, exhibit altered arbuscule functionality. Furthermore, in contrast to wild type, mycorrhization did not lead to a higher phosphate concentration in berries of both mutants. These results suggest that the mutations considered interfere with arbuscular mycorrhiza inducing systemic changes in plant phenology and fruits metabolism. We hypothesize a cross talk mechanism between AM and ripening processes that involves genes related to ethylene and light signaling.

  14. Effect of microstructure on the impact toughness and temper embrittlement of SA508Gr.4N steel for advanced pressure vessel materials.

    PubMed

    Yang, Zhiqiang; Liu, Zhengdong; He, Xikou; Qiao, Shibin; Xie, Changsheng

    2018-01-09

    The effect of microstructure on the impact toughness and the temper embrittlement of a SA508Gr.4N steel was investigated. Martensitic and bainitic structures formed in this material were examined via scanning electron microscopy, electron backscatter diffraction, transmission electron microscopy, and Auger electron spectroscopy (AES) analysis. The martensitic structure had a positive effect on both the strength and toughness. Compared with the bainitic structure, this structure consisted of smaller blocks and more high-angle grain boundaries (HAGBs). Changes in the ultimate tensile strength and toughness of the martensitic structure were attributed to an increase in the crack propagation path. This increase resulted from an increased number of HAGBs and refinement of the sub-structure (block). The AES results revealed that sulfur segregation is higher in the martensitic structure than in the bainitic structure. Therefore, the martensitic structure is more susceptible to temper embrittlement than the bainitic structure.

  15. Accumulation of CD11b+Gr-1+ cells in the lung, blood and bone marrow of mice infected with highly pathogenic H5N1 and H1N1 influenza viruses

    PubMed Central

    Kotur, Mark S.; Stark, Gregory V.; Warren, Richard L.; Kasoji, Manjula; Craft, Jeremy L.; Albrecht, Randy A.; García-Sastre, Adolfo; Katze, Michael G.; Waters, Katrina M.; Vasconcelos, Daphne; Sabourin, Patrick J.; Bresler, Herbert S.; Sabourin, Carol L.

    2017-01-01

    Infection with pathogenic influenza viruses isassociated with intense inflammatory disease. Here, we investigated the innate immune response in mice infectedwith H5N1 A/Vietnam/1203/04 and with reassortanthuman H1N1 A/Texas/36/91 viruse s containing the virulence genes hemagglutinin (HA), neuraminidase (NA) and NS1 of the 1918 pandemic virus. Inclusion of the 1918 HAand NA glycoproteins rendered a seasonal H1N1 virus capable of inducing an exacerbated host innate immuneresponse similar to that observed for highly pathogenicA/Vietnam/1203/04 virus. Infection with 1918 HA/NA:Tx/91 and A/Vietnam/1203/04 were associated with severelung pathology, increased cytokine and chemokine production, and significant immune cell changes, including the presence of CD11b+Gr-1+cells in the blood, lung and bone marrow. Significant differential gene expression in the lung included pathways for cell death, apoptosis, production and response to reactive oxygen radicals, as well asarginine and proline meta bolism and chemokines associated with monocyte and neutrophil/granulocyte accumulation and/or activation. Arginase was produced in the lungof animals infected with A/Vietnam/1204. These results demonstrate that the innate immune cell response resultsin t he accumulation of CD11b+Gr-1+cells and products that have previously been shown to contribute to T cellsuppression. PMID:23397329

  16. CMOS integration of high-k/metal gate transistors in diffusion and gate replacement (D&GR) scheme for dynamic random access memory peripheral circuits

    NASA Astrophysics Data System (ADS)

    Dentoni Litta, Eugenio; Ritzenthaler, Romain; Schram, Tom; Spessot, Alessio; O’Sullivan, Barry; Machkaoutsan, Vladimir; Fazan, Pierre; Ji, Yunhyuck; Mannaert, Geert; Lorant, Christophe; Sebaai, Farid; Thiam, Arame; Ercken, Monique; Demuynck, Steven; Horiguchi, Naoto

    2018-04-01

    Integration of high-k/metal gate stacks in peripheral transistors is a major candidate to ensure continued scaling of dynamic random access memory (DRAM) technology. In this paper, the CMOS integration of diffusion and gate replacement (D&GR) high-k/metal gate stacks is investigated, evaluating four different approaches for the critical patterning step of removing the N-type field effect transistor (NFET) effective work function (eWF) shifter stack from the P-type field effect transistor (PFET) area. The effect of plasma exposure during the patterning step is investigated in detail and found to have a strong impact on threshold voltage tunability. A CMOS integration scheme based on an experimental wet-compatible photoresist is developed and the fulfillment of the main device metrics [equivalent oxide thickness (EOT), eWF, gate leakage current density, on/off currents, short channel control] is demonstrated.

  17. Systemic Scedosporium prolificans infection in an 11-month-old Border collie with cobalamin deficiency secondary to selective cobalamin malabsorption (canine Imerslund-Gräsbeck syndrome).

    PubMed

    Erles, K; Mugford, A; Barfield, D; Leeb, T; Kook, P H

    2018-04-01

    An 11-month-old Border collie presented collapsed and continued to deteriorate rapidly despite supportive treatment. The dog had a history of failure to thrive and recurring respiratory infection. Laboratory abnormalities included neutrophilic leucocytosis, Heinz body anaemia, hyperammonaemia, hyperbilirubinaemia, proteinuria and hypocobalaminaemia. Post-mortem examination revealed multi-focal necrosis within the heart, kidneys, pancreas, liver, meninges and cerebral cortex. Fungal hyphae in lesions were identified as Scedosporium prolificans following culture. Subsequent genotyping confirmed that the dog carried the CUBN:c.8392delC mutation in a homozygous state, verifying hereditary cobalamin deficiency (a.k.a. Imerslund-Gräsbeck syndrome). Cobalamin deficiency may have been a predisposing factor for the development of systemic fungal infection in this dog. © 2017 British Small Animal Veterinary Association.

  18. Radiosynthesis and radiopharmacological evaluation of [N-methyl-11C]Org 34850 as a glucocorticoid receptor (GR)-binding radiotracer.

    PubMed

    Wuest, Frank; Kniess, Torsten; Henry, Brian; Peeters, Bernardus W M M; Wiegerinck, Peter H G; Pietzsch, Jens; Bergmann, Ralf

    2009-02-01

    The radiosynthesis of [N-methyl-(11)C]Org 34850 as a potential brain glucocorticoid receptor (GR)-binding radiotracer is described. The radiosynthesis was accomplished via N-methylation of the corresponding desmethyl precursor with [(11)C]methyl triflate in a remotely controlled synthesis module to give the desired compound in a radiochemical yield of 23+/-5% (decay-corrected, based upon [(11)C]CO(2)) at a specific activity of 47+/-12 GBq/micromol (n=15) at the end-of-synthesis (EOS). The radiochemical purity after semi-preparative HPLC purification exceeded 95%. The total synthesis time was 35-40 min after end-of-bombardment (EOB). The radiotracer is rapidly metabolized in rat plasma leading to the formation of two more hydrophilic metabolites as the major metabolites. Radiopharmacological evaluation involving biodistribution and small animal PET imaging in normal Wistar rats showed that the compound [N-methyl-(11)C]Org 34850 is not able to sufficiently penetrate the blood-brain barrier. Therefore, compound [N-methyl-(11)C]Org 34850 seems not to be a suitable PET radiotracer for imaging rat brain GRs. However, involvement of Pgp or species differences requires further clarification to establish whether the radiotracer [N-methyl-(11)C]Org 34850 may still represent a suitable candidate for imaging GRs in humans.

  19. Performance analysis of the GR712RC dual-core LEON3FT SPARC V8 processor in an asymmetric multi-processing environment

    NASA Astrophysics Data System (ADS)

    Giusi, Giovanni; Liu, Scige J.; Galli, Emanuele; Di Giorgio, Anna M.; Farina, Maria; Vertolli, Nello; Di Lellis, Andrea M.

    2016-07-01

    In this paper we present the results of a series of performance tests carried out on a prototype board mounting the Cobham Gaisler GR712RC Dual Core LEON3FT processor. The aim was the characterization of the performances of the dual core processor when used for executing a highly demanding lossless compression task, acting on data segments continuously copied from the static memory to the processor RAM. The selection of the compression activity to evaluate the performances was driven by the possibility of a comparison with previously executed tests on the Cobham/Aeroflex Gaisler UT699 LEON3FT SPARC™ V8. The results of the test activity have shown a factor 1.6 of improvement with respect to the previous tests, which can easily be improved by adopting a faster onboard board clock, and provided indications on the best size of the data chunks to be used in the compression activity.

  20. Tribological Characteristics of Submicron SiC(p)-GR(p)/Zn-35Al-1Mg Composites in Semisolidification Casting process

    NASA Astrophysics Data System (ADS)

    Liu, S.; Fang, Z. W.; Li, L. X.

    2018-05-01

    Uniform SiC(p)-GR(p)/Zn-35Al-1Mg composites were prepared by powder pressing and semisolidification stirring-casting process by adding submicron silicon carbide and graphite reinforcement particles in an aluminum-zinc alloy matrix. Micro Vickers hardness and microstructures of the novel composites were studied, and their wear properties and wear temperature were measured for different load and friction conditions. The results show that silicon carbide and graphite particles homogeneously mix in the matrix, while contained silicon carbide particles improve the matrix hardness to 8.4%, graphite improves the matrix hardness to 16.8%, but two of them, combined, reduce the matrix hardness to 7.6%; the rate of temperature rise of the zinc-aluminum matrix alloy is the highest than the other three composites and is up to 48.5° C/s at 1.69MPa. At 0.56MPa and sliding 26.4km, the graphite composite anti-wear effect is optimal, while at 1.13MPa, the wear resistance of silicon carbide and graphite compound particles is the best; in the other case of only silicon carbide particles, the wear resistance is increased to 35% at 1.69MPa and 26.4km, and its anti-wear effects are excellent.

  1. Clinical study comparing probiotic Lactobacillus GR-1 and RC-14 with metronidazole vaginal gel to treat symptomatic bacterial vaginosis.

    PubMed

    Anukam, Kingsley C; Osazuwa, Emmanuel; Osemene, Gibson I; Ehigiagbe, Felix; Bruce, Andrew W; Reid, Gregor

    2006-10-01

    Bacterial vaginosis (BV) is particularly common in black women, and in Nigeria it is often caused by Mycoplasma, as well as Atopobium, Prevotella and Gardnerella sp. Antimicrobial metronidazole oral therapy is poorly effective in eradicating the condition and restoring the Lactobacillus microbiota in the vagina. In this study, 40 women diagnosed with BV by discharge, fishy odor, sialidase positive test and Nugent Gram stain scoring, were randomized to receive either two dried capsules containing Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 each night for 5 days, or 0.75% metronidazole gel, applied vaginally twice a day (in the morning and evening). Follow-up at day 6, 15 and 30 showed cure of BV in significantly more probiotic treated subjects (16, 17 and 18/20, respectively) compared to metronidazole treatment (9, 9 and 11/20: P=0.016 at day 6, P=0.002 at day 15 and P=0.056 at day 30). This is the first report of an effective (90%) cure of BV using probiotic lactobacilli. Given the correlation between BV and HIV, and the high risk of the latter in Nigeria, intravaginal use of lactobacilli could provide women with a self-use therapy, similar to over-the-counter anti-yeast medication, for treatment of urogenital infections.

  2. Influence of xc functional on thermal-elastic properties of Ceria: A DFT-based Debye-Grüneisen model approach

    NASA Astrophysics Data System (ADS)

    Lee, Ji-Hwan; Tak, Youngjoo; Lee, Taehun; Soon, Aloysius

    Ceria (CeO2-x) is widely studied as a choice electrolyte material for intermediate-temperature (~ 800 K) solid oxide fuel cells. At this temperature, maintaining its chemical stability and thermal-mechanical integrity of this oxide are of utmost importance. To understand their thermal-elastic properties, we firstly test the influence of various approximations to the density-functional theory (DFT) xc functionals on specific thermal-elastic properties of both CeO2 and Ce2O3. Namely, we consider the local-density approximation (LDA), the generalized gradient approximation (GGA-PBE) with and without additional Hubbard U as applied to the 4 f electron of Ce, as well as the recently popularized hybrid functional due to Heyd-Scuseria-Ernzehof (HSE06). Next, we then couple this to a volume-dependent Debye-Grüneisen model to determine the thermodynamic quantities of ceria at arbitrary temperatures. We find an explicit description of the strong correlation (e.g. via the DFT + U and hybrid functional approach) is necessary to have a good agreement with experimental values, in contrast to the mean-field treatment in standard xc approximations (such as LDA or GGA-PBE). We acknowledge support from Samsung Research Funding Center of Samsung Electronics (SRFC-MA1501-03).

  3. Corrosion rate of API 5L Gr. X60 multipurpose steel pipeline under combined effect of water and crude oil

    NASA Astrophysics Data System (ADS)

    Miao, Jian; Wang, Qiang

    2016-09-01

    Multipurpose pipeline is often seriously corroded during its service life, and the phenomenon is more prominent once the transportation medium is changed. Electrochemical polarization curves and impedance spectroscopy of the API 5L Gr. X60 steel pipeline's corrosion process in sedimentary water with different ion types and their concentrations have been studied in this work. The results showed that the corrosion rates were found to be 0.00418 and 0.00232 mm/a for pure water and crude oil, respectively. However, for the mixtures of water and crude oil (with water content increased from 0.2 vol% to 10 vol%), the corrosion rate increased consistently and reached a maximum value of 0.15557 mm/a for 10 vol% water in crude oil. The effect of the concentration of various ions, namely, chloride, bicarbonate and sulfate in (oil/water) mixtures on the corrosion rate was characterized by weight-loss method. The results showed that with increasing the ions' concentrations, the corresponding exchange current density increased significantly. The results were further supported by the observations of corrosion morphology using scanning electron microscopy and are helpful in devising guidelines which would help in reducing corrosion in multipurpose transport pipelines involving a change of transported medium during their service life.

  4. Integrating sphere-based photoacoustic setup for simultaneous absorption coefficient and Grüneisen parameter measurements of biomedical liquids

    NASA Astrophysics Data System (ADS)

    Villanueva, Yolanda; Hondebrink, Erwin; Petersen, Wilma; Steenbergen, Wiendelt

    2015-03-01

    A method for simultaneously measuring the absorption coefficient μa and Grüneisen parameter Γ of biological absorbers in photoacoustics is designed and implemented using a coupled-integrating sphere system. A soft transparent tube with inner diameter of 0.58mm is used to mount the liquid absorbing sample horizontally through the cavity of two similar and adjacent integrating spheres. One sphere is used for measuring the sample's μa using a continuous halogen light source and a spectrometer fiber coupled to the input and output ports, respectively. The other sphere is used for simultaneous photoacoustic measurement of the sample's Γ using an incident pulsed light with wavelength of 750nm and a flat transducer with central frequency of 5MHz. Absolute optical energy and pressure measurements are not necessary. However, the derived equations for determining the sample's μa and Γ require calibration of the setup using aqueous ink dilutions. Initial measurements are done with biological samples relevant to biomedical imaging such as human whole blood, joint and cyst fluids. Absorption of joint and cyst fluids is enhanced using a contrast agent like aqueous indocyanine green dye solution. For blood sample, measured values of μa = 0.580 +/- 0.016 mm-1 and Γ = 0.166 +/- 0.006 are within the range of values reported in literature. Measurements with the absorbing joint and cyst fluid samples give Γ values close to 0.12, which is similar to that of water and plasma.

  5. Epidemiological characteristics of Malassezia folliculitis and use of the May-Grünwald-Giemsa stain to diagnose the infection.

    PubMed

    Durdu, Murat; Güran, Mümtaz; Ilkit, Macit

    2013-08-01

    Various bacterial, fungal, parasitic, and viral pathogens can cause folliculitis, which is often mistakenly treated with antibiotics for months or even years. A laboratory diagnosis is required before therapy can be planned. Here, we describe the prevalence and risk factors, as well as the clinical, cytological, and mycological characteristics, of patients with Malassezia folliculitis (MF) in Adana, Turkey. We also report the treatment responses of the MF patients and describe the Malassezia spp. using culture-based molecular methods. Cytological examinations were performed in 264 folliculitis patients, 49 of whom (18.5%) were diagnosed with MF. The positivity of the May-Grünwald-Giemsa (MGG) smear was higher (100%) than that of the potassium hydroxide test (81.6%). Using Wood's light, yellow-green fluorescence was observed in 66.7% of the MF patients. Identification using the rDNA internal transcribed spacer region revealed that Malassezia globosa was the most common species, followed by Malassezia sympodialis, Malassezia restricta, and Malassezia furfur. The MF patients were treated with itraconazole capsules (200 mg/d) for 2 weeks. Complete recovery was observed in 79.6% of the patients. These novel findings help improve our current understanding of the epidemiological characteristics of MF and establish MGG as a practical tool for the diagnosis of MF. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. S100A8 Production in CXCR2-Expressing CD11b+Gr-1high Cells Aggravates Hepatitis in Mice Fed a High-Fat and High-Cholesterol Diet.

    PubMed

    Mukai, Kaori; Miyagi, Takuya; Nishio, Kumiko; Yokoyama, Yoshinobu; Yoshioka, Teppei; Saito, Yoshinobu; Tanaka, Satoshi; Shigekawa, Minoru; Nawa, Takatoshi; Hikita, Hayato; Sakamori, Ryotaro; Yoshihara, Harumasa; Imai, Yasuharu; Hiramatsu, Naoki; Tatsumi, Tomohide; Takehara, Tetsuo

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease with a spectrum of presentations. S100A8 has been suggested to play a pivotal role as an endogenous immune-activator in inflammatory diseases. In this study, we investigated the involvement of S100A8 in the development of NAFLD. We used a diet model of NAFLD, in which mice were fed either a high-fat and high-cholesterol diet (HFHCD) or a normal diet (ND) as a control. We also assessed liver tissues from patients with NAFLD, including patients with nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). HFHCD-fed mice, but not ND-fed mice, developed steatohepatitis. S100A8 expression was significantly elevated in the livers of HFHCD-fed mice compared with the controls. S100A8 was exclusively expressed in CXCR2-expressing CD11b(+)Gr-1(high) cells, which significantly increased in the livers of HFHCD-fed mice. These cells were F4/80 negative and did not possess a suppressor function. TNF-α expression was enhanced by S100A8 in primary liver leukocytes or a hepatocyte cell line and significantly elevated in the livers of HFHCD-fed mice. TNF-α was primarily produced from CD11b(+)F4/80(+) cells in liver leukocytes in response to S100A8. TNF-α deficiency attenuated hepatitis in HFHCD-fed mice. S100A8 was significantly more expressed in the liver tissues of patients with NASH than in those of patients with NAFL. In conclusion, these results suggest that S100A8 is primarily produced from CXCR2-expressing CD11b(+)Gr-1(high) cells, and it upregulates TNF-α production in CD11b(+)F4/80(+) cells through cellular cross-talk, which is an important mechanism in the development of NAFLD. Copyright © 2015 by The American Association of Immunologists, Inc.

  7. Can the super model (SUMO) method improve hydrological simulations? Exploratory tests with the GR hydrological models

    NASA Astrophysics Data System (ADS)

    Santos, Léonard; Thirel, Guillaume; Perrin, Charles

    2017-04-01

    Errors made by hydrological models may come from a problem in parameter estimation, uncertainty on observed measurements, numerical problems and from the model conceptualization that simplifies the reality. Here we focus on this last issue of hydrological modeling. One of the solutions to reduce structural uncertainty is to use a multimodel method, taking advantage of the great number and the variability of existing hydrological models. In particular, because different models are not similarly good in all situations, using multimodel approaches can improve the robustness of modeled outputs. Traditionally, in hydrology, multimodel methods are based on the output of the model (the simulated flow series). The aim of this poster is to introduce a different approach based on the internal variables of the models. The method is inspired by the SUper MOdel (SUMO, van den Berge et al., 2011) developed for climatology. The idea of the SUMO method is to correct the internal variables of a model taking into account the values of the internal variables of (an)other model(s). This correction is made bilaterally between the different models. The ensemble of the different models constitutes a super model in which all the models exchange information on their internal variables with each other at each time step. Due to this continuity in the exchanges, this multimodel algorithm is more dynamic than traditional multimodel methods. The method will be first tested using two GR4J models (in a state-space representation) with different parameterizations. The results will be presented and compared to traditional multimodel methods that will serve as benchmarks. In the future, other rainfall-runoff models will be used in the super model. References van den Berge, L. A., Selten, F. M., Wiegerinck, W., and Duane, G. S. (2011). A multi-model ensemble method that combines imperfect models through learning. Earth System Dynamics, 2(1) :161-177.

  8. Numerical modeling analysis of the mesoscale environment conducive to two tornado events using the COSMO.Gr model over Greece

    NASA Astrophysics Data System (ADS)

    Avgoustoglou, E.; Matsangouras, I. T.; Pytharoulis, I.; Kamperakis, N.; Mylonas, M.; Nastos, P. T.; Bluestein, H. W.

    2018-08-01

    The COnsortium for Small-scale MOdeling (COSMO) was formed in October 1998, and its general goal is to develop, improve and maintain a non-hydrostatic limited-area atmospheric model. The COSMO model has been designed both for operational numerical weather prediction (NWP) as well as various scientific applications on the meso-β and meso-γ scale. Two tornado case studies were selected to investigate the ability of COSMO model to depict the characteristics of severe convective weather, which favoured the development of the associated storms. The first tornado (TR01) occurred, close to Ag. Ilias village, 8 Km north-western of Aitoliko city over western Greece on February 7, 2013, while the second tornado (TR02) was developed close to Palio Katramio village, 8 Km southern from Xanthi city over northern Greece on November 25, 2015. Although both tornadoes had a short lifetime, they caused significant damages. The COSMO.GR atmospheric model was initialized with analysis from the European Centre for Medium-Range Weather Forecasts (ECMWF). The resulting numerical products with spatial resolution of 0.02° (∼ 2 km) over the geographical domain of Greece depicted very well the severe convective conditions close to tornadoes formation. The Energy Helicity Index (EHI) diagnostic variable in both numerical simulations showed a gradual increase of values closing to the location and time of the tornadogenesis. Similar to EHI, the storm relative helicity (SRH) spatio-temporal analysis followed a gradual increase prior to the tornadogenesis events and was reduced after them.

  9. Non-invasive screening for Alzheimer's disease by sensing salivary sugar using Drosophila cells expressing gustatory receptor (Gr5a) immobilized on an extended gate ion-sensitive field-effect transistor (EG-ISFET) biosensor.

    PubMed

    Lau, Hui-Chong; Lee, In-Kyu; Ko, Pan-Woo; Lee, Ho-Won; Huh, Jeung-Soo; Cho, Won-Ju; Lim, Jeong-Ok

    2015-01-01

    Body fluids are often used as specimens for medical diagnosis. With the advent of advanced analytical techniques in biotechnology, the diagnostic potential of saliva has been the focus of many studies. We recently reported the presence of excess salivary sugars, in patients with Alzheimer's disease (AD). In the present study, we developed a highly sensitive, cell-based biosensor to detect trehalose levels in patient saliva. The developed biosensor relies on the overexpression of sugar sensitive gustatory receptors (Gr5a) in Drosophila cells to detect the salivary trehalose. The cell-based biosensor was built on the foundation of an improved extended gate ion-sensitive field-effect transistor (EG-ISFET). Using an EG-ISFET, instead of a traditional ion-sensitive field-effect transistor (ISFET), resulted in an increase in the sensitivity and reliability of detection. The biosensor was designed with the gate terminals segregated from the conventional ISFET device. This design allows the construction of an independent reference and sensing region for simultaneous and accurate measurements of samples from controls and patients respectively. To investigate the efficacy of the cell-based biosensor for AD screening, we collected 20 saliva samples from each of the following groups: participants diagnosed with AD, participants diagnosed with Parkinson's disease (PD), and a control group composed of healthy individuals. We then studied the response generated from the interaction of the salivary trehalose of the saliva samples and the Gr5a in the immobilized cells on an EG-ISFET sensor. The cell-based biosensor significantly distinguished salivary sugar, trehalose of the AD group from the PD and control groups. Based on these findings, we propose that salivary trehalose, might be a potential biomarker for AD and could be detected using our cell-based EG-ISFET biosensor. The cell-based EG-ISFET biosensor provides a sensitive and direct approach for salivary sugar detection and

  10. Effect of Cutting Parameters on Thrust Force and Surface Roughness in Drilling of Al-2219/B4C/Gr Metal Matrix Composites

    NASA Astrophysics Data System (ADS)

    Ravindranath, V. M.; Basavarajappa, G. S. Shiva Shankar S.; Suresh, R.

    2016-09-01

    In aluminium matrix composites, reinforcement of hard ceramic particle present inside the matrix which causes tool wear, high cutting forces and poor surface finish during machining. This paper focuses on effect of cutting parameters on thrust force, surface roughness and burr height during drilling of MMCs. In the present work, discuss the influence of spindle speed and feed rate on drilling the pure base alloy (Al-2219), mono composite (Al- 2219+8% B4C) and hybrid composite (Al-2219+8%B4C+3%Gr). The composites were fabricated using liquid metallurgy route. The drilling experiments were conducted by CNC machine with TiN coated HSS tool, M42 (Cobalt grade) and carbide tools at various spindle speeds and feed rates. The thrust force, surface roughness and burr height of the drilled hole were investigated in mono composite and hybrid composite containing graphite particles, the experimental results show that the feed rate has more influence on thrust force and surface roughness. Lesser thrust force and discontinuous chips were produced during machining of hybrid composites when compared with mono and base alloy during drilling process. It is due to solid lubricant property of graphite which reduces the lesser thrust force, burr height and lower surface roughness. When machining with Carbide tool at low feed and high speeds good surface finish was obtained compared to other two types of cutting tool materials.

  11. A Frameshift Mutation in the Cubilin Gene (CUBN) in Border Collies with Imerslund-Gräsbeck Syndrome (Selective Cobalamin Malabsorption)

    PubMed Central

    Owczarek-Lipska, Marta; Jagannathan, Vidhya; Drögemüller, Cord; Lutz, Sabina; Glanemann, Barbara

    2013-01-01

    Imerslund-Gräsbeck syndrome (IGS) or selective cobalamin malabsorption has been described in humans and dogs. IGS occurs in Border Collies and is inherited as a monogenic autosomal recessive trait in this breed. Using 7 IGS cases and 7 non-affected controls we mapped the causative mutation by genome-wide association and homozygosity mapping to a 3.53 Mb interval on chromosome 2. We re-sequenced the genome of one affected dog at ∼10× coverage and detected 17 non-synonymous variants in the critical interval. Two of these non-synonymous variants were in the cubilin gene (CUBN), which is known to play an essential role in cobalamin uptake from the ileum. We tested these two CUBN variants for association with IGS in larger cohorts of dogs and found that only one of them was perfectly associated with the phenotype. This variant, a single base pair deletion (c.8392delC), is predicted to cause a frameshift and premature stop codon in the CUBN gene. The resulting mutant open reading frame is 821 codons shorter than the wildtype open reading frame (p.Q2798Rfs*3). Interestingly, we observed an additional nonsense mutation in the MRC1 gene encoding the mannose receptor, C type 1, which was in perfect linkage disequilibrium with the CUBN frameshift mutation. Based on our genetic data and the known role of CUBN for cobalamin uptake we conclude that the identified CUBN frameshift mutation is most likely causative for IGS in Border Collies. PMID:23613799

  12. Impact of the maze operation combined with left-sided valve surgery on the change in tricuspid regurgitation over time.

    PubMed

    Kim, Hyung-Kwan; Kim, Yong-Jin; Kim, Kwang-Il; Jo, Sang-Ho; Kim, Ki-Bong; Ahn, Hyuk; Sohn, Dae-Won; Oh, Byung-Hee; Lee, Myoung-Mook; Park, Young-Bae; Choi, Yun-Shik

    2005-08-30

    Atrial fibrillation (AF) has been reported to be a predisposing factor for the progression of TR in patients with previous mitral or combined mitral/aortic valve surgery. We hypothesized that the maze operation (MAZE) can prevent the progression of tricuspid regurgitation (TR) in these patients. We analyzed 170 patients (age, 45.5+/-10.9 years) who had undergone mitral or combined mitral/aortic valve surgery. On the basis of preoperative rhythm, patients were divided into 3 groups; GrI was composed of 44 patients with sinus rhythm, GrII of 48 who had undergone MAZE, and GrIII of 78 with AF who had not undergone MAZE. Echocardiographic examinations were performed before, immediately after, and 92.2+/-17.2 (range, 50 to 131) months after surgery. Preoperative and immediate postoperative clinical and echocardiographic parameters were similar among the groups. Insignificant TR at the immediate postoperative examination worsened with time in 7.3% of GrI (3 of 41), 12.8% of GrII (6 of 47), and 38.8% of GrIII (26 of 67) patients at the final examination (P=0.63 for GrI versus GrII, P=0.001 for GrI versus GrIII, P=0.005 for GrII versus GrIII). The incidence of significant TR at the final echocardiographic examination was higher in GrIII (39.7%) compared with GrI (9.1%) and GrII (14.6%) (P=0.001 for GrI versus GrIII, P=0.005 for GrII versus GrIII), whereas GrI and GrII did not show any difference (P=0.63). By multivariate analysis, the only factor identified to prevent TR progression was the group factor (GrI and GrII versus GrIII, P=0.002 and P=0.005, respectively). In a subgroup analysis of GrII according to the presence or absence of atrial mechanical activity, the absence of atrial mechanical activity was identified as an independent parameter for the progression of TR (P=0.001). AF predisposes patients undergoing mitral valve surgery to the progression of TR, which can be prevented by MAZE. This additional benefit of MAZE is largely dependent on the restoration and

  13. Equation of state and thermodynamic Grüneisen parameter of monoclinic 1,1-diamino-2,2-dinitroethylene

    NASA Astrophysics Data System (ADS)

    Zhang, Jianzhong; Velisavljevic, Nenad; Zhu, Jinlong; Wang, Liping

    2016-10-01

    In situ synchrotron x-ray diffraction experiments were conducted on 1,1-diamino-2,2-dinitroethylene (FOX-7) at pressures up to 6.8 GPa and temperatures up to 485 K. Within the resolution of the present diffraction data, our results do not reveal evidence for a pressure-induced structural phase transition near 2 GPa, previously observed in several vibrational spectroscopy experiments. Based on unit-cell volume measurements, the least-squares fit using the third-order Birch-Murnaghan equation of state (EOS) yields K 0  =  12.6  ±  1.4 GPa and K0\\prime   =  11.3  ±  2.1 for the α-phase of FOX-7, which are in good agreement with recently reported values for the deuterated sample, indicating that the effect of hydrogen-deuterium substitution on the compressibility of FOX-7 is negligibly small. A thermal EOS is also obtained for the α-phase of FOX-7, including pressure dependence of thermal expansivity, (∂α/∂P)T  =  -7.0  ±  2.0  ×  10-5 K-1 GPa-1, and temperature derivative of the bulk modulus, (∂K T/∂T)P  =  -1.1  ×  10-2 GPa K-1. From these EOS parameters, we calculate heat capacity at constant volume (C V) and thermodynamic Grüneisen parameter (γ TH) as a function of temperature. At ambient conditions, the calculated γ TH is 1.055, which is in good agreement with the value (1.09) previously obtained from density functional theory (DFT). The obtained C V, however, is 13% larger than that calculated from the first-principles calculations, indicating that the dispersion correction in the DFT calculations may need to be further improved for describing intermolecular interactions of molecular crystals.

  14. Equation of state and thermodynamic Grüneisen parameter of monoclinic 1,1-diamino-2,2-dinitroethylene.

    PubMed

    Zhang, Jianzhong; Velisavljevic, Nenad; Zhu, Jinlong; Wang, Liping

    2016-10-05

    In situ synchrotron x-ray diffraction experiments were conducted on 1,1-diamino-2,2-dinitroethylene (FOX-7) at pressures up to 6.8 GPa and temperatures up to 485 K. Within the resolution of the present diffraction data, our results do not reveal evidence for a pressure-induced structural phase transition near 2 GPa, previously observed in several vibrational spectroscopy experiments. Based on unit-cell volume measurements, the least-squares fit using the third-order Birch-Murnaghan equation of state (EOS) yields K 0  =  12.6  ±  1.4 GPa and [Formula: see text]  =  11.3  ±  2.1 for the α-phase of FOX-7, which are in good agreement with recently reported values for the deuterated sample, indicating that the effect of hydrogen-deuterium substitution on the compressibility of FOX-7 is negligibly small. A thermal EOS is also obtained for the α-phase of FOX-7, including pressure dependence of thermal expansivity, (∂α/∂P)T  =  -7.0  ±  2.0  ×  10(-5) K(-1) GPa(-1), and temperature derivative of the bulk modulus, (∂K T/∂T)P  =  -1.1  ×  10(-2) GPa K(-1). From these EOS parameters, we calculate heat capacity at constant volume (C V) and thermodynamic Grüneisen parameter (γ TH) as a function of temperature. At ambient conditions, the calculated γ TH is 1.055, which is in good agreement with the value (1.09) previously obtained from density functional theory (DFT). The obtained C V, however, is 13% larger than that calculated from the first-principles calculations, indicating that the dispersion correction in the DFT calculations may need to be further improved for describing intermolecular interactions of molecular crystals.

  15. Radioimmunotherapy (RIT) Dose-Escalation Studies in Prostate Cancer Using Anti-PSMA Antibody 177Lu-J591: RIT Alone and RIT in Combination with Docetaxel

    DTIC Science & Technology

    2010-10-01

    count < 15,000 > 7 days or need for > 3 plt transfusions in 30 days • Gr 4 neutropenia > 7 days • Febrile neutropenia • Attributable Gr > 3...11% No febrile neutropenia (no growth factor use) • Transaminitis Transient Gr 1 AST 29% (1 Gr 2) Need for transfusions 6 pts...No pts had significant bleeding; 2 received plt transfusions (cohort 6) • Neutropenia Gr 0 = 40%; Gr 1-2 = 32%; Gr 3 = 29%; Gr 4

  16. Highly-stable and -flexible graphene/(CF3SO2)2NH/graphene transparent conductive electrodes for organic solar cells

    NASA Astrophysics Data System (ADS)

    Seo, Sang Woo; Lee, Ha Seung; Shin, Dong Hee; Kim, Ju Hwan; Jang, Chan Wook; Kim, Jong Min; Kim, Sung; Choi, Suk-Ho

    2017-10-01

    We first employ highly-stable and -flexible (CF3SO2)2NH-doped graphene (TFSA/GR) and GR-encapsulated TFSA/GR (GR/TFSA/GR) transparent conductive electrodes (TCEs) prepared on polyethylene terephthalate substrates for flexible organic solar cells (OSCs). Compared to conventional indium tin oxide (ITO) TCEs, the TFSA-doped-GR TCEs show higher optical transmittance and larger sheet resistance. The TFSA/GR and GR/TFSA/GR TCEs show work functions of 4.89 ± 0.16 and 4.97 ± 0.18 eV, respectively, which are not only larger than those of the ITO TCEs but also indicate p-type doping of GR, and are therefore more suitable for anode TCEs of OSCs. In addition, typical GR/TFSA/GR-TCE OSCs are much more mechanically flexible than the ITO-TCE ones with their photovoltaic parameters being similar, as proved by bending tests as functions of cycle and curvature.

  17. Effect of carbamate pesticides on perforin, granzymes A-B-3/K, and granulysin in human natural killer cells.

    PubMed

    Li, Qing; Kobayashi, Maiko; Kawada, Tomoyuki

    2015-09-01

    We previously found that ziram, a carbamate pesticide, significantly reduced perforin, granzyme A (GrA), granzyme B (GrB), granzyme 3/K (Gr3/K), and granulysin (GRN) levels in NK-92MI cells, a human natural killer (NK) cell line. To investigate whether other carbamate pesticides also show similar toxicity on human NK cells, we conducted further experiments with NK-92CI cells, a human NK cell line, using a more sensitive assay. We previously confirmed that NK-92CI cells express CD56, perforin, GrA, GrB, Gr3/K, and GRN and are highly cytotoxic to K562 cells in a chromium release assay, which are more sensitive to organophosphorus pesticides and ziram than the NK-92MI cell line. NK-92CI cells were treated with ziram, thiram, maneb, or carbaryl at various concentrations for 4-24 h at 37°C in vitro. Thereafter, intracellular levels of perforin, GrA, GrB, Gr3/K, and GRN were determined by flow cytometry. It was found that all carbamate pesticides significantly reduced the intracellular levels of perforin, GrA, GrB, Gr3/K, and GRN in NK-92CI cells in a dose-dependent manner. However, the strength of the effect differed among the pesticides, and the order was thiram > ziram > maneb > carbaryl. In addition, it was also found that the degree of the reductions differed among the five proteins, with perforin more sensitive to pesticides than GRN, GrA, GrB, and Gr3/K, and the order was perforin > GRN > Gr3/K ≒ GrA ≒ GrB. © The Author(s) 2015.

  18. EPSAH, an exopolysaccharide from Aphanothece halophytica GR02, improves both cellular and humoral immunity as a novel polysaccharide adjuvant.

    PubMed

    Zhu, Lei; Zhang, Fan; Yang, Li-Jun; Ge, Yang; Wei, Qing-Fang; Ou, Yu

    2016-07-01

    EPSAH is an exopolysaccharide from Aphanothece halophytica GR02. The present study was designed to evaluate its toxicity and adjuvant potential in the specific cellular and humoral immune responses in ovalbumin (OVA) in mice. EPSAH did not cause any mortality and side effects when the mice were administered subcutaneously twice at the dose of 50 mg·kg(-1). Hemolytic activity in vitro indicated that EPSAH was non-hemolytic. Splenocyte proliferation in vitro was assayed with different concentrations of EPSAH. The mice were immunized subcutaneously with OVA 0.1 mg alone or with OVA 0.1 mg dissolved in saline containing Alum (0.2 mg) or EPSAH (0.2, 0.4, or 0.8 mg) on Day 1 and 15. Two weeks later, splenocyte proliferation, natural killer (NK) cell activity, production of cytokines IL-2 from splenocytes, and serum OVA-specific antibody titers were measured. Phagocytic activity, production of pro-inflammatory cytokines IL-1 and IL-12 in mice peritoneal macrophages were also determined. EPSAH showed a dose-dependent stimulating effect on mitogen-induced proliferation. The Con A-, LPS-, and OVA-induced splenocyte proliferation and the serum OVA-specific IgG, IgG1, and IgG2a antibody titers in the immunized mice were significantly enhanced. EPSAH also significantly promoted the production of Th1 cytokine IL-2. Besides, EPSAH remarkably increased the killing activities of NK cells from splenocytes in the immunized mice. In addition, EPSAH enhanced phagocytic activity and the generation of pro-inflammatory cytokines IL-1 and IL-12 in macrophages. These results indicated that EPSAH had a strong potential to increase both cellular and humoral immune responses, particularly promoting the development of Th1 polarization. Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  19. Time dependence of volcano inflation: mass influx or viscoelastic relaxation? Insights from Grímsvötn volcano, Iceland

    NASA Astrophysics Data System (ADS)

    Segall, P.

    2017-12-01

    Distinguishing magma chamber pressurization from relaxation of a viscoelastic aureole surrounding the chamber based on geodetic measurements has remained challenging. Elastic models with mass inflow proportional to the pressure difference between the chamber and a deep reservoir predict exponentially decaying flux. For a spherical chamber surrounded by a Maxwell viscoelastic shell with pressure dependent recharge, the surface deformation is the sum of two exponentials (Segall, 2016). GPS displacements following eruptions of Grímsvötn, Iceland in 2004 and 2011 exhibit rapid post-eruptive inflation (time scale of 0.1 yr), followed by inflation with a much longer time constant. Markov Chain Monte Carlo inversion with the viscoelastic model shows the GPS time series can be fit with viscosity of 2e16 Pa-s, and a relatively incompressible magma, B = beta_c/ (beta_m + beta_c) > 0.6, where beta_m and beta_c are chamber and magma compressibility. The latter appears to conflict with the ratio of erupted volume to geodetically inferred source volume change, rv 10, obtained for the best fitting spherical (Mogi ) source (Hreinsdóttir, 2014). Since rv = 1/B, this implies a relatively compressible melt, B 0.1. Reexamination of the co-eruptive GPS and tilt data with the more general ellipsoidal model of Cervelli (2013), reveals that the best fitting sources are oblate (b/a 3), deeper, and with larger volume changes, rv 3, relative to spherical models. Oblate magma chambers are consistent with seismic tomography. FEM calculations including free surface effects lead to even larger co-eruptive volume changes, smaller rv and hence larger B. I conclude that the data are consistent with rapid post-eruptive inflation driven by viscoelastic relaxation with a relatively incompressible magma, although other interpretations will be discussed.

  20. Alternative splicing: a novel mechanism of regulation identified in the chorismate mutase gene of the potato cyst nematode Globodera rostochiensis.

    PubMed

    Lu, Shun-Wen; Tian, Duanhua; Borchardt-Wier, Harmony B; Wang, Xiaohong

    2008-11-01

    Chorismate mutase (CM) secreted from the stylet of plant-parasitic nematodes plays an important role in plant parasitism. We isolated and characterized a new nematode CM gene (Gr-cm-1) from the potato cyst nematode, Globodera rostochiensis. The Gr-cm-1 gene was found to exist in the nematode genome as a single-copy gene that has two different alleles, Gr-cm-1A and Gr-cm-1B, both of which could give rise to two different mRNA transcripts of Gr-cm-1 and Gr-cm-1-IRII. In situ mRNA hybridization showed that the Gr-cm-1 gene was exclusively expressed within the subventral oesophageal gland cells of the nematode. Gr-cm-1 was demonstrated to encode a functional CM (GR-CM-1) potentially having a dimeric structure as the secreted bacterial *AroQ CMs. Gr-cm-1-IRII, generated by retention of intron 2 of the Gr-cm-1 pre-mRNA through alternative splicing (AS), would encode a truncated protein (GR-CM-1t) lacking the CM domain with no CM activity. The quantitative real-time reverse transcription-PCR assay revealed that splicing of the Gr-cm-1 gene was developmentally regulated; Gr-cm-1 was up-regulated whereas Gr-cm-1-IRII was down-regulated in early nematode parasitic stages compared to the preparasitic juvenile stage. Low-temperature SDS-PAGE analysis revealed that GR-CM-1 could form homodimers when expressed in Escherichia coli and the dimerization domain was retained in the truncated GR-CM-1t protein. The specific interaction between the two proteins was demonstrated in yeast. Our data suggested that the novel splice variant might function as a dominant negative isoform through heterodimerization with the full-length GR-CM-1 protein and that AS may represent an important mechanism for regulating CM activity during nematode parasitism.

  1. Cytological diagnosis of basal cell carcinoma and actinic keratosis, using Papanicolaou and May-Grünwald-Giemsa stained cutaneous tissue smear.

    PubMed

    Christensen, E; Bofin, A; Gudmundsdóttir, I; Skogvoll, E

    2008-10-01

    Cytology may become the diagnostic method of choice with the advent of new non-invasive treatments for non-melanoma skin cancer, as the sampling technique for cytology entails little tissue disfiguration. The aim of this study was to compare and evaluate the diagnostic performance of scrape cytology using two different cytological staining techniques, and to evaluate additional touch imprint cytology, with that of histopathology of basal cell carcinoma (BCC) and actinic keratosis (AK). We investigated 50 BCC and 28 AK histologically verified lesions, from 41 and 25 patients, respectively. Two separate skin scrape samples and one touch imprint sample were taken from each lesion. The smears were stained with Papanicolaou (Pap) or May-Grünwald-Giemsa (MGG) stains. All cytological specimens were examined in random order by pathologists without knowledge of the histology. Cytodiagnostic results were compared with the histopathological report. Scrape cytodiagnosis agreed with histopathology in 48 (Pap) and 47 (MGG) of the 50 BCC cases, and in 26 of 28 (Pap) and 21 of 26 (MGG) AK cases, yielding sensitivities of 96%, 94%, 93% and 81%, respectively. No significant difference in sensitivity between the two staining methods was found but a trend towards higher Pap sensitivity for AK was noted (P = 0.10). Touch imprint cytology confirmed histopathology in 38 of the 77 cases of BCC and AK. Cytological diagnosis with either Pap or MGG stain for BCC and AK is reliable, and differentiates well between BCC and AK. Imprint cytology proved to be non-diagnostic in half of the examined cases.

  2. Neonatal microbial colonization in mice promotes prolonged dominance of CD11b(+)Gr-1(+) cells and accelerated establishment of the CD4(+) T cell population in the spleen.

    PubMed

    Kristensen, Matilde B; Metzdorff, Stine B; Bergström, Anders; Damlund, Dina S M; Fink, Lisbeth N; Licht, Tine R; Frøkiær, Hanne

    2015-09-01

    To assess the microbial influence on postnatal hematopoiesis, we examined the role of early life microbial colonization on the composition of leukocyte subsets in the neonatal spleen. A high number of CD11b(+)Gr-1(+) splenocytes present perinatally was sustained for a longer period in conventionally colonized (CONV) mice than in mono-colonized (MC) and germfree (GF) mice, and the CD4(+) T cell population established faster in CONV mice. At the day of birth, compared to GF mice, the expression of Cxcl2 was up-regulated and Arg1 down-regulated in livers of CONV mice. This coincided with lower abundance of polylobed cells in the liver of CONV mice. An earlier peak in the expression of the genes Tjp1, Cdh1, and JamA in intestinal epithelial cells of CONV mice indicated an accelerated closure of the epithelial barrier. In conclusion, we have identified an important microbiota-dependent neonatal hematopoietic event, which we suggest impacts the subsequent development of the T cell population in the murine spleen.

  3. Long-Term Use of Probiotic-Containing Yogurts Is a Safe Way to Prevent Helicobacter pylori: Based on a Mongolian Gerbil's Model

    PubMed Central

    Kuo, Chao-Hung; Wang, Sophie S. W.; Lu, Chien-Yu; Hu, Huang-Ming; Kuo, Fu-Chen; Weng, Bi-Chuang; Wu, Chun-Chieh; Liu, Chung-Jung; Tsai, Pei-Yun; Lee, Tsung-Cheng; Chen, Li-Wei; Cheng, Kuang-Hung; Chang, Lin-Li; Wu, Deng-Chyang

    2013-01-01

    Background. The suppression of Helicobacter pylori (H. pylori) decreases H. pylori-related diseases. The probiotics have an inhibitory effect on H. pylori. Aim. We investigated the effects of long-term use of yogurt on H. pylori based on Mongolian gerbils' model. Materials and Methods. Yogurt (containing a supplement of Lactobacillus acidophilus, Bifidobacterium lactis, etc.) was used. Forty-six gerbils were divided into five groups. All groups were inoculated with H. pylori for 5 to 8 weeks. The yogurt was given as follows: Group (Gr.) A: from 1st to 4th week; Gr. B from 5th to 8th week; Gr. C: from 17th week to sacrifice; Gr. D: from 5th week to sacrifice. Gerbils were sacrificed on the 52nd week. Histology was evaluated according to the Sydney system. Results. The positive rates of H. pylori were 60% (Gr. A), 75% (Gr. B), 67% (Gr. C), 44% (Gr. D), and 100% (Gr. E). Gr. D showed lower inflammatory score. Only Gr. E (60%) had intestinal metaplasia. Gr. D showed higher IL-10 and lower TNF-α expression than Gr. E. Conclusion. Long-term intake of yogurt could decrease H. pylori infection. The long-term use of yogurt would be an alternative strategy to manage H. pylori infection. PMID:24349780

  4. Electrochemical sensors and biosensors based on less aggregated graphene.

    PubMed

    Bo, Xiangjie; Zhou, Ming; Guo, Liping

    2017-03-15

    As a novel single-atom-thick sheet of sp 2 hybridized carbon atoms, graphene (GR) has attracted extensive attention in recent years because of its unique and remarkable properties, such as excellent electrical conductivity, large theoretical specific surface area, and strong mechanical strength. However, due to the π-π interaction, GR sheets are inclined to stack together, which may seriously degrade the performance of GR with the unique single-atom layer. In recent years, an increasing number of GR-based electrochemical sensors and biosensors are reported, which may reflect that GR has been considered as a kind of hot and promising electrode material for electrochemical sensor and biosensor construction. However, the active sites on GR surface induced by the irreversible GR aggregations would be deeply secluded inside the stacked GR sheets and therefore are not available for the electrocatalysis. So the alleviation or the minimization of the aggregation level for GR sheets would facilitate the exposure of active sites on GR and effectively upgrade the performance of GR-based electrochemical sensors and biosensors. Less aggregated GR with low aggregation and high dispersed structure can be used in improving the electrochemical activity of GR-based electrochemical sensors or biosensors. In this review, we summarize recent advances and new progress for the development of electrochemical sensors based on less aggregated GR. To achieve such goal, many strategies (such as the intercalation of carbon materials, surface modification, and structural engineering) have been applied to alleviate the aggregation level of GR in order to enhance the performance of GR-based electrochemical sensors and biosensors. Finally, the challenges associated with less aggregated GR-based electrochemical sensors and biosensors as well as related future research directions are discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Arbitrary conditional discriminative functions of meaningful stimuli and enhanced equivalence class formation.

    PubMed

    Nedelcu, Roxana I; Fields, Lanny; Arntzen, Erik

    2015-03-01

    Equivalence class formation by college students was influenced through the prior acquisition of conditional discriminative functions by one of the abstract stimuli (C) in the to-be-formed classes. Participants in the GR-0, GR-1, and GR-5 groups attempted to form classes under the simultaneous protocol, after mastering 0, 1, or 5 conditional relations between C and other abstract stimuli (V, W, X, Y, Z) that were not included in the to-be-formed classes (ABCDE). Participants in the GR-many group attempted to form classes that contained four abstract stimuli and one meaningful picture as the C stimulus. In the GR-0, GR-1, GR-5, and GR-many groups, classes were formed by 17, 25, 58, and 67% of participants, respectively. Thus, likelihood of class formation was enhanced by the prior formation of five C-based conditional relations (the GR-5 vs. GR-0 condition), or the inclusion of a meaningful stimulus as a class member (the GR-many vs. GR-0 condition). The GR-5 and GR-many conditions produced very similar yields, indicating that class formation was enhanced to a similar degree by including a meaningful stimulus or an abstract stimulus that had become a member of five conditional relations prior to equivalence class formation. Finally, the low and high yields produced by the GR-1 and GR-5 conditions showed that the class enhancement effect of the GR-5 condition was due to the number of conditional relations established during preliminary training and not to the sheer amount of reinforcement provided while learning these conditional relations. Class enhancement produced by meaningful stimuli, then, can be attributed to their acquired conditional discriminative functions as well as their discriminative, connotative, and denotative properties. © Society for the Experimental Analysis of Behavior.

  6. The effect of various concentration of tilapia (Oreochromis sp.) surimi for edible coating on the shelf-life of Pangasius sp. fillets

    NASA Astrophysics Data System (ADS)

    Purnama, M. A. P.; Agustono; Sahidu, A. M.

    2018-04-01

    Pangasius sp. fillets prone to deterioration the quality that will affect the appearance and the shelf life of fillets. The effort to extend the shelf life of fish fillet that is by using an edible coating. Surimi can be used as a protein-based edible coating because they have superior inhibitory and mechanical properties compared to the polysaccharides based material. Surimi can be made from freshwater tilapia (Oreochromis sp.) fish. The experimental design used was Completely Randomized Design (CRD) with five treatments of surimi (0 gr, 2 gr, 4 gr, 6 gr, 8 gr) with four replications. The results showed that Pangasius sp. fillets with an edible coating 8 gr surimi have the highest value in the organoleptic test. The pH testing on Pangasius sp. fillets with edible coating 2 gr, 4 gr, 6 gr, and 8 gr surimi from the 0th hour to 18th hour have increased but slower than Pangasius sp. fillets without edible coating surimi. The best value of Total Plate Count (TPC) test is in edible coating 6 gr and 8 gr surimi as it is in accordance with SNI 2696:2013 at room temperature storage until the 18th hours.

  7. The enhanced efficiency of graphene-silicon solar cells by electric field doping.

    PubMed

    Yu, Xuegong; Yang, Lifei; Lv, Qingmin; Xu, Mingsheng; Chen, Hongzheng; Yang, Deren

    2015-04-28

    The graphene-silicon (Gr-Si) Schottky junction solar cell has been recognized as one of the most low-cost candidates in photovoltaics due to its simple fabrication process. However, the low Gr-Si Schottky barrier height largely limits the power conversion efficiency of Gr-Si solar cells. Here, we demonstrate that electric field doping can be used to tune the work function of a Gr film and therefore improve the photovoltaic performance of the Gr-Si solar cell effectively. The electric field doping effects can be achieved either by connecting the Gr-Si solar cell to an external power supply or by polarizing a ferroelectric polymer layer integrated in the Gr-Si solar cell. Exploration of both of the device architecture designs showed that the power conversion efficiency of Gr-Si solar cells is more than twice of the control Gr-Si solar cells. Our study opens a new avenue for improving the performance of Gr-Si solar cells.

  8. On the fractional Eulerian numbers and equivalence of maps with long term power-law memory (integral Volterra equations of the second kind) to Grünvald-Letnikov fractional difference (differential) equations.

    PubMed

    Edelman, Mark

    2015-07-01

    In this paper, we consider a simple general form of a deterministic system with power-law memory whose state can be described by one variable and evolution by a generating function. A new value of the system's variable is a total (a convolution) of the generating functions of all previous values of the variable with weights, which are powers of the time passed. In discrete cases, these systems can be described by difference equations in which a fractional difference on the left hand side is equal to a total (also a convolution) of the generating functions of all previous values of the system's variable with the fractional Eulerian number weights on the right hand side. In the continuous limit, the considered systems can be described by the Grünvald-Letnikov fractional differential equations, which are equivalent to the Volterra integral equations of the second kind. New properties of the fractional Eulerian numbers and possible applications of the results are discussed.

  9. Brain-Derived Neurotrophic Factor Signaling Rewrites the Glucocorticoid Transcriptome via Glucocorticoid Receptor Phosphorylation

    PubMed Central

    Lambert, W. Marcus; Xu, Chong-Feng; Neubert, Thomas A.; Chao, Moses V.

    2013-01-01

    Abnormal glucocorticoid and neurotrophin signaling has been implicated in numerous psychiatric disorders. However, the impact of neurotrophic signaling on glucocorticoid receptor (GR)-dependent gene expression is not understood. We therefore examined the impact of brain-derived neurotrophic factor (BDNF) signaling on GR transcriptional regulatory function by gene expression profiling in primary rat cortical neurons stimulated with the selective GR agonist dexamethasone (Dex) and BDNF, alone or in combination. Simultaneous treatment with BDNF and Dex elicited a unique set of GR-responsive genes associated with neuronal growth and differentiation and also enhanced the induction of a large number of Dex-sensitive genes. BDNF via its receptor TrkB enhanced the transcriptional activity of a synthetic GR reporter, suggesting a direct effect of BDNF signaling on GR function. Indeed, BDNF treatment induces the phosphorylation of GR at serine 155 (S155) and serine 287 (S287). Expression of a nonphosphorylatable mutant (GR S155A/S287A) impaired the induction of a subset of BDNF- and Dex-regulated genes. Mechanistically, BDNF-induced GR phosphorylation increased GR occupancy and cofactor recruitment at the promoter of a BDNF-enhanced gene. GR phosphorylation in vivo is sensitive to changes in the levels of BDNF and TrkB as well as stress. Therefore, BDNF signaling specifies and amplifies the GR transcriptome through a coordinated GR phosphorylation-dependent detection mechanism. PMID:23878391

  10. The Microtubule-Associated Protein Doublecortin-Like Regulates the Transport of the Glucocorticoid Receptor in Neuronal Progenitor Cells

    PubMed Central

    Fitzsimons, Carlos P.; Ahmed, Suaad; Wittevrongel, Christiaan F. W.; Schouten, Theo G.; Dijkmans, Thomas F.; Scheenen, Wim J. J. M.; Schaaf, Marcel J. M.; Ronald de Kloet, E.; Vreugdenhil, Erno

    2008-01-01

    In neuronal cells, activated glucocorticoid receptor (GR) translocates to the nucleus guided by the cytoskeleton. However, the detailed mechanisms underlying GR translocation remain unclear. Using gain and loss of function studies, we report here for the first time that the microtubule-associated protein doublecortin-like (DCL) controls GR translocation to the nucleus. DCL overexpression in COS-1 cells, neuroblastoma cells, and rat hippocampus organotypic slice cultures impaired GR translocation and decreased GR-dependent transcriptional activity, measured by a specific reporter gene assay, in COS-1 cells. Moreover, DCL and GR directly interact on microtubule bundles formed by DCL overexpression. A C-terminal truncated DCL with conserved microtubule-bundling activity did not influence GR translocation. In N1E-115 mouse neuroblastoma cells and neuronal progenitor cells in rat hippocampus organotypic slice cultures, laser-scanning confocal microscopy showed colabeling of endogenously expressed DCL and GR. In these systems, RNA-interference-mediated DCL knockdown hampered GR translocation. Thus, we conclude that DCL expression is tightly regulated to adequately control GR transport. Because DCL is primarily expressed in neuronal progenitor cells, our results introduce this microtubule-associated protein as a new modulator of GR signaling in this cell type and suggest the existence of cell-specific mechanisms regulating GR translocation to the nucleus. PMID:17975023

  11. Glyphosate Effects on Plant Mineral Nutrition, Crop Rhizosphere Microbiota, and Plant Disease in Glyphosate-Resistant Crops

    PubMed Central

    2012-01-01

    Claims have been made recently that glyphosate-resistant (GR) crops sometimes have mineral deficiencies and increased plant disease. This review evaluates the literature that is germane to these claims. Our conclusions are: (1) although there is conflicting literature on the effects of glyphosate on mineral nutrition on GR crops, most of the literature indicates that mineral nutrition in GR crops is not affected by either the GR trait or by application of glyphosate; (2) most of the available data support the view that neither the GR transgenes nor glyphosate use in GR crops increases crop disease; and (3) yield data on GR crops do not support the hypotheses that there are substantive mineral nutrition or disease problems that are specific to GR crops. PMID:23013354

  12. Biogenic hydroxysulfate green rust, a potential electron acceptor for SRB activity

    NASA Astrophysics Data System (ADS)

    Zegeye, Asfaw; Huguet, Lucie; Abdelmoula, Mustapha; Carteret, Cédric; Mullet, Martine; Jorand, Frédéric

    2007-11-01

    Microbiological reduction of a biogenic sulfated green rust (GR2(SO42-)), was examined using a sulfate reducing bacterium ( Desulfovibrio alaskensis). Experiments investigated whether GR2(SO42-) could serve as a sulfate source for D. alaskensis anaerobic respiration by analyzing mineral transformation. Batch experiments were conducted using lactate as the electron donor and biogenic GR2(SO42-) as the electron acceptor, at circumneutral pH in unbuffered medium. GR2(SO42-) transformation was monitored with time by X-ray diffraction (XRD), Transmission Mössbauer Spectroscopy (TMS), Diffuse Reflectance Infrared Fourier Transform Spectroscopy (DRIFTS), Transmission Electron Microscopy (TEM) and X-ray Photoelectron Spectroscopy (XPS). The reduction of sulfate anions and the formation of iron sulfur mineral were clearly identified by XPS analyses. TMS showed the formation of additional mineral as green rust (GR) and vivianite. XRD analyses discriminated the type of the newly formed GR as GR1. The formed GR1 was GR1(CO32-) as indicated by DRIFTS analysis. Thus, the results presented in this study indicate that D. alaskensis cells were able to use GR2(SO42-) as an electron acceptor. GR1(CO32-), vivianite and an iron sulfur compound were formed as a result of GR2(SO42-) reduction by D. alaskensis. Hence, in environments where geochemical conditions promote biogenic GR2(SO42-) formation, this mineral could stimulate the anaerobic respiration of sulfate reducing bacteria.

  13. Addition of Lubiprostone to polyethylene glycol(PEG) enhances the quality & efficacy of colonoscopy preparation: a randomized, double-blind, placebo controlled trial.

    PubMed

    Banerjee, Rupa; Chaudhari, Hrushikesh; Shah, Nirish; Saravanan, Arjunan; Tandan, Manu; Reddy, D Nageshwar

    2016-10-13

    Adequate bowel preparation is an essential prerequisite for complete mucosal visualization during colonoscopy. Polyethylene glycol (PEG) solutions are commonly used. However the large volume of the solution is often poorly tolerated. Addition of Lubiprostone (LB) could improve the adequacy of standard PEG preparation & reduce requirement. The aims to assess adequacy of PEG preparation with addition of single dose LB (24mcg) vs placebo and efficacy of reduced dose PEG + LB compared with full dose PEG + LB. Single center prospective double blind randomized controlled trial. Part I: 442 patients for colonoscopy randomized to receive placebo (GrA) or single dose of LB (GrB) prior to PEG preparation. Quality of bowel preparation graded 0-9 according to Boston Bowel Preparation Scale (BBPS). BBPS-9: excellent and BBPS 0-4: repeat procedure. Part II: 146 patients randomized to receive LB + 1.5 L PEG (GrC; 75) or LB + 1 L PEG (GrD; 71). BBPS score compared with GrB (2 L PEG). Part I: 442 patients (221 GrA & 221 Gr B). LB resulted in significant improvement in total BBPS (7.44 + 0.14 vs. 6.36 + 0.16, p < 0.0001). 66.5 % Gr B vs 38 % Gr A had excellent prep; 42.5 % GrB vs 24 % GrA had adequate prep. Repeat procedure needed 9.5 % Gr B vs 16.7 % Gr A (P < 0.01). Part II: No difference in BBPS scores with lower doses (Gr C&D) compared to standard (GrB) (Mean BBPS 7.44 + 0.14 GrA,7.30 + 0.25 GrC;7.25 + 0.26 GrD;p >0.05). Single dose LB prior to PEG significantly enhanced bowel preparation compared to PEG alone. There was no significant difference in quality of preparation with lower doses of PEG when combined with LB. The study protocol was approved by institutional review board and the trial was registered on March 22, 2011 with clinicaltrials.gov ( NCT01324284 ).

  14. Investigation of thermal energy transport interface of hybrid graphene-carbon nanotube/polyethylene nanocomposites.

    PubMed

    Liu, Feng; Liu, Xuyang; Hu, Ning; Ning, Huiming; Atobe, Satoshi; Yan, Cheng; Mo, Fuhao; Fu, Shaoyun; Zhang, Jianyu; Wang, Yu; Mu, Xiaojing

    2017-10-31

    It is well known the thermal properties of three-dimensional (3-D) hybrid graphene (GR)-carbon nanotube (CNT) structures are not superior to that of the individual GR and CNT, however, the 3-D hybrid GR-CNT structures can effectively improve the thermal properties of polymer matrix. Therefore, understanding the thermal energy transport in the interface between polymer matrix and 3-D hybrid GR-CNT structure is essential. Here, the enhancement mechanism of interfacial thermal transport of hybrid GR-CNT structure was explored by applying non-equilibrium molecular dynamics (NEMD) simulations. Three different types of hybrid GR-CNT structures were built. The influences of CNT radius and CNT type for the hybrid GR-CNT on the interfacial thermal properties were also analyzed. Computational results show that among the three different types of hybrid GR-CNT structures, the Model-I, i.e., the covalent bond hybrid GR-CNT structures are of the best interfacial thermal properties. Meanwhile, the CNT radius of hybrid GR-CNT structure has a great influence on the interfacial thermal properties.

  15. Differential effects of the new glucocorticoid receptor antagonist ORG 34517 and RU486 (mifepristone) on glucocorticoid receptor nuclear translocation in the AtT20 cell line.

    PubMed

    Peeters, B W M M; Ruigt, G S F; Craighead, M; Kitchener, P

    2008-12-01

    Glucocorticoid agonists bind to cytoplasmic glucocorticoid receptors (GRs) and subsequently translocate as an agonist-GR complex into the nucleus. In the nucleus the complex regulates the transcription of target genes. A number of GR antagonists (RU486, progesterone, RU40555) have also been shown to induce receptor translocation. These compounds should be regarded as partial agonists. For the nonselective progesterone receptor antagonists, RTI3021-012 and RTI3021-022, it was shown that GR antagonism is possible without the induction of GR translocation. In the present studies, the new GR antagonist, ORG 34517, was investigated for its potential to induce GR translocation and to antagonize corticosterone-induced GR translocation in the AtT20 (mouse pituitary) cell line. ORG 34517 was compared to RU486. In contrast to RU486, ORG 34517 (at doses up to 3 x 10(-7) M) did not induce GR translocation, but was able to block corticosterone (3 x 10(-8) M) induced GR translocation. ORG 34517 can be regarded as a true competitive GR antagonist without partial agonistic activities.

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

    Li, Qun-Yi; Zhang, Meng; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai

    Selective antagonists of the glucocorticoid receptor (GR) are desirable for the treatment of hypercortisolemia associated with Cushing's syndrome, psychic depression, obesity, diabetes, neurodegenerative diseases, and glaucoma. NC3327, a non-steroidal small molecule with potent binding affinity to GR (K{sub i} = 13.2 nM), was identified in a high-throughput screening effort. As a full GR antagonist, NC3327 greatly inhibits the dexamethasone (Dex) induction of marker genes involved in hepatic gluconeogenesis, but has a minimal effect on matrix metalloproteinase 9 (MMP-9), a GR responsive pro-inflammatory gene. Interestingly, the compound recruits neither coactivators nor corepressors to the GR complex but competes with glucocorticoids formore » the interaction between GR and a coactivator peptide. Moreover, NC3327 does not trigger GR nuclear translocation, but significantly blocks Dex-induced GR transportation to the nucleus, and thus appears to be a 'competitive' GR antagonist. Therefore, the non-steroidal compound, NC3327, may represent a new class of GR antagonists as potential therapeutics for a variety of cortisol-related endocrine disorders.« less

  17. Autoregulation of human relaxin-2 gene expression critically involves relaxin and glucocorticoid receptor binding to glucocorticoid response half-sites in the relaxin-2 promoter.

    PubMed

    Dschietzig, Thomas; Bartsch, Cornelia; Wessler, Silja; Baumann, Gert; Stangl, Karl

    2009-06-05

    Relaxin peptides act in brain, reproductive and cardiovascular systems, kidneys, and connective tissue through different G protein-coupled receptors. We reported that human relaxin-2 and porcine relaxin are both agonists at the human glucocorticoid receptor (GR). Here, we investigated the possible auto-regulation of relaxin-2 gene expression via recently discovered GR-binding sites in the relaxin-2 promoter. We found that porcine relaxin increased the secretion of human relaxin-like immunoreactivity in HeLa and THP-1 cells. Silencing of GR gene expression completely abolished this effect whereas transfection of wild-type GR into naturally GR-devoid HT-29 cells established relaxin sensitivity. Relaxin was shown to stimulate CAT expression driven by different deletion constructs of the 5'-flanking region of the relaxin-2 promoter. In chromatin immunoprecipitation assays, we detected both GR and relaxin binding to the relaxin-2 promoter. Gel shift assays indicated binding of relaxin-activated GR to half-GREs located between 160 and 200 bp upstream of transcription start but not to the GRE at -900 bp. Relaxin bound to human GR and displaced established GR agonists. Immunofluorescence experiments visualized nuclear co-localization of relaxin and GR in response to relaxin. In conclusion, we have identified a positive auto-regulatory loop of human relaxin-2 expression which involves GR and relaxin/GR binding to half-GREs in the relaxin-2 promoter.

  18. Improving the photocatalytic performance of graphene-TiO2 nanocomposites via a combined strategy of decreasing defects of graphene and increasing interfacial contact.

    PubMed

    Zhang, Yanhui; Zhang, Nan; Tang, Zi-Rong; Xu, Yi-Jun

    2012-07-07

    Incessant interest has been shown in the synthesis of graphene (GR)-semiconductor nanocomposites as photocatalysts aiming to utilize the excellent electron conductivity of GR to lengthen the lifetime of photoexcited charge carriers in the semiconductor and, hence, improve the photoactivity. However, research works focused on investigating how to make sufficient use of the unique electron conductivity of GR to design a more efficient GR-semiconductor photocatalyst have been quite lacking. Here, we show a proof-of-concept study on improving the photocatalytic performance of GR-TiO(2) nanocomposites via a combined strategy of decreasing defects of GR and improving the interfacial contact between GR and the semiconductor TiO(2). The GR-TiO(2) nanocomposite fabricated by this approach is able to make more sufficient use of the electron conductivity of GR, by which the lifetime and transfer of photoexcited charge carriers of GR-TiO(2) upon visible light irradiation will be improved more efficiently. This in turn leads to the enhancement of visible-light-driven photoactivity of GR-TiO(2) toward selective transformation of alcohols to corresponding aldehydes using molecular oxygen as a benign oxidant under ambient conditions. It is anticipated that our current work would inform ongoing efforts to exploit the rational design of smart, more efficient GR-semiconductor photocatalysts for conversion of solar to chemical energy by heterogeneous photocatalysis.

  19. Purification and properties of glutathione reductase from liver of the anoxia-tolerant turtle, Trachemys scripta elegans.

    PubMed

    Willmore, William G; Storey, Kenneth B

    2007-03-01

    Glutathione reductase (GR) is a homodimeric flavoprotein that catalyzes the reduction of oxidized glutathione (GSSG) using NADPH as a cofactor. The enzyme is a major component of cellular defense mechanisms against oxidative injury. In this study, GR was purified from the liver of the anoxia-tolerant turtle, Trachemys scripta elegans. The overall fold purifications were 13.3- and 12.1-fold with final specific activities of 5.5 and 1.44 U/mg of protein for control and anoxic turtle GR, respectively. SDS-PAGE of purified turtle liver GR showed a single protein band at approximately 55 kDa. Reverse phase HPLC of turtle GR revealed a single peak that had the same retention time as yeast GR. No new isoform of GR was detected in liver of T. s. elegans during anoxia. The K (m) values of turtle GR for GSSG and NADPH was 44.6 and 6.82 microM, respectively, suggesting a substantially higher affinity of turtle GR toward GSSG than most other vertebrates. Unlike other human GR, NADP(+ )did not inhibit turtle GR activity. The activation energy of turtle GR, calculated from the slope of the Arrhenius plot, was 32.2 +/- 2.64 kJ/mol. Turtle GR had high activity under a broad pH range (having activity between pHs 4 and 10; optimal activity at pH 6.5) and the enzyme maintains activity under the pH drop that occurs under anoxic conditions. The high affinity of turtle GR suggests that turtles have high redox buffering capacity of tissues to protect against oxidative stress encountered during anoxia/reoxygenation.

  20. Intracellular Serine Protease Inhibitor SERPINB4 Inhibits Granzyme M-Induced Cell Death

    PubMed Central

    de Koning, Pieter J. A.; Kummer, J. Alain; de Poot, Stefanie A. H.; Quadir, Razi; Broekhuizen, Roel; McGettrick, Anne F.; Higgins, Wayne J.; Devreese, Bart; Worrall, D. Margaret; Bovenschen, Niels

    2011-01-01

    Granzyme-mediated cell death is the major pathway for cytotoxic lymphocytes to kill virus-infected and tumor cells. In humans, five different granzymes (i.e. GrA, GrB, GrH, GrK, and GrM) are known that all induce cell death. Expression of intracellular serine protease inhibitors (serpins) is one of the mechanisms by which tumor cells evade cytotoxic lymphocyte-mediated killing. Intracellular expression of SERPINB9 by tumor cells renders them resistant to GrB-induced apoptosis. In contrast to GrB, however, no physiological intracellular inhibitors are known for the other four human granzymes. In the present study, we show that SERPINB4 formed a typical serpin-protease SDS-stable complex with both recombinant and native human GrM. Mutation of the P2-P1-P1′ triplet in the SERPINB4 reactive center loop completely abolished complex formation with GrM and N-terminal sequencing revealed that GrM cleaves SERPINB4 after P1-Leu. SERPINB4 inhibited GrM activity with a stoichiometry of inhibition of 1.6 and an apparent second order rate constant of 1.3×104 M−1s−1. SERPINB4 abolished cleavage of the macromolecular GrM substrates α-tubulin and nucleophosmin. Overexpression of SERPINB4 in tumor cells inhibited recombinant GrM-induced as well as NK cell-mediated cell death and this inhibition depended on the reactive center loop of the serpin. As SERPINB4 is highly expressed by squamous cell carcinomas, our results may represent a novel mechanism by which these tumor cells evade cytotoxic lymphocyte-induced GrM-mediated cell death. PMID:21857942

  1. Meat quality, proximate composition and muscle fatty acid profile of young llamas (Lama glama) supplemented with hay or concentrate during the dry season.

    PubMed

    Mamani-Linares, L W; Gallo, C B

    2014-01-01

    Thirty llamas were used to study the effect of a 90 day feed supplementation on meat quality, chemical composition and muscle fatty acid profile. Treatments were: GR=llama on native pasture until slaughter; GR+SH=like GR, but with overnight free access to barley/alfalfa hay; and GR+SC=like GR, but with overnight free access to a wheat bran/sorghum grain concentrate. The supplementation had no effect on postmortem pH and temperature decline in the Longissimus lumborum muscle (LLM), cooking losses nor Warner-Bratzler shear force values (P>0.05). Meat from GR+SC llama had higher fat content in LLM (P<0.05) compared to GR and GR+SH llama. Intramuscular fat from GR+SH llama showed higher (P<0.01) proportions of polyunsaturated fatty acids, higher (P<0.05) polyunsaturated fatty acids/saturated fatty acids and desirable fatty acids ratio, lower (P<0.05) omega-6/omega-3 (n-6/n-3) ratio, and higher (P<0.01) conjugated linoleic acid. © 2013.

  2. Negative Correlation between the Diffusion Coefficient and Transcriptional Activity of the Glucocorticoid Receptor.

    PubMed

    Mikuni, Shintaro; Yamamoto, Johtaro; Horio, Takashi; Kinjo, Masataka

    2017-08-25

    The glucocorticoid receptor (GR) is a transcription factor, which interacts with DNA and other cofactors to regulate gene transcription. Binding to other partners in the cell nucleus alters the diffusion properties of GR. Raster image correlation spectroscopy (RICS) was applied to quantitatively characterize the diffusion properties of EGFP labeled human GR (EGFP-hGR) and its mutants in the cell nucleus. RICS is an image correlation technique that evaluates the spatial distribution of the diffusion coefficient as a diffusion map. Interestingly, we observed that the averaged diffusion coefficient of EGFP-hGR strongly and negatively correlated with its transcriptional activities in comparison to that of EGFP-hGR wild type and mutants with various transcriptional activities. This result suggests that the decreasing of the diffusion coefficient of hGR was reflected in the high-affinity binding to DNA. Moreover, the hyper-phosphorylation of hGR can enhance the transcriptional activity by reduction of the interaction between the hGR and the nuclear corepressors.

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

    Togi, Sumihito; Nakasuji, Misa; Muromoto, Ryuta

    Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded latency-associated nuclear antigen (LANA), which interacts with cellular proteins, plays a central role in modification of viral and/or cellular gene expression. Here, we show that LANA associates with glucocorticoid receptor (GR), and that LANA enhances the transcriptional activity of GR. Co-immunoprecipitation revealed a physical interaction between LANA and GR in transiently transfected 293T and HeLa cells. In human B-lymphoma cells, LANA overexpression enhanced GR activity and cell growth suppression following glucocorticoid stimulation. Furthermore, confocal microscopy showed that activated GR was bound to LANA and accumulated in the nucleus, leading to an increase in binding of activatedmore » GR to the glucocorticoid response element of target genes. Taken together, KSHV-derived LANA acts as a transcriptional co-activator of GR. Our results might suggest a careful use of glucocorticoids in the treatment of patients with KSHV-related malignancies such as Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman disease. - Highlights: • KSHV-LANA enhances the transcriptional activity of GR in 293T and HeLa cells. • KSHV-LANA physically associates with GR. • KSHV-LANA enhances GR activation and cell growth suppression in human B-lymphocytes. • KSHV-LANA influences the nuclear retention and DNA binding activity of GR.« less

  4. Engineering the unique 2D mat of graphene to achieve graphene-TiO2 nanocomposite for photocatalytic selective transformation: what advantage does graphene have over its forebear carbon nanotube?

    PubMed

    Zhang, Yanhui; Tang, Zi-Rong; Fu, Xianzhi; Xu, Yi-Jun

    2011-09-27

    Increasing interest has been devoted to synthesizing graphene (GR)-semiconductor nanocomposites as photocatalysts for potential applications, which is very similar to its forebear carbon nanotube (CNT)-semiconductor photocatalysts. Unfortunately, a thoughtful and inevitable comparison between GR- and CNT-semiconductors as photocatalysts is often neglected in literature. This situation may give incomplete or exaggerated information on the contribution role of GR to enhance the semiconductor photocatalytic activity, as compared to CNT. Thus, our knowledge regarding the specific advantage of GR over CNT on how to design more efficient GR-semiconductor nanocomposites and understanding the origin of their enhanced photocatalytic performance is far from satisfactory. By taking the TiO(2) semiconductor as an example, we conceptually demonstrate how to synthesize a more efficient GR-TiO(2) nanocomposite as a visible light photocatalyst toward selective oxidation of alcohols under mild conditions. Comparison between GR-TiO(2) and CNT-TiO(2) discloses the prominent advantage of GR over CNT on both controlling the morphology of GR-TiO(2) nanocomposite and enhancing the photocatalytic activity of TiO(2). This work clearly highlights the importance and necessity for a comparison investigation between GR- and CNT-semiconductors as photocatalysts, which will promote our in-depth fundamental understanding on the analogy and difference between GR and CNT on controlling the morphology of GR (or CNT)-semiconductor nanocomposites and enhancing the photocatalytic performance. Therefore, we appeal the photocatalysis community to pay attention to this respect rather than separately imposing hype on the miracle of GR in much the same way as its carbon forebears, which could significantly advance our rational fabrication of smart GR-semiconductor nanocomposites for artificial photosynthesis. © 2011 American Chemical Society

  5. Ray-tracing in pseudo-complex General Relativity

    NASA Astrophysics Data System (ADS)

    Schönenbach, T.; Caspar, G.; Hess, P. O.; Boller, T.; Müller, A.; Schäfer, M.; Greiner, W.

    2014-07-01

    Motivated by possible observations of the black hole candidate in the centre of our Galaxy and the galaxy M87, ray-tracing methods are applied to both standard General Relativity (GR) and a recently proposed extension, the pseudo-complex GR (pc-GR). The correction terms due to the investigated pc-GR model lead to slower orbital motions close to massive objects. Also the concept of an innermost stable circular orbit is modified for the pc-GR model, allowing particles to get closer to the central object for most values of the spin parameter a than in GR. Thus, the accretion disc, surrounding a massive object, is brighter in pc-GR than in GR. Iron Kα emission-line profiles are also calculated as those are good observables for regions of strong gravity. Differences between the two theories are pointed out.

  6. Molecular and Functional Characterization of GR2-R1 Event Based Backcross Derived Lines of Golden Rice in the Genetic Background of a Mega Rice Variety Swarna

    PubMed Central

    Bollinedi, Haritha; S., Gopala Krishnan; Prabhu, Kumble Vinod; Singh, Nagendra Kumar; Mishra, Sushma; Khurana, Jitendra P.; Singh, Ashok Kumar

    2017-01-01

    Homozygous Golden Rice lines developed in the background of Swarna through marker assisted backcross breeding (MABB) using transgenic GR2-R1 event as a donor for the provitamin A trait have high levels of provitamin A (up to 20 ppm) but are dwarf with pale green leaves and drastically reduced panicle size, grain number and yield as compared to the recurrent parent, Swarna. In this study, we carried out detailed morphological, biochemical and molecular characterization of these lines in a quest to identify the probable reasons for their abnormal phenotype. Nucleotide blast analysis with the primer sequences used to amplify the transgene revealed that the integration of transgene disrupted the native OsAux1 gene, which codes for an auxin transmembrane transporter protein. Real time expression analysis of the transgenes (ZmPsy and CrtI) driven by endosperm-specific promoter revealed the leaky expression of the transgene in the vegetative tissues. We propose that the disruption of OsAux1 disturbed the fine balance of plant growth regulators viz., auxins, gibberellic acid and abscisic acid, leading to the abnormalities in the growth and development of the lines homozygous for the transgene. The study demonstrates the conserved roles of OsAux1 gene in rice and Arabidopsis. PMID:28068433

  7. Molecular and Functional Characterization of GR2-R1 Event Based Backcross Derived Lines of Golden Rice in the Genetic Background of a Mega Rice Variety Swarna.

    PubMed

    Bollinedi, Haritha; S, Gopala Krishnan; Prabhu, Kumble Vinod; Singh, Nagendra Kumar; Mishra, Sushma; Khurana, Jitendra P; Singh, Ashok Kumar

    2017-01-01

    Homozygous Golden Rice lines developed in the background of Swarna through marker assisted backcross breeding (MABB) using transgenic GR2-R1 event as a donor for the provitamin A trait have high levels of provitamin A (up to 20 ppm) but are dwarf with pale green leaves and drastically reduced panicle size, grain number and yield as compared to the recurrent parent, Swarna. In this study, we carried out detailed morphological, biochemical and molecular characterization of these lines in a quest to identify the probable reasons for their abnormal phenotype. Nucleotide blast analysis with the primer sequences used to amplify the transgene revealed that the integration of transgene disrupted the native OsAux1 gene, which codes for an auxin transmembrane transporter protein. Real time expression analysis of the transgenes (ZmPsy and CrtI) driven by endosperm-specific promoter revealed the leaky expression of the transgene in the vegetative tissues. We propose that the disruption of OsAux1 disturbed the fine balance of plant growth regulators viz., auxins, gibberellic acid and abscisic acid, leading to the abnormalities in the growth and development of the lines homozygous for the transgene. The study demonstrates the conserved roles of OsAux1 gene in rice and Arabidopsis.

  8. Seismic tremor signals from Bárðarbunga, Grímsvötn and other glacier covered volcanoes in Iceland's Vatnajökull ice cap

    NASA Astrophysics Data System (ADS)

    Vogfjörd, Kristin S.; Eibl, Eva; Bean, Chris; Roberts, Matthew; Ófeigsson, Benedikt; Jóhannesson, Tómas

    2016-04-01

    Many of Iceland's most active volcanoes, like Grímsvötn and Bárðarbunga are located under glaciers giving rise to a range of volcanic hazards having both local and cross-border effects on humans, infrastructures and aviation. Volcanic eruptions under ice can lead to explosive hydromagmatic volcanism and generate small to catastrophic subglacial floods that may take hours to days to emerge from the glacier edge. Unrest in subglacial hydrothermal systems and the draining of subglacial meltwater can also lead to flood hazards. These processes and magma-ice interactions in general, generate seismic tremor signals that are commonly observed on seismic systems during volcanic unrest and/or eruptions. The tremor signals exhibit certain characteristics in frequency content, amplitude and behavior with time, but their characteristics overlap. Ability to discriminate between the different processes in real-time or near-real time can support early eruption and flood warnings and help mitigate their detrimental effects. One of the goals set forth in the FUTUREVOLC volcano supersite project was in fact to understand and discriminate between the different types of seismic tremor recorded at subglacial volcanoes. In that pursuit, the seismic network was expanded into the Vatnajökull glacier with four permanent stations on rock and in the ice, in addition to three seismic arrays installed at the ice margin, to enable location and possible tracking of the tremor sources. To track subglacial floods with better resolution three GPS receivers were also installed on the ice, one in an ice cauldron above the Skaftárkatlar geothermal melting area and two down glacier, above the track of the expected subglacial flood. During FUTUREVOLC this infrastructure has recorded all the types of process expected: Magmatic dyke intrusion and propagation from Bárðarbunga, subaerial fissure eruption of that magma at Holuhraun, two subglacial floods, one small and one large, draining from the

  9. Cobalt nanoparticles/nitrogen-doped graphene with high nitrogen doping efficiency as noble metal-free electrocatalysts for oxygen reduction reaction.

    PubMed

    Liang, Jingwen; Hassan, Mehboob; Zhu, Dongsheng; Guo, Liping; Bo, Xiangjie

    2017-03-15

    Nitrogen-doped graphene (N/GR) has been considered as active metal-free electrocatalysts for oxygen reduction reaction (ORR). However, the nitrogen (N) doping efficiency is very low and only few N atoms are doped into the framework of GR. To boost the N doping efficiency, in this work, a confined pyrolysis method with high N doping efficiency is used for the preparation of cobalt nanoparticles/nitrogen-doped GR (Co/N/GR). Under the protection of SiO 2 , the inorganic ligand NH 3 in cobalt amine complex ([Co(NH 3 ) 6 ] 3+ ) is trapped in the confined space and then can be effectively doped into the framework of GR without the introduction of any carbon residues. Meanwhile, due to the redox reaction between the cobalt ions and carbon atoms of GR, Co nanoparticles are supported into the framework of N/GR. Due to prevention of GR layer aggregation with SiO 2 , the Co/N/GR with high dispersion provides sufficient surface area and maximum opportunity for the exposure of Co nanoparticles and active sites of N dopant. By combination of enhanced N doping efficiency, Co nanoparticles and high dispersion of GR sheets, the Co/N/GR is remarkably active, cheap and selective noble-metal free catalysts for ORR. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Selected physico-mechanical characteristics of cryogenic and ambient ground turmeric

    NASA Astrophysics Data System (ADS)

    Barnwal, Pradyuman; Mohite, Ashish M.; Singh, Krishna K.; Kumar, Pankaj

    2014-03-01

    In this communication, selected physicomechanical characteristics of ground turmeric (cv. Prabha) were investigated for cryogenic and ambient grinding conditions of turmeric at different moisture contents (4, 6, 8 and 10% w.b.). A cryogenic grinder (Model: 100 UPZ, Hosokawa Alpine, Germany) and a micro pulverizer (hammer mill) were used for cryogenic and ambient grinding, respectively. The ground turmeric was graded in three grades viz. Gr-I, Gr-II and Gr-III with a sieve shaker using BSS Nos. 40, 85 and pan, respectively. Tap densities for cryogenic and ambient ground turmeric decreased from 678.7 (Gr-I) to 546.7 kgm-3 (Gr-III) and from 642.3 (Gr-I) to 468.6 kgm-3 (Gr-III), respectively, with the moisture increase. The angle of repose for cryogenic and ambient ground turmeric increased linearly from 26.85 (Gr-I) to 34.0° (Gr-III) and from 23.10 (Gr-I) to 28.06° (Gr-III), respectively with the increase in moisture content. The static coefficient of friction was the highest on plywood surface followed by mild steel sheet and galvanized iron sheet. The cryoground samples were found better in colour. Thermal conductivity of cryo-ground samples was higher than that of ambient ground samples. These physico-mechanical characteristics of cryogenic and ambient ground turmeric will be helpful for packaging, handling, and storage.

  11. Radioimmunotherapy (RIT) Dose-Escalation Studies in Prostate Cancer Using Anti-PSMA Antibody 177Lu-J591: RIT Alone and RIT in Combination with Docetaxel

    DTIC Science & Technology

    2008-10-01

    for > 3 platelet transfusion in 30 days • Gr 4 neutropenia • Febrile neutropenia • Attributable Gr > 3 non-hematologic toxicity (excluding infusion...0% No febrile neutropenia (no growth factor use) • Transaminitis (n=12 evaluable) Transient Gr 1 17% (no Gr > 1) Figure-1...therapies and 36% progressed on 1-4 lines of chemotherapy including docetaxel. No DLT’s have been seen. 2 pts experienced reversible Gr 3 neutropenia

  12. Corticosteroid receptor gene expression is related to sex and social behaviour in a social fish.

    PubMed

    O'Connor, Constance M; Rodela, Tammy M; Mileva, Viktoria R; Balshine, Sigal; Gilmour, Kathleen M

    2013-03-01

    Circulating corticosteroids have been related to social status in a variety of species. However, our understanding of corticosteroid receptor expression and its relationship with sociality is still in its infancy. Knowledge of variation in receptor expression is critical to understand the physiological relevance of differences in circulating corticosteroid concentrations. In this study, we examined corticosteroid receptor gene expression in relation to dominance rank, sex, and social behaviour in the highly social cichlid fish, Neolamprologus pulcher. We examined the relative gene expression of the three known teleost corticosteroid receptors: glucocorticoid receptor 1 (GR1), glucocorticoid receptor 2 (GR2), and the mineralocorticoid receptor (MR) in liver and brain tissue of dominant and subordinate N. pulcher males and females. Phylogenetic analysis revealed the N. pulcher gene originally described as GR2, clustered with other teleost GR1 genes, while the originally-described N. pulcher GR1 gene clustered with the GR2 genes of other teleosts. Therefore we propose a change in the original nomenclature of the N. pulcher GRs: GR1 (formerly GR2) and GR2 (formerly GR1) and adopt this new nomenclature throughout this manuscript. Liver MR transcript levels were higher in males than females, and positively related to submissive behaviour. Liver GR2 (formerly GR1) transcript levels were also higher in males than females. Collectively, the results demonstrate sex differences in corticosteroid receptor abundance, and suggest tissue- and receptor-specific roles for corticosteroid receptors in mediating aspects of social behaviour. Copyright © 2012. Published by Elsevier Inc.

  13. Carbon dioxide receptor genes in cotton bollworm Helicoverpa armigera

    NASA Astrophysics Data System (ADS)

    Xu, Wei; Anderson, Alisha

    2015-04-01

    Carbon dioxide (CO2) is important in insect ecology, eliciting a range of behaviours across different species. Interestingly, the numbers of CO2 gustatory receptors (GRs) vary among insect species. In the model organism Drosophila melanogaster, two GRs (DmelGR21a and DmelGR63a) have been shown to detect CO2. In the butterfly, moth, beetle and mosquito species studied so far, three CO2 GR genes have been identified, while in tsetse flies, four CO2 GR genes have been identified. In other species including honeybees, pea aphids, ants, locusts and wasps, no CO2 GR genes have been identified from the genome. These genomic differences may suggest different mechanisms for CO2 detection exist in different insects but, with the exception of Drosophila and mosquitoes, limited attention has been paid to the CO2 GRs in insects. Here, we cloned three putative CO2 GR genes from the cotton bollworm Helicoverpa armigera and performed phylogenetic and expression analysis. All three H. armigera CO2 GRs (HarmGR1, HarmGR2 and HarmGR3) are specifically expressed in labial palps, the CO2-sensing tissue of this moth. HarmGR3 is significantly activated by NaHCO3 when expressed in insect Sf9 cells but HarmGR1 and HarmGR2 are not. This is the first report characterizing the function of lepidopteran CO2 receptors, which contributes to our general understanding of the molecular mechanisms of insect CO2 gustatory receptors.

  14. Slip Activity in Single Grains Extracted from Polycrystalline Specimen by X-Ray Line Broadening (Preprint)

    DTIC Science & Technology

    2010-01-01

    4 6 8 0.005 0.010 -101-3 -110-2 1-10-2F W H M [ 1 /n m ] K [ 1/nm ] Gr #44 Gr #50 Gr #72 -101-1 1-101 (a...0 2 4 6 0.000 0.005 0.010 (b) K2Ccalc [ 1/nm ] FW H M [ 1 /n m ] Gr #44 Gr #50 Gr #72 17 Figure 5. The FWHM (in 1/nm scales) in...Preprint 01 January 2010 – 01 January 2010 4 . TITLE AND SUBTITLE SLIP ACTIVITY IN SINGLE GRAINS EXTRACTED FROM POLYCRYSTALLINE SPECIMEN BY X-RAY

  15. Global Precipitation Measurement (GPM) Validation Network

    NASA Technical Reports Server (NTRS)

    Schwaller, Mathew; Moris, K. Robert

    2010-01-01

    The method averages the minimum TRMM PR and Ground Radar (GR) sample volumes needed to match-up spatially/temporally coincident PR and GR data types. PR and GR averages are calculated at the geometric intersection of the PR rays with the individual Ground Radar(GR)sweeps. Along-ray PR data are averaged only in the vertical, GR data are averaged only in the horizontal. Small difference in PR & GR reflectivity high in the atmosphere, relatively larger differences. Version 6 TRMM PR underestimates rainfall in the case of convective rain in the lower part of the atmosphere by 30 to 40 percent.

  16. Role of the chromatin landscape and sequence in determining cell type-specific genomic glucocorticoid receptor binding and gene regulation

    PubMed Central

    Huska, Matthew R.; Jurk, Marcel; Schöpflin, Robert; Starick, Stephan R.; Schwahn, Kevin; Cooper, Samantha B.; Yamamoto, Keith R.; Thomas-Chollier, Morgane; Vingron, Martin

    2017-01-01

    Abstract The genomic loci bound by the glucocorticoid receptor (GR), a hormone-activated transcription factor, show little overlap between cell types. To study the role of chromatin and sequence in specifying where GR binds, we used Bayesian modeling within the universe of accessible chromatin. Taken together, our results uncovered that although GR preferentially binds accessible chromatin, its binding is biased against accessible chromatin located at promoter regions. This bias can only be explained partially by the presence of fewer GR recognition sequences, arguing for the existence of additional mechanisms that interfere with GR binding at promoters. Therefore, we tested the role of H3K9ac, the chromatin feature with the strongest negative association with GR binding, but found that this correlation does not reflect a causative link. Finally, we find a higher percentage of promoter–proximal GR binding for genes regulated by GR across cell types than for cell type-specific target genes. Given that GR almost exclusively binds accessible chromatin, we propose that cell type-specific regulation by GR preferentially occurs via distal enhancers, whose chromatin accessibility is typically cell type-specific, whereas ubiquitous target gene regulation is more likely to result from binding to promoter regions, which are often accessible regardless of cell type examined. PMID:27903902

  17. Structure of Greyhound hemoglobin: origin of high oxygen affinity.

    PubMed

    Bhatt, Veer S; Zaldívar-López, Sara; Harris, David R; Couto, C Guillermo; Wang, Peng G; Palmer, Andre F

    2011-05-01

    This study presents the crystal structure of Greyhound hemoglobin (GrHb) determined to 1.9 Å resolution. GrHb was found to crystallize with an α₁β₁ dimer in the asymmetric unit and belongs to the R2 state. Oxygen-affinity measurements combined with the fact that GrHb crystallizes in the R2 state despite the high-salt conditions used for crystallization strongly indicate that GrHb can serve as a model high-oxygen-affinity hemoglobin (Hb) for higher mammals, especially humans. Structural analysis of GrHb and its comparison with the R2-state of human Hb revealed several regions that can potentially contribute to the high oxygen affinity of GrHb and serve to rationalize the additional stability of the R2-state of GrHb. A previously well studied hydrophobic cluster of bar-headed goose Hb near α119 was also incorporated in the comparison between GrHb and human Hb. Finally, a structural comparison with generic dog Hb and maned wolf Hb was conducted, revealing that in contrast to GrHb these structures belong to the R state of Hb and raising the intriguing possibility of an additional allosteric factor co-purifying with GrHb that can modulate its quaternary structure.

  18. Xenobiotics and the Glucocorticoid Receptor

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

    Gulliver, Linda S M, E-mail: linda.gulliver@otago.

    Glucocorticoid Receptor (GR) is present in virtually every human cell type. Representing a nuclear receptor superfamily, GR has several different isoforms essentially acting as ligand-dependent transcription factors, regulating glucocorticoid-responsive gene expression in both a positive and a negative manner. Although the natural ligand of the Glucocorticoid Receptor, glucocorticoids (GC) represent only some of the multiple ligands for GR. Xenobiotics, ubiquitous in the environment, bind to GR and are also capable of activating or repressing GR gene expression, thereby modulating GR cell and tissue-specific downstream effects in a multitude of ways that include responses to inflammatory, allergic, metabolic, neoplastic and autoimmunemore » processes. Many xenobiotics, if inadequately metabolized by xenobiotic metabolizing enzymes and not wholly eliminated, could have deleterious toxic effects with potentially lethal consequences. This review examines GR, the genomic and non-genomic actions of natural and synthetic GC and the body's handling of xenobiotic compounds, before reviewing what is presently known about GR's interactions with many of the more commonly encountered and some of the less well known GR-associated xenobiotics. GR promiscuity and crosstalk with other signaling pathways is discussed, alongside novel roles for GR that include mood disorder and addiction. A knowledge of GR interactions with xenobiotics is increasingly relevant when considering aging populations and the related prevalence of neoplastic disease, together with growing concerns around human exposure to mixtures of chemicals in the environment. Furthermore, escalating rates of obesity, Type 2 diabetes; autoimmune, allergy, addiction and mood disorder-related pathologies, require novel targeted interventions and GR appears a promising pharmacological candidate. - Highlights: • Biological impact of xenobiotics acting through Glucocorticoid Receptor. • Promiscuity of Glucocorticoid

  19. Low serum albumin may predict the need for gastric resection in patients with perforated peptic ulcer.

    PubMed

    Seow, J G; Lim, Y R; Shelat, V G

    2017-06-01

    Perforated peptic ulcer (PPU) is a common surgical emergency and treatment involves omental patch repair (PR). Gastric resection (GR) is reserved for difficult pathologies. We audit the outcomes of GR at our institution and evaluate the pre-operative factors predicting the need for GR. This is a single-institution, retrospective study of patients with PPU who underwent surgery from 2004 to 2012. Demographics, clinical presentation and intra-operative findings were studied to identify factors predicting the need for GR in PPU. An audit of clinical outcomes and mortality for all patients with GR is reported. 537 (89.6 %) patients underwent PR and 62 (10.4 %) patients GR. Old age (p < 0.0001), female sex (p = 0.0123), non-steroidal anti-inflammatory drugs (NSAIDs) usage (p = 0.0008), previous history of peptic ulcer disease (PUD) (p = 0.0159), low hemoglobin (p < 0.0001), low serum albumin (p < 0.0001), high serum creatinine (p = 0.0030), high urea (p = 0.0006) and large ulcer size (p < 0.0001) predict the need for GR. On multivariate analysis only low serum albumin (OR 5.57, 95 % CI 1.56-19.84, p = 0.008) predicted the need for GR. The presence of Helicobacter pylori infection was protective against GR (OR 0.25, 95 %CI 0.14-0.44, p < 0.0001). Morbidity and mortality of GR was 27.7 and 24.2 %, respectively. GR is needed in one in ten cases of PPU. Low serum albumin predicted the need for GR on multivariate analysis. Morbidity and mortality of GR remains high.

  20. Pattern of heat shock factor and heat shock protein expression in lymphocytes of bipolar patients: increased HSP70-glucocorticoid receptor heterocomplex.

    PubMed

    Bei, E S; Salpeas, V; Alevizos, B; Anagnostara, C; Pappa, D; Moutsatsou, P

    2013-11-01

    Bipolar disorder (BD), a stress-related disease, is characterized by altered glucocorticoid receptor (GR) signalling. Stress response includes activation of heat shock factor (HSF) and subsequent heat shock protein (HSP) synthesis which regulate GR folding and function. The objective of this study was to investigate the possible role of HSFs, HSPs and their interaction with GR in BD. We applied immunoprecipitation, SDS-PAGE/Western blot analysis and electrophoretic mobility shift assay (EMSA) in lymphocytes (whole cell or nuclear extracts) from BD patients and healthy subjects and determined the HSPs (HSP90 and HSP70), the heterocomplexes HSP90-GR and HSP70-GR, the HSFs (HSF1 and HSF4) as well as the HSF-DNA binding. The HSP70-GR heterocomplex was elevated (p < 0.05) in BD patients vs healthy subjects, and nuclear HSP70 was reduced (p ≤ 0.01) in bipolar manic patients. Protein levels of HSF1, HSF4, HSP90, HSP90-GR heterocomplex, and HSF-DNA binding remained unaltered in BD patients vs healthy subjects. The corresponding effect sizes (ES) indicated a large ES for HSP70-GR, HSP70, HSF-DNA binding and HSF4, and a medium ES for HSP90, HSF1 and HSP90-GR between healthy subjects and bipolar patients. Significant correlations among HSFs, HSPs, GR and HSP70-GR heterocomplex were observed in healthy subjects, which were abrogated in bipolar patients. The higher interaction between GR and HSP70 and the disturbances in the relations among heat shock response parameters and GR as observed in our BD patients may provide novel insights into the contribution of these factors in BD aetiopathogenesis. Copyright © 2013. Published by Elsevier Ltd.

  1. Central glucocorticoid receptors regulate the upregulation of spinal cannabinoid-1 receptors after peripheral nerve injury in rats.

    PubMed

    Wang, Shuxing; Lim, Grewo; Mao, Ji; Sung, Backil; Yang, Liling; Mao, Jianren

    2007-09-01

    Previous studies have shown that peripheral nerve injury upregulated both glucocorticoid receptors (GR) and cannabinoid-1 receptors (CB1R) within the spinal cord dorsal horn in rats. However, the relationship between the expression of spinal GR and CB1R after nerve injury remains unclear. Here, we examined the hypothesis that the upregulation of spinal CB1R induced by chronic constriction nerve injury (CCI) in rats would be regulated by spinal GR. CCI induced the upregulation of spinal CB1R primarily within the ipsilateral spinal cord dorsal horn as revealed by Western blot and immunohistochemistry. The expression of CB1R in CCI rats was substantially attenuated by intrathecal treatment with either the GR antagonist RU38486 or a GR antisense oligonucleotide given twice daily for postoperative day 1-6, whereas the expression of spinal CB1R was enhanced following intrathecal administration of a GR sense oligonucleotide twice daily for postoperative day 1-6. Furthermore, the upregulation of spinal CB1R after nerve injury was prevented in adrenalectomized rats, which was at least partially restored with the intrathecal administration of an exogenous GR agonist dexamethasone, indicating that corticosteroids (endogenous GR agonists) were critical to spinal GR actions. Since the development of neuropathic pain behaviors in CCI rats was attenuated by either RU38486 or a GR antisense oligonucleotide, these results suggest that CB1R is a downstream target for spinal GR actions contributory to the mechanisms of neuropathic pain.

  2. Role of Pro-637 and Gln-642 in human glucocorticoid receptors and Ser-843 and Leu-848 in mineralocorticoid receptors in their differential responses to cortisol and aldosterone.

    PubMed

    Mani, Orlando; Nashev, Lyubomir G; Livelo, Christopher; Baker, Michael E; Odermatt, Alex

    2016-05-01

    Mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) are descended from a common ancestral corticoid receptor. The basis for specificities of human MR for aldosterone and human GR for glucocorticoids, such as cortisol, bearing 17α-hydroxyl-groups, is incompletely understood. Differences in MR at S843 and L848 and GR at the corresponding P637 and Q642 have been proposed as important in their different responses to glucocorticoids with 17α-hydroxyl-groups. We investigated the impact of these residues on binding affinity (Ki) and transcriptional activation (EC50) of mutants MR-S843P, MR-L848Q and MR-S843P/L848Q and mutants GR-P637S, GR-Q642L and GR-P637S/Q642L in the presence of different corticosteroids. Aldosterone, cortisol and corticosterone had similar affinities for wild-type MR and all mutants, while dexamethasone had increased affinity for the three mutants. However, transactivation of MR-S843P and MR-S843P/L848Q by all four steroids was significantly lower than for wild-type MR. In contrast, transactivation of MR-L848Q tended to be 3-fold higher for cortisol and corticosterone and increased 7-fold for dexamethasone, indicating that MR-L848Q has an increased response to glucocorticoids, while retaining a strong response to aldosterone. Compared to wild-type GR, GR-P637S and GR-Q642L had increased affinities and significantly increased transcriptional activity with aldosterone and corticosterone, and GR-P637S had similar transcriptional activity with cortisol and dexamethasone, while GR-Q642L and GR-P637S/Q642L had a significant decrease in transcriptional activity with cortisol and dexamethasone. 3D-models of these MR and GR mutants revealed that dexamethasone and aldosterone, respectively, fit nicely into the steroid-binding pocket, consistent with the affinity of dexamethasone for MR mutants and aldosterone for GR mutants. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Pseudo and true visible light photocatalytic activity of nanotube titanic acid/graphene composites

    NASA Astrophysics Data System (ADS)

    Wang, Xiaodong; Liu, Xiaogang; Xue, Xiaoxiao; Pan, Hui; Zhang, Min; Li, Qiuye; Yu, Laigui; Yang, Jianjun; Zhang, Zhijun

    2013-09-01

    Nanotube titanic acid/graphene (NTA/Gr) composites were prepared by an easy hydrothermal treatment of graphene oxide (GO) and NTA in a mixed solvent of ethanol-water. As-prepared NTA/Gr composites and GO were characterized by means of Fourier transform infrared spectrometry, X-ray diffraction, diffuse-reflection spectrometry, thermal analysis, and transmission electron microscopy. Besides, the photocatalytic activities of as-prepared NTA/Gr composites were evaluated by monitoring the degradation of methyl orange (MO) under visible light irradiation. It has been found that extending hydrothermal reaction time (24 h instead of 3 h) leads to great changes in the morphology and crystal structure of as-prepared composites. Namely, the orthorhombic NTA (ca. 10 nm in diameter) in the composite transformed to anatase TiO2 particle (ca. 20-30 nm in diameter) while the Gr sheets (with micrometers-long wrinkles) in it transformed to a few Gr fragments (ca. 50 nm in diameter). Correspondingly, the NTA/Gr composite transformed to titanium dioxide/graphene (TiO2/Gr) composite. In the meantime, pure GO only has adsorption effect but it has no photocatalytic activity in the visible light region. Nevertheless, increasing Gr ratio results in enhanced visible light absorption capability and photocatalytic activity of NTA/Gr composites as well as the TiO2/Gr composites. This demonstrates that the true visible light photocatalytic activity of NTA/Gr composites as well as the TiO2/Gr composites for the degradation of MO is not as excellent as expected, and their high apparent activity is attributed to the strong adsorption of MO on the composites.

  4. Glyphosate-Resistant and Conventional Canola (Brassica napus L.) Responses to Glyphosate and Aminomethylphosphonic Acid (AMPA) Treatment.

    PubMed

    Corrêa, Elza Alves; Dayan, Franck E; Owens, Daniel K; Rimando, Agnes M; Duke, Stephen O

    2016-05-11

    Glyphosate-resistant (GR) canola contains two transgenes that impart resistance to the herbicide glyphosate: (1) the microbial glyphosate oxidase gene (gox) encoding the glyphosate oxidase enzyme (GOX) that metabolizes glyphosate to aminomethylphosphonic acid (AMPA) and (2) cp4 that encodes a GR form of the glyphosate target enzyme 5-enolpyruvylshikimic acid-3-phosphate synthase. The objectives of this research were to determine the phytotoxicity of AMPA to canola, the relative metabolism of glyphosate to AMPA in GR and conventional non-GR (NGR) canola, and AMPA pool sizes in glyphosate-treated GR canola. AMPA applied at 1.0 kg ha(-1) was not phytotoxic to GR or NGR. At this AMPA application rate, NGR canola accumulated a higher concentration of AMPA in its tissues than GR canola. At rates of 1 and 3.33 kg ae ha(-1) of glyphosate, GR canola growth was stimulated. This stimulatory effect is similar to that of much lower doses of glyphosate on NGR canola. Both shikimate and AMPA accumulated in tissues of these glyphosate-treated plants. In a separate experiment in which young GR and NGR canola plants were treated with non-phytotoxic levels of [(14)C]-glyphosate, very little glyphosate was metabolized in NGR plants, whereas most of the glyphosate was metabolized to AMPA in GR plants at 7 days after application. Untreated leaves of GR plants accumulated only metabolites (mostly AMPA) of glyphosate, indicating that GOX activity is very high in the youngest leaves. These data indicate that more glyphosate is transformed to AMPA rapidly in GR canola and that the accumulated AMPA is not toxic to the canola plant.

  5. An 8.68% efficiency chemically-doped-free graphene-silicon solar cell using silver nanowires network buried contacts.

    PubMed

    Yang, Lifei; Yu, Xuegong; Hu, Weidan; Wu, Xiaolei; Zhao, Yan; Yang, Deren

    2015-02-25

    Graphene-silicon (Gr-Si) heterojunction solar cells have been recognized as one of the most low-cost candidates in photovoltaics due to its simple fabrication process. However, the high sheet resistance of chemical vapor deposited (CVD) Gr films is still the most important limiting factor for the improvement of the power conversion efficiency of Gr-Si solar cells, especially in the case of large device-active area. In this work, we have fabricated a novel transparent conductive film by hybriding a monolayer Gr film with silver nanowires (AgNWs) network soldered by the graphene oxide (GO) flakes. This Gr-AgNWs hybrid film exhibits low sheet resistance and larger direct-current to optical conductivity ratio, quite suitable for solar cell fabrication. An efficiency of 8.68% has been achieved for the Gr-AgNWs-Si solar cell, in which the AgNWs network acts as buried contacts. Meanwhile, the Gr-AgNWs-Si solar cells have much better stability than the chemically doped Gr-Si solar cells. These results show a new route for the fabrication of high efficient and stable Gr-Si solar cells.

  6. Evaluation of pulmonary and systemic toxicity following lung exposure to graphite nanoplates: a member of the graphene-based nanomaterial family.

    PubMed

    Roberts, Jenny R; Mercer, Robert R; Stefaniak, Aleksandr B; Seehra, Mohindar S; Geddam, Usha K; Chaudhuri, Ishrat S; Kyrlidis, Angelos; Kodali, Vamsi K; Sager, Tina; Kenyon, Allison; Bilgesu, Suzan A; Eye, Tracy; Scabilloni, James F; Leonard, Stephen S; Fix, Natalie R; Schwegler-Berry, Diane; Farris, Breanne Y; Wolfarth, Michael G; Porter, Dale W; Castranova, Vincent; Erdely, Aaron

    2016-06-21

    Graphene, a monolayer of carbon, is an engineered nanomaterial (ENM) with physical and chemical properties that may offer application advantages over other carbonaceous ENMs, such as carbon nanotubes (CNT). The goal of this study was to comparatively assess pulmonary and systemic toxicity of graphite nanoplates, a member of the graphene-based nanomaterial family, with respect to nanoplate size. Three sizes of graphite nanoplates [20 μm lateral (Gr20), 5 μm lateral (Gr5), and <2 μm lateral (Gr1)] ranging from 8-25 nm in thickness were characterized for difference in surface area, structure,, zeta potential, and agglomeration in dispersion medium, the vehicle for in vivo studies. Mice were exposed by pharyngeal aspiration to these 3 sizes of graphite nanoplates at doses of 4 or 40 μg/mouse, or to carbon black (CB) as a carbonaceous control material. At 4 h, 1 day, 7 days, 1 month, and 2 months post-exposure, bronchoalveolar lavage was performed to collect fluid and cells for analysis of lung injury and inflammation. Particle clearance, histopathology and gene expression in lung tissue were evaluated. In addition, protein levels and gene expression were measured in blood, heart, aorta and liver to assess systemic responses. All Gr samples were found to be similarly composed of two graphite structures and agglomerated to varying degrees in DM in proportion to the lateral dimension. Surface area for Gr1 was approximately 7-fold greater than Gr5 and Gr20, but was less reactive reactive per m(2). At the low dose, none of the Gr materials induced toxicity. At the high dose, Gr20 and Gr5 exposure increased indices of lung inflammation and injury in lavage fluid and tissue gene expression to a greater degree and duration than Gr1 and CB. Gr5 and Gr20 showed no or minimal lung epithelial hypertrophy and hyperplasia, and no development of fibrosis by 2 months post-exposure. In addition, the aorta and liver inflammatory and acute phase genes were transiently

  7. Controls of soil hydraulic characteristics on modeling groundwater recharge under different climatic conditions

    NASA Astrophysics Data System (ADS)

    Wang, Tiejun; Franz, Trenton E.; Zlotnik, Vitaly A.

    2015-02-01

    To meet the challenge of estimating spatially varying groundwater recharge (GR), increasing attention has been given to the use of vadose zone models (VZMs). However, the application of this approach is usually constrained by the lack of field soil hydraulic characteristics (SHCs) required by VZMs. To tackle this issue, SHCs based on the van Genuchten or Brooks-Corey model are generally estimated by pedotransfer functions or taken from texture based class averages. With the increasing use of this method, it is important to elucidate the controls of SHCs on computing GR mostly due to the high nonlinearity of the models. In this study, it is hypothesized that the nonlinear controls of SHCs on computing GR would vary with climatic conditions. To test this hypothesis, a widely used VZM along with two SHCs datasets for sand and loamy sand is used to compute GR at four sites in the continental Unites States with a significant gradient of precipitation (P). The simulation results show that the distribution patterns of mean annual GR ratios (GR ‾ / P ‾ , where GR ‾ and P ‾ are mean annual GR and P, respectively) vary considerably across the sites, largely depending on soil texture and climatic conditions at each site. It is found that GR ‾ / P ‾ is mainly controlled by the shape factor n in the van Genuchten model and the nonlinear effect of n on GR ‾ / P ‾ varies with climatic conditions. Specifically, for both soil textures, the variability in GR ‾ / P ‾ is smallest at the Andrews Forest with the highest P ‾ (191.3 cm/year) and GR ‾ / P ‾ is least sensitive to n; whereas, the variability in GR ‾ / P ‾ at the Konza Prairie (P ‾ = 84.2 cm/year) is the largest and GR ‾ / P ‾ is most sensitive to n. With further decreasing P ‾ , the nonlinear effect of n weakens at the Barta Brothers (P ‾ = 57.3 cm/year) and Sevilleta (P ‾ = 20.3 cm/year), leading to smaller GR ‾ / P ‾ variability at those two sites than at the Konza Prairie. The

  8. Role of the chromatin landscape and sequence in determining cell type-specific genomic glucocorticoid receptor binding and gene regulation.

    PubMed

    Love, Michael I; Huska, Matthew R; Jurk, Marcel; Schöpflin, Robert; Starick, Stephan R; Schwahn, Kevin; Cooper, Samantha B; Yamamoto, Keith R; Thomas-Chollier, Morgane; Vingron, Martin; Meijsing, Sebastiaan H

    2017-02-28

    The genomic loci bound by the glucocorticoid receptor (GR), a hormone-activated transcription factor, show little overlap between cell types. To study the role of chromatin and sequence in specifying where GR binds, we used Bayesian modeling within the universe of accessible chromatin. Taken together, our results uncovered that although GR preferentially binds accessible chromatin, its binding is biased against accessible chromatin located at promoter regions. This bias can only be explained partially by the presence of fewer GR recognition sequences, arguing for the existence of additional mechanisms that interfere with GR binding at promoters. Therefore, we tested the role of H3K9ac, the chromatin feature with the strongest negative association with GR binding, but found that this correlation does not reflect a causative link. Finally, we find a higher percentage of promoter-proximal GR binding for genes regulated by GR across cell types than for cell type-specific target genes. Given that GR almost exclusively binds accessible chromatin, we propose that cell type-specific regulation by GR preferentially occurs via distal enhancers, whose chromatin accessibility is typically cell type-specific, whereas ubiquitous target gene regulation is more likely to result from binding to promoter regions, which are often accessible regardless of cell type examined. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  9. Ultrasound assisted simultaneous reduction and direct functionalization of graphene oxide with thermal and cytotoxicity profile.

    PubMed

    Maktedar, Shrikant S; Avashthi, Gopal; Singh, Man

    2017-01-01

    The new sonochemical approach for simultaneous reduction and direct functionalization of graphene oxide (GrO) has been developed. The GrO was functionalized with 2-Aminobenzoxazole (2-ABOZ) in twenty min with complete deletion of hazardous steps. The significance of ultrasound was exemplified with the comparative conventional methods. The newly prepared f-(2-ABOZ)GrO was extensively characterized with near edge X-ray absorption fine structure (NEXAFS) spectroscopy, 13 C solid state NMR, XPS, XRD, HRTEM, SAED, AFM, Raman, UV-vis, FTIR and TGA. The thermal stability of f-(2-ABOZ)GrO was confirmed with total percentage weight loss in TGA. The biological activity of f-(2-ABOZ)GrO was explored with MCF-7 and Vero cell lines. The inherent cytotoxicity was evaluated with SRB assay at 10, 20, 40 and 80μgmL -1 . The estimated cell viabilities were >78% with f-(2-ABOZ) GrO. A high cytocompatibility of f-(2-ABOZ)GrO was ensured with in vitro evaluation on living cell lines, and low toxicity of f-(2-ABOZ)GrO was confirmed its excellent biocompatibility. The morphological effect on Vero cell line evidently supports the formation of biocompatible f-(2-ABOZ)GrO. Therefore, f-(2-ABOZ)GrO was emerged as an advanced functional material for thermally stable biocompatible coatings. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Baicalin promotes hippocampal neurogenesis via SGK1- and FKBP5-mediated glucocorticoid receptor phosphorylation in a neuroendocrine mouse model of anxiety/depression

    PubMed Central

    Zhang, Kuo; Pan, Xing; Wang, Fang; Ma, Jie; Su, Guangyue; Dong, Yingxu; Yang, Jingyu; Wu, Chunfu

    2016-01-01

    Antidepressants increase hippocampal neurogenesis by activating the glucocorticoid receptor (GR), but excessive GR activation impairs hippocampal neurogenesis, suggesting that normal GR function is crucial for hippocampal neurogenesis. Baicalin was reported to regulate the expression of GR and facilitate hippocampal neurogenesis, but the underlying molecular mechanisms are still unknown. In this study, we used the chronic corticosterone (CORT)-induced mouse model of anxiety/depression to assess antidepressant-like effects of baicalin and illuminate possible molecular mechanisms by which baicalin affects GR-mediated hippocampal neurogenesis. We found that oral administration of baicalin (40, 80 or 160 mg/kg) for 4 weeks alleviated several chronic CORT-induced anxiety/depression-like behaviors. Baicalin also increased Ki-67- and DCX-positive cells to restore chronic CORT-induced suppression of hippocampal neurogenesis. Moreover, baicalin normalized the chronic CORT-induced decrease in GR protein levels, the increase in GR nuclear translocation and the increase in GR phosphorylation at Ser203 and Ser211. Finally, chronic CORT exposure increased the level of FK506-binding protein 51 (FKBP5) and of phosphorylated serum- and glucocorticoid-inducible kinase 1 (SGK1) at Ser422 and Thr256, whereas baicalin normalized these changes. Together, our findings suggest that baicalin improves anxiety/depression-like behaviors and promotes hippocampal neurogenesis. We propose that baicalin may normalize GR function through SGK1- and FKBP5-mediated GR phosphorylation. PMID:27502757

  11. Neonatal growth restriction-related leptin deficiency enhances leptin-triggered sympathetic activation and central angiotensin II receptor-dependent stress-evoked hypertension.

    PubMed

    Peotta, Veronica; Rahmouni, Kamal; Segar, Jeffrey L; Morgan, Donald A; Pitz, Kate M; Rice, Olivia M; Roghair, Robert D

    2016-08-01

    Neonatal growth restriction (nGR) leads to leptin deficiency and increases the risk of hypertension. Previous studies have shown nGR-related hypertension is normalized by neonatal leptin (nLep) and exacerbated by psychological stress. With recent studies linking leptin and angiotensin signaling, we hypothesized that nGR-induced nLep deficiency increases adult leptin sensitivity; leading to leptin- or stress-induced hypertension, through a pathway involving central angiotensin II type 1 receptors. We randomized mice with incipient nGR, by virtue of their presence in large litters, to vehicle or physiologic nLep supplementation (80 ng/g/d). Adult caloric intake and arterial pressure were monitored at baseline, during intracerebroventricular losartan infusion and during systemic leptin administration. nGR increased leptin-triggered renal sympathetic activation and hypertension with increased leptin receptor expression in the arcuate nucleus of the hypothalamus; all of those nGR-associated phenotypes were normalized by nLep. nGR mice also had stress-related hyperphagia and hypertension, but only the stress hypertension was blocked by central losartan infusion. nGR leads to stress hypertension through a pathway that involves central angiotensin II receptors, and nGR-associated leptin deficiency increases leptin-triggered hypertension in adulthood. These data suggest potential roles for preservation of neonatal growth and nLep supplementation in the prevention of nGR-related hypertension.

  12. Modulation of glacier ablation by tephra coverage from Eyjafjallajökull and Grímsvötn volcanoes, Iceland: an automated field experiment

    NASA Astrophysics Data System (ADS)

    Möller, Rebecca; Möller, Marco; Kukla, Peter A.; Schneider, Christoph

    2018-01-01

    We report results from a field experiment investigating the influence of volcanic tephra coverage on glacier ablation. These influences are known to be significantly different from those of moraine debris on glaciers due to the contrasting grain size distribution and thermal conductivity. Thus far, the influences of tephra deposits on glacier ablation have rarely been studied. For the experiment, artificial plots of two different tephra types from Eyjafjallajökull and Grímsvötn volcanoes were installed on a snow-covered glacier surface of Vatnajökull ice cap, Iceland. Snow-surface lowering and atmospheric conditions were monitored in summer 2015 and compared to a tephra-free reference site. For each of the two volcanic tephra types, three plots of variable thickness ( ˜ 1.5, ˜ 8.5 and ˜ 80 mm) were monitored. After limiting the records to a period of reliable measurements, a 50-day data set of hourly records was obtained, which can be downloaded from the Pangaea data repository (https://www.pangaea.de; doi:10.1594/PANGAEA.876656). The experiment shows a substantial increase in snow-surface lowering rates under the ˜ 1.5 and ˜ 8.5 mm tephra plots when compared to uncovered conditions. Under the thick tephra cover some insulating effects could be observed. These results are in contrast to other studies which depicted insulating effects for much thinner tephra coverage on bare-ice glacier surfaces. Differences between the influences of the two different petrological types of tephra exist but are negligible compared to the effect of tephra coverage overall.

  13. Detection and Location of Transverse Matrix Cracks in Cross-Ply Gr/Ep Composites Using Acoustic Emission

    NASA Technical Reports Server (NTRS)

    Prosser, W. H.; Jackson, K. E.; Kellas, S.; Smith, B. T.; McKeon, J.; Friedman, A.

    1995-01-01

    Transverse matrix cracking in cross-ply gr/ep laminates was studied with advanced acoustic emission (AE) techniques. The primary goal of this research was to measure the load required to initiate the first transverse matrix crack in cross-ply laminates of different thicknesses. Other methods had been previously used for these measurements including penetrant enhanced radiography, optical microscopy, and audible acoustic microphone measurements. The former methods required that the mechanical test be paused for measurements at load intervals. This slowed the test procedure and did not provide the required resolution in load. With acoustic microphones, acoustic signals from cracks could not be clearly differentiated from other noise sources such as grip damage, specimen slippage, or test machine noise. A second goal for this work was to use the high resolution source location accuracy of the advanced acoustic emission techniques to determine whether the crack initiation site was at the specimen edge or in the interior of the specimen.In this research, advanced AE techniques using broad band sensors, high capture rate digital waveform acquisition, and plate wave propagation based analysis were applied to cross-ply composite coupons with different numbers of 0 and 90 degree plies. Noise signals, believed to be caused by grip damage or specimen slipping, were eliminated based on their plate wave characteristics. Such signals were always located outside the sensor gage length in the gripped region of the specimen. Cracks were confirmed post-test by microscopic analysis of a polished specimen edge, backscatter ultrasonic scans, and in limited cases, by penetrant enhanced radiography. For specimens with three or more 90 degree plies together, there was an exact 1-1 correlation between AE crack signals and observed cracks. The ultrasonic scans and some destructive sectioning analysis showed that the cracks extended across the full width of the specimen. Furthermore, the

  14. Glucocorticoid receptor gene expression and promoter CpG modifications throughout the human brain.

    PubMed

    Cao-Lei, Lei; Suwansirikul, Songkiet; Jutavijittum, Prapan; Mériaux, Sophie B; Turner, Jonathan D; Muller, Claude P

    2013-11-01

    Glucocorticoids and the glucocorticoid (GR) and mineralocorticoid (MR) receptors have been implicated in many processes, particularly in negative feedback regulation of the hypothalamic-pituitary-adrenal axis. Epigenetically programmed GR alternative promoter usage underlies transcriptional control of GR levels, generation of GR 3' splice variants, and the overall GC response in the brain. No detailed analysis of GR first exons or GR transcript variants throughout the human brain has been reported. Therefore we investigated post mortem tissues from 28 brain regions of 5 individuals. GR first exons were expressed throughout the healthy human brain with no region-specific usage patterns. First exon levels were highly inter-correlated suggesting that they are co-regulated. GR 3' splice variants (GRα and GR-P) were equally distributed in all regions, and GRβ expression was always low. GR/MR ratios showed significant differences between the 28 tissues with the highest ratio in the pituitary gland. Modification levels of individual CpG dinucleotides, including 5-mC and 5-hmC, in promoters 1D, 1E, 1F, and 1H were low, and diffusely clustered; despite significant heterogeneity between the donors. In agreement with this clustering, sum modification levels rather than individual CpG modifications correlated with GR expression. Two-way ANOVA showed that this sum modification was both promoter and brain region specific, but that there was however no promoter*tissue interaction. The heterogeneity between donors may however hide such an interaction. In both promoters 1F and 1H modification levels correlated with GRα expression suggesting that 5-mC and 5-hmC play an important role in fine tuning GR expression levels throughout the brain. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Sequence family variant loss from the AZFc interval of the human Y chromosome, but not gene copy loss, is strongly associated with male infertility

    PubMed Central

    Machev, N; Saut, N; Longepied, G; Terriou, P; Navarro, A; Levy, N; Guichaoua, M; Metzler-Guillemai..., C; Collignon, P; Frances, A; Belougne, J; Clemente, E; Chiaroni, J; Chevillard, C; Durand, C; Ducourneau, A; Pech, N; McElreavey, K; Mattei, M; Mitchell, M

    2004-01-01

    Background: Complete deletion of the complete AZFc interval of the Y chromosome is the most common known genetic cause of human male infertility. Two partial AZFc deletions (gr/gr and b1/b3) that remove some copies of all AZFc genes have recently been identified in infertile and fertile populations, and an association study indicates that the resulting gene dose reduction represents a risk factor for spermatogenic failure. Methods: To determine the incidence of various partial AZFc deletions and their effect on fertility, we combined quantitative and qualitative analyses of the AZFc interval at the DAZ and CDY1 loci in 300 infertile men and 399 control men. Results: We detected 34 partial AZFc deletions (32 gr/gr deletions), arising from at least 19 independent deletion events, and found gr/gr deletion in 6% of infertile and 3.5% of control men (p>0.05). Our data provide evidence for two large AZFc inversion polymorphisms, and for relative hot and cold spots of unequal crossing over within the blocks of homology that mediate gr/gr deletion. Using SFVs (sequence family variants), we discriminate DAZ1/2, DAZ3/4, CDY1a (proximal), and CDY1b (distal) and define four types of DAZ-CDY1 gr/gr deletion. Conclusions: The only deletion type to show an association with infertility was DAZ3/4-CDY1a (p = 0.042), suggesting that most gr/gr deletions are neutral variants. We see a stronger association, however, between loss of the CDY1a SFV and infertility (p = 0.002). Thus, loss of this SFV through deletion or gene conversion could be a major risk factor for male infertility. PMID:15520406

  16. Molecular regulation of urea cycle function by the liver glucocorticoid receptor.

    PubMed

    Okun, Jürgen G; Conway, Sean; Schmidt, Kathrin V; Schumacher, Jonas; Wang, Xiaoyue; de Guia, Roldan; Zota, Annika; Klement, Johanna; Seibert, Oksana; Peters, Achim; Maida, Adriano; Herzig, Stephan; Rose, Adam J

    2015-10-01

    One of the major side effects of glucocorticoid (GC) treatment is lean tissue wasting, indicating a prominent role in systemic amino acid metabolism. In order to uncover a novel aspect of GCs and their intracellular-receptor, the glucocorticoid receptor (GR), on metabolic control, we conducted amino acid and acylcarnitine profiling in human and mouse models of GC/GR gain- and loss-of-function. Blood serum and tissue metabolite levels were determined in Human Addison's disease (AD) patients as well as in mouse models of systemic and liver-specific GR loss-of-function (AAV-miR-GR) with or without dexamethasone (DEX) treatments. Body composition and neuromuscular and metabolic function tests were conducted in vivo and ex vivo, the latter using precision cut liver slices. A serum metabolite signature of impaired urea cycle function (i.e. higher [ARG]:[ORN + CIT]) was observed in human (CTRL: 0.45 ± 0.03, AD: 1.29 ± 0.04; p < 0.001) and mouse (AAV-miR-NC: 0.97 ± 0.13, AAV-miR-GR: 2.20 ± 0.19; p < 0.001) GC/GR loss-of-function, with similar patterns also observed in liver. Serum urea levels were consistently affected by GC/GR gain- (∼+32%) and loss (∼-30%) -of-function. Combined liver-specific GR loss-of-function with DEX treatment revealed a tissue-autonomous role for the GR to coordinate an upregulation of liver urea production rate in vivo and ex vivo, and prevent hyperammonaemia and associated neuromuscular dysfunction in vivo. Liver mRNA expression profiling and GR-cistrome mining identified Arginase I (ARG1) a urea cycle gene targeted by the liver GR. The liver GR controls systemic and liver urea cycle function by transcriptional regulation of ARG1 expression.

  17. High-fat diet-induced hepatic steatosis reduces glucagon receptor content in rat hepatocytes: potential interaction with acute exercise

    PubMed Central

    Charbonneau, Alexandre; Unson, Cecilia G; Lavoie, Jean-Marc

    2007-01-01

    Studies have revealed that high-fat (HF) diets promote hyperglycaemia, whole-body insulin resistance and non-alcoholic fatty liver disease (NAFLD). Recently, hepatic glucagon resistance has been shown to occur in rats fed a HF diet. More precisely, diet-induced obesity (DIO) reduces the number of hepatic plasma membrane glucagon receptors (GR), which results in a diminished response to glucagon during a hyperglucagonaemic clamp. The present study was undertaken to test the hypothesis that a HF-DIO is associated with a desensitization and destruction of the hepatic GR. We also hypothesized that a single bout of endurance exercise would modify the GR cellular distribution under our DIO model. Male rats were either fed a standard (sd) or a HF diet for two weeks. Each group was subdivided into a non-exercised (Rest) and an acute exercised (EX) group. The HF diet resulted in a reduction of total hepatic GR (55%) and hepatic plasma membrane GR protein content (20%). These changes were accompanied by a significant increase in endosomal and lysosomal GR content with the feeding of a HF diet. The reduction of GR plasma membrane as well as the increase in endosomal GR was strongly correlated with an increase of PKC-α, suggesting a role of PKC-α in GR desensitization. EX increased significantly PKC-α protein content in both diets, suggesting a role of PKC-α in EX-induced GR desensitization. The present results suggest that liver lipid infiltration plays a role in reducing glucagon action in the liver through a reduction in total cellular and plasma membrane GR content. Furthermore, the GR desensitization observed in our in vivo model of HF diet-induced hepatic steatosis and in EX individuals may be regulated by PKC-α. PMID:17053032

  18. In situ sonochemical reduction and direct functionalization of graphene oxide: A robust approach with thermal and biomedical applications.

    PubMed

    Maktedar, Shrikant S; Mehetre, Shantilal S; Avashthi, Gopal; Singh, Man

    2017-01-01

    The rapid, robust, scalable and non-hazardous sonochemical approach for in situ reduction and direct functionalization of graphene oxide has been developed for non-toxic biomedical applications. The graphene oxide (GrO) was directly functionalized with tryptamine (TA) without using any hazardous acylating and coupling reagents. The reaction was completed within 20min. An impact of ultrasound was inferred for a direct functionalization with other conventional methods. The evolved electronic states were confirmed with near edge X-ray absorption fine structure (NEXAFS). The direct covalent functionalization and formation of f-(TA) GrO was proven with FTIR, 13 C solid state NMR, XPS, XRD, Raman' HRTEM, AFM and TGA. The total percentage weight loss in TGA confirms an enhanced thermal stability of f-(TA) GrO. The f-(TA) GrO was further explored for an investigation of in vitro antimicrobial activity to ensure the health and environmental safety. An outstanding antibacterial activity of f-(TA) GrO was found against gram positive Staphylococcus aureus at MIC 128mgmL -1 . It confirms a suitability of f-(TA) GrO for thermally stable antibacterial coating. The f-(TA) GrO showed 39.14-48.9% antioxidant activities, evaluated with 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical assay. The inherent cytotoxicity of f-(TA) GrO was evaluated with SRB assay to living cells, MCF-7 and Vero. The estimated cell viabilities were >80% upon addition of f-(TA) GrO over a wide concentration range of 10-80μgmL -1 . The high cytocompatibility of f-(TA) GrO confirms the low toxicity and an excellent biocompatibility. The morphological effect on Vero cell line, evidently confirmed the biocompatibility of f-(TA) GrO. Therefore, f-(TA) GrO was emerged as an advanced functional biomaterial for thermal and biomedical applications. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Monoclonal antibodies against the rat liver glucocorticoid receptor.

    PubMed Central

    Okret, S; Wikström, A C; Wrange, O; Andersson, B; Gustafsson, J A

    1984-01-01

    Splenic cells from one BALB/c mouse and one C57/BL mouse, immunized with purified rat liver glucocorticoid receptor (GR), were fused with the mouse myeloma cell line Sp 2/0-Ag 14. Screening for production of anti-GR-antibodies by the hybridomas was carried out with an enzyme-linked immunosorbent assay, using partially purified rat liver GR as antigen. Further screening was by a second-antibody immunoprecipitation assay using [3H]triamcinolone acetonide-GR complex from rat liver cytosol as tracer. Hybridomas from 10 different microplate wells, positive in both assays, were successfully cloned by the limiting dilution method to monoclonality. The different origins of the monoclonal antibodies were confirmed by their various isoelectric points when analyzed by isoelectric focusing. Four of the monoclonal hybridoma cell lines secreted IgM antibodies; two, IgG1; three, IgG2a; and one, IgG2b. The GR-antibody complex was identified in glycerol density gradients by a shift of the 4S GR to an 8.5S or 19S GR-antibody complex when incubated with monoclonal IgG or IgM antibody, respectively. The 10 monoclonal antibodies recognized different determinants on the GR, all situated on that domain of the receptor that is separate from the ligand and DNA-binding domains. Also, the cross-reactivity to the mouse liver GR varied among the monoclonal antibodies. No cross-reactivity was observed to the human lymphocytic GR. NaDodSO4 electrophoresis of a 0.5% pure GR preparation followed by immunoblotting using one of the monoclonal antibodies identified a single peptide with a molecular weight of 94,000, identical to the purified rat liver GR. Images PMID:6200880

  20. Differential regulation of the transcriptional activity of the glucocorticoid receptor through site-specific phosphorylation.

    PubMed

    Kumar, Raj; Calhoun, William J

    2008-12-01

    Post-translational modifications such as phosphorylation are known to play an important role in the gene regulation by the transcription factors including the nuclear hormone receptor superfamily of which the glucocorticoid receptor (GR) is a member. Protein phosphorylation often switches cellular activity from one state to another. Like many other transcription factors, the GR is a phosphoprotein, and phosphorylation plays an important role in the regulation of GR activity. Cell signaling pathways that regulate phosphorylation of the GR and its associated proteins are important determinants of GR function under various physiological conditions. While the role of many phosphorylation sites in the GR is still not fully understood, the role of others is clearer. Several aspects of transcription factor function, including DNA binding affinity, interaction of transactivation domains with the transcription initiation complex, and shuttling between the cytoplasmic compartments, have all been linked to site-specific phosphorylation. All major phosphorylation sites in the human GR are located in the N-terminal domain including the major transactivation domain, AF1. Available literature clearly indicates that many of these potential phosphorylation sites are substrates for multiple kinases, suggesting the potential for a very complex regulatory network. Phosphorylated GR interacts favorably with critical coregulatory proteins and subsequently enhances transcriptional activity. In addition, the activities and specificities of coregulators may be subject to similar regulation by phosphorylation. Regulation of the GR activity due to phosphorylation appears to be site-specific and dependent upon specific cell signaling cascade. Taken together, site-specific phosphorylation and related kinase pathways play an important role in the action of the GR, and more precise mechanistic information will lead to fuller understanding of the complex nature of gene regulation by the GR- and

  1. A sugar gustatory receptor identified from the foregut of cotton bollworm Helicoverpa armigera.

    PubMed

    Xu, Wei; Zhang, Hui-Jie; Anderson, Alisha

    2012-12-01

    Helicoverpa armigera (Hübner) is one of the most polyphagous and cosmopolitan pest species, the larvae of which feed on numerous important crops. The gustatory system is critical in guiding insect feeding behavior. Here, we identified a gustatory receptor from H. armigera, HaGR9, which shows high levels of identity to DmGR43a from Drosophila melanogaster and BmGR9 from Bombyx mori. Reverse transcriptase PCR (RT-PCR) revealed HaGR9 is highly expressed in larval foregut, with little or no expression in other chemosensory tissues. Membrane topology studies indicated that, like two previously studied B. mori GRs, BmGR8 and BmGR53, HaGR9 has an inverted topology relative to G protein-coupled receptors (GPCRs), an intracellular N-terminus and an extracellular C-terminus. Calcium imaging studies confirmed HaGR9 is a sugar receptor showing dose-dependent responses to D-galactose, D-maltose, and D-fructose. This highly-expressed foregut-specific gustatory receptor may contribute to the regulation of larval feeding behavior.

  2. Glyphosate resistance in Ambrosia trifida: Part 1. Novel rapid cell death response to glyphosate.

    PubMed

    Van Horn, Christopher R; Moretti, Marcelo L; Robertson, Renae R; Segobye, Kabelo; Weller, Stephen C; Young, Bryan G; Johnson, William G; Schulz, Burkhard; Green, Amanda C; Jeffery, Taylor; Lespérance, Mackenzie A; Tardif, François J; Sikkema, Peter H; Hall, J Christopher; McLean, Michael D; Lawton, Mark B; Sammons, R Douglas; Wang, Dafu; Westra, Philip; Gaines, Todd A

    2018-05-01

    Glyphosate-resistant (GR) Ambrosia trifida is now present in the midwestern United States and in southwestern Ontario, Canada. Two distinct GR phenotypes are known, including a rapid response (GR RR) phenotype, which exhibits cell death within hours after treatment, and a non-rapid response (GR NRR) phenotype. The mechanisms of resistance in both GR RR and GR NRR remain unknown. Here, we present a description of the RR phenotype and an investigation of target-site mechanisms on multiple A. trifida accessions. Glyphosate resistance was confirmed in several accessions, and whole-plant levels of resistance ranged from 2.3- to 7.5-fold compared with glyphosate-susceptible (GS) accessions. The two GR phenotypes displayed similar levels of resistance, despite having dramatically different phenotypic responses to glyphosate. Glyphosate resistance was not associated with mutations in EPSPS sequence, increased EPSPS copy number, EPSPS quantity, or EPSPS activity. These encompassing results suggest that resistance to glyphosate in these GR RR A. trifida accessions is not conferred by a target-site resistance mechanism. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  3. Granzyme M and K release in human experimental endotoxemia.

    PubMed

    Wensink, Annette C; Wiewel, Maryse A; Jongeneel, Lieneke H; Boes, Marianne; van der Poll, Tom; Hack, C Erik; Bovenschen, Niels

    2016-07-01

    Granzymes are serine proteases involved in killing of tumor cells and virally infected cells. However, granzymes are also upregulated in blood under inflammatory conditions and contribute to cytokine release and processing. Here, we show that granzyme M (GrM) and to a lesser extent GrK are transiently elevated in the circulation following LPS administration in humans. GrM is released upon stimulation of whole blood with LPS or the gram-negative bacteria Escherichia coli BL21, Pseudomonas aeruginosa, and Neisseria meningitidis. GrK is only released upon stimulation with P. aeruginosa. Thus, GrM and GrK are differentially released in response to LPS and gram-negative bacteria. Copyright © 2016 Elsevier GmbH. All rights reserved.

  4. Hydrodynamic properties of the gonadotropin receptor from a murine Leydig tumor cell line are altered by desensitization

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

    Rebois, R.V.; Bradley, R.M.; Titlow, C.C.

    1987-10-06

    The murine Leydig tumor cell line 1 (MLTC-1) contains gonadotropin receptors (GR) that are coupled to adenylate cyclase through the stimulatory guanine nucleotide binding protein (G/sub s/). The binding of human choriogonadotropin (hGC) causes MLTC-1 cells to accumulate cAMP. With time, the ability of MLTC-1 cells to respond to hCG is attenuated by a process called desensitization. The hydrodynamic properties of GR from control and desensitized MLTC-1 cells were studied. Sucrose density gradient sedimentation in H/sub 2/O and D/sub 2/O and gel filtration chromatography were used to estimate the Stokes radius (a), partial specific volume (v/sub c/), sedimentation coefficient (s/submore » 20,w/), and molecular weight (M/sub r/) of the detergent-solubilized hormone-receptor complex (hCG-GR). (/sup 125/I)hCG was bound to MLTC-1 cells under conditions that allow (37/sup 0/C) or prevent (0/sup 0/C) desensitization, and hCG-GR was solubilized in Triton X-100. In the absence of desensitization, control hCG-GR had a M/sub r/ of 213,000, whereas desensitized hCG-GR had a M/sub r/ of 158,000. Deglycosylated hCG (DG-HCG) is an antagonist that binds to GR with high affinity but fails to stimulate adenylate cyclase or cause desensitization. (/sup 125/I)DG-hCG was bound to MLTC-1 cells and DG-hCG-GR solubilized in Triton X-100. The hydrodynamic properties of DG-hCG-GR were the same as that for control hCG-GR. There was no evidence for the association of adenylate cyclase or G/sub s/ with GR in Triton X-100 solubilized preparations. When hCG was cross-linked to GR and solubilized with sodium dodecyl sulfate (SDS), the M/sub r/ was found to be 116,000, which was similar to that determined by SDS-polyacrylamide gel electrophoresis and less than that of the Triton X-100 solubilized control hCG-GR.« less

  5. Graphene transforms wide band gap ZnS to a visible light photocatalyst. The new role of graphene as a macromolecular photosensitizer.

    PubMed

    Zhang, Yanhui; Zhang, Nan; Tang, Zi-Rong; Xu, Yi-Jun

    2012-11-27

    We report the assembly of nanosized ZnS particles on the 2D platform of a graphene oxide (GO) sheet by a facile two-step wet chemistry process, during which the reduced graphene oxide (RGO, also called GR) and the intimate interfacial contact between ZnS nanoparticles and the GR sheet are achieved simultaneously. The ZnS-GR nanocomposites exhibit visible light photoactivity toward aerobic selective oxidation of alcohols and epoxidation of alkenes under ambient conditions. In terms of structure-photoactivity correlation analysis, we for the first time propose a new photocatalytic mechanism where the role of GR in the ZnS-GR nanocomposites acts as an organic dye-like macromolecular "photosensitizer" for ZnS instead of an electron reservoir. This novel photocatalytic mechanism is distinctly different from all previous research on GR-semiconductor photocatalysts, for which GR is claimed to behave as an electron reservoir to capture/shuttle the electrons photogenerated from the semiconductor. This new concept of the reaction mechanism in graphene-semiconductor photocatalysts could provide a new train of thought on designing GR-based composite photocatalysts for targeting applications in solar energy conversion, promoting our in-depth thinking on the microscopic charge carrier transfer pathway connected to the interface between the GR and the semiconductor.

  6. Younger Elementary Students Waste More School Lunch Foods than Older Elementary Students

    PubMed Central

    Niaki, Shahrbanou F.; Moore, Carolyn E.; Chen, Tzu-An

    2016-01-01

    Background Children may not receive the nutritional benefits from school lunch meals if they do not eat the foods served. Objective This study investigated whether there were differences in school lunch foods consumed and wasted by grade level of elementary school students. Design In this cross-sectional study, anonymous meal observations were conducted after students selected their reimbursable school lunch meals in the cafeteria lunch line. The amount of foods selected and consumed was recorded using the quarter waste method and food waste was calculated using the information recorded. Participants/setting During the spring of 2013, eight elementary schools (50% low income) enrolling children in kindergarten through grade 5 in one school district in the Houston, Texas area were selected by the Child Nutrition Director. Main outcome measures The amount of kilocalories (kcal) and foods consumed and the percentage wasted were assessed. Statistical analyses performed Analysis of Covariance (ANCOVA) and post hoc analysis were used to examine food consumption and plate waste by grade level [kindergarten and grade 1 (K-Gr1), grade 2 and 3 (Gr2-3) and grade four and five (Gr4-5)], controlling for student sex and school level free/reduced priced meal eligibility (FRP). Results There were 568 nonrandom lunch meal observations of students included in the analyses. Approximately 48% of the observations were from boys; 50% were from low income schools, and were evenly divided by grade. In general, students in K-Gr1 consumed fewer kcal than both Gr2-3 and Gr4-5 students, and Gr2-3 students consumed significantly fewer kcal than Gr4-5 students. K-Gr1 students also consumed less and wasted more total and red-orange vegetables, total/whole/refined grains, and total protein foods than the older students. Gr2-3 students wasted more calories and total grains than Gr4-5 students. K-Gr1 wasted more fruit than Gr2-3 students. Conclusions Overall, younger students in elementary schools

  7. Age related differences of selected Hatha yoga practices on anthropometric characteristics, muscular strength and flexibility of healthy individuals

    PubMed Central

    Halder, Kaushik; Chatterjee, Abhirup; Pal, Rameshwar; Tomer, Omveer S; Saha, Mantu

    2015-01-01

    Background: Physiological benefits of yoga on volunteers of a particular age group are available. However, reports on efficacy of a specific yoga package on the populace of different age groups from similar occupational background is still very limited. Therefore, the present study was conducted to appraise the effect of a specific Hatha yoga package on anthropometric characteristics, flexibility and muscular strength of healthy individuals of different age groups from similar occupational trade. Materials and Methods: A total of 71 participants (Group All) from Indian Air Force ground personnel volunteered and age wise divided into 3 groups - (i) Group I (Gr. - I) (n1 = 27, 20-29 years), (ii) Group II (Gr. - II) (n2 = 21, 30-39 years) and (iii) Group III (Gr. - III) (n3 = 23, 40-49 years). All the participants undergone selected Hatha yoga training for 1 h daily for a period of 12 weeks. Parameters were recorded before and after the training. Pre and post training differences were assessed by Student's t-test. Results: Body weight (All, Gr. - II and Gr. - III [all P < 0.05]), body mass index (Gr. - II and Gr. - III [both P < 0.01]) and fat% (Gr. - II and III [both P < 0.05]) were decreased significantly. Neck circumference was increased significantly in Gr. - I (P < 0.05) but decreased significantly in Gr. - III (P < 0.05). Chest circumference (All (P < 0.001), in Gr. - I and II [both P < 0.05]), grip strength (All [left: P < 0.01 and right: P < 0.05], in Gr. - I [left: P < 0.05 and right: P < 0.01], in Gr. - II [right: P < 0.05] and in Gr. - III [left: P < 0.05 and right: P < 0.01]), back leg strength (group wise P < 0.001, P < 0.05, P < 0.01 and P < 0.05 respectively) and flexibility (all P < 0.001) were increased significantly. Summary and Conclusion: Hatha yoga can improve anthropometric characteristics, muscular strength and flexibility among volunteers of different age group and can also be helpful in preventing and attenuating age related deterioration of

  8. Regulation of the glucocorticoid receptor via a BET-dependent enhancer drives antiandrogen resistance in prostate cancer.

    PubMed

    Shah, Neel; Wang, Ping; Wongvipat, John; Karthaus, Wouter R; Abida, Wassim; Armenia, Joshua; Rockowitz, Shira; Drier, Yotam; Bernstein, Bradley E; Long, Henry W; Freedman, Matthew L; Arora, Vivek K; Zheng, Deyou; Sawyers, Charles L

    2017-09-11

    In prostate cancer, resistance to the antiandrogen enzalutamide (Enz) can occur through bypass of androgen receptor (AR) blockade by the glucocorticoid receptor (GR). In contrast to fixed genomic alterations, here we show that GR-mediated antiandrogen resistance is adaptive and reversible due to regulation of GR expression by a tissue-specific enhancer. GR expression is silenced in prostate cancer by a combination of AR binding and EZH2-mediated repression at the GR locus, but is restored in advanced prostate cancers upon reversion of both repressive signals. Remarkably, BET bromodomain inhibition resensitizes drug-resistant tumors to Enz by selectively impairing the GR signaling axis via this enhancer. In addition to revealing an underlying molecular mechanism of GR-driven drug resistance, these data suggest that inhibitors of broadly active chromatin-readers could have utility in nuanced clinical contexts of acquired drug resistance with a more favorable therapeutic index.

  9. Correlation of Serum and Salivary Cytokines Level With Clinical Parameters in Metabolic Syndrome With Periodontitis.

    PubMed

    Chauhan, Abhishek; Yadav, Suraj Singh; Dwivedi, Pradeep; Lal, Nand; Usman, Kauser; Khattri, Sanjay

    2016-09-01

    Metabolic Syndrome (MS) and chronic oral condition (periodontitis [PD]) are state of inflammation. The study was conducted to determine alterations in serum and salivary cytokines level in MS and/or chronic PD in the North Indian population. This cross-sectional study carried out in northern part of India. The study subjects of similar ethnicity were recruited according to International Diabetes Federation (IDF) criteria for MS, while chronic PD was diagnosed on the basis of packet depth and clinical attachment level. ELISA method was employed to assess cytokine level. All subjects were divided in four groups Gr A (MS + PD), B (MS), C (PD), and a control Gr D. The serum and salivary tumor necrosis factor alpha (TNF-α) level in Gr A, B, and C was significantly higher than Gr D (P < 0.05). Serum interleukin-10 (IL-10) level in Gr A, B, and C was lower than Gr D (P < 0.05), but this difference was not significant between Gr C and Gr D. Serum IL-10 level in Gr A was significantly lower than Gr C (P < 0.05). Salivary IL-10 level was not significantly altered in any group. Proinflammatory marker TNF-α has correlation with clinical parameters in patients of MS having PD. The study suggests level of salivary TNF-α may be utilized as a surrogate marker of MS and PD. © 2016 Wiley Periodicals, Inc.

  10. EGFR-targeted granzyme B expressed in NK cells enhances natural cytotoxicity and mediates specific killing of tumor cells.

    PubMed

    Oberoi, Pranav; Jabulowsky, Robert A; Bähr-Mahmud, Hayat; Wels, Winfried S

    2013-01-01

    Natural killer (NK) cells are highly specialized effectors of the innate immune system that hold promise for adoptive cancer immunotherapy. Their cell killing activity is primarily mediated by the pro-apoptotic serine protease granzyme B (GrB), which enters targets cells with the help of the pore-forming protein perforin. We investigated expression of a chimeric GrB fusion protein in NK cells as a means to augment their antitumoral activity. For selective targeting to tumor cells, we fused the epidermal growth factor receptor (EGFR) peptide ligand transforming growth factor α (TGFα) to human pre-pro-GrB. Established human NKL natural killer cells transduced with a lentiviral vector expressed this GrB-TGFα (GrB-T) molecule in amounts comparable to endogenous wildtype GrB. Activation of the genetically modified NK cells by cognate target cells resulted in the release of GrB-T together with endogenous granzymes and perforin, which augmented the effector cells' natural cytotoxicity against NK-sensitive tumor cells. Likewise, GrB-T was released into the extracellular space upon induction of degranulation with PMA and ionomycin. Secreted GrB-T fusion protein displayed specific binding to EGFR-overexpressing tumor cells, enzymatic activity, and selective target cell killing in the presence of an endosomolytic activity. Our data demonstrate that ectopic expression of a targeted GrB fusion protein in NK cells is feasible and can enhance antitumoral activity of the effector cells.

  11. Increased antidepressant sensitivity after prefrontal cortex glucocorticoid receptor gene deletion in mice.

    PubMed

    Hussain, Rifat J; Jacobson, Lauren

    2015-01-01

    Our laboratory has previously shown that antidepressants regulate glucocorticoid receptor (GR) expression in the prefrontal cortex (PFC). To determine if PFC GR are involved in antidepressant effects on behavior or hypothalamic-pituitary-adrenocortical (HPA) axis activity, we treated floxed GR male mice with saline or 15 or 30 mg/kg/d imipramine after PFC injection of adeno-associated virus 2/9 vectors transducing expression of Cre recombinase, to knock-down GR (PFC-GRKD), or green fluorescent protein (PFC-GFP), to serve as a control. The pattern of virally transduced GR deletion, common to all imipramine treatment groups, included the infralimbic, prelimbic, and medial anterior cingulate cortex at its largest extent, but was confined to the prelimbic and anterior cingulate cortex at its smallest extent. PFC GR knock-down increased behavioral sensitivity to imipramine, with imipramine-treated PFC-GRKD but not PFC-GFP mice exhibiting significant decreases in depression-like immobility during forced swim. PFC GR deletion did not alter general locomotor activity. The 30 mg/kg dose of imipramine increased plasma corticosterone levels immediately after a 5-min forced swim, but PFC GR knock-down had no significant effect on plasma corticosterone under these experimental conditions. We conclude that PFC GR knock-down, likely limited to the medial prelimbic and anterior cingulate cortices, can increase behavioral sensitivity to antidepressants. These findings indicate a novel role for PFC GR in influencing antidepressant response. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Discrimination between NL1- and NL2-Mediated Nuclear Localization of the Glucocorticoid Receptor

    PubMed Central

    Savory, Joanne G. A.; Hsu, Brian; Laquian, Ian R.; Giffin, Ward; Reich, Terry; Haché, Robert J. G.; Lefebvre, Yvonne A.

    1999-01-01

    Glucocorticoid receptor (GR) cycles between a free liganded form that is localized to the nucleus and a heat shock protein (hsp)-immunophilin-complexed, unliganded form that is usually localized to the cytoplasm but that can also be nuclear. In addition, rapid nucleocytoplasmic exchange or shuttling of the receptor underlies its localization. Nuclear import of liganded GR is mediated through a well-characterized sequence, NL1, adjacent to the receptor DNA binding domain and a second, uncharacterized motif, NL2, that overlaps with the ligand binding domain. In this study we report that rapid nuclear import (half-life [t1/2] of 4 to 6 min) of agonist- and antagonist-treated GR and the localization of unliganded, hsp-associated GRs to the nucleus in G0 are mediated through NL1 and correlate with the binding of GR to pendulin/importin α. By contrast, NL2-mediated nuclear transfer of GR occurred more slowly (t1/2 = 45 min to 1 h), was agonist specific, and appeared to be independent of binding to importin α. Together, these results suggest that NL2 mediates the nuclear import of GR through an alternative nuclear import pathway. Nuclear export of GR was inhibited by leptomycin B, suggesting that the transfer of GR to the cytoplasm is mediated through the CRM1-dependent pathway. Inhibition of GR nuclear export by leptomycin B enhanced the nuclear localization of both unliganded, wild-type GR and hormone-treated NL1− GR. These results highlight that the subcellular localization of both liganded and unliganded GRs is determined, at least in part, by a flexible equilibrium between the rates of nuclear import and export. PMID:9891038

  13. Growth restriction, leptin, and the programming of adult behavior in mice.

    PubMed

    Meyer, Lauritz R; Zhu, Vivian; Miller, Alise; Roghair, Robert D

    2014-12-15

    Prematurity and neonatal growth restriction (GR) are risk factors for autism and attention deficit hyperactivity disorder (ADHD). Leptin production is suppressed during periods of undernutrition, and we have shown that isolated neonatal leptin deficiency leads to adult hyperactivity while neonatal leptin supplementation normalizes the brain morphology of GR mice. We hypothesized that neonatal leptin would prevent the development of GR-associated behavioral abnormalities. From postnatal day 4-14, C57BL/6 mice were randomized to daily injections of saline or leptin (80ng/g), and GR was identified by a weanling weight below the tenth percentile. The behavioral phenotypes of GR and control mice were assessed beginning at 4 months. Within the tripartite chamber, GR mice had significantly impaired social interaction. Baseline escape times from the Barnes maze were faster for GR mice (65+/-6s vs 87+/-7s for controls, p<0.05), but GR mice exhibited regression in their escape times on days 2 and 3 (56% regressed vs 22% of control saline mice, p<0.05). Compared to controls, GR mice entered the open arms of the elevated plus maze more often and stayed there longer (72+/-10s vs 36+/-5s, p<0.01). Neonatal leptin supplementation normalized the behavior of GR mice across all behavioral assays. In conclusion, GR alters the social interactions, learning and activity of mice, and supplementation with the neurotrophic hormone leptin mitigates these effects. We speculate neonatal leptin deficiency may contribute to the adverse neurodevelopmental outcomes associated with postnatal growth restriction, and postnatal leptin therapy may be protective. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Three-dimensional fusion of spaceborne and ground radar reflectivity data using a neural network-based approach

    NASA Astrophysics Data System (ADS)

    Kou, Leilei; Wang, Zhuihui; Xu, Fen

    2018-03-01

    The spaceborne precipitation radar onboard the Tropical Rainfall Measuring Mission satellite (TRMM PR) can provide good measurement of the vertical structure of reflectivity, while ground radar (GR) has a relatively high horizontal resolution and greater sensitivity. Fusion of TRMM PR and GR reflectivity data may maximize the advantages from both instruments. In this paper, TRMM PR and GR reflectivity data are fused using a neural network (NN)-based approach. The main steps included are: quality control of TRMM PR and GR reflectivity data; spatiotemporal matchup; GR calibration bias correction; conversion of TRMM PR data from Ku to S band; fusion of TRMM PR and GR reflectivity data with an NN method; interpolation of reflectivity data that are below PR's sensitivity; blind areas compensation with a distance weighting-based merging approach; combination of three types of data: data with the NN method, data below PR's sensitivity and data within compensated blind areas. During the NN fusion step, the TRMM PR data are taken as targets of the training NNs, and gridded GR data after horizontal downsampling at different heights are used as the input. The trained NNs are then used to obtain 3D high-resolution reflectivity from the original GR gridded data. After 3D fusion of the TRMM PR and GR reflectivity data, a more complete and finer-scale 3D radar reflectivity dataset incorporating characteristics from both the TRMM PR and GR observations can be obtained. The fused reflectivity data are evaluated based on a convective precipitation event through comparison with the high resolution TRMM PR and GR data with an interpolation algorithm.

  15. How automatic is the musical stroop effect? Commentary on “the musical stroop effect: opening a new avenue to research on automatisms” by l. Grégoire, P. Perruchet, and B. Poulin-Charronnat (Experimental Psychology, 2013, vol. 60, pp. 269–278).

    PubMed

    Moeller, Birte; Frings, Christian

    2014-01-01

    Grégoire, Perruchet, and Poulin-Charronnat (2013) investigated a musical variant of the reversed Stroop effect. According to the authors, one big advantage of this variant is that the automaticity of note naming can be better controlled than in other Stroop variants as musicians are very practiced in note reading whereas non-musicians are not. In this comment we argue that at present the exact impact of automaticity in this Stroop variant remains somewhat unclear for at least three reasons, namely due to the type of information that is automatically retrieved when notes are encountered, due to the possible influence of object-based attention, and finally due to the fact that the exact influence of expertise on interference cannot be pinpointed with an extreme group design.

  16. Cryptic glucocorticoid receptor-binding sites pervade genomic NF-κB response elements.

    PubMed

    Hudson, William H; Vera, Ian Mitchelle S de; Nwachukwu, Jerome C; Weikum, Emily R; Herbst, Austin G; Yang, Qin; Bain, David L; Nettles, Kendall W; Kojetin, Douglas J; Ortlund, Eric A

    2018-04-06

    Glucocorticoids (GCs) are potent repressors of NF-κB activity, making them a preferred choice for treatment of inflammation-driven conditions. Despite the widespread use of GCs in the clinic, current models are inadequate to explain the role of the glucocorticoid receptor (GR) within this critical signaling pathway. GR binding directly to NF-κB itself-tethering in a DNA binding-independent manner-represents the standing model of how GCs inhibit NF-κB-driven transcription. We demonstrate that direct binding of GR to genomic NF-κB response elements (κBREs) mediates GR-driven repression of inflammatory gene expression. We report five crystal structures and solution NMR data of GR DBD-κBRE complexes, which reveal that GR recognizes a cryptic response element between the binding footprints of NF-κB subunits within κBREs. These cryptic sequences exhibit high sequence and functional conservation, suggesting that GR binding to κBREs is an evolutionarily conserved mechanism of controlling the inflammatory response.

  17. Electrolyte and composition effects on the performances of asymmetric supercapacitors constructed with Mn3O4 nanoparticles-graphene nanocomposites

    NASA Astrophysics Data System (ADS)

    Xiao, Yuanhua; Cao, Yongbo; Gong, Yuyin; Zhang, Aiqin; Zhao, Jihong; Fang, Shaoming; Jia, Dianzeng; Li, Feng

    2014-01-01

    Nanocomposites of Mn3O4 nanoparticles and graphene (GR) nanosheets - Mn3O4@GR can be made by growing Mn3O4 nanoparticles directly on the surfaces of GR in solvothermal reactions. The asymmetric supercapacitors constructed with Mn3O4@GR as positive and activated carbon (AC) as negative electrodes, respectively, show highly enhanced performances in energy storage. It was found that the electrolytes employed in constructing electrodes of the devices can influence the performances of Mn3O4@GR supercapacitors dramatically. Compared to their energy density in KOH electrolyte, the devices exhibit improved charge storage performances in Na2SO4 electrolyte. Furthermore, the charge storage abilities of the devices are closely related to the amount of Mn3O4 nanoparticles loaded onto the surface of GR nanosheets. The performances of Mn3O4@GR//AC asymmetric supercapacitors can be optimized by carefully tailoring the composition of electrode materials and adjusting the electrolytes for making the devices.

  18. Coregulator profiling of the glucocorticoid receptor in lymphoid malignancies

    PubMed Central

    Clarisse, Dorien; Thommis, Jonathan; Van Wesemael, Karlien; Houtman, René; Ratman, Dariusz; Tavernier, Jan; Offner, Fritz; Beck, Ilse; De Bosscher, Karolien

    2017-01-01

    Coregulators cooperate with nuclear receptors, such as the glucocorticoid receptor (GR), to enhance or repress transcription. These regulatory proteins are implicated in cancer, yet, their role in lymphoid malignancies, including multiple myeloma (MM) and acute lymphoblastic leukemia (ALL), is largely unknown. Here, we report the use and extension of the microarray assay for real-time nuclear receptor coregulator interactions (MARCoNI) technology to detect coregulator associations with endogenous GR in cell lysates. We use MARCoNI to determine the GR coregulator profile of glucocorticoid-sensitive (MM and ALL) and glucocorticoid-resistant (ALL) cells, and identify common and unique coregulators for different cell line comparisons. Overall, we identify SRC-1/2/3, PGC-1α, RIP140 and DAX-1 as the strongest interacting coregulators of GR in MM and ALL cells and show that the interaction strength does not correlate with GR protein levels. Lastly, as a step towards patient samples, we determine the GR coregulator profile of peripheral blood mononuclear cells. We profile the interactions between GR and coregulators in MM and ALL cells and suggest to further explore the GR coregulator profile in hematological patient samples. PMID:29312638

  19. Coregulator profiling of the glucocorticoid receptor in lymphoid malignancies.

    PubMed

    Clarisse, Dorien; Thommis, Jonathan; Van Wesemael, Karlien; Houtman, René; Ratman, Dariusz; Tavernier, Jan; Offner, Fritz; Beck, Ilse; De Bosscher, Karolien

    2017-12-12

    Coregulators cooperate with nuclear receptors, such as the glucocorticoid receptor (GR), to enhance or repress transcription. These regulatory proteins are implicated in cancer, yet, their role in lymphoid malignancies, including multiple myeloma (MM) and acute lymphoblastic leukemia (ALL), is largely unknown. Here, we report the use and extension of the microarray assay for real-time nuclear receptor coregulator interactions (MARCoNI) technology to detect coregulator associations with endogenous GR in cell lysates. We use MARCoNI to determine the GR coregulator profile of glucocorticoid-sensitive (MM and ALL) and glucocorticoid-resistant (ALL) cells, and identify common and unique coregulators for different cell line comparisons. Overall, we identify SRC-1/2/3, PGC-1α, RIP140 and DAX-1 as the strongest interacting coregulators of GR in MM and ALL cells and show that the interaction strength does not correlate with GR protein levels. Lastly, as a step towards patient samples, we determine the GR coregulator profile of peripheral blood mononuclear cells. We profile the interactions between GR and coregulators in MM and ALL cells and suggest to further explore the GR coregulator profile in hematological patient samples.

  20. Ultradian hormone stimulation induces glucocorticoid receptor-mediated pulses of gene transcription.

    PubMed

    Stavreva, Diana A; Wiench, Malgorzata; John, Sam; Conway-Campbell, Becky L; McKenna, Mervyn A; Pooley, John R; Johnson, Thomas A; Voss, Ty C; Lightman, Stafford L; Hager, Gordon L

    2009-09-01

    Studies on glucocorticoid receptor (GR) action typically assess gene responses by long-term stimulation with synthetic hormones. As corticosteroids are released from adrenal glands in a circadian and high-frequency (ultradian) mode, such treatments may not provide an accurate assessment of physiological hormone action. Here we demonstrate that ultradian hormone stimulation induces cyclic GR-mediated transcriptional regulation, or gene pulsing, both in cultured cells and in animal models. Equilibrium receptor-occupancy of regulatory elements precisely tracks the ligand pulses. Nascent RNA transcripts from GR-regulated genes are released in distinct quanta, demonstrating a profound difference between the transcriptional programs induced by ultradian and constant stimulation. Gene pulsing is driven by rapid GR exchange with response elements and by GR recycling through the chaperone machinery, which promotes GR activation and reactivation in response to the ultradian hormone release, thus coupling promoter activity to the naturally occurring fluctuations in hormone levels. The GR signalling pathway has been optimized for a prompt and timely response to fluctuations in hormone levels, indicating that biologically accurate regulation of gene targets by GR requires an ultradian mode of hormone stimulation.

  1. Challenges in graphene integration for high-frequency electronics

    NASA Astrophysics Data System (ADS)

    Giannazzo, F.; Fisichella, G.; Greco, G.; Roccaforte, F.

    2016-06-01

    This paper provides an overview of the state-of-the-art research on graphene (Gr) for high-frequency (RF) devices. After discussing current limitations of lateral Gr RF transistors, novel vertical devices concepts such as the Gr Base Hot Electron Transistor (GBHET) will be introduced and the main challenges in Gr integration within these architectures will be discussed. In particular, a GBHET device based on Gr/AlGaN/GaN heterostructure will be considered. An approach to the fabrication of this heterostructure by transfer of CVD grown Gr on copper to the AlGaN surface will be presented. The morphological and electrical properties of this system have been investigated at nanoscale by atomic force microscopy (AFM) and conductive atomic force microscopy (CAFM). In particular, local current-voltage measurements by the CAFM probe revealed the formation of a Schottky contact with low barrier height (˜0.41 eV) and excellent lateral uniformity between Gr and AlGaN. Basing on the electrical parameters extracted from this characterization, the theoretical performances of a GBHET formed by a metal/Al2O3/Gr/AlGaN/GaN stack have been evaluated.

  2. J-R fracture characteristics of ferritic steels for RPVs and RCS piping of nuclear power plants

    NASA Astrophysics Data System (ADS)

    Yoon, Ji-Hyun; Lee, Bong-Sang; Hong, Jun-Hwa

    2001-10-01

    J-R fracture resistance tests have been performed on 3 heats of SA508-Gr.3 nuclear reactor pressure vessel (RPV) steel as well as 2 heats of SA516-Gr.70 and a heat of SA508-Gr.1a steels for nuclear reactor coolant system (RCS) piping. For the latter two steels, dynamic in addition to static J-R fracture resistances were investigated. From the test results of the SA508-Gr.3 steels, the J-R fracture resistance was superior in the following order: Si-killing steel, modified VCD steel and VCD steel. Microstructural analyses were carried out to correlate J-R fracture resistances with microstructural characteristics. According to the test results for SA508-Gr.1a and SA516-Gr.70 steels, all of the tested steels showed steep drops in fracture resistance at certain temperature and loading rate combinations. One heat of SA516-Gr.70 steel was very sensitive to dynamic strain aging and its fracture resistance was significantly low. It was concluded that microstructural and chemical factors affect the J-R fracture and DSA characteristics of SA516-Gr.70 steels.

  3. DFT Studies of Graphene-Functionalised Derivatives of Capecitabine

    NASA Astrophysics Data System (ADS)

    Aramideh, Mehdi; Mirzaei, Mahmoud; Khodarahmi, Ghadamali; Gülseren, Oğuz

    2017-11-01

    Cancer is one of the major problems for so many people around the world; therefore, dedicating efforts to explore efficient therapeutic methodologies is very important for researchers of life sciences. In this case, nanostructures are expected to be carriers of medicinal compounds for targeted drug design and delivery purposes. Within this work, the graphene (Gr)-functionalised derivatives of capecitabine (CAP), as a representative anticancer, have been studied based on density functional theory calculations. Two different sizes of Gr molecular models have been used for the functionalisation of CAP counterparts, CAP-Gr3 and CAP-Gr5, to explore the effects of Gr-functionalisation on the original properties of CAP. All singular and functionalised molecular models have been optimised and the molecular and atomic scale properties have been evaluated for the optimised structures. Higher formation favourability has been obtained for CAP-Gr5 in comparison with CAP-Gr3 and better structural stability has been obtained in the water-solvated system than the isolated gas-phase system for all models. The CAP-Gr5 model could play a better role of electron transferring in comparison with the CAP-Gr3 model. As a concluding remark, the molecular properties of CAP changed from singular to functionalised models whereas the atomic properties remained almost unchanged, which is expected for a carrier not to use significant perturbations to the original properties of the carried counterpart.

  4. Reduced glucocorticoid receptor expression predicts bladder tumor recurrence and progression.

    PubMed

    Ishiguro, Hitoshi; Kawahara, Takashi; Zheng, Yichun; Netto, George J; Miyamoto, Hiroshi

    2014-08-01

    To assess the levels of glucocorticoid receptor (GR) expression in bladder tumors because the status and its prognostic value remain largely unknown. We immunohistochemically stained for GR in bladder tumor and matched non-neoplastic bladder tissue specimens. Overall, GR was positive in 129 (87%) of 149 urothelial tumors, which was significantly (P=.026) lower than in non-neoplastic urothelium (90 [96%] of 94). Forty-two (79%) of 53 low-grade tumors vs 45 (47%) of 96 high-grade carcinomas (P<.001) and 61 (73%) of 84 non-muscle-invasive (NMI) tumors vs 26 (40%) of 65 muscle-invasive (MI) carcinomas (P<.001) were moderately to strongly immunoreactive for GR. Kaplan-Meier and log-rank tests revealed that loss or weak positivity of GR significantly or marginally correlated with recurrence of NMI tumors (P=.025), progression of MI tumors (P=.082), and cancer-specific survival of MI tumors (P=.067). Multivariate analysis identified low GR expression as a strong predictor for recurrence of NMI tumors (P=.034). GR expression was downregulated in bladder tumors compared with nonneoplastic bladder tumors and in high-grade/MI tumors compared with low-grade/NMI tumors. Decreased expression of GR, as an independent prognosticator, predicted recurrence of NMI tumors. These results support experimental evidence suggesting an inhibitory role of GR signals in bladder cancer outgrowth. Copyright© by the American Society for Clinical Pathology.

  5. Differential Subcellular Localization of the Glucocorticoid Receptor in Distinct Neural Stem and Progenitor Populations of the Mouse Telencephalon In Vivo

    PubMed Central

    Tsiarli, Maria A.; Monaghan, A. Paula; DeFranco, Donald B.

    2013-01-01

    Glucocorticoids are given to pregnant women at risk for premature delivery to promote lung maturation. Despite reports of detrimental effects of glucocorticoids on telencephalic neural stem/progenitor cells (NSPCs), the regional and cellular expression of the glucocorticoid receptor (GR) in various NSPC populations in the intact brain has not been thoroughly assessed. Therefore in this study we performed a detailed analysis of GR protein expression in the developing mouse ventral and dorsal telencephalon in vivo. At embryonic day 11.5 (E11.5), the majority of Pax6-positive radial glial cells (RGCs) and Tbr2-positive intermediate progenitor cells (IPCs) expressed nuclear GR, while a small number of RGCs on the apical ventricular zone (aVZ), expressed cytoplasmic GR. However, on E13.5, the latter population of RGCs increased in size, whereas abventricular NSPCs and especially neurons of the cortical plate, expressed nuclear GR. In IPCs, GR was always nuclear. A similar expression profile was observed throughout the ventral telencephalon, hippocampus and olfactory bulb, with NSPCs of the aVZ primarily expressing cytoplasmic GR, while abventricular NSPCs and mature cells primarily expressed nuclear GR. Close to birth, nuclear GR accumulated within specific cortical areas such as layer V, the subplate and CA1 area of the hippocampus. In summary, our data show that GR protein is present in early NSPCs of the dorsal and ventral telencephalon at E11.5 and primarily occupies the nucleus. Moreover, our study suggests that the subcellular localization of the receptor may be subjected to region and neurodevelopmental stage-specific regulation. PMID:23751362

  6. Synthesis of surface molecular imprinted TiO2/graphene photocatalyst and its highly efficient photocatalytic degradation of target pollutant under visible light irradiation

    NASA Astrophysics Data System (ADS)

    Lai, Cui; Wang, Man-Man; Zeng, Guang-Ming; Liu, Yun-Guo; Huang, Dan-Lian; Zhang, Chen; Wang, Rong-Zhong; Xu, Piao; Cheng, Min; Huang, Chao; Wu, Hai-Peng; Qin, Lei

    2016-12-01

    The molecular imprinted TiO2/graphene photocatalyst (MIP-TiO2/GR) was successfully prepared with bisphenol A (BPA) as the template molecule (target pollutant) and o-phenylenediamine (OPDA) as functional monomers by the surface molecular imprinting method. The combination between BPA and OPDA led to the formation of the precursor, and the subsequent polymerization of OPDA initiated by ultraviolet radiation can ensure the realization of MIP-TiO2/GR. The samples were characterized by SEM, EDS, XRD, BET, UV-vis DRS and Zeta potential. In addition, adsorption capacities, adsorption selectivity and visible light photocatalytic performances of MIP-TiO2/GR and non-imprinted TiO2/graphene (NIP-TiO2/GR) were evaluated. Moreover, the effects of pH and initial BPA concentration on removal efficiency of BPA were also investigated. The results showed that MIP-TiO2/GR exhibited better adsorption capacity and adsorption selectivity towards the template molecule compared to NIP-TiO2/GR due to the imprinted cavities on the surface of MIP-TiO2/GR. Moreover, the photocatalytic activity of MIP-TiO2/GR toward the target molecules was stronger than that of NIP-TiO2/GR as a result of large adsorption capacity to target molecules and narrow band gap energy on MIP-TiO2/GR. Therefore, modifying the photocatalyst by the surface molecular imprinting is a promising method to improve the molecule recognition and photocatalytic efficiency of photocatalyst for target pollutant.

  7. Structure and Dynamic Properties of a Glucocorticoid Receptor-Induced Chromatin Transition

    PubMed Central

    Fletcher, Terace M.; Ryu, Byung-Woo; Baumann, Christopher T.; Warren, Barbour S.; Fragoso, Gilberto; John, Sam; Hager, Gordon L.

    2000-01-01

    Activation of the mouse mammary tumor virus (MMTV) promoter by the glucocorticoid receptor (GR) is associated with a chromatin structural transition in the B nucleosome region of the viral long terminal repeat (LTR). Recent evidence indicates that this transition extends upstream of the B nucleosome, encompassing a region larger than a single nucleosome (G. Fragoso, W. D. Pennie, S. John, and G. L. Hager, Mol. Cell. Biol. 18:3633–3644). We have reconstituted MMTV LTR DNA into a polynucleosome array using Drosophila embryo extracts. We show binding of purified GR to specific GR elements within a large, multinucleosome array and describe a GR-induced nucleoprotein transition that is dependent on ATP and a HeLa nuclear extract. Previously uncharacterized GR binding sites in the upstream C nucleosome region are involved in the extended region of chromatin remodeling. We also show that GR-dependent chromatin remodeling is a multistep process; in the absence of ATP, GR binds to multiple sites on the chromatin array and prevents restriction enzyme access to recognition sites. Upon addition of ATP, GR induces remodeling and a large increase in access to enzymes sites within the transition region. These findings suggest a dynamic model in which GR first binds to chromatin after ligand activation, recruits a remodeling activity, and is then lost from the template. This model is consistent with the recent description of a “hit-and-run” mechanism for GR action in living cells (J. G. McNally, W. G. Müller, D. Walker, and G. L. Hager, Science 287:1262–1264, 2000). PMID:10938123

  8. Pilot evaluation of four experimental conditioning treatments to improve the bond strength between resin cement and Y-TZP ceramic.

    PubMed

    Monaco, Carlo; Cardelli, Paolo; Scotti, Roberto; Valandro, Luiz Felipe

    2011-02-01

    This study evaluated the bond strength between resin cement and Y-TZP ceramic (Yttrium-stabilized Tetragonal Zirconia Polycrystalline) submitted to different surface conditionings. Fifty Y-TZP ceramic discs (Ø= 10 mm) were allocated into five groups: Gr1 (control)-no conditioning; Gr2-tribochemical silica coating (30-μm SiO(2)) before sintering; Gr3-air abrasion with 50-μm Al(2)O(3) before sintering; Gr4-air abrasion with 110-μ Al(2)O(3) before sintering; Gr5 - air abrasion with 50-μm Al(2)O(3) after sintering. After specimen preparation, cylinders of composite resin were prepared and immediately cemented onto the ceramic. A shear test was performed. One-way ANOVA indicated a statistically significant difference among the groups (p= 0.0019). The mean shear bond strengths (MPa) were: Gr1 = 4.7 ± 0.8,(b) Gr2 = 4.6 ± 0.9,(b) Gr3 = 6.4 ± 1.0,(a) Gr4 = 6.5 ± 1.8,(a) Gr5 = 6 ± 1.3(ab) (same superscript letter indicates statistical similarity). Adhesive fracture between the ceramic and resin cement was the most common failure. No complete cohesive fracture at the ceramic or composite cylinders was noted. Within the limitations of this study, additional surface treatment with air abrasion before and after sintering provided a significant increase in bond strength. Tribochemical silica coating before sintering was not effective as a surface treatment. © 2011 by The American College of Prosthodontists.

  9. Separation of an associated 90K heat shock protein from the glucocorticoid receptor complex

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

    Miller-Diener, A.; Kirsch, T.; Grove, B.

    1986-05-01

    A 90K heat shock protein(HSP), observed to copurify with the glucocorticoid receptor(GR), can be separated from the complex by 2 methods, allowing investigation of the role of HSP on kinase activity that was previously reported to be inherent to purified activated GR. Na/sub 2/MoO/sub 4/ stabilized unactivated rat hepatic GR complexes have been purified to >10,000-fold using a purification scheme that involves batchwise treatment of cytosol with phosphocellulose/DNAcellulose, elution from an affinity resin, gel filtration and ion exchange chromatography. Samples were subjected to 10-20% gradient SDS-PAGE. Proteins were transferred to nitrocellulose and blotted against monoclonal antibodies to GR(3A6), HSP ormore » nonspecific IgM/G. Immunoblots indicated that HSP was separated from unactivated GR complexes at the affinity step prior to elution of GR with active steroid. GR eluted from the resin with /sup 3/H Triamcinolone acetonide or /sup 3/H Dexamethasone mesylate had an apparent M/sub r/ = 94-96,000 for the steroid binding subunit and is recognized by 3A6. Purification of GR minus the affinity step resulted in copurification of HSP throughout the procedure. However, after Sephadex G75 filtration and subsequent incubation at 25/sup 0/C, 30 min., HSP was separated from activated (DNA binding) GR on DEAE cellulose-52. HSP did not enhance or inhibit /sup 32/P incorporation of the 94K steroid binding subunit nor did it affect phosphorylation of histones by GR.« less

  10. Reduction of infarct size by gentle reperfusion without activation of reperfusion injury salvage kinases in pigs.

    PubMed

    Musiolik, Judith; van Caster, Patrick; Skyschally, Andreas; Boengler, Kerstin; Gres, Petra; Schulz, Rainer; Heusch, Gerd

    2010-01-01

    Reperfusion is mandatory to salvage ischaemic myocardium from infarction, but also induces additional reperfusion injury and contributes to infarct size (IS). Gentle reperfusion (GR) has been proposed to attenuate reperfusion injury, but this remains contentious. We now investigated whether (i) GR reduces IS and (ii) GR is associated with the activation of reperfusion injury salvage kinases (RISK). Anaesthetized pigs were subjected to 90 min left anterior descending coronary artery hypoperfusion and 120 min reperfusion. GR was induced by slowly increasing coronary inflow back to baseline over 30 min, using an exponential algorithm [F(t) = F(i)+e(-(0.1)(t)((min)-3)).(F(b)-F(i)); F(b), coronary inflow at baseline; F(i), coronary inflow during ischaemia; n = 12]. Pigs subjected to immediate full reperfusion (IFR; n = 13) served as controls. IS was determined by triphenyl tetrazolium chloride staining. The expression level of phosphorylated RISK proteins was determined by western blot analysis in myocardial biopsies taken at baseline, after 80-85 min ischaemia and at 10, 30, and 120 min reperfusion. In additional experiments with IFR (n = 3) and GR (n = 3), the PI3-AKT and MEK1/2-ERK1/2 pathways were pharmacologically blocked (BL). IS was 37 +/- 2% (mean +/- SEM) of the area at risk with IFR and 29 +/- 1% (P < 0.05) with GR. RISK phosphorylation was similar between GR and IFR at baseline and 85 min ischaemia. At 10 min reperfusion, RISK phosphorylation was increased with IFR, but not with GR. At 30 and 120 min reperfusion, RISK phosphorylation was still greater with IFR than GR. RISK blockade did not abolish the IS reduction by GR (BL-IFR: 27 +/- 4% of the area at risk; BL-GR: 42 +/- 5%; P < 0.05). Gentle reperfusion reduces infarct size in pigs, but RISK activation is not causally involved in this infarct size reduction.

  11. Arabidopsis GLUTATHIONE REDUCTASE1 Plays a Crucial Role in Leaf Responses to Intracellular Hydrogen Peroxide and in Ensuring Appropriate Gene Expression through Both Salicylic Acid and Jasmonic Acid Signaling Pathways1[C][W][OA

    PubMed Central

    Mhamdi, Amna; Hager, Jutta; Chaouch, Sejir; Queval, Guillaume; Han, Yi; Taconnat, Ludivine; Saindrenan, Patrick; Gouia, Houda; Issakidis-Bourguet, Emmanuelle; Renou, Jean-Pierre; Noctor, Graham

    2010-01-01

    Glutathione is a major cellular thiol that is maintained in the reduced state by glutathione reductase (GR), which is encoded by two genes in Arabidopsis (Arabidopsis thaliana; GR1 and GR2). This study addressed the role of GR1 in hydrogen peroxide (H2O2) responses through a combined genetic, transcriptomic, and redox profiling approach. To identify the potential role of changes in glutathione status in H2O2 signaling, gr1 mutants, which show a constitutive increase in oxidized glutathione (GSSG), were compared with a catalase-deficient background (cat2), in which GSSG accumulation is conditionally driven by H2O2. Parallel transcriptomics analysis of gr1 and cat2 identified overlapping gene expression profiles that in both lines were dependent on growth daylength. Overlapping genes included phytohormone-associated genes, in particular implicating glutathione oxidation state in the regulation of jasmonic acid signaling. Direct analysis of H2O2-glutathione interactions in cat2 gr1 double mutants established that GR1-dependent glutathione status is required for multiple responses to increased H2O2 availability, including limitation of lesion formation, accumulation of salicylic acid, induction of pathogenesis-related genes, and signaling through jasmonic acid pathways. Modulation of these responses in cat2 gr1 was linked to dramatic GSSG accumulation and modified expression of specific glutaredoxins and glutathione S-transferases, but there is little or no evidence of generalized oxidative stress or changes in thioredoxin-associated gene expression. We conclude that GR1 plays a crucial role in daylength-dependent redox signaling and that this function cannot be replaced by the second Arabidopsis GR gene or by thiol systems such as the thioredoxin system. PMID:20488891

  12. Arabidopsis GLUTATHIONE REDUCTASE1 plays a crucial role in leaf responses to intracellular hydrogen peroxide and in ensuring appropriate gene expression through both salicylic acid and jasmonic acid signaling pathways.

    PubMed

    Mhamdi, Amna; Hager, Jutta; Chaouch, Sejir; Queval, Guillaume; Han, Yi; Taconnat, Ludivine; Saindrenan, Patrick; Gouia, Houda; Issakidis-Bourguet, Emmanuelle; Renou, Jean-Pierre; Noctor, Graham

    2010-07-01

    Glutathione is a major cellular thiol that is maintained in the reduced state by glutathione reductase (GR), which is encoded by two genes in Arabidopsis (Arabidopsis thaliana; GR1 and GR2). This study addressed the role of GR1 in hydrogen peroxide (H(2)O(2)) responses through a combined genetic, transcriptomic, and redox profiling approach. To identify the potential role of changes in glutathione status in H(2)O(2) signaling, gr1 mutants, which show a constitutive increase in oxidized glutathione (GSSG), were compared with a catalase-deficient background (cat2), in which GSSG accumulation is conditionally driven by H(2)O(2). Parallel transcriptomics analysis of gr1 and cat2 identified overlapping gene expression profiles that in both lines were dependent on growth daylength. Overlapping genes included phytohormone-associated genes, in particular implicating glutathione oxidation state in the regulation of jasmonic acid signaling. Direct analysis of H(2)O(2)-glutathione interactions in cat2 gr1 double mutants established that GR1-dependent glutathione status is required for multiple responses to increased H(2)O(2) availability, including limitation of lesion formation, accumulation of salicylic acid, induction of pathogenesis-related genes, and signaling through jasmonic acid pathways. Modulation of these responses in cat2 gr1 was linked to dramatic GSSG accumulation and modified expression of specific glutaredoxins and glutathione S-transferases, but there is little or no evidence of generalized oxidative stress or changes in thioredoxin-associated gene expression. We conclude that GR1 plays a crucial role in daylength-dependent redox signaling and that this function cannot be replaced by the second Arabidopsis GR gene or by thiol systems such as the thioredoxin system.

  13. Current transport in graphene/AlGaN/GaN vertical heterostructures probed at nanoscale.

    PubMed

    Fisichella, Gabriele; Greco, Giuseppe; Roccaforte, Fabrizio; Giannazzo, Filippo

    2014-08-07

    Vertical heterostructures combining two or more graphene (Gr) layers separated by ultra-thin insulating or semiconductor barriers represent very promising systems for next generation electronics devices, due to the combination of high speed operation with wide-range current modulation by a gate bias. They are based on the specific mechanisms of current transport between two-dimensional-electron-gases (2DEGs) in close proximity. In this context, vertical devices formed by Gr and semiconductor heterostructures hosting an "ordinary" 2DEG can be also very interesting. In this work, we investigated the vertical current transport in Gr/Al(0.25)Ga(0.75)N/GaN heterostructures, where Gr is separated from a high density 2DEG by a ∼ 24 nm thick AlGaN barrier layer. The current transport from Gr to the buried 2DEG was characterized at nanoscale using conductive atomic force microscopy (CAFM) and scanning capacitance microscopy (SCM). From these analyses, performed both on Gr/AlGaN/GaN and on AlGaN/GaN reference samples using AFM tips with different metal coatings, the Gr/AlGaN Schottky barrier height ΦB and its lateral uniformity were evaluated, as well as the variation of the carrier densities of graphene (ngr) and AlGaN/GaN 2DEG (ns) as a function of the applied bias. A low Schottky barrier (∼ 0.40 eV) with excellent spatial uniformity was found at the Gr/AlGaN interface, i.e., lower compared to the measured values for metal/AlGaN contacts, which range from ∼ 0.6 to ∼ 1.1 eV depending on the metal workfunction. The electrical behavior of the Gr/AlGaN contact has been explained by Gr interaction with AlGaN donor-like surface states located in close proximity, which are also responsible of high n-type Gr doping (∼ 1.3 × 10(13) cm(-2)). An effective modulation of ns by the Gr Schottky contact was demonstrated by capacitance analysis under reverse bias. From this basic understanding of transport properties in Gr/AlGaN/GaN heterostructures, novel vertical field effect

  14. Low Phase Noise Fiber Optics Links for Space Applications

    DTIC Science & Technology

    2005-07-13

    photo- oscillateur intégré pour 17 dB de pertes optiques Liaison active à 874,2 MHz avec photo- oscillateur intégré pour 18 dB de pertes optiques Liaison...active à 874,2 MHz avec photo- oscillateur intégré pour 20 dB de pertes optiques Liaison active à 874,2 MHz avec photo- oscillateur intégré pour 23 dB...de pertes optiques Liaison active à 874,2 MHz avec photo- oscillateur intégré pour 25 dB de pertes optiques Liaison active à 874,2 MHz avec photo

  15. A report on the current status of grand rounds in radiology residency programs in the United States.

    PubMed

    Yablon, Corrie M; Wu, Jim S; Slanetz, Priscilla J; Eisenberg, Ronald L

    2011-12-01

    A national needs assessment of radiology program directors was performed to characterize grand rounds (GR) programs, assess the perceived educational value of GR programs, and determine the impact of the recent economic downturn on GR. A 28-question survey was developed querying the organizational logistics of GR programs, types of speakers, content of talks, honoraria, types of speakers invited, response to the economic downturn, types of speaker interaction with residents, and perceived educational value of GR. Questions were in multiple-choice, yes-or-no, and five-point Likert-type formats. The survey was distributed to the program directors of all radiology residencies within the United States. Fifty-seven of 163 programs responded, resulting in a response rate of 36%. Thirty-eight programs (67%) were university residencies and 10 (18%) were university affiliated. Eighty-two percent of university and 60% of university-affiliated residencies had their own GR programs, while only 14% of community and no military residencies held GR. GR were held weekly in 18% of programs, biweekly in 8%, monthly in 42%, bimonthly in 16%, and less frequently than every 2 months in 16%. All 38 programs hosting GR reported a broad spectrum of presentations, including talks on medical education (66%), clinical and evidence-based medicine (55%), professionalism (45%), ethics (45%), quality assurance (34%), global health (26%), and resident presentations (26%). All programs invited speakers from outside the institution, but there was variability with regard to the frequency of visits and whether invited speakers were from out of town. As a result of recent economic events, one radiology residency (3%) completely canceled its GR program. Others decreased the number of speakers from outside their cities (40%) or decreased the number of speakers from within their own cities (16%). Honoraria were paid to speakers by 95% of responding programs. Most program directors (79%) who had their own

  16. Structural health monitoring of the Gröndals Bridge in Sweden: the behaviour of CFRP strengthening in cold temperature

    NASA Astrophysics Data System (ADS)

    Hejll, Arvid; Täljsten, Björn; Carolin, Anders

    2006-03-01

    To obtain a better knowledge of existing structures behaviour monitoring can be used. The use of monitoring in bridge structures by the use of instruments to assess the integrity of structures is not new and there are reports from structures tested as early as in the 19th century according to ISIS Canada1 However, the term SHM (Structural Health Monitoring) is relatively new to civil engineering and the driving force to implement SHM comes from recognising the limitations of conventional visual inspections and evaluations using conservative codes of practice. The possibilities to monitor existing structures with help of the rapidly evolving Information Technology are to day carried out. The objective of SHM is to monitor the in-situ behaviour of a structure accurately and efficiently, to assess its performance under various service conditions, to detect damage or deterioration, and to determine the health or condition of the structure1. In Sweden strengthening and periodic monitoring of a large freivorbau bridge (pre-stresed concrete box girder bridge) has been carried out, the Gröndals Bridge. The bridge is located in Stockholm and is approximately 400 m in length with a free span of 120 m. It was opened to tram traffic in year 2000. Just after opening cracks were noticed in the webs, these cracks have then increased, the size of the largest cracks exceeded 0.5 mm, and at the end of year 2001 the bridge was temporarily strengthened. This was carried out with externally placed prestressed steel stays. The reason for cracking is quite clear but the responsibility is still debated. Nevertheless, it was evidently that the bridge needed to be strengthened. The strengthening methods used were CFRP plates in the Service Limit State (SLS) and prestressed dywidag stays in the Ultimate Limit State (ULS). The strengthening was carried out during year 2002. At the same time monitoring of the bridge commenced, using LVDT crack gauges as well as optical fibre sensors. This

  17. Guidelines for May-Grünwald-Giemsa staining in haematology and non-gynaecological cytopathology: recommendations of the French Society of Clinical Cytology (SFCC) and of the French Association for Quality Assurance in Anatomic and Cytologic Pathology (AFAQAP).

    PubMed

    Piaton, E; Fabre, M; Goubin-Versini, I; Bretz-Grenier, M-F; Courtade-Saïdi, M; Vincent, S; Belleannée, G; Thivolet, F; Boutonnat, J; Debaque, H; Fleury-Feith, J; Vielh, P; Egelé, C; Bellocq, J-P; Michiels, J-F; Cochand-Priollet, B

    2016-10-01

    Since the guidelines of the International Committee for Standardisation in Haematology (ICSH) in 1984 and those of the European Committee for External Quality Assessment Programmes in Laboratory Medicine (EQALM) in 2004, no leading organisation has published technical recommendations for the preparation of air-dried cytological specimens using May-Grünwald-Giemsa (MGG) staining. Literature data were retrieved using reference books, baseline-published studies, articles extracted from PubMed/Medline and Google Scholar, and online-available industry datasheets. The present review addresses all pre-analytical issues concerning the use of Romanowsky's stains (including MGG) in haematology and non-gynaecological cytopathology. It aims at serving as actualised, best practice recommendations for the proper handling of air-dried cytological specimens. It, therefore, appears complementary to the staining criteria of the non-gynaecological diagnostic cytology handbook edited by the United Kingdom National External Quality Assessment Service (UK-NEQAS) in February 2015. © 2016 John Wiley & Sons Ltd.

  18. Differential subcellular localization of the glucocorticoid receptor in distinct neural stem and progenitor populations of the mouse telencephalon in vivo.

    PubMed

    Tsiarli, Maria A; Paula Monaghan, A; Defranco, Donald B

    2013-07-26

    Glucocorticoids are given to pregnant women at risk for premature delivery to promote lung maturation. Despite reports of detrimental effects of glucocorticoids on telencephalic neural stem/progenitor cells (NSPCs), the regional and cellular expressions of the glucocorticoid receptor (GR) in various NSPC populations in the intact brain have not been thoroughly assessed. Therefore in this study we performed a detailed analysis of GR protein expression in the developing mouse ventral and dorsal telencephalon in vivo. At embryonic day 11.5 (E11.5), the majority of Pax6-positive radial glial cells (RGCs) and Tbr2-positive intermediate progenitor cells (IPCs) expressed nuclear GR, while a small number of RGCs on the apical ventricular zone (aVZ), expressed cytoplasmic GR. However, on E13.5, the latter population of RGCs increased in size, whereas abventricular NSPCs and especially neurons of the cortical plate, expressed nuclear GR. In IPCs, GR was always nuclear. A similar expression profile was observed throughout the ventral telencephalon, hippocampus and olfactory bulb, with NSPCs of the aVZ primarily expressing cytoplasmic GR, while abventricular NSPCs and mature cells primarily expressed nuclear GR. Close to birth, nuclear GR accumulated within specific cortical areas such as layer V, the subplate and CA1 area of the hippocampus. In summary, our data show that GR protein is present in early NSPCs of the dorsal and ventral telencephalon at E11.5 and primarily occupies the nucleus. Moreover, our study suggests that the subcellular localization of the receptor may be subjected to region and neurodevelopmental stage-specific regulation. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Characterization of an Adhesion Molecule that Mediates Leukocyte Rolling on 24 h Cytokine- or Lipopolysaccharide-stimulated Bovine Endothelial Cells under Flow Conditions

    PubMed Central

    Jutila, Mark A.; Wilson, Eric; Kurk, Sandy

    1997-01-01

    Bovine γ/δ T cells and neutrophils roll on 24 h cytokine- or lipopolysaccharide-stimulated bovine fetal umbilical cord endothelial cells in assays done under physiological flow. An antibody directed against E- and L-selectin has minimal blocking effect on this rolling interaction. mAbs were raised against the stimulated bovine endothelial cells and screened for inhibition of γ/δ T cell rolling. One mAb (GR113) was identified that recognizes an antigen (GR antigen) selectively expressed by stimulated bovine endothelial cells isolated from fetal umbilical cord, mesenteric lymph nodes, and aorta. GR113 blocked bovine γ/δ T cell as well as neutrophil rolling on the 24 h-activated endothelial cells. The GR antigen was constitutively expressed at low levels on the cell surface of platelets and its expression was not upregulated after stimulation of these cells with thrombin or phorbol myristate acetate. However, stimulated platelets released a soluble, functionally active form of the molecule that selectively bound in solution to γ/δ T cells in a mixed lymphocyte preparation. GR113 mAb blocked the binding of the soluble platelet molecule to the γ/δ T cells. Soluble GR antigen also bound a subset of human lymphocytes. Cutaneous lymphocyte-associated antigen (CLA) bright human lymphocytes exhibited the greatest capacity to bind the GR antigen, though CLA was not required for binding. Subsets of both human CD4 and CD8 T cells bound the GR antigen. Immunoprecipitation experiments showed the GR antigen to be 110-120 kD M r. The binding of soluble GR antigen was inhibited by EDTA and O-sialoglycoprotease, but not neuraminidase treatment of the target cells. PMID:9362530

  20. Downregulation of spinal glutamate transporter EAAC1 following nerve injury is regulated by central glucocorticoid receptors in rats.

    PubMed

    Wang, Shuxing; Lim, Grewo; Yang, Liling; Sung, Backil; Mao, Jianren

    2006-01-01

    Previous studies have shown that glucocorticoid receptors (GR) were upregulated, whereas glutamate transporters were downregulated, within the spinal cord dorsal horn after peripheral nerve injury. However, the relationship between the expression of spinal GR and glutamate transporter after nerve injury remains unknown. In the present study, we examined the hypothesis that central GR would regulate the expression of spinal glutamate transporter EAAC1 following chronic constriction nerve injury (CCI) in rats. CCI induced a significant downregulation of EAAC1 expression primarily within the ipsilateral spinal cord dorsal horn when examined on postoperative day 7 using both Western blot and immunohistochemistry. The downregulation of EAAC1 was significantly diminished after either the GR antagonist RU38486 (4 > 2 = 0.5 microg = vehicle) or a GR antisense oligonucleotide was administered intrathecally twice daily for postoperative day 1-6. Moreover, CCI induced a significant downregulation of nuclear factor kappaB (NF-kappaB) within the ipsilateral spinal cord dorsal horn, which also was attenuated by either RU38486 (4 > 2 = 0.5 microg = vehicle) or a GR antisense oligonucleotide. The immunohistochemical data indicated a pattern of colocalization between GR and EAAC1 as well as GR and NF-kappaB within the spinal cord dorsal horn. Since, NF-kappaB has been shown to regulate the expression of those cellular elements linked to inflammation and tissue injury and its activity can be negatively regulated by GR activation, these results suggest that spinal GR through NF-kappaB may play a significant role in the regulation of EAAC1 expression after peripheral nerve injury, a cellular pathway that may contribute to the development of neuropathic pain behaviors in rats.

  1. Graphene as a nanocarrier for tamoxifen induces apoptosis in transformed cancer cell lines of different origins.

    PubMed

    Misra, Santosh K; Kondaiah, Paturu; Bhattacharya, Santanu; Rao, C N R

    2012-01-09

    A cationic amphiphile, cholest-5en-3β-oxyethyl pyridinium bromide (PY(+) -Chol), is able to efficiently disperse exfoliated graphene (GR) in water by the physical adsorption of PY(+) -Chol on the surface of GR to form stable, dark aqueous suspensions at room temperature. The GR-PY(+) -Chol suspension can then be used to solubilize Tamoxifen Citrate (TmC), a breast cancer drug, in water. The resulting TmC-GR-PY(+) -Chol is stable for a long time without any precipitation. Fluorescence emission and UV absorption spectra indicate the existence of noncovalent interactions between TmC, GR, and PY(+) -Chol in these suspensions. Electron microscopy shows the existence of segregated GR sheets and TmC 'ribbons' in the composite suspensions. Atomic force microscopy indicates the presence of 'extended' structures of GR-PY(+) -Chol, which grows wider in the presence of TmC. The slow time-dependent release of TmC is noticed in a reconstituted cell culture medium, a property useful as a drug carrier. TmC-GR-PY(+) -Chol selectively enhanced the cell death (apoptosis) of the transformed cancer cells compared to normal cells. This potency is found to be true for a wide range of transformed cancer cells viz. HeLa, A549, ras oncogene-transformed NIH3T3, HepG2, MDA-MB231, MCF-7, and HEK293T compared to the normal cell HEK293 in vitro. Confocal microscopy confirmed the high efficiency of TmC-GR-PY(+) -Chol in delivering the drug to the cells, compared to the suspensions devoid of GR. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Linking in situ LAI and fine resolution remote sensing data to map reference LAI over cropland and grassland using geostatistical regression method

    NASA Astrophysics Data System (ADS)

    He, Yaqian; Bo, Yanchen; Chai, Leilei; Liu, Xiaolong; Li, Aihua

    2016-08-01

    Leaf Area Index (LAI) is an important parameter of vegetation structure. A number of moderate resolution LAI products have been produced in urgent need of large scale vegetation monitoring. High resolution LAI reference maps are necessary to validate these LAI products. This study used a geostatistical regression (GR) method to estimate LAI reference maps by linking in situ LAI and Landsat TM/ETM+ and SPOT-HRV data over two cropland and two grassland sites. To explore the discrepancies of employing different vegetation indices (VIs) on estimating LAI reference maps, this study established the GR models for different VIs, including difference vegetation index (DVI), normalized difference vegetation index (NDVI), and ratio vegetation index (RVI). To further assess the performance of the GR model, the results from the GR and Reduced Major Axis (RMA) models were compared. The results show that the performance of the GR model varies between the cropland and grassland sites. At the cropland sites, the GR model based on DVI provides the best estimation, while at the grassland sites, the GR model based on DVI performs poorly. Compared to the RMA model, the GR model improves the accuracy of reference LAI maps in terms of root mean square errors (RMSE) and bias.

  3. Adipocyte Glucocorticoid Receptor Deficiency Attenuates Aging- and HFD-Induced Obesity and Impairs the Feeding-Fasting Transition.

    PubMed

    Mueller, Kristina M; Hartmann, Kerstin; Kaltenecker, Doris; Vettorazzi, Sabine; Bauer, Mandy; Mauser, Lea; Amann, Sabine; Jall, Sigrid; Fischer, Katrin; Esterbauer, Harald; Müller, Timo D; Tschöp, Matthias H; Magnes, Christoph; Haybaeck, Johannes; Scherer, Thomas; Bordag, Natalie; Tuckermann, Jan P; Moriggl, Richard

    2017-02-01

    Glucocorticoids (GCs) are important regulators of systemic energy metabolism, and aberrant GC action is linked to metabolic dysfunctions. Yet, the extent to which normal and pathophysiological energy metabolism depend on the GC receptor (GR) in adipocytes remains unclear. Here, we demonstrate that adipocyte GR deficiency in mice significantly impacts systemic metabolism in different energetic states. Plasma metabolomics and biochemical analyses revealed a marked global effect of GR deficiency on systemic metabolite abundance and, thus, substrate partitioning in fed and fasted states. This correlated with a decreased lipolytic capacity of GR-deficient adipocytes under postabsorptive and fasting conditions, resulting from impaired signal transduction from β-adrenergic receptors to adenylate cyclase. Upon prolonged fasting, the impaired lipolytic response resulted in abnormal substrate utilization and lean mass wasting. Conversely, GR deficiency attenuated aging-/diet-associated obesity, adipocyte hypertrophy, and liver steatosis. Systemic glucose tolerance was improved in obese GR-deficient mice, which was associated with increased insulin signaling in muscle and adipose tissue. We conclude that the GR in adipocytes exerts central but diverging roles in the regulation of metabolic homeostasis depending on the energetic state. The adipocyte GR is indispensable for the feeding-fasting transition but also promotes adiposity and associated metabolic disorders in fat-fed and aged mice. © 2017 by the American Diabetes Association.

  4. Maltose-Binding Protein Enhances Secretion of Recombinant Human Granzyme B Accompanied by In Vivo Processing of a Precursor MBP Fusion Protein

    PubMed Central

    Dälken, Benjamin; Jabulowsky, Robert A.; Oberoi, Pranav; Benhar, Itai; Wels, Winfried S.

    2010-01-01

    Background The apoptosis-inducing serine protease granzyme B (GrB) is an important factor contributing to lysis of target cells by cytotoxic lymphocytes. Expression of enzymatically active GrB in recombinant form is a prerequisite for functional analysis and application of GrB for therapeutic purposes. Methods and Findings We investigated the influence of bacterial maltose-binding protein (MBP) fused to GrB via a synthetic furin recognition motif on the expression of the MBP fusion protein also containing an N-terminal α-factor signal peptide in the yeast Pichia pastoris. MBP markedly enhanced the amount of GrB secreted into culture supernatant, which was not the case when GrB was fused to GST. MBP-GrB fusion protein was cleaved during secretion by an endogenous furin-like proteolytic activity in vivo, liberating enzymatically active GrB without the need of subsequent in vitro processing. Similar results were obtained upon expression of a recombinant fragment of the ErbB2/HER2 receptor protein or GST as MBP fusions. Conclusions Our results demonstrate that combination of MBP as a solubility enhancer with specific in vivo cleavage augments secretion of processed and functionally active proteins from yeast. This strategy may be generally applicable to improve folding and increase yields of recombinant proteins. PMID:21203542

  5. Hydrothermal synthesis of graphene/nickel oxide nanocomposites used as the electrode for supercapacitors.

    PubMed

    Zhou, Zhongnian; Ni, Haifang; Fan, Li-Zhen

    2014-07-01

    Graphene (GR)-based nanocomposites with different mass ratios of NiO and GR are prepared via hydrothermal method using Ni(NO3)2 as the origin of nickel and urea as the hydrolysis-controlling agent. The morphology and electrochemical performance of the GR/NiO nanocomposites are closely associated with the mass ratios of GR to NiO. The chemical composition and morphology of the composites together with the pure GR and NiO are characterized by thermogravimetric analysis (TGA), X-ray diffraction (XRD), scanning electron microscope (SEM), and transmission electron microscope (TEM). It is found that the GR sheets and NiO particles form uniform nanocomposites with the NiO particles absorbed on the GR surface. A specific capacitance of 384 F g(-1) at a current density of 0.1 A g(-1) is achieved when the coating amount of NiO is up to 74 wt%. In addition, the attenuation of the specific capacitance is less than 6% after 500 cycles, indicating such nanocomposite has excellent cycling performance.

  6. Glyphosate Can Decrease Germination of Glyphosate-Resistant Soybeans.

    PubMed

    Gomes, Marcelo Pedrosa; Bicalho, Elisa Monteze; Smedbol, Élise; Cruz, Fernanda Vieira da Silva; Lucotte, Marc; Garcia, Queila Souza

    2017-03-22

    We investigated the effects of different concentrations of glyphosate acid and one of its formulations (Roundup) on seed germination of two glyphosate-resistant (GR) and one non-GR variety of soybean. As expected, the herbicide affected the shikimate pathway in non-GR seeds but not in GR seeds. We observed that glyphosate can disturb the mitochondrial electron transport chain, leading to H 2 O 2 accumulation in soybean seeds, which was, in turn, related to lower seed germination. In addition, GR seeds showed increased activity of antioxidant systems when compared to non-GR seeds, making them less vulnerable to oxidative stress induced by glyphosate. The differences in the responses of GR varieties to glyphosate exposure corresponded to their differences in enzymatic activity related to H 2 O 2 scavenging and mitochondrial complex III (the proposed site of ROS induction by glyphosate). Our results showed that glyphosate ought to be used carefully as a pre-emergence herbicide in soybean field crop systems because this practice may reduce seed germination.

  7. The control of Asian rust by glyphosate in glyphosate-resistant soybeans.

    PubMed

    Feng, Paul C C; Clark, Celeste; Andrade, Gabriella C; Balbi, Maria C; Caldwell, Pat

    2008-04-01

    Glyphosate is a widely used broad-spectrum herbicide. Recent studies in glyphosate-resistant (GR) crops have shown that, in addition to its herbicidal activity, glyphosate exhibits activity against fungi, thereby providing disease control benefits. In GR wheat, glyphosate has shown both preventive and curative activities against Puccinia striiformis f. sp. tritici (Erikss) CO Johnston and Puccinia triticina Erikss, which cause stripe and leaf rusts respectively. Laboratory studies confirmed earlier observations that glyphosate has activity against Phakopsora pachyrhizi Syd & P Syd which causes Asian soybean rust (ASR) in GR soybeans. The results showed that glyphosate at rates between 0.84 and 1.68 kg ha(-1) delayed the onset of ASR in GR soybeans. However, field trials conducted in Argentina and Brazil under natural infestations showed variable ASR control from application of glyphosate in GR soybeans. Further field studies are ongoing to define the activity of glyphosate against ASR. These results demonstrate the disease control activities of glyphosate against rust diseases in GR wheat and GR soybeans. Copyright (c) 2007 Society of Chemical Industry.

  8. Graphene and poly(methyl methacrylate) composite laminates on flexible substrates for volatile organic compound detection

    NASA Astrophysics Data System (ADS)

    Rattanabut, Chanoknan; Wongwiriyapan, Winadda; Muangrat, Worawut; Bunjongpru, Win; Phonyiem, Mayuree; Song, Young Jae

    2018-04-01

    In this paper, we present a gas sensor for volatile organic compound (VOC) detection based on graphene and poly(methyl methacrylate) (GR/PMMA) composite laminates fabricated using CVD-grown graphene. Graphene was transferred to a poly(ethylene terephthalate) (PET) substrate by PMMA-supported wet transfer process without PMMA removal in order to achieve the deposition of GR/PMMA composite laminates on PET. The GR/PMMA and graphene sensors show completely different sensitivities to VOC vapors. The GR/PMMA and graphene sensors showed the highest sensitivities to dichloromethane (DCM). The response of the GR/PMMA sensor to DCM was 3 times higher than that of the graphene sensor but the GR/PMMA sensor hardly responded to acetone, chloroform, or benzene. The sensing mechanism of the graphene sensor can be based on the dielectric constant of VOCs, the size of VOC molecule, and electron hopping effects on defect graphene, while that of the GR/PMMA sensor can be explained in terms of the polymer swelling owing to the Hansen solubility parameter.

  9. GLUCOCORTICOID RECEPTOR EXPRESSION DURING THE DEVELOPMENT OF THE EMBRYONIC MOUSE SECONDARY PALATE

    EPA Science Inventory

    Glucocorticoids are important regulators of embryonic growth and development. hese effects are mediated through glucocorticoid receptors (GR) which bind to glucocorticoid response elements upstream of regulated genes. his study examines the expression of GR and GR mRNA in embryon...

  10. Comparative Evaluation of the Etching Pattern of Er,Cr:YSGG & Acid Etching on Extracted Human Teeth-An ESEM Analysis

    PubMed Central

    Mazumdar, Dibyendu; Ranjan, Shashi; Krishna, Naveen Kumar; Kole, Ravindra; Singh, Priyankar; Lakiang, Deirimika; Jayam, Chiranjeevi

    2016-01-01

    Introduction Etching of enamel and dentin surfaces increases the surface area of the substrate for better bonding of the tooth colored restorative materials. Acid etching is the most commonly used method. Recently, hard tissue lasers have been used for this purpose. Aim The aim of the present study was to evaluate and compare the etching pattern of Er,Cr:YSGG and conventional etching on extracted human enamel and dentin specimens. Materials and Methods Total 40 extracted non-diseased teeth were selected, 20 anterior and 20 posterior teeth each for enamel and dentin specimens respectively. The sectioned samples were polished by 400 grit Silicon Carbide (SiC) paper to a thickness of 1.0 ± 0.5 mm. The enamel and dentin specimens were grouped as: GrE1 & GrD1 as control specimens, GrE2 & GrD2 were acid etched and GrE3 & GrD3 were lased. Acid etching was done using Conditioner 36 (37 % phosphoric acid) according to manufacturer instructions. Laser etching was done using Er,Cr:YSGG (Erbium, Chromium : Ytrium Scandium Gallium Garnet) at power settings of 3W, air 70% and water 20%. After surface treatment with assigned agents the specimens were analyzed under ESEM (Environmental Scanning Electron Microscope) at X1000 and X5000 magnification. Results Chi Square and Student “t” statistical analysis was used to compare smear layer removal and etching patterns between GrE2-GrE3. GrD2 and GrD3 were compared for smear layer removal and diameter of dentinal tubule opening using the same statistical analysis. Chi-square test for removal of smear layer in any of the treated surfaces i.e., GrE2-E3 and GrD2-D3 did not differ significantly (p>0.05). While GrE2 showed predominantly type I etching pattern (Chi-square=2.78, 0.05

    0.10) and GrE3 showed type III etching (Chi-square=4.50, p<0.05). The tubule diameters were measured using GSA (Gesellschaft fur Softwareentwicklung und Analytik, Germany) image analyzer and the ‘t’ value of student ‘t’ test was 18.10 which was a

  11. A Ground Validation Network for the Global Precipitation Measurement Mission

    NASA Technical Reports Server (NTRS)

    Schwaller, Mathew R.; Morris, K. Robert

    2011-01-01

    A prototype Validation Network (VN) is currently operating as part of the Ground Validation System for NASA's Global Precipitation Measurement (GPM) mission. The VN supports precipitation retrieval algorithm development in the GPM prelaunch era. Postlaunch, the VN will be used to validate GPM spacecraft instrument measurements and retrieved precipitation data products. The period of record for the VN prototype starts on 8 August 2006 and runs to the present day. The VN database includes spacecraft data from the Tropical Rainfall Measuring Mission (TRMM) precipitation radar (PR) and coincident ground radar (GR) data from operational meteorological networks in the United States, Australia, Korea, and the Kwajalein Atoll in the Marshall Islands. Satellite and ground radar data products are collected whenever the PR satellite track crosses within 200 km of a VN ground radar, and these data are stored permanently in the VN database. VN products are generated from coincident PR and GR observations when a significant rain event occurs. The VN algorithm matches PR and GR radar data (including retrieved precipitation data in the case of the PR) by calculating averages of PR reflectivity (both raw and attenuation corrected) and rain rate, and GR reflectivity at the geometric intersection of the PR rays with the individual GR elevation sweeps. The algorithm thus averages the minimum PR and GR sample volumes needed to "matchup" the spatially coincident PR and GR data types. The result of this technique is a set of vertical profiles for a given rainfall event, with coincident PR and GR samples matched at specified heights throughout the profile. VN data can be used to validate satellite measurements and to track ground radar calibration over time. A comparison of matched TRMM PR and GR radar reflectivity factor data found a remarkably small difference between the PR and GR radar reflectivity factor averaged over this period of record in stratiform and convective rain cases when

  12. Feasibility analysis of using inverse modeling for estimating natural groundwater recharge from a large-scale soil moisture monitoring network

    NASA Astrophysics Data System (ADS)

    Wang, Tiejun; Franz, Trenton E.; Yue, Weifeng; Szilagyi, Jozsef; Zlotnik, Vitaly A.; You, Jinsheng; Chen, Xunhong; Shulski, Martha D.; Young, Aaron

    2016-02-01

    Despite the importance of groundwater recharge (GR), its accurate estimation still remains one of the most challenging tasks in the field of hydrology. In this study, with the help of inverse modeling, long-term (6 years) soil moisture data at 34 sites from the Automated Weather Data Network (AWDN) were used to estimate the spatial distribution of GR across Nebraska, USA, where significant spatial variability exists in soil properties and precipitation (P). To ensure the generality of this study and its potential broad applications, data from public domains and literature were used to parameterize the standard Hydrus-1D model. Although observed soil moisture differed significantly across the AWDN sites mainly due to the variations in P and soil properties, the simulations were able to capture the dynamics of observed soil moisture under different climatic and soil conditions. The inferred mean annual GR from the calibrated models varied over three orders of magnitude across the study area. To assess the uncertainties of the approach, estimates of GR and actual evapotranspiration (ETa) from the calibrated models were compared to the GR and ETa obtained from other techniques in the study area (e.g., remote sensing, tracers, and regional water balance). Comparison clearly demonstrated the feasibility of inverse modeling and large-scale (>104 km2) soil moisture monitoring networks for estimating GR. In addition, the model results were used to further examine the impacts of climate and soil on GR. The data showed that both P and soil properties had significant impacts on GR in the study area with coarser soils generating higher GR; however, different relationships between GR and P emerged at the AWDN sites, defined by local climatic and soil conditions. In general, positive correlations existed between annual GR and P for the sites with coarser-textured soils or under wetter climatic conditions. With the rapidly expanding soil moisture monitoring networks around the

  13. Region-specific Alterations in Glucocorticoid Receptor Expression in the Postmortem Brain of Teenage Suicide Victims

    PubMed Central

    Pandey, Ghanshyam N.; Rizavi, Hooriyah S.; Ren, Xinguo; Dwivedi, Yogesh; Palkovits, Miklós

    2013-01-01

    Introduction Abnormal function of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the pathophysiology of depression and suicide. The purpose of this study was to test the hypothesis that the reported dysregulation of the HPA axis in suicide may be related to a disturbed feedback inhibition caused by decreased corticoid receptors in the brain. We therefore determined the protein and gene expression of glucocorticoid (GR) and mineralocorticoid receptors (MR) in the postmortem brain of teenage suicide victims and matched normal controls. Methods Protein and mRNA expression of GR (GR-α and GR-β) and MR and the mRNA expression of glucocorticoid-induced leucine zipper (GILZ), a target gene for GR were determined by immunolabeling using Western blot technique and the real-time RT-polymerase chain reaction (qPCR) technique in the prefrontal cortex (PFC), hippocampus, subiculum, and amygdala obtained from 24 teenage suicide victims and 24 teenage control subjects. Results We observed that protein and gene expression of GR-α was significantly decreased in the PFC and amygdala, but not in the hippocampus or subiculum, of teenage suicide victims compared with normal control subjects. Also, the mRNA levels of GR inducible target gene GILZ was significantly decreased in PFC and amygdaloid nuclei but not in hippocampus compared with controls. In contrast, no significant differences were observed in protein or gene expression of MR in any of the areas studied between teenage suicide victims and normal control subjects. There was no difference in the expression of GR-β in the PFC between suicide victims and normal controls. Conclusions These results suggested that the observed dysregulation of the HPA axis in suicide may be related to a decreased expression of GR-α and GR inducible genes in the PFC and amygdala of teenage suicide victims. The reason why GR receptors are not dysregulated in the hippocampus or subiculum, presumably two sites of stress action

  14. Expression of glucocorticoid receptor and early growth response gene 1 during postnatal development of two inbred strains of mice exposed to early life stress.

    PubMed

    Navailles, Sylvia; Zimnisky, Ross; Schmauss, Claudia

    2010-07-01

    Early life stress can elicit profound changes in adult gene expression and behavior. One consequence of early life stress is a decreased expression of glucocorticoid receptors (GRs) in the frontal cortex and hippocampus. However, neither the time of onset nor the mechanism(s) leading to decreased GR expression during postnatal development are known. The present study used two inbred strains of mice that differ in their behavioral responsiveness to stress (Balb/c and C57Bl/6), exposed them to an established paradigm of early life stress (infant maternal separation), and measured their expression of frontal cortical and hippocampal GRs and the putative transcriptional activator of the GR gene, early growth response gene (egr)-1, at defined stages of postnatal development. In both strains, real-time RT-PCR experiments revealed that decreased expression of GR in adolescence and adulthood is, in fact, preceded by increased GR expression during early life stress exposure. Thus, the early life stress-induced disruption of the normal stress-hyporesponsive period during infancy is accompanied by increased GR expression. Moreover, chronic treatment with the antidepressant drug fluoxetine during adolescence or adulthood reversed the effect of early life stress on adult GR mRNA expression. In contrast to the strain-independent effect of early life stress on GR expression, however, changes in egr-1 expression occurred only in Balb/c mice, and unlike the biphasic developmental changes in GR mRNA expression, egr-1 mRNA was decreased throughout postnatal development. Moreover, there was no consistent overlap of anatomic regions affected by decreased GR and egr-1 protein expression. Thus, in Balb/c mice, changes in GR and egr-1 expression can independently contribute to the phenotypes resulting from early life stress exposure. These findings illustrate that the impact of early life stress on gene expression changes is modulated by the genetic background and that the persistent

  15. Evaluation of Surface Roughness of Ceramic and Resin Composite Material Used for Conservative Indirect Restorations, after Repolishing by Intraoral Means.

    PubMed

    Vrochari, Areti D; Petropoulou, Aikaterini; Chronopoulos, Vasilios; Polydorou, Olga; Massey, Ward; Hellwig, Elmar

    2017-06-01

    To evaluate and compare the mean surface roughness (Ra) of one ceramic and one resin composite material used for indirect restorations, after grinding and repolishing by intraoral means. The materials used were the lithium disilicate glass ceramic IPS e.max Press (EMP) and the indirect resin composite restoration system Gradia (GR). Twelve specimen disks were prepared from each material according to the manufacturer of each material. Five initial measurements of the Ra (Ra 1 ) were made on each specimen as a referral basis, and the specimens were ground with a fine (red) diamond bur. The specimens were repolished using (a) Komet Dialite Polishing Kit for EMP and (b) Enhance Finishing and Polishing System and Prisma Gloss Polishing Paste for GR. Five final Ra (Ra 2 ) measurements were performed on each specimen. All measurements were made using a laser profilometer. Scanning electron microscopy (SEM) was also used to visualize the initial surface morphology and the morphological changes on the specimens' surface after repolishing. A highly significant difference was found between Ra 1EMP and Ra 2EMP (p < 0.001), between Ra 1GR and Ra 2GR (p < 0.001), as well as between Ra 2EMP and Ra 2GR (p < 0.001), when compared in pairs. A highly significant difference (p < 0.001) was also found between ΔRa EMP and ΔRa GR , with ΔRa GR being higher than ΔRa EMP . The Ra GR values were higher than the Ra EMP values at all times. SEM revealed that both EMP and GR repolished surfaces presented with irregularities; however, in GR specimens major voids and craters were present. EMP was found to perform better when polished by intraoral means compared with GR. Both materials exhibited Ra 2 above the critical threshold for increased plaque accumulation and periodontal inflammation. If enamel-to-enamel roughness found in occlusal contact areas is considered as baseline, both materials were clinically acceptable after repolishing. © 2015 by the American College of Prosthodontists.

  16. General Relativity and Cosmology: Unsolved Questions and Future Directions

    NASA Astrophysics Data System (ADS)

    Debono, Ivan; Smoot, George F.

    2016-09-01

    For the last 100 years, General Relativity (GR) has taken over the gravitational theory mantle held by Newtonian Gravity for the previous 200 years. This article reviews the status of GR in terms of its self-consistency, completeness, and the evidence provided by observations, which have allowed GR to remain the champion of gravitational theories against several other classes of competing theories. We pay particular attention to the role of GR and gravity in cosmology, one of the areas in which one gravity dominates and new phenomena and effects challenge the orthodoxy. We also review other areas where there are likely conflicts pointing to the need to replace or revise GR to represent correctly observations and consistent theoretical framework. Observations have long been key both to the theoretical liveliness and viability of GR.We conclude with a discussion of the likely developments over the next 100 years.

  17. The sensitivity of the Greenland Ice Sheet to glacial-interglacial oceanic forcing

    NASA Astrophysics Data System (ADS)

    Tabone, Ilaria; Blasco, Javier; Robinson, Alexander; Alvarez-Solas, Jorge; Montoya, Marisa

    2018-04-01

    Observations suggest that during the last decades the Greenland Ice Sheet (GrIS) has experienced a gradually accelerating mass loss, in part due to the observed speed-up of several of Greenland's marine-terminating glaciers. Recent studies directly attribute this to warming North Atlantic temperatures, which have triggered melting of the outlet glaciers of the GrIS, grounding-line retreat and enhanced ice discharge into the ocean, contributing to an acceleration of sea-level rise. Reconstructions suggest that the influence of the ocean has been of primary importance in the past as well. This was the case not only in interglacial periods, when warmer climates led to a rapid retreat of the GrIS to land above sea level, but also in glacial periods, when the GrIS expanded as far as the continental shelf break and was thus more directly exposed to oceanic changes. However, the GrIS response to palaeo-oceanic variations has yet to be investigated in detail from a mechanistic modelling perspective. In this work, the evolution of the GrIS over the past two glacial cycles is studied using a three-dimensional hybrid ice-sheet-shelf model. We assess the effect of the variation of oceanic temperatures on the GrIS evolution on glacial-interglacial timescales through changes in submarine melting. The results show a very high sensitivity of the GrIS to changing oceanic conditions. Oceanic forcing is found to be a primary driver of GrIS expansion in glacial times and of retreat in interglacial periods. If switched off, palaeo-atmospheric variations alone are not able to yield a reliable glacial configuration of the GrIS. This work therefore suggests that considering the ocean as an active forcing should become standard practice in palaeo-ice-sheet modelling.

  18. A ubiquitin carboxyl extension protein secreted from a plant-parasitic nematode Globodera rostochiensis is cleaved in planta to promote plant parasitism.

    PubMed

    Chronis, Demosthenis; Chen, Shiyan; Lu, Shunwen; Hewezi, Tarek; Carpenter, Sara C D; Loria, Rosemary; Baum, Thomas J; Wang, Xiaohong

    2013-04-01

    Nematode effector proteins originating from esophageal gland cells play central roles in suppressing plant defenses and in formation of the plant feeding cells that are required for growth and development of cyst nematodes. A gene (GrUBCEP12) encoding a unique ubiquitin carboxyl extension protein (UBCEP) that consists of a signal peptide for secretion, a mono-ubiquitin domain, and a 12 amino acid carboxyl extension protein (CEP12) domain was cloned from the potato cyst nematode Globodera rostochiensis. This GrUBCEP12 gene was expressed exclusively within the nematode's dorsal esophageal gland cell, and was up-regulated in the parasitic second-stage juvenile, correlating with the time when feeding cell formation is initiated. We showed that specific GrUBCEP12 knockdown via RNA interference reduced nematode parasitic success, and that over-expression of the secreted Gr(Δ) (SP) UBCEP12 protein in potato resulted in increased nematode susceptibility, providing direct evidence that this secreted effector is involved in plant parasitism. Using transient expression assays in Nicotiana benthamiana, we found that Gr(Δ) (SP) UBCEP12 is processed into free ubiquitin and a CEP12 peptide (GrCEP12) in planta, and that GrCEP12 suppresses resistance gene-mediated cell death. A target search showed that expression of RPN2a, a gene encoding a subunit of the 26S proteasome, was dramatically suppressed in Gr(Δ) (SP) UBCEP12 but not GrCEP12 over-expression plants when compared with control plants. Together, these results suggest that, when delivered into host plant cells, Gr(Δ) (SP) UBCEP12 becomes two functional units, one acting to suppress plant immunity and the other potentially affecting the host 26S proteasome, to promote feeding cell formation. © 2013 The Authors The Plant Journal © 2013 Blackwell Publishing Ltd.

  19. Glucocorticoid receptor represses brain-derived neurotrophic factor expression in neuron-like cells.

    PubMed

    Chen, Hui; Lombès, Marc; Le Menuet, Damien

    2017-04-12

    Brain-derived neurotrophic factor (BDNF) is involved in many functions such as neuronal growth, survival, synaptic plasticity and memorization. Altered expression levels are associated with many pathological situations such as depression, epilepsy, Alzheimer's, Huntington's and Parkinson's diseases. Glucocorticoid receptor (GR) is also crucial for neuron functions, via binding of glucocorticoid hormones (GCs). GR actions largely overlap those of BDNF. It has been proposed that GR could be a regulator of BDNF expression, however the molecular mechanisms involved have not been clearly defined yet. Herein, we analyzed the effect of a GC agonist dexamethasone (DEX) on BDNF expression in mouse neuronal primary cultures and in the newly characterized, mouse hippocampal BZ cell line established by targeted oncogenesis. Mouse Bdnf gene exhibits a complex genomic structure with 8 untranslated exons (I to VIII) splicing onto one common and unique coding exon IX. We found that DEX significantly downregulated total BDNF mRNA expression by around 30%. Expression of the highly expressed exon IV and VI containing transcripts was also reduced by DEX. The GR antagonist RU486 abolished this effect, which is consistent with specific GR-mediated action. Transient transfection assays allowed us to define a short 275 bp region within exon IV promoter responsible for GR-mediated Bdnf repression. Chromatin immunoprecipitation experiments demonstrated GR recruitment onto this fragment, through unidentified transcription factor tethering. Altogether, GR downregulates Bdnf expression through direct binding to Bdnf regulatory sequences. These findings bring new insights into the crosstalk between GR and BDNF signaling pathways both playing a major role in physiology and pathology of the central nervous system.

  20. Charge-transfer channel in quantum dot-graphene hybrid materials

    NASA Astrophysics Data System (ADS)

    Cao, Shuo; Wang, Jingang; Ma, Fengcai; Sun, Mengtao

    2018-04-01

    The energy band theory of a classical semiconductor can qualitatively explain the charge-transfer process in low-dimensional hybrid colloidal quantum dot (QD)-graphene (GR) materials; however, the definite charge-transfer channels are not clear. Using density functional theory (DFT) and time-dependent DFT, we simulate the hybrid QD-GR nanostructure, and by constructing its orbital interaction diagram, we show the quantitative coupling characteristics of the molecular orbitals (MOs) of the hybrid structure. The main MOs are derived from the fragment MOs (FOs) of GR, and the Cd13Se13 QD FOs merge with the GR FOs in a certain proportion to afford the hybrid system. Upon photoexcitation, electrons in the GR FOs jump to the QD FOs, leaving holes in the GR FOs, and the definite charge-transfer channels can be found by analyzing the complex MOs coupling. The excited electrons and remaining holes can also be localized in the GR or the QD or transfer between the QD and GR with different absorption energies. The charge-transfer process for the selected excited states of the hybrid QD-GR structure are testified by the charge difference density isosurface. The natural transition orbitals, charge-transfer length analysis and 2D site representation of the transition density matrix also verify the electron-hole delocalization, localization, or coherence chacracteristics of the selected excited states. Therefore, our research enhances understanding of the coupling mechanism of low-dimensional hybrid materials and will aid in the design and manipulation of hybrid photoelectric devices for practical application in many fields.

  1. Epigenetic changes in the hypothalamic proopiomelanocortin and glucocorticoid receptor genes in the ovine fetus after periconceptional undernutrition.

    PubMed

    Stevens, Adam; Begum, Ghazala; Cook, Alice; Connor, Kristin; Rumball, Christopher; Oliver, Mark; Challis, John; Bloomfield, Frank; White, Anne

    2010-08-01

    Maternal food restriction is associated with the development of obesity in offspring. This study examined how maternal undernutrition in sheep affects the fetal hypothalamic glucocorticoid receptor (GR) and the appetite-regulating neuropeptides, proopiomelanocortin (POMC) and neuropeptide Y, which it regulates. In fetuses from ewes undernourished from -60 to +30 d around conception, there was increased histone H3K9 acetylation (1.63-fold) and marked hypomethylation (62% decrease) of the POMC gene promoter but no change in POMC expression. In the same group, acetylation of histone H3K9 associated with the hypothalamic GR gene was increased 1.60-fold and the GR promoter region was hypomethylated (53% decrease). In addition, there was a 4.7-fold increase in hypothalamic GR expression but no change in methylation of GR gene expression in the anterior pituitary or hippocampus. Interestingly, hypomethylation of both POMC and GR promoter markers in fetal hypothalami was also identified after maternal undernutrition from -60 to 0 d and -2 to +30 d. In comparison, the Oct4 gene, was hypermethylated in both control and underfed groups. Periconceptional undernutrition is therefore associated with marked epigenetic changes in hypothalamic genes. Increase in GR expression in the undernourished group may contribute to fetal programming of a predisposition to obesity, via altered GR regulation of POMC and neuropeptide Y. These epigenetic changes in GR and POMC in the hypothalamus may also predispose the offspring to altered regulation of food intake, energy expenditure, and glucose homeostasis later in life.

  2. Charge-transfer channel in quantum dot-graphene hybrid materials.

    PubMed

    Cao, Shuo; Wang, Jingang; Ma, Fengcai; Sun, Mengtao

    2018-04-06

    The energy band theory of a classical semiconductor can qualitatively explain the charge-transfer process in low-dimensional hybrid colloidal quantum dot (QD)-graphene (GR) materials; however, the definite charge-transfer channels are not clear. Using density functional theory (DFT) and time-dependent DFT, we simulate the hybrid QD-GR nanostructure, and by constructing its orbital interaction diagram, we show the quantitative coupling characteristics of the molecular orbitals (MOs) of the hybrid structure. The main MOs are derived from the fragment MOs (FOs) of GR, and the Cd 13 Se 13 QD FOs merge with the GR FOs in a certain proportion to afford the hybrid system. Upon photoexcitation, electrons in the GR FOs jump to the QD FOs, leaving holes in the GR FOs, and the definite charge-transfer channels can be found by analyzing the complex MOs coupling. The excited electrons and remaining holes can also be localized in the GR or the QD or transfer between the QD and GR with different absorption energies. The charge-transfer process for the selected excited states of the hybrid QD-GR structure are testified by the charge difference density isosurface. The natural transition orbitals, charge-transfer length analysis and 2D site representation of the transition density matrix also verify the electron-hole delocalization, localization, or coherence chacracteristics of the selected excited states. Therefore, our research enhances understanding of the coupling mechanism of low-dimensional hybrid materials and will aid in the design and manipulation of hybrid photoelectric devices for practical application in many fields.

  3. Transcriptome analysis of reproductive-stage Arabidopsis plants exposed gamma-ray irradiation at various doses.

    PubMed

    Hwang, Sun-Goo; Kim, Dong Sub; Kim, Jin-Baek; Hwang, Jung Eun; Park, Hyun Mi; Kim, Jin Hyuk; Jang, Cheol Seong

    2016-08-01

    Gamma rays (GR) induce significant changes in the structure and expression of genes involved in the regulation of diverse biochemical and physiological processes. Arabidopsis plants exhibit different growth and development patterns in response to exposure to GR. The effects on gene expression of different radiation doses of GR (100 and 800 Gy) administered to Arabidopsis plants were examined at the reproductive stage. We irradiated 26-day-old plants with three replications [developmental stages 5.1-6.0, according to Boyes et al. ( 2001 )] using a GR irradiator (60 Co, ca. 150 TBq capacity, Atomic Energy of Canada Limited, Ontario, Canada) at the Korea Atomic Energy Research Institute. Plants were treated with 100, 200, 300, 400, 800, 1200, 1600, or 2000 Gy, and the doses were made from varying the distance to the source. We conducted a high-throughput screening analysis and detected 883 GR-responsive genes that showed significant changes; these were involved in several putative metabolic pathways related to biotic stress. Additionally, five overrepresented cis-regulatory elements were identified in the 1-kb upstream regions of GR-responsive genes by using motif enrichment analysis. We also detected three GR-responsive genes associated with stamen development and confirmed their co-regulation with functionally interacting genes. This finding suggests that a network-based analysis is a viable approach to identify significant GR-responsive genes associated with the reproductive stage of Arabidopsis. Our results provide further insights into the complex biological systems involved in the response to different doses of GR in plants.

  4. Propagation peculiarities of mean field massive gravity

    DOE PAGES

    Deser, S.; Waldron, A.; Zahariade, G.

    2015-07-28

    Massive gravity (mGR) describes a dynamical “metric” on a fiducial, background one. We investigate fluctuations of the dynamics about mGR solutions, that is about its “mean field theory”. Analyzing mean field massive gravity (m¯GR) propagation characteristics is not only equivalent to studying those of the full non-linear theory, but also in direct correspondence with earlier analyses of charged higher spin systems, the oldest example being the charged, massive spin 3/2 Rarita–Schwinger (RS) theory. The fiducial and mGR mean field background metrics in the m¯GR model correspond to the RS Minkowski metric and external EM field. The common implications in bothmore » systems are that hyperbolicity holds only in a weak background-mean-field limit, immediately ruling both theories out as fundamental theories; a situation in stark contrast with general relativity (GR) which is at least a consistent classical theory. Moreover, even though both m¯GR and RS theories can still in principle be considered as predictive effective models in the weak regime, their lower helicities then exhibit superluminal behavior: lower helicity gravitons are superluminal as compared to photons propagating on either the fiducial or background metric. Thus our approach has uncovered a novel, dispersive, “crystal-like” phenomenon of differing helicities having differing propagation speeds. As a result, this applies both to m¯GR and mGR, and is a peculiar feature that is also problematic for consistent coupling to matter.« less

  5. Effect of orthophosphate on the oxidation products of Fe(II)-Fe(III) hydroxycarbonate: the transformation of green rust to ferrihydrite

    NASA Astrophysics Data System (ADS)

    Benali, Omar; Abdelmoula, Mustapha; Refait, Philippe; Génin, Jean-Marie Robert

    2001-06-01

    Hydroxycarbonate green rust GR(CO 32-) has been synthesized by oxidation of aqueous suspensions of Fe(OH) 2 by aeration at the air-liquid interface, in the presence of HCO 3- ions at pH 7.5 to 9. During the oxidation of GR(CO 32-), ferrihydrite formed first and then turned into goethite by dissolution and precipitation. The oxidation of GR(CO 32-) in the presence of orthophosphate ions, which were added as Na 2HPO 4 · 7H 2O salt, also involved the formation of ferrihydrite but not that of goethite, because the dissolution of ferrihydrite is inhibited by the adsorption of phosphate ions on its surface. The oxidation was slowed down because of the suppression of the catalytic effect of iron(III) hydroxide on the oxidation of Fe(II). In anoxic conditions without phosphate, a mixture of GR(CO 32-), goethite, and ferrihydrite was observed to transform spontaneously into a mixture of siderite and magnetite. It is thermodynamically consistent, which shows that GR(CO 32-) is metastable with respect to the two-phase system FeCO 3-Fe 3O 4. In the presence of phosphate, this transformation was inhibited and GR(CO 32-) did not transform in anoxic conditions. Anionic phosphate species dissolved in solution did not give rise to a corresponding GR, i.e., phosphate species did not substitute for carbonate inside the interlayers of the GR. Moreover, iron phosphates did not appear, neither during the oxidation of GR(CO 32-) in the presence of oxygen nor in anoxic conditions.

  6. Gold Rods Irradiated with Ultrasound for Combination of Hyperthermia and Cancer Chemotherapy.

    PubMed

    Barros, Andre; Austerlitz, Carlos; Gkigkitzis, Ioannis; Campos, Diana; Andrade, Jeyce; Peixoto, Christina; Aguiar, Jaciana; Nascimento, Silene; Silva, Teresinha G; Haranas, Ioannis

    2017-01-01

    The aim of this study was to analyze feasibility (in vitro and in vivo) the use of hyperthermia produced by gold rods irradiated with ultrasound and their combination with chemotherapy with doxorubicin. initially was determined the cell viability and Hsp70 levels after treatment by gold rods irradiated with ultrasound (GR+U) in cell culture. The pretreatment with GR+U combined with doxorubicin (DOX) was evaluated from IC 50 , caspase-3 expression and mechanisms of cell death by electron microscopy. For evaluate the in vivo effects was used solid Ehrlich carcinoma (SEC) Tumor. The animals received three treatments with the combination of GR+U+DOX over 16 days. The cell viability was completely inhibited after 40 min of treatment with GR+U and significant increases the expression of HSP70 was only observed after 10 min of treatment. GR+U+DOX presented significant reduction of IC 50 representing 50.7%, 76.5% 45.2% and 46.6% for cell lines K562, NCI-H292, Hep-2 and MCF-7 respectively. GR+U+DOX presented significant reduction of IC 50 representing 50.7%, 76.5% 45.2% and 46.6% for cell lines K562, NCI-H292, Hep-2 and MCF-7 respectively. The caspase-3 level and ultraestructural analysis showed that treatment with GR+U+DOX enhances induction of apoptosis. Pretreatment with GR+U combined with doxorubicin (1 mg) showed 87% inhibition against SEC. and no showed cardiotoxic effect. The combined treatment of GR+U and DOX exhibit synergistic characteristics observed by increasing the efficiency of doxorubicin.

  7. GR@PPA 2.8: Initial-state jet matching for weak-boson production processes at hadron collisions

    NASA Astrophysics Data System (ADS)

    Odaka, Shigeru; Kurihara, Yoshimasa

    2012-04-01

    The initial-state jet matching method introduced in our previous studies has been applied to the event generation of single W and Z production processes and diboson (WW, WZ and ZZ) production processes at hadron collisions in the framework of the GR@PPA event generator. The generated events reproduce the transverse momentum spectra of weak bosons continuously in the entire kinematical region. The matrix elements (ME) for hard interactions are still at the tree level. As in previous versions, the decays of weak bosons are included in the matrix elements. Therefore, spin correlations and phase-space effects in the decay of weak bosons are exact at the tree level. The program package includes custom-made parton shower programs as well as ME-based hard interaction generators in order to achieve self-consistent jet matching. The generated events can be passed to general-purpose event generators to make the simulation proceed down to the hadron level. Catalogue identifier: ADRH_v3_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADRH_v3_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 112 146 No. of bytes in distributed program, including test data, etc.: 596 667 Distribution format: tar.gz Programming language: Fortran; with some included libraries coded in C and C++ Computer: All Operating system: Any UNIX-like system RAM: 1.6 Mega bytes at minimum Classification: 11.2 Catalogue identifier of previous version: ADRH_v2_0 Journal reference of previous version: Comput. Phys. Comm. 175 (2006) 665 External routines: Bash and Perl for the setup, and CERNLIB, ROOT, LHAPDF, PYTHIA according to the user's choice. Does the new version supersede the previous version?: No, this version supports only a part of the processes included in the previous versions. Nature of problem: We

  8. The aryl hydrocarbon receptor and glucocorticoid receptor interact to activate human metallothionein 2A

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

    Sato, Shoko, E-mail: satosho@rs.tus.ac.jp; Shirakawa, Hitoshi, E-mail: shirakah@m.tohoku.ac.jp; Tomita, Shuhei, E-mail: tomita@med.tottori-u.ac.jp

    2013-11-15

    Although the aryl hydrocarbon receptor (AHR) and glucocorticoid receptor (GR) play essential roles in mammalian development, stress responses, and other physiological events, crosstalk between these receptors has been the subject of much debate. Metallothioneins are classic glucocorticoid-inducible genes that were reported to increase upon treatment with AHR agonists in rodent tissues and cultured human cells. In this study, the mechanism of human metallothionein 2A (MT2A) gene transcription activation by AHR was investigated. Cotreatment with 3-methylcholanthrene and dexamethasone, agonists of AHR and GR respectively, synergistically increased MT2A mRNA levels in HepG2 cells. MT2A induction was suppressed by RNA interference against AHRmore » or GR. Coimmunoprecipitation experiments revealed a physical interaction between AHR and GR proteins. Moreover, chromatin immunoprecipitation assays indicated that AHR was recruited to the glucocorticoid response element in the MT2A promoter. Thus, we provide a novel mechanism whereby AHR modulates expression of human MT2A via the glucocorticoid response element and protein–protein interactions with GR. - Highlights: • Aryl hydrocarbon receptor forms a complex with glucocorticoid receptor in cells. • Human metallothionein gene is regulated by the AHR and GR interaction. • AHR–GR complex binds to glucocorticoid response element in metallothionein gene. • We demonstrated a novel transcriptional mechanism via AHR and GR interaction.« less

  9. Hsp90 Inhibition Results in Glucocorticoid Receptor Degradation in Association with Increased Sensitivity to Paclitaxel in Triple-Negative Breast Cancer.

    PubMed

    Agyeman, Abena S; Jun, Wesley J; Proia, David A; Kim, Caroline R; Skor, Maxwell N; Kocherginsky, Masha; Conzen, Suzanne D

    2016-04-01

    Targetable molecular drivers for triple-negative breast cancer (TNBC) have been difficult to identify; therefore, standard treatment remains limited to conventional chemotherapy. Recently, new-generation small-molecule Hsp90 inhibitors (e.g., ganetespib and NVP-AUY922) have demonstrated improved safety and activity profiles over the first-generation ansamycin class. In breast cancer, clinical responses have been observed in a subset of TNBC patients following ganetespib monotherapy; however, the underlying biology of Hsp90 inhibitor treatment and tumor response is not well understood. Glucocorticoid receptor (GR) activity in TNBC is associated with chemotherapy resistance. Here, we find that treatment of TNBC cell lines with ganetespib resulted in GR degradation and decreased GR-mediated gene expression. Ganetespib-associated GR degradation also sensitized TNBC cells to paclitaxel-induced cell death both in vitro and in vivo. The beneficial effect of the Hsp90 inhibitor on paclitaxel-induced cytotoxicity was reduced when GR was depleted in TNBC cells but could be recovered with GR overexpression. These findings suggest that GR-regulated anti-apoptotic and pro-proliferative signaling networks in TNBC are disrupted by Hsp90 inhibitors, thereby sensitizing TNBC to paclitaxel-induced cell death. Thus, GR+ TNBC patients may be a subgroup of breast cancer patients who are most likely to benefit from adding an Hsp90 inhibitor to taxane therapy.

  10. Gromwell (Lithospermum erythrorhizon) root extract protects against glycation and related inflammatory and oxidative stress while offering UV absorption capability.

    PubMed

    Glynn, Kelly M; Anderson, Penny; Fast, David J; Koedam, James; Rebhun, John F; Velliquette, Rodney A

    2018-06-15

    Glycation and advanced glycation endproducts (AGE) damage skin which is compounded by AGE-induced oxidative stress and inflammation. Lip and facial skin could be susceptible to glycation damage as they are chronically stressed. As Gromwell (Lithospermum erythrorhizon) root (GR) has an extensive traditional medicine history that includes providing multiple skin benefits, our objective was to determine if GR extract and its base naphthoquinone, shikonin, might protect skin by inhibiting glycation, increasing oxidative defenses, suppressing inflammatory responses, and offering ultraviolet (UV) absorptive potential in lip and facial cosmetic matrices. We show GR extract and shikonin dose-dependently inhibited glycation and enhanced oxidative defenses through nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) activation. Inflammatory targets, nuclear factor kappa light chain enhancer of activated B cells (NFκB) and tumor necrosis factor alpha (TNFα), were suppressed by GR extract and shikonin. Glyoxalase 1 (GLO1) and glutathione synthesis genes were significantly upregulated by GR extract and shikonin. GR extract boosted higher wavelength UV absorption in select cosmetic matrices. Rationale for the use of GR extract and shikonin are supported by our research. By inhibiting glycation, modulating oxidative stress, suppressing inflammation, and UV-absorptive properties, GR extract and shikonin potentially offer multiple skin benefits. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  11. Investigation of Tribological Behavior of a Novel Hybrid Composite Prepared with Al-Coconut Shell Ash Mixed with Graphite

    NASA Astrophysics Data System (ADS)

    Siva Sankara Raju, R.; Panigrahi, M. K.; Ganguly, R. I.; Srinivasa Rao, G.

    2017-08-01

    The present investigation develops a next-generation hybrid Al metal matrix composite using coconut shell ash (CSA) and graphite (Gr) reinforcement. Stir-casting is adapted to prepare an Al-1100-based composite. Three other composites of Al-Al2O3, Al-Al2O3-Gr, and Al-CSA are prepared that contain equivalent volume fractions of Al2O3, CSA, and Gr. These assist in comparisons among the three composites and the developed hybrid Al-CSA-Gr composite. The study reveals that the addition of 3 pct Gr improves the specific strength, toughness, and tribological properties. The Al-CSA composite shows better mechanical properties, such as tensile strength and hardness, than the other three composites. Gr addition helps the hybrid Al-CSA-Gr composite to attain better tribological properties with a slightly lower specific strength. Scanning electron microscopy studies of the worn material surfaces corroborate the findings of the abrasion testing. Elemental analyses by energy-dispersive X-ray spectroscopy of the debris from the counter-face of the tribo surface confirm the presence of Al, O, Si, Fe, Mn, and C.

  12. [Effects of jingui shenqi pill combined prednisone on expression of glucocorticoid receptor and its clinical effect in treating bullous pemphigoid patients].

    PubMed

    Liu, Bao-guo; Li, Zhi-ying; Du, Ming

    2006-10-01

    To investigate the effect of Jingui Shenqi Pill (JSP) on the expression of glucocorticoid receptor (GR) in the skin lesion and its clinical effect in treating bullous pemphigoid (BP) patients. Thirty BP patients were randomly divided into the treatment group (n=15) treated with JSP plus prednisone and the prednisone group (n=15) with prednisone alone both for 4 weeks. And a normal control group was set up also. Expressions of GR-alpha and GR-beta in the skin lesion of BP patients and the normal skin of the normal control were detected by immunohistochemical assay. Results The total effective rate was 93.33% in the treatment group, significantly higher than that in the prednisone group which was 73.33% (P < 0.05); GR-alpha expression was higher in the treatment group than that in other two groups (P < 0.01), while GR-beta expression in the treatment group was lower than that in the prednisone group (P < 0.01). JSP could increase GR-alpha expression and decrease GR-beta expression in the skin lesion of BP patients, so as to improve sensitivity of skin to glucocorticoid.

  13. A simple preparation of graphite/gelatin composite for electrochemical detection of dopamine.

    PubMed

    Rajkumar, Chellakannu; Thirumalraj, Balamurugan; Chen, Shen-Ming; Chen, His-An

    2017-02-01

    In this study, we demonstrate a simple preparation of graphite (GR) sheets assisted with gelatin (GLN) polypeptide composite was developed for sensitive detection of dopamine (DA) sensor. The GR/GLN composite was prepared by GR powder in GLN solution (5mg/mL) via sonication process. The prepared GR/GLN composite displays well dispersion ability in biopolymer matrix and characterized via scanning electron microscope (SEM), Fourier transform infrared (FTIR) spectroscopy and electrochemical impedance spectroscopy (EIS) studies. The GR/GLN modified electrode showed an excellent electrocatalytic activity toward the oxidation of DA, suggesting that the successful formation of GR sheets crosslinked with the functional groups of GLN polypeptide. In addition, the GR/GLN modified electrode achieved a wide linear response ranging from 0.05 to 79.5μM with a detection limit of 0.0045μM. The calculated analytical sensitivity of the sensor was 1.36±0.02μAμM -1 cm -2 . Conversely, the modified electrode demonstrates a good storage stability, reproducibility and repeatability. In addition, the sensor manifests the determination of DA in human serum and urine samples for practical applications. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Kinetic Study on Mutagenic Chemical Degradation through Three Pot Synthesiszed Graphene@ZnO Nanocomposite

    PubMed Central

    Shoeb, Mohd; Singh, Braj Raj; Mobin, Mohammad; Afreen, Gul; Khan, Wasi; Naqvi, Alim H.

    2015-01-01

    The study was taken up with the objective to synthesize graphene-zinc oxide nano particles (NPs) nanocomposite (Gr@ZnO-Nc) via In-situ synthesis method. The structural, optical, thermal, electrical and photocatalytic properties of the synthesized Gr@ZnO-Nc were studied. The characterization data confirmed that the ZnO NPs were successfully incorporated into the graphene sheets. Further, TGA/DTA results exhibited an enhanced thermal stability of the Gr@ZnO-Nc compared with the graphene. The Gr@ZnO-Nc, graphene sheets were uniformly wrapped by ZnO NPs, which can protect graphene and delay their oxidation in air. The synthesized Gr@ZnO-Nc was used for the efficient photodegradation of a carcinogenic methyl orange (MO) dye. The results exhibited promising photodegradation of the MO dye under UV light irradiation through the production of reactive oxygen species (ROS). The promising effect of Gr@ZnO-Nc on the photodegradation properties was conferred by the large surface area which increased adsorption capacity, and the strong electron transfer ability. Thus, it is encouraging to conclude that the synthesized Gr@ZnO-Nc has environmental significance with its utility in remediation in the hazardous MO dye. PMID:26287672

  15. Dissolution kinetics as a function of the Gibbs free energy of reaction: An experimental study based on albite feldspar

    NASA Astrophysics Data System (ADS)

    Hellmann, Roland; Tisserand, Delphine

    2006-01-01

    Here we report on an experimental investigation of the relation between the dissolution rate of albite feldspar and the Gibbs free energy of reaction, Δ Gr. The experiments were carried out in a continuously stirred flow-through reactor at 150 °C and pH (150 °C) 9.2. The dissolution rates R are based on steady-state Si and Al concentrations and sample mass loss. The overall relation between Δ Gr and R was determined over a free energy range of -150 < Δ Gr < -15.6 kJ mol -1. The data define a continuous and highly non-linear, sigmoidal relation between R and Δ Gr that is characterized by three distinct free energy regions. The region furthest from equilibrium, delimited by -150 < Δ Gr < -70 kJ mol -1, represents an extensive dissolution rate plateau with an average rate R¯=1.0×10-8molm-2s-1. In this free energy range the rates of dissolution are constant and independent of Δ Gr, as well as [Si] and [Al]. The free energy range delimited by -70 ⩽ Δ Gr ⩽ -25 kJ mol -1, referred to as the 'transition equilibrium' region, is characterized by a sharp decrease in dissolution rates with increasing Δ Gr, indicating a very strong inverse dependence of the rates on free energy. Dissolution nearest equilibrium, defined by Δ Gr > -25 kJ mol -1, represents the 'near equilibrium' region where the rates decrease as chemical equilibrium is approached, but with a much weaker dependence on Δ Gr. The lowest rate measured in this study, R = 6.2 × 10 -11 mol m -2 s -1 at Δ Gr = -16.3 kJ mol -1, is more than two orders of magnitude slower than the plateau rate. The data have been fitted to a rate equation (adapted from Burch et al. [Burch, T. E., Nagy, K. L., Lasaga, A. C., 1993. Free energy dependence of albite dissolution kinetics at 80 °C and pH 8.8. Chem. Geol.105, 137-162]) that represents the sum of two parallel reactions R=k1[1-exp(-ng)]+k2[1-exp(-g)], where k1 and k2 are rate constants that have been determined by regression, with values 1.02 × 10 -8 and 1

  16. Bacterial consortia at different wine fermentation phases of two typical Central European grape varieties: Blaufränkisch (Frankovka modrá) and Grüner Veltliner (Veltlínske zelené).

    PubMed

    Godálová, Zuzana; Kraková, Lucia; Puškárová, Andrea; Bučková, Mária; Kuchta, Tomáš; Piknová, Ľubica; Pangallo, Domenico

    2016-01-18

    This is the first study focused to bacterial diversity and dynamic during the vinification of two important Central Europe grape vines: Blaufränkisch and Grüner Veltliner. The investigation strategy included culture-dependent and culture-independent approaches. Four different agar media were utilized for the isolation of various bacteria occurring in several fermentation stages. The isolates were clustered by fluorescent-ITS PCR and, one or more representatives of each cluster, were identified by 16 rRNA gene sequencing. The culture-independent approach, based on 16S rRNA gene amplification, combined the denaturing gradient gel electrophoresis (DGGE) method and the construction of bacterial clone library for each wine fermentation step. A complex bacterial community was identified, comprising different lactic acid bacteria and acetic acid bacteria, such as Leuconostoc spp., Lactobacillus spp. and Gluconobacter spp. Other OTUs and bacterial isolates embraced the Actinobacteria, Bacilli, Alpha-, Beta- and Gamma-proteobacteria classes. Different taxa already detected by recent studies, such as Sphingomonas, Variovorax, Pantoea, Enterobacter and Tatumella, were detected confirming the continuous occurrence of these kinds of bacteria in wine environment. Moreover, novel genera (Amycolatopsis, Hydrogenophilus, Snodgrassella, Telluria, Gilliamella, Lelliottia, and Lonsdale quercina) never detected before were recognized, too. The role of these, until now anonymous, bacteria during vinification deserves investigation, which could open a new research field in wine technology. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Glucocorticoid receptors participate in the opiate withdrawal-induced stimulation of rats NTS noradrenergic activity and in the somatic signs of morphine withdrawal.

    PubMed

    Navarro-Zaragoza, Javier; Hidalgo, Juana M; Laorden, M Luisa; Milanés, M Victoria

    2012-08-01

    Recent evidence suggests that glucocorticoid receptor (GR) is a major molecular substrate of addictive properties of drugs of abuse. Hence, we performed a series of experiments to further characterize the role of GR signalling in opiate withdrawal-induced physical signs of dependence, enhanced noradrenaline (NA) turnover in the hypothalamic paraventricular nucleus (PVN) and tyrosine hydroxylase (TH) phosphorylation (activation) as well as GR expression in the nucleus of the solitary tract noradrenergic cell group (NTS-A₂). The role of GR signalling was assessed by i.p. pretreatment of the selective GR antagonist, mifepristone. Rats were implanted with two morphine (or placebo) pellets. Six days later, rats were pretreated with mifepristone or vehicle 30 min before naloxone and physical signs of abstinence, NA turnover, TH activation, GR expression and the hypothalamus-pituitary-adrenocortical axis activity were measured using HPLC, immunoblotting and RIA. Mifepristone alleviated the somatic signs of naloxone-induced opiate withdrawal. Mifepristone attenuated the increase in the NA metabolite, 3-methoxy-4-hydroxyphenylethylen glycol (MHPG), in the PVN, and the enhanced NA turnover observed in morphine-withdrawn rats. Mifepristone antagonized the TH phosphorylation at Ser³¹ and the expression of c-Fos expression induced by morphine withdrawal. Finally, naloxone-precipitated morphine withdrawal induced up-regulation of GR in the NTS. These results suggest that the physical signs of opiate withdrawal, TH activation and stimulation of noradrenergic pathways innervating the PVN are modulated by GR signalling. Overall, the present data suggest that drugs targeting the GR may ameliorate stress and aversive effects associated with opiate withdrawal. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  18. A general strategy toward graphitized carbon coating on iron oxides as advanced anodes for lithium-ion batteries.

    PubMed

    Ding, Chunyan; Zhou, Weiwei; Wang, Bin; Li, Xin; Wang, Dong; Zhang, Yong; Wen, Guangwu

    2017-08-25

    Integration of carbon materials with benign iron oxides is blazing a trail in constructing high-performance anodes for lithium-ion batteries (LIBs). In this paper, a unique general, simple, and controllable strategy is developed toward in situ uniform coating of iron oxide nanostructures with graphitized carbon (GrC) layers. The basic synthetic procedure only involves a simple dip-coating process for the loading of Ni-containing seeds and a subsequent Ni-catalyzed chemical vapor deposition (CVD) process for the growth of GrC layers. More importantly, the CVD treatment is conducted at a quite low temperature (450 °C) and with extremely facile liquid carbon sources consisting of ethylene glycol (EG) and ethanol (EA). The GrC content of the resulting hybrids can be controllably regulated by altering the amount of carbon sources. The electrochemical results reveal remarkable performance enhancements of iron oxide@GrC hybrids compared with pristine iron oxides in terms of high specific capacity, excellent rate and cycling performance. This can be attributed to the network-like GrC coating, which can improve not only the electronic conductivity but also the structural integrity of iron oxides. Moreover, the lithium storage performance of samples with different GrC contents is measured, manifesting that optimized electrochemical property can be achieved with appropriate carbon content. Additionally, the superiority of GrC coating is demonstrated by the advanced performance of iron oxide@GrC compared with its corresponding counterpart, i.e., iron oxides with amorphous carbon (AmC) coating. All these results indicate the as-proposed protocol of GrC coating may pave the way for iron oxides to be promising anodes for LIBs.

  19. Free-standing graphene/vanadium oxide composite as binder-free electrode for asymmetrical supercapacitor.

    PubMed

    Deng, Lingjuan; Gao, Yihong; Ma, Zhanying; Fan, Guang

    2017-11-01

    Preparation of free-standing electrode materials with three-dimensional network architecture has emerged as an effective strategy for acquiring advanced portable and wearable power sources. Herein, graphene/vanadium oxide (GR/V 2 O 5 ) free-standing monolith composite has been prepared via a simple hydrothermal process. Flexible GR sheets acted as binder to connect the belt-like V 2 O 5 for assembling three-dimensional network architecture. The obtained GR/V 2 O 5 composite can be reshaped into GR/V 2 O 5 flexible film which exhibits more compact structure by ultrasonication and vacuum filtration. A high specific capacitance of 358Fg -1 for GR/V 2 O 5 monolith compared with that of GR/V 2 O 5 flexible film (272Fg -1 ) has been achieved in 0.5molL -1 K 2 SO 4 solution when used as binder free electrodes in three-electrode system. An asymmetrical supercapacitor has been assembled using GR/V 2 O 5 monolith as positive electrode and GR monolith as negative electrode, and it can be reversibly charged-discharged at a cell voltage of 1.7V in 0.5molL -1 K 2 SO 4 electrolyte. The asymmetrical capacitor can deliver an energy density of 26.22Whkg -1 at a power density of 425Wkg -1 , much higher than that of the symmetrical supercapacitor based on GR/V 2 O 5 monolith electrode. Moreover, the asymmetrical supercapacitor preserves 90% of its initial capacitance over 1000 cycles at a current density of 5Ag -1 . Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Antibacterial Effects of Glycyrrhetinic Acid and Its Derivatives on Staphylococcus aureus

    PubMed Central

    Oyama, Kentaro; Kawada-Matsuo, Miki; Oogai, Yuichi; Hayashi, Tetsuya; Nakamura, Norifumi; Komatsuzawa, Hitoshi

    2016-01-01

    Staphylococcus aureus is a major pathogen in humans and causes serious problems due to antibiotic resistance. We investigated the antimicrobial effect of glycyrrhetinic acid (GRA) and its derivatives against 50 clinical S. aureus strains, including 18 methicillin-resistant strains. The minimum inhibitory concentrations (MICs) of GRA, dipotassium glycyrrhizate, disodium succinoyl glycyrrhetinate (GR-SU), stearyl glycyrrhetinate and glycyrrhetinyl stearate were evaluated against various S. aureus strains. Additionally, we investigated the bactericidal effects of GRA and GR-SU against two specific S. aureus strains. DNA microarray analysis was also performed to clarify the mechanism underlying the antibacterial activity of GR-SU. We detected the antimicrobial activities of five agents against S. aureus strains. GRA and GR-SU showed strong antibacterial activities compared to the other three agents tested. At a higher concentration (above 2x MIC), GRA and GR-SU showed bactericidal activity, whereas at a concentration of 1x MIC, they showed a bacteriostatic effect. Additionally, GRA and GR-SU exhibited a synergistic effect with gentamicin. The expression of a large number of genes (including transporters) and metabolic factors (carbohydrates and amino acids) was altered by the addition of GR-SU, suggesting that the inhibition of these metabolic processes may influence the degree of the requirement for carbohydrates or amino acids. In fact, the requirement for carbohydrates or amino acids was increased in the presence of either GRA or GR-SU. GRA and GR-SU exhibited strong antibacterial activity against several S. aureus strains, including MRSA. This activity may be partly due to the inhibition of several pathways involved in carbohydrate and amino acid metabolism. PMID:27820854

  1. Characterization of a Novel Dithiocarbamate Glutathione Reductase Inhibitor and Its Use as a Tool to Modulate Intracellular Glutathione*

    PubMed Central

    Seefeldt, Teresa; Zhao, Yong; Chen, Wei; Raza, Ashraf S.; Carlson, Laura; Herman, Jocqueline; Stoebner, Adam; Hanson, Sarah; Foll, Ryan; Guan, Xiangming

    2009-01-01

    Thiol redox state (TRS) is an important parameter to reflect intracellular oxidative stress and is associated with various normal and abnormal biochemical processes. Agents that can be used to increase intracellular TRS will be valuable tools in TRS-related research. Glutathione reductase (GR) is a critical enzyme in the homeostasis of TRS. The enzyme catalyzes the reduction of GSSG to GSH to maintain a high GSH:GSSG ratio. Inhibition of the enzyme can be used to increase TRS. Despite the reports of various GR inhibitors, N,N-bis(2-chloroethyl)-N-nitrosourea, an anticancer drug with IC50 = 647 μm against yeast GR, remains the most commonly used GR inhibitor in the literature. However, the toxicity caused by nonspecific interactions, as well as inhibition of DNA synthesis, complicates the use of N,N-bis(2-chloroethyl)-N-nitrosourea as a GR inhibitor. We report 2-acetylamino-3-[4-(2-acetylamino-2-carboxyethylsulfanylthiocarbonylamino)phenylthiocarbamoylsulfanyl]propionic acid (2-AAPA) as a novel irreversible GR inhibitor. 2-AAPA was prepared by one-step synthesis from commercially available reagents. The Ki and kinact of 2-AAPA against yeast GR were determined to be 56 μm and 0.1 min–1, respectively. At the concentration that produced >80% yeast GR inhibition, 2-AAPA showed no inhibition against glutamylcysteine synthetase, glutathione synthetase, catalase, and superoxide dismutase, but minimal inhibition against glutathione S-transferase and glutathione peroxidase. In CV-1 cells, 2-AAPA (0.1 mm) produced 97% GR inhibition, 25% GSH reduction, and a 5-fold increase in GSSG in 20 min. The compound can be a useful tool in TRS-related research. PMID:19049979

  2. INTRARENAL GHRELIN RECEPTOR INHIBITION AMELIORATES ANGIOTENSIN II-DEPENDENT HYPERTENSION IN RATS.

    PubMed

    Kemp, Brandon A; Howell, Nancy L; Padia, Shetal H

    2018-06-20

    The intrarenal ghrelin receptor (GR) is localized to collecting duct (CD) cells where it increases αENaC-dependent sodium reabsorption in rodents. We hypothesized that chronic GR inhibition with intrarenal GR siRNA lowers blood pressure (BP) in Angiotensin II-dependent hypertension via reductions in αENaC-dependent sodium reabsorption. Uninephrectomized Sprague-Dawley rats (N=121) received subcutaneous osmotic pumps for chronic systemic delivery of Angiotensin II or vehicle (5% dextrose in water). Rats also received intrarenal infusion of vehicle, GR siRNA, or scrambled (SCR) siRNA. In rats receiving intrarenal vehicle or intrarenal SCR siRNA, systemic Angiotensin II infusion increased sodium retention and BP on day 1, and BP remained elevated throughout the 5-day study. These rats also demonstrated increased CD GR expression after 5 days of infusion. However, intrarenal GR siRNA infusion prevented Angiotensin II-mediated sodium retention on day 1, induced a continuously negative cumulative sodium balance compared with Angiotensin II alone, and reduced BP chronically. Glomerular filtration rate and renal blood flow remained unchanged in GR siRNA-infused rats. Systemic Angiotensin II infusion also increased serum aldosterone levels, CD αENaC and pSGK1 expression in rats with intrarenal SCR siRNA; however these effects were not observed in the presence of intrarenal GR siRNA, despite exposure to the same systemic Angiotensin II. These data demonstrate that chronic inhibition of intrarenal GR activity significantly reduces αENaC -dependent sodium retention, resulting in a negative cumulative sodium balance, thereby ameliorating Angiotensin II-induced hypertension in rats. Renal GRs represent a novel therapeutic target for the treatment of hypertension and other sodium-retaining states.

  3. Evolution of Serum 25OHD in Response to Vitamin D3–Fortified Yogurts Consumed by Healthy Menopausal Women: A 6-Month Randomized Controlled Trial Assessing the Interactions between Doses, Baseline Vitamin D Status, and Seasonality

    PubMed Central

    Bonjour, Jean-Philippe; Dontot-Payen, Flore; Rouy, Emilien; Walrand, Stephane; Rousseau, Brigitte

    2018-01-01

    ABSTRACT Background: Adequate vitamin D status contributes to bone fragility risk reduction and possibly other pathological conditions that occur with aging. In response to pharmaceutical vitamin D3 supplements, several studies have documented the influence of doses, baseline status, and seasonality on serum 25-hydroyvitamin D (s25OHD). Objective: Using fortified yogurt, we investigated in one randomized controlled trial how both baseline status, as assessed by measuring s25OHD prior the onset of the trial, and the season of enrollment quantitatively influenced the response to the supplemented (Suppl.) of vitamin D3 (VitD3) in healthy community-dwelling women. Methods: A 24-week controlled trial was conducted in menopausal women (mean age: 61.5). Participants were randomized into 3 groups (Gr): Gr.Suppl.0, time controls maintaining dietary habits; Gr.Suppl.5 and Gr.Suppl.10 consuming one and two 125-g servings of VitD3-fortified yogurts with 5- and 10-µg daily doses, respectively. The 16 intervention weeks lasted from early January to mid-August, the 8 follow-up weeks, without product, from late August to mid-October. Before enrollment, subjects were randomized into 2 s25OHD strata: low stratum (LoStr): 25–50 nmol/L; high stratum (HiStr): >50–75 nmol/L. Results: All enrolled participants adhered to the protocol throughout the 24-week study: Gr.Suppl.0 (n = 45), Gr.Suppl.5 (n = 44), and Gr.Suppl.10 (n = 44). Over the 16 intervention and 8 follow-up weeks, s25OHD increased in both supplemented groups, more in Gr.Suppl.10 than in Gr.Suppl.5. At the end of the intervention, the subject proportion with s25OHD ≥ 50 nmol/L was 37.8, 54.5, and 63.6% in Gr.Suppl.0, Gr.Suppl.5, and Gr.Suppl.10, respectively. The constant rate of s25OHD per supplemental VitD3 microgram was greater in LoStr than HiStr. The s25OHD increase was greater with late (mid-March) than early (mid-January) inclusion. Conclusion: This randomized trial demonstrates (1) a dose-dependent s25OHD

  4. Evolution of Serum 25OHD in Response to Vitamin D3-Fortified Yogurts Consumed by Healthy Menopausal Women: A 6-Month Randomized Controlled Trial Assessing the Interactions between Doses, Baseline Vitamin D Status, and Seasonality.

    PubMed

    Bonjour, Jean-Philippe; Dontot-Payen, Flore; Rouy, Emilien; Walrand, Stephane; Rousseau, Brigitte

    2018-01-01

    Adequate vitamin D status contributes to bone fragility risk reduction and possibly other pathological conditions that occur with aging. In response to pharmaceutical vitamin D 3 supplements, several studies have documented the influence of doses, baseline status, and seasonality on serum 25-hydroyvitamin D (s25OHD). Using fortified yogurt, we investigated in one randomized controlled trial how both baseline status, as assessed by measuring s25OHD prior the onset of the trial, and the season of enrollment quantitatively influenced the response to the supplemented (Suppl.) of vitamin D 3 (VitD 3 ) in healthy community-dwelling women. A 24-week controlled trial was conducted in menopausal women (mean age: 61.5). Participants were randomized into 3 groups (Gr): Gr.Suppl.0, time controls maintaining dietary habits; Gr.Suppl.5 and Gr.Suppl.10 consuming one and two 125-g servings of VitD 3 -fortified yogurts with 5- and 10-µg daily doses, respectively. The 16 intervention weeks lasted from early January to mid-August, the 8 follow-up weeks, without product, from late August to mid-October. Before enrollment, subjects were randomized into 2 s25OHD strata: low stratum (LoStr): 25-50 nmol/L; high stratum (HiStr): >50-75 nmol/L. All enrolled participants adhered to the protocol throughout the 24-week study: Gr.Suppl.0 (n = 45), Gr.Suppl.5 (n = 44), and Gr.Suppl.10 (n = 44). Over the 16 intervention and 8 follow-up weeks, s25OHD increased in both supplemented groups, more in Gr.Suppl.10 than in Gr.Suppl.5. At the end of the intervention, the subject proportion with s25OHD ≥ 50 nmol/L was 37.8, 54.5, and 63.6% in Gr.Suppl.0, Gr.Suppl.5, and Gr.Suppl.10, respectively. The constant rate of s25OHD per supplemental VitD 3 microgram was greater in LoStr than HiStr. The s25OHD increase was greater with late (mid-March) than early (mid-January) inclusion. This randomized trial demonstrates (1) a dose-dependent s25OHD improvement related to fortified yogurt consumption; (2) an

  5. Pollination and reproduction of an invasive plant inside and outside its ancestral range

    NASA Astrophysics Data System (ADS)

    Petanidou, Theodora; Price, Mary V.; Bronstein, Judith L.; Kantsa, Aphrodite; Tscheulin, Thomas; Kariyat, Rupesh; Krigas, Nikos; Mescher, Mark C.; De Moraes, Consuelo M.; Waser, Nickolas M.

    2018-05-01

    Comparing traits of invasive species within and beyond their ancestral range may improve our understanding of processes that promote aggressive spread. Solanum elaeagnifolium (silverleaf nightshade) is a noxious weed in its ancestral range in North America and is invasive on other continents. We compared investment in flowers and ovules, pollination success, and fruit and seed set in populations from Arizona, USA ("AZ") and Greece ("GR"). In both countries, the populations we sampled varied in size and types of present-day disturbance. Stature of plants increased with population size in AZ samples whereas GR plants were uniformly tall. Taller plants produced more flowers, and GR plants produced more flowers for a given stature and allocated more ovules per flower. Similar functional groups of native bees pollinated in AZ and GR populations, but visits to flowers decreased with population size and we observed no visits in the largest GR populations. As a result, plants in large GR populations were pollen-limited, and estimates of fecundity were lower on average in GR populations despite the larger allocation to flowers and ovules. These differences between plants in our AZ and GR populations suggest promising directions for further study. It would be useful to sample S. elaeagnifolium in Mediterranean climates within the ancestral range (e.g., in California, USA), to study asexual spread via rhizomes, and to use common gardens and genetic studies to explore the basis of variation in allocation patterns and of relationships between visitation and fruit set.

  6. Lateral assembly of oxidized graphene flakes into large-scale transparent conductive thin films with a three-dimensional surfactant 4-sulfocalix[4]arene

    PubMed Central

    Sundramoorthy, Ashok K.; Wang, Yilei; Wang, Jing; Che, Jianfei; Thong, Ya Xuan; Lu, Albert Chee W.; Chan-Park, Mary B.

    2015-01-01

    Graphene is a promising candidate material for transparent conductive films because of its excellent conductivity and one-carbon-atom thickness. Graphene oxide flakes prepared by Hummers method are typically several microns in size and must be pieced together in order to create macroscopic films. We report a macro-scale thin film fabrication method which employs a three-dimensional (3-D) surfactant, 4-sulfocalix[4]arene (SCX), as a lateral aggregating agent. After electrochemical exfoliation, the partially oxidized graphene (oGr) flakes are dispersed with SCX. The SCX forms micelles, which adsorb on the oGr flakes to enhance their dispersion, also promote aggregation into large-scale thin films under vacuum filtration. A thin oGr/SCX film can be shaved off from the aggregated oGr/SCX cake by immersing the cake in water. The oGr/SCX thin-film floating on the water can be subsequently lifted from the water surface with a substrate. The reduced oGr (red-oGr) films can be as thin as 10−20 nm with a transparency of >90% and sheet resistance of 890 ± 47 kΩ/sq. This method of electrochemical exfoliation followed by SCX-assisted suspension and hydrazine reduction, avoids using large amounts of strong acid (unlike Hummers method), is relatively simple and can easily form a large scale conductive and transparent film from oGr/SCX suspension. PMID:26040436

  7. Insight into the Role of Size Modulation on Tuning the Band Gap and Photocatalytic Performance of Semiconducting Nitrogen-Doped Graphene.

    PubMed

    Yang, Mei-Ling; Zhang, Nan; Lu, Kang-Qiang; Xu, Yi-Jun

    2017-04-04

    Considerable attention has been focused on transforming graphene (GR) into semiconducting GR by diverse strategies, which can perform as one type of promising photocatalyst toward various photoredox reactions. Herein, we report a facile alkali-assisted hydrothermal method for simultaneous tailoring of the lateral size of GR and nitrogen (N) doping into the GR matrix, by which small-sized N-doped GR (S-NGR) can be obtained. For comparison, large-sized N-doped GR (L-NGR) has also been achieved through the same hydrothermal treatment except for the addition of alkali. The photocatalytic activity test shows that S-NGR exhibits much higher activity than L-NGR toward the degradation of organic pollutants under visible-light irradiation. Structure-photoactivity correlation analysis and characterization suggest that the underlying origin for the significantly enhanced visible-light photoactivity of S-NGR in comparison with L-NGR can be assigned to the lateral size decrease in the NGR sheet, which is able to tune the band gap of semiconducting NGR, to facilitate the separation and transfer of photogenerated charge carriers, and to improve the adsorption capacity of NGR toward the reactant. It is expected that this work will cast new light on the judicious utilization of semiconducting GR with controlled size modulation and heteroatom doping to tune its physicochemical properties, thereby advancing further developments in the rational design of more efficient semiconducting GR materials for diverse applications in photocatalysis.

  8. Brain region- and sex-specific modulation of mitochondrial glucocorticoid receptor phosphorylation in fluoxetine treated stressed rats: effects on energy metabolism.

    PubMed

    Adzic, Miroslav; Lukic, Iva; Mitic, Milos; Djordjevic, Jelena; Elaković, Ivana; Djordjevic, Ana; Krstic-Demonacos, Marija; Matić, Gordana; Radojcic, Marija

    2013-12-01

    Antidepressants affect glucocorticoid receptor (GR) functioning partly through modulation of its phosphorylation but their effects on mitochondrial GR have remained undefined. We investigated the ability of chronic fluoxetine treatment to affect chronic stress-induced changes of mitochondrial GR and its phosphoisoforms (pGRs) in the prefrontal cortex and hippocampus of female and male rats. Since mitochondrial GR regulates oxidative phosphorylation, expression of mitochondrial-encoded subunits of cytochrome (cyt) c oxidase and its activity were also investigated. Chronic stress caused accumulation of the GR in mitochondria of female prefrontal cortex, while the changes in the hippocampus were sex-specific at the levels of pGRs. Expression of mitochondrial COXs genes corresponded to chronic stress-modulated mitochondrial GR in both tissues of both genders and to cyt c oxidase activity in females. Moreover, the metabolic parameters in stressed animals were affected by fluoxetine therapy only in the hippocampus. Namely, fluoxetine effects on mitochondrial COXs and cyt c oxidase activity in the hippocampus seem to be conveyed through pGR232 in females, while in males this likely occurs through other mechanisms. In summary, sex-specific regulation of cyt c oxidase by the stress and antidepressant treatment and its differential convergence with mitochondrial GR signaling in the prefrontal cortex and hippocampus could contribute to clarification of sex-dependent vulnerability to stress-related disorders and sex-specific clinical impact of antidepressants. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Atmospheric processes affecting the separation of volcanic ash and SO2 in volcanic eruptions: inferences from the May 2011 Grímsvötn eruption

    NASA Astrophysics Data System (ADS)

    Prata, Fred; Woodhouse, Mark; Huppert, Herbert E.; Prata, Andrew; Thordarson, Thor; Carn, Simon

    2017-09-01

    The separation of volcanic ash and sulfur dioxide (SO2) gas is sometimes observed during volcanic eruptions. The exact conditions under which separation occurs are not fully understood but the phenomenon is of importance because of the effects volcanic emissions have on aviation, on the environment, and on the earth's radiation balance. The eruption of Grímsvötn, a subglacial volcano under the Vatnajökull glacier in Iceland during 21-28 May 2011 produced one of the most spectacular examples of ash and SO2 separation, which led to errors in the forecasting of ash in the atmosphere over northern Europe. Satellite data from several sources coupled with meteorological wind data and photographic evidence suggest that the eruption column was unable to sustain itself, resulting in a large deposition of ash, which left a low-level ash-rich atmospheric plume moving southwards and then eastwards towards the southern Scandinavian coast and a high-level predominantly SO2 plume travelling northwards and then spreading eastwards and westwards. Here we provide observational and modelling perspectives on the separation of ash and SO2 and present quantitative estimates of the masses of ash and SO2 that erupted, the directions of transport, and the likely impacts. We hypothesise that a partial column collapse or sloughing fed with ash from pyroclastic density currents (PDCs) occurred during the early stage of the eruption, leading to an ash-laden gravity intrusion that was swept southwards, separated from the main column. Our model suggests that water-mediated aggregation caused enhanced ash removal because of the plentiful supply of source water from melted glacial ice and from entrained atmospheric water. The analysis also suggests that ash and SO2 should be treated with separate source terms, leading to improvements in forecasting the movement of both types of emissions.

  10. Plastid-Localized Glutathione Reductase2–Regulated Glutathione Redox Status Is Essential for Arabidopsis Root Apical Meristem Maintenance[C][W

    PubMed Central

    Yu, Xin; Pasternak, Taras; Eiblmeier, Monika; Ditengou, Franck; Kochersperger, Philip; Sun, Jiaqiang; Wang, Hui; Rennenberg, Heinz; Teale, William; Paponov, Ivan; Zhou, Wenkun; Li, Chuanyou; Li, Xugang; Palme, Klaus

    2013-01-01

    Glutathione is involved in thiol redox signaling and acts as a major redox buffer against reactive oxygen species, helping to maintain a reducing environment in vivo. Glutathione reductase (GR) catalyzes the reduction of glutathione disulfide (GSSG) into reduced glutathione (GSH). The Arabidopsis thaliana genome encodes two GRs: GR1 and GR2. Whereas the cytosolic/peroxisomal GR1 is not crucial for plant development, we show here that the plastid-localized GR2 is essential for root growth and root apical meristem (RAM) maintenance. We identify a GR2 mutant, miao, that displays strong inhibition of root growth and severe defects in the RAM, with GR activity being reduced to ∼50%. miao accumulates high levels of GSSG and exhibits increased glutathione oxidation. The exogenous application of GSH or the thiol-reducing agent DTT can rescue the root phenotype of miao, demonstrating that the RAM defects in miao are triggered by glutathione oxidation. Our in silico analysis of public microarray data shows that auxin and glutathione redox signaling generally act independently at the transcriptional level. We propose that glutathione redox status is essential for RAM maintenance through both auxin/PLETHORA (PLT)-dependent and auxin/PLT-independent redox signaling pathways. PMID:24249834

  11. Determination of Optimal Harvest Time of Chuchung Variety Green Rice(®) (Oryza sativa L.) with High Contents of GABA, γ-Oryzanol, and α-Tocopherol.

    PubMed

    Kim, Hoon; Kim, Oui-Woung; Ha, Ae Wha; Park, Soojin

    2016-06-01

    In our previous study, an early-maturing variety of rice (Oryza sativa L.), Jinbu can have feature with unique green color, various phytochemicals as well as nutritive components by the optimal early harvesting, called Green Rice(®) (GR). The aims of the present field experiments were to evaluate the changes in the weight of 1,000 kernels, yield, and contents of proximate and bioactive compounds in Chuchung, a mid-late maturing variety, during the pre-harvest maturation of rough rice and to research the appropriate harvest time and potent bioactivity of Chuchung GR. The weights of 1,000 kernels of Chuchung GR dramatically increased until 27 days after heading (DAH). The yields of Chuchung GR declined after 27 DAH and significantly declined to 0.0% after 45 DAH. The caloric value and total mineral contents were higher in the GR than in the full ripe stage, the brown rice (BR). In the GR, the contents of bioactive compounds, such as γ-aminobutyric acid, γ-oryzanol, and α-tocopherol, were much higher (P<0.05) than those in the BR, specifically during 24~27 DAH. Therefore, bioactive Chuchung GR can be produced with a reasonable yield at 24~27 DAH and it could be useful for applications in various nutritive and functional food products.

  12. Uterine glucocorticoid receptors are critical for fertility in mice through control of embryo implantation and decidualization

    PubMed Central

    Whirledge, Shannon D.; Oakley, Robert H.; Myers, Page H.; Lydon, John P.; DeMayo, Francesco; Cidlowski, John A.

    2015-01-01

    In addition to the well-characterized role of the sex steroid receptors in fertility and reproduction, organs of the female reproductive tract are also regulated by the hypothalamic–pituitary–adrenal axis. These endocrine organs are sensitive to stress-mediated actions of glucocorticoids, and the mouse uterus contains high levels of the glucocorticoid receptor (GR). Although the presence of GR in the uterus is well established, uterine glucocorticoid signaling has been largely ignored in terms of its reproductive and/or immunomodulatory functions on fertility. To define the direct in vivo function of glucocorticoid signaling in adult uterine physiology, we generated a uterine-specific GR knockout (uterine GR KO) mouse using the PRcre mouse model. The uterine GR KO mice display a profound subfertile phenotype, including a significant delay to first litter and decreased pups per litter. Early defects in pregnancy are evident as reduced blastocyst implantation and subsequent defects in stromal cell decidualization, including decreased proliferation, aberrant apoptosis, and altered gene expression. The deficiency in uterine GR signaling resulted in an exaggerated inflammatory response to induced decidualization, including altered immune cell recruitment. These results demonstrate that GR is required to establish the necessary cellular context for maintaining normal uterine biology and fertility through the regulation of uterine-specific actions. PMID:26598666

  13. Determination of Optimal Harvest Time of Chuchung Variety Green Rice® (Oryza sativa L.) with High Contents of GABA, γ-Oryzanol, and α-Tocopherol

    PubMed Central

    Kim, Hoon; Kim, Oui-Woung; Ha, Ae Wha; Park, Soojin

    2016-01-01

    In our previous study, an early-maturing variety of rice (Oryza sativa L.), Jinbu can have feature with unique green color, various phytochemicals as well as nutritive components by the optimal early harvesting, called Green Rice® (GR). The aims of the present field experiments were to evaluate the changes in the weight of 1,000 kernels, yield, and contents of proximate and bioactive compounds in Chuchung, a mid-late maturing variety, during the pre-harvest maturation of rough rice and to research the appropriate harvest time and potent bioactivity of Chuchung GR. The weights of 1,000 kernels of Chuchung GR dramatically increased until 27 days after heading (DAH). The yields of Chuchung GR declined after 27 DAH and significantly declined to 0.0% after 45 DAH. The caloric value and total mineral contents were higher in the GR than in the full ripe stage, the brown rice (BR). In the GR, the contents of bioactive compounds, such as γ-aminobutyric acid, γ-oryzanol, and α-tocopherol, were much higher (P<0.05) than those in the BR, specifically during 24~27 DAH. Therefore, bioactive Chuchung GR can be produced with a reasonable yield at 24~27 DAH and it could be useful for applications in various nutritive and functional food products. PMID:27390725

  14. Glucocorticoid receptor expression on circulating leukocytes in healthy and asthmatic adolescents in response to exercise

    PubMed Central

    Lu, Kim D.; Cooper, Dan; Haddad, Fadia; Zaldivar, Frank; Kraft, Monica; Radom-Aizik, Shlomit

    2017-01-01

    Background Poor aerobic fitness is associated with worsening of asthma symptoms and fitness training may improve asthma control. The mechanism linking fitness with asthma is not known. We hypothesized that repeated bouts of exercise would lead to a downregulation of glucocorticoid receptor (GR) expression on circulating leukocytes reflecting a reduced responsiveness to stress. Methods In a prospective exercise training intervention of healthy and asthmatic adolescents, GR expression in leukocytes was measured using flow cytometry in response to a brief exercise challenge before and after the training intervention. PBMC gene expression of GR, GRβ, HSP70, and TGFβ1, 2 were determined using RT-PCR. Results Peak V̇O2 increased by 14.6 ± 2.3% indicating an effective training (p<0.01). There was a significant difference in GR expression among leukocyte subtypes, with highest expression in eosinophils. Following the training intervention, there was a significant decrease in baseline GR expression (p<0.05) in leukocyte and monocyte subtypes in both healthy and asthmatic adolescents. Conclusions This is the first study in adolescents to show that exercise training reduces GR expression on circulating leukocytes. We speculate that exercise training downregulates the stress response in general, manifested by decreased GR expression, and may explain why improving fitness improves asthma health. PMID:28796240

  15. Switchable Ionic Liquids: An Environmentally Friendly Medium to Synthesise Nanoparticulate Green Rust

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

    Lao, David; Kukkadapu, Ravi; Kovarik, Libor

    Under anoxic conditions, a novel nanoparticulate green rust with carbonate (nano GR) was synthesized by addition of methanol to degassed switchable ionic liquid (SWIL) solution comprised of 1-hexanol, diazabicycloundec-7-ene (DBU), CO2 and Fe(C2H3O2)2 (Fe(OAc)2). Variable temperature Mössbauer spectroscopy studies indicated the product to be predominantly GR while TEM-SAED method confirmed it be nanoparticulate in nature. Experiments with and without methanol in the SWIL medium suggest that methanol may be responsible for Fe(II) oxidation to Fe(III) necessary for GR formation. Studies with Ar instead of CO2 trigger gas indicated that CO2 is essential for GR formation. Conditions to generate CO32- anionmore » was most likely provided by basic environment of the medium. The nano GR suspension was very reactive and instantaneously oxidized completely to a reddish-brown precipitate upon exposure to ambient atmosphere. The nature of the oxidized sample is not certain. The oxidized product, however, appears to be a mix of ferric green rust- [GR(CO32-]*; major] and ferrihydrite-like minerals. To our knowledge, this is first report of use of environmentally-friendly SWIL reagents to synthesize very reactive nano GR materials.« less

  16. Expression of glucocorticoid receptor isoforms and associations with serine/arginine-rich protein 30c and 40 in patients with systemic lupus erythematosus.

    PubMed

    Guan, Yan-Chun; Jiang, Lei; Ma, Liang-Liang; Sun, Xiang-Nan; Yu, Dan-Dan; Liu, Jing; Qu, Dong-Xia; Fang, Mei-Yun

    2015-01-01

    To investigate the expression of glucocorticoid receptor (GR) isoforms in patients with systemic lupus erythematosus (SLE), confirm the main GR isoforms involving in glucocorticoids (GC) resistance, and explore the associations of GR isoforms with serine/arginine-rich protein (SRp) 30c and SRp40. Seventy patients with SLE and thirty-eight age- and sex-matched controls were recruited. All patients received prednisone (0.5-1 mg/kg/d) as their routine therapy. According to the therapeutic effect, patients were divided into glucocorticoid-resistant (GCR) and glucocorticoid-sensitive (GCS) groups. Transcript levels of GRα, GRβ, GRγ, GR-P, SRp30c and SRp40 in peripheral blood mononuclear cells (PBMCs) were determined by real-time PCR. GRα and GRβ proteins were detected by western blotting. Trial registration number is ChiCTR-RCH-12002808. Four GR transcripts in SLE patients showed the following trend: GRα (51.85%) > GR-P (23.78%) > GRγ (13.08%) >GRβ (0.03%). GR-P transcript and ratio of GRα/GR-P in SLE patients were significantly higher than that in controls (p<0.05). GRα transcript and protein as well as SRp40 transcript in GCS group were significantly higher than that in the GCR group before GC treatment (p<0.05). In the GCS group, GRα transcript and SRp40 transcript were significantly higher after GC treatment than that before GC treatment (p<0.05). In the GCR group, GR-P transcript was significantly higher after GC treatment than that before GC treatment (p<0.05). Positive correlation between SRp40 and GRα transcript was found (p<0.05). Additionally, SLE Disease Activity Index scores were significantly negatively correlated with GRα transcript and protein expression (p<0.05). Our data demonstrated that the decreased expression of GRα might be the evidence of high disease activity and help to predict GC resistance. GR-P isoform might be implicated in the development of resistance. Additionally, the preliminary finding suggested that SRp40 might be

  17. The Sensitivity of the Greenland Ice Sheet to Glacial-Interglacial Oceanic Forcing

    NASA Astrophysics Data System (ADS)

    Tabone, I.; Blasco Navarro, J.; Robinson, A.; Alvarez-Solas, J.; Montoya, M.

    2017-12-01

    Up to now, the scientific community has mainly focused on the sensitivity of the Greenland Ice Sheet (GrIS) to atmospheric variations. However, several studies suggest that the enhanced ice mass loss experienced by the GrIS in the past decades is directly connected to the increasing North Atlantic temperatures. Melting of GrIS outlet glaciers triggers grounding-line retreat increasing ice discharge into the ocean. This new evidence leads to consider the ocean as a relevant driver to be taken into account when modeling the evolution of the GrIS. The ice-ocean interaction is a primary factor controling not only the likely future retreat of GrIS outlet glaciers, or the huge ice loss in past warming climates, but also, and more strongly, the past GrIS glacial expansion. The latter assumption is supported by reconstructions which propose the GrIS to be fully marine-based during glacials, and thus more exposed to the influence of the ocean. Here, for the first time, we investigate the response of the GrIS to past oceanic changes using a three-dimensional hybrid ice-sheet/ice-shelf model, which combines the Shallow Ice Approximation (SIA) for slow grounded ice sheets and the Shallow Shelf Approximation (SSA) in ice shelves and ice streams. The model accounts for a time-dependent parametrisation of the marine basal melting rate, which is used to reproduce past oceanic variations. In this work simulations of the last two glacial cycles are performed. Our results show that the GrIS is very sensitive to the ocean-triggered submarine melting (freezing). Mild oceanic temperature variations lead to a rapid retreat (expansion) of the GrIS margins, which, inducing a dynamic adjustment of the grounded ice sheet, drive the evolution of the whole ice sheet. Our results strongly suggest the need to consider the ocean as an active forcing in paleo ice sheet models.

  18. The Progestin-Only Contraceptive Medroxyprogesterone Acetate, but Not Norethisterone Acetate, Enhances HIV-1 Vpr-Mediated Apoptosis in Human CD4+ T Cells through the Glucocorticoid Receptor

    PubMed Central

    Tomasicchio, Michele; Avenant, Chanel; Du Toit, Andrea; Ray, Roslyn M.; Hapgood, Janet P.

    2013-01-01

    The glucocorticoid receptor (GR) regulates several physiological functions, including immune function and apoptosis. The HIV-1 virus accessory protein, viral protein R (Vpr), can modulate the transcriptional response of the GR. Glucocorticoids (GCs) and Vpr have been reported to induce apoptosis in various cells, including T-cells. We have previously shown that the injectable contraceptive, medroxyprogesterone acetate (MPA) is a partial to full agonist for the GR, unlike norethisterone acetate (NET-A). We investigated the functional cross talk between the GR and Vpr in inducing apoptosis in CD4+ T-cells, in the absence and presence of GCs and these progestins, as well as progesterone. By using flow cytometry, we show that, in contrast to NET-A and progesterone, the synthetic GR ligand dexamethasone (Dex), cortisol and MPA induce apoptosis in primary CD4+ T-cells. Furthermore, the C-terminal part of the Vpr peptide, or HIV-1 pseudovirus, together with Dex or MPA further increased the apoptotic phenotype, unlike NET-A and progesterone. By a combination of Western blotting, PCR and the use of receptor- selective agonists, we provide evidence that the GR and the estrogen receptor are the only steroid receptors expressed in peripheral blood mononuclear cells. These results, together with the findings that RU486, a GR antagonist, prevents Dex-, MPA- and Vpr-mediated apoptosis, provide evidence for the first time that GR agonists or partial agonists increase apoptosis in primary CD4+ T-cells via the GR. We show that apoptotic induction involves differential expression of key apoptotic genes by both Vpr and GCs/MPA. This work suggests that contraceptive doses of MPA but not NET-A or physiological doses of progesterone could potentially accelerate depletion of CD4+ T-cells in a GR-dependent fashion in HIV-1 positive women, thereby contributing to immunodeficiency. The results imply that choice of progestin used in contraception may be critical to susceptibility and

  19. G-CSF/anti-G-CSF antibody complexes drive the potent recovery and expansion of CD11b+Gr-1+ myeloid cells without compromising CD8+ T cell immune responses

    PubMed Central

    2013-01-01

    Background Administration of recombinant G-CSF following cytoreductive therapy enhances the recovery of myeloid cells, minimizing the risk of opportunistic infection. Free G-CSF, however, is expensive, exhibits a short half-life, and has poor biological activity in vivo. Methods We evaluated whether the biological activity of G-CSF could be improved by pre-association with anti-G-CSF mAb prior to injection into mice. Results We find that the efficacy of G-CSF therapy can be enhanced more than 100-fold by pre-association of G-CSF with an anti-G-CSF monoclonal antibody (mAb). Compared with G-CSF alone, administration of G-CSF/anti-G-CSF mAb complexes induced the potent expansion of CD11b+Gr-1+ myeloid cells in mice with or without concomitant cytoreductive treatment including radiation or chemotherapy. Despite driving the dramatic expansion of myeloid cells, in vivo antigen-specific CD8+ T cell immune responses were not compromised. Furthermore, injection of G-CSF/anti-G-CSF mAb complexes heightened protective immunity to bacterial infection. As a measure of clinical value, we also found that antibody complexes improved G-CSF biological activity much more significantly than pegylation. Conclusions Our findings provide the first evidence that antibody cytokine complexes can effectively expand myeloid cells, and furthermore, that G-CSF/anti-G-CSF mAb complexes may provide an improved method for the administration of recombinant G-CSF. PMID:24279871

  20. Comparative Corrosion Behavior of Two Palladium Containing Titanium Alloys

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

    Lian, T; Yashiki, T; Nakayama, T

    2006-02-05

    The ASTM standard B 265 provides the requirements for the chemical composition of titanium (Ti) alloys. It is planned to use corrosion resistant and high strength titanium alloys to fabricate the drip shield at the proposed Yucca Mountain Repository. Titanium grade (Gr) 7 (R52400) and other Ti alloys are currently being characterized for this application. Ti Gr 7 contains 0.15% Palladium (Pd) to increase its corrosion performance. In this article we report results on the comparative short term corrosion behavior of Ti Gr 7 and a Ruthenium (Ru) containing alloy (Ti Gr 33). Ti Gr 33 also contains a smallmore » amount of Pd. Limited electrochemical testing such as polarization resistance and cyclic potentiodynamic curves showed that both alloys have a similar corrosion behavior in the tested environments.« less

  1. COMPARATIVE CORROSION BEHAVIOR OF TWO PALLADIUM CONTAINING TITANIUM ALLOYS

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

    T. Lian, T. Yashiki, T. Nakayama, T. Nakanishi, R. B. Rebak

    2006-07-23

    The ASTM standard B 265 provides the requirements for the chemical composition of titanium (Ti) alloys. It is planned to use corrosion resistant and high strength titanium alloys to fabricate the drip shield at the proposed Yucca Mountain Repository. Titanium grade (Gr) 7 (R52400) and other Ti alloys are currently being characterized for this application. Ti Gr 7 contains 0.15% Palladium (Pd) to increase its corrosion performance. In this article we report results on the comparative short term corrosion behavior of Ti Gr 7 and a Ruthenium (Ru) containing alloy (Ti Gr 33). Ti Gr 33 also contains a smallmore » amount of Pd. Limited electrochemical testing such as polarization resistance and cyclic potentiodynamic curves showed that both alloys have a similar corrosion behavior in the tested environments.« less

  2. Cationic Biomimetic Particles of Polystyrene/Cationic Bilayer/Gramicidin for Optimal Bactericidal Activity.

    PubMed

    Xavier, Gabriel R S; Carmona-Ribeiro, Ana M

    2017-12-02

    Nanostructured particles of polystyrene sulfate (PSS) covered by a cationic lipid bilayer of dioctadecyldimethylammonium bromide (DODAB) incorporated gramicidin D (Gr) yielding optimal and broadened bactericidal activity against both Escherichia coli and Staphylococcus aureus . The adsorption of DODAB/Gr bilayer onto PSS nanoparticles (NPs) increased the zeta-average diameter by 8-10 nm, changed the zeta-potential of the NPs from negative to positive, and yielded a narrow size distributions for the PSS/DODAB/Gr NPs, which displayed broad and maximal microbicidal activity at very small concentrations of the antimicrobials, namely, 0.057 and 0.0057 mM DODAB and Gr, respectively. The results emphasized the advantages of highly-organized, nanostructured, and cationic particles to achieve hybrid combinations of antimicrobials with broad spectrum activity at considerably reduced DODAB and Gr concentrations.

  3. Epigenetic regulation of the glucocorticoid receptor promoter 1(7) in adult rats.

    PubMed

    Witzmann, Simone R; Turner, Jonathan D; Mériaux, Sophie B; Meijer, Onno C; Muller, Claude P

    2012-11-01

    Regulation of glucocorticoid receptor (GR) levels is an important stress adaptation mechanism. Transcription factor Nfgi-a and environmentally induced Gr promoter 1 7 methylation have been implicated in fine-tuning the expression of Gr 1 7 transcripts. Here, we investigated Gr promoter 1 7 methylation and Gr 1 7 expression in adult rats exposed to either acute or chronic stress paradigms. A strong negative correlation was observed between the sum of promoter-wide methylation levels and Gr 1 7 transcript levels, independent of the stressor. Methylation of individual sites did not, however, correlate with transcript levels. This suggested that promoter 1 7 was directly regulated by promoter-wide DNA methylation. Although acute stress increased Ngfi-a expression in the hypothalamic paraventricular nucleus (PVN), Gr 1 7 transcript levels remained unaffected despite low methylation levels. Acute stress had little effect on these low methylation levels, except at four hippocampal CpGs. Chronic stress altered the corticosterone response to an acute stressor. In the adrenal and pituitary glands, but not in the brain, this was accompanied by an increase in methylation levels in orchestrated clusters rather than individual CpGs. PVN methylation levels, unaffected by acute or chronic stress, were significantly more variable within- than between-groups, suggesting that they were instated probably during the perinatal period and represent a pre-established trait. Thus, in addition to the known perinatal programming, the Gr 1 7 promoter is epigenetically regulated by chronic stress in adulthood, and retains promoter-wide tissue-specific plasticity. Differences in methylation susceptibility between the PVN in the perinatal period and the peripheral HPA axis tissues in adulthood may represent an important "trait" vs. "state" regulation of the Gr gene.

  4. Early Formation of Serum Advanced Glycation End-Products in Children with Type 1 Diabetes Mellitus: Relationship with Glycemic Control.

    PubMed

    Jaisson, Stéphane; Souchon, Pierre-François; Desmons, Aurore; Salmon, Anne-Sophie; Delemer, Brigitte; Gillery, Philippe

    2016-05-01

    To quantify serum advanced glycation end-products (AGEs) at the onset of type 1 diabetes mellitus and to determine their potential usefulness as retrospective indicators of glycemic balance. Carboxymethyllysine (CML) and pentosidine concentrations were determined by liquid chromatography-tandem mass spectrometry in 3 groups of children with type 1 diabetes mellitus: group (Gr) 1, subjects included at disease onset (n = 36); Gr2, subjects with diabetes of 5 years duration (n = 48); Gr3, subjects with diabetes of 10 years duration and in control subjects (n = 33). Hemoglobin A1c (HbA1c) values were recorded over the entire course of treatment for assessing long-term glycemic balance. Serum AGE concentrations were increased in all groups of subjects with diabetes compared with control subjects, but were highest in Gr1 (for CML: 0.155, 0.306, 0.219, and 0.224 mmol/mol Lys in control, Gr1, Gr2, and Gr3 subjects, respectively; for pentosidine: 312, 492, 365, and 403 nmol/mol Lys, respectively). AGE concentrations were closely correlated with HbA1c values (r = 0.78 for CML; r = 0.49 for pentosidine). In Gr2 and Gr3, the overall glycemic balance estimated by average HbA1c values was positively correlated with CML and pentosidine concentrations, especially in the first year of follow-up. Our results indicate that AGE concentrations are elevated in serum at the time of diabetes mellitus diagnosis, suggesting that the deleterious role of AGEs in the development of long-term complications should be taken into account even at the initial stages of the disease. Moreover, in some circumstances, AGEs could serve as surrogate markers of HbA1c for monitoring glycemic control. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Pathophysiology of Glucocorticoid Signaling.

    PubMed

    Vitellius, Géraldine; Trabado, Séverine; Bouligand, Jérôme; Delemer, Brigitte; Lombès, Marc

    2018-06-01

    Glucocorticoids (GC), such as cortisol or dexamethasone, control various physiological functions, notably those involved in development, metabolism, inflammatory processes and stress, and exert most of their effects upon binding to the glucocorticoid receptor (GR, encoded by NR3C1 gene). GC signaling follows several consecutive steps leading to target gene transactivation, including ligand binding, nuclear translocation of ligand-activated GR complexes, DNA binding, coactivator interaction and recruitment of functional transcriptional machinery. Any step may be impaired and may account for altered GC signaling. Partial or generalized glucocorticoid resistance syndrome may result in a reduced level of functional GR, a decreased hormone affinity and binding, a defect in nuclear GR translocation, a decrease or lack of DNA binding and/or post-transcriptional GR modifications. To date, 26 loss-of-function NR3C1 mutations have been reported in the context of hypertension, hirsutism, adrenal hyperplasia or metabolic disorders. These clinical signs are generally associated with biological features including hypercortisolism without negative regulatory feedback loop on the hypothalamic-pituitary-adrenal axis. Patients had often low plasma aldosterone and renin levels despite hypertension. Only one GR gain-of-function mutation has been described associating Cushing's syndrome phenotype with normal urinary-free cortisol. Some GR polymorphisms (ER22/23EK, GR-9β) have been linked to glucocorticoid resistance and a healthier metabolic profile whereas some others seemed to be associated with GC hypersensitivity (N363S, BclI), increasing cardiovascular risk (diabetes type 2, visceral obesity). This review focuses on the earlier findings on the pathophysiology of GR signaling and presents criteria facilitating identification of novel NR3C1 mutations in selected patients. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  6. Relationship of ambient air pollutants and hazardous household factors with birth weight among Bedouin-Arabs.

    PubMed

    Yitshak-Sade, Maayan; Novack, Lena; Landau, Daniella; Kloog, Itai; Sarov, Batia; Hershkovitz, Reli; Karakis, Isabella

    2016-10-01

    Air pollution and meteorology exposures during pregnancy have been suggested to be associated with Birth Weight (BW). Yet, the individual medical background and close household environment is rarely addressed. We aimed to evaluate the independent association of BW with meteorological and air pollution exposures during pregnancy, in addition to individual, parental and household risk factors, among the Bedouin-Arab population in Southern Israel; a semi nomadic population, featured by low socio-economic levels and poor housing and household environment. In a retrospective cohort study we enrolled pregnant women upon their arrival in the local hospital for delivery during December 2011-April 2013. We interviewed the women and collected data on socio-demographic characteristics, medical history and household environmental hazards. Air pollution (NO2, SO2, CO, Ozone and Particulate Matter <2.5 μ and 10 μ in diameter) and meteorological data (temperature, relative humidity), retrieved from 13 monitoring sites, were linked to each woman based on the proximity of her residential address. A total of 959 women were eligible for the study, half of them resided in temporary tribal localities. Ozone IQR elevation in the 3rd trimester was associated with 0.119 gr decrease in BW (95%CI -0.127 gr; -0.112 gr); temperature IQR elevation in the 3rd trimester was associated with 0.002 gr (95%CI -0.004 gr; -0.001 gr) decrease in BW. Waste in the house surroundings was associated with a decrease of 117.27 gr in BW (95%CI -209.19 gr; -25.34 gr). Although exposure to high levels of temperature and O3 were associated with lower BW, the contribution of poor household environment indicators to BW reduction was substantially higher. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Mutations of glucocorticoid receptor differentially affect AF2 domain activity in a steroid-selective manner to alter the potency and efficacy of gene induction and repression†

    PubMed Central

    Tao, Yong-guang; Xu, Yong; Xu, H. Eric; Simons, S. Stoney

    2009-01-01

    The transcriptional activity of steroid hormones is intimately associated with their structure. Deacylcortivazol (DAC) contains several features that were predicted to make it an inactive glucocorticoid. Nevertheless, gene induction and repression by complexes of glucocorticoid receptor (GR) with DAC occurs with greater potency (lower EC50) than, and equal efficacy (maximal activity, or Amax) to, the very active and smaller synthetic glucocorticoid dexamethasone (Dex). Guided by a recent x-ray structure of DAC bound to the GR ligand binding domain (LBD), we now report that several point mutants in the LBD have little effect on the binding of either agonist steroid. However, these same mutations dramatically alter the Amax and/or EC50 of exogenous and endogenous genes in a manner that depends on steroid structure. In some cases, Dex is no longer a full agonist. These properties appear to result from a preferential inactivation of the AF2 activation domain in the GR LBD of Dex-, but not DAC-, bound receptors. The Dex-bound receptors display normal binding to, but greatly reduced response to, the coactivator TIF2, thus indicating a defect in the transmission efficiency of GR-steroid complex information to the coactivator TIF2. In addition, all GR mutants that are active in gene induction with either Dex or DAC have greatly reduced activity in gene repression. This contrasts with the reports of GR mutations preferentially suppressing GR-mediated induction. The properties of these GR mutants in gene induction support the hypothesis that the Amax and EC50 of GR-controlled gene expression can be independently modified, indicate that the receptor can be modified to favor activity with a specific agonist steroid, and suggest that new ligands with suitable substituents may be able to affect the same LBD conformational changes and thereby broaden the therapeutic applications of glucocorticoid steroids PMID:18578507

  8. A phase 2 consortium (P2C) trial of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) for advanced adenocarcinoma of the pancreas.

    PubMed

    Attia, Steven; Kolesar, Jill; Mahoney, Michelle R; Pitot, Henry C; Laheru, Daniel; Heun, James; Huang, Wei; Eickhoff, Jens; Erlichman, Charles; Holen, Kyle D

    2008-08-01

    3-Aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, Triapine) is a novel small molecule inhibitor of ribonucleotide reductase (RR) with clinical signs of activity in pancreatic cancer. Therefore, the Phase 2 Consortium (P2C) initiated a trial (two single stage studies with planned interim analysis) of 3-AP at 96 mg/m(2) intravenously days 1-4 and 15-18 of a 28-day cycle in both chemotherapy-naive and gemcitabine-refractory (GR) patients with advanced pancreatic cancer. The primary endpoint was survival at six months (chemotherapy-naive) and four months (GR). Secondary endpoints were toxicity, response, overall survival, time to progression and mechanistic studies. Fifteen patients were enrolled including one chemotherapy-naïve and 14 GR. The chemotherapy-naïve patient progressed during cycle 1 with grade 3 and 4 toxicities. Of 14 GR patients, seven received two cycles, six received one cycle and one received eight cycles. Progression precluded further treatment in 11 GR patients. Additionally, one died of an ileus in cycle 1 considered related to treatment and two stopped treatment due to toxicity. Five GR patients had grade 4 toxicities possibly related to 3-AP and six GR patients had grade 3 fatigue. Toxicities and lack of meaningful clinical benefit prompted early study closure. Four-month survival in GR patients was 21% (95% CI: 8-58%). Correlative studies confirmed that 3-AP increased the percentage of S-phase buccal mucosal cells, the presence of multidrug resistance gene polymorphisms appeared to predict leukopenia, and baseline pancreatic tumor RR M2 expression was low relative to other tumors treated with 3-AP. In conclusion, this regimen appears inactive against predominantly GR pancreatic cancer. RR M2 protein may not have a critical role in the malignant potential of pancreatic cancer.

  9. A phase 2 consortium (P2C) trial of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) for advanced adenocarcinoma of the pancreas

    PubMed Central

    Attia, Steven; Kolesar, Jill; Mahoney, Michelle R.; Pitot, Henry C.; Laheru, Daniel; Heun, James; Huang, Wei; Eickhoff, Jens; Erlichman, Charles

    2015-01-01

    Summary 3-Aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, Triapine®) is a novel small molecule inhibitor of ribonucleotide reductase (RR) with clinical signs of activity in pancreatic cancer. Therefore, the Phase 2 Consortium (P2C) initiated a trial (two single stage studies with planned interim analysis) of 3-AP at 96 mg/m2 intravenously days 1–4 and 15–18 of a 28-day cycle in both chemotherapy-naive and gemcitabine-refractory (GR) patients with advanced pancreatic cancer. The primary endpoint was survival at six months (chemotherapy-naive) and four months (GR). Secondary endpoints were toxicity, response, overall survival, time to progression and mechanistic studies. Fifteen patients were enrolled including one chemotherapy-naïve and 14 GR. The chemotherapy-naïve patient progressed during cycle 1 with grade 3 and 4 toxicities. Of 14 GR patients, seven received two cycles, six received one cycle and one received eight cycles. Progression precluded further treatment in 11 GR patients. Additionally, one died of an ileus in cycle 1 considered related to treatment and two stopped treatment due to toxicity. Five GR patients had grade 4 toxicities possibly related to 3-AP and six GR patients had grade 3 fatigue. Toxicities and lack of meaningful clinical benefit prompted early study closure. Four-month survival in GR patients was 21% (95% CI: 8–58%). Correlative studies confirmed that 3-AP increased the percentage of S-phase buccal mucosal cells, the presence of multidrug resistance gene polymorphisms appeared to predict leukopenia, and baseline pancreatic tumor RR M2 expression was low relative to other tumors treated with 3-AP. In conclusion, this regimen appears inactive against predominantly GR pancreatic cancer. RR M2 protein may not have a critical role in the malignant potential of pancreatic cancer. PMID:18278438

  10. Two-dimensional Core-collapse Supernova Explosions Aided by General Relativity with Multidimensional Neutrino Transport

    NASA Astrophysics Data System (ADS)

    O’Connor, Evan P.; Couch, Sean M.

    2018-02-01

    We present results from simulations of core-collapse supernovae in FLASH using a newly implemented multidimensional neutrino transport scheme and a newly implemented general relativistic (GR) treatment of gravity. We use a two-moment method with an analytic closure (so-called M1 transport) for the neutrino transport. This transport is multienergy, multispecies, velocity dependent, and truly multidimensional, i.e., we do not assume the commonly used “ray-by-ray” approximation. Our GR gravity is implemented in our Newtonian hydrodynamics simulations via an effective relativistic potential that closely reproduces the GR structure of neutron stars and has been shown to match GR simulations of core collapse quite well. In axisymmetry, we simulate core-collapse supernovae with four different progenitor models in both Newtonian and GR gravity. We find that the more compact proto–neutron star structure realized in simulations with GR gravity gives higher neutrino luminosities and higher neutrino energies. These differences in turn give higher neutrino heating rates (upward of ∼20%–30% over the corresponding Newtonian gravity simulations) that increase the efficacy of the neutrino mechanism. Three of the four models successfully explode in the simulations assuming GREP gravity. In our Newtonian gravity simulations, two of the four models explode, but at times much later than observed in our GR gravity simulations. Our results, in both Newtonian and GR gravity, compare well with several other studies in the literature. These results conclusively show that the approximation of Newtonian gravity for simulating the core-collapse supernova central engine is not acceptable. We also simulate four additional models in GR gravity to highlight the growing disparity between parameterized 1D models of core-collapse supernovae and the current generation of 2D models.

  11. Science Adventures Calendar

    Science.gov Websites

    :00 AM - 2:30 PM for Students, Gr.4-6 July, 2018 9-13 Best Games Ever! Your Own!, 9:00 AM - 12:00 PM for Students, Gr.5-8 9-13 The Forces are with You!, 9:00 AM - 12:00 PM for Students, Gr.1-4 14 Games

  12. Protective coatings for composite tubes in space applications

    NASA Technical Reports Server (NTRS)

    Dursch, Harry W.; Hendricks, Carl L.

    1987-01-01

    Protective coatings for graphite/epoxy (Gr/Ep) tubular structures for a manned Space Station truss structure were evaluated. The success of the composite tube truss structure depends on its stability to long-term exposure to the low earth orbit (LEO) environment, with particular emphasis placed on atomic oxygen. Concepts for protectively coating Gr/Ep tubes include use of inorganic coated metal foils and electroplating. These coatings were applied to Gr/Ep tubes and then subjected to simulated LEO environment to evaluate survivability of coatings and coated tubes. Evaluation included: atomic oxygen resistance, changes in optical properties and adhesion, abrasion resistance, surface preparation required, coating uniformity, and formation of microcracks in the Gr/Ep tubes caused by thermal cycling. Program results demonstrated that both phosphoric and chromic acid anodized Al foil provided excellent adhesion to Gr/Ep tubes and exhibited stable optical properties when subjected to simulated LEO environment. The SiO2/Al coatings sputtered onto Al foils also resulted in an excellent protective coating. Electroplated Ni exhibited unacceptable adhesion loss to Gr/Ep tubes during atomic oxygen exposure.

  13. Protective coatings for composite tubes in space applications

    NASA Technical Reports Server (NTRS)

    Dursch, Harry W.; Hendricks, Carl L.

    1987-01-01

    Protective coatings for graphite/epoxy (Gr/Ep) tubular structures for a Manned Space Station truss structure were evaluated. The success of the composite tube truss structure depends on its stability to long-term exposure to the Low Earth Orbit (LEO) environment with particular emphasis placed on atomic oxygen. Concepts for protectively coating Gr/Ep tubes include use of inorganic coated metal foils and electroplating. These coatings were applied to Gr/Ep tubes and then subjected to simulated LEO environmnet to evaluate survivability of coatings and coated tubes. Evaluation included: atomic oxygen resistance, changes in optical properties and adhesion, abrasion resistancem surface preparation required, coating uniformity, and formation of microcracks in the Gr/Ep tubes caused by thermal cycling. Program results demonstrated that both phosphoric and chromic acid anodized Al foil provided excellent adhesion to Gr/Ep tubes and exhibited stable optical properties when subjected to simulated LEO environment. The SiO2/Al coatings speuttered onto Al foils also resulted in an excellent protective coating. Electroplated Ni exhibited unaccepatble adhesion loss to Gr/Ep tubes during atomic oxygen exposure.

  14. Preparation of β-cyclodextrin entrapped graphite composite for sensitive detection of dopamine.

    PubMed

    Palanisamy, Selvakumar; Sakthinathan, S; Chen, Shen-Ming; Thirumalraj, Balamurugan; Wu, Tsung-Han; Lou, Bih-Show; Liu, Xiaoheng

    2016-01-01

    A simple dopamine (DA) electrochemical sensor was developed based on a screen-printed carbon electrode (SPCE) modified with β-cyclodextrin entrapped graphite (GR/β-CD) composite for the first time. The polar hydroxyl groups on the β-CD rims interact with polar groups of edges of GR sheets resulting into the high dispersion ability of GR in β-CD solution. The GR/β-CD modified electrode exhibited a higher electrochemical response to DA with a lower oxidation potential (0.224V) than that of bare/β-CD (0.38V) and GR (0.525V) modified SPCEs, revealing an excellent electro-oxidation behavior of GR/β-CD composite toward DA. Under optimum conditions, the fabricated sensor detects the DA in the linear concentration range from 0.1 to 58.5μM with a limit of detection of 0.011μM and the sensitivity of 1.27±0.02μAμM(-1)cm(-2). The fabricated sensor also exhibits the excellent repeatability, practicality, reproducibility, storage stability along with acceptable selectivity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Glucocorticoid receptor activation inhibits p53-induced apoptosis of MCF10Amyc cells via induction of protein kinase Cε.

    PubMed

    Aziz, Moammir H; Shen, Hong; Maki, Carl G

    2012-08-24

    Glucocorticoid receptor (GR) is a ligand-dependent transcription factor that can promote apoptosis or survival in a cell-specific manner. Activated GR has been reported to inhibit apoptosis in mammary epithelial cells and breast cancer cells by increasing pro-survival gene expression. In this study, activated GR inhibited p53-dependent apoptosis in MCF10A cells and human mammary epithelial cells that overexpress the MYC oncogene. Specifically, GR agonists hydrocortisone or dexamethasone inhibited p53-dependent apoptosis induced by cisplatin, ionizing radiation, or the MDM2 antagonist Nutlin-3. In contrast, the GR antagonist RU486 sensitized the cells to apoptosis by these agents. Apoptosis inhibition was associated with maintenance of mitochondrial membrane potential, diminished caspase-3 and -7 activation, and increased expression at both the mRNA and protein level of the anti-apoptotic PKC family member PKCε. Knockdown of PKCε via siRNA targeting reversed the protective effect of dexamethasone and restored apoptosis sensitivity. These data provide evidence that activated GR can inhibit p53-dependent apoptosis through induction of the anti-apoptotic factor PKCε.

  16. Studies on graphene zinc-oxide nanocomposites photoanodes for high-efficient dye-sensitized solar cells

    NASA Astrophysics Data System (ADS)

    Effendi, N. A. S.; Samsi, N. S.; Zawawi, S. A.; Hassan, O. H.; Zakaria, R.; Yahya, M. Z. A.; Ali, A. M. M.

    2017-09-01

    A dye-sensitized solar cells (DSSCs) using a nanocomposite (NC) semiconductor film, consisting of graphene layer and ZnO nanosheets (Gr-ZnO) is fabricated by electrodeposition process. The DSSCs based on Gr-ZnO NC were determined via electrochemical impedance spectra (EIS), UV-Visible diffused reflectance spectroscopy (UV-Vis), and photovoltaic performances J-V curves to substantiate the explanations. Impedance spectra shows that a smaller charge transport time constant occurs in DSSCs based on Gr-ZnO NC comparing to ZnO. This improved the electron collecting efficiency significantly, resulting in high open circuit voltage. Moreover, Gr-ZnO NC shows an efficient photoinduced charge separation and transportation can be achieved at the interface thus exhibit excellent potential for photocurrent generation compared with sole ZnO. Gr-ZnO NC obtained a maximum photocurrent response for an open-circuit voltage and a power conversion efficiency of 0.96 V and 7.01% respectively, which is doubled from sole ZnO. The fabricated Gr-ZnO NC cells show better performances compared to conventional ZnO structure reference cell.

  17. Drought susceptibility of modern rice varieties: an effect of linkage of drought tolerance with undesirable traits

    PubMed Central

    Vikram, Prashant; Swamy, B. P. Mallikarjuna; Dixit, Shalabh; Singh, Renu; Singh, Bikram P.; Miro, Berta; Kohli, Ajay; Henry, Amelia; Singh, N. K.; Kumar, Arvind

    2015-01-01

    Green Revolution (GR) rice varieties are high yielding but typically drought sensitive. This is partly due to the tight linkage between the loci governing plant height and drought tolerance. This linkage is illustrated here through characterization of qDTY1.1, a QTL for grain yield under drought that co-segregates with the GR gene sd1 for semi-dwarf plant height. We report that the loss of the qDTY1.1 allele during the GR was due to its tight linkage in repulsion with the sd1 allele. Other drought-yield QTLs (qDTY) also showed tight linkage with traits rejected in GR varieties. Genetic diversity analysis for 11 different qDTY regions grouped GR varieties separately from traditional drought-tolerant varieties, and showed lower frequency of drought tolerance alleles. The increased understanding and breaking of the linkage between drought tolerance and undesirable traits has led to the development of high-yielding drought-tolerant dwarf lines with positive qDTY alleles and provides new hope for extending the benefits of the GR to drought-prone rice-growing regions. PMID:26458744

  18. Activated glucocorticoid receptor interacts with the INHAT component Set/TAF-Ibeta and releases it from a glucocorticoid-responsive gene promoter, relieving repression: implications for the pathogenesis of glucocorticoid resistance in acute undifferentiated leukemia with Set-Can translocation.

    PubMed

    Ichijo, Takamasa; Chrousos, George P; Kino, Tomoshige

    2008-02-13

    Set/template-activating factor (TAF)-Ibeta, part of the Set-Can oncogene product found in acute undifferentiated leukemia, is a component of the inhibitor of acetyltransferases (INHAT) complex. Set/TAF-Ibeta interacted with the DNA-binding domain of the glucocorticoid receptor (GR) in yeast two-hybrid screening, and repressed GR-induced transcriptional activity of a chromatin-integrated glucocorticoid-responsive and a natural promoter. Set/TAF-Ibeta was co-precipitated with glucocorticoid response elements (GREs) of these promoters in the absence of dexamethasone, while addition of the hormone caused dissociation of Set/TAF-Ibeta from and attraction of the p160-type coactivator GRIP1 to the promoter GREs. Set-Can fusion protein, on the other hand, did not interact with GR, was constitutively co-precipitated with GREs and suppressed GRIP1-induced enhancement of GR transcriptional activity and histone acetylation. Thus, Set/TAF-Ibeta acts as a ligand-activated GR-responsive transcriptional repressor, while Set-Can does not retain physiologic responsiveness to ligand-bound GR, possibly contributing to the poor responsiveness of Set-Can-harboring leukemic cells to glucocorticoids.

  19. Activated Glucocorticoid Receptor Interacts with the INHAT Component Set/TAF-Iβ and Releases it from a Glucocorticoid-responsive Gene Promoter, Relieving Repression: Implications for the Pathogenesis of Glucocorticoid Resistance in Acute Undifferentiated Leukemia with Set-Can Translocation

    PubMed Central

    Ichijo, Takamasa; Chrousos, George P.; Kino, Tomoshige

    2008-01-01

    SUMMARY Set/template-activating factor (TAF)-Iβ, part of the Set-Can oncogene product found in acute undifferentiated leukemia, is a component of the inhibitor of acetyltransferases (INHAT) complex. Set/TAF-Iβ interacted with the DNA-binding domain of the glucocorticoid receptor (GR) in yeast two-hybrid screening, and repressed GR-induced transcriptional activity of a chromatin-integrated glucocorticoid-responsive and a natural promoter. Set/TAF-Iβ was co-precipitated with glucocorticoid response elements (GREs) of these promoters in the absence of dexamethasone, while addition of the hormone caused dissociation of Set/TAF-Iβ from and attraction of the p160-type coactivator GRIP1 to the promoter GREs. Set-Can fusion protein, on the other hand, did not interact with GR, was constitutively co-precipitated with GREs and suppressed GRIP1-induced enhancement of GR transcriptional activity and histone acetylation. Thus, Set/TAF-Iβ acts as a ligand-activated GR-responsive transcriptional repressor, while Set-Can does not retain physiologic responsiveness to ligand-bound GR, possibly contributing to the poor responsiveness of Set-Can-harboring leukemic cells to glucocorticoids. PMID:18096310

  20. Graphene and CdS nanocomposite: a facile interface for construction of DNA-based electrochemical biosensor and its application to the determination of phenformin.

    PubMed

    Zeng, Lijiao; Wang, Rui; Zhu, Lihua; Zhang, Jingdong

    2013-10-01

    Graphene/cadmium sulphide (GR-CdS) nanocomposite was synthesized via a low temperature process in aqueous solution. The as-prepared nanocomposite was characterized by scanning electron microscopy, UV-visible spectroscopy, Fourier transform infrared spectroscopy, and X-ray diffraction. The impedance analysis indicated that GR-CdS nanocomposite possessed outstanding electrochemical performance for facile electron transfer. When DNA was immobilized on GR-CdS (DNA/GR-CdS) modified electrode, the electrochemical oxidation of guanine and adenine in DNA residue bases was significantly promoted. Due to the interaction of DNA with phenformin, the voltammetric current of guanine or adenine on the DNA/GR-CdS electrode was decreased when phenformin was present in the electrolytic solution. Under optimized conditions, the signal of guanine on DNA/GR-CdS electrode decreased linearly with increasing the concentration of phenformin in the range of 1.0×10(-6)molL(-1) to 1.0×10(-3)molL(-1). The proposed DNA-based electrochemical biosensor was successfully applied to the determination of phenformin in real samples. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Ionised gas structure of 100 kpc in an over-dense region of the galaxy group COSMOS-Gr30 at z 0.7

    NASA Astrophysics Data System (ADS)

    Epinat, B.; Contini, T.; Finley, H.; Boogaard, L. A.; Guérou, A.; Brinchmann, J.; Carton, D.; Michel-Dansac, L.; Bacon, R.; Cantalupo, S.; Carollo, M.; Hamer, S.; Kollatschny, W.; Krajnović, D.; Marino, R. A.; Richard, J.; Soucail, G.; Weilbacher, P. M.; Wisotzki, L.

    2018-01-01

    We report the discovery of a 104 kpc2 gaseous structure detected in [O II]λλ3727, 3729 in an over-dense region of the COSMOS-Gr30 galaxy group at z 0.725 with deep MUSE Guaranteed Time Observations. We estimate the total amount of diffuse ionised gas to be of the order of ( 5 ± 3) × 1010 M⊙ and explore its physical properties to understand its origin and the source(s) of the ionisation. The MUSE data allow the identification of a dozen group members that are embedded in this structure through emission and absorption lines. We extracted spectra from small apertures defined for both the diffuse ionised gas and the galaxies. We investigated the kinematics and ionisation properties of the various galaxies and extended gas regions through line diagnostics (R23, O32, and [O III]/Hβ) that are available within the MUSE wavelength range. We compared these diagnostics to photo-ionisation models and shock models. The structure is divided into two kinematically distinct sub-structures. The most extended sub-structure of ionised gas is likely rotating around a massive galaxy and displays filamentary patterns that link some galaxies. The second sub-structure links another massive galaxy that hosts an active galactic nucleus (AGN) to a low-mass galaxy, but it also extends orthogonally to the AGN host disc over 35 kpc. This extent is likely ionised by the AGN itself. The location of small diffuse regions in the R23 vs. O32 diagram is compatible with photo-ionisation. However, the location of three of these regions in this diagram (low O32, high R23) can also be explained by shocks, which is supported by their high velocity dispersions. One edge-on galaxy shares the same properties and may be a source of shocks. Regardless of the hypothesis, the extended gas seems to be non-primordial. We favour a scenario where the gas has been extracted from galaxies by tidal forces and AGN triggered by interactions between at least the two sub-structures. Based on observations made with

  2. Increased Biomass, Seed Yield and Stress Tolerance Is Conferred in Arabidopsis by a Novel Enzyme from the Resurrection Grass Sporobolus stapfianus That Glycosylates the Strigolactone Analogue GR24

    PubMed Central

    Islam, Sharmin; Griffiths, Cara A.; Blomstedt, Cecilia K.; Le, Tuan-Ngoc; Gaff, Donald F.; Hamill, John D.; Neale, Alan D.

    2013-01-01

    Isolation of gene transcripts from desiccated leaf tissues of the resurrection grass, Sporobolus stapfianus, resulted in the identification of a gene, SDG8i, encoding a Group 1 glycosyltransferase (UGT). Here, we examine the effects of introducing this gene, under control of the CaMV35S promoter, into the model plant Arabidopsis thaliana. Results show that Arabidopsis plants constitutively over-expressing SDG8i exhibit enhanced growth, reduced senescence, cold tolerance and a substantial improvement in protoplasmic drought tolerance. We hypothesise that expression of SDG8i in Arabidopsis negatively affects the bioactivity of metabolite/s that mediate/s environmentally-induced repression of cell division and expansion, both during normal development and in response to stress. The phenotype of transgenic plants over-expressing SDG8i suggests modulation in activities of both growth- and stress-related hormones. Plants overexpressing the UGT show evidence of elevated auxin levels, with the enzyme acting downstream of ABA to reduce drought-induced senescence. Analysis of the in vitro activity of the UGT recombinant protein product demonstrates that SDG8i can glycosylate the synthetic strigolactone analogue GR24, evoking a link with strigolactone-related processes in vivo. The large improvements observed in survival of transgenic Arabidopsis plants under cold-, salt- and drought-stress, as well as the substantial increases in growth rate and seed yield under non-stress conditions, indicates that overexpression of SDG8i in crop plants may provide a novel means of increasing plant productivity. PMID:24224034

  3. Analysis of the Glucocorticoid Receptor in Spontaneous and Drug-induced Steroid Resistant Mutants Isolated from the Human Leukemic Cell Line CEM-C7

    DTIC Science & Technology

    1991-01-04

    be due to defects in GR function. However, the loss of GR function in x" S49 cells is paralleled by the loss of GR mRNA which is not seen in x’ OEM ...in the protein transcription factor IIIA from Xepopus oocytes. EMBO J. 4: 1609-1614. Milgrom. E.; Atger, M.; Baulieu, E.-E. 1973 Acidophilic

  4. Differential expression of a fructose receptor gene in honey bee workers according to age and behavioral role.

    PubMed

    Takada, Tomoyuki; Sasaki, Taiyo; Sato, Ryoichi; Kikuta, Shingo; Inoue, Maki N

    2018-02-01

    Honey bee (Apis mellifera) workers contribute to the maintenance of colonies in various ways. The primary functions of workers are divided into two types depending on age: young workers (nurses) primarily engage in such behaviors as cleaning and food handling within the hive, whereas older workers (foragers) acquire floral nutrients beyond the colony. Concomitant with this age-dependent change in activity, physiological changes occur in the tissues and organs of workers. Nurses supply younger larvae with honey containing high levels of glucose and supply older larvae with honey containing high levels of fructose. Given that nurses must determine both the concentration and type of sugar used in honey, gustatory receptors (Gr) expressed in the chemosensory organs likely play a role in distinguishing between sugars. Glucose is recognized by Gr1 in honey bees (AmGr1); however, it remains unclear which Gr are responsible for fructose recognition. This study aimed to identify fructose receptors in honey bees and reported that AmGr3, when transiently expressed in Xenopus oocytes, responded only to fructose, and to no other sugars. We analyzed expression levels of AmGr3 to identify which tissues and organs of workers are involved in fructose recognition and determined that expression of AmGr3 was particularly high in the antennae and legs of nurses. Our results suggest that nurses use their antennae and legs to recognize fructose, and that AmGr3 functions as an accurate nutrient sensor used to maintain food quality in honey bee hives. © 2017 Wiley Periodicals, Inc.

  5. Glyphosate resistance in Ambrosia trifida: Part 2. Rapid response physiology and non-target-site resistance.

    PubMed

    Moretti, Marcelo L; Van Horn, Christopher R; Robertson, Renae; Segobye, Kabelo; Weller, Stephen C; Young, Bryan G; Johnson, William G; Douglas Sammons, R; Wang, Dafu; Ge, Xia; d' Avignon, André; Gaines, Todd A; Westra, Philip; Green, Amanda C; Jeffery, Taylor; Lespérance, Mackenzie A; Tardif, François J; Sikkema, Peter H; Christopher Hall, J; McLean, Michael D; Lawton, Mark B; Schulz, Burkhard

    2018-05-01

    The glyphosate-resistant rapid response (GR RR) resistance mechanism in Ambrosia trifida is not due to target-site resistance (TSR) mechanisms. This study explores the physiology of the rapid response and the possibility of reduced translocation and vacuolar sequestration as non-target-site resistance (NTSR) mechanisms. GR RR leaf discs accumulated hydrogen peroxide within minutes of glyphosate exposure, but only in mature leaf tissue. The rapid response required energy either as light or exogenous sucrose. The combination of phenylalanine and tyrosine inhibited the rapid response in a dose-dependent manner. Reduced glyphosate translocation was observed in GR RR, but only when associated with tissue death caused by the rapid response. Nuclear magnetic resonance studies indicated that glyphosate enters the cytoplasm and reaches chloroplasts, and it is not moved into the vacuole of GR RR, GR non-rapid response or glyphosate-susceptible A. trifida. The GR RR mechanism of resistance is not associated with vacuole sequestration of glyphosate, and the observed reduced translocation is likely a consequence of rapid tissue death. Rapid cell death was inhibited by exogenous application of aromatic amino acids phenylalanine and tyrosine. The mechanism by which these amino acids inhibit rapid cell death in the GR RR phenotype remains unknown, and it could involve glyphosate phytotoxicity or other agents generating reactive oxygen species. Implications of these findings are discussed. The GR RR mechanism is distinct from the currently described glyphosate TSR or NTSR mechanisms in other species. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  6. Factors affecting operational tolerance after pediatric living-donor liver transplantation: impact of early post-transplant events and HLA match.

    PubMed

    Ohe, Hidenori; Waki, Kayo; Yoshitomi, Mami; Morimoto, Takeshi; Nafady-Hego, Hanaa; Satoda, Naoki; Li, Ying; Zhao, Xiangdong; Sakaguchi, Shimon; Uemoto, Shinji; Bishop, G Alex; Koshiba, Takaaki

    2012-01-01

    Pediatric recipients of living-donor liver transplants (LDLT) can often discontinue immunosuppression (IS). We examined factors affecting development of operational tolerance (OT), defined as off IS for >1 year, in this population. A historic cohort analysis was conducted in 134 pediatric primary semi-allogeneic LDLT. Multivariate logistic regression analysis was used. The frequency of peripheral regulatory T cells (Tregs) was determined at >10 years post-Tx by FACS analysis. IS was successfully discontinued in 84 tolerant patients (Gr-tol), but not in 50 intolerant patients (Gr-intol). The Gr-intol consisted of 24 patients with rejection (Gr-rej) and 26 with fibrosis of grafts (Gr-fib). The absence of early rejection [odds ratio (OR) 2.79, 95% CI 1.11-7.02, P = 0.03], was a positive independent predictor, whereas HLA-A mismatch (0.18, 0.03-0.91, P = 0.04) was a negative predictor. HLA-DR mismatches did not affect OT. The Treg frequency was significantly decreased in Gr-intol (4.9%) compared with Gr-tol (7.6%) (P = 0.003). There were increased levels of tacrolimus in the first week in Gr-Tol (P = 0.02). Although HLA-B mismatch (8.73, 1.09-70.0, P = 0.04) was a positive independent predictor of OT, its clinical significance remains doubtful. In this large cohort of pediatric LDLT recipients, absence of early rejection, HLA-A match and the later predominance of Tregs are factors associated with OT. © 2011 The Authors. Transplant International © 2011 European Society for Organ Transplantation.

  7. The Great Recession worsened blood pressure and blood glucose levels in American adults.

    PubMed

    Seeman, Teresa; Thomas, Duncan; Merkin, Sharon Stein; Moore, Kari; Watson, Karol; Karlamangla, Arun

    2018-03-27

    Longitudinal, individual-specific data from the Multi-Ethnic Study of Atherosclerosis (MESA) provide support for the hypothesis that the 2008 to 2010 Great Recession (GR) negatively impacted the health of US adults. Results further advance understanding of the relationship by ( i ) illuminating hypothesized greater negative impacts in population subgroups exposed to more severe impacts of the GR and ( ii ) explicitly controlling for confounding by individual differences in age-related changes in health over time. Analyses overcome limitations of prior work by ( i ) employing individual-level data that avoid concerns about ecological fallacy associated with prior reliance on group-level data, ( ii ) using four waves of data before the GR to estimate and control for underlying individual-level age-related trends, ( iii ) focusing on objective, temporally appropriate health outcomes rather than mortality, and ( iv ) leveraging a diverse cohort to investigate subgroup differences in the GR's impact. Innovative individual fixed-effects modeling controlling for individual-level age-related trajectories yielded substantively important insights: ( i ) significant elevations post-GR for blood pressure and fasting glucose, especially among those on medication pre-GR, and ( ii ) reductions in prevalence and intensity of medication use post-GR. Important differences in the effects of the GR are seen across subgroups, with larger effects among younger adults (who are likely still in the labor force) and older homeowners (whose declining home wealth likely reduced financial security, with less scope for recouping losses during their lifetime); least affected were older adults without a college degree (whose greater reliance on Medicare and Social Security likely provided more protection from the recession).

  8. Assessment of the Etiologic Factors of Gingival Recession in a Group of Patients in Northwest Iran

    PubMed Central

    Lafzi, Ardeshir; Abolfazli, Nader; Eskandari, Amir

    2009-01-01

    Background and aims Gingival recession (GR), a common problem in periodontium, is associated with various etiologic factors. There is controversy over the role and importance of these factors. The aim of this study was to evaluate the etiologic factors of GR in a group of subjects in Northwest Iran. Materials and methods In this case-control study, patients referring to a university clinic (123 patients with GR and 123 patients without GR) were evaluated. Patients were examined by an experienced periodontist. A checklist assessing the history of systemic disease, smoking, radiotherapy, orthodontic treatment, chemical and mechanical trauma, tooth-brushing method, type of occlusion, axial inclination of tooth, width and thickness of keratinized gingiva, presence of calculus, prosthesis, faulty restorations and food impaction, and frenum pull was completed for each patient. Chi-square test was used for data analysis. Results Presence of calculus was significantly associated with GR in the evaluated patients (P = 0.000). Low width and thickness of keratinized gingiva, smoking and traumatic tooth brushing were other significant factors (P < 0.05). The type of occlusion, axial inclination of teeth, existence of prosthesis, high frenal attachment, radiotherapy, systemic diseases and chemical trauma were not significantly associated with GR in the evaluated patients (P > 0.05). Conclusion Supra- and sub-gingival calculus, inadequate width and thickness of keratinized tissue, and incorrect tooth brushing techniques are most important etiologic factors of GR. Oral hygiene instructions including correct tooth brushing techniques as well as scaling and root planing with periodic recalls can play a significant role in prevention of GR. PMID:23230492

  9. Rectal Toxicity After Proton Therapy For Prostate Cancer: An Analysis of Outcomes of Prospective Studies Conducted at the University of Florida Proton Therapy Institute

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

    Colaco, Rovel J.; Hoppe, Bradford S.; Flampouri, Stella

    2015-01-01

    Purpose: Study goals were to characterize gastrointestinal effects of proton therapy (PT) in a large cohort of patients treated for prostate cancer, identify factors associated with rectal bleeding (RB), and compare RB between patients receiving investigational protocols versus those in outcome-tracking protocols. Methods and Materials: A total of 1285 consecutive patients were treated with PT between August 2006 and May 2010. Potential pre-existing clinical and treatment-related risk factors for rectal toxicity were recorded. Common Terminology Criteria for Adverse Events version 3.0 was used to score toxicity. Results: Transient RB was the predominant grade 2 or higher (GR2+) toxicity after PT,more » accounting for 95% of gastrointestinal events. GR1 RB occurred in 217 patients (16.9%), GR2 RB in 187 patients (14.5%), and GR3 in 11 (0.9%) patients. There were no GR4 or GR5 events. Univariate analyses showed correlations between GR2+ RB and anticoagulation therapy (P=.008) and rectal and rectal wall dose-volume histogram (DVH) parameters (P<.001). On multivariate analysis, anticoagulation therapy (P=.0034), relative volume of rectum receiving 75 Gy (V75; P=.0102), and relative rectal wall V75 (P=.0017) were significant predictors for G2+ RB. Patients treated with investigational protocols had toxicity rates similar to those receiving outcome-tracking protocols. Conclusions: PT was associated with a low rate of GR2+ gastrointestinal toxicity, predominantly transient RB, which was highly correlated with anticoagulation and rectal DVH parameters. Techniques that limit rectal exposure should be used when possible.« less

  10. Assessment of the etiologic factors of gingival recession in a group of patients in northwest iran.

    PubMed

    Lafzi, Ardeshir; Abolfazli, Nader; Eskandari, Amir

    2009-01-01

    Gingival recession (GR), a common problem in periodontium, is associated with various etiologic factors. There is controversy over the role and importance of these factors. The aim of this study was to evaluate the etiologic factors of GR in a group of subjects in Northwest Iran. In this case-control study, patients referring to a university clinic (123 patients with GR and 123 patients without GR) were evaluated. Patients were examined by an experienced periodontist. A checklist assessing the history of systemic disease, smoking, radiotherapy, orthodontic treatment, chemical and mechanical trauma, tooth-brushing method, type of occlusion, axial inclination of tooth, width and thickness of keratinized gingiva, presence of calculus, prosthesis, faulty restorations and food impaction, and frenum pull was completed for each patient. Chi-square test was used for data analysis. Presence of calculus was significantly associated with GR in the evaluated patients (P = 0.000). Low width and thickness of keratinized gingiva, smoking and traumatic tooth brushing were other significant factors (P < 0.05). The type of occlusion, axial inclination of teeth, existence of prosthesis, high frenal attachment, radiotherapy, systemic diseases and chemical trauma were not significantly associated with GR in the evaluated patients (P > 0.05). Supra- and sub-gingival calculus, inadequate width and thickness of keratinized tissue, and incorrect tooth brushing techniques are most important etiologic factors of GR. Oral hygiene instructions including correct tooth brushing techniques as well as scaling and root planing with periodic recalls can play a significant role in prevention of GR.

  11. Sensitivity of Spaceborne and Ground Radar Comparison Results to Data Analysis Methods and Constraints

    NASA Technical Reports Server (NTRS)

    Morris, Kenneth R.; Schwaller, Mathew

    2011-01-01

    With the availability of active weather radar observations from space from the Precipitation Radar (PR) on board the Tropical Rainfall Measuring Mission (TR.MM) satellite, numerous studies have been performed comparing PR reflectivity and derived rain rates to similar observations from ground-based weather radars (GR). These studies have used a variety of algorithms to compute matching PR and GR volumes for comparison. Most studies have used a fixed 3-dimensional Cartesian grid centered on the ground radar, onto which the PR and GR data are interpolated using a proprietary approach and/or commonly available GR analysis software (e.g., SPRINT, REORDER). Other studies have focused on the intersection of the PR and GR viewing geometries either explicitly or using a hybrid of the fixed grid and PR/GR common fields of view. For the Dual-Frequency Precipitation Radar (DPR) of the upcoming Global Precipitation Measurement (GPM) mission, a prototype DPR/GR comparison algorithm based on similar TRMM PR data has been developed that defines the common volumes in terms of the geometric intersection of PR and GR rays, where smoothing of the PR and GR data are minimized and no interpolation is performed. The PR and GR volume-averaged reflectivity values of each sample volume are accompanied by descriptive metadata, for attributes including the variability and maximum of the reflectivity within the sample volume, and the fraction of range gates in the sample average having reflectivity values above an adjustable detection threshold (typically taken to be 18 dBZ for the PR). Sample volumes are further characterized by rain type (Stratiform or Convective), proximity to the melting layer, underlying surface (land/water/mixed), and the time difference between the PR and GR observations. The mean reflectivity differences between the PR and GR can differ between data sets produced by the different analysis methods; and for the GPM prototype, by the type of constraints and

  12. Design of Copper and Titanium Dioxide Nanoparticles Doped with Reduced Graphene Oxide for Hydrogen Evolution by Water Splitting

    NASA Astrophysics Data System (ADS)

    Yang, Yuhao; Huang, Wenhuan

    2018-05-01

    TiO2-graphene (P25-GR, PG) nanocomposite was fabricated from P25 titania and graphite oxide by hydrothermal method, and then Cu nanoparticles (Cu NPs) were assembled in P25-GR composite (Cu- P25-GR, CPG) under microwave-assisted chemical reduction. The prepared samples were characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), UV-Vis absorption (UV-Vis) and Raman spectroscopies. Cu NPs were well dispersed on the surface of PG and are in metallic state. The ternary Cu-P25-GR (CPG) nanocomposites show an extended light absorption range and more efficient charge separation properties compared to binary P25-GR (PG) composite. Methylene blue photodegradation experiment proved that surface plasmon resonance (SPR) phenomenon had an effect on photoreaction efficiency. The corresponding hydrogen evolution rate for CPG prepared using 0.002 M Cu(NO3)2 solution was 10 times higher than with pure P25, and 2.3 times higher than with PG in the same test conditions. The improved photocatalytic performance can be attributed to the presence of GR in the prepared composite and to the SPR effect, leading to the longer lifetime of photogenerated electronhole pairs and faster interfacial charge transfer rate. We expect that our work would be useful for the further exploration of GR-based nanocomposites.

  13. Simple preparation and highly selective detection of silver ions using an electrochemical sensor based on sulfur-doped graphene and a 3,3',5,5'-tetramethylbenzidine composite modified electrode.

    PubMed

    Fu, Yang; Yang, Yajie; Tuersun, Tayierjiang; Yu, Yuan; Zhi, Jinfang

    2018-04-30

    A novel electrochemical sensor based on sulfur (S)-doped graphene (S-Gr) and a 3,3',5,5'-tetramethylbenzidine (TMB) composite (S-Gr-TMB) modified glassy carbon (GCE) electrode for highly selective quantitative detection of silver ions (Ag+) were fabricated. The S-Gr-TMB composite was first prepared via electrostatic interaction between TMB and S-Gr and then, the composite was coated on the surface of GCE. The resultant S-Gr-TMB/GCE electrode showed a significant voltammetric response to Ag+ at 0.3 V vs. Ag/AgCl due to the synergistic effect of S-Gr and TMB. The sensor showed good linearity from 50 μM to 400 μM with a detection limit of 2.15 μM towards the determination of Ag+. In addition, after the addition of Fe3+ and other metal ions, including Al3+, Ca2+, Cd2+, Co2+, Cu2+, K+, Mg2+, Na+, Ni2+, Pb2+ and Zn2+, in the same concentration, the current signal remained almost unchanged, revealing that the proposed electrochemical sensor exhibited a high selectivity for Ag+, which solves the nonselective problem of TMB as a spectral probe. This enhanced detection performance is attributed to two factors: (1) S-Gr has excellent electrical conductivity; (2) the coupling interactions between Ag-S are speculated to result in strengthened enrichment for Ag and good selective performance.

  14. U(VI) Reduction by Biogenic and Abiotic Hydroxycarbonate Green Rusts: Impacts on U(IV) Speciation and Stability Over Time

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

    Yan, Sen; Boyanov, Maxim I.; Mishra, Bhoopesh

    Green rusts (GRs) are redox active Fe II-Fe III minerals that form in the environment via various biotic and abiotic processes. Although both biogenic (BioGR) and abiotic (ChemGR) GRs have been shown to reduce U VI, the dynamics of the transformations and the speciation and stability of the resulting U IV phases are poorly understood. We used carbonate extraction and XAFS spectroscopy to investigate the products of U VI reduction by BioGR and ChemGR. The results show that both GRs can rapidly remove U VI from synthetic groundwater via reduction to U IV. The initial products in the ChemGR systemmore » are solids-associated U IV-carbonate complexes that gradually transform to nanocrystalline uraninite over time, leading to a decrease in the proportion of carbonate-extractable U from ~95% to ~10%. In contrast, solid-phase U IV atoms in the BioGR system remain relatively extractable, non-uraninite U IV species over the same reaction period. The presence of calcium and carbonate in groundwater significantly increase the extractability of U IV in the BioGR system. Furthermore, these data provide new insights into the transformations of U under anoxic conditions in groundwater that contains calcium and carbonate, and have major implications for predicting uranium stability within redox dynamic environments and designing approaches for the remediation of uranium-contaminated groundwater.« less

  15. U(VI) Reduction by Biogenic and Abiotic Hydroxycarbonate Green Rusts: Impacts on U(IV) Speciation and Stability Over Time

    DOE PAGES

    Yan, Sen; Boyanov, Maxim I.; Mishra, Bhoopesh; ...

    2018-04-09

    Green rusts (GRs) are redox active Fe II-Fe III minerals that form in the environment via various biotic and abiotic processes. Although both biogenic (BioGR) and abiotic (ChemGR) GRs have been shown to reduce U VI, the dynamics of the transformations and the speciation and stability of the resulting U IV phases are poorly understood. We used carbonate extraction and XAFS spectroscopy to investigate the products of U VI reduction by BioGR and ChemGR. The results show that both GRs can rapidly remove U VI from synthetic groundwater via reduction to U IV. The initial products in the ChemGR systemmore » are solids-associated U IV-carbonate complexes that gradually transform to nanocrystalline uraninite over time, leading to a decrease in the proportion of carbonate-extractable U from ~95% to ~10%. In contrast, solid-phase U IV atoms in the BioGR system remain relatively extractable, non-uraninite U IV species over the same reaction period. The presence of calcium and carbonate in groundwater significantly increase the extractability of U IV in the BioGR system. Furthermore, these data provide new insights into the transformations of U under anoxic conditions in groundwater that contains calcium and carbonate, and have major implications for predicting uranium stability within redox dynamic environments and designing approaches for the remediation of uranium-contaminated groundwater.« less

  16. Evaluation of the efficacy of perorally administered glutamic acid-chelated iron and iron-dextran injected subcutaneously in Duroc and Norwegian Landrace piglets.

    PubMed

    Egeli, A K; Framstad, T

    1998-02-01

    The goals of this study were to evaluate the effect of orally administered amino acid-chelated iron (Fe) compared to injected Fe-dextran on haematology and weight gain in two different breeds raised under commercial conditions. Altogether 92 Duroc (D) pigs and 84 Norwegian Landrace (L) pigs from two different herds were included in the study. The day after birth the litters were divided in two groups (split litters). Group (Gr.) 1 was given 4 ml of a 50% solution of Super Fe-MAX (52 mg glutamic acid-chelated Fe in a water solution) orally, while Gr. 2 was subcutaneously (s.c.) injected with Idofer (180 mg Fe as ferridextran). Until weaning at 5 weeks, all the piglets had free access to a 3% solution of Super Fe-MAX (0.78 mg Fe/ml), access to pelleted food being given from 1 week of age. The piglets were weighed and bled before treatment the day after birth (day 1) and on days 4, 7, 14, 21 and 35. All piglets were weighed on days 28 and 49, while 72 of the L pigs were also weighed on days 77, 98 and 119. At weaning D pigs in Gr. 1 and Gr. 2 had a mean body weight of 8.64 kg and 8.30 kg, respectively, the corresponding figures for the L pigs being 10.82 kg and 10.34 kg. As regards the 72 L pigs followed to day 119, the mean weight in Gr. 1 and Gr. 2 was 80.6 kg and 80.2 kg, respectively. A significantly lower weight gain in the piglets with a birth weight below 1.2 kg in Gr. 2 compared with Gr. 1 indicated that excess administration of Fe to small piglets may have a detrimental effect on weight gain. From day 7 (D pigs) and on days 14 and 21 (L pigs), Gr. 2 had a significantly higher haemoglobin concentration (Hb) than Gr. 1. Nevertheless, Hb levels were also adequate in Gr. 1 in both breeds. There was a negative correlation between changes in Hb during the first weeks and the initial value. Though haematological values seemed to show inter-breed differences, with higher average erythrocyte counts (RBC) and Hb and lower mean cell volume (MCV) in the D pigs, the

  17. [Control of postoperative hemorrhage in isolated coronary bypass surgery: comparison of tranexamic acid effects in off-pump surgery with aprotinin effects in conventional surgery].

    PubMed

    Bordalo, Alvaro D B; Nobre, Angelo L; Silva, Fernanda; Serpa, Carlos; Cravino, João

    2011-01-01

    In spite of the strong criticism elicited thereafter, the results of a multicentric study on the consequences of several perioperative anti-hemorrhagic strategies in cardiac surgery, published five years ago, led to the aprotinin (Aprot) withdrawal from the market and its progressive replacement by tranexamic acid (TrAc) in many surgical departments. To evaluate the hemostatic effects and clinical consequences of TrAc use or non-use in off-pump coronary bypass surgery (CABG) and compare them with those of Aprot use or non-use in conventional (conv) CABG. Retrospective analysis of 2 groups (Gr) of patients (pts): GrA - 252 pts undergoing isolated conv CABG (GrA1 - 185 pts submitted to an intra-operative full-dose Aprot protocol; GrA2 - 67 pts operated without Aprot); GrB - 383 pts undergoing isolated off-pump CABG (GrB1 - 136 pts submitted to an intra-operative low-dose TrAc protocol; GrB2 - 247 pts operated in absence of TrAc). Pre-operative clinical characteristics (GrA1 vs GrA2, GrB1 vs GrB2): mean age (years) - 65 vs 64 (NS), 64 vs 64; female gender - 20% vs 21% (NS), 23% vs 20% (NS); logistic Euroscore - 5.1% vs 6.2% (NS), 6.3% vs 5.5% (NS); chronic renal failure - 21% vs 27% (NS), 27% vs 25% (NS); diffuse coronary artery disease - 34% vs 42% (NS), 36% vs 30% (NS); pre-operative betablocker treatment - 64% vs 55% (NS), 74% vs 71% (NS); statin therapy for > 3 months - 78% vs 82% (NS), 81% vs 85% (NS). Pts have been operated by 4 surgeons largely experienced in both CABG modalities. Antiplatelet therapy was stopped => 4 days prior to surgery (but aspirin was maintained in high-risk pts). Results (GrA1 vs GrA2, GrB1 vs GrB2): 1) Bleeding (mL/pt - mean): 783 vs 1375 (p < 0.001), 1061 vs 1368 (p < 0.001); blood loss > 1500 mL (%pts) - 5.4% vs 34% (p < 0.0001), 12% vs 28% (p < 0.001); surgical re-exploration for bleeding - 1.1% vs 3.0% (NS), 2.2% vs 2.0% (NS). 2) Transfusion of blood products (U/pt - mean): plasma - 0.56 vs 2.19 (p < 0.001), 1

  18. A comparative study of nitrite reduction by synthetic and biogenic Fe(II-III) hydroxysalts green rusts: Evidence for hydroxyl-nitrite green rust formation as an intermediate reaction product.

    NASA Astrophysics Data System (ADS)

    Ona-Nguema, G.; Guerbois, D.; Morin, G.; Zhang, Y.; Noel, V.; Brest, J.

    2013-12-01

    The occurrence of high nitrite concentrations as a result of anthropogenic activities is an important water quality concern as it is highly toxic to human and fauna, and it is used as a nitrogen source for the assimilation process. The toxicity of nitrite is related to its transformation into carcinogenic N-nitroso compounds, which are suspected to be responsible for some gastric cancers, and to its ability to convert the hemoglobin to methaemoglobin what is then unable to fix oxygen and to transport it to the tissues, involving hypoxia and the blue-baby syndrome [1]. To reduce the adverse effect of nitrite on human health and on macroalgal blooms, any process enhancing the transformation of nitrite ions to nitrogen gas is of interest for the remediation of natural environments. To achieve this purpose the use of processes involving Fe(II)-containing minerals could be considered as one of the best options. Green-rusts are mixed Fe(II-III) layered double hydroxides commonly found in anoxic zones of natural environments such as sediments and hydromorphic soils. In such anoxic environments, green rust minerals play an important role in the biogeochemical redox cycling of iron and nitrogen, and can affect the speciation and mobility of many organic and inorganic contaminants. The present study investigates the reduction of nitrite by two synthetic and two biogenic green rusts. On the one hand, Fe(II-III) hydroxychloride and Fe(II-III) hydroxycarbonate green rusts were used as synthetic interlayer forms of GR, which are referred to as ';syn-GR(CO3)' and ';syn-GR(Cl)', respectively. On the other hand, the study was performed with biogenic Fe(II-III) hydroxycarbonate green rusts obtained from the bioreduction of two ferric precursors, either Fe(III)-oxyhydroxycarbonate or lepidocrocite; these biogenic green rusts are referred to as ';bio-GR(CO3)F' and ';bio-GR(CO3)L', respectively. For synthetic green rusts, results showed that the oxidation of both syn-GR(CO3) and syn-GR

  19. Late glacial and Holocene history of the Greenland Ice Sheet margin, Nunatarssuaq, Northwestern Greenland

    NASA Astrophysics Data System (ADS)

    Farnsworth, L. B.; Kelly, M. A.; Axford, Y.; Bromley, G. R.; Osterberg, E. C.; Howley, J. A.; Zimmerman, S. R. H.; Jackson, M. S.; Lasher, G. E.; McFarlin, J. M.

    2015-12-01

    Defining the late glacial and Holocene fluctuations of the Greenland Ice Sheet (GrIS) margin, particularly during periods that were as warm or warmer than present, provides a longer-term perspective on present ice margin fluctuations and informs how the GrIS may respond to future climate conditions. We focus on mapping and dating past GrIS extents in the Nunatarssuaq region of northwestern Greenland. During the summer of 2014, we conducted geomorphic mapping and collected rock samples for 10Be surface exposure dating as well as subfossil plant samples for 14C dating. We also obtained sediment cores from an ice-proximal lake. Preliminary 10Be ages of boulders deposited during deglaciation of the GrIS subsequent to the Last Glacial Maximum range from ~30-15 ka. The apparently older ages of some samples indicate the presence of 10Be inherited from prior periods of exposure. These ages suggest deglaciation occurred by ~15 ka however further data are needed to test this hypothesis. Subfossil plants exposed at the GrIS margin on shear planes date to ~ 4.6-4.8 cal. ka BP and indicate less extensive ice during middle Holocene time. Additional radiocarbon ages from in situ subfossil plants on a nunatak date to ~3.1 cal. ka BP. Geomorphic mapping of glacial landforms near Nordsø, a large proglacial lake, including grounding lines, moraines, paleo-shorelines, and deltas, indicate the existence of a higher lake level that resulted from a more extensive GrIS margin likely during Holocene time. A fresh drift limit, characterized by unweathered, lichen-free clasts approximately 30-50 m distal to the modern GrIS margin, is estimated to be late Holocene in age. 10Be dating of samples from these geomorphic features is in progress. Radiocarbon ages of subfossil plants exposed by recent retreat of the GrIS margin suggest that the GrIS was at or behind its present location at AD ~1650-1800 and ~1816-1889. Results thus far indicate that the GrIS margin in northwestern Greenland

  20. Geometric Verification of Dynamic Wave Arc Delivery With the Vero System Using Orthogonal X-ray Fluoroscopic Imaging.

    PubMed

    Burghelea, Manuela; Verellen, Dirk; Poels, Kenneth; Gevaert, Thierry; Depuydt, Tom; Tournel, Koen; Hung, Cecilia; Simon, Viorica; Hiraoka, Masahiro; de Ridder, Mark

    2015-07-15

    The purpose of this study was to define an independent verification method based on on-board orthogonal fluoroscopy to determine the geometric accuracy of synchronized gantry-ring (G/R) rotations during dynamic wave arc (DWA) delivery available on the Vero system. A verification method for DWA was developed to calculate O-ring-gantry (G/R) positional information from ball-bearing positions retrieved from fluoroscopic images of a cubic phantom acquired during DWA delivery. Different noncoplanar trajectories were generated in order to investigate the influence of path complexity on delivery accuracy. The G/R positions detected from the fluoroscopy images (DetPositions) were benchmarked against the G/R angulations retrieved from the control points (CP) of the DWA RT plan and the DWA log files recorded by the treatment console during DWA delivery (LogActed). The G/R rotational accuracy was quantified as the mean absolute deviation ± standard deviation. The maximum G/R absolute deviation was calculated as the maximum 3-dimensional distance between the CP and the closest DetPositions. In the CP versus DetPositions comparison, an overall mean G/R deviation of 0.13°/0.16° ± 0.16°/0.16° was obtained, with a maximum G/R deviation of 0.6°/0.2°. For the LogActed versus DetPositions evaluation, the overall mean deviation was 0.08°/0.15° ± 0.10°/0.10° with a maximum G/R of 0.3°/0.4°. The largest decoupled deviations registered for gantry and ring were 0.6° and 0.4° respectively. No directional dependence was observed between clockwise and counterclockwise rotations. Doubling the dose resulted in a double number of detected points around each CP, and an angular deviation reduction in all cases. An independent geometric quality assurance approach was developed for DWA delivery verification and was successfully applied on diverse trajectories. Results showed that the Vero system is capable of following complex G/R trajectories with maximum deviations during DWA

  1. Expression map of a complete set of gustatory receptor genes in chemosensory organs of Bombyx mori.

    PubMed

    Guo, Huizhen; Cheng, Tingcai; Chen, Zhiwei; Jiang, Liang; Guo, Youbing; Liu, Jianqiu; Li, Shenglong; Taniai, Kiyoko; Asaoka, Kiyoshi; Kadono-Okuda, Keiko; Arunkumar, Kallare P; Wu, Jiaqi; Kishino, Hirohisa; Zhang, Huijie; Seth, Rakesh K; Gopinathan, Karumathil P; Montagné, Nicolas; Jacquin-Joly, Emmanuelle; Goldsmith, Marian R; Xia, Qingyou; Mita, Kazuei

    2017-03-01

    Most lepidopteran species are herbivores, and interaction with host plants affects their gene expression and behavior as well as their genome evolution. Gustatory receptors (Grs) are expected to mediate host plant selection, feeding, oviposition and courtship behavior. However, due to their high diversity, sequence divergence and extremely low level of expression it has been difficult to identify precisely a complete set of Grs in Lepidoptera. By manual annotation and BAC sequencing, we improved annotation of 43 gene sequences compared with previously reported Grs in the most studied lepidopteran model, the silkworm, Bombyx mori, and identified 7 new tandem copies of BmGr30 on chromosome 7, bringing the total number of BmGrs to 76. Among these, we mapped 68 genes to chromosomes in a newly constructed chromosome distribution map and 8 genes to scaffolds; we also found new evidence for large clusters of BmGrs, especially from the bitter receptor family. RNA-seq analysis of diverse BmGr expression patterns in chemosensory organs of larvae and adults enabled us to draw a precise organ specific map of BmGr expression. Interestingly, most of the clustered genes were expressed in the same tissues and more than half of the genes were expressed in larval maxillae, larval thoracic legs and adult legs. For example, BmGr63 showed high expression levels in all organs in both larval and adult stages. By contrast, some genes showed expression limited to specific developmental stages or organs and tissues. BmGr19 was highly expressed in larval chemosensory organs (especially antennae and thoracic legs), the single exon genes BmGr53 and BmGr67 were expressed exclusively in larval tissues, the BmGr27-BmGr31 gene cluster on chr7 displayed a high expression level limited to adult legs and the candidate CO 2 receptor BmGr2 was highly expressed in adult antennae, where few other Grs were expressed. Transcriptional analysis of the Grs in B. mori provides a valuable new reference for

  2. Dibutyltin Disrupts Glucocorticoid Receptor Function and Impairs Glucocorticoid-Induced Suppression of Cytokine Production

    PubMed Central

    Gumy, Christel; Chandsawangbhuwana, Charlie; Dzyakanchuk, Anna A.; Kratschmar, Denise V.; Baker, Michael E.; Odermatt, Alex

    2008-01-01

    Background Organotins are highly toxic and widely distributed environmental chemicals. Dibutyltin (DBT) is used as stabilizer in the production of polyvinyl chloride plastics, and it is also the major metabolite formed from tributyltin (TBT) in vivo. DBT is immunotoxic, however, the responsible targets remain to be defined. Due to the importance of glucocorticoids in immune-modulation, we investigated whether DBT could interfere with glucocorticoid receptor (GR) function. Methodology We used HEK-293 cells transiently transfected with human GR as well as rat H4IIE hepatoma cells and native human macrophages and human THP-1 macrophages expressing endogenous receptor to study organotin effects on GR function. Docking of organotins was used to investigate the binding mechanism. Principal Findings We found that nanomolar concentrations of DBT, but not other organotins tested, inhibit ligand binding to GR and its transcriptional activity. Docking analysis indicated that DBT inhibits GR activation allosterically by inserting into a site close to the steroid-binding pocket, which disrupts a key interaction between the A-ring of the glucocorticoid and the GR. DBT inhibited glucocorticoid-induced expression of phosphoenolpyruvate carboxykinase (PEPCK) and tyrosine-aminotransferase (TAT) and abolished the glucocorticoid-mediated transrepression of TNF-α-induced NF-κB activity. Moreover, DBT abrogated the glucocorticoid-mediated suppression of interleukin-6 (IL-6) and TNF-α production in lipopolysaccharide (LPS)-stimulated native human macrophages and human THP-1 macrophages. Conclusions DBT inhibits ligand binding to GR and subsequent activation of the receptor. By blocking GR activation, DBT may disturb metabolic functions and modulation of the immune system, providing an explanation for some of the toxic effects of this organotin. PMID:18958157

  3. Dibutyltin disrupts glucocorticoid receptor function and impairs glucocorticoid-induced suppression of cytokine production.

    PubMed

    Gumy, Christel; Chandsawangbhuwana, Charlie; Dzyakanchuk, Anna A; Kratschmar, Denise V; Baker, Michael E; Odermatt, Alex

    2008-01-01

    Organotins are highly toxic and widely distributed environmental chemicals. Dibutyltin (DBT) is used as stabilizer in the production of polyvinyl chloride plastics, and it is also the major metabolite formed from tributyltin (TBT) in vivo. DBT is immunotoxic, however, the responsible targets remain to be defined. Due to the importance of glucocorticoids in immune-modulation, we investigated whether DBT could interfere with glucocorticoid receptor (GR) function. We used HEK-293 cells transiently transfected with human GR as well as rat H4IIE hepatoma cells and native human macrophages and human THP-1 macrophages expressing endogenous receptor to study organotin effects on GR function. Docking of organotins was used to investigate the binding mechanism. We found that nanomolar concentrations of DBT, but not other organotins tested, inhibit ligand binding to GR and its transcriptional activity. Docking analysis indicated that DBT inhibits GR activation allosterically by inserting into a site close to the steroid-binding pocket, which disrupts a key interaction between the A-ring of the glucocorticoid and the GR. DBT inhibited glucocorticoid-induced expression of phosphoenolpyruvate carboxykinase (PEPCK) and tyrosine-aminotransferase (TAT) and abolished the glucocorticoid-mediated transrepression of TNF-alpha-induced NF-kappaB activity. Moreover, DBT abrogated the glucocorticoid-mediated suppression of interleukin-6 (IL-6) and TNF-alpha production in lipopolysaccharide (LPS)-stimulated native human macrophages and human THP-1 macrophages. DBT inhibits ligand binding to GR and subsequent activation of the receptor. By blocking GR activation, DBT may disturb metabolic functions and modulation of the immune system, providing an explanation for some of the toxic effects of this organotin.

  4. The role of digestive factors in determining glycemic response in a multiethnic Asian population.

    PubMed

    Tan, Verena Ming Hui; Ooi, Delicia Shu Qin; Kapur, Jeevesh; Wu, Ting; Chan, Yiong Huak; Henry, Christiani Jeyakumar; Lee, Yung Seng

    2016-06-01

    There are wide inter-individual differences in glycemic response (GR). We aimed to examine key digestive parameters that influence inter-individual and ethnic differences in GR in healthy Asian individuals. Seventy-five healthy male subjects (25 Chinese, 25 Malays, and 25 Asian-Indians) were served equivalent available carbohydrate amounts (50 g) of jasmine rice (JR) and basmati rice (BR) on separate occasions. Postprandial blood glucose concentrations were measured at fasting (-5 and 0 min) and at 15- to 30-min interval over 180 min. Mastication parameters (number of chews per mouth and chewing time per mouthful), saliva α-amylase activity, AMY1 gene copy numbers and gastric emptying rate were measured to investigate their relationships with GR. The GR for jasmine rice was significantly higher than for basmati rice (P < 0.001). The median number of AMY1 gene copies was 6, with a range of 2-15. There was a significant positive relationship between AMY1 copy number and α-amylase activity (P = 0.002). There were no significant ethnic differences in GR. For both rice varieties, the number of chews per mouthful was positively associated with the GR (JR, P = 0.011; BR, P = 0.005), while chewing time per mouthful showed a negative association (JR, P = 0.039; BR, P = 0.016). Ethnicity, salivary α-amylase activity, particle size distribution, gastric emptying rate and AMY1 gene copy numbers were not significant contributors to GR (P > 0.05). Mastication parameters contribute significantly to GR. Eating slowly and having larger food boluses before swallowing (less chewing), both potentially modifiable, may be beneficial in glycemic control.

  5. A hotspot in the glucocorticoid receptor DNA-binding domain susceptible to loss of function mutation

    PubMed Central

    Banuelos, Jesus; Shin, Soon Cheon; Lu, Nick Z.

    2015-01-01

    Glucocorticoids (GCs) are used to treat a variety of inflammatory disorders and certain cancers. However, GC resistance occurs in subsets of patients. We found that EL4 cells, a GC-resistant mouse thymoma cell line, harbored a point mutation in their GC receptor (GR) gene, resulting in the substitution of arginine 493 by a cysteine in the second zinc finger of the DNA-binding domain. Allelic discrimination analyses revealed that the R493C mutation occurred on both alleles. In the absence of GCs, the GR in EL4 cells localized predominantly in the cytoplasm and upon dexamethasone treatment underwent nuclear translocation, suggesting the ligand binding ability of the GR in EL4 cells was intact. In transient transfection assays, the R493C mutant could not transactivate the MMTV-luciferase reporter. Site-directed mutagenesis to revert the R493C mutation restored the transactivation activity. Cotransfection experiments showed that the R493C mutant did not inhibit the transcriptional activities of the wild-type GR. In addition, the R493C mutant did not repress either the AP-1 or NF-κB reporters as effectively as WT GR. Furthermore, stable expression of the WT GR in the EL4 cells enabled GC-mediated gene regulation, specifically upregulation of IκBα and downregulation of interferon γ and interleukin 17A. Arginine 493 is conserved among multiple species and all human nuclear receptors and its mutation has also been found in the human GR, androgen receptor, and mineralocorticoid receptor. Thus, R493 is necessary for the transcriptional activity of the GR and a hotspot for mutations that result in GC resistance. PMID:25676786

  6. The transformed glucocorticoid receptor has a lower steroid-binding affinity than the nontransformed receptor

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

    Nemoto, Takayuki; Ohara-Nemoto, Yuko; Denis, M.

    1990-02-20

    High-salt treatment of cytosolic glucocorticoid receptor (GR) preparations reduces the steroid-binding ability of the receptor and induces the conversion of the receptor from a nontransformed (non-DNA-binding) 9S form to a transformed (DNA-binding) 4S entity. Therefore, the authors decided to investigate the possible relationship between these two phenomena. The binding of ({sup 3}H)triamcinolone acetonide (({sup 3}H)TA) to the 9S form was almost saturated at a concentration of 20 nM, whereas ({sup 3}H)TA was hardly bound to the 4S form at this concentration. The 4S form was efficiently labeled at 200 nM. Scatchard analysis of the GR showed the presence of twomore » types of binding sites. In the absence of molybdate, the ratio of the lower affinity site was increased, but the total number of binding sites was not modified. The GR with the low ({sup 3}H)TA-binding affinity bound to DNA-cellulose even in its unliganded state, whereas the form with the high affinity did not. These results indicate that the transformed GR has a reduced ({sup 3}H)TA-binding affinity as compared to the nontransformed GR. The steroid-binding domain (amino acids 477-777) and the DNA- and steroid-binding domains (amino acids 415-777) of the human GR were expressed in Escherichia coli as protein A fused proteins. Taken together, these results suggest that the component(s) associating with the nontransformed GR, possibly the heat shock protein hsp 90, play(s) an important role in stabilizing the GR in a high-affinity state for steroids.« less

  7. Simulating changes in cropping practices in conventional and glyphosate-resistant maize. II. Weed impacts on crop production and biodiversity.

    PubMed

    Colbach, Nathalie; Darmency, Henri; Fernier, Alice; Granger, Sylvie; Le Corre, Valérie; Messéan, Antoine

    2017-05-01

    Overreliance on the same herbicide mode of action leads to the spread of resistant weeds, which cancels the advantages of herbicide-tolerant (HT) crops. Here, the objective was to quantify, with simulations, the impact of glyphosate-resistant (GR) weeds on crop production and weed-related wild biodiversity in HT maize-based cropping systems differing in terms of management practices. We (1) simulated current conventional and probable HT cropping systems in two European regions, Aquitaine and Catalonia, with the weed dynamics model FLORSYS; (2) quantified how much the presence of GR weeds contributed to weed impacts on crop production and biodiversity; (3) determined the effect of cultural practices on the impact of GR weeds and (4) identified which species traits most influence weed-impact indicators. The simulation study showed that during the analysed 28 years, the advent of glyphosate resistance had little effect on plant biodiversity. Glyphosate-susceptible populations and species were replaced by GR ones. Including GR weeds only affected functional biodiversity (food offer for birds, bees and carabids) and weed harmfulness when weed effect was initially low; when weed effect was initially high, including GR weeds had little effect. The GR effect also depended on cultural practices, e.g. GR weeds were most detrimental for species equitability when maize was sown late. Species traits most harmful for crop production and most beneficial for biodiversity were identified, using RLQ analyses. None of the species presenting these traits belonged to a family for which glyphosate resistance was reported. An advice table was built; the effects of cultural practices on crop production and biodiversity were synthesized, explained, quantified and ranked, and the optimal choices for each management technique were identified.

  8. Lagrangian transport in a class of three-dimensional buoyancy-driven flows

    NASA Astrophysics Data System (ADS)

    Contreras, Sebastian; Speetjens, Michel; Clercx, Herman

    2017-11-01

    The study concerns the Lagrangian dynamics of three-dimensional (3D) buoyancy-driven cavity flows under steady and laminar conditions due to a global temperature gradient imposed via an opposite hot and cold sidewall. This serves as archetypal configuration for natural-convection flows in which gravity is perpendicular to the global temperature gradient. Limited insight into the Lagrangian properties of this class of flows motivates this study. The 3D Lagrangian dynamics are investigated in terms of the generic structure of the Lagrangian flow topology that is described in terms of the Grashof number (Gr) and the Prandtl number (Pr). Gr is the principal control parameter for the flow topology: vanishing Gr yields a state of closed streamlines (integrable state); increasing Gr causes the formation of toroidal coherent structures embedded in chaotic streamlines governed by Hamiltonian mechanisms. Fluid inertia prevails for ``smaller'' Gr. A buoyancy-induced bifurcation of the flow topology occurs for ``larger'' Gr and underlies the emergence of ``secondary rolls'' and secondary tori for ``larger'' Pr. Stagnation points and corresponding manifold interactions are key to the dynamics. S.C. acknowledges financial support from Consejo Nacional de Ciencia y Tecnología (CONACYT).

  9. Rapid, single-step most-probable-number method for enumerating fecal coliforms in effluents from sewage treatment plants

    NASA Technical Reports Server (NTRS)

    Munoz, E. F.; Silverman, M. P.

    1979-01-01

    A single-step most-probable-number method for determining the number of fecal coliform bacteria present in sewage treatment plant effluents is discussed. A single growth medium based on that of Reasoner et al. (1976) and consisting of 5.0 gr. proteose peptone, 3.0 gr. yeast extract, 10.0 gr. lactose, 7.5 gr. NaCl, 0.2 gr. sodium lauryl sulfate, and 0.1 gr. sodium desoxycholate per liter is used. The pH is adjusted to 6.5, and samples are incubated at 44.5 deg C. Bacterial growth is detected either by measuring the increase with time in the electrical impedance ratio between the innoculated sample vial and an uninnoculated reference vial or by visual examination for turbidity. Results obtained by the single-step method for chlorinated and unchlorinated effluent samples are in excellent agreement with those obtained by the standard method. It is suggested that in automated treatment plants impedance ratio data could be automatically matched by computer programs with the appropriate dilution factors and most probable number tables already in the computer memory, with the corresponding result displayed as fecal coliforms per 100 ml of effluent.

  10. Seasonal changes in cortisol sensitivity and glucocorticoid receptor affinity and number in leukocytes of coho salmon

    USGS Publications Warehouse

    Maule, Alec G.; Schreck, Carl B.; Sharpe, Cameron

    1993-01-01

    To determine if there were organ-specific changes in immune responses or immune-endocrine interaction, we monitored in vitro immune response, cortisol sensitivity and number and affinity of glucocorticoid receptors (GR) in leukocytes from freshwater-adapted juvenile coho salmon (Oncorhynchus kisutch) during the physiological changes that prepare them to enter the marine environment. During this period, absolute immune response declined, but splenic leukocytes generated more antibody-producing cells than did cells from anterior kidney. Splenic leukocytes were initially more sensitive to the suppressive effects of cortisol and had fewer GR than leukocytes from the anterior kidney. Leukocytes from the anterior kidney were initially insensitive to cortisol but developed sensitivity at about the same time as the dissociation constant and number of GR increased. In vitro incubation of anterior kidney leukocytes in cortisol altered GR variables when experiments were conducted during March through September but not during November through February. In some years, changes in GR or immune responses were correlated with plasma cortisol titers, but in other years there was no correlation. Thus, the exact relation between cortisol, GR and immune response in anadromous salmonids is unclear and other factors are involved.

  11. Why do human B cells secrete granzyme B? Insights into a novel B-cell differentiation pathway.

    PubMed

    Hagn, Magdalena; Jahrsdörfer, Bernd

    2012-11-01

    B cells are generally believed to operate as producers of high affinity antibodies to defend the body against microorganisms, whereas cellular cytotoxicity is considered as an exclusive prerogative of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). In conflict with this dogma, recent studies have demonstrated that the combination of interleukin-21 (IL-21) and B-cell receptor (BCR) stimulation enables B cells to produce and secrete the active form of the cytotoxic serine protease granzyme B (GrB). Although the production of GrB by B cells is not accompanied by that of perforin as in the case of many other GrB-secreting cells, recent findings suggest GrB secretion by B cells may play a significant role in early antiviral immune responses, in the regulation of autoimmune responses, and in cancer immunosurveillance. Here, we discuss in detail how GrB-secreting B cells may influence a variety of immune processes. A better understanding of the role that GrB-secreting B cells are playing in the immune system may allow for the development and improvement of novel immunotherapeutic approaches against infectious, autoimmune and malignant diseases.

  12. Geophysical data analysis and visualization using the Grid Analysis and Display System

    NASA Technical Reports Server (NTRS)

    Doty, Brian E.; Kinter, James L., III

    1995-01-01

    Several problems posed by the rapidly growing volume of geophysical data are described, and a selected set of existing solutions to these problems is outlined. A recently developed desktop software tool called the Grid Analysis and Display System (GrADS) is presented. The GrADS' user interface is a natural extension of the standard procedures scientists apply to their geophysical data analysis problems. The basic GrADS operations have defaults that naturally map to data analysis actions, and there is a programmable interface for customizing data access and manipulation. The fundamental concept of the GrADS' dimension environment, which defines both the space in which the geophysical data reside and the 'slice' of data which is being analyzed at a given time, is expressed The GrADS' data storage and access model is described. An argument is made in favor of describable data formats rather than standard data formats. The manner in which GrADS users may perform operations on their data and display the results is also described. It is argued that two-dimensional graphics provides a powerful quantitative data analysis tool whose value is underestimated in the current development environment which emphasizes three dimensional structure modeling.

  13. Tuning near-gap electronic structure, interface charge transfer and visible light response of hybrid doped graphene and Ag3PO4 composite: Dopant effects

    PubMed Central

    He, Chao-Ni; Huang, Wei-Qing; Xu, Liang; Yang, Yin-Cai; Zhou, Bing-Xin; Huang, Gui-Fang; Peng, P.; Liu, Wu-Ming

    2016-01-01

    The enhanced photocatalytic performance of doped graphene (GR)/semiconductor nanocomposites have recently been widely observed, but an understanding of the underlying mechanisms behind it is still out of reach. As a model system to study the dopant effects, we investigate the electronic structures and optical properties of doped GR/Ag3PO4 nanocomposites using the first-principles calculations, demonstrating that the band gap, near-gap electronic structure and interface charge transfer of the doped GR/Ag3PO4(100) composite can be tuned by the dopants. Interestingly, the doping atom and C atoms bonded to dopant become active sites for photocatalysis because they are positively or negatively charged due to the charge redistribution caused by interaction. The dopants can enhance the visible light absorption and photoinduced electron transfer. We propose that the N atom may be one of the most appropriate dopants for the GR/Ag3PO4 photocatalyst. This work can rationalize the available experimental results about N-doped GR-semiconductor composites, and enriches our understanding on the dopant effects in the doped GR-based composites for developing high-performance photocatalysts. PMID:26923338

  14. Numerical binary black hole mergers in dynamical Chern-Simons gravity: Scalar field

    NASA Astrophysics Data System (ADS)

    Okounkova, Maria; Stein, Leo C.; Scheel, Mark A.; Hemberger, Daniel A.

    2017-08-01

    Testing general relativity in the nonlinear, dynamical, strong-field regime of gravity is one of the major goals of gravitational wave astrophysics. Performing precision tests of general relativity (GR) requires numerical inspiral, merger, and ringdown waveforms for binary black hole (BBH) systems in theories beyond GR. Currently, GR and scalar-tensor gravity are the only theories amenable to numerical simulations. In this article, we present a well-posed perturbation scheme for numerically integrating beyond-GR theories that have a continuous limit to GR. We demonstrate this scheme by simulating BBH mergers in dynamical Chern-Simons gravity (dCS), to linear order in the perturbation parameter. We present mode waveforms and energy fluxes of the dCS pseudoscalar field from our numerical simulations. We find good agreement with analytic predictions at early times, including the absence of pseudoscalar dipole radiation. We discover new phenomenology only accessible through numerics: a burst of dipole radiation during merger. We also quantify the self-consistency of the perturbation scheme. Finally, we estimate bounds that GR-consistent LIGO detections could place on the new dCS length scale, approximately ℓ≲O (10 ) km .

  15. Electronic states of aryl radical functionalized graphenes: Density functional theory study

    NASA Astrophysics Data System (ADS)

    Tachikawa, Hiroto; Kawabata, Hiroshi

    2016-06-01

    Functionalized graphenes are known as a high-performance molecular device. In the present study, the structures and electronic states of the aryl radical functionalized graphene have been investigated by the density functional theory (DFT) method to elucidate the effects of functionalization on the electronic states of graphene (GR). Also, the mechanism of aryl radical reaction with GR was investigated. The benzene, biphenyl, p-terphenyl, and p-quaterphenyl radicals [denoted by (Bz) n (n = 1-4), where n means numbers of benzene rings in aryl radical] were examined as aryl radicals. The DFT calculation of GR-(Bz) n (n = 1-4) showed that the aryl radical binds to the carbon atom of GR, and a C-C single bond was formed. The binding energies of aryl radicals to GR were calculated to be ca. 6.0 kcal mol-1 at the CAM-B3LYP/6-311G(d,p) level. It was found that the activation barrier exists in the aryl radical addition: the barrier heights were calculated to be 10.0 kcal mol-1. The electronic states of GR-(Bz) n were examined on the basis of theoretical results.

  16. The role of the substrate in Graphene/Silicon photodiodes

    NASA Astrophysics Data System (ADS)

    Luongo, G.; Giubileo, F.; Iemmo, L.; Di Bartolomeo, A.

    2018-01-01

    The Graphene/Silicon (Gr/Si) junction can function as a Schottky diode with performances strictly related to the quality of the interface. Here, we focus on the substrate geometry and on its effects on Gr/Si junction physics. We fabricate and study the electrical and optical behaviour of two types of devices: one made of a Gr/Si planar junction, the second realized with graphene on an array of Si nanotips. We show that the Gr/Si flat device exhibits a reverse photocurrent higher than the forward current and achieves a photoresponsivity of 2.5 A/W. The high photoresponse is due to the charges photogenerated in Si below a parasitic graphene/SiO2/Si structure, which are injected into the Gr/Si junction region. The other device with graphene on Si-tips displays a reverse current that grows exponentially with the bias. We explain this behaviour by taking into account the tip geometry of the substrate, which magnifies the electric field and shifts the Fermi level of graphene, thus enabling fine-tuning of the Schottky barrier height. The Gr/Si-tip device achieves a higher photoresponsivity, up to 3 A/W, likely due to photocharge internal multiplication.

  17. Temporal variability of glucocorticoid receptor activity is functionally important for the therapeutic action of fluoxetine in the hippocampus.

    PubMed

    Lee, M-S; Kim, Y-H; Park, W-S; Park, O-K; Kwon, S-H; Hong, K S; Rhim, H; Shim, I; Morita, K; Wong, D L; Patel, P D; Lyons, D M; Schatzberg, A F; Her, S

    2016-02-01

    Previous studies have shown inconsistent results regarding the actions of antidepressants on glucocorticoid receptor (GR) signalling. To resolve these inconsistencies, we used a lentiviral-based reporter system to directly monitor rat hippocampal GR activity during stress adaptation. Temporal GR activation was induced significantly by acute stress, as demonstrated by an increase in the intra-individual variability of the acute stress group compared with the variability of the non-stress group. However, the increased intra-individual variability was dampened by exposure to chronic stress, which was partly restored by fluoxetine treatment without affecting glucocorticoid secretion. Immobility in the forced-swim test was negatively correlated with the intra-individual variability, but was not correlated with the quantitative GR activity during fluoxetine therapy; this highlights the temporal variability in the neurobiological links between GR signalling and the therapeutic action of fluoxetine. Furthermore, we demonstrated sequential phosphorylation between GR (S224) and (S232) following fluoxetine treatment, showing a molecular basis for hormone-independent nuclear translocation and transcriptional enhancement. Collectively, these results suggest a neurobiological mechanism by which fluoxetine treatment confers resilience to the chronic stress-mediated attenuation of hypothalamic-pituitary-adrenal axis activity.

  18. Probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 may help downregulate TNF-Alpha, IL-6, IL-8, IL-10 and IL-12 (p70) in the neurogenic bladder of spinal cord injured patient with urinary tract infections: a two-case study.

    PubMed

    Anukam, Kingsley C; Hayes, Keith; Summers, Kelly; Reid, Gregor

    2009-01-01

    The management of urinary tract infection (UTI) in individuals with spinal cord injury (SCI) continues to be of concern, due to complications that can occur. An emerging concept that is a common underlying pathophysiological process is involved, wherein pathogens causing UTI have a role in inflammatory progression. We hypothesized that members of the commensal flora, such as lactobacilli, may counter this reaction through anti-inflammatory mediation. This was assessed in a pilot two-patient study in which probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri were administered to one patient and placebo to another, both along with antibiotics to treat acute UTI. Urinary TNF-alpha was significantly downregulated (P = .015) in the patient who received the probiotic and who used intermittent catheterization compared with patient on placebo and using an indwelling catheter. The extent to which this alteration resulted in improved well-being in spinal cord injured patients remains to be determined in a larger study.

  19. Genesis analysis of high-gamma ray sandstone reservoir and its log evaluation techniques: a case study from the Junggar basin, northwest China.

    PubMed

    Wang, Liang; Mao, Zhiqiang; Sun, Zhongchun; Luo, Xingping; Song, Yong; Liu, Zhen

    2013-01-01

    In the Junggar basin, northwest China, many high gamma-ray (GR) sandstone reservoirs are found and routinely interpreted as mudstone non-reservoirs, with negative implications for the exploration and exploitation of oil and gas. Then, the high GR sandstone reservoirs' recognition principles, genesis, and log evaluation techniques are systematically studied. Studies show that the sandstone reservoirs with apparent shale content greater than 50% and GR value higher than 110API can be regarded as high GR sandstone reservoir. The high GR sandstone reservoir is mainly and directly caused by abnormally high uranium enrichment, but not the tuff, feldspar or clay mineral. Affected by formation's high water sensitivity and poor borehole quality, the conventional logs can not recognize reservoir and evaluate the physical property of reservoirs. Then, the nuclear magnetic resonance (NMR) logs is proposed and proved to be useful in reservoir recognition and physical property evaluation.

  20. Genesis Analysis of High-Gamma Ray Sandstone Reservoir and Its Log Evaluation Techniques: A Case Study from the Junggar Basin, Northwest China

    PubMed Central

    Wang, Liang; Mao, Zhiqiang; Sun, Zhongchun; Luo, Xingping; Song, Yong; Liu, Zhen

    2013-01-01

    In the Junggar basin, northwest China, many high gamma-ray (GR) sandstone reservoirs are found and routinely interpreted as mudstone non-reservoirs, with negative implications for the exploration and exploitation of oil and gas. Then, the high GR sandstone reservoirs' recognition principles, genesis, and log evaluation techniques are systematically studied. Studies show that the sandstone reservoirs with apparent shale content greater than 50% and GR value higher than 110API can be regarded as high GR sandstone reservoir. The high GR sandstone reservoir is mainly and directly caused by abnormally high uranium enrichment, but not the tuff, feldspar or clay mineral. Affected by formation's high water sensitivity and poor borehole quality, the conventional logs can not recognize reservoir and evaluate the physical property of reservoirs. Then, the nuclear magnetic resonance (NMR) logs is proposed and proved to be useful in reservoir recognition and physical property evaluation. PMID:24078797

  1. Using Nonequilibrium Alloying Techniques for Corrosion Inhibition in Gr/ Al and Gr/Mg Metal Matrix Composites

    DTIC Science & Technology

    1994-06-15

    of AI-12Mg-13Sf Before and After Heat Treament at 400C for 1, 2 and 8 hre and 5000C for I hr, Polarized in Quiescent 0. IM NaCI, pH 8, 2W°C. 8 0.8 AI...C4 4R o00qI i co c cc o !00§ " 00- 0-coo 88 88-- o IMM CCO 00 PP0M 3I34 -1.2 M9 - TreaMent #1 .1.4 ~ 1.5 .7 -6 -5 -4 -3 -2 - Current Denedty, log (A

  2. α Actinin 4 (ACTN4) Regulates Glucocorticoid Receptor-mediated Transactivation and Transrepression in Podocytes*

    PubMed Central

    Zhao, Xuan; Khurana, Simran; Charkraborty, Sharmistha; Tian, Yuqian; Sedor, John R.; Bruggman, Leslie A.; Kao, Hung-Ying

    2017-01-01

    Glucocorticoids are a general class of steroids that possess renoprotective activity in glomeruli through their interaction with the glucocorticoid receptor. However, the mechanisms by which glucocorticoids ameliorate proteinuria and glomerular disease are not well understood. In this study, we demonstrated that α actinin 4 (ACTN4), an actin-cross-linking protein known to coordinate cytoskeletal organization, interacts with the glucocorticoid receptor (GR) in the nucleus of human podocytes (HPCs), a key cell type in the glomerulus critical for kidney filtration function. The GR-ACTN4 complex enhances glucocorticoid response element (GRE)-driven reporter activity. Stable knockdown of ACTN4 by shRNA in HPCs significantly reduces dexamethasone-mediated induction of GR target genes and GRE-driven reporter activity without disrupting dexamethasone-induced nuclear translocation of GR. Synonymous mutations or protein expression losses in ACTN4 are associated with kidney diseases, including focal segmental glomerulosclerosis, characterized by proteinuria and podocyte injury. We found that focal segmental glomerulosclerosis-linked ACTN4 mutants lose their ability to bind liganded GR and support GRE-mediated transcriptional activity. Mechanistically, GR and ACTN4 interact in the nucleus of HPCs. Furthermore, disruption of the LXXLL nuclear receptor-interacting motif present in ACTN4 results in reduced GR interaction and dexamethasone-mediated transactivation of a GRE reporter while still maintaining its actin-binding activity. In contrast, an ACTN4 isoform, ACTN4 (Iso), that loses its actin-binding domain is still capable of potentiating a GRE reporter. Dexamethasone induces the recruitment of ACTN4 and GR to putative GREs in dexamethasone-transactivated promoters, SERPINE1, ANGPLT4, CCL20, and SAA1 as well as the NF-κB (p65) binding sites on GR-transrepressed promoters such as IL-1β, IL-6, and IL-8. Taken together, our data establish ACTN4 as a transcriptional co

  3. The role of synoptic weather variability in Greenland ice sheet dynamics

    NASA Astrophysics Data System (ADS)

    Walker, J. M.; Radic, V.

    2017-12-01

    Much of the large uncertainty in predictions of future global sea level rise is due to our limited understanding of Greenland ice sheet (GrIS) motion and its interactions with climate. Over the next century, climate models predict that the GrIS will experience not only gradual warming, but also changes in atmospheric circulation, hydrology, and weather, including a northward shift of the North Atlantic storm track, with greater frequency and intensity of rain storms over the GrIS. Recent studies of GrIS dynamics have focused on the effects of increased seasonal mean meltwater on ice velocities, finding only a modest impact due to compensation by subglacial drainage systems, but subglacial hydraulic theory indicates that variability on shorter timescales is also relevant: short-term surges in meltwater or rainfall can overload drainage systems at rates faster than they can adjust, leading to water pressure spikes and ice acceleration. If the magnitude or frequency of these transient ice accelerations increase substantially as synoptic weather patterns change over the next century, there could be a significant cumulative impact on seasonal mean ice velocities. However, this issue has not been addressed in the literature and represents a major source of uncertainty. In this study, we investigate the role of synoptic weather variability in GrIS dynamics, with the ultimate goal of evaluating the relationships between extreme weather events and ice sheet flow in different seasons and regions of the GrIS. As a first step, we apply the machine learning technique of self-organizing maps to atmospheric reanalysis data to categorize the predominant synoptic weather systems over the GrIS domain, evaluating atmospheric moisture transport and rainfall to assess the impacts of each weather system on GrIS surface hydrology. The preliminary results presented here will be used in conjunction with ice velocity satellite measurements in future work, to identify any correlations

  4. Peripheral Arterial and Venous Response to Tilt Test after a 60-Day Bedrest with and without Countermeasures (ES-IBREP)

    PubMed Central

    Coupé, Mickael; Bai, Yanqiang; Gauquelin-Koch, Guillemette; Jiang, Shizhong; Aubry, Patrick; Wan, Yumin; Custaud, Marc-Antoine; Li, Yinghui

    2012-01-01

    We quantified the impact of 60-day head-down bed rest (HDBR) with countermeasures on arterial and venous response to tilt. Methods: Twenty-one males: 7 control (Con), 7 resistive vibration exercise (RVE) and 7 Chinese herb (Herb) were assessed. Subjects were identified as finisher (F) or non-finishers (NF) at the post-HDBR 20-min tilt test. The cerebral (MCA), femoral (FEM) arterial flow velocity and leg vascular resistance (FRI), the portal vein section (PV), the flow redistribution ratios (MCA/FEM; MCA/PV), the tibial (Tib), gastrocnemius (Gast), and saphenous (Saph) vein sections were measured by echography and Doppler ultrasonography. Arterial and venous parameters were measured at 3-min pre-tilt in the supine position, and at 1 min before the end of the tilt. Results: At post-HDBR tilt, MCA decreased more compared with pre-HDBR tilt in the Con, RVE, and Herb groups, the MCA/FEM tended to decrease in the Con and Herb groups (not significant) but remained stable in the RVE gr. FRI dropped in the Con gr, but remained stable in the Herb gr and increased in the RVE gr. PV decreased less in the Con and Herb groups but remained unchanged in the RVE gr. MCA/PV decreased in the Con and Herb groups, but increased to a similar extent in the RVE gr. Gast section significantly increased more in the Con gr only, whereas Tib section increased more in the Con and Herb groups but not in the RVE gr. The percent change in Saph section was similar at pre- and post-HDBR tilt. Conclusion: In the Con gr, vasoconstriction was reduced in leg and splanchnic areas. RVE and Herb contributed to prevent the loss of vasoconstriction in both areas, but the effect of RVE was higher. RVE and Herb contributed to limit Gast distension whereas only RVE had a protective effect on the Tib. PMID:22412933

  5. REVIEWS OF TOPICAL PROBLEMS Gravitational radiation of systems and the role of their force field

    NASA Astrophysics Data System (ADS)

    Nikishov, Anatolii I.; Ritus, Vladimir I.

    2011-02-01

    Gravitational radiation (GR) from compact relativistic systems with a known energy-momentum tensor (EMT) and GR from two masses elliptically orbiting their common center of inertia are considered. In the ultrarelativistic limit, the GR spectrum of a charge rotating in a uniform magnetic field, a Coulomb field, a magnetic moment field, and a combination of the last two fields differs by a factor 4πGm2Γ2/e2 (Γ being of the order of the charge Lorentz factor) from its electromagnetic radiation (EMR) spectrum. This factor is independent of the radiation frequency but does depend on the wave vector direction and the way the field behaves outside of the orbit. For a plane wave external field, the proportionality between the gravitational and electromagnetic radiation spectra is exact, whatever the velocity of the charge. Qualitative estimates of Γ are given for a charge moving ultrarelativistically in an arbitrary field, showing that it is of the order of the ratio of the nonlocal and local source contributions to the GR. The localization of external forces near the orbit violates the proportionality of the spectra and reduces GR by about the Lorentz factor squared. The GR spectrum of a rotating relativistic string with masses at the ends is given, and it is shown that the contributions by the masses and string are of the same order of magnitude. In the nonrelativistic limit, the harmonics of GR spectra behave universally for all the rotating systems considered. A trajectory method is developed for calculating the GR spectrum. In this method, the spatial (and hence polarization) components of the conserved EMT are calculated in the long wavelength approximation from the time component of the EMTs of the constituent masses of the system. Using this method, the GR spectrum of two masses moving in elliptic orbits about their common center of inertia is calculated, as are the relativistic corrections to it.

  6. Glycaemic responses to liquid food supplements among three Asian ethnic groups.

    PubMed

    Tey, Siew Ling; Van Helvoort, Ardy; Henry, Christiani Jeyakumar

    2016-12-01

    A limited number of studies have compared the glycaemic index (GI) and glycaemic responses (GR) to solid foods between Caucasians and Asians. These studies have demonstrated that Asians have greater GI and GR values for solid foods than Caucasians. However, no study has compared the GI and GR to liquids among various Asian ethnic groups. A total of forty-eight males and females (16 Chinese, 16 Indians, and 16 Malay) took part in this randomised, crossover study. Glycaemic response to the reference food (glucose beverage) was measured on three occasions, and GR to three liquids were measured on one occasion each. Liquids with different macronutrient ratio's and carbohydrate types were chosen to be able to evaluate the response to products with different GIs. Blood glucose concentrations were measured in duplicate at baseline (-5 and 0 min) and once at 15, 30, 45, 60, 90, and 120 min after the commencement of beverage consumption. There were statistically significant differences in GI and GR between the three liquids (P < 0.01 in all cases). However, there were no statistically significant differences in GI and GR for the liquids between the ethnic groups (Chinese vs. Indian vs. Malay). The GR for three different types of liquid nutritional supplements did not differ between the three main ethnic groups in Asia. It appears that the GI of liquid food derived from one Asian ethnicity can be applicable to other Asian populations.

  7. An energy dependent earthquake frequency-magnitude distribution

    NASA Astrophysics Data System (ADS)

    Spassiani, I.; Marzocchi, W.

    2017-12-01

    The most popular description of the frequency-magnitude distribution of seismic events is the exponential Gutenberg-Richter (G-R) law, which is widely used in earthquake forecasting and seismic hazard models. Although it has been experimentally well validated in many catalogs worldwide, it is not yet clear at which space-time scales the G-R law still holds. For instance, in a small area where a large earthquake has just happened, the probability that another very large earthquake nucleates in a short time window should diminish because it takes time to recover the same level of elastic energy just released. In short, the frequency-magnitude distribution before and after a large earthquake in a small area should be different because of the different amount of available energy.Our study is then aimed to explore a possible modification of the classical G-R distribution by including the dependence on an energy parameter. In a nutshell, this more general version of the G-R law should be such that a higher release of energy corresponds to a lower probability of strong aftershocks. In addition, this new frequency-magnitude distribution has to satisfy an invariance condition: when integrating over large areas, that is when integrating over infinite energy available, the G-R law must be recovered.Finally we apply a proposed generalization of the G-R law to different seismic catalogs to show how it works and the differences with the classical G-R law.

  8. A minichaperone-based fusion system for producing insoluble proteins in soluble stable forms.

    PubMed

    Sharapova, Olga A; Yurkova, Maria S; Fedorov, Alexey N

    2016-02-01

    We have developed a fusion system for reliable production of insoluble hydrophobic proteins in soluble stable forms. A carrier is thermophilic minichaperone, GroEL apical domain (GrAD), a 15 kDa monomer able to bind diverse protein substrates. The Met-less variant of GrAD has been made for further convenient use of Met-specific CNBr chemical cleavage, if desired. The Met-less GrAD retained stability and solubility of the original protein. Target polypeptides can be fused to either C-terminus or N-terminus of GrAD. The system has been tested with two unrelated insoluble proteins fused to the C-terminus of GrAD. One of the proteins was also fused to GrAD N-terminus. The fusions formed inclusion bodies at 25°C and above and were partly soluble only at lower expression temperatures. Most importantly, however, after denaturation in urea, all fusions without exception were completely renatured in soluble stable forms that safely survived freezing-thawing as well as lyophilization. All fusions for both tested target proteins retained solubility at high concentrations for days. Functional analysis revealed that a target protein may retain functionality in the fusion. Convenience features include potential thermostability of GrAD fusions, capacity for chemical and enzymatic cleavage of a target and His6 tag for purification. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Novel functions of prototype foamy virus Gag glycine- arginine-rich boxes in reverse transcription and particle morphogenesis.

    PubMed

    Müllers, Erik; Uhlig, Tobias; Stirnnagel, Kristin; Fiebig, Uwe; Zentgraf, Hanswalter; Lindemann, Dirk

    2011-02-01

    Prototype foamy virus (PFV) Gag lacks the characteristic orthoretroviral Cys-His motifs that are essential for various steps of the orthoretroviral replication cycle, such as RNA packaging, reverse transcription, infectivity, integration, and viral assembly. Instead, it contains three glycine-arginine-rich boxes (GR boxes) in its C terminus that putatively represent a functional equivalent. We used a four-plasmid replication-deficient PFV vector system, with uncoupled RNA genome packaging and structural protein translation, to analyze the effects of deletion and various substitution mutations within each GR box on particle release, particle-associated protein composition, RNA packaging, DNA content, infectivity, particle morphology, and intracellular localization. The degree of viral particle release by all mutants was similar to that of the wild type. Only minimal effects on Pol encapsidation, exogenous reverse transcriptase (RT) activity, and genomic viral RNA packaging were observed. In contrast, particle-associated DNA content and infectivity were drastically reduced for all deletion mutants and were undetectable for all alanine substitution mutants. Furthermore, GR box I mutants had significant changes in particle morphology, and GR box II mutants lacked the typical nuclear localization pattern of PFV Gag. Finally, it could be shown that GR boxes I and III, but not GR box II, can functionally complement each other. It therefore appears that, similar to the orthoretroviral Cys-His motifs, the PFV Gag GR boxes are important for RNA encapsidation, genome reverse transcription, and virion infectivity as well as for particle morphogenesis.

  10. Grosnaja ABCs: Magnesium isotope compositions

    NASA Technical Reports Server (NTRS)

    Goswami, J. N.; Srinivasan, G.; Ulyanov, A. A.

    1993-01-01

    Three CAI's from the Grosnaja CV3 chondrite were analyzed for their magnesium isotopic compositions by the ion microprobe. The selected CAI's represent three distinct types: GR4(compact Type A), GR7(Type B) and GR2(Type C). Petrographic studies indicate that all three Grosnaja inclusions were subjected to secondary alterations. The Type A CAI GR4 is primarily composed of melilite with spinel and pyroxene occurring as minor phases. The rim of the inclusion does not exhibit distinct layered structure and secondary alteration products (garnet, Fe-rich olivine and Na-rich plagioclase) are present in some localized areas near the rim region. The average major element compositions of different mineral phases in GR4 are given. Preliminary REE data suggest a depletion of HREE relative to LREE by about a factor of 3 without any clear indication of interelement fractionation. The CAI GR7 has textural and minerological characteristics similar to Type B inclusions. The REE data show a pattern that is similar to Group 6 with enrichment in Eu and Yb. In addition, a depletion of HREE compared to LREE is also evident in this object. Melilite composition shows a broad range of akermanite content (Ak(sub 15-55)). Detailed petrographic study is in progress. GR2 is a anorthite-rich Type C inclusion with large plagioclase laths intergrown with Ti-rich pyroxene. The average plagioclase composition is close to pure anorthite (An99).

  11. Functional effects of polymorphisms on glucocorticoid receptor modulation of human anxiogenic substance-P gene promoter activity in primary amygdala neurones

    PubMed Central

    Hay, Colin W.; Shanley, Lynne; Davidson, Scott; Cowie, Philip; Lear, Marissa; McGuffin, Peter; Riedel, Gernot; McEwan, Iain J.; MacKenzie, Alasdair

    2014-01-01

    Summary Expression or introduction of the neuropeptide substance-P (SP; encoded by the TAC1 gene in humans and Tac1 in rodents) in the amygdala induces anxiety related behaviour in rodents. In addition, pharmacological antagonism of the main receptor of SP in humans; NK1, is anxiolytic. In the current study, we show that the Tac1 locus is up-regulated in primary rat amygdala neurones in response to activation of the glucocorticoid receptor (GR); a classic component of the stress response. Using a combination of bioinformatics, electrophoretic mobility shift assays (EMSA) and reporter plasmid magnetofection into rat primary amygdala neurones we identified a highly conserved GR response sequence (2GR) in the human TAC1 promoter that binds GR in response to dexamethasone (Dex) or forskolin. We also identified a second GR binding site in the human promoter that was polymorphic and whose T-allele is only found in Japanese and Chinese populations. We present evidence that the T-allele of SNPGR increases the activity of the TAC1 promoter through de-sequestration or de-repression of 2GR. The identification of Dex/forskolin response elements in the TAC1 promoter in amygdala neurones suggests a possible link in the chain of molecular events connecting GR activation and anxiety. In addition, the discovery of a SNP which can alter this response may have implications for our understanding of the role of regulatory variation in susceptibility to stress in specific populations. PMID:25001955

  12. Electrochemical performance of 2D polyaniline anchored CuS/Graphene nano-active composite as anode material for lithium-ion battery.

    PubMed

    Iqbal, Shahid; Bahadur, Ali; Saeed, Aamer; Zhou, Kebin; Shoaib, Muhammad; Waqas, Muhammad

    2017-09-15

    Lithium-ion battery (LIB) is a revolutionary step in the electric energy storage technology for making green environment. In the present communication, a LIB anode material was constructed by using graphene/polyaniline/CuS nanocomposite (GR/PANI/CuS NC) as a high-performance electrode. Initially, pure covellite CuS nanoplates (NPs) of the hexagonal structure were synthesized by hydrothermal route and then GR/PANI/CuS NC was fabricated by in-situ polymerization of aniline in the presence of CuS NPs and graphene nanosheets (GR NSs) as host matrix. GR/PANI/CuS NC-based LIB has shown the superior reversible current capacity of 1255mAhg -1 , a high cycling stability with more than 99% coulombic efficiency over 250 cycles even at a high current density of 5Ag -1 , low volume expansion, and excellent power capabilities. Galvanostatic charge/discharge tests and cyclic voltammetry analysis were used to investigate electrochemical properties. The electrochemical test proves that GR/PANI/CuS NC is promising anode material for LIB. The crystal phases and purity of the GR/PANI/CuS NC were confirmed by X-ray diffraction (XRD). Scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray (EDX) and X-ray photoelectron spectroscopy (XPS) were employed to examine the morphology, size, chemical composition, and phase structure of the synthesized GR/PANI/CuS NC. Copyright © 2017. Published by Elsevier Inc.

  13. Large Grüneisen Gamma of Dense Silicate Liquids: More Experiments and a First Self- consistent Model

    NASA Astrophysics Data System (ADS)

    Asimow, P. D.; Mosenfelder, J. L.; Ahrens, T. J.; Sun, D.

    2007-12-01

    The Grüneisen parameter, γ, of solid materials normally decreases upon compression, approximately as γρq = constant where q=1. However, multiple lines of evidence now indicate the opposite behavior in silicate liquids, in which γ increases upon compression (i.e., q<0). This was observed in shock-melted (Mg,Fe)2SiO4 liquid by Brown et al. [1] via comparison of the Hugoniot and release velocity. We observed the same behavior in Mg2SiO4 liquid (q ≤ -1.5) from comparison of the Hugoniots of forsterite and wadsleyite [2]. First-principles molecular dynamics simulations of MgSiO3 liquid [3] confirm that γ increases with density and show that γ in the liquid phase mimics solids with similar Si coordination state. Hence a continuous increase in γ of silicate liquids to lowermost mantle pressures, well beyond the range where transition to six-coordination of Si is complete, suggests that even higher-coordinated species are forming in the melt and by extension there may be 8- coordinated silicate minerals with stability fields beginning not very far above the Earth's core-mantle boundary pressure [4]. We present new experimental evidence for this behavior in another liquid composition. The Hugoniot of 1400°C anorthite-diopside eutectic liquid was measured at low pressure by Rigden et al. [5] and extended to 110 GPa by our recent work. We collected a Hugoniot point on a solid aggregate of the same composition initially at room temperature, shocked into the melt regime at 133 GPa. The difference in internal energy between this point and the hot liquid Hugoniot allows determination of the γ of this aluminosilicate liquid at 50% compression; the result fits q = -1.85±0.2, entirely consistent with the behavior of enstatite, forsterite, and Fe- bearing olivine liquids. We suggested on the basis of an approximate calculation that the large γ of dense silicate liquids yields a liquid isentrope steeper than the liquidus of a lower mantle magma ocean [2]. Here we show a

  14. A fructose receptor functions as a nutrient sensor in the Drosophila brain

    PubMed Central

    Miyamoto, Tetsuya; Slone, Jesse; Song, Xiangyu; Amrein, Hubert

    2012-01-01

    SUMMARY Internal nutrient sensors play important roles in feeding behavior, yet their molecular structure and mechanism of action are poorly understood. Using Ca2+ imaging and behavioral assays, we show that the Gustatory Receptor 43a functions as a narrowly tuned fructose receptor in taste neurons. Remarkably, GR43a also functions as a fructose receptor in the brain. Interestingly, hemolymph fructose levels are tightly linked to feeding status: after nutritious carbohydrate consumption, fructose levels rise several fold and reach a concentration sufficient to activate GR43a in the brain. By using different feeding paradigms and artificial activation of Gr43a-expressing brain neurons, we show that GR43a is both necessary and sufficient to sense hemolymph fructose and promote feeding in hungry flies, but suppress feeding in satiated flies. Thus, our studies indicate that the Gr43a-expressing brain neurons function as a nutrient sensor for hemolymph fructose and assign opposing valence to feeding experiences in a satiation-dependent manner. PMID:23178127

  15. Adjuvant treatment or primary topical monotherapy for ocular surface squamous neoplasia: a systematic review.

    PubMed

    Viani, Gustavo Arruda; Fendi, Ligia Issa de

    2017-01-01

    In this systematic review, we evaluated studies involving adjuvant and primary topical treatment for ocular surface squamous neoplasia (OSSN). The findings were: (i) adjuvant 5-fluorouracil (5-FU) reduces the risk of relapse after surgical excision with mild side effects [level Ib, grade of recommendation (GR) A]. (ii) Primary topical mitomycin (MMC) produces a high rate of complete response, low recurrence rate, and mild side effects (level Ib, GR A). (iii) Primary chemotherapy versus adjuvant chemotherapy produce similar rates of recurrence, with no significant difference (level IIb, GR B). (iv) Adjuvant 5-FU versus MMC showed no significant differences, with mild side effects in both groups and a better toxicity profile for MMC (level III, GR C). (v) Primary topical 5-FU versus MMC versus interferon (IFN) showed similar rates of tumor recurrence, mild side effects for all drugs, and more severe side effects in the 5-FU arm, followed successively by MMC and IFN (level III, GR C).

  16. Peroxisome proliferator-activated receptor {alpha} agonist-induced down-regulation of hepatic glucocorticoid receptor expression in SD rats

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

    Chen Xiang; Li Ming; Sun Weiping

    2008-04-18

    It was reported that glucocorticoid production was inhibited by fenofibrate through suppression of type-1 11{beta}-hydroxysteroid dehydrogenase gene expression in liver. The inhibition might be a negative-feedback regulation of glucocorticoid receptor (GR) activity by peroxisome proliferator-activated receptor alpha (PPAR{alpha}), which is quickly induced by glucocorticoid in the liver. However, it is not clear if GR expression is changed by fenofibrate-induced PPAR{alpha} activation. In this study, we tested this possibility in the liver of Sprague-Dawley rats. GR expression was reduced by fenofibrate in a time- and does-dependent manner. The inhibition was observed in liver, but not in fat and muscle. The corticosteronemore » level in the blood was increased significantly by fenofibrate. These effects of fenofibrate were abolished by PPAR{alpha} inhibitor MK886, suggesting that fenofibrate activated through PPAR{alpha}. In conclusion, inhibition of GR expression may represent a new molecular mechanism for the negative feedback regulation of GR activity by PPAR{alpha}.« less

  17. Liver-selective glucocorticoid antagonists: a novel treatment for type 2 diabetes.

    PubMed

    von Geldern, Thomas W; Tu, Noah; Kym, Philip R; Link, James T; Jae, Hwan-Soo; Lai, Chunqiu; Apelqvist, Theresa; Rhonnstad, Patrik; Hagberg, Lars; Koehler, Konrad; Grynfarb, Marlena; Goos-Nilsson, Annika; Sandberg, Johnny; Osterlund, Marie; Barkhem, Tomas; Höglund, Marie; Wang, Jiahong; Fung, Steven; Wilcox, Denise; Nguyen, Phong; Jakob, Clarissa; Hutchins, Charles; Färnegårdh, Mathias; Kauppi, Björn; Ohman, Lars; Jacobson, Peer B

    2004-08-12

    Hepatic blockade of glucocorticoid receptors (GR) suppresses glucose production and thus decreases circulating glucose levels, but systemic glucocorticoid antagonism can produce adrenal insufficiency and other undesirable side effects. These hepatic and systemic responses might be dissected, leading to liver-selective pharmacology, when a GR antagonist is linked to a bile acid in an appropriate manner. Bile acid conjugation can be accomplished with a minimal loss of binding affinity for GR. The resultant conjugates remain potent in cell-based functional assays. A novel in vivo assay has been developed to simultaneously evaluate both hepatic and systemic GR blockade; this assay has been used to optimize the nature and site of the linker functionality, as well as the choice of the GR antagonist and the bile acid. This optimization led to the identification of A-348441, which reduces glucose levels and improves lipid profiles in an animal model of diabetes. Copyright 2004 American Chemical Society

  18. O-ribosyl-phosphate purine as a constant modified nucleotide located at position 64 in cytoplasmic initiator tRNAs(Met) of yeasts.

    PubMed Central

    Glasser, A L; Desgres, J; Heitzler, J; Gehrke, C W; Keith, G

    1991-01-01

    The unknown modified nucleotide G*, isolated from both Schizosaccharomyces pombe and Torulopsis utilis initiator tRNAs(Met), has been identified as an O-ribosyl-(1"----2')-guanosine-5"-phosphate, called Gr(p), by means of HPLC, UV-absorption, mass spectrometry and periodate oxidation procedures. By comparison with the previously published structure of Ar(p) isolated from Saccharomyces cerevisiae initiator tRNA(Met), the (1"----2')-glycosidic bond in Gr(p) has been postulated to have a beta-spatial conformation. The modified nucleotide Gr(p) is located at position 64 in the tRNA(Met) molecules, i.e. at the same position as Ar(p). Since we have also characterized Gr(p) in Candida albicans initiator tRNA(Met), the phosphoribosylation of purine 64 can be considered as a constant nucleotide modification in the cytoplasmic initiator tRNAs(Met) of all yeast species so far sequenced. Precise evidence for the presence of Gr(p) in initiator tRNAs(Met) of several plants is also reported. PMID:1656390

  19. How glucocorticoid receptors modulate the activity of other transcription factors: a scope beyond tethering.

    PubMed

    Ratman, Dariusz; Vanden Berghe, Wim; Dejager, Lien; Libert, Claude; Tavernier, Jan; Beck, Ilse M; De Bosscher, Karolien

    2013-11-05

    The activity of the glucocorticoid receptor (GR), a nuclear receptor transcription factor belonging to subclass 3C of the steroid/thyroid hormone receptor superfamily, is typically triggered by glucocorticoid hormones. Apart from driving gene transcription via binding onto glucocorticoid response elements in regulatory regions of particular target genes, GR can also inhibit gene expression via transrepression, a mechanism largely based on protein:protein interactions. Hereby GR can influence the activity of other transcription factors, without contacting DNA itself. GR is known to inhibit the activity of a growing list of immune-regulating transcription factors. Hence, GCs still rule the clinic for treatments of inflammatory disorders, notwithstanding concomitant deleterious side effects. Although patience is a virtue when it comes to deciphering the many mechanisms GR uses to influence various signaling pathways, the current review is testimony of the fact that groundbreaking mechanistic work has been accumulating over the past years and steadily continues to grow. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  20. The influence of the concentration of Sr ions on the crystal and magnetic structures of Ba{sub 2} –{sub x}Sr{sub x}FeMoO{sub 6} double perovskites (x = 0–1.6)

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

    Turchenko, V. A., E-mail: turchenko@jinr.ru; Kalanda, N. A.; Kovalev, L. V.

    2017-01-15

    The crystal and magnetic structures of a solid solution of double perovskite Ba{sub 2–} {sub x}Sr{sub x}FeMoO{sub 6} (x = 0–1.6) have been investigated by neutron diffraction. The high-resolution diffraction patterns have provided precise information about the changes in the crystal and magnetic structures with an increase in the strontium content and data on the behavior of the sample microstructure. Replacement of barium with strontium leads to a change in the lattice symmetry from cubic (x = 0, sp. gr. Fm3̄m)) to tetragonal (x = 0.4, sp. gr. I4/m). At x = 1.0, the symmetry is either tetragonal (sp. gr.more » I4/m) or orthorhombic (sp. gr. Fmmm), and at x = 1.6 the symmetry becomes again tetragonal (sp. gr. I4/m). The values of the Curie temperature and microstrain increase with an increase in the strontium content.« less

  1. Tool to address green roof widespread implementation effect in flood characteristics for water management planning

    NASA Astrophysics Data System (ADS)

    Tassi, R.; Lorenzini, F.; Allasia, D. G.

    2015-06-01

    In the last decades, new approaches were adopted to manage stormwater as close to its source as possible through technologies and devices that preserve and recreate natural landscape features. Green Roofs (GR) are examples of these devices that are also incentivized by city's stormwater management plans. Several studies show that GR decreases on-site runoff from impervious surfaces, however, the analysis of the effect of widespread implementation of GR in the flood characteristics at the urban basin scale in subtropical areas are little discussed, mainly because of the absence of data. Thereby, this paper shows results related to the monitoring of an extensive modular GR under subtropical weather conditions, the development of a rainfall-runoff model based on the modified Curve Number (CN) and SCS Triangular Unit Hydrograph (TUH) methods and the analysis of large-scale impact of GR by modelling different basins. The model was calibrated against observed data and showed that GR absorbed almost all the smaller storms and reduced runoff even during the most intense rainfall. The overall CN was estimated in 83 (consistent with available literature) with the shape of hydrographs well reproduced. Large-scale modelling (in basins ranging from 0.03 ha to several square kilometers) showed that the widespread use of GRs reduced peak flows (volumes) around 57% (48%) at source and 38% (32%) at the basin scale. Thus, this research validated a tool for the assessment of structural management measures (specifically GR) to address changes in flood characteristics in the city's water management planning. From the application of this model it was concluded that even if the efficiency of GR decreases as the basin scale increase they still provide a good option to cope with urbanization impact.

  2. Cytokines Alter Glucocorticoid Receptor Phosphorylation in Airway Cells

    PubMed Central

    Bouazza, Belaid; Krytska, Kateryna; Debba-Pavard, Manel; Amrani, Yassine; Honkanen, Richard E.; Tran, Jennifer

    2012-01-01

    Corticosteroid insensitivity (CSI) represents a profound challenge in managing patients with asthma. We recently demonstrated that short exposure of airway smooth muscle cells (ASMCs) to proasthmatic cytokines drastically reduced their responsiveness to glucocorticoids (GCs), an effect that was partially mediated via interferon regulatory factor-1, suggesting the involvement of additional mechanisms (Am J Respir Cell Mol Biol 2008;38:463–472). Although GC receptor (GR) can be phosphorylated at multiple serines in the N-terminal region, the major phosphorylation sites critical for GR transcriptional activity are serines 211 (Ser211) and 226 (Ser226). We tested the novel hypothesis that cytokine-induced CSI in ASMCs is due to an impaired GR phosphorylation. Cells were treated with TNF-α (10 ng/ml) and IFN-γ (500 UI/ml) for 6 hours and/or fluticasone (100 nm) added 2 hours before. GR was constitutively phosphorylated at Ser226 but not at Ser211 residues. Cytokines dramatically suppressed fluticasone-induced phosphorylation of GR on Ser211 but not on Ser226 residues while increasing the expression of Ser/Thr protein phosphatase (PP)5 but not that of PP1 or PP2A. Transfection studies using a reporter construct containing GC responsive elements showed that the specific small interfering RNA–induced mRNA knockdown of PP5, but not that of PP1 or PP2A, partially prevented the cytokine suppressive effects on GR-meditated transactivation activity. Similarly, cytokines failed to inhibit GC-induced GR-Ser211 phosphorylation when expression of PP5 was suppressed. We propose that the novel mechanism that proasthmatic cytokine-induced CSI in ASMCs is due, in part, to PP5-mediated impairment of GR-Ser211 phosphorylation. PMID:22592921

  3. PA1 Protein, a New Competitive Decelerator Acting at More than One Step to Impede Glucocorticoid Receptor-mediated Transactivation*

    PubMed Central

    Zhang, Zhenhuan; Sun, Yunguang; Cho, Young-Wook; Chow, Carson C.; Simons, S. Stoney

    2013-01-01

    Numerous cofactors modulate the gene regulatory activity of glucocorticoid receptors (GRs) by affecting one or more of the following three major transcriptional properties: the maximal activity of agonists (Amax), the potency of agonists (EC50), and the partial agonist activity of antisteroids (PAA). Here, we report that the recently described nuclear protein, Pax2 transactivation domain interaction protein (PTIP)-associated protein 1 (PA1), is a new inhibitor of GR transactivation. PA1 suppresses Amax, increases the EC50, and reduces the PAA of an exogenous reporter gene in a manner that is independent of associated PTIP. PA1 is fully active with, and strongly binds to, the C-terminal half of GR. PA1 reverses the effects of the coactivator TIF2 on GR-mediated gene induction but is unable to augment the actions of the corepressor SMRT. Analysis of competition assays between PA1 and TIF2 with an exogenous reporter indicates that the kinetic definition of PA1 action is a competitive decelerator at two sites upstream from where TIF2 acts. With the endogenous genes IGFBP1 and IP6K3, PA1 also represses GR induction, increases the EC50, and decreases the PAA. ChIP and re-ChIP experiments indicate that PA1 accomplishes this inhibition of the two genes via different mechanisms as follows: PA1 appears to increase GR dissociation from and reduce GR transactivation at the IGFBP1 promoter regions but blocks GR binding to the IP6K3 promoter. We conclude that PA1 is a new competitive decelerator of GR transactivation and can act at more than one molecularly defined step in a manner that depends upon the specific gene. PMID:23161582

  4. PA1 protein, a new competitive decelerator acting at more than one step to impede glucocorticoid receptor-mediated transactivation.

    PubMed

    Zhang, Zhenhuan; Sun, Yunguang; Cho, Young-Wook; Chow, Carson C; Simons, S Stoney

    2013-01-04

    Numerous cofactors modulate the gene regulatory activity of glucocorticoid receptors (GRs) by affecting one or more of the following three major transcriptional properties: the maximal activity of agonists (A(max)), the potency of agonists (EC(50)), and the partial agonist activity of antisteroids (PAA). Here, we report that the recently described nuclear protein, Pax2 transactivation domain interaction protein (PTIP)-associated protein 1 (PA1), is a new inhibitor of GR transactivation. PA1 suppresses A(max), increases the EC(50), and reduces the PAA of an exogenous reporter gene in a manner that is independent of associated PTIP. PA1 is fully active with, and strongly binds to, the C-terminal half of GR. PA1 reverses the effects of the coactivator TIF2 on GR-mediated gene induction but is unable to augment the actions of the corepressor SMRT. Analysis of competition assays between PA1 and TIF2 with an exogenous reporter indicates that the kinetic definition of PA1 action is a competitive decelerator at two sites upstream from where TIF2 acts. With the endogenous genes IGFBP1 and IP6K3, PA1 also represses GR induction, increases the EC(50), and decreases the PAA. ChIP and re-ChIP experiments indicate that PA1 accomplishes this inhibition of the two genes via different mechanisms as follows: PA1 appears to increase GR dissociation from and reduce GR transactivation at the IGFBP1 promoter regions but blocks GR binding to the IP6K3 promoter. We conclude that PA1 is a new competitive decelerator of GR transactivation and can act at more than one molecularly defined step in a manner that depends upon the specific gene.

  5. Transient ice mass variations over Greenland detected by the combination of GPS and GRACE data

    NASA Astrophysics Data System (ADS)

    Zhang, B.; Liu, L.; Khan, S. A.; van Dam, T. M.; Zhang, E.

    2017-12-01

    Over the past decade, the Greenland Ice Sheet (GrIS) has been undergoing significant warming and ice mass loss. Such mass loss was not always a steady process but had substantial temporal and spatial variabilities. Here we apply multi-channel singular spectral analysis to crustal deformation time series measured at about 50 Global Positioning System (GPS) stations mounted on bedrock around the Greenland coast and mass changes inferred from Gravity Recovery and Climate Experiment (GRACE) to detect transient changes in ice mass balance over the GrIS. We detect two transient anomalies: one is a negative melting anomaly (Anomaly 1) that peaked around 2010; the other is a positive melting anomaly (Anomaly 2) that peaked between 2012 and 2013. The GRACE data show that both anomalies caused significant mass changes south of 74°N but negligible changes north of 74°N. Both anomalies caused the maximum mass change in southeast GrIS, followed by in west GrIS near Jakobshavn. Our results also show that the mass change caused by Anomaly 1 first reached the maximum in late 2009 in the southeast GrIS and then migrated to west GrIS. However, in Anomaly 2, the southeast GrIS was the last place that reached the maximum mass change in early 2013 and the west GrIS near Jakobshavn was the second latest place that reached the maximum mass change. Most of the GPS data show similar spatiotemporal patterns as those obtained from the GRACE data. However, some GPS time series show discrepancies in either space or time, because of data gaps and different sensitivities of mass loading change. Namely, loading deformation measured by GPS can be significantly affected by local dynamical mass changes, which, yet, has little impact on GRACE observations.

  6. Is rigid endoscopy necessary with childhood corrosive ingestion? a retrospective comparative analysis of 458 cases.

    PubMed

    Bosnali, O; Moralioglu, S; Celayir, A; Pektas, O Z

    2017-02-01

    The aim of this study was to determine the necessity of endoscopy in cases in which a corrosive substance was ingested and to find a practical way to avoid unnecessary endoscopies for similar cases in the future. The clinical records of 458 hospitalized cases with clinical histories of corrosive substance ingestion between January 2007 and December 2013 were retrospectively reviewed. The demographics of the cases, the ingested substances, and the rigid endoscopy findings were evaluated. The three most commonly ingested corrosive agents were household bleach (22.9%), household degreaser (15.9%), and drain cleaner (13.1%). Rigid esophagoscopy was performed in 367 of the 458 cases. Corrosive agents were grouped according to their purpose of household use; eight groups were created. The degree of corrosive injury observed in the different groups was compared with the degree of injury caused by household bleach. Among the corrosive agent groups, dishwashing machine products (Gr.1), laundry products (Gr.2), liquid cleaners (Gr.3), and household bleach (Gr.4) did not cause high-grade injuries. The resulting injuries and esophagoscopy results among the above groups, whether symptomatic or not, did not differ from one another. Corrosive agents such as drain cleaner (Gr.6), household degreaser (Gr.7), and several other acidic products (Gr.8) caused high-grade injuries in the esophagus; however, lime remover/HCl (Gr.5) did not. Thus, hospitalization and rigid endoscopy seem unnecessary to assess esophageal injury in most cases, if the ingested corrosive agent fits into group 1, 2, 3, or 4 and if the patient can be easily fed. Esophagoscopy is useful to shorten the hospitalization times in cases where strong corrosive agents were ingested, such as those in groups 5, 6, 7, and 8. © 2016 International Society for Diseases of the Esophagus.

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

    Getachew, Yonas, E-mail: yonas.getachew@utsouthwestern.edu; Cusimano, Frank A.; James, Laura P.

    The role of the immune system, specifically NK, NKT and CD3 cells, in acetaminophen (APAP) induced liver injury remains inconsistently defined. In the present study, wild type (C57BL/6J) mice and granzyme B deficient (GrB −/−) mice were treated with acetaminophen to assess the role of the immune system in acute liver injury. Doses of acetaminophen that induced sub lethal liver injury in wild type mice unexpectedly produced fatal hepatotoxicity in granzyme B deficient (GrB −/−) mice. Analysis revealed that GrB −/− mice had an increased population of intrahepatic CD3 (+), CD4 (−), and CD8 (−) lymphocytes expressing the CD69 activationmore » marker and Fas ligand. Depletion of these cells in the GrB −/− and wild type mice made them less susceptible to APAP injury, while depletion of NK1.1 (+) cells or both CD4 (+) and CD8 (+) T cells failed to provide the same hepatoprotection. Transfer of the GrB −/− IHLs further exacerbated liver injury and increased mortality in wild type mice but not in LRP/LPR mice, lacking fas expression. Conclusions: Acetaminophen toxicity is enhanced by the presence of activated, FasL expressing intrahepatic CD3 (+), CD4 (−), CD8 (−), NK1.1 (−) T cells. Depletion of these cells from GrB −/− mice and wild type mice greatly reduces mortality and improves the course of liver injury recovery. - Highlights: • Intrahepatic lymphocytes (IHLs) from GrB −/− mice harbor activated DNT cells. • IHLs from GrB −/− mice exhibit enhanced Fas ligand expression. • Acetaminophen toxicity is enhanced by activated, FasL expressing DNT cells.« less

  8. Green Rust: Structure, Redox Reaction Mechanisms, Transformation and Colloidal Behaviour

    NASA Astrophysics Data System (ADS)

    Stipp, S.; Skovbjerg, L.; Christiansen, B.; Hansson, E.; Utsunomiya, S.; Schild, D.; Geckeis, H.; Ewing, R.

    2006-05-01

    Green rust (GR) forms where pH is neutral to basic, iron concentration is high and oxidation potential provides a small amount of Fe(III). GR is best known from metallic iron corrosion but it has also been reported in soil. It typically forms nano-particles, so surface area is high. It has a layered structure and is reactive, adsorbing species on its surface, providing exchange of interlayer ions, and allowing reaction of redox active species. Corroding stainless-steel canisters in a concrete and steel radioactive waste repository would offer geochemical conditions for GR formation. We used surface-sensitive and high resolution techniques (atomic force microscopy, AFM, transmission electron microscopy, TEM, X-ray photoelectron spectroscopy, XPS) to supplement data from traditional methods (X-ray diffraction, XRD, and wet chemistry). The purpose was to refine structural and compositional parameters for green rust sulfate; to define trace component uptake mechanisms; and to assess potential mobility of GR colloids and thus, sorbed radionuclides. Green rust reduced dissolved Np(V), Cr(VI) and Se(VI), rapidly decreasing solution concentration. High resolution TEM and AFM images showed that chromate penetrates GR interlayers to a distance of about 100 nm from crystal edges. It reduces to Cr(III), blocking further movement and GR transforms topotactically to Cr- goethite, thus immobilising the contaminant in a phase significantly less soluble than pure goethite. Further oxidation results in dissolution of GR and growth of more Cr-goethite. In-situ AFM imaging showed that GR can nucleate and grow both in solution and on minerals typical of fractures in granite, i.e. graphite, muscovite, biotite, quartz and amorphous silica. Particles are more likely to stick to each other or to a substrate than to remain monodispersed.

  9. Mismodeling in gravitational-wave astronomy: The trouble with templates

    NASA Astrophysics Data System (ADS)

    Sampson, Laura; Cornish, Neil; Yunes, Nicolás

    2014-03-01

    Waveform templates are a powerful tool for extracting and characterizing gravitational wave signals, acting as highly restrictive priors on the signal morphologies that allow us to extract weak events buried deep in the instrumental noise. The templates map the waveform shapes to physical parameters, thus allowing us to produce posterior probability distributions for these parameters. However, there are attendant dangers in using highly restrictive signal priors. If strong field gravity is not accurately described by general relativity (GR), then using GR templates may result in fundamental bias in the recovered parameters, or even worse, a complete failure to detect signals. Here we study such dangers, concentrating on three distinct possibilities. First, we show that there exist modified theories compatible with all existing observations that would fail to be detected by the LIGO/Virgo network using searches based on GR templates, but which would be detected using a one parameter post-Einsteinian extension. Second, we study modified theories that produce departures from GR that turn on suddenly at a critical frequency, producing waveforms that do not directly fit into the simplest parametrized post-Einsteinian (ppE) scheme. We show that even the simplest ppE templates are still capable of picking up these strange signals and diagnosing a departure from GR. Third, we study whether using inspiral-only ppE waveforms for signals that include merger and ringdown can lead to problems in misidentifying a GR departure. We present a simple technique that allows us to self-consistently identify the inspiral portion of the signal, and thus remove these potential biases, allowing GR tests to be performed on higher mass signals that merge within the detector band. We close by studying a parametrized waveform model that may allow us to test GR using the full inspiral-merger-ringdown signal.

  10. Novel regulation of 25-hydroxyvitamin D3 24-hydroxylase (24(OH)ase) transcription by glucocorticoids: cooperative effects of the glucocorticoid receptor, C/EBP beta, and the Vitamin D receptor in 24(OH)ase transcription.

    PubMed

    Dhawan, Puneet; Christakos, Sylvia

    2010-08-15

    Glucocorticoid-induced bone loss has been proposed to involve direct effects on bone cells as well as alterations in calcium absorption and excretion. Since vitamin D is important for the maintenance of calcium homeostasis, in the present study the effects of glucocorticoids on vitamin D metabolism through the expression of 24(OH)ase, an enzyme involved in the catabolism of 1,25(OH)(2)D(3), were examined. Injection of vitamin D replete mice with dexamethasone (dex) resulted in a significant induction in 24(OH)ase mRNA in kidney, indicating a regulatory effect of glucocorticoids on vitamin D metabolism. Whether glucocorticoids can affect 24(OH)ase transcription is not known. Here we demonstrate for the first time a glucocorticoid receptor (GR) dependent enhancement of 1,25(OH)(2)D(3)-induced 24(OH)ase transcription. Dex treatment of GR and vitamin D receptor (VDR) transfected COS-7 cells and dex treatment of osteoblastic cells (in which VDR and GR are present endogenously) potentiated 1,25(OH)(2)D(3)-induced 24(OH)ase transcription. In addition, GR was found to cooperate with C/EBP beta to enhance VDR-mediated 24(OH)ase transcription. Using the rat 24(OH)ase promoter with the C/EBP site mutated, GR-mediated potentiation of 1,25(OH)(2)D(3)-induced 24(OH)ase transcription was inhibited. Immunoprecipitation indicated that that GR can interact with C/EBP beta and ChIP/re-ChIP analysis showed that C/EBP beta and GR bind simultaneously to the 24(OH)ase promoter. These findings indicate a novel mechanism whereby glucocorticoids can alter VDR-mediated 24(OH)ase transcription through functional cooperation between C/EBP beta and GR that results in an enhanced ability of C/EBP beta to cooperate with VDR in the regulation of 24(OH)ase. (c) 2010 Wiley-Liss, Inc.

  11. Compound A, a Selective Glucocorticoid Receptor Modulator, Enhances Heat Shock Protein Hsp70 Gene Promoter Activation

    PubMed Central

    Beck, Ilse M.; Drebert, Zuzanna J.; Hoya-Arias, Ruben; Bahar, Ali A.; Devos, Michael; Clarisse, Dorien; Desmet, Sofie; Bougarne, Nadia; Ruttens, Bart; Gossye, Valerie; Denecker, Geertrui; Lievens, Sam; Bracke, Marc; Tavernier, Jan; Declercq, Wim; Gevaert, Kris; Berghe, Wim Vanden; Haegeman, Guy; De Bosscher, Karolien

    2013-01-01

    Compound A possesses glucocorticoid receptor (GR)-dependent anti-inflammatory properties. Just like classical GR ligands, Compound A can repress NF-κB-mediated gene expression. However, the monomeric Compound A-activated GR is unable to trigger glucocorticoid response element-regulated gene expression. The heat shock response potently activates heat shock factor 1 (HSF1), upregulates Hsp70, a known GR chaperone, and also modulates various aspects of inflammation. We found that the selective GR modulator Compound A and heat shock trigger similar cellular effects in A549 lung epithelial cells. With regard to their anti-inflammatory mechanism, heat shock and Compound A are both able to reduce TNF-stimulated IκBα degradation and NF-κB p65 nuclear translocation. We established an interaction between Compound A-activated GR and Hsp70, but remarkably, although the presence of the Hsp70 chaperone as such appears pivotal for the Compound A-mediated inflammatory gene repression, subsequent novel Hsp70 protein synthesis is uncoupled from an observed CpdA-induced Hsp70 mRNA upregulation and hence obsolete in mediating CpdA’s anti-inflammatory effect. The lack of a Compound A-induced increase in Hsp70 protein levels in A549 cells is not mediated by a rapid proteasomal degradation of Hsp70 or by a Compound A-induced general block on translation. Similar to heat shock, Compound A can upregulate transcription of Hsp70 genes in various cell lines and BALB/c mice. Interestingly, whereas Compound A-dependent Hsp70 promoter activation is GR-dependent but HSF1-independent, heat shock-induced Hsp70 expression alternatively occurs in a GR-independent and HSF1-dependent manner in A549 lung epithelial cells. PMID:23935933

  12. Fiber post cementation strategies: effect of mechanical cycling on push-out bond strength and cement polymerization stress.

    PubMed

    Bergoli, Cesar Dalmolin; Amaral, Marina; Boaro, Leticia Cristina; Braga, Roberto Ruggiero; Valandro, Luiz Felipe

    2012-08-01

    To evaluate the effect of mechanical cycling and cementation strategies on the push-out bond strength between fiber posts and root dentin and the polymerization stresses produced using three resin cements. Eighty bovine mandibular teeth were sectioned to a length of 16 mm, prepared to 12 mm, and embedded in self-curing acrylic resin. The specimens were then distributed into 8 groups (n = 10): Gr1 - Scotchbond Multi Purpose + RelyX ARC; Gr2 - Scotchbond Multi Purpose + RelyX ARC + mechanical cycling; Gr3 - AdheSE + Multilink Automix; Gr4 - AdheSE + Multilink Automix + mechanical cycling; Gr5 - phosphoric acid + RelyX U100 (self-adhesive cement); Gr6 - phosphoric acid+ RelyX U100 + mechanical cycling; Gr7 - RelyX U100; Gr8 - RelyX U100 + mechanical cycling. The values obtained from the push-out bond strength test were submitted to two-way ANOVA and Tukey's test (p = 0.05), while the values obtained from the polymerization stress test were subjected to one-way ANOVA and Tukey's test (α = 0.05). Mechanical cycling did not affect the bond strength values (p = 0.236), while cementation strategies affected the push-out bond strength (p < 0.001). Luting with RelyX U100 and Scotch Bond Multi Purpose + RelyX ARC yielded higher push-out bond strength values. The polymerization stress results were affected by the factor "cement" (p = 0.0104): the self-adhesive cement RelyX U100 exhibited the lowest values, RelyX ARC resulted in the highest values, while Multilink Automix presented values statistically similar to the other two cements. The self-adhesive cement appears to be a good alternative for luting fiber posts due to the high push-out bond strengths and lower polymerization stress values.

  13. Bupropion induces social anxiety in adolescent mice: Influence of housing conditions.

    PubMed

    Gómez, Carmen; Redolat, Rosa; Carrasco, Carmen

    2017-08-01

    The antidepressant bupropion has received increasing attention as a pharmacological tool to treat addiction although little is known about its effects on social behaviour in adolescents. The present study aimed to evaluate if environmental housing conditions influence bupropion's actions on social behaviour of adolescent mice. Mice were either group- or individually housed for 2-weeks and then randomly divided into 2 cohorts: half of the mice remained in the initial housing condition and the other half were changed to isolated conditions for further 2-weeks. The following groups were compared: isolated/isolated (ISO/ISO), isolated/group-housed (ISO/GR), group-housed/isolated (GR/ISO), and group-housed/group-housed (GR/GR). The effects of bupropion (40, 20, 10mg/kg) or saline on social interaction were assessed for each housing condition. Social encounters were evaluated using ethological analysis. Data showed significant effects of bupropion on grooming and digging. This drug diminished time mice allocated to these behavioural categories in all housing conditions. In ISO/GR and GR/ISO conditions, bupropion increased environmental exploration (non-social exploration and exploration from a distance), reduced social investigation and increased avoidance/flee and defence/submission behaviours. An augment of avoidance/flee during social interactions was observed in bupropion-treated mice in GR/GR housing condition. These results suggest that this drug exhibits anxiogenic-like properties in social encounters between adolescent mice, especially when a transition in housing conditions has been experienced during this period. Changes in housing conditions may be a useful model for evaluating the effects of bupropion on social behaviour and the role of environmental housing conditions. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  14. Evaluation of a colorimetric reagent strip assay for urine specific gravity.

    PubMed

    Kirschbaum, B B

    1983-06-01

    N-Multistix SG provides a convenient colorimetric assay for the determination of the specific gravity (sp. gr.) of freshly voided urine. When compared with results obtained by standard hydrometry, the colorimetric assay sp. gr. was observed to decrease by as much as 0.010 units as urine pH increased from 5 to 7. Moderate levels of proteinuria that did not alter hydrometer readings effectively raised the colorimetric sp. gr. by 0.005-0.010 units. The colorimetric assay was almost completely insensitive to clinically encountered concentrations of glucose and urea but responded appropriately to monovalent salts. The magnitude of these observed discrepancies places serious limitations on the value of the colorimetric sp. gr. measurement.

  15. Should idiopathic facial aseptic granuloma be considered granulomatous rosacea? Report of three pediatric cases.

    PubMed

    Neri, Iria; Raone, Beatrice; Dondi, Arianna; Misciali, Cosimo; Patrizi, Annalisa

    2013-01-01

    Idiopathic facial aseptic granuloma (IFAG), or pyodermite froide du visage, is a skin disease reported only in children and characterized by painless red nodules usually located on the cheeks. Its etiology is still unclear, but some authors considered the possibility that IFAG might be included in the spectrum of granulomatous rosacea (GR). The histopathological features of IFAG and GR are quite similar, showing perifolliculitis, granulomas, folliculitis, and lymphocytes and plasmacells around epithelioid histiocytes. In the present article, we discuss three cases in which an association between a facial nodule, compatible with both IFAG and GR, and recurrent chalazia make us support the hypothesis that IFAG should be considered as GR. © 2012 Wiley Periodicals, Inc.

  16. Effects of thermal cycling on composite materials for space structures

    NASA Technical Reports Server (NTRS)

    Tompkins, Stephen S.

    1989-01-01

    The effects of thermal cycling on the thermal and mechanical properties of composite materials that are candidates for space structures are briefly described. The results from a thermal analysis of the orbiting Space Station Freedom is used to define a typical thermal environment and the parameters that cause changes in the thermal history. The interactions of this environment with composite materials are shown and described. The effects of this interaction on the integrity as well as the properties of GR/thermoset, Gr/thermoplastic, Gr/metal and Gr/glass composite materials are discussed. Emphasis is placed on the effects of the interaction that are critical to precision spacecraft. Finally, ground test methodology are briefly discussed.

  17. Schottky barrier at graphene/metal oxide interfaces: insight from first-principles calculations

    NASA Astrophysics Data System (ADS)

    Cheng, Kai; Han, Nannan; Su, Yan; Zhang, Junfeng; Zhao, Jijun

    2017-02-01

    Anode materials play an important role in determining the performance of lithium ion batteries. In experiment, graphene (GR)/metal oxide (MO) composites possess excellent electrochemical properties and are promising anode materials. Here we perform density functional theory calculations to explore the interfacial interaction between GR and MO. Our result reveals generally weak physical interactions between GR and several MOs (including Cu2O, NiO). The Schottky barrier height (SBH) in these metal/semiconductor heterostructures are computed using the macroscopically averaged electrostatic potential method, and the role of interfacial dipole is discussed. The calculated SBHs below 1 eV suggest low contact resistance; thus these GR/MO composites are favorable anode materials for better lithium ion batteries.

  18. Schottky barrier at graphene/metal oxide interfaces: insight from first-principles calculations.

    PubMed

    Cheng, Kai; Han, Nannan; Su, Yan; Zhang, Junfeng; Zhao, Jijun

    2017-02-06

    Anode materials play an important role in determining the performance of lithium ion batteries. In experiment, graphene (GR)/metal oxide (MO) composites possess excellent electrochemical properties and are promising anode materials. Here we perform density functional theory calculations to explore the interfacial interaction between GR and MO. Our result reveals generally weak physical interactions between GR and several MOs (including Cu2O, NiO). The Schottky barrier height (SBH) in these metal/semiconductor heterostructures are computed using the macroscopically averaged electrostatic potential method, and the role of interfacial dipole is discussed. The calculated SBHs below 1 eV suggest low contact resistance; thus these GR/MO composites are favorable anode materials for better lithium ion batteries.

  19. Preparation of layered graphene and tungsten oxide hybrids for enhanced performance supercapacitors.

    PubMed

    Xing, Ling-Li; Huang, Ke-Jing; Fang, Lin-Xia

    2016-11-01

    Tungsten oxide (WO 3 ), which was originally poor in capacitive performance, is made into an excellent electrode material for supercapacitors by dispersing it on graphene (Gr). The obtained Gr-WO 3 hybrids are characterized by X-ray diffraction, Raman spectroscopy, high-resolution transmission electron microscopy and scanning electron microscopy techniques, and evaluated as electrode materials for high-performance supercapacitors by cyclic voltammetry, galvanostatic charge-discharge curves and electrochemical impedance spectroscopy. A great improvement in specific capacitance is achieved with the present hybrids, from 255 F g -1 for WO 3 nanoparticles to 580 F g -1 for Gr-WO 3 hybrids (scanned at 1 A g -1 in 2 M KOH over a potential window of 0 to 0.45 V). The Gr-WO 3 hybrid exhibits an excellent high rate capability and good cycling stability with more than 92% capacitance retention over 1000 cycles at a current density of 5 A g -1 . The enhancement in supercapacitor performance of Gr-WO 3 is not only attributed to its unique nanostructure with large specific surface area, but also its excellent electro-conductivity, which facilitates efficient charge transport and promotes electrolyte diffusion. As a whole, this work indicates that Gr-WO 3 hybrids are a promising electrode material for high-performance supercapacitors.

  20. Mass spectrometry-based metabolic profiling of gemcitabine-sensitive and gemcitabine-resistant pancreatic cancer cells.

    PubMed

    Fujimura, Yoshinori; Ikenaga, Naoki; Ohuchida, Kenoki; Setoyama, Daiki; Irie, Miho; Miura, Daisuke; Wariishi, Hiroyuki; Murata, Masaharu; Mizumoto, Kazuhiro; Hashizume, Makoto; Tanaka, Masao

    2014-03-01

    Gemcitabine resistance (GR) is one of the critical issues for therapy for pancreatic cancer, but the mechanism still remains unclear. Our aim was to increase the understanding of GR by metabolic profiling approach. To establish GR cells, 2 human pancreatic cancer cell lines, SUIT-2 and CAPAN-1, were exposed to increasing concentration of gemcitabine. Both parental and chemoresistant cells obtained by this treatment were subjected to metabolic profiling based on liquid chromatography-mass spectrometry. Multivariate statistical analyses, both principal component analysis and orthogonal partial least squares discriminant analysis, distinguished metabolic signature of responsiveness and resistance to gemcitabine in both SUIT-2 and CAPAN-1 cells. Among significantly different (P < 0.005) metabolite peaks between parental and GR cells, we identified metabolites related to several metabolic pathways such as amino acid, nucleotide, energy, cofactor, and vitamin pathways. Decreases in glutamine and proline levels as well as increases in aspartate, hydroxyproline, creatine, and creatinine levels were observed in chemoresistant cells from both cell lines. These results suggest that metabolic profiling can isolate distinct features of pancreatic cancer in the metabolome of gemcitabine-sensitive and GR cells. These findings may contribute to the biomarker discovery and an enhanced understanding of GR in pancreatic cancer.