Sample records for binary gr mus

  1. Investigation of Times of Minima of Selected Early-Type Eclipsing Binaries

    NASA Astrophysics Data System (ADS)

    Mayer, Pavel; Wolf, Marek; Niarchos, P. G.; Gazeas, K. D.; Manimanis, V. N.; Chochol, Drahomír

    2006-08-01

    New precise times of minimum light for several early-type eclipsing binaries were obtained at three observatories. The changes of period of the following measured binaries are discussed: V1182 Aql, LY Aur, SZ Cam, FZ CMa, QZ Car, LZ Cen, V606 Cen, AH Cep and TU~Mus.

  2. 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.

  3. Testing general relativity using gravitational wave signals from the inspiral, merger and ringdown of binary black holes

    NASA Astrophysics Data System (ADS)

    Ghosh, Abhirup; Johnson-McDaniel, Nathan K.; Ghosh, Archisman; Kant Mishra, Chandra; Ajith, Parameswaran; Del Pozzo, Walter; Berry, Christopher P. L.; Nielsen, Alex B.; London, Lionel

    2018-01-01

    Advanced LIGO’s recent observations of gravitational waves (GWs) from merging binary black holes have opened up a unique laboratory to test general relativity (GR) in the highly relativistic regime. One of the tests used to establish the consistency of the first LIGO event with a binary black hole merger predicted by GR was the inspiral-merger-ringdown consistency test. This involves inferring the mass and spin of the remnant black hole from the inspiral (low-frequency) part of the observed signal and checking for the consistency of the inferred parameters with the same estimated from the post-inspiral (high-frequency) part of the signal. Based on the observed rate of binary black hole mergers, we expect the advanced GW observatories to observe hundreds of binary black hole mergers every year when operating at their design sensitivities, most of them with modest signal to noise ratios (SNRs). Anticipating such observations, this paper shows how constraints from a large number of events with modest SNRs can be combined to produce strong constraints on deviations from GR. Using kludge modified GR waveforms, we demonstrate how this test could identify certain types of deviations from GR if such deviations are present in the signal waveforms. We also study the robustness of this test against reasonable variations of a variety of different analysis parameters.

  4. 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.

  5. 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.

  6. 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.

  7. The 1984 eclipse of the symbiotic binary SY Muscae

    NASA Technical Reports Server (NTRS)

    Kenyon, S. J.; Michalitisianos, A. G.; Lutz, J. H.; Kafatos, M.

    1985-01-01

    Data from IUE spectra obtained with the 10 x 20-arcsec aperture on May 13, 1984, and optical spectrophotometry obtained with an SIT vidicon on the 1.5-m telescope at CTIO on April 29-May 1, 1984, are reported for the symbiotic binary SY Mus. The data are found to be consistent with a model of a red-giant secondary of 60 solar radii which completely eclipses the hot primary every 627 d but only partially eclipses the 75-solar-radius He(+) region surrounding the primary. The distance to SY Mus is estimated as 1.3 kpc. It is suggested that the large Balmer decrement in eclipse, with (H-alpha)/(H-beta) = 8.3 and (H-beta)/(H-gamma) = 1.5, is associated with an electron density of about 10 to the 10th/cu cm.

  8. Orbital Period Increase in ES Ceti

    NASA Astrophysics Data System (ADS)

    de Miguel, Enrique; Patterson, Joseph; Kemp, Jonathan; Myers, Gordon; Rea, Robert; Krajci, Thomas; Monard, Berto; Cook, Lewis M.

    2018-01-01

    We report a long-term study of the eclipse times in the 10 minute helium binary ES Ceti. The binary period increases rapidly, with P/\\dot{P}=6.2× {10}6 years. This is consistent with the assumption that gravitational radiation (GR) drives the mass transfer, and it appears to be the first dynamical evidence that GR is indeed the driver of evolution in this class of very old cataclysmic variables—the AM Canum Venaticorum stars.

  9. Rotating and Binary Stars in General Relativit

    NASA Astrophysics Data System (ADS)

    Shapiro, Stuart

    The inspiral and coalescence of compact binary stars is one of the most challenging problems in theoretical astrophysics. Only recently have advances in numerical relativity made it possible to explore this topic in full general relativity (GR). The mergers of compact binaries have important consequences for the detection of gravitational waves. In addition, the coalescence of binary neutron stars (NSNSs) and binary black-hole neutron stars (BHNSs) may hold the key for resolving other astrophysical puzzles, such as the origin of short-hard gamma-ray bursts (GRBs). While simulations of these systems in full GR are now possible, only the most idealized treatments have been performed to date. More detailed physics, including magnetic fields, black hole spin, a realistic hot, nuclear equation of state and neutrino transport must be incorporated. Only then will we be able to identify reliably future sources that may be detected simultaneously in gravitational waves and as GRBs. Likewise, the coalescence of binary black holes (BHBHs) is now a solved problem in GR, but only in vacuum. Simulating the coalescence of BHBHs in the gaseous environments likely to be found in nearby galaxy cores or in merging galaxies is crucial to identifying an electromagnetic signal that might accompany the gravitational waves produced during the merger. The coalescence of a binary white dwarf-neutron star (WDNS) has only recently been treated in GR, but GR is necessary to explore tidal disruption scenarios in which the capture of WD debris by the NS may lead to catastrophic collapse. Alternatively, the NS may survive and the merger might result in the formation of pulsar planets. The stability of rotating neutron stars in these and other systems has not been fully explored in GR, and the final fate of unstable stars has not been determined in many cases, especially in the presence of magnetic fields and differential rotation. These systems will be probed observationally by current NASA instruments, such as HST, CHANDRA, SWIFT and FERMI, and by future NASA detectors, such as NuStar, ASTRO-H, GEMS, JWST, and, possibly, GEN-X and SGO (a Space-Based Gravitational-Wave Observatory). Treating all of these phenomena theoretically requires the same computational machinery: a fully relativistic code that simultaneously solves Einstein s equations for the gravitational field, Maxwell s equations for the electromagnetic field and the equations of relativistic magnetohydrodynamics for the plasma, all in three spatial dimensions plus time. Recent advances we have made in constructing such a code now make it possible for us to solve these fundamental, closely related computational problems, some for the first time.

  10. Recent Observations of the Neglected Southern Eclipsing Binary Systems V343 Cen, UY Mus, HT Aps, and V1961 Sgr

    NASA Astrophysics Data System (ADS)

    Faulkner, D. R.; Samec, R. G.; Stoddard, M. L.; McKenzie, R.; Rebar, D.; Lavoie, G. D.; Moody, S.; Miller, J.; Van Hamme, W.

    2002-12-01

    As a part of our continuing search for solar type binaries with impacting gas streams, we present light curves of V343 Cen, UY Mus, HT Aps, and V1961 Sgr. These are all neglected variables whose observing histories show little or no observations since their discovery. The CCD observations were taken at the 0.9-m at CTI0 in the UBVRI Johnson-Cousins system. The observations were taken in on 2002, May 31-June 8 and 2001, May 16 - 23 respectively. UY Mus is a near contact binary with a large difference in eclipse depths of V = 0.67 mag. Otherwise the curve appears symmetric. The times of minimum light determined from our data are HJD Min I = 242047.62316(6) and Min II = 2452050.4874(3) where the value in parentheses is the standard error in the last decimal place. V1961 Sgr (GCVS 6848 485) is a W UMa binary with a difference in eclipse depths of V = 0.11 mag and a possible variable spot area causing a V = 0.04 mag variation in MAX I from night to night. HT Aps is a near contact solar type binary with a large difference in eclipse depths of V= 0.47 mag and a somewhat asymmetric (difference in maxima, V= 0.4 mag) light curve. It is a possibly a candidate for a binary with a gas stream. One time of minimum light determined from our data is HJD Min I = 2452331.63725 (12). V343 Cen is a near contact binary with a large difference in eclipse depths of V= 0.42 mag and distortions that give evidence of a gas stream collision. The difference in maxima is V = 0.07 mag. The curve shows little variation over the 4 day interval of observation. Light curves analyses, new period determinations and photometric data will be presented for these variables. Acknowledgements: We wish to thank the American Astronomical Society for their continued support of our undergraduate research programs through their small research grants. Faulkner and Samec were visiting Astronomers, Cerro Tololo InterAmerican Observatory, National Optical Astronomical Observatories, which are operated by the Association of Universities for Research in Astronomy, Inc. under contract with the National Science Foundation.

  11. Wind asymmetry imprint in the UV light curves of the symbiotic binary SY Mus

    NASA Astrophysics Data System (ADS)

    Shagatova, N.; Skopal, A.

    2017-06-01

    Context. Light curves (LCs) of some symbiotic stars show a different slope of the ascending and descending branch of their minimum profile. The origin of this asymmetry is not well understood. Aims: We explain this effect in the ultraviolet LCs of the symbiotic binary SY Mus. Methods: We model the continuum fluxes in the spectra obtained by the International Ultraviolet Explorer at ten wavelengths, from 1280 to 3080 Å. We consider that the white dwarf radiation is attenuated by H0 atoms, H- ions, and free electrons in the red giant wind. Variation in the nebular component is approximated by a sine wave along the orbit as suggested by spectral energy distribution models. The model includes asymmetric wind velocity distribution and the corresponding ionization structure of the binary. Results: We determined distribution of the H0 and H+, as well as upper limits of H- and H0 column densities in the neutral and ionized region at the selected wavelengths as functions of the orbital phase. Corresponding models of the LCs match well the observed continuum fluxes. In this way, we suggested the main UV continuum absorbing (scattering) processes in the circumbinary environment of S-type symbiotic stars. Conclusions: The asymmetric profile of the ultraviolet LCs of SY Mus is caused by the asymmetric distribution of the circumstellar matter at the near-orbital-plane area. Table 1 is only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/602/A71

  12. 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 .

  13. A Gamma-Ray Burst Model Via Compressional Heating of Binary Neutron Stars

    NASA Astrophysics Data System (ADS)

    Salmonson, J. D.; Wilson, J. R.; Mathews, G. J.

    1998-12-01

    We present a model for gamma-ray bursts based on the compression of neutron stars in close binary systems. General relativistic (GR) simulations of close neutron star binaries have found compression of the neutron stars estimated to produce 1053 ergs of thermal neutrinos on a timescale of seconds. The hot neutron stars will emit neutrino pairs which will partially recombine to form 1051 to 1052 ergs of electron-positron (e^-e^+) pair plasma. GR hydrodynamic computational modeling of the e^-e^+ plasma flow and recombination yield a gamma-ray burst in good agreement with general characteristics (duration ~10 seconds, spectrum peak energy ~100 keV, total energy ~1051 ergs) of many observed gamma-ray bursts.

  14. A massive pulsar in a compact relativistic binary.

    PubMed

    Antoniadis, John; Freire, Paulo C C; Wex, Norbert; Tauris, Thomas M; Lynch, Ryan S; van Kerkwijk, Marten H; Kramer, Michael; Bassa, Cees; Dhillon, Vik S; Driebe, Thomas; Hessels, Jason W T; Kaspi, Victoria M; Kondratiev, Vladislav I; Langer, Norbert; Marsh, Thomas R; McLaughlin, Maura A; Pennucci, Timothy T; Ransom, Scott M; Stairs, Ingrid H; van Leeuwen, Joeri; Verbiest, Joris P W; Whelan, David G

    2013-04-26

    Many physically motivated extensions to general relativity (GR) predict substantial deviations in the properties of spacetime surrounding massive neutron stars. We report the measurement of a 2.01 ± 0.04 solar mass (M⊙) pulsar in a 2.46-hour orbit with a 0.172 ± 0.003 M⊙ white dwarf. The high pulsar mass and the compact orbit make this system a sensitive laboratory of a previously untested strong-field gravity regime. Thus far, the observed orbital decay agrees with GR, supporting its validity even for the extreme conditions present in the system. The resulting constraints on deviations support the use of GR-based templates for ground-based gravitational wave detectors. Additionally, the system strengthens recent constraints on the properties of dense matter and provides insight to binary stellar astrophysics and pulsar recycling.

  15. Topology of black hole binary-single interactions

    NASA Astrophysics Data System (ADS)

    Samsing, Johan; Ilan, Teva

    2018-05-01

    We present a study on how the outcomes of binary-single interactions involving three black holes (BHs) distribute as a function of the initial conditions; a distribution we refer to as the topology. Using a N-body code that includes BH finite sizes and gravitational wave (GW) emission in the equation of motion (EOM), we perform more than a million binary-single interactions to explore the topology of both the Newtonian limit and the limit at which general relativistic (GR) effects start to become important. From these interactions, we are able to describe exactly under which conditions BH collisions and eccentric GW capture mergers form, as well as how GR in general modifies the Newtonian topology. This study is performed on both large- and microtopological scales. We further describe how the inclusion of GW emission in the EOM naturally leads to scenarios where the binary-single system undergoes two successive GW mergers.

  16. General Relativity solutions in modified gravity

    NASA Astrophysics Data System (ADS)

    Motohashi, Hayato; Minamitsuji, Masato

    2018-06-01

    Recent gravitational wave observations of binary black hole mergers and a binary neutron star merger by LIGO and Virgo Collaborations associated with its optical counterpart constrain deviation from General Relativity (GR) both on strong-field regime and cosmological scales with high accuracy, and further strong constraints are expected by near-future observations. Thus, it is important to identify theories of modified gravity that intrinsically possess the same solutions as in GR among a huge number of theories. We clarify the three conditions for theories of modified gravity to allow GR solutions, i.e., solutions with the metric satisfying the Einstein equations in GR and the constant profile of the scalar fields. Our analysis is quite general, as it applies a wide class of single-/multi-field scalar-tensor theories of modified gravity in the presence of matter component, and any spacetime geometry including cosmological background as well as spacetime around black hole and neutron star, for the latter of which these conditions provide a necessary condition for no-hair theorem. The three conditions will be useful for further constraints on modified gravity theories as they classify general theories of modified gravity into three classes, each of which possesses i) unique GR solutions (i.e., no-hair cases), ii) only hairy solutions (except the cases that GR solutions are realized by cancellation between singular coupling functions in the Euler-Lagrange equations), and iii) both GR and hairy solutions, for the last of which one of the two solutions may be selected dynamically.

  17. 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.

  18. Optimizing the experimental design using the house mouse (Mus musculus L.) as a model for determining grain feeding preferences

    USDA-ARS?s Scientific Manuscript database

    Technical Abstract: BACKGROUND: There is little research evaluating flavor preferences among wheat varieties. We previously demonstrated that mice exert very strong preferences when given binary mixtures of wheat varieties. We plan to utilize mice to identify varieties and genes associated with pref...

  19. Stress Increases Peripheral Axon Growth and Regeneration through Glucocorticoid Receptor-Dependent Transcriptional Programs

    PubMed Central

    Alexander, Jessica K.; Madalena, Kathryn M.; Motti, Dario; Quach, Tam; Zha, Alicia; Webster Marketon, Jeanette

    2017-01-01

    Abstract Stress and glucocorticoid (GC) release are common behavioral and hormonal responses to injury or disease. In the brain, stress/GCs can alter neuron structure and function leading to cognitive impairment. Stress and GCs also exacerbate pain, but whether a corresponding change occurs in structural plasticity of sensory neurons is unknown. Here, we show that in female mice (Mus musculus) basal GC receptor (Nr3c1, also known as GR) expression in dorsal root ganglion (DRG) sensory neurons is 15-fold higher than in neurons in canonical stress-responsive brain regions (M. musculus). In response to stress or GCs, adult DRG neurite growth increases through mechanisms involving GR-dependent gene transcription. In vivo, prior exposure to an acute systemic stress increases peripheral nerve regeneration. These data have broad clinical implications and highlight the importance of stress and GCs as novel behavioral and circulating modifiers of neuronal plasticity. PMID:28828403

  20. Formation of Tidal Captures and Gravitational Wave Inspirals in Binary-single Interactions

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

    Samsing, Johan; MacLeod, Morgan; Ramirez-Ruiz, Enrico

    We perform the first systematic study of how dynamical stellar tides and general relativistic (GR) effects affect the dynamics and outcomes of binary-single interactions. For this, we have constructed an N -body code that includes tides in the affine approximation, where stars are modeled as self-similar ellipsoidal polytropes, and GR corrections using the commonly used post-Newtonian formalism. Using this numerical formalism, we are able resolve the leading effect from tides and GR across several orders of magnitude in both stellar radius and initial target binary separation. We find that the main effect from tides is the formation of two-body tidalmore » captures that form during the chaotic and resonant evolution of the triple system. The two stars undergoing the capture spiral in and merge. The inclusion of tides can thus lead to an increase in the stellar coalescence rate. We also develop an analytical framework for calculating the cross section of tidal inspirals between any pair of objects with similar mass. From our analytical and numerical estimates, we find that the rate of tidal inspirals relative to collisions increases as the initial semimajor axis of the target binary increases and the radius of the interacting tidal objects decreases. The largest effect is therefore found for triple systems hosting white dwarfs and neutron stars (NSs). In this case, we find the rate of highly eccentric white dwarf—NS mergers to likely be dominated by tidal inspirals. While tidal inspirals occur rarely, we note that they can give rise to a plethora of thermonuclear transients, such as Ca-rich transients.« less

  1. Infrared Spectroscopy of Symbiotic Stars. XI. Orbits for Southern S-type Systems: Hen 3-461, SY Mus, Hen 3-828, AND AR Pav

    NASA Astrophysics Data System (ADS)

    Fekel, Francis C.; Hinkle, Kenneth H.; Joyce, Richard R.; Wood, Peter R.

    2017-01-01

    Employing new infrared radial velocities, we have computed spectroscopic orbits of the cool giants in four southern S-type symbiotic systems. The orbits for two of the systems, Hen 3-461 and Hen 3-828, have been determined for the first time, while orbits of the other two, SY Mus and AR Pav, have previously been determined. For the latter two systems, we compare our results with those in the literature. The low mass of the secondary of SY Mus suggests that it has gone through a common envelope phase. Hen 3-461 has an orbital period of 2271 days, one of the longest currently known for S-type symbiotic systems. That period is very different from the orbital period proposed previously from its photometric variations. The other three binaries have periods between 600 and 700 day, values that are typical for S-type symbiotic orbits. Basic properties of the M giant components and the distance to each system are determined.

  2. INFRARED SPECTROSCOPY OF SYMBIOTIC STARS. XI. ORBITS FOR SOUTHERN S-TYPE SYSTEMS: HEN 3-461, SY MUS, HEN 3-828, AND AR PAV

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

    Fekel, Francis C.; Hinkle, Kenneth H.; Joyce, Richard R.

    Employing new infrared radial velocities, we have computed spectroscopic orbits of the cool giants in four southern S-type symbiotic systems. The orbits for two of the systems, Hen 3-461 and Hen 3-828, have been determined for the first time, while orbits of the other two, SY Mus and AR Pav, have previously been determined. For the latter two systems, we compare our results with those in the literature. The low mass of the secondary of SY Mus suggests that it has gone through a common envelope phase. Hen 3-461 has an orbital period of 2271 days, one of the longest currently known for S-type symbiotic systems.more » That period is very different from the orbital period proposed previously from its photometric variations. The other three binaries have periods between 600 and 700 day, values that are typical for S-type symbiotic orbits. Basic properties of the M giant components and the distance to each system are determined.« less

  3. Physical Parameters of Components in Close Binary Systems: IV

    NASA Astrophysics Data System (ADS)

    Gazeas, K. D.; Baran, A.; Niarchos, P.; Zola, S.; Kreiner, J. M.; Ogloza, W.; Rucinski, S. M.; Zakrzewski, B.; Siwak, M.; Pigulski, A.; Drozdz, M.

    2005-03-01

    The paper presents new geometric, photometric and absolute parameters, derived from combined spectroscopic and photometric solutions, for ten contact binary systems. The analysis shows that three systems (EF Boo, GM Dra and SW Lac) are of W-type with shallow to moderate contact. Seven systems (V417 Aql, AH Aur, YY CrB, UX Eri, DZ Psc, GR Vir and NN Vir) are of A-type in a deep contact configuration. For six systems (V417 Aql, YY CrB, GM Dra, UX Eri, SW Lac and GR Vir) a spot model is introduced to explain the O'Connell effect in their light curves. The photometric and geometric elements of the systems are combined with the spectroscopic data taken at David Dunlap Observatory to yield the absolute parameters of the components.

  4. 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).

  5. Testing Modified Gravity Theories via Wide Binaries and GAIA

    NASA Astrophysics Data System (ADS)

    Pittordis, Charalambos; Sutherland, Will

    2018-06-01

    The standard ΛCDM model based on General Relativity (GR) including cold dark matter (CDM) is very successful at fitting cosmological observations, but recent non-detections of candidate dark matter (DM) particles mean that various modified-gravity theories remain of significant interest. The latter generally involve modifications to GR below a critical acceleration scale ˜10-10 m s-2. Wide-binary (WB) star systems with separations ≳ 5 kAU provide an interesting test for modified gravity, due to being in or near the low-acceleration regime and presumably containing negligible DM. Here, we explore the prospects for new observations pending from the GAIA spacecraft to provide tests of GR against MOND or TeVes-like theories in a regime only partially explored to date. In particular, we find that a histogram of (3D) binary relative velocities, relative to equilibrium circular velocity predicted from the (2D) projected separation predicts a rather sharp feature in this distribution for standard gravity, with an 80th (90th) percentile value close to 1.025 (1.14) with rather weak dependence on the eccentricity distribution. However, MOND/TeVeS theories produce a shifted distribution, with a significant increase in these upper percentiles. In MOND-like theories without an external field effect, there are large shifts of order unity. With the external field effect included, the shifts are considerably reduced to ˜0.04 - 0.08, but are still potentially detectable statistically given reasonably large samples and good control of contaminants. In principle, followup of GAIA-selected wide binaries with ground-based radial velocities accurate to ≲ 0.03 { km s^{-1}} should be able to produce an interesting new constraint on modified-gravity theories.

  6. TIGER: A data analysis pipeline for testing the strong-field dynamics of general relativity with gravitational wave signals from coalescing compact binaries

    NASA Astrophysics Data System (ADS)

    Agathos, M.; Del Pozzo, W.; Li, T. G. F.; Van Den Broeck, C.; Veitch, J.; Vitale, S.

    2014-04-01

    The direct detection of gravitational waves with upcoming second-generation gravitational wave observatories such as Advanced LIGO and Advanced Virgo will allow us to probe the genuinely strong-field dynamics of general relativity (GR) for the first time. We have developed a data analysis pipeline called TIGER (test infrastructure for general relativity), which uses signals from compact binary coalescences to perform a model-independent test of GR. In this paper we focus on signals from coalescing binary neutron stars, for which sufficiently accurate waveform models are already available which can be generated fast enough on a computer that they can be used in Bayesian inference. By performing numerical experiments in stationary, Gaussian noise, we show that for such systems, TIGER is robust against a number of unmodeled fundamental, astrophysical, and instrumental effects, such as differences between waveform approximants, a limited number of post-Newtonian phase contributions being known, the effects of neutron star tidal deformability on the orbital motion, neutron star spins, and instrumental calibration errors.

  7. Orbital period changes of OB-type contact binaries and their implications for the triplicity, formation and evolution of this type of binary stars

    NASA Astrophysics Data System (ADS)

    Qian, S.-B.; Kreiner, J. M.; Liu, L.; He, J.-J.; Zhu, L.-Y.; Yuan, J.-Z.; Dai, Z.-B.

    2007-08-01

    Orbital period variations of NINE well-observed OB-type contact binary stars, LY Aur, BH Cen, V382 CYg, V729 Cyg, AW Lac, TU Mus, RZ Pyx, V701 Sco and CT Tau, are investigated in detail. Of the nine systems, V701 Sco and CT Tau are two contact binaries containing twin components with a mass ratio of unit, LY Aur and V729 Cyg have the longest period among contact binary stars (P=4.0 and 6.6 days, respectively), and BH Cen and V701 Sco are the members of two extremely young galactic cluster IC 2994 and NGC 6383. It is discovered that, apart from the two systems with twin components (V701 Sco and CT Tau), the orbital periods of the rest SEVEN binary stars show a long-term increase. This is different from the situations of the late-type (W UMa-type) contact binaries where both secular period increase and decrease are usually encountered, indicating that magnetic field may play an important role in causing the long-term period decrease of W UMa-type contact binary stars. The fact that no long-term continuous period variations were found for V701 Sco and CT Tau may suggest that contact binary with twin components can be in an equilibrium. Based on the rates of period changes (dP/dt) of the SEVEN sample binary stars, statistical relations between dP/dt and orbital period (P) and the mean density of the secondary component were found. Our results suggest that the period increases of the short-period systems (P<2 days) may be mainly caused by a mass transfer from the less massive component to the more massive one, while for the long-period ones (P>2 days), LY Aur and V729 Cyg, their period increases may be resulted from a combination of stellar wind and mass transfer from the secondary to the primary. Meanwhile, cyclic period changes are found for all of the nine binary systems. Those periodic variations can be plausibly explained as the results of light-travel time effects suggesting that they are triple systems. The astrophysical parameters of the tertiary components in the nine systems have been determined. The tertiary components in the seven binaries, BH Cen, V382 Cyg, AW Lac, TU Mus, RZ Pyx, V701 Sco and CT Tau, may be invisible, while those in LY Aur and V729 Cyg may be the fainter visual companions in the two systems. It is possible that the tertiary components in those binaries played an important role for the formations and evolutions of the contact configurations by bringing angular momentum out from the central systems. Thus they have initial short period and can evolve into a contact configuration in a short timescale.

  8. Black Hole Accretion Discs on a Moving Mesh

    NASA Astrophysics Data System (ADS)

    Ryan, Geoffrey

    2017-01-01

    We present multi-dimensional numerical simulations of black hole accretion disks relevant for the production of electromagnetic counterparts to gravitational wave sources. We perform these simulations with a new general relativistic version of the moving-mesh magnetohydrodynamics code DISCO which we will present. This open-source code, GR-DISCO uses an orbiting and shearing mesh which moves with the dominant flow velocity, greatly improving the numerical accuracy of the thermodynamic variables in supersonic flows while also reducing numerical viscosity and greatly increasing computational efficiency by allowing for a larger time step. We have used GR-DISCO to study black hole accretion discs subject to gravitational torques from a binary companion, relevant for both current and future supermassive binary black hole searches and also as a possible electromagnetic precursor mechanism for LIGO events. Binary torques in these discs excite spiral shockwaves which effectively transport angular momentum in the disc and propagate through the innermost stable orbit, leading to stress corresponding to an alpha-viscosity of 10-2. We also present three-dimensional GRMHD simulations of neutrino dominated accretion flows (NDAFs) occurring after a binary neutron star merger in order to elucidate the conditions for electromagnetic transient production accompanying these gravitational waves sources expected to be detected by LIGO in the near future.

  9. NICER and MAXI Observations of Two Large X-ray Flares from RS CVn Binaries

    NASA Astrophysics Data System (ADS)

    Drake, Stephen A.; Hamaguchi, Kenji; Corcoran, Michael Francis; Iwakiri, Wataru; Sasaki, Ryo; Kawai, Hiroki; Tsuboi, Yohko; Enoto, Teruaki; NICER Science Team

    2018-01-01

    NICER has observed two giant X-ray flares on the active binary systems, GT Mus and UX Ari, in response to their detections by the MAXI all-sky X-ray monitor onboard the ISS, with a delay of about a day in each case. The large effective area of the NICER X-ray optics means that high signal-to-noise spectra with more than 200,000 counts were obtained in relatively short exposures totaling less than an hour in each set of observations.MAXI detected a transient of 5.5 x 10^-10 erg/s/cm2 at the position of the active RS CVn binary GT Mus (G5/8 III + ?) early on 2017 July 19. NICER started its observations about 1 day later, and intermittently monitored the decay for the next 2.5 days, accumulating about 1,600 seconds exposure. The NICER light curve shows a smooth, gradual flux decline by a factor of two for the first 2 days, followed by an apparent flattening in the last half day. The dominant plasma temperature remained at ~40 million K during this period, suggesting an ongoing continuous heating during the decay phase.NICER also followed up another MAXI-detected flare in October 2017, this one from the nearby active system, UX Ari. NICER's X-ray spectrum shows clear neon and oxygen lines, while the emissionfrom iron ions is not as prominent as it is in most flares, implying an abundance of only ~10% solar which is significantly lower than previous inferred coronal Fe abundances for this star, although this result is dependent on the NICER gain correction.

  10. Agrobacterium-mediated transformation of Fraxinus pennsylvanica hypocotyls and plant regeneration

    Treesearch

    Ningxia Du; Paula M. Pijut

    2009-01-01

    A genetic transformation protocol for green ash (Fraxinus pennsylvanica) hypocotyl explants was developed. Green ash hypocotyls were transformed using Agrobacterium tumefaciens strain EHA105 harboring binary vector pq35GR containing the neomycin phosphotransferase (nptII) and β-glucuronidase (GUS) fusion...

  11. 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.

  12. Probing Strong-field General Relativity with Gravitational Waves

    NASA Astrophysics Data System (ADS)

    Pretorius, Frans

    We are on the verge of a new era in astrophysics as a world-wide effort to observe the universe with gravitational waves takes hold---ground based laser interferometers (Hz to kHz), pulsar timing (micro to nano Hz), measurements of polarization of the cosmic microwave background (sub-nano Hz), and the planned NASA/ESA mission LISA (.1 mHz to .1 Hz). This project will study the theoretical nature of gravitational waves (GWs) emitted by two sources in the LISA band, namely supermassive-black-hole (SMBH) binary mergers, and extreme-mass-ratio-inspirals (EMRI's)---the merger of a stellar mass black hole, neutron star, or white dwarf with a SMBH. The primary goal will be to ascertain how well LISA, by observing these sources, could answer the following related questions about the fundamental nature of strong-field gravity: Does Einstein's theory of general relativity (GR) describe the geometry of black holes in the universe? What constraints can GW observations of SMBH mergers and EMRIs place on alternative theories of gravity? If there are deviations from GR, are there statistics that could give indications of a deviation if sources are detected using a search strategy based solely on GR waveforms? The primary reasons for focusing on LISA sources to answer these questions are (a) binary SMBH mergers could be detected by LISA with exquisitely high signal-to- noise, allowing enough parameters of the system to be accurately extracted to perform consistency checks of the underlying theory, (b) EMRIs will spend numerous orbits close to the central black hole, and thus will be quite sensitive to even small near-horizon deviations from GR. One approach to develop the requisite knowledge and tools to answer these questions is to study a concrete, theoretically viable alternative to GR. We will focus on the dynamical variant of Chern-Simons modified gravity (CSMG), which is interesting for several reasons, chief among which are (1) that CSMG generically arises in both string theory and loop quantum gravity, and (2) that although CSMG is consistent with all present day tests of GR, it still allows for significant, near-horizon deformations in the geometry of rotating (Kerr) black holes. Here is a brief list of the steps and research methodology we will employ:
(i) Obtain the equivalent of the full Kerr solution in CSMG using numerical methods. (ii) Explore the structure of GWs emitted by EMRIs about the CS rotating black hole solution. Given simulated LISA noise curves, we can then address the questions posed above within the context of CSMG. (iii) Simulate the latter stages of comparable mass SMBH binary mergers in CSMG by numerically solving the full CSMG field equations to learn about highly dynamical, non- linear GR deformations. We can then repeat the analysis of (ii). (iv) Study whether CSMG GWs fit in the recently proposed parameterized post- Einsteinian (ppE) framework, to study generic deviations from GR in a statistical fashion. One can then repeat the analysis of (ii) but within the ppE scheme. We believe this proposed work is of significance and import to both the objectives of this solicitation, and the interests of NASA---knowing the nature of strong-field gravity will be one of the keys to unraveling the origin of the universe, and will tell us how black holes behave and interact with their environs, the details of which are important in understanding the formation and evolution of structure in the universe. Furthermore, these questions are best suited to be answered by LISA, a planned joint NASA-ESA mission. The ultimate success of LISA is very much dependent on (amongst other things) how well the community understands the complete nature of gravitational wave sources.

  13. [A description of children and adolescents with somatic unexplained physical symptoms in a Dutch mental health care institution].

    PubMed

    Kouijzer, M E J; Loman, F; van der Feltz-Cornelis, C M

    2013-01-01

    Medically unexplained symptoms (MUS) occur frequently in children and adolescents. Treatment of MUS in children and adolescents takes place mainly in mental health care (MHC) institutions, as does the treatment of adults with MUS. However, there is hardly any literature about the prevalence of MUS in children and adolescents in MHC. To study the prevalence of MUS in children and adolescents in Dutch MHC. Comparisons were drawn between children and adolescents with MUS and those without MUS who had been referred to a Dutch MHC institution. Children and adolescents with MUS had more anxiety and depression and more introvert personality characteristics than children and adolescents without MUS. However, the quality of life of children and adolescents with MUS was similar to that of children and adolescents without MUS. One in five children and adolescents in Dutch MHC had MUS. These children and adolescents had introverted personality characteristics and showed anxious and depressed behavior, withdrawn-depressed behavior, and thought problems. The quality of life of children and adolescents with MUS and those without MUS was below average.

  14. RESONANT POST-NEWTONIAN ECCENTRICITY EXCITATION IN HIERARCHICAL THREE-BODY SYSTEMS

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

    Naoz, Smadar; Kocsis, Bence; Loeb, Abraham

    2013-08-20

    We study the secular, hierarchical three-body problem to first-order in a post-Newtonian expansion of general relativity (GR). We expand the first-order post-Newtonian Hamiltonian to leading-order in the ratio of the semi-major axis of the two orbits. In addition to the well-known terms that correspond to the GR precession of the inner and outer orbits, we find a new secular post-Newtonian interaction term that can affect the long-term evolution of the triple. We explore the parameter space for highly inclined and eccentric systems, where the Kozai-Lidov mechanism can produce large-amplitude oscillations in the eccentricities. The standard lore, i.e., that GR effectsmore » suppress eccentricity, is only consistent with the parts of phase space where the GR timescales are several orders of magnitude shorter than the secular Newtonian one. In other parts of phase space, however, post-Newtonian corrections combined with the three-body ones can excite eccentricities. In particular, for systems where the GR timescale is comparable to the secular Newtonian timescales, the three-body interactions give rise to a resonant-like eccentricity excitation. Furthermore, for triples with a comparable-mass inner binary, where the eccentric Kozai-Lidov mechanism is suppressed, post-Newtonian corrections can further increase the eccentricity and lead to orbital flips even when the timescale of the former is much longer than the timescale of the secular Kozai-Lidov quadrupole perturbations.« less

  15. Maltose Uptake by the Novel ABC Transport System MusEFGK2I Causes Increased Expression of ptsG in Corynebacterium glutamicum

    PubMed Central

    Henrich, Alexander; Kuhlmann, Nora; Eck, Alexander W.; Krämer, Reinhard

    2013-01-01

    The Gram-positive Corynebacterium glutamicum efficiently metabolizes maltose by a pathway involving maltodextrin and glucose formation by 4-α-glucanotransferase, glucose phosphorylation by glucose kinases, and maltodextrin degradation via maltodextrin phosphorylase and α-phosphoglucomutase. However, maltose uptake in C. glutamicum has not been investigated. Interestingly, the presence of maltose in the medium causes increased expression of ptsG in C. glutamicum by an unknown mechanism, although the ptsG-encoded glucose-specific EII permease of the phosphotransferase system itself is not required for maltose utilization. We identified the maltose uptake system as an ABC transporter encoded by musK (cg2708; ATPase subunit), musE (cg2705; substrate binding protein), musF (cg2704; permease), and musG (cg2703; permease) by combination of data obtained from characterization of maltose uptake and reanalyses of transcriptome data. Deletion of the mus gene cluster in C. glutamicum Δmus abolished maltose uptake and utilization. Northern blotting and reverse transcription-PCR experiments revealed that musK and musE are transcribed monocistronically, whereas musF and musG are part of an operon together with cg2701 (musI), which encodes a membrane protein of unknown function with no homologies to characterized proteins. Characterization of growth and [14C]maltose uptake in the musI insertion strain C. glutamicum IMcg2701 showed that musI encodes a novel essential component of the maltose ABC transporter of C. glutamicum. Finally, ptsG expression during cultivation on different carbon sources was analyzed in the maltose uptake-deficient strain C. glutamicum Δmus. Indeed, maltose uptake by the novel ABC transport system MusEFGK2I is required for the positive effect of maltose on ptsG expression in C. glutamicum. PMID:23543710

  16. Raman spectroscopic study of synthetic pyrope-grossular garnets: structural implications

    NASA Astrophysics Data System (ADS)

    Du, Wei; Han, Baofu; Clark, Simon Martin; Wang, Yichuan; Liu, Xi

    2018-02-01

    A study of the effect of substitution of Mg and Ca in garnet solid solution (Grtss) was carried out using Raman spectroscopy to probe changes to the crystal lattice. The garnet solid solutions with composition changing along pyrope (Py; Mg3Al2Si3O12) and grossular (Gr; Ca3Al2Si3O12) binary were synthesized from glass at 6 GPa and 1400 °C and a second series of Grtss with composition Py40Gr60 were synthesized at 6 GPa but different temperatures from 1000 to 1400 °C. Raman mode assignments were made based on a comparison with the two end members pyrope and grossular, which show consistent result with literature study on single crystals data. The correlation between the Raman mode frequencies and compositional changes along the pyrope-grossular binary suggests a two-mode behavior for Mg and Ca cations in the garnet structure. The full widths at half-maximum of selected Raman modes increase on moving away from the end members and are about double the end-member values in the mid-position, where the frequencies closely linearly change with composition. The frequencies of the translational modes of the SiO4 tetrahedron (T(SiO4)) show large deviations from linearity indicating a strong kinematic coupling with the translational modes of the Ca and Mg cations. The anomalies in T(SiO4) are linked to mixing unit cell volume, suggesting that the nonlinear mixing volume behavior along the pyrope-grossular binary is related to the resistance of the Si-O bond to expansion and compression, which is caused by substitution of Mg and Ca cations in the dodecahedral sites. Annealing temperature also shows effect on Raman mode frequencies, but the main factor controlling the changes in mode frequencies along pyrope-grossular binary is composition.

  17. Use of repetitive DNA sequences to distinguish Mus musculus and Mus caroli cells by in situ hybridization.

    PubMed

    Siracusa, L D; Chapman, V M; Bennett, K L; Hastie, N D; Pietras, D F; Rossant, J

    1983-02-01

    Mammalian chimaeras have proved useful for investigating early steps in embryonic development. However, a complete clonal analysis of cell lineages has been limited by the lack of a marker which is ubiquitous and can distinguish parental cell types in situ. We have developed a cell marker system which fulfils these criteria. Chimaeric mice were successfully produced from two mouse species which possess sufficient genetic differences to allow unequivocal identification of parental cell types. DNA-DNA in situ hybridization with cloned, species-specific sequences was performed to distinguish the parental cell types. We have identified a cloned, Mus musculus satellite DNA sequence which shows hybridization differences between Mus musculus and Mus caroli DNA. This clone was used a a probe in in situ hybridizations to bone marrow chromosomes from Mus musculus, Mus caroli, and an interspecific F1 hybrid. The clone could qualitatively distinguish Mus musculus from Mus caroli chromosomes after in situ hybridization, even when they were derived from the same F1 hybrid cell. Quantitation of this hybridization to interphase nuclei from bone marrow spreads indicates that the probe can successfully distinguish Mus musculus from Mus caroli cells and can determine the percentage contribution of Mus musculus in mixtures of bone marrow cells of these species and in chimaeric bone marrow cell preparations.

  18. Phosphorylation by CK2 regulates MUS81/EME1 in mitosis and after replication stress.

    PubMed

    Palma, Anita; Pugliese, Giusj Monia; Murfuni, Ivana; Marabitti, Veronica; Malacaria, Eva; Rinalducci, Sara; Minoprio, Anna; Sanchez, Massimo; Mazzei, Filomena; Zolla, Lello; Franchitto, Annapaola; Pichierri, Pietro

    2018-06-01

    The MUS81 complex is crucial for preserving genome stability through the resolution of branched DNA intermediates in mitosis. However, untimely activation of the MUS81 complex in S-phase is dangerous. Little is known about the regulation of the human MUS81 complex and how deregulated activation affects chromosome integrity. Here, we show that the CK2 kinase phosphorylates MUS81 at Serine 87 in late-G2/mitosis, and upon mild replication stress. Phosphorylated MUS81 interacts with SLX4, and this association promotes the function of the MUS81 complex. In line with a role in mitosis, phosphorylation at Serine 87 is suppressed in S-phase and is mainly detected in the MUS81 molecules associated with EME1. Loss of CK2-dependent MUS81 phosphorylation contributes modestly to chromosome integrity, however, expression of the phosphomimic form induces DSBs accumulation in S-phase, because of unscheduled targeting of HJ-like DNA intermediates, and generates a wide chromosome instability phenotype. Collectively, our findings describe a novel regulatory mechanism controlling the MUS81 complex function in human cells. Furthermore, they indicate that, genome stability depends mainly on the ability of cells to counteract targeting of branched intermediates by the MUS81/EME1 complex in S-phase, rather than on a correct MUS81 function in mitosis.

  19. Destabilization of strigolactone receptor DWARF14 by binding of ligand and E3-ligase signaling effector DWARF3

    PubMed Central

    Zhao, Li-Hua; Zhou, X Edward; Yi, Wei; Wu, Zhongshan; Liu, Yue; Kang, Yanyong; Hou, Li; de Waal, Parker W; Li, Suling; Jiang, Yi; Scaffidi, Adrian; Flematti, Gavin R; Smith, Steven M; Lam, Vinh Q; Griffin, Patrick R; Wang, Yonghong; Li, Jiayang; Melcher, Karsten; Xu, H Eric

    2015-01-01

    Strigolactones (SLs) are endogenous hormones and exuded signaling molecules in plant responses to low levels of mineral nutrients. Key mediators of the SL signaling pathway in rice include the α/β-fold hydrolase DWARF 14 (D14) and the F-box component DWARF 3 (D3) of the ubiquitin ligase SCFD3 that mediate ligand-dependent degradation of downstream signaling repressors. One perplexing feature is that D14 not only functions as the SL receptor but is also an active enzyme that slowly hydrolyzes diverse natural and synthetic SLs including GR24, preventing the crystallization of a binary complex of D14 with an intact SL as well as the ternary D14/SL/D3 complex. Here we overcome these barriers to derive a structural model of D14 bound to intact GR24 and identify the interface that is required for GR24-mediated D14-D3 interaction. The mode of GR24-mediated signaling, including ligand recognition, hydrolysis by D14, and ligand-mediated D14-D3 interaction, is conserved in structurally diverse SLs. More importantly, D14 is destabilized upon the binding of ligands and D3, thus revealing an unusual mechanism of SL recognition and signaling, in which the hormone, the receptor, and the downstream effectors are systematically destabilized during the signal transduction process. PMID:26470846

  20. Distributing Earthquakes Among California's Faults: A Binary Integer Programming Approach

    NASA Astrophysics Data System (ADS)

    Geist, E. L.; Parsons, T.

    2016-12-01

    Statement of the problem is simple: given regional seismicity specified by a Gutenber-Richter (G-R) relation, how are earthquakes distributed to match observed fault-slip rates? The objective is to determine the magnitude-frequency relation on individual faults. The California statewide G-R b-value and a-value are estimated from historical seismicity, with the a-value accounting for off-fault seismicity. UCERF3 consensus slip rates are used, based on geologic and geodetic data and include estimates of coupling coefficients. The binary integer programming (BIP) problem is set up such that each earthquake from a synthetic catalog spanning millennia can occur at any location along any fault. The decision vector, therefore, consists of binary variables, with values equal to one indicating the location of each earthquake that results in an optimal match of slip rates, in an L1-norm sense. Rupture area and slip associated with each earthquake are determined from a magnitude-area scaling relation. Uncertainty bounds on the UCERF3 slip rates provide explicit minimum and maximum constraints to the BIP model, with the former more important to feasibility of the problem. There is a maximum magnitude limit associated with each fault, based on fault length, providing an implicit constraint. Solution of integer programming problems with a large number of variables (>105 in this study) has been possible only since the late 1990s. In addition to the classic branch-and-bound technique used for these problems, several other algorithms have been recently developed, including pre-solving, sifting, cutting planes, heuristics, and parallelization. An optimal solution is obtained using a state-of-the-art BIP solver for M≥6 earthquakes and California's faults with slip-rates > 1 mm/yr. Preliminary results indicate a surprising diversity of on-fault magnitude-frequency relations throughout the state.

  1. 50 CFR 665.15 - Prohibitions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., 665.399, or 665.599, any bottomfish MUS, crustacean MUS, western Pacific pelagic MUS, precious coral, seamount groundfish or coral reef ecosystem MUS. (m) Fail to comply with a term or condition governing the...

  2. 50 CFR 665.15 - Prohibitions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., 665.399, or 665.599, any bottomfish MUS, crustacean MUS, western Pacific pelagic MUS, precious coral, seamount groundfish or coral reef ecosystem MUS. (m) Fail to comply with a term or condition governing the...

  3. 50 CFR 665.15 - Prohibitions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ..., 665.399, or 665.599, any bottomfish MUS, crustacean MUS, western Pacific pelagic MUS, precious coral, seamount groundfish or coral reef ecosystem MUS. (m) Fail to comply with a term or condition governing the...

  4. 50 CFR 665.15 - Prohibitions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., 665.399, or 665.599, any bottomfish MUS, crustacean MUS, western Pacific pelagic MUS, precious coral, seamount groundfish or coral reef ecosystem MUS. (m) Fail to comply with a term or condition governing the...

  5. 50 CFR 665.15 - Prohibitions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ..., 665.399, or 665.599, any bottomfish MUS, crustacean MUS, western Pacific pelagic MUS, precious coral, seamount groundfish or coral reef ecosystem MUS. (m) Fail to comply with a term or condition governing the...

  6. The DNA repair endonuclease Mus81 facilitates fast DNA replication in the absence of exogenous damage

    PubMed Central

    Fu, Haiqing; Martin, Melvenia M.; Regairaz, Marie; Huang, Liang; You, Yang; Lin, Chi-Mei; Ryan, Michael; Kim, RyangGuk; Shimura, Tsutomu; Pommier, Yves; Aladjem, Mirit I.

    2015-01-01

    The Mus81 endonuclease resolves recombination intermediates and mediates cellular responses to exogenous replicative stress. Here, we show that Mus81 also regulates the rate of DNA replication during normal growth by promoting replication fork progression while reducing the frequency of replication initiation events. In the absence of Mus81 endonuclease activity, DNA synthesis is slowed and replication initiation events are more frequent. In addition, Mus81 deficient cells fail to recover from exposure to low doses of replication inhibitors and cell viability is dependent on the XPF endonuclease. Despite an increase in replication initiation frequency, cells lacking Mus81 use the same pool of replication origins as Mus81-expressing cells. Therefore, decelerated DNA replication in Mus81 deficient cells does not initiate from cryptic or latent origins not used during normal growth. These results indicate that Mus81 plays a key role in determining the rate of DNA replication without activating a novel group of replication origins. PMID:25879486

  7. MUS81 is associated with cell proliferation and cisplatin sensitivity in serous ovarian cancer

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

    Xie, Suhong; Zheng, Hui; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai

    The dysfunction of DNA damage repair (DDR) pathway contributes to tumorigenesis and drug-resistance in cancer. MUS81 is a member of the conserved xeroderma pigmentosum group F (XPF) family protein of endonucleases, which is important to the DDR pathway. However, the role of MUS81 in the development of ovarian cancer remains uncertain. To explore the expression of MUS81 and its association to serous ovarian cancer (SOC), 43 biopsies of SOC patients were detected by qRT-PCR, and 29 specimens were further performed by immunohistochemistry analysis. Here, we observed that MUS81 was over-expressed in SOC tissues at both transcript and protein levels, andmore » the expression level of MUS81 protein in ovarian cancer cell lines was also higher than that in human normal ovarian surface epithelial cell line (HOSEpiC). We also found that down-regulation of MUS81 expression in ovarian cancer cells inhibited cell proliferation and colony formation ability, and influenced cell cycle progression. Moreover, inhibition of MUS81 expression induced cellular senescence and enhanced the antitumor effect of cisplatin. Down-regulation of MUS81 expression could suppress the growth and development of SOC. These results indicate that MUS81 might play important roles in the progression of SOC and influence the antitumor effect of cisplatin. - Highlights: • MUS81 was overexpression in serous ovarian cancer (SOC). • Meanwhile down-regulation of inhibited cell proliferation and influenced cell cycle progression. • Inhibition of MUS81 induced cell cellular senescence and enhanced the antitumor effect of cisplatin. • Down-regulation of MUS81 expression could suppress the growth and development of SOC.« less

  8. First-principles study on the thermal expansion of Ni-X binary alloys based on the quasi-harmonic Debye model

    NASA Astrophysics Data System (ADS)

    Shin, Yongjin; Jung, Woo-Sang; Lee, Young-Su

    2016-11-01

    In this study, we use the quasi-harmonic Debye model to predict the coefficient of thermal expansion of Ni- X binary alloys. The method bridges between the macroscopic elastic behavior and thermodynamic properties of materials without an expensive calculation of the volume dependence of the phonon density of states. Furthermore, the Grüneisen parameter is derived from the volume dependence of the Debye temperature, which is calculated from the first-principles elastic stiffness constants. The experimental coefficient of thermal expansion (CTE) of pure nickel is well reproduced, especially in the low temperature region. Among the few alloying elements tested, Al is predicted to slightly decrease the CTE whereas Mo and W are more effective in reducing the CTE. For the cases of Ni-X binary alloy systems, where the variation in the CTE is relatively small, the method used here appears to perform better than certain other formulations that rely entirely on the energy vs. volume relationship.

  9. Medically Unexplained and Explained Physical Symptoms in the General Population: Association with Prevalent and Incident Mental Disorders

    PubMed Central

    van Eck van der Sluijs, Jonna; ten Have, Margreet; Rijnders, Cees; van Marwijk, Harm; de Graaf, Ron; van der Feltz-Cornelis, Christina

    2015-01-01

    Background Clinical studies have shown that Medically Unexplained Symptoms (MUS) are related to common mental disorders. It is unknown how often common mental disorders occur in subjects who have explained physical symptoms (PHY), MUS or both, in the general population, what the incidence rates are, and whether there is a difference between PHY and MUS in this respect. Aim To study the prevalence and incidence rates of mood, anxiety and substance use disorders in groups with PHY, MUS and combined MUS and PHY compared to a no-symptoms reference group in the general population. Method Data were derived from the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2), a nationally representative face-to-face survey of the general population aged 18-64 years. We selected subjects with explained physical symptoms only (n=1952), with MUS only (n=177), with both MUS and PHY (n=209), and a reference group with no physical symptoms (n=4168). The assessment of common mental disorders was through the Composite International Diagnostic Interview 3.0. Multivariate logistic regression analyses were used to examine the association between group membership and the prevalence and first-incidence rates of comorbid mental disorders, adjusted for socio-demographic characteristics. Results MUS were associated with the highest prevalence rates of mood and anxiety disorders, and combined MUS and PHY with the highest prevalence rates of substance disorder. Combined MUS and PHY were associated with a higher incidence rate of mood disorder only (OR 2.9 (95%CI:1.27,6.74)). Conclusion In the general population, PHY, MUS and the combination of both are related to mood and anxiety disorder, but odds are highest for combined MUS and PHY in relation to substance use disorder. Combined MUS and PHY are related to a greater incidence of mood disorder. These findings warrant further research into possibilities to improve recognition and early intervention in subjects with combined MUS and PHY. PMID:25853676

  10. Resolved Companions of Cepheids: Testing the Candidates with X-Ray Observations

    NASA Astrophysics Data System (ADS)

    Evans, Nancy Remage; Pillitteri, Ignazio; Wolk, Scott; Karovska, Margarita; Tingle, Evan; Guinan, Edward; Engle, Scott; Bond, Howard E.; Schaefer, Gail H.; Mason, Brian D.

    2016-04-01

    We have made XMM-Newton observations of 14 Galactic Cepheids that have candidate resolved (≥5″) companion stars based on our earlier HST Wide Field Camera 3 (WFC3) imaging survey. Main-sequence stars that are young enough to be physical companions of Cepheids are expected to be strong X-ray producers in contrast to field stars. XMM-Newton exposures were set to detect essentially all companions hotter than spectral type M0 (corresponding to 0.5 M⊙). The large majority of our candidate companions were not detected in X-rays, and hence are not confirmed as young companions. One resolved candidate (S Nor #4) was unambiguously detected, but the Cepheid is a member of a populous cluster. For this reason, it is likely that S Nor #4 is a cluster member rather than a gravitationally bound companion. Two further Cepheids (S Mus and R Cru) have X-ray emission that might be produced by either the Cepheid or the candidate resolved companion. A subsequent Chandra observation of S Mus shows that the X-rays are at the location of the Cepheid/spectroscopic binary. R Cru and also V659 Cen (also X-ray bright) have possible companions closer than 5″ (the limit for this study) which are the likely sources of X-rays. One final X-ray detection (V473 Lyr) has no known optical companion, so the prime suspect is the Cepheid itself. It is a unique Cepheid with a variable amplitude. The 14 stars that we observed with XMM constitute 36% of the 39 Cepheids found to have candidate companions in our HST/WFC3 optical survey. No young probable binary companions were found with separations of ≥5″ or 4000 au. Based on observations obtained with XMM-Newton, an ESA science mission with instruments and contributions directly funded by ESA Member States and the USA (NASA).

  11. One normal void and residual following MUS surgery is all that is necessary in most patients.

    PubMed

    Ballard, Paul; Shawer, Sami; Anderson, Colette; Khunda, Aethele

    2018-04-01

    There is considerable variation worldwide on how the assessment of voiding function is performed following midurethral sling (MUS) surgery. There is potentially a financial cost, and reduction in efficiency when patient discharge is delayed. Using our current practice of two normal void and residual (V&R) readings before discharge, the aim of this retrospective study was to evaluate the likelihood of an abnormal second V&R test if the first V&R test was normal in order to determine if a policy of discharge after only one satisfactory V&R test is reasonable. Data from 400 patients who had had MUS surgery with or without other procedures were collected. Our unit protocol included two consecutive voids of greater than 200 ml with residuals less than 150 ml before discharge. The patients were divided into the following groups: MUS only, MUS plus anterior colporrhaphy (AR) plus any other procedures (MUS/AR), and MUS with any non-AR procedures (MUS+). Complete datasets were available for 335 patients. Once inadequate tests (low volume voids <200 ml) had been excluded (28% overall), the likelihood of an abnormal second V&R test if the first test was normal was 7.1% overall, but 3.6% for MUS, 11.5% for MUS/AR and 8.6% for MUS+. The findings in the MUS-only group indicate that it is probably safe to discharge patients after one satisfactory V&R test, as long as safety measures such as 'open access' are available so that patients have unhindered readmission if problems arise.

  12. Damage tolerance protein Mus81 associates with the FHA1 domain of checkpoint kinase Cds1.

    PubMed

    Boddy, M N; Lopez-Girona, A; Shanahan, P; Interthal, H; Heyer, W D; Russell, P

    2000-12-01

    Cds1, a serine/threonine kinase, enforces the S-M checkpoint in the fission yeast Schizosaccharomyces pombe. Cds1 is required for survival of replicational stress caused by agents that stall replication forks, but how Cds1 performs these functions is largely unknown. Here we report that the forkhead-associated-1 (FHA1) protein-docking domain of Cds1 interacts with Mus81, an evolutionarily conserved damage tolerance protein. Mus81 has an endonuclease homology domain found in the XPF nucleotide excision repair protein. Inactivation of mus81 reveals a unique spectrum of phenotypes. Mus81 enables survival of deoxynucleotide triphosphate starvation, UV radiation, and DNA polymerase impairment. Mus81 is essential in the absence of Bloom's syndrome Rqh1 helicase and is required for productive meiosis. Genetic epistasis studies suggest that Mus81 works with recombination enzymes to properly replicate damaged DNA. Inactivation of Mus81 triggers a checkpoint-dependent delay of mitosis. We propose that Mus81 is involved in the recruitment of Cds1 to aberrant DNA structures where Cds1 modulates the activity of damage tolerance enzymes.

  13. Testing Chern-Simons modified gravity with observations of extreme-mass-ratio binaries

    NASA Astrophysics Data System (ADS)

    Canizares, P.; Gair, J. R.; Sopuerta, C. F.

    2012-06-01

    Extreme-Mass-Ratio Inspirals (EMRIs) are one of the most promising sources of gravitational waves (GWs) for space-based detectors like the Laser Interferometer Space Antenna (LISA). EMRIs consist of a compact stellar object orbiting around a massive black hole (MBH). Since EMRI signals are expected to be long lasting (containing of the order of hundred thousand cycles), they will encode the structure of the MBH gravitational potential in a precise way such that features depending on the theory of gravity governing the system may be distinguished. That is, EMRI signals may be used to test gravity and the geometry of black holes. However, the development of a practical methodology for computing the generation and propagation of GWs from EMRIs in theories of gravity different than General Relativity (GR) has only recently begun. In this paper, we present a parameter estimation study of EMRIs in a particular modification of GR, which is described by a four-dimensional Chern-Simons (CS) gravitational term. We focus on determining to what extent a space-based GW observatory like LISA could distinguish between GR and CS gravity through the detection of GWs from EMRIs.

  14. Clostridial Binary Toxins: Basic Understandings that Include Cell Surface Binding and an Internal "Coup de Grâce".

    PubMed

    Stiles, Bradley G

    2017-01-01

    Clostridium species can make a remarkable number of different protein toxins, causing many diverse diseases in humans and animals. The binary toxins of Clostridium botulinum, C. difficile, C. perfringens, and C. spiroforme are one group of enteric-acting toxins that attack the actin cytoskeleton of various cell types. These enterotoxins consist of A (enzymatic) and B (cell binding/membrane translocation) components that assemble on the targeted cell surface or in solution, forming a multimeric complex. Once translocated into the cytosol via endosomal trafficking and acidification, the A component dismantles the filamentous actin-based cytoskeleton via mono-ADP-ribosylation of globular actin. Knowledge of cell surface receptors and how these usurped, host-derived molecules facilitate intoxication can lead to novel ways of defending against these clostridial binary toxins. A molecular-based understanding of the various steps involved in toxin internalization can also unveil therapeutic intervention points that stop the intoxication process. Furthermore, using these bacterial proteins as medicinal shuttle systems into cells provides intriguing possibilities in the future. The pertinent past and state-of-the-art present, regarding clostridial binary toxins, will be evident in this chapter.

  15. Joint Molecule Resolution Requires the Redundant Activities of MUS-81 and XPF-1 during Caenorhabditis elegans Meiosis

    PubMed Central

    O'Neil, Nigel J.; Martin, Julie S.; Youds, Jillian L.; Ward, Jordan D.; Petalcorin, Mark I. R.; Rose, Anne M.; Boulton, Simon J.

    2013-01-01

    The generation and resolution of joint molecule recombination intermediates is required to ensure bipolar chromosome segregation during meiosis. During wild type meiosis in Caenorhabditis elegans, SPO-11-generated double stranded breaks are resolved to generate a single crossover per bivalent and the remaining recombination intermediates are resolved as noncrossovers. We discovered that early recombination intermediates are limited by the C. elegans BLM ortholog, HIM-6, and in the absence of HIM-6 by the structure specific endonuclease MUS-81. In the absence of both MUS-81 and HIM-6, recombination intermediates persist, leading to chromosome breakage at diakinesis and inviable embryos. MUS-81 has an additional role in resolving late recombination intermediates in C. elegans. mus-81 mutants exhibited reduced crossover recombination frequencies suggesting that MUS-81 is required to generate a subset of meiotic crossovers. Similarly, the Mus81-related endonuclease XPF-1 is also required for a subset of meiotic crossovers. Although C. elegans gen-1 mutants have no detectable meiotic defect either alone or in combination with him-6, mus-81 or xpf-1 mutations, mus-81;xpf-1 double mutants are synthetic lethal. While mus-81;xpf-1 double mutants are proficient for the processing of early recombination intermediates, they exhibit defects in the post-pachytene chromosome reorganization and the asymmetric disassembly of the synaptonemal complex, presumably triggered by crossovers or crossover precursors. Consistent with a defect in resolving late recombination intermediates, mus-81; xpf-1 diakinetic bivalents are aberrant with fine DNA bridges visible between two distinct DAPI staining bodies. We were able to suppress the aberrant bivalent phenotype by microinjection of activated human GEN1 protein, which can cleave Holliday junctions, suggesting that the DNA bridges in mus-81; xpf-1 diakinetic oocytes are unresolved Holliday junctions. We propose that the MUS-81 and XPF-1 endonucleases act redundantly to process late recombination intermediates to form crossovers during C. elegans meiosis. PMID:23874209

  16. Organization of the motor-unit pool for different directions of isometric contraction of the first dorsal interosseous muscle.

    PubMed

    Lei, Yuming; Suresh, Nina L; Rymer, William Z; Hu, Xiaogang

    2018-01-01

    Muscle force generation involves recruitment and firing rate modulation of motor units (MUs). The control of MUs in producing multidirectional forces remains unclear. We studied MU recruitment and firing properties, recorded from the first dorsal interosseous muscle, for 3 different directions of contraction: abduction; abduction/flexion combination; and flexion. MUs were recruited systematically at higher threshold force during flexion. Larger MUs were recruited and firing rates of MUs were lower during abduction. There was an orderly recruitment of MUs according to MU size regardless of contraction direction, obeying the "size principle." Firing rates of earlier-recruited MUs were consistently higher than later-recruited MUs, affirming the "onion-skin" property. Our findings suggest that the size principle and onion-skin organization together provide a general description of MU recruitment patterns and firing properties. The directional alternations of MU control properties likely reflect changes in neural drive to the muscle. Muscle Nerve 57: E85-E93, 2018. © 2017 Wiley Periodicals, Inc.

  17. Experts' opinions on the management of medically unexplained symptoms in primary care. A qualitative analysis of narrative reviews and scientific editorials.

    PubMed

    Heijmans, Mieke; Olde Hartman, Tim C; van Weel-Baumgarten, Evelyn; Dowrick, Christopher; Lucassen, Peter L B J; van Weel, Chris

    2011-08-01

    The feasibility as well as the suitability of several therapies for medically unexplained symptoms (MUS) in primary care applied by the family physician (FP) appeared to be low. FPs need effective and acceptable strategies to manage these functionally impaired patients. To review important and effective elements in the treatment of patients with MUS in primary care according to experts in MUS research. We performed a systematic search of narrative reviews and scientific editorials in Medline and PsycINFO and triangulated our findings by conducting a focus group with MUS experts. We included 7 scientific editorials and 23 narrative reviews. According to MUS experts, the most important elements in the treatment of MUS are creating a safe therapeutic environment, generic interventions (such as motivational interviewing, giving tangible explanations, reassurance and regularly scheduled appointments) and specific interventions (such as cognitive approaches and pharmacotherapy). Furthermore, MUS experts indicate that a multi-component approach in which these three important elements are combined are most helpful for patients with MUS. In contrast to most specific interventions, opinions of MUS experts regarding generic interventions and creating a safe therapeutic relationship seem to be more based on theory and experience than on quantitative research. MUS experts highlight the importance of generic interventions and doctor-patient communication and relationship. However, studies showing the effectiveness of these elements in the management of MUS in primary care is still scarce. Research as well as medical practice should focus more on these non-specific aspects of the medical consultation.

  18. Nova Mus 2008 = QY Mus

    NASA Astrophysics Data System (ADS)

    Templeton, Matthew R.

    2008-10-01

    Nova Mus 2008 = QY Mus was discovered by William Liller, Vina del Mar, Chile, on 2008 September 28.998 UT at magnitude 8.6 (Tech Pan film + orange filter). The position is RA = 13h 16m 36.44s , Dec = -67d 36m 47.8s (from P. Nelson). This object was announced as a nova in IAU Circular 8990 (Daniel W.E. Green, editor). The nova classification was determined using low-resolution spectra by W. Liller indicating the presence of broad H-alpha lines at least 2300 angstroms wide. Several observers confirmed the nova and provided photometry. The position above was provided by Peter Nelson (Ellinbank, Vic., Aus.), and is averaged from four separate exposures (rms error approx. 0.4 arcseconds). The GCVS team have formally designated Nova Mus 2008 as QY MUS. Observations should be reported to the AAVSO International Database as QY MUS.

  19. Psychosocial correlates, psychological distress, and quality of life in patients with medically unexplained symptoms: a primary care study in Karachi, Pakistan.

    PubMed

    Husain, Muhammad Ishrat; Chaudhry, Nasim; Morris, Julie; Zafar, Shehla Naeem; Jaffery, Farhat; Rahman, Raza; Duddu, Venu; Husain, Nusrat

    2015-01-01

    To examine the psychosocial correlates and association of psychological distress and quality of life (QOL) in patients with medically unexplained symptoms (MUS) compared to those with medically explained symptoms (MES) in a primary care setting in Karachi, Pakistan. A cross-sectional study of 472 patients attending GP clinics between March and August 2009 in Karachi. Participants completed questionnaires to assess demographic details, somatic symptoms, anxiety, depression, and QOL. The patients' GP recorded whether the presenting complaint was medically unexplained or medically explained. MUS subjects in our study were more educated, had better social support and fewer financial problems, were less depressed and had a better QOL than subjects who had medically explained symptoms (non-MUS). Both groups (MUS and non-MUS) were comparable in terms of anxiety and number of somatic symptoms, but non-MUS subjects were more depressed than the MUS group. In a regression analysis, the number of somatic symptoms and lower levels of anxiety predicted poorer QOL in this sample. Whether these symptoms were medically explained (or not) did not seem to contribute significantly to the QOL. Our findings confirm that even in the developing world, patients with MUS are common among primary care attendees. However, patients with MUS in urban Karachi, Pakistan may differ from Western MUS subjects in the role of stress, support, and anxiety in their presentation, and may be reflective of a conceptually different group of difficulties. © 2015, The Author(s).

  20. Multi-User Space Link Extension (SLE) System

    NASA Technical Reports Server (NTRS)

    Perkins, Toby

    2013-01-01

    The Multi-User Space (MUS) Link Extension system, a software and data system, provides Space Link Extension (SLE) users with three space data transfer services in timely, complete, and offline modes as applicable according to standards defined by the Consultative Committee for Space Data Systems (CCSDS). MUS radically reduces the schedule, cost, and risk of implementing a new SLE user system, minimizes operating costs with a lights-out approach to SLE, and is designed to require no sustaining engineering expense during its lifetime unless changes in the CCSDS SLE standards, combined with new provider implementations, force changes. No software modification to MUS needs to be made to support a new mission. Any systems engineer with Linux experience can begin testing SLE user service instances with MUS starting from a personal computer (PC) within five days. For flight operators, MUS provides a familiar-looking Web page for entering SLE configuration data received from SLE. Operators can also use the Web page to back up a space mission's entire set of up to approximately 500 SLE service instances in less than five seconds, or to restore or transfer from another system the same amount of data from a MUS backup file in about the same amount of time. Missions operate each MUS SLE service instance independently by sending it MUS directives, which are legible, plain ASCII strings. MUS directives are usually (but not necessarily) sent through a TCP-IP (Transmission Control Protocol Internet Protocol) socket from a MOC (Mission Operations Center) or POCC (Payload Operations Control Center) system, under scripted control, during "lights-out" spacecraft operation. MUS permits the flight operations team to configure independently each of its data interfaces; not only commands and telemetry, but also MUS status messages to the MOC. Interfaces can use single- or multiple-client TCP/IP server sockets, TCP/IP client sockets, temporary disk files, the system log, or standard in, standard out, or standard error as applicable. By defining MUS templates in ASCII, the flight operations team can include any MUS system variable in telemetry or command headers or footers, and/or in status messages. Data fields can be arranged within messages in different sequences, according to the mission s needs. The only constraints imposed are on the format of MUS directive strings, and some bare minimum logical requirements that must be met in order for MUS to read the mission control center's spacecraft command inputs. The MUS system imposes no limits or constraints on the numbers and combinations of missions and SLE service instances that it will support simultaneously. At any time, flight operators may add, change, delete, bind, connect, or disconnect.

  1. Dbf4-dependent kinase and the Rtt107 scaffold promote Mus81-Mms4 resolvase activation during mitosis.

    PubMed

    Princz, Lissa N; Wild, Philipp; Bittmann, Julia; Aguado, F Javier; Blanco, Miguel G; Matos, Joao; Pfander, Boris

    2017-03-01

    DNA repair by homologous recombination is under stringent cell cycle control. This includes the last step of the reaction, disentanglement of DNA joint molecules (JMs). Previous work has established that JM resolving nucleases are activated specifically at the onset of mitosis. In case of budding yeast Mus81-Mms4, this cell cycle stage-specific activation is known to depend on phosphorylation by CDK and Cdc5 kinases. Here, we show that a third cell cycle kinase, Cdc7-Dbf4 (DDK), targets Mus81-Mms4 in conjunction with Cdc5-both kinases bind to as well as phosphorylate Mus81-Mms4 in an interdependent manner. Moreover, DDK-mediated phosphorylation of Mms4 is strictly required for Mus81 activation in mitosis, establishing DDK as a novel regulator of homologous recombination. The scaffold protein Rtt107, which binds the Mus81-Mms4 complex, interacts with Cdc7 and thereby targets DDK and Cdc5 to the complex enabling full Mus81 activation. Therefore, Mus81 activation in mitosis involves at least three cell cycle kinases, CDK, Cdc5 and DDK Furthermore, tethering of the kinases in a stable complex with Mus81 is critical for efficient JM resolution. © 2017 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

  2. Damage-dependent regulation of MUS81-EME1 by Fanconi anemia complementation group A protein

    PubMed Central

    Benitez, Anaid; Yuan, Fenghua; Nakajima, Satoshi; Wei, Leizhen; Qian, Liangyue; Myers, Richard; Hu, Jennifer J.; Lan, Li; Zhang, Yanbin

    2014-01-01

    MUS81-EME1 is a DNA endonuclease involved in replication-coupled repair of DNA interstrand cross-links (ICLs). A prevalent hypothetical role of MUS81-EME1 in ICL repair is to unhook the damage by incising the leading strand at the 3′ side of an ICL lesion. In this study, we report that purified MUS81-EME1 incises DNA at the 5′ side of a psoralen ICL residing in fork structures. Intriguingly, ICL repair protein, Fanconi anemia complementation group A protein (FANCA), greatly enhances MUS81-EME1-mediated ICL incision. On the contrary, FANCA exhibits a two-phase incision regulation when DNA is undamaged or the damage affects only one DNA strand. Studies using truncated FANCA proteins indicate that both the N- and C-moieties of the protein are required for the incision regulation. Using laser-induced psoralen ICL formation in cells, we find that FANCA interacts with and recruits MUS81 to ICL lesions. This report clarifies the incision specificity of MUS81-EME1 on ICL damage and establishes that FANCA regulates the incision activity of MUS81-EME1 in a damage-dependent manner. PMID:24170812

  3. Crystal structures of the structure-selective nuclease Mus81-Eme1 bound to flap DNA substrates

    PubMed Central

    Gwon, Gwang Hyeon; Jo, Aera; Baek, Kyuwon; Jin, Kyeong Sik; Fu, Yaoyao; Lee, Jong-Bong; Kim, YoungChang; Cho, Yunje

    2014-01-01

    The Mus81-Eme1 complex is a structure-selective endonuclease with a critical role in the resolution of recombination intermediates during DNA repair after interstrand cross-links, replication fork collapse, or double-strand breaks. To explain the molecular basis of 3′ flap substrate recognition and cleavage mechanism by Mus81-Eme1, we determined crystal structures of human Mus81-Eme1 bound to various flap DNA substrates. Mus81-Eme1 undergoes gross substrate-induced conformational changes that reveal two key features: (i) a hydrophobic wedge of Mus81 that separates pre- and post-nick duplex DNA and (ii) a “5′ end binding pocket” that hosts the 5′ nicked end of post-nick DNA. These features are crucial for comprehensive protein-DNA interaction, sharp bending of the 3′ flap DNA substrate, and incision strand placement at the active site. While Mus81-Eme1 unexpectedly shares several common features with members of the 5′ flap nuclease family, the combined structural, biochemical, and biophysical analyses explain why Mus81-Eme1 preferentially cleaves 3′ flap DNA substrates with 5′ nicked ends. PMID:24733841

  4. Mus308 Processes Oxygen and Nitrogen Ethylation DNA Damage in Germ Cells of Drosophila

    PubMed Central

    Díaz-Valdés, Nancy; Comendador, Miguel A.; Sierra, L. María

    2010-01-01

    The D. melanogaster mus308 gene, highly conserved among higher eukaryotes, is implicated in the repair of cross-links and of O-ethylpyrimidine DNA damage, working in a DNA damage tolerance mechanism. However, despite its relevance, its possible role on the processing of different DNA ethylation damages is not clear. To obtain data on mutation frequency and on mutation spectra in mus308 deficient (mus308−) conditions, the ethylating agent diethyl sulfate (DES) was analysed in postmeiotic male germ cells. These data were compared with those corresponding to mus308 efficient conditions. Our results indicate that Mus308 is necessary for the processing of oxygen and N-ethylation damage, for the survival of fertilized eggs depending on the level of induced DNA damage, and for an influence of the DNA damage neighbouring sequence. These results support the role of mus308 in a tolerance mechanism linked to a translesion synthesis pathway and also to the alternative end-joinig system. PMID:20936147

  5. Social characteristics and care needs of older persons with medically unexplained symptoms: a case-control study.

    PubMed

    Hanssen, Denise J C; Oude Voshaar, Richard C; Naarding, Paul; Rabeling-Keus, Inge M; Olde Hartman, Tim C; Lucassen, Peter L B J

    2016-12-01

    Research in younger patients with medically unexplained symptoms (MUS) has shown impairments in social functioning, such as loneliness and a reduced quality of the patient-doctor relationship. As far as we know, no studies have been performed on social functioning in older MUS patients; self-reported care needs of older MUS patients remain unknown. To explore social characteristics and care needs of older persons with chronic MUS, when compared to older persons with chronic medically explained symptoms (MES). Patient characteristics of 107 older persons (>60 years) with chronic MUS were compared to 150 older persons with chronic MES in a case-control design. Participants were recruited via advertisements, general practices and a specialized clinic. All participants completed questionnaires on social functioning; the Camberwell Assessment of Need for the Elderly was used to draw up care needs. Linear regression analyses were performed to explore the association between social characteristics and group (MUS/MES), adjusted for demographic and physical determinants. Multiple chi-square tests were performed to detect between-group differences regarding care needs. After adjustments, older MUS patients were slightly but significantly lonelier, reported a somewhat lower quality of their patient-doctor relationship, but reported equal social support levels when compared to MES patients. MUS patients more often reported unmet care needs regarding health and information provision about their health status. Only small differences in social functioning were found between older MUS and MES patients. Possibly, training future doctors in giving acceptable explanations for the patient's complaints could improve the unmet care need of information provision in older MUS patients. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Measuring engagement with music: development of an informant-report questionnaire.

    PubMed

    Vanstone, Ashley D; Wolf, Michael; Poon, Tina; Cuddy, Lola L

    2016-01-01

    This study describes the development of the Music Engagement Questionnaire (MusEQ), a 35-item scale to measure engagement with music in daily life. Music has implications for well-being and for therapy, notably for individuals living with dementia. A number of excellent scales or questionnaires are now available to measure music engagement. Unlike these scales, the MusEQ may be completed by either the participant or an informant. Study 1 drew on a community-based sample of 391 participants. Exploratory factor analysis revealed six interpretable factors, which formed the basis for construction of six subscales. Study 2 applied the MusEQ to a group of participants with Alzheimer's disease (AD; n = 16) as well as a group of neurotypical older adults (OA; n = 16). Informants completed the MusEQ, and the OA group also completed the self-report version of the MusEQ. Both groups had an interview in which they described the place music had in their lives. These interviews were scored by three independent raters. The MusEQ showed excellent internal consistency. Five of the factor-derived subscales showed good or excellent internal consistency. MusEQ scores were moderately correlated with a global rating of 'musicality' and with music education. There was strong agreement between self-report and informant-report data. MusEQ scores showed a significant positive relationship to independent ratings of music engagement. The MusEQ provides a meaningful and reliable option for measuring music engagement among participants who are unable to complete a self-report questionnaire.

  7. Muscular urinary sphincter: electrically stimulated myoplasty for functional sphincter reconstruction.

    PubMed

    Palacio, M M; Van Aalst, V C; Perez Abadia, G A; Stremel, R W; Werker, P M; Ren, X; Petty, G D; Heilman, S J; Van Savage, J G; Garcia Fernandez, A; Kon, M; Tobin, G R; Barker, J H

    1998-11-01

    To reconstruct an electrically stimulated muscular urinary sphincter (MUS) using a tailored gracilis muscle free flap with intact nerve. Unilateral surgically tailored gracilis muscle free flaps were transferred into the pelvis in eight dogs, leaving the obturator nerve intact. The muscle's pedicle vessels were anastomosed to the inferior epigastric artery and vein in the pelvis and the muscle was wrapped around the bladder neck. Electrodes were inserted into the MUS and connected to a programmable pulse generator. After 8 weeks of training the MUS, the pulse generator was programmed to be "on" for 4 hours and "off' for 15 minutes in a continuous cycle. Urodynamic studies were performed periodically, and at the end of the experiment the MUS and proximal urethra were harvested for histology. Three control dogs had sham operations. All MUS's functioned well following the procedure. Histology of the MUS/urethra complex showed no evidence of stricture. Except for one dog, all urethras were easily catheterized. This electrically stimulated innervated free-flap MUS technique effectively increases bladder outlet resistance without producing urethral obstruction.

  8. Entropy coders for image compression based on binary forward classification

    NASA Astrophysics Data System (ADS)

    Yoo, Hoon; Jeong, Jechang

    2000-12-01

    Entropy coders as a noiseless compression method are widely used as final step compression for images, and there have been many contributions to increase of entropy coder performance and to reduction of entropy coder complexity. In this paper, we propose some entropy coders based on the binary forward classification (BFC). The BFC requires overhead of classification but there is no change between the amount of input information and the total amount of classified output information, which we prove this property in this paper. And using the proved property, we propose entropy coders that are the BFC followed by Golomb-Rice coders (BFC+GR) and the BFC followed by arithmetic coders (BFC+A). The proposed entropy coders introduce negligible additional complexity due to the BFC. Simulation results also show better performance than other entropy coders that have similar complexity to the proposed coders.

  9. Performance Evaluation of UHF Fading Satellite Channel by Simulation for Different Modulation Schemes

    DTIC Science & Technology

    1992-12-01

    views expressed in this thesis are those of the author end do net reflect olicsia policy or pokletsm of the Deperteaset of Defame or the US...utempl u v= cncd (2,1,6,G64,u,zeros(l,12));%Convolutional encoding mm=bm(2,v); %Binary to M-ary conversion clear v u; mm=inter(50,200,mm);%Interleaving (50...save result err B. CNCD.X (CONVOLUTIONAL ENCODER FUNCTION) function (v,vr] - cncd (n,k,m,Gr,u,r) % CONVOLUTIONAL ENCODER % Paul H. Moose % Naval

  10. Tracking motor units longitudinally across experimental sessions with high‐density surface electromyography

    PubMed Central

    Martinez‐Valdes, E.; Negro, F.; Laine, C. M.; Falla, D.; Mayer, F.

    2017-01-01

    Key points Classic motor unit (MU) recording and analysis methods do not allow the same MUs to be tracked across different experimental sessions, and therefore, there is limited experimental evidence on the adjustments in MU properties following training or during the progression of neuromuscular disorders.We propose a new processing method to track the same MUs across experimental sessions (separated by weeks) by using high‐density surface electromyography.The application of the proposed method in two experiments showed that individual MUs can be identified reliably in measurements separated by weeks and that changes in properties of the tracked MUs across experimental sessions can be identified with high sensitivity.These results indicate that the behaviour and properties of the same MUs can be monitored across multiple testing sessions.The proposed method opens new possibilities in the understanding of adjustments in motor unit properties due to training interventions or the progression of pathologies. Abstract A new method is proposed for tracking individual motor units (MUs) across multiple experimental sessions on different days. The technique is based on a novel decomposition approach for high‐density surface electromyography and was tested with two experimental studies for reliability and sensitivity. Experiment I (reliability): ten participants performed isometric knee extensions at 10, 30, 50 and 70% of their maximum voluntary contraction (MVC) force in three sessions, each separated by 1 week. Experiment II (sensitivity): seven participants performed 2 weeks of endurance training (cycling) and were tested pre–post intervention during isometric knee extensions at 10 and 30% MVC. The reliability (Experiment I) and sensitivity (Experiment II) of the measured MU properties were compared for the MUs tracked across sessions, with respect to all MUs identified in each session. In Experiment I, on average 38.3% and 40.1% of the identified MUs could be tracked across two sessions (1 and 2 weeks apart), for the vastus medialis and vastus lateralis, respectively. Moreover, the properties of the tracked MUs were more reliable across sessions than those of the full set of identified MUs (intra‐class correlation coefficients ranged between 0.63—0.99 and 0.39–0.95, respectively). In Experiment II, ∼40% of the MUs could be tracked before and after the training intervention and training‐induced changes in MU conduction velocity had an effect size of 2.1 (tracked MUs) and 1.5 (group of all identified motor units). These results show the possibility of monitoring MU properties longitudinally to document the effect of interventions or the progression of neuromuscular disorders. PMID:28032343

  11. Fasciculations in nerve and muscle disorders - A prospective study of muscle ultrasound compared to electromyography.

    PubMed

    Johansson, M T; Ellegaard, H R; Tankisi, H; Fuglsang-Frederiksen, A; Qerama, E

    2017-11-01

    We examined the clinical utility of muscle ultrasound (MUS) in detecting fasciculations in patients with nerve and muscle disorders (NMD) and investigated the impact on diagnostic sensitivity when combining electromyography (EMG) and MUS. We included 58 consecutive patients suspected to have NMD and 38 healthy subjects (HS). Patients and HS underwent MUS in 14 skeletal and two bulbar muscles and the video recordings of the MUS were anonymised. Only patients underwent EMG. The follow-up diagnoses were: 15 Amyotrophic lateral sclerosis (ALS), 15 polyneuropathy, 14 patients had other diagnoses (disease-control group) and 14 patients had no pathological findings. MUS detected more muscles with fasciculations among ALS patients compared to all other groups. In ALS patients, the dominating pattern of fasciculations was continuous (45%). More proximal muscles showed fasciculations among ALS patients compared to all other patient groups. MUS was more sensitive than EMG in detecting fasciculations (58% vs. 48%). When combining the two methods, the sensitivity in detecting fasciculations increased to 65%. Fasciculations in nine muscles could predict the ALS diagnosis with high sensitivity and specificity. MUS is a sensitive tool in detecting fasciculations in patients with NMD and performs well compared to EMG in diagnosing ALS. MUS may add valuable information in the clinic, especially in diagnosing ALS. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  12. Temperature modulation of the visible and near infrared absorption and scattering coefficients of human skin.

    PubMed

    Khalil, Omar S; Yeh, Shu-Jen; Lowery, Michael G; Wu, Xiaomao; Hanna, Charles F; Kantor, Stanislaw; Jeng, Tzyy-Wen; Kanger, Johannes S; Bolt, Rene A; de Mul, Frits F

    2003-04-01

    We determine temperature effect on the absorption and reduced scattering coefficients (mu(a) and mu(s)(')) of human forearm skin. Optical and thermal simulation data suggest that mu( a) and mu(s)(') are determined within a temperature-controlled depth of approximately 2 mm. Cutaneous mu(s)(') change linearly with temperature. Change in mu(a) was complex and irreversible above body normal temperatures. Light penetration depth (delta) in skin increased on cooling, with considerable person-to-person variations. We attribute the effect of temperature on mu(s)(') to change in refractive index mismatch, and its effect on mu(a) to perfusion changes. The reversible temperature effect on mu (s)(' ) was maintained during more than 90 min. contact between skin and the measuring probe, where temperature was modulated between 38 and 22 degrees C for multiple cycles While temperature modulated mu(s)(' ) instantaneously and reversibly, mu(a) exhibited slower response time and consistent drift. There was a statistically significant upward drift in mu(a) and a mostly downward drift in mu( s)(') over the contact period. The drift in temperature-induced fractional change in mu(s)(') was less statistically significant than the drift in mu(s)('). Deltamu( s)(') values determined under temperature modulation conditions may have less nonspecific drift than mu(s)(') which may have significance for noninvasive determination of analytes in human tissue.

  13. Transvaginal prolapse repair with or without the addition of a midurethral sling in women with genital prolapse and stress urinary incontinence: a randomised trial.

    PubMed

    van der Ploeg, J M; Oude Rengerink, K; van der Steen, A; van Leeuwen, J H S; Stekelenburg, J; Bongers, M Y; Weemhoff, M; Mol, B W; van der Vaart, C H; Roovers, J-P W R

    2015-06-01

    To compare transvaginal prolapse repair combined with midurethral sling (MUS) versus prolapse repair only. Multi-centre randomised trial. Fourteen teaching hospitals in the Netherlands. Women with symptomatic stage two or greater pelvic organ prolapse (POP), and subjective or objective stress urinary incontinence (SUI) without prolapse reduction. Women were randomly assigned to undergo vaginal prolapse repair with or without MUS. Analysis was according to intention to treat. The primary outcome at 12 months' follow-up was the absence of urinary incontinence (UI) assessed with the Urogenital Distress Inventory and treatment for SUI or overactive bladder. Secondary outcomes included complications. One hundred and thirty-four women were analysed at 12 months' follow-up (63 in MUS and 71 in control group). More women in the MUS group reported the absence of UI and SUI; respectively 62% versus 30% UI (relative risk [RR] 2.09; 95% confidence interval [CI] 1.39-3.15) and 78% versus 39% SUI (RR 1.97; 95% CI 1.44-2.71). Fewer women underwent treatment for postoperative SUI in the MUS group (10% versus 37%; RR 0.26; 95% CI 0.11-0.59). In the control group, 12 women (17%) underwent MUS after prolapse surgery versus none in the MUS group. Severe complications were more common in the MUS group, but the difference was not statistically significant (16% versus 6%; RR 2.82; 95% CI 0.93-8.54). Women with prolapse and co-existing SUI are less likely to have SUI after transvaginal prolapse repair with MUS compared with prolapse repair only. However, only 17% of the women undergoing POP surgery needed additional MUS. A well-informed decision balancing risks and benefits of both strategies should be tailored to individual women. © 2015 Royal College of Obstetricians and Gynaecologists.

  14. Partial AZFc duplications not deletions are associated with male infertility in the Yi population of Yunnan Province, China.

    PubMed

    Ye, Jun-jie; Ma, Li; Yang, Li-juan; Wang, Jin-huan; Wang, Yue-li; Guo, Hai; Gong, Ning; Nie, Wen-hui; Zhao, Shu-hua

    2013-09-01

    There are many reports on associations between spermatogenesis and partial azoospermia factor c (AZFc) deletions as well as duplications; however, results are conflicting, possibly due to differences in methodology and ethnic background. The purpose of this study is to investigate the association of AZFc polymorphisms and male infertility in the Yi ethnic population, residents within Yunnan Province, China. A total of 224 infertile patients and 153 fertile subjects were selected in the Yi ethnic population. The study was performed by sequence-tagged site plus/minus (STS+/-) analysis followed by gene dosage and gene copy definition analysis. Y haplotypes of 215 cases and 115 controls were defined by 12 binary markers using single nucleotide polymorphism on Y chromosome (Y-SNP) multiplex assays based on single base primer extension technology. The distribution of Y haplotypes was not significantly different between the case and control groups. The frequencies of both gr/gr (7.6% vs. 8.5%) and b2/b3 (6.3% vs. 8.5%) deletions do not show significant differences. Similarly, single nucleotide variant (SNV) analysis shows no significant difference of gene copy definition between the cases and controls. However, the frequency of partial duplications in the infertile group (4.0%) is significantly higher than that in the control group (0.7%). Further, we found a case with sY1206 deletion which had two CDY1 copies but removed half of DAZ genes. Our results show that male infertility is associated with partial AZFc duplications, but neither gr/gr nor b2/b3 deletions, suggesting that partial AZFc duplications rather than deletions are risk factors for male infertility in Chinese-Yi population.

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

    Chen, Juncheng; Wang, Xiaofeng; Li, Junzheng

    We present extensive optical observations of the normal Type Ic supernova (SN) 2007gr, spanning from about one week before maximum light to more than one year thereafter. The optical light and color curves of SN 2007gr are very similar to those of the broad-lined Type Ic SN 2002ap, but the spectra show remarkable differences. The optical spectra of SN 2007gr are characterized by unusually narrow lines, prominent carbon lines, and slow evolution of the line velocity after maximum light. The earliest spectrum (taken at t = –8 days) shows a possible signature of helium (He I λ5876 at a velocitymore » of ∼19,000 km s{sup –1}). Moreover, the larger intensity ratio of the [O I] λ6300 and λ6364 lines inferred from the early nebular spectra implies a lower opacity of the ejecta shortly after the explosion. These results indicate that SN 2007gr perhaps underwent a less energetic explosion of a smaller-mass Wolf-Rayet star (∼8-9 M{sub ☉}) in a binary system, as favored by an analysis of the progenitor environment through pre-explosion and post-explosion Hubble Space Telescope images. In the nebular spectra, asymmetric double-peaked profiles can be seen in the [O I] λ6300 and Mg I] λ4571 lines. We suggest that the two peaks are contributed by the blueshifted and rest-frame components. The similarity in velocity structure and the different evolution of the strength of the two components favor an aspherical explosion with the ejecta distributed in a torus or disk-like geometry, but inside the ejecta the O and Mg have different distributions.« less

  16. Medically unexplained symptoms, somatisation disorder and hypochondriasis: course and prognosis. A systematic review.

    PubMed

    olde Hartman, Tim C; Borghuis, Machteld S; Lucassen, Peter L B J; van de Laar, Floris A; Speckens, Anne E; van Weel, Chris

    2009-05-01

    To study the course of medically unexplained symptoms (MUS), somatisation disorder, and hypochondriasis, and related prognostic factors. Knowledge of prognostic factors in patients presenting persistent MUS might improve our understanding of the naturalistic course and the identification of patients with a high risk of a chronic course. A comprehensive search of Medline, PsycInfo, CINAHL, and EMBASE was performed to select studies focusing on patients with MUS, somatisation disorder, and hypochondriasis, and assessing prognostic factors. Studies focusing on patients with single-symptom unexplained disorder or distinctive functional somatic syndromes were excluded. A best-evidence synthesis for the interpretation of results was used. Only six studies on MUS, six studies on hypochondriasis, and one study on abridged somatisation could be included. Approximately 50% to 75% of the patients with MUS improve, whereas 10% to 30% of patients with MUS deteriorate. In patients with hypochondriasis, recovery rates vary between 30% and 50%. In studies on MUS and hypochondriasis, we found some evidence that the number of somatic symptoms at baseline influences the course of these conditions. Furthermore, the seriousness of the condition at baseline seemed to influence the prognosis. Comorbid anxiety and depression do not seem to predict the course of hypochondriasis. Due to the limited numbers of studies and their high heterogeneity, there is a lack of rigorous empirical evidence to identify relevant prognostic factors in patients presenting persistent MUS. However, it seems that a more serious condition at baseline is associated with a worse outcome.

  17. Potential of MuS1 Transgenic Tobacco for Phytoremediation of the Urban Soils Contaminated with Cadmium

    NASA Astrophysics Data System (ADS)

    Kim, K. H.; Kim, Y. N.; Kim, S. H.

    2010-05-01

    Urban soils are prone to contamination by trace elements such as Cd, Cu, Pb and Zn. Phytoremediation is one of the attractive remediation methods for soils contaminated with trace elements due to its non-destructive and environmentally-friendly characteristic. Scientists have tried to find hyper-accumulator plants in nature or to develop transgenic plant through genetic engineering. This study was carried out to identify a potential of MuS1 transgenic tobacco for phytoremediation of the urban soils contaminated with Cd. MuS1 is known as a multiple stress related gene with several lines. The previous study using RT-PCR showed that the expression of MuS1 gene in tobacco plant induced tolerance to Cd stress. For this study, MuS1 transgenic tobacco and wild-type tobacco (control) were cultivated in a hydroponic system treated with Cd (0, 50, 100 and 200μM Cd) for 3 weeks. At harvest, both tobacco and nutrient solution were collected and were analyzed for Cd. Effect of Cd treatment on morphological change of the tobacco leaves was also observed by variable-pressure scanning electron microscopy (VP-SEM). The tolerance of MuS1 transgenic tobacco to Cd stress was better than that of wild-type tobacco at all Cd levels. Especially, wild-type tobacco showed chlorosis and withering with 200μM Cd treatment, whereas MuS1 transgenic tobacco gradually recovered from Cd damage. Wild-type tobacco accumulated more Cd (4.65mg per plant) than MuS1 transgenic tobacco (2.37mg per plant) with 200μM Cd treatment. Cd translocation rate from root to leaves was 81.8 % for wild-type tobacco compared to 37.1 % for MuS1 transgenic tobacco. Result of VP-SEM showed that the number of trichome in the leaves for wild-type tobacco increased in comparison with that for untreated samples after 3 weeks, while that for MuS1 transgenic tobacco was not changed by Cd treatment. Results showed that the mechanism of the recovery of the MuS1 tobacco plant was not by high level of Cd uptake and accumulation in the plant but by revealing resistance to Cd through inducing less Cd uptake and/or more Cd immobilization around roots, resulting in less translocation to shoot. In conclusion, this study showed a potential to use MuS1 transgenic tobacco for phytoremediation of the urban soils contaminated with Cd.

  18. 50 CFR 665.425 - Prohibitions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ..., possess or land any Mariana coral reef ecosystem MUS in any low-use MPA as defined in § 665.399 unless: (1...; or (3) The Mariana coral reef ecosystem MUS possessed on board the vessel originated outside the... other documentation. (b) Fish for, take, or retain any Mariana coral reef ecosystem MUS species: (1...

  19. 50 CFR 665.125 - Prohibitions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., possess or land any American Samoa coral reef ecosystem MUS in any low-use MPA as defined in § 665.99... American Samoa coral reef ecosystem MUS possessed on board the vessel originated outside the management... documentation. (b) Fish for, take, or retain any American Samoa coral reef ecosystem MUS species: (1) That is...

  20. 50 CFR 665.125 - Prohibitions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., possess or land any American Samoa coral reef ecosystem MUS in any low-use MPA as defined in § 665.99... American Samoa coral reef ecosystem MUS possessed on board the vessel originated outside the management... documentation. (b) Fish for, take, or retain any American Samoa coral reef ecosystem MUS species: (1) That is...

  1. 50 CFR 665.425 - Prohibitions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., possess or land any Mariana coral reef ecosystem MUS in any low-use MPA as defined in § 665.399 unless: (1...; or (3) The Mariana coral reef ecosystem MUS possessed on board the vessel originated outside the... other documentation. (b) Fish for, take, or retain any Mariana coral reef ecosystem MUS species: (1...

  2. 50 CFR 665.125 - Prohibitions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ..., possess or land any American Samoa coral reef ecosystem MUS in any low-use MPA as defined in § 665.99... American Samoa coral reef ecosystem MUS possessed on board the vessel originated outside the management... documentation. (b) Fish for, take, or retain any American Samoa coral reef ecosystem MUS species: (1) That is...

  3. 50 CFR 665.425 - Prohibitions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., possess or land any Mariana coral reef ecosystem MUS in any low-use MPA as defined in § 665.399 unless: (1...; or (3) The Mariana coral reef ecosystem MUS possessed on board the vessel originated outside the... other documentation. (b) Fish for, take, or retain any Mariana coral reef ecosystem MUS species: (1...

  4. 50 CFR 665.425 - Prohibitions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ..., possess or land any Mariana coral reef ecosystem MUS in any low-use MPA as defined in § 665.399 unless: (1...; or (3) The Mariana coral reef ecosystem MUS possessed on board the vessel originated outside the... other documentation. (b) Fish for, take, or retain any Mariana coral reef ecosystem MUS species: (1...

  5. 50 CFR 665.125 - Prohibitions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ..., possess or land any American Samoa coral reef ecosystem MUS in any low-use MPA as defined in § 665.99... American Samoa coral reef ecosystem MUS possessed on board the vessel originated outside the management... documentation. (b) Fish for, take, or retain any American Samoa coral reef ecosystem MUS species: (1) That is...

  6. 50 CFR 665.125 - Prohibitions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., possess or land any American Samoa coral reef ecosystem MUS in any low-use MPA as defined in § 665.99... American Samoa coral reef ecosystem MUS possessed on board the vessel originated outside the management... documentation. (b) Fish for, take, or retain any American Samoa coral reef ecosystem MUS species: (1) That is...

  7. 50 CFR 665.425 - Prohibitions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., possess or land any Mariana coral reef ecosystem MUS in any low-use MPA as defined in § 665.399 unless: (1...; or (3) The Mariana coral reef ecosystem MUS possessed on board the vessel originated outside the... other documentation. (b) Fish for, take, or retain any Mariana coral reef ecosystem MUS species: (1...

  8. New polymorphic markers in the vicinity of the pearl locus on mouse chromosome 13.

    PubMed

    Xu, H P; Yanak, B L; Wigler, M H; Gorin, M B

    1996-01-01

    We have used a Mus domesticus/-Mus spretus congenic animal that was selected for retention of Mus spretus DNA around the pearl locus to create a highly polymorphic region suitable for screening new markers. Representation difference analysis (RDA) was performed with either DNA from the congenic animal or C57BL/6J as the driver for subtraction. Four clones were identified, characterized, and converted to PCR-based polymorphic markers. Three of the four markers equally subdivide a 10-cM interval containing the pearl locus, with the fourth located centromeric to it. These markers have been placed on the mouse genetic map by use of an interspecific backcross panel between Mus domesticus (C57BL/6J) and Mus spretus generated by The Jackson Laboratory.

  9. What is the problem with medically unexplained symptoms for GPs? A meta-synthesis of qualitative studies.

    PubMed

    Johansen, May-Lill; Risor, Mette Bech

    2017-04-01

    To gain a deeper understanding of challenges faced by GPs when managing patients with MUS. We used meta-ethnography to synthesize qualitative studies on GPs' perception and management of MUS. The problem with MUS for GPs is the epistemological incongruence between dominant disease models and the reality of meeting patients suffering from persistent illness. GPs have used flexible approaches to manage the situation, yet patients and doctors have had parallel negative experiences of being stuck, untrustworthy and helpless. In the face of cognitive incongruence, GPs have strived to achieve relational congruence with their patients. This has led to parallel positive experiences of mutual trust and validation. With more experience, some GPs seem to overcome the incongruences, and later studies point towards a reframing of the MUS problem. For GPs, the challenge with MUS is most importantly at an epistemological level. Hence, a full reframing of the problem of MUS for GPs (and for patients) implies broad changes in basic medical knowledge and education. Short-term: Improve management of patients with MUS by transferring experience-based, reality-adjusted knowledge from senior GPs to juniors. Long-term: Work towards new models of disease that integrate knowledge from all relevant disciplines. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Repeat associated mechanisms of genome evolution and function revealed by the Mus caroli and Mus pahari genomes

    PubMed Central

    Thybert, David; Roller, Maša; Navarro, Fábio C.P.; Fiddes, Ian; Streeter, Ian; Feig, Christine; Martin-Galvez, David; Kolmogorov, Mikhail; Janoušek, Václav; Akanni, Wasiu; Aken, Bronwen; Aldridge, Sarah; Chakrapani, Varshith; Chow, William; Clarke, Laura; Cummins, Carla; Doran, Anthony; Dunn, Matthew; Goodstadt, Leo; Howe, Kerstin; Howell, Matthew; Josselin, Ambre-Aurore; Karn, Robert C.; Laukaitis, Christina M.; Jingtao, Lilue; Martin, Fergal; Muffato, Matthieu; Nachtweide, Stefanie; Quail, Michael A.; Sisu, Cristina; Stanke, Mario; Stefflova, Klara; Van Oosterhout, Cock; Veyrunes, Frederic; Ward, Ben; Yang, Fengtang; Yazdanifar, Golbahar; Zadissa, Amonida; Adams, David J.; Brazma, Alvis; Gerstein, Mark; Paten, Benedict; Pham, Son; Keane, Thomas M.; Odom, Duncan T.; Flicek, Paul

    2018-01-01

    Understanding the mechanisms driving lineage-specific evolution in both primates and rodents has been hindered by the lack of sister clades with a similar phylogenetic structure having high-quality genome assemblies. Here, we have created chromosome-level assemblies of the Mus caroli and Mus pahari genomes. Together with the Mus musculus and Rattus norvegicus genomes, this set of rodent genomes is similar in divergence times to the Hominidae (human-chimpanzee-gorilla-orangutan). By comparing the evolutionary dynamics between the Muridae and Hominidae, we identified punctate events of chromosome reshuffling that shaped the ancestral karyotype of Mus musculus and Mus caroli between 3 and 6 million yr ago, but that are absent in the Hominidae. Hominidae show between four- and sevenfold lower rates of nucleotide change and feature turnover in both neutral and functional sequences, suggesting an underlying coherence to the Muridae acceleration. Our system of matched, high-quality genome assemblies revealed how specific classes of repeats can play lineage-specific roles in related species. Recent LINE activity has remodeled protein-coding loci to a greater extent across the Muridae than the Hominidae, with functional consequences at the species level such as reproductive isolation. Furthermore, we charted a Muridae-specific retrotransposon expansion at unprecedented resolution, revealing how a single nucleotide mutation transformed a specific SINE element into an active CTCF binding site carrier specifically in Mus caroli, which resulted in thousands of novel, species-specific CTCF binding sites. Our results show that the comparison of matched phylogenetic sets of genomes will be an increasingly powerful strategy for understanding mammalian biology. PMID:29563166

  11. Driving carbon flux through exogenous butyryl-CoA: Acetate CoA-transferase to produce butyric acid at high titer in Thermobifida fusca.

    PubMed

    Deng, Yu; Mao, Yin; Zhang, Xiaojuan

    2015-12-20

    Butyric acid, a 4-carbon short chain fatty acid, is widely used in chemical, food, and pharmaceutical industries. The low activity of butyryl-CoA: acetate CoA-transferase in Thermobifida fusca muS, a thermophilic actinobacterium whose optimal temperature was 55°C, was found to hinder the accumulation of high yield of butyric acid. In order to solve this problem, an exogenous butyryl-CoA: acetate CoA-transferase gene (actA) from Thermoanaerobacterium thermosaccharolyticum DSM571 was integrated into the chromosome of T. fusca muS by replacing celR gene, forming T. fusca muS-1. We demonstrated that on 5g/L cellulose, the yield of butyric acid by the engineered muS-1 strain was increased by 42.9 % compared to the muS strain. On 100g/L of cellulose, the muS-1 strain could consume 90.5% of total cellulose in 144h, with 33.2g/L butyric acid produced. Furthermore, on the mix substrates including the major components of biomass: cellulose, xylose, mannose and galactose, 70.4g/L butyric acid was produced in 168h by fed-batch fermentation. To validate the ability of fermenting biomass, the muS-1 strain was grown on the milled corn stover ranging from 200 to 250μm. The muS-1 strain had the highest butyrate titer 17.1g/L on 90g/L corn stover. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. 50 CFR 665.627 - Allowable gear and gear restrictions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Island Area Fisheries § 665.627 Allowable gear and gear restrictions. (a) Coral reef ecosystem MUS may be.../submersibles. (b) PRIA coral reef ecosystem MUS may not be taken by means of poisons, explosives, or... established to be fishing for coral reef ecosystem MUS in the management area is prohibited. (c) PRIA coral...

  13. 50 CFR 665.427 - Allowable gear and gear restrictions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Archipelago Fisheries § 665.427 Allowable gear and gear restrictions. (a) Mariana coral reef ecosystem MUS may... vehicles/submersibles. (b) Mariana coral reef ecosystem MUS may not be taken by means of poisons... subpart who is established to be fishing for Mariana coral reef ecosystem MUS in the management area is...

  14. 50 CFR 665.127 - Allowable gear and gear restrictions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Fisheries § 665.127 Allowable gear and gear restrictions. (a) American Samoa coral reef ecosystem MUS may be.../submersibles. (b) American Samoa coral reef ecosystem MUS may not be taken by means of poisons, explosives, or... established to be fishing for coral reef ecosystem MUS in the management area is prohibited. (c) Existing FEP...

  15. 50 CFR 665.127 - Allowable gear and gear restrictions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Fisheries § 665.127 Allowable gear and gear restrictions. (a) American Samoa coral reef ecosystem MUS may be.../submersibles. (b) American Samoa coral reef ecosystem MUS may not be taken by means of poisons, explosives, or... established to be fishing for coral reef ecosystem MUS in the management area is prohibited. (c) Existing FEP...

  16. 50 CFR 665.427 - Allowable gear and gear restrictions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Archipelago Fisheries § 665.427 Allowable gear and gear restrictions. (a) Mariana coral reef ecosystem MUS may... vehicles/submersibles. (b) Mariana coral reef ecosystem MUS may not be taken by means of poisons... subpart who is established to be fishing for Mariana coral reef ecosystem MUS in the management area is...

  17. 50 CFR 665.127 - Allowable gear and gear restrictions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Fisheries § 665.127 Allowable gear and gear restrictions. (a) American Samoa coral reef ecosystem MUS may be.../submersibles. (b) American Samoa coral reef ecosystem MUS may not be taken by means of poisons, explosives, or... established to be fishing for coral reef ecosystem MUS in the management area is prohibited. (c) Existing FEP...

  18. 50 CFR 665.14 - Reporting and recordkeeping.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... of each landing of coral reef ecosystem MUS. (d) Sales report. The operator of any fishing vessel... copying upon request by an authorized officer. (4) Coral reef ecosystem MUS. Any person who has a special... effort, landings and sales for coral reef ecosystem MUS by this subpart and §§ 665.120 through 665.128...

  19. 50 CFR 665.227 - Allowable gear and gear restrictions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Fisheries § 665.227 Allowable gear and gear restrictions. (a) Hawaii coral reef ecosystem MUS may be taken.../submersibles. (b) Hawaii coral reef ecosystem MUS may not be taken by means of poisons, explosives, or... established to be fishing for Hawaii coral reef ecosystem MUS in the Hawaii management area is prohibited. (c...

  20. 50 CFR 665.627 - Allowable gear and gear restrictions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Island Area Fisheries § 665.627 Allowable gear and gear restrictions. (a) Coral reef ecosystem MUS may be.../submersibles. (b) PRIA coral reef ecosystem MUS may not be taken by means of poisons, explosives, or... established to be fishing for coral reef ecosystem MUS in the management area is prohibited. (c) PRIA coral...

  1. 50 CFR 665.427 - Allowable gear and gear restrictions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Archipelago Fisheries § 665.427 Allowable gear and gear restrictions. (a) Mariana coral reef ecosystem MUS may... vehicles/submersibles. (b) Mariana coral reef ecosystem MUS may not be taken by means of poisons... subpart who is established to be fishing for Mariana coral reef ecosystem MUS in the management area is...

  2. 50 CFR 665.227 - Allowable gear and gear restrictions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Fisheries § 665.227 Allowable gear and gear restrictions. (a) Hawaii coral reef ecosystem MUS may be taken.../submersibles. (b) Hawaii coral reef ecosystem MUS may not be taken by means of poisons, explosives, or... established to be fishing for Hawaii coral reef ecosystem MUS in the Hawaii management area is prohibited. (c...

  3. 50 CFR 665.627 - Allowable gear and gear restrictions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Island Area Fisheries § 665.627 Allowable gear and gear restrictions. (a) Coral reef ecosystem MUS may be.../submersibles. (b) PRIA coral reef ecosystem MUS may not be taken by means of poisons, explosives, or... established to be fishing for coral reef ecosystem MUS in the management area is prohibited. (c) PRIA coral...

  4. 50 CFR 665.227 - Allowable gear and gear restrictions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Fisheries § 665.227 Allowable gear and gear restrictions. (a) Hawaii coral reef ecosystem MUS may be taken.../submersibles. (b) Hawaii coral reef ecosystem MUS may not be taken by means of poisons, explosives, or... established to be fishing for Hawaii coral reef ecosystem MUS in the Hawaii management area is prohibited. (c...

  5. 50 CFR 665.127 - Allowable gear and gear restrictions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Fisheries § 665.127 Allowable gear and gear restrictions. (a) American Samoa coral reef ecosystem MUS may be.../submersibles. (b) American Samoa coral reef ecosystem MUS may not be taken by means of poisons, explosives, or... established to be fishing for coral reef ecosystem MUS in the management area is prohibited. (c) Existing FEP...

  6. 50 CFR 665.427 - Allowable gear and gear restrictions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Archipelago Fisheries § 665.427 Allowable gear and gear restrictions. (a) Mariana coral reef ecosystem MUS may... vehicles/submersibles. (b) Mariana coral reef ecosystem MUS may not be taken by means of poisons... subpart who is established to be fishing for Mariana coral reef ecosystem MUS in the management area is...

  7. 50 CFR 665.627 - Allowable gear and gear restrictions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Island Area Fisheries § 665.627 Allowable gear and gear restrictions. (a) Coral reef ecosystem MUS may be.../submersibles. (b) PRIA coral reef ecosystem MUS may not be taken by means of poisons, explosives, or... established to be fishing for coral reef ecosystem MUS in the management area is prohibited. (c) PRIA coral...

  8. 50 CFR 665.627 - Allowable gear and gear restrictions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Island Area Fisheries § 665.627 Allowable gear and gear restrictions. (a) Coral reef ecosystem MUS may be.../submersibles. (b) PRIA coral reef ecosystem MUS may not be taken by means of poisons, explosives, or... established to be fishing for coral reef ecosystem MUS in the management area is prohibited. (c) PRIA coral...

  9. 50 CFR 665.14 - Reporting and recordkeeping.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... of each landing of coral reef ecosystem MUS. (d) Sales report. The operator of any fishing vessel... copying upon request by an authorized officer. (4) Coral reef ecosystem MUS. Any person who has a special... effort, landings and sales for coral reef ecosystem MUS by this subpart and §§ 665.120 through 665.128...

  10. 50 CFR 665.227 - Allowable gear and gear restrictions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Fisheries § 665.227 Allowable gear and gear restrictions. (a) Hawaii coral reef ecosystem MUS may be taken.../submersibles. (b) Hawaii coral reef ecosystem MUS may not be taken by means of poisons, explosives, or... established to be fishing for Hawaii coral reef ecosystem MUS in the Hawaii management area is prohibited. (c...

  11. 50 CFR 665.14 - Reporting and recordkeeping.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... of each landing of coral reef ecosystem MUS. (d) Sales report. The operator of any fishing vessel... copying upon request by an authorized officer. (4) Coral reef ecosystem MUS. Any person who has a special... effort, landings and sales for coral reef ecosystem MUS by this subpart and §§ 665.120 through 665.128...

  12. 50 CFR 665.227 - Allowable gear and gear restrictions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Fisheries § 665.227 Allowable gear and gear restrictions. (a) Hawaii coral reef ecosystem MUS may be taken.../submersibles. (b) Hawaii coral reef ecosystem MUS may not be taken by means of poisons, explosives, or... established to be fishing for Hawaii coral reef ecosystem MUS in the Hawaii management area is prohibited. (c...

  13. 50 CFR 665.427 - Allowable gear and gear restrictions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Archipelago Fisheries § 665.427 Allowable gear and gear restrictions. (a) Mariana coral reef ecosystem MUS may... vehicles/submersibles. (b) Mariana coral reef ecosystem MUS may not be taken by means of poisons... subpart who is established to be fishing for Mariana coral reef ecosystem MUS in the management area is...

  14. 50 CFR 665.127 - Allowable gear and gear restrictions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Fisheries § 665.127 Allowable gear and gear restrictions. (a) American Samoa coral reef ecosystem MUS may be.../submersibles. (b) American Samoa coral reef ecosystem MUS may not be taken by means of poisons, explosives, or... established to be fishing for coral reef ecosystem MUS in the management area is prohibited. (c) Existing FEP...

  15. Individual Differences in Animal Stress Models: Considering Resilience, Vulnerability, and the Amygdala in Mediating the Effects of Stress and Conditioned Fear on Sleep.

    PubMed

    Wellman, Laurie L; Fitzpatrick, Mairen E; Hallum, Olga Y; Sutton, Amy M; Williams, Brook L; Sanford, Larry D

    2016-06-01

    To examine the REM sleep response to stress and fearful memories as a potential marker of stress resilience and vulnerability and to assess the role of the basolateral amygdala (BLA) in mediating the effects of fear memory on sleep. Outbred Wistar rats were surgically implanted with electrodes for recording EEG and EMG and with bilateral guide cannulae directed at the BLA. Data loggers were placed intraperitoneally to record core body temperature. After recovery from surgery, the rats received shock training (ST: 20 footshocks, 0.8 mA, 0.5-s duration, 60-s interstimulus interval) and afterwards received microinjections of the GABAA agonist muscimol (MUS; 1.0 μM) to inactivate BLA or microinjections of vehicle (VEH) alone. Subsequently, the rats were separated into 4 groups (VEH-vulnerable (VEH-Vul; n = 14), VEH-resilient (VEH-Res; n = 13), MUS-vulnerable (MUS-Vul; n = 8), and MUS-resilient (MUS-Res; n = 11) based on whether or not REM was decreased, compared to baseline, during the first 4 h following ST. We then compared sleep, freezing, and the stress response (stress-induced hyperthermia, SIH) across groups to determine the effects of ST and fearful context re-exposure alone (CTX). REM was significantly reduced on the ST day in both VEH-Vul and MUS-Vul rats; however, post-ST MUS blocked the reduction in REM on the CTX day in the MUS-Vul group. The VEH-Res and MUS-Res rats showed similar levels of REM on both ST and CTX days. The effects of post-ST inactivation of BLA on freezing and SIH were minimal. Outbred Wistar rats can show significant individual differences in the effects of stress on REM that are mediated by BLA. These differences in REM can be independent of behavioral fear and the peripheral stress response, and may be an important biomarker of stress resilience and vulnerability. © 2016 Associated Professional Sleep Societies, LLC.

  16. Motor units in the human medial gastrocnemius muscle are not spatially localized or functionally grouped.

    PubMed

    Héroux, Martin E; Brown, Harrison J; Inglis, J Timothy; Siegmund, Gunter P; Blouin, Jean-Sébastien

    2015-08-15

    Human medial gastrocnemius (MG) motor units (MUs) are thought to occupy small muscle territories or regions, with low-threshold units preferentially located distally. We used intramuscular recordings to measure the territory of muscle fibres from MG MUs and determine whether these MUs are grouped by recruitment threshold or joint action (ankle plantar flexion and knee flexion). The territory of MUs from the MG muscle varied from somewhat localized to highly distributed, with approximately half the MUs spanning at least half the length and width of the muscle. There was also no evidence of regional muscle activity based on MU recruitment thresholds or joint action. The CNS does not have the means to selectively activate regions of the MG muscle based on task requirements. Human medial gastrocnemius (MG) motor units (MUs) are thought to occupy small muscle territories, with low-threshold units preferentially located distally. In this study, subjects (n = 8) performed ramped and sustained isometric contractions (ankle plantar flexion and knee flexion; range: ∼1-40% maximal voluntary contraction) and we measured MU territory size with spike-triggered averages from fine-wire electrodes inserted along the length (seven electrodes) or across the width (five electrodes) of the MG muscle. Of 69 MUs identified along the length of the muscle, 32 spanned at least half the muscle length (≥ 6.9 cm), 11 of which spanned all recording sites (13.6-17.9 cm). Distal fibres had smaller pennation angles (P < 0.05), which were accompanied by larger territories in MUs with fibres located distally (P < 0.05). There was no distal-to-proximal pattern of muscle activation in ramp contraction (P = 0.93). Of 36 MUs identified across the width of the muscle, 24 spanned at least half the muscle width (≥ 4.0 cm), 13 of which spanned all recording sites (8.0-10.8 cm). MUs were not localized (length or width) based on recruitment threshold or contraction type, nor was there a relationship between MU territory size and recruitment threshold (Spearman's rho = -0.20 and 0.13, P > 0.18). MUs in the human MG have larger territories than previously reported and are not localized based on recruitment threshold or joint action. This indicates that the CNS does not have the means to selectively activate regions of the MG muscle based on task requirements. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  17. Repeat associated mechanisms of genome evolution and function revealed by the Mus caroli and Mus pahari genomes.

    PubMed

    Thybert, David; Roller, Maša; Navarro, Fábio C P; Fiddes, Ian; Streeter, Ian; Feig, Christine; Martin-Galvez, David; Kolmogorov, Mikhail; Janoušek, Václav; Akanni, Wasiu; Aken, Bronwen; Aldridge, Sarah; Chakrapani, Varshith; Chow, William; Clarke, Laura; Cummins, Carla; Doran, Anthony; Dunn, Matthew; Goodstadt, Leo; Howe, Kerstin; Howell, Matthew; Josselin, Ambre-Aurore; Karn, Robert C; Laukaitis, Christina M; Jingtao, Lilue; Martin, Fergal; Muffato, Matthieu; Nachtweide, Stefanie; Quail, Michael A; Sisu, Cristina; Stanke, Mario; Stefflova, Klara; Van Oosterhout, Cock; Veyrunes, Frederic; Ward, Ben; Yang, Fengtang; Yazdanifar, Golbahar; Zadissa, Amonida; Adams, David J; Brazma, Alvis; Gerstein, Mark; Paten, Benedict; Pham, Son; Keane, Thomas M; Odom, Duncan T; Flicek, Paul

    2018-04-01

    Understanding the mechanisms driving lineage-specific evolution in both primates and rodents has been hindered by the lack of sister clades with a similar phylogenetic structure having high-quality genome assemblies. Here, we have created chromosome-level assemblies of the Mus caroli and Mus pahari genomes. Together with the Mus musculus and Rattus norvegicus genomes, this set of rodent genomes is similar in divergence times to the Hominidae (human-chimpanzee-gorilla-orangutan). By comparing the evolutionary dynamics between the Muridae and Hominidae, we identified punctate events of chromosome reshuffling that shaped the ancestral karyotype of Mus musculus and Mus caroli between 3 and 6 million yr ago, but that are absent in the Hominidae. Hominidae show between four- and sevenfold lower rates of nucleotide change and feature turnover in both neutral and functional sequences, suggesting an underlying coherence to the Muridae acceleration. Our system of matched, high-quality genome assemblies revealed how specific classes of repeats can play lineage-specific roles in related species. Recent LINE activity has remodeled protein-coding loci to a greater extent across the Muridae than the Hominidae, with functional consequences at the species level such as reproductive isolation. Furthermore, we charted a Muridae-specific retrotransposon expansion at unprecedented resolution, revealing how a single nucleotide mutation transformed a specific SINE element into an active CTCF binding site carrier specifically in Mus caroli , which resulted in thousands of novel, species-specific CTCF binding sites. Our results show that the comparison of matched phylogenetic sets of genomes will be an increasingly powerful strategy for understanding mammalian biology. © 2018 Thybert et al.; Published by Cold Spring Harbor Laboratory Press.

  18. The basolateral amygdala can mediate the effects of fear memory on sleep independently of fear behavior and the peripheral stress response.

    PubMed

    Wellman, Laurie L; Fitzpatrick, Mairen E; Hallum, Olga Y; Sutton, Amy M; Williams, Brook L; Sanford, Larry D

    2017-01-01

    Fear conditioning associated with inescapable shock training (ST) and fearful context re-exposure (CR) alone can produce significant behavioral fear, a stress response and alterations in subsequent REM sleep. These alterations may vary among animals and are mediated by the basolateral nucleus of the amygdala (BLA). Here, we used the GABA A agonist, muscimol (Mus), to inactivate BLA prior to CR and examined the effects on sleep, freezing and stress-induced hyperthermia (SIH). Wistar rats (n=28) were implanted with electrodes for recording sleep, data loggers for recording core body temperature, and with cannulae aimed bilaterally into BLA. After recovery, the animals were habituated to the injection procedure and baseline sleep was recorded. On experimental day 1, rats received ST (20 footshocks, 0.8mA, 0.5s duration, 60s interstimulus interval). On experimental day 7, the rats received microinjections (0.5μl) into BLA of either Mus (1.0μM; n=13) or vehicle (Veh; n=15) prior to CR (CR1). On experimental day 21, the animals experienced a second CR (CR2) without Mus. For analysis, the rats were separated into 4 groups: (Veh-vulnerable (Veh-Vul; n=8), Veh-resilient (Veh-Res; n=7), Mus-vulnerable (Mus-Vul; n=7), and Mus-resilient (Mus-Res; n=6)) based on whether or not REM was decreased, compared to baseline, during the first 4h following ST. Pre-CR1 inactivation of BLA did not alter freezing or SIH, but did block the reduction in REM in the Mus-Vul group compared to the Veh-Vul group. These data indicate that BLA is an important region for mediating the effects of fearful memories on sleep. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Vaginal prolapse repair with or without a midurethral sling in women with genital prolapse and occult stress urinary incontinence: a randomized trial.

    PubMed

    van der Ploeg, J Marinus; Oude Rengerink, Katrien; van der Steen, Annemarie; van Leeuwen, Jules H Schagen; van der Vaart, C Huub; Roovers, Jan-Paul W R

    2016-07-01

    We compared pelvic organ prolapse (POP) repair with and without midurethral sling (MUS) in women with occult stress urinary incontinence (SUI). This was a randomized trial conducted by a consortium of 13 teaching hospitals assessing a parallel cohort of continent women with symptomatic stage II or greater POP. Women with occult SUI were randomly assigned to vaginal prolapse repair with or without MUS. Women without occult SUI received POP surgery. Main outcomes were the absence of SUI at the 12-month follow-up based on the Urogenital Distress Inventory and the need for additional treatment for SUI. We evaluated 231 women, of whom 91 randomized as follows: 43 to POP surgery with and 47 without MUS. A greater number of women in the MUS group reported absence of SUI [86 % vs. 48 %; relative risk (RR) 1.79; 95 % confidence interval (CI) 1.29-2.48]. No women in the MUS group received additional treatment for postoperative SUI; six (13 %) in the control group had a secondary MUS. Women with occult SUI reported more urinary symptoms after POP surgery and more often underwent treatment for postoperative SUI than women without occult SUI. Women with occult SUI had a higher risk of reporting SUI after POP surgery compared with women without occult SUI. Adding a MUS to POP surgery reduced the risk of postoperative SUI and the need for its treatment in women with occult SUI. Of women with occult SUI undergoing POP-only surgery, 13 % needed additional MUS. We found no differences in global impression of improvement and quality of life.

  20. The Basolateral Amygdala Can Mediate the Effects of Fear Memory on Sleep Independently of Fear Behavior and the Peripheral Stress Response

    PubMed Central

    Wellman, Laurie L.; Fitzpatrick, Mairen E.; Hallum, Olga Y.; Sutton, Amy M.; Williams, Brook L.; Sanford, Larry D.

    2016-01-01

    Fear conditioning associated with inescapable shock training (ST) and fearful context re-exposure (CR) alone can produce significant behavioral fear, a stress response and alterations in subsequent REM sleep. These alterations may vary among animals and are mediated by the basolateral nucleus of the amygdala (BLA). Here, we used the GABAA agonist, muscimol (Mus), to inactivate BLA prior to CR and examined the effects on sleep, freezing and stress-induced hyperthermia (SIH). Wistar rats (n=28) were implanted with electrodes for recording sleep, data loggers for recording core body temperature, and with cannulae aimed bilaterally into BLA. After recovery, the animals were habituated to the injection procedure and baseline sleep was recorded. On experimental day 1, rats received ST (20 footshocks, 0.8mA, 0.5s duration, 60s interstimulus interval). On experimental day 7, the rats received microinjections (0.5ul) into BLA of either Mus (1.0uM; n = 13) or vehicle (Veh; n = 15) prior to CR (CR1). On experimental day 21, the animals experienced a second CR (CR2) without Mus. For analysis, the rats were separated into 4 groups: (Veh-vulnerable (Veh-Vul; n=8), Veh-resilient (Veh-Res; n=7), Mus-vulnerable (Mus-Vul; n=7), and Mus-resilient (Mus-Res; n=6)) based on whether or not REM was decreased, compared to baseline, during the first 4 h following ST. Pre-CR1 inactivation of BLA did not alter freezing or SIH, but did block the reduction in REM in the Mus-Vul group compared to the Veh-Vul group. These data indicate that BLA is an important region for mediating the effects of fearful memories on sleep. PMID:27818268

  1. Assessment of Volumetric-Modulated Arc Therapy for Constant and Variable Dose Rates

    PubMed Central

    De Ornelas-Couto, Mariluz; Mihaylov, Ivaylo; Dogan, Nesrin

    2017-01-01

    Purpose: The aim of this study is to compare the effects of dose rate on volumetric-modulated arc therapy plans to determine optimal dose rates for prostate and head and neck (HN) cases. Materials and Methods: Ten prostate and ten HN cases were retrospectively studied. For each case, seven plans were generated: one variable dose rate (VDR) and six constant dose rate (CDR) (100–600 monitor units [MUs]/min) plans. Prescription doses were: 80 Gy to planning target volume (PTV) for the prostate cases, and 70, 60, and 54 Gy to PTV1, PTV2, and PTV3, respectively, for HN cases. Plans were normalized to 95% of the PTV and PTV1, respectively, with the prescription dose. Plans were assessed using Dose-Volume-Histogram metrics, homogeneity index, conformity index, MUs, and delivery time. Results: For the prostate cases, significant differences were found for rectum D35 between VDR and all CDR plans, except CDR500. Furthermore, VDR was significantly different than CDR100 and 200 for bladder D50. Delivery time for all CDR plans and MUs for CDR400–600 were significantly higher when compared to VDR. HN cases showed significant differences between VDR and CDR100, 500 and 600 for D2 to the cord and brainstem. Significant differences were found for delivery time and MUs for all CDR plans, except CDR100 for number of MUs. Conclusion: The most significant differences were observed in delivery time and number of MUs. All-in-all, the best CDR for prostate cases was found to be 300 MUs/min and 200 or 300 MUs/min for HN cases. However, VDR plans are still the choice in terms of MU efficiency and plan quality. PMID:29296033

  2. Identification of rRNA gene loci in the wild mouse (Mus musculus molossinus) captured at Hachioji, Tokyo.

    PubMed

    Ito, Tsuyoshi; Osawa, Susumu; Shibata, Hideshi; Kanda, Naotoshi

    2007-12-01

    Mus musculus (M. m.) molossinus has been considered an independent subspecies of Mus musculus. To elucidate the evolutional origin of this subspecies, we carried out double-color FISH using 18s-28s ribosomal DNA and mouse chromosome paint probes. Among eleven rDNA loci detected, five loci on chromosomes 12, 15, 16, 18 and 19 were common to both Mus musculus (M. m.) musculus and M. m. molossinus and the other six loci, on chromosomes 1, 5, 10, 11, 13 and 17, were characteristic in M. m. molossinus. As M. m. molossinus is thought to originate from a hybrid between ancestral colonies of M. m. musculus and Mus musculus castaneus, we supposed that these six rDNA loci might have evolved after geographical isolation of the ancestral hybrid animals from M. m. musculus and M. m. castaneus.

  3. mus304 encodes a novel DNA damage checkpoint protein required during Drosophila development

    PubMed Central

    Brodsky, Michael H.; Sekelsky, Jeff J.; Tsang, Garson; Hawley, R. Scott; Rubin, Gerald M.

    2000-01-01

    Checkpoints block cell cycle progression in eukaryotic cells exposed to DNA damaging agents. We show that several Drosophila homologs of checkpoint genes, mei-41, grapes, and 14-3-3ε, regulate a DNA damage checkpoint in the developing eye. We have used this assay to show that the mutagen-sensitive gene mus304 is also required for this checkpoint. mus304 encodes a novel coiled-coil domain protein, which is targeted to the cytoplasm. Similar to mei-41, mus304 is required for chromosome break repair and for genomic stability. mus304 animals also exhibit three developmental defects, abnormal bristle morphology, decreased meiotic recombination, and arrested embryonic development. We suggest that these phenotypes reflect distinct developmental consequences of a single underlying checkpoint defect. Similar mechanisms may account for the puzzling array of symptoms observed in humans with mutations in the ATM tumor suppressor gene. PMID:10733527

  4. Crystal structure of the Mus81-Eme1 complex.

    PubMed

    Chang, Jeong Ho; Kim, Jeong Joo; Choi, Jung Min; Lee, Jung Hoon; Cho, Yunje

    2008-04-15

    The Mus81-Eme1 complex is a structure-specific endonuclease that plays an important role in rescuing stalled replication forks and resolving the meiotic recombination intermediates in eukaryotes. We have determined the crystal structure of the Mus81-Eme1 complex. Both Mus81 and Eme1 consist of a central nuclease domain, two repeats of the helix-hairpin-helix (HhH) motif at their C-terminal region, and a linker helix. While each domain structure resembles archaeal XPF homologs, the overall structure is significantly different from those due to the structure of a linker helix. We show that a flexible intradomain linker that formed with 36 residues in the nuclease domain of Eme1 is essential for the recognition of DNA. We identified several basic residues lining the outer surface of the active site cleft of Mus81 that are involved in the interaction with a flexible arm of a nicked Holliday junction (HJ). These interactions might contribute to the optimal positioning of the opposite junction across the nick into the catalytic site, which provided the basis for the "nick and counternick" mechanism of Mus81-Eme1 and for the nicked HJ to be the favored in vitro substrate of this enzyme.

  5. Establishment of a Transgenic Zebrafish Line for Superficial Skin Ablation and Functional Validation of Apoptosis Modulators In Vivo

    PubMed Central

    Chen, Chi-Fang; Chu, Che-Yu; Chen, Te-Hao; Lee, Shyh-Jye; Shen, Chia-Ning; Hsiao, Chung-Der

    2011-01-01

    Background Zebrafish skin is composed of enveloping and basal layers which form a first-line defense system against pathogens. Zebrafish epidermis contains ionocytes and mucous cells that aid secretion of acid/ions or mucous through skin. Previous studies demonstrated that fish skin is extremely sensitive to external stimuli. However, little is known about the molecular mechanisms that modulate skin cell apoptosis in zebrafish. Methodology/Principal Findings This study aimed to create a platform to conduct conditional skin ablation and determine if it is possible to attenuate apoptotic stimuli by overexpressing potential apoptosis modulating genes in the skin of live animals. A transgenic zebrafish line of Tg(krt4:NTR-hKikGR)cy17 (killer line), which can conditionally trigger apoptosis in superficial skin cells, was first established. When the killer line was incubated with the prodrug metrodinazole, the superficial skin displayed extensive apoptosis as judged by detection of massive TUNEL- and active caspase 3-positive signals. Great reductions in NTR-hKikGR+ fluorescent signals accompanied epidermal cell apoptosis. This indicated that NTR-hKikGR+ signal fluorescence can be utilized to evaluate apoptotic events in vivo. After removal of metrodinazole, the skin integrity progressively recovered and NTR-hKikGR+ fluorescent signals gradually restored. In contrast, either crossing the killer line with testing lines or transiently injecting the killer line with testing vectors that expressed human constitutive active Akt1, mouse constitutive active Stat3, or HPV16 E6 element displayed apoptosis-resistant phenotypes to cytotoxic metrodinazole as judged by the loss of reduction in NTR-hKikGR+ fluorescent signaling. Conclusion/Significance The killer/testing line binary system established in the current study demonstrates a nitroreductase/metrodinazole system that can be utilized to conditionally perform skin ablation in a real-time manner, and provides a valuable tool to visualize and quantify the anti-apoptotic potential of interesting target genes in vivo. The current work identifies a potential use for transgenic zebrafish as a high-throughput platform to validate potential apoptosis modulators in vivo. PMID:21655190

  6. A spiritual problem? Primary care physicians' and psychiatrists' interpretations of medically unexplained symptoms.

    PubMed

    Shin, Jiwon Helen; Yoon, John D; Rasinski, Kenneth A; Koenig, Harold G; Meador, Keith G; Curlin, Farr A

    2013-03-01

    Patients commonly present to their physicians with medically unexplained symptoms (MUS), and there is no consensus about how physicians should interpret or treat such symptoms. To examine how variations in physicians' interpretations of MUS are associated with physicians' religious characteristics and with physician specialty (primary care vs. psychiatry). A national survey of a stratified random sample of 1,504 primary care physicians and 512 psychiatrists in 2009-2010. The extent to which physicians believe MUS reflect a root problem that is spiritual in nature or result from conditions that scientific research will eventually explain, and whether such patients would benefit from attention to their relationships, attention to their spiritual life, taking medications, and/or treatment by physicians. Response rate was 63 % (1,208/1,909). More religious/spiritual physicians were more likely to believe that MUS reflect a spiritual problem (55 % for high vs. 24 % for low spirituality; OR = 2.8, 1.7-4.5) and that these patients would benefit from paying attention to their spiritual life (79 % for high vs. 55 % for low spirituality; OR = 3.1, 1.8-5.3). Psychiatrists were more likely to believe that scientific research will one day explain MUS (66 % vs. 52 %; OR = 1.9, 1.4-2.5) and that these symptoms will improve with treatment by a physician (54 % vs. 35 %; OR = 2.4, 1.8-3.3). They were less likely to believe that MUS reflect a spiritual problem (23 % vs. 38 %; OR = 0.5, 0.4-0.8). Physicians' interpretations of MUS vary widely, depending in part on physicians' religious characteristics and specialty. One in three physicians believes that patients with MUS have root problems that are spiritual in nature. Physicians who are more religious or spiritual are more likely to think of MUS as stemming from spiritual concerns. Psychiatrists are more optimistic that these patients will get better with treatment by physicians.

  7. MusTRD can regulate postnatal fiber-specific expression.

    PubMed

    Issa, Laura L; Palmer, Stephen J; Guven, Kim L; Santucci, Nicole; Hodgson, Vanessa R M; Popovic, Kata; Joya, Josephine E; Hardeman, Edna C

    2006-05-01

    Human MusTRD1alpha1 was isolated as a result of its ability to bind a critical element within the Troponin I slow upstream enhancer (TnIslow USE) and was predicted to be a regulator of slow fiber-specific genes. To test this hypothesis in vivo, we generated transgenic mice expressing hMusTRD1alpha1 in skeletal muscle. Adult transgenic mice show a complete loss of slow fibers and a concomitant replacement by fast IIA fibers, resulting in postural muscle weakness. However, developmental analysis demonstrates that transgene expression has no impact on embryonic patterning of slow fibers but causes a gradual postnatal slow to fast fiber conversion. This conversion was underpinned by a demonstrable repression of many slow fiber-specific genes, whereas fast fiber-specific gene expression was either unchanged or enhanced. These data are consistent with our initial predictions for hMusTRD1alpha1 and suggest that slow fiber genes contain a specific common regulatory element that can be targeted by MusTRD proteins.

  8. Roles of SLX1–SLX4, MUS81–EME1, and GEN1 in avoiding genome instability and mitotic catastrophe

    PubMed Central

    Sarbajna, Shriparna; Davies, Derek; West, Stephen C.

    2014-01-01

    The resolution of recombination intermediates containing Holliday junctions (HJs) is critical for genome maintenance and proper chromosome segregation. Three pathways for HJ processing exist in human cells and involve the following enzymes/complexes: BLM–TopoIIIα–RMI1–RMI2 (BTR complex), SLX1–SLX4–MUS81–EME1 (SLX–MUS complex), and GEN1. Cycling cells preferentially use the BTR complex for the removal of double HJs in S phase, with SLX–MUS and GEN1 acting at temporally distinct phases of the cell cycle. Cells lacking SLX–MUS and GEN1 exhibit chromosome missegregation, micronucleus formation, and elevated levels of 53BP1-positive G1 nuclear bodies, suggesting that defects in chromosome segregation lead to the transmission of extensive DNA damage to daughter cells. In addition, however, we found that the effects of SLX4, MUS81, and GEN1 depletion extend beyond mitosis, since genome instability is observed throughout all phases of the cell cycle. This is exemplified in the form of impaired replication fork movement and S-phase progression, endogenous checkpoint activation, chromosome segmentation, and multinucleation. In contrast to SLX4, SLX1, the nuclease subunit of the SLX1–SLX4 structure-selective nuclease, plays no role in the replication-related phenotypes associated with SLX4/MUS81 and GEN1 depletion. These observations demonstrate that the SLX1–SLX4 nuclease and the SLX4 scaffold play divergent roles in the maintenance of genome integrity in human cells. PMID:24831703

  9. What's 'difficult'? A multi-stage qualitative analysis of secondary care specialists' experiences with medically unexplained symptoms.

    PubMed

    Maatz, Anke; Wainwright, Megan; Russell, Andrew J; Macnaughton, Jane; Yiannakou, Yan

    2016-11-01

    The term 'difficult' is pervasively used in relation to medically unexplained symptoms (MUS) and patients with MUS. This article scrutinises the use of the term by analysing interview data from a study of secondary care specialists' experiences with and attitudes towards patients suffering from MUS. Qualitative design employing semi-structured open-ended interviews systematically analysed in three stages: first, data were analysed according to the principles of content analysis. The analysis subsequently focused on the use of the term 'difficult'. Iterations of the term were extracted by summative analysis and thematic coding revealed its different meanings. Finally, alternative expressions were explored. Three NHS trust secondary care hospitals in North-East England. 17 senior clinicians from seven medical and two surgical specialities. Unsolicited use of the term 'difficult' was common. 'Difficult' was rarely used as a patient characteristic or to describe the therapeutic relationship. Participants used 'difficult' to describe their experience of diagnosing, explaining, communicating and managing these conditions and their own emotional reactions. Health care system deficits and the conceptual basis for MUS were other facets of 'difficult'. Participants also reported experiences that were rewarding and positive. This study shows that blanket statements such as 'difficult patients' mask the complexity of doctors' experiences in the context of MUS. Our nuanced analysis of the use of 'difficult' challenges preconceived attitudes. This can help counter the unreflexive perpetuation of negative evaluations that stigmatize patients with MUS, encourage greater acknowledgement of doctors' emotions, and lead to more appropriate conceptualizations and management of MUS. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Changes in contractile properties and action potentials of motor units in the rat medial gastrocnemius muscle during maturation.

    PubMed

    Dobrzynska, Z; Celichowski, J

    2016-02-01

    The early phase of development of muscles stops following the disappearance of embryonic and neonatal myosin and the elimination of polyneuronal innervation of muscle fibres with the formation of motor units (MUs), but later the muscle mass still considerably increases. It is unknown whether the three types are visible among newly formed MUs soon after the early postnatal period and whether their proportion is similar to that in adult muscle. Moreover, the processes responsible for MU-force regulation by changes in motoneuronal firing rate as well as properties of motor unit action potentials (MUAPs) during maturation are unknown. Three groups of Wistar rats were investigated - 1 month old, 2 months old and the adult, 9 months old. The basic contractile properties and action potentials of MUs in the medial gastrocnemius (MG) muscle were analysed. The three types of MUs were distinguishable in all age groups, but higher proportion of slow MUs was noticed in young rats (29%, 18% and 11% in 1, 2 and 9 months rats, respectively). The fatigue index for fast fatigable MUs in 1 month old rats was about 2 times higher than in 9 months old rats. The twitch time parameters of fast MUs were shortened during the maturation; for these units, the force-frequency curves in young rats were shifted towards lower frequencies, which suggested that fast motoneurons of young animals generate lower firing rates. Higher twitch-to-tetanus ratios noted for the three MU types in young rats suggested the smaller role of rate coding in force regulation processes, and the higher role of MU recruitment in young rats. No significant differences in MUAP parameters between two groups of young and adult animals were observed. Concluding, the maturation process evokes deeper changes in fast MUs than in slow ones.

  11. Individual Differences in Animal Stress Models: Considering Resilience, Vulnerability, and the Amygdala in Mediating the Effects of Stress and Conditioned Fear on Sleep

    PubMed Central

    Wellman, Laurie L.; Fitzpatrick, Mairen E.; Hallum, Olga Y.; Sutton, Amy M.; Williams, Brook L.; Sanford, Larry D.

    2016-01-01

    Study Objectives: To examine the REM sleep response to stress and fearful memories as a potential marker of stress resilience and vulnerability and to assess the role of the basolateral amygdala (BLA) in mediating the effects of fear memory on sleep. Methods: Outbred Wistar rats were surgically implanted with electrodes for recording EEG and EMG and with bilateral guide cannulae directed at the BLA. Data loggers were placed intraperitoneally to record core body temperature. After recovery from surgery, the rats received shock training (ST: 20 footshocks, 0.8 mA, 0.5-s duration, 60-s interstimulus interval) and afterwards received microinjections of the GABAA agonist muscimol (MUS; 1.0 μM) to inactivate BLA or microinjections of vehicle (VEH) alone. Subsequently, the rats were separated into 4 groups (VEH-vulnerable (VEH-Vul; n = 14), VEH-resilient (VEH-Res; n = 13), MUS-vulnerable (MUS-Vul; n = 8), and MUS-resilient (MUS-Res; n = 11) based on whether or not REM was decreased, compared to baseline, during the first 4 h following ST. We then compared sleep, freezing, and the stress response (stress-induced hyperthermia, SIH) across groups to determine the effects of ST and fearful context re-exposure alone (CTX). Results: REM was significantly reduced on the ST day in both VEH-Vul and MUS-Vul rats; however, post-ST MUS blocked the reduction in REM on the CTX day in the MUS-Vul group. The VEH-Res and MUS-Res rats showed similar levels of REM on both ST and CTX days. The effects of post-ST inactivation of BLA on freezing and SIH were minimal. Conclusions: Outbred Wistar rats can show significant individual differences in the effects of stress on REM that are mediated by BLA. These differences in REM can be independent of behavioral fear and the peripheral stress response, and may be an important biomarker of stress resilience and vulnerability. Citation: Wellman LL, Fitzpatrick ME, Hallum OY, Sutton AM, Williams BL, Sanford LD. Individual differences in animal stress models: considering resilience, vulnerability, and the amygdala in mediating the effects of stress and conditioned fear on sleep. SLEEP 2016;39(6):1293–1303. PMID:27091518

  12. Recurrent Urinary Tract Infection After Midurethral Sling: A Retrospective Study.

    PubMed

    Hammett, Jessica; Lukman, Revana; Oakes, Megan; Whitcomb, Emily L

    Our primary objective was to estimate the proportion of patients with culture-proven urinary tract infection (UTI) and recurrent UTI after midurethral sling (MUS), as well as to evaluate their risk factors. Our secondary objective was to characterize the difference in the proportion of patients with recurrent UTI before and after MUS. We conducted a retrospective study of patients who underwent MUS from 2009 to 2012 within a large health maintenance organization and subsequently had documentation of at least 1 positive urine culture (>100 K CFU/mL) within 1 year. Validated procedural and diagnostic codes were used to identify patients undergoing MUS and the diagnosis of UTI, respectively. Of the 7461 MUS performed, 883 (12%) patients had at least 1 culture-proven UTI and 258 (3.5%) patients met the definition of recurrent UTI postoperatively. Of those 883 patients, 89 (10%) patients met the definition of recurrent UTI before, and 258 (29%) patients after, MUS. McNemar χ test revealed that patients were more likely to have recurrent UTI after MUS compared with before (P < 0.0001). In multivariate logistic regression, Caucasian (odds ratio [OR], 1.60, 95% confidence interval [95% CI], 1.12-2.29; P = 0.01) and African-American (OR, 3.42; 95% CI, 1.42-8.29; P = 0.01) ethnicity, older age (OR, 1.02; 95% CI, 1.00-1.04; P = 0.03), and a history of recurrent UTI (OR 3.79, 95% CI 1.88-7.93, P = 0.0003) were risk factors for postoperative recurrent UTI. In this population, preoperative recurrent UTI was the only modifiable risk factor associated with an increased risk of postoperative recurrent UTI.

  13. Superovulation and in vitro oocyte maturation in three species of mice (Mus musculus, Mus spretus and Mus spicilegus).

    PubMed

    Martín-Coello, J; González, R; Crespo, C; Gomendio, M; Roldan, E R S

    2008-10-01

    Mouse oocytes can be obtained via superovulation or using in vitro maturation although several factors, including genetic background, may affect response. Our previous studies have identified various mouse species as models to understand the role of sexual selection on the evolution of sperm traits and function. In order to do comparative studies of sperm-oocyte interaction, we sought reliable methods for oocyte superovulation and in vitro maturation in mature females of three mouse species (genus Mus). When 5 IU pregnant mare's serum gonadotrophin (PMSG) and 5 IU human chorionic gonadotrophin (hCG) were injected 48 h apart, and oocytes collected 14 h post-hCG, good responses were obtained in Mus musculus (18+/-1.3 oocytes/female; mean+/-S.E.M.) and Mus spretus (12+/-0.8), but no ovulation was seen in Mus spicilegus. Changes in PMSG or hCG doses, or longer post-hCG intervals, did not improve results. Use of PMSG/luteinizing hormone (LH) resulted in good responses in M. musculus (19+/-1.2) and M. spretus (12+/-1.1) but not in M. spicilegus (5+/-0.9) with ovulation not increasing with higher LH doses. Follicular puncture 48 h after PMSG followed by in vitro maturation led to a high oocyte yield in the three species (M. musculus, 23+/-0.9; M. spretus, 17+/-1.1; M. spicilegus, 10+/-0.9) with a consistently high maturation rates. In vitro fertilization of both superovulated and in vitro matured oocytes resulted in a high proportion of fertilization (range: 83-87%) in the three species. Thus, in vitro maturation led to high yields in all three species. These results will allow future studies on gamete interaction in these closely related species and the role of sexual selection in gamete compatibility.

  14. Allergenic proteins are fragmented in low concentrations of sodium hypochlorite.

    PubMed

    Chen, P; Eggleston, P A

    2001-07-01

    To facilitate allergen removal from indoor environments, it would be helpful to have household cleaning products that modified allergenic activity. Because NaOCl dissolves proteins in high concentrations and is both capable of killing bacteria and viruses and inactivating viral antigens at somewhat lower concentrations, we explored its effects on Mus m 1 and other indoor allergens. To examine the ability of NaOCl to reduce the allergenicity of Mus m 1 and other indoor allergens. Using purified mouse urinary allergen, we examined the effect on protein measured by Coomassie protein assay and on Mus m 1 measured by ELISA. We also examined the effects using SDS/PAGE and Western blots probed with sheep anti-Mus m 1 and with allergic human serum. When NaOCl and Mus m 1 were combined in a molar ratio of 100 : 1, IgE binding to Mus m 1 on Western blot was significantly reduced. At higher NaOCl concentrations the protein appeared to fragment and eventually became undetectable. Fragmentation appeared to be random in that peptides of a wide range of apparent molecular weight were produced. The reaction was complete within 1-2 min at OCl : pr ratios of greater than 200 : 1 and was optimal at pH 7.4. Immunological activity of other allergens (Fel d 1, Bla g 1, Der p 1) was decreased in vitro and dried allergen extracts were removed from surfaces. Adding an extraneous protein, BSA, to NaOCl:Mus m 1 solutions decreased the effect of NaOCl on the allergen. We concluded that NaOCl at concentrations commonly used in household products is capable of dramatically affecting allergenic protein.

  15. Mus81 and Yen1 promote reciprocal exchange during mitotic recombination to maintain genome integrity in budding yeast

    PubMed Central

    Ho, Chu Kwen; Mazón, Gerard; Lam, Alicia F.; Symington, Lorraine S.

    2010-01-01

    Holliday junction (HJ) resolution is required for segregation of chromosomes and for formation of crossovers during homologous recombination. The identity of the resolvase(s) that functions in vivo has yet to be established, although several proteins able to cut HJs in vitro have been identified as candidates in yeasts and mammals. Using an assay to detect unselected products of mitotic recombination we found a significant decrease in crossovers in the Saccharomyces cerevisiae mus81Δ mutant. Yen1 serves a back-up function responsible for resolving intermediates in mus81Δ mutants, or when conversion tracts are short. In the absence of both Mus81 and Yen1 intermediates are not channeled exclusively to non-crossover recombinants, but instead are processed by Pol32-dependent break-induced replication (BIR). The channeling of recombination from reciprocal exchange to BIR results in greatly increased spontaneous loss of heterozygosity (LOH) and chromosome mis-segregation in the mus81Δ yen1Δ mutant, typical of the genomic instability found in tumor cells. PMID:21172663

  16. Determination of thiamine HCl and pyridoxine HCl in pharmaceutical preparations using UV-visible spectrophotometry and genetic algorithm based multivariate calibration methods.

    PubMed

    Ozdemir, Durmus; Dinc, Erdal

    2004-07-01

    Simultaneous determination of binary mixtures pyridoxine hydrochloride and thiamine hydrochloride in a vitamin combination using UV-visible spectrophotometry and classical least squares (CLS) and three newly developed genetic algorithm (GA) based multivariate calibration methods was demonstrated. The three genetic multivariate calibration methods are Genetic Classical Least Squares (GCLS), Genetic Inverse Least Squares (GILS) and Genetic Regression (GR). The sample data set contains the UV-visible spectra of 30 synthetic mixtures (8 to 40 microg/ml) of these vitamins and 10 tablets containing 250 mg from each vitamin. The spectra cover the range from 200 to 330 nm in 0.1 nm intervals. Several calibration models were built with the four methods for the two components. Overall, the standard error of calibration (SEC) and the standard error of prediction (SEP) for the synthetic data were in the range of <0.01 and 0.43 microg/ml for all the four methods. The SEP values for the tablets were in the range of 2.91 and 11.51 mg/tablets. A comparison of genetic algorithm selected wavelengths for each component using GR method was also included.

  17. Capacity allocation mechanism based on differentiated QoS in 60 GHz radio-over-fiber local access network

    NASA Astrophysics Data System (ADS)

    Kou, Yanbin; Liu, Siming; Zhang, Weiheng; Shen, Guansheng; Tian, Huiping

    2017-03-01

    We present a dynamic capacity allocation mechanism based on the Quality of Service (QoS) for different mobile users (MU) in 60 GHz radio-over-fiber (RoF) local access networks. The proposed mechanism is capable for collecting the request information of MUs to build a full list of MU capacity demands and service types at the Central Office (CO). A hybrid algorithm is introduced to implement the capacity allocation which can satisfy the requirements of different MUs at different network traffic loads. Compared with the weight dynamic frames assignment (WDFA) scheme, the Hybrid scheme can keep high priority MUs in low delay and maintain the packet loss rate less than 1% simultaneously. At the same time, low priority MUs have a relatively better performance.

  18. Food habits of introduced rodents in high-elevation shrubland of Haleakala National Park, Maui, Hawai'i

    USGS Publications Warehouse

    Cole, F. Russell; Loope, Lloyd L.; Medeiros, Arthur C.; Howe, Cameron E.; Anderson, Laurel J.

    2000-01-01

    Mus musculus and Rattus rattus are ubiquitous consumers in the high-elevation shrubland of Haleakala National Park. Food habits of these two rodent species were determined from stomach samples obtained by snaptrapping along transects located at four different elevations during November 1984 and February, May, and August 1985. Mus musculus fed primarily on fruits, grass seeds, and arthropods. Rattus rattus ate various fruits, dicot leaves, and arthropods. Arthropods, many of which are endemic, were taken frequently by Mus musculus throughout the year at the highest elevation where plant food resources were scarce. Araneida, Lepidoptera (primarily larvae), Coleoptera, and Homoptera were the main arthropod taxa taken. These rodents, particularly Mus musculus, exert strong predation pressure on populations of arthropod species, including locally endemic species on upper Haleakala Volcano.

  19. Genes Altered by Intracisternal A Particles in Mouse Mammary Tumorigenesis

    DTIC Science & Technology

    1997-07-01

    mouse Mus musculus as well as most other rodents (1). They are defective retroviruses which contain 3’ and 5’ long terminal repeat (LTR) sequences and... musculus (C57BL/6J) X Mus spretus backcross was obtained for The Jackson Laboratory (Bar Harbor, Maine) and used for localization of the pl7b(kokopelli...understand the nature of the potential mutation found in the tumors I decided to localize pl7b within the mouse genome. I screened a Mus musculus musculus X

  20. Immunologic Control of Mus musculus Papillomavirus Type 1

    PubMed Central

    Peng, Shiwen; Chang, Yung-Nien; Hung, Chien-Fu; Roden, Richard B. S.

    2015-01-01

    Persistent papillomas developed in ~10% of out-bred immune-competent SKH-1 mice following MusPV1 challenge of their tail, and in a similar fraction the papillomas were transient, suggesting potential as a model. However, papillomas only occurred in BALB/c or C57BL/6 mice depleted of T cells with anti-CD3 antibody, and they completely regressed within 8 weeks after depletion was stopped. Neither CD4+ nor CD8+ T cell depletion alone in BALB/c or C57BL/6 mice was sufficient to permit visible papilloma formation. However, low levels of MusPV1 were sporadically detected by either genomic DNA-specific PCR analysis of local skin swabs or in situ hybridization of the challenge site with an E6/E7 probe. After switching to CD3+ T cell depletion, papillomas appeared upon 14/15 of mice that had been CD4+ T cell depleted throughout the challenge phase, 1/15 of CD8+ T cell depleted mice, and none in mice without any prior T cell depletion. Both control animals and those depleted with CD8-specific antibody generated MusPV1 L1 capsid-specific antibodies, but not those depleted with CD4-specific antibody prior to T cell depletion with CD3 antibody. Thus, normal BALB/c or C57BL/6 mice eliminate the challenge dose, whereas infection is suppressed but not completely cleared if their CD4 or CD8 T cells are depleted, and recrudescence of MusPV1 is much greater in the former following treatment with CD3 antibody, possibly reflecting their failure to generate capsid antibody. Systemic vaccination of C57BL/6 mice with DNA vectors expressing MusPV1 E6 or E7 fused to calreticulin elicits potent CD8 T cell responses and these immunodominant CD8 T cell epitopes were mapped. Adoptive transfer of a MusPV1 E6-specific CD8+ T cell line controlled established MusPV1 infection and papilloma in RAG1-knockout mice. These findings suggest the potential of immunotherapy for HPV-related disease and the importance of host immunogenetics in the outcome of infection. PMID:26495972

  1. Black Holes, Gravitational Waves, and LISA

    NASA Technical Reports Server (NTRS)

    Baker, John

    2009-01-01

    Binary black hole mergers are central to many key science objectives of the Laser Interferometer Space Antenna (LISA). For many systems the strongest part of the signal is only understood by numerical simulations. Gravitational wave emissions are understood by simulations of vacuum General Relativity (GR). I discuss numerical simulation results from the perspective of LISA's needs, with indications of work that remains to be done. Some exciting scientific opportunities associated with LISA observations would be greatly enhanced if prompt electromagnetic signature could be associated. I discuss simulations to explore this possibility. Numerical simulations are important now for clarifying LISA's science potential and planning the mission. We also consider how numerical simulations might be applied at the time of LISA's operation.

  2. Genetic structure of lake whitefish (Coregonus clupeaformis) in Lake Michigan

    USGS Publications Warehouse

    VanDeHey, J.A.; Sloss, Brian L.; Peeters, Paul J.; Sutton, T.M.

    2009-01-01

    Genetic relationships among lake whitefish (Coregonus clupeaformis) spawning aggregates in Lake Michigan were assessed and used to predict a stock or management unit (MU) model for the resource. We hypothesized that distinct spawning aggregates represented potential MUs and that differences at molecular markers underlie population differentiation. Genetic stock identification using 11 microsatellite loci indicated the presence of six genetic MUs. Resolved MUs corresponded to geographically proximate spawning aggregates clustering into genetic groups. Within MUs, analyses suggested that all but one delineated MU was a stable grouping (i.e., no between-population differences), with the exception being the Hog Island - Traverse Bay grouping. Elk Rapids was the most genetically divergent population within Lake Michigan. However, low F st values suggested that moderate to high levels of gene flow occur or have occurred in the past between MUs. Significant tests of isolation by distance and low pairwise Fst values potentially led to conflicting results between traditional analyses and a Bayesian approach. This data set could provide baseline data from which a comprehensive mixed-stock analysis could be performed, allowing for more efficient and effective management of this economically and socially important resource.

  3. Oocytes from pachytene to dictyotene can easily be analysed in neonatal rodents.

    PubMed

    Singh, A P; Maerzke, S; von Deimling, O; Raman, R; Sperling, K; Neitzel, H

    1993-11-01

    We have investigated the dynamics of meiotic prophase I in neonatal ovaries from different wild rodent species, from a laboratory strain of Mus musculus and from Mus musculus x Mus spretus F1 hybrids. We found that almost all stages of prophase I were regularly present in neonatal ovaries from these species and that their transcriptional activity can be assessed by [3H]-uridine incorporation, indicating that postnatal analysis of meiotic chromosomes and synapsis may be conducted as an alternative to the investigation of foetal ovaries.

  4. X-Ray Detection of the Cluster Containing the Cepheid S Mus

    NASA Astrophysics Data System (ADS)

    Evans, Nancy Remage; Pillitteri, Ignazio; Wolk, Scott; Guinan, Edward; Engle, Scott; Bond, Howard E.; Schaefer, Gail H.; Karovska, Margarita; DePasquale, Joseph; Tingle, Evan

    2014-04-01

    The galactic Cepheid S Muscae has recently been added to the important list of Cepheids linked to open clusters, in this case the sparse young cluster ASCC 69. Low-mass members of a young cluster are expected to have rapid rotation and X-ray activity, making X-ray emission an excellent way to discriminate them from old field stars. We have made an XMM-Newton observation centered on S Mus and identified a population of X-ray sources whose near-IR Two Micron All Sky Survey counterparts lie at locations in the J, (J - K) color-magnitude diagram consistent with cluster membership at the distance of S Mus. Their median energy and X-ray luminosity are consistent with young cluster members as distinct from field stars. These strengthen the association of S Mus with the young cluster, making it a potential Leavitt law (period-luminosity relation) calibrator.

  5. Interspecies Variation in the Susceptibility of a Wild-Derived Colony of Mice to Pinworms (Aspiculuris tetraptera).

    PubMed

    Curtis, Ryan C; Murray, Jill K; Campbell, Polly; Nagamori, Yoko; Molnar, Adam; Jackson, Todd A

    2017-01-01

    Pinworms are common parasites in wild and laboratory rodents. Despite their relative nonpathogenicity in immunocompetent models, pinworm infections add an unwanted variable and may confound some types of research. For this reason, health monitoring programs and biosecurity measures aim to minimize the spread of pinworm infections into colonies free from the organisms. Wild-derived and laboratory strains of mice have shown varied susceptibility to infection with Aspiculuris tetraptera, the most commonly found murine pinworm. In particular, susceptibility is increased in wild-derived mice, young animals, and males. Routine surveillance at our institution revealed pinworm infection (A. tetraptera only) within a colony of multiple, wild-derived species of Mus, although only specific species showed positive results during initial sampling. To assess whether species-associated differences in susceptibility were present, we analyzed fecal egg counts of A. tetraptera in every cage of the colony. Our results revealed significant differences in susceptibility between various species and subspecies of Mus. Egg counts were significantly higher in Mus spicilegus than Mus m. domesticus (WSB/EiJ) and Mus macedonicus. Mus spretus had higher egg counts than M. m. domesticus (WSB/EiJ), M. m. musculus (PWK/PhJ), and M. macedonicus. Egg counts did not differ in regard to age, sex, or number of mice per cage. As wild-derived mouse models continue to compliment research largely based on laboratory strains, it will be important to understand host-parasite interactions and their effects on research, particularly studies evaluating immune responses, behavior, growth, and other physiologic parameters.

  6. Big Five personality traits and medically unexplained symptoms in later life.

    PubMed

    van Dijk, S D M; Hanssen, D; Naarding, P; Lucassen, P; Comijs, H; Oude Voshaar, R

    2016-10-01

    Personality dysfunction has been postulated as the most clinically salient problem of persons suffering from medically unexplained symptoms (MUS) but empirical studies are scarce. This study aims to compare the personality profile of older patients suffering from MUS with two comparison groups and a control group. Ninety-six older patients with MUS were compared with 153 frequent attenders in primary care suffering from medically explained symptoms (MES), 255 patients with a past-month depressive disorder (DSM-IV-TR), and a control group of 125 older persons. The Big Five personality domains (NEO-Five-Factor Inventory) were compared between groups by multiple ANCOVAs adjusted for age, sex, education, partner status and cognitive functioning. Linear regression analyses were applied to examine the association between health anxiety (Whitley Index) and somatization (Brief Symptom Inventory). The four groups differed with respect to neuroticism (P<0.001), extraversion (P<0.001), and agreeableness (P=0.045). Post hoc analyses, showed that MUS patients compared to controls scored higher on neuroticism and agreeableness, and compared to depressed patients lower on neuroticism and higher on extraversion as well agreeableness. Interestingly, MUS and MES patients had a similar personality profile. Health anxiety and somatization were associated with a higher level of neuroticism and a lower level of extraversion and conscientiousness, irrespective whether the physical symptom was explained or not. Older patients with MUS have a specific personality profile, comparable to MES patients. Health anxiety and somatization may be better indicators of psychopathology than whether a physical symptom is medically explained or not. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  7. Distinguishing intrinsic from extrinsic factors underlying firing rate saturation in human motor units

    PubMed Central

    Lester, Rosemary A.; Johns, Richard K.

    2014-01-01

    During voluntary contraction, firing rates of individual motor units (MUs) increase modestly over a narrow force range beyond which little additional increase in firing rate is seen. Such saturation of MU discharge may be a consequence of extrinsic factors that limit net synaptic excitation acting on motor neurons (MNs) or may be due to intrinsic properties of the MNs. Two sets of experiments involving recording of human biceps brachii MUs were carried out to evaluate saturation. In the first set, the extent of saturation was quantified for 136 low-threshold MUs during isometric ramp contractions. Firing rate-force data were best fit by a saturating function for 90% of MUs recorded with a maximum rate of 14.8 ± 2.0 impulses/s. In the second set of experiments, to distinguish extrinsic from intrinsic factors underlying saturation, we artificially augmented descending excitatory drive to biceps MNs by activation of muscle spindle afferents through tendon vibration. We examined the change in firing rate caused by tendon vibration in 96 MUs that were voluntarily activated at rates below and at saturation. Vibration had little effect on the discharge of MUs that were firing at saturation frequencies but strongly increased firing rates of the same units when active at lower frequencies. These results indicate that saturation is likely caused by intrinsic mechanisms that prevent further increases in firing rate in the presence of increasing synaptic excitation. Possible intrinsic cellular mechanisms that limit firing rates of motor units during voluntary effort are discussed. PMID:25475356

  8. [The Chinese expert consensus on clinical practice of "medically unexplained symptoms"].

    PubMed

    2017-02-01

    "Medically unexplained symptoms" (MUS) are commonly seen in all clinical specialties. The preliminary investigations in China show a prevalence of MUS in 4.15%-18.2% of clinical patients. Based on international and national guidelines and the most advanced studies, a Chinese expert consensus on clinical practice of MUS is reached through three rounds of discussion seminars by 25 experts from various specialties including psychiatry, internal medicine, surgery, gynecology-obstetrics, otorhinolar-yngology and traditional Chinese medicine. Clinical doctors should be alert of patients whose discomfort complaints cannot be explained by organic conditions after thorough physical examination and necessary laboratory tests. MUS should be recognized as early as possible so as to avoid complicating iatrogenic factors. A full bio-psycho-social evaluation of the patient is the basic structure of understanding MUS patients. In clinical practice, a trustful doctor-patient relationship is the first step of successful treatment. Then after a reasonable clinical evaluation, explain to the patient that it is a harmless functional symptom, communicate with the patient and reach an acceptable therapeutic goal, help the patient understand the symptoms in a psycho-somatic aspect and rebuild confidence of getting back to normal life. Patients with mild symptoms can be treated by doctors in various specialties, from whom the patient seeks help. Patients with severe symptoms need multi-disciplinary care including specific psychotherapy. Pharmaceutical treatment includes symptom alleviating drugs and antidepressants. In clinical care of patients with "MUS" , a full bio-psycho-social evaluation, a good doctor-patient relationship, a treatment plan according to the severity of symptoms, and a multi-disciplinary cooperation should be noted and practiced.

  9. A cost-effectiveness analysis of conservative versus surgical management for the initial treatment of stress urinary incontinence.

    PubMed

    Richardson, Monica L; Sokol, Eric R

    2014-11-01

    We sought to determine whether conservative or surgical therapy is more cost effective for the initial treatment of stress urinary incontinence (SUI). We created a decision tree model to compare costs and cost effectiveness of 3 strategies for the initial treatment of SUI: (1) continence pessary, (2) pelvic floor muscle therapy (PFMT), and (3) midurethral sling (MUS). We identified probabilities of SUI after 12 months of use of a pessary, PFMT, or MUS using published data. Parameter estimates included Health Utility Indices of no incontinence (.93) and persistent incontinence (0.7) after treatment. Morbidities associated with MUS included mesh erosion, retention, de novo urge incontinence, and recurrent SUI. Cost data were derived from Medicare in 2012 US dollars. One- and 2-way sensitivity analysis was used to examine the effect of varying rates of pursuing surgery if conservative management failed and rates of SUI cure with pessaries and PFMT. The primary outcome was an incremental cost-effectiveness ratio threshold <$50,000. Compared to PFMT, initial treatment of SUI with MUS was the more cost-effective strategy with an incremental cost-effectiveness ratio of $32,132/quality-adjusted life year. Initial treatment with PFMT was also acceptable as long as subjective cure was >35%. In 3-way sensitivity analysis, subjective cure would need to be >40.5% for PFMT and 43.5% for a continence pessary for the MUS scenario to not be the preferred strategy. At 1 year, MUS is more cost effective than a continence pessary or PFMT for the initial treatment for SUI. Copyright © 2014. Published by Elsevier Inc.

  10. Does body mass index influence the outcome of midurethral sling procedures for stress urinary incontinence?

    PubMed

    Xia, Ziyuan; Qian, Jialei; Chen, Yuntian; Liao, Banghua; Luo, Deyi

    2017-06-01

    Whether midurethral sling (MUS) procedures are as effective in obese women as they are in women of normal weight is still a matter of controversy. The objective of this study was to determine if body mass index (BMI) influences the outcome of MUS procedures for stress urinary incontinence (SUI). We searched electronic databases including EMBASE, MEDLINE, Web of Science and Ovid evidence-based medicine reviews to identify studies that explored the association between BMI and outcomes of MUS procedures. The studies were rated using the Newcastle-Ottawa scale; the meta-analysis was performed using Review Manager 5.3 software. This review included 11 studies, 6 prospective cohort studies and 5 retrospective studies, with a total of 2,846 patients. The objective success rates of MUS in patients with BMI >25 kg/m 2 (overweight and obese) were lower than in patients with BMI 18.5 - <25 kg/m 2 (normal weight; RR = 0.93, 95 % CI 0.89 - 0.97; P = 0.002). The objective success rates were not significantly different between the overweight group (BMI 25 - <30 kg/m 2 ) and the obese group (BMI ≥30 kg/m 2 ; RR = 0.95, 95 % CI 0.89 - 1.01; P = 0.08). There were no significant differences in subjective outcomes among the different BMI groups: BMI ≥25 kg/m 2 versus 18.5 - <25 kg/m 2 (RR = 1.03, 95 % CI 0.97 - 1.10; P = 0.29), and BMI ≥30 kg/m 2 versus 25 - <30 kg/m 2 (RR = 0.98, 95 % CI 0.92 - 1.04; P = 0.55). The objective success rates of MUS were lower in overweight and obese patients; however, the subjective outcomes of MUS were not significantly different among normal weight, overweight and obese patients. The MUS procedure is as effective in obese women as in women of normal weight, and therefore surgeons should not consider BMI >25 kg/m 2 as a risk factor when discussing the suitability of the MUS procedure in a patient with SUI.

  11. [Studies of the repair of radiation-induced genetic damage in Drosophila]. Final progress report

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

    Hawley, R.S.

    1998-11-01

    This research focuses on the structure of the mei-41 gene and elucidation of the role the mei-41 gene product plays in both recombination and repair. Genetic and molecular studies are continuing on the mus308 locus and the mus312 and mei-9 genes. The author views mus312 as a very likely candidate for a gene required for both chromosome pairing/synopsis and for double strand break repair. A thorough genetic study has been initiated of this locus and of the cytology of the meiotic and mitotic defects of mutations at this locus.

  12. The MusIC method: a fast and quasi-optimal solution to the muscle forces estimation problem.

    PubMed

    Muller, A; Pontonnier, C; Dumont, G

    2018-02-01

    The present paper aims at presenting a fast and quasi-optimal method of muscle forces estimation: the MusIC method. It consists in interpolating a first estimation in a database generated offline thanks to a classical optimization problem, and then correcting it to respect the motion dynamics. Three different cost functions - two polynomial criteria and a min/max criterion - were tested on a planar musculoskeletal model. The MusIC method provides a computation frequency approximately 10 times higher compared to a classical optimization problem with a relative mean error of 4% on cost function evaluation.

  13. Motor unit activity within the depth of the masseter characterized by an adapted scanning EMG technique.

    PubMed

    van Dijk, J P; Eiglsperger, U; Hellmann, D; Giannakopoulos, N N; McGill, K C; Schindler, H J; Lapatki, B G

    2016-09-01

    To study motor unit activity in the medio-lateral extension of the masseter using an adapted scanning EMG technique that allows studying the territories of multiple motor units (MUs) in one scan. We studied the m. masseter of 10 healthy volunteers in whom two scans were performed. A monopolar scanning needle and two pairs of fine-wire electrodes were inserted into the belly of the muscle. The signals of the fine wire electrodes were decomposed into the contribution of single MUs and used as a trigger for the scanning needle. In this manner multiple MU territory scans were obtained simultaneously. We determined 161 MU territories. The maximum number of territories obtained in one scan was 15. The median territory size was 4.0mm. Larger and smaller MU territories were found throughout the muscle. The presented technique showed its feasibility in obtaining multiple MU territories in one scan. MUs were active throughout the depth of the muscle. The distribution of electrical and anatomical size of MUs substantiates the heterogeneous distribution of MUs throughout the muscle volume. This distributed activity may be of functional significance for the stabilization of the muscle during force generation. Copyright © 2016 International Federation of Clinical Neurophysiology. All rights reserved.

  14. Patterns of motor recruitment can be determined using surface EMG.

    PubMed

    Wakeling, James M

    2009-04-01

    Previous studies have reported how different populations of motor units (MUs) can be recruited during dynamic and locomotor tasks. It was hypothesised that the higher-threshold units would contribute higher-frequency components to the sEMG spectra due to their faster conduction velocities, and thus recruitment patterns that increase the proportion of high-threshold units active would lead to higher-frequency elements in the sEMG spectra. This idea was tested by using a model of varying recruitment coupled to a three-layer volume conductor model to generate a series of sEMG signals. The recruitment varied from (A) orderly recruitment where the lowest-threshold MUs were initially activated and higher-threshold MUs were sequentially recruited as the contraction progressed, (B) a recurrent inhibition model that started with orderly recruitment, but as the higher-threshold units were activated they inhibited the lower-threshold MUs (C) nine models with intermediate properties that were graded between these two extremes. The sEMG was processed using wavelet analysis and the spectral properties quantified by their mean frequency, and an angle theta that was determined from the principal components of the spectra. Recruitment strategies that resulted in a greater proportion of faster MUs being active had a significantly lower theta and higher mean frequency.

  15. Nova Mus 2018 (PNV J11261220-6531086) Is Forming Dust

    NASA Astrophysics Data System (ADS)

    Walter, Frederick M.

    2018-02-01

    Nova Mus 2018 (PNV J11261220-6531086) was discovered by R Kaufman on 2018 Jan 14.486, and reported by P. Schmeer in vsnet-alert 21772. The first detection was 2018 Jan 3.24 (ASAS-SN, reported in the TOCP).

  16. Paradigm Shifts in Voluntary Force Control and Motor Unit Behaviors with the Manipulated Size of Visual Error Perception

    PubMed Central

    Chen, Yi-Ching; Lin, Yen-Ting; Chang, Gwo-Ching; Hwang, Ing-Shiou

    2017-01-01

    The detection of error information is an essential prerequisite of a feedback-based movement. This study investigated the differential behavior and neurophysiological mechanisms of a cyclic force-tracking task using error-reducing and error-enhancing feedback. The discharge patterns of a relatively large number of motor units (MUs) were assessed with custom-designed multi-channel surface electromyography following mathematical decomposition of the experimentally-measured signals. Force characteristics, force-discharge relation, and phase-locking cortical activities in the contralateral motor cortex to individual MUs were contrasted among the low (LSF), normal (NSF), and high scaling factor (HSF) conditions, in which the sizes of online execution errors were displayed with various amplification ratios. Along with a spectral shift of the force output toward a lower band, force output with a more phase-lead became less irregular, and tracking accuracy was worse in the LSF condition than in the HSF condition. The coherent discharge of high phasic (HP) MUs with the target signal was greater, and inter-spike intervals were larger, in the LSF condition than in the HSF condition. Force-tracking in the LSF condition manifested with stronger phase-locked EEG activity in the contralateral motor cortex to discharge of the (HP) MUs (LSF > NSF, HSF). The coherent discharge of the (HP) MUs during the cyclic force-tracking predominated the force-discharge relation, which increased inversely to the error scaling factor. In conclusion, the size of visualized error gates motor unit discharge, force-discharge relation, and the relative influences of the feedback and feedforward processes on force control. A smaller visualized error size favors voluntary force control using a feedforward process, in relation to a selective central modulation that enhance the coherent discharge of (HP) MUs. PMID:28348530

  17. Characterization of Mus musculus Papillomavirus 1 Infection In Situ Reveals an Unusual Pattern of Late Gene Expression and Capsid Protein Localization

    PubMed Central

    Handisurya, Alessandra; Day, Patricia M.; Thompson, Cynthia D.; Buck, Christopher B.; Pang, Yuk-Ying S.; Lowy, Douglas R.

    2013-01-01

    Full-length genomic DNA of the recently identified laboratory mouse papillomavirus 1 (MusPV1) was synthesized in vitro and was used to establish and characterize a mouse model of papillomavirus pathobiology. MusPV1 DNA, whether naked or encapsidated by MusPV1 or human papillomavirus 16 (HPV 16) capsids, efficiently induced the outgrowth of papillomas as early as 3 weeks after application to abraded skin on the muzzles and tails of athymic NCr nude mice. High concentrations of virions were extracted from homogenized papillomatous tissues and were serially passaged for >10 generations. Neutralization by L1 antisera confirmed that infectious transmission was capsid mediated. Unexpectedly, the skin of the murine back was much less susceptible to virion-induced papillomas than the muzzle or tail. Although reporter pseudovirions readily transduced the skin of the back, infection with native MusPV1 resulted in less viral genome amplification and gene expression on the back, including reduced expression of the L1 protein and very low expression of the L2 protein, results that imply skin region-specific control of postentry aspects of the viral life cycle. Unexpectedly, L1 protein on the back was predominantly cytoplasmic, while on the tail the abundant L1 was cytoplasmic in the lower epithelial layers and nuclear in the upper layers. Nuclear localization of L1 occurred only in cells that coexpressed the minor capsid protein, L2. The pattern of L1 protein staining in the infected epithelium suggests that L1 expression occurs earlier in the MusPV1 life cycle than in the life cycle of high-risk HPV and that virion assembly is regulated by a previously undescribed mechanism. PMID:24067981

  18. Paradigm Shifts in Voluntary Force Control and Motor Unit Behaviors with the Manipulated Size of Visual Error Perception.

    PubMed

    Chen, Yi-Ching; Lin, Yen-Ting; Chang, Gwo-Ching; Hwang, Ing-Shiou

    2017-01-01

    The detection of error information is an essential prerequisite of a feedback-based movement. This study investigated the differential behavior and neurophysiological mechanisms of a cyclic force-tracking task using error-reducing and error-enhancing feedback. The discharge patterns of a relatively large number of motor units (MUs) were assessed with custom-designed multi-channel surface electromyography following mathematical decomposition of the experimentally-measured signals. Force characteristics, force-discharge relation, and phase-locking cortical activities in the contralateral motor cortex to individual MUs were contrasted among the low (LSF), normal (NSF), and high scaling factor (HSF) conditions, in which the sizes of online execution errors were displayed with various amplification ratios. Along with a spectral shift of the force output toward a lower band, force output with a more phase-lead became less irregular, and tracking accuracy was worse in the LSF condition than in the HSF condition. The coherent discharge of high phasic (HP) MUs with the target signal was greater, and inter-spike intervals were larger, in the LSF condition than in the HSF condition. Force-tracking in the LSF condition manifested with stronger phase-locked EEG activity in the contralateral motor cortex to discharge of the (HP) MUs (LSF > NSF, HSF). The coherent discharge of the (HP) MUs during the cyclic force-tracking predominated the force-discharge relation, which increased inversely to the error scaling factor. In conclusion, the size of visualized error gates motor unit discharge, force-discharge relation, and the relative influences of the feedback and feedforward processes on force control. A smaller visualized error size favors voluntary force control using a feedforward process, in relation to a selective central modulation that enhance the coherent discharge of (HP) MUs.

  19. Variability of quadriceps femoris motor neuron discharge and muscle force in human aging.

    PubMed

    Welsh, Seth J; Dinenno, Devin V; Tracy, Brian L

    2007-05-01

    The purpose was to determine the contribution of visual feedback and the effect of aging on the variability of knee extensor (KE) muscle force and motor unit (MU) discharge. Single MUs were recorded during two types of isometric trials, (1) visual feedback provided (VIS) and then removed (NOVIS) during the trial (34 MUs from young, 32 from elderly), and (2) only NOVIS (66 MUs from young, 77 from elderly) during the trial. Recruitment threshold (RT) ranged from 0-37% MVC. Standard deviation (SD) and coefficient of variation (CV) of muscle force and MU interspike interval (ISI) was measured during steady contractions at target forces ranging from 0.3 to 54% MVC. Force drift (<0.5 Hz) was removed before analysis. VIS/NOVIS trials: the decrease in the CV of ISI from VIS to NOVIS was greater for MUs from elderly (12.5 +/- 4.1 to 9.94 +/- 2.6%) than young (10.6 +/- 3.3 to 10.3 +/- 2.8%, age group x vision interaction, P = 0.006). The change in CV of force from VIS to NOVIS was significantly greater for elderly (1.45 to 1.05%) than young (1.42 to 1.41%). NOVIS only trials: for all MUs, the average RT (6.6 +/- 7.7 % MVC), target force above RT (1.20 +/- 2.7% MVC), SD of ISI (0.012 +/- 0.005 s), and CV of ISI (11.1 +/- 3.3%) were similar for young and elderly MUs. The CV of force was similar between age groups for trials between 0 and 3% MVC (1.74 +/- 0.74%) and was greater for young subjects from 3 to 10% MVC (1.47 +/- 0.5 vs. 1.21 +/- 0.4%) and >10% MVC (1.44 +/- 0.6 vs. 1.01 +/- 0.3%). The CV of ISI was similar between age groups for MUs in 0-3, 3-10, and >10% bins of RT. Thus, the contribution of visuomotor correction to the variability of motor unit discharge and force is greater for elderly adults. The presence of visual feedback appears to be necessary to find greater discharge variability in motor units from the knee extensors of elderly adults.

  20. Magnetic properties of mixed sulfides MUS/sub 3/ (M = V, Cr, Nb, Ta)

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

    Nutsubidze, P.V.; Chechernikov, V.I.; Gracheva, N.V.

    1985-08-01

    The authors synthesized US/sub 2/ (Beta-US/sub 2/), VS, CrS, NbS, and TaS by the vacuum-thermal method in quartz ampules heated to 1170 degrees K. They homogenized and sintered these samples and remixed and sintered appropriate amounts to form MUS/sub 2/, which crystallizes in a rhombic structure. They studied the magnetic properties of MUS/sub 2/ on a vibration magnetometer in the range 75500 degrees K. The results of their analysis of the magnetic coefficients proved consistent with thermodynamic theory. They present their data in a series of four charts and two tables.

  1. The highest-frequency kHz QPOs in neutron star low mass X-ray binaries

    NASA Astrophysics Data System (ADS)

    van Doesburgh, Marieke; van der Klis, Michiel; Morsink, Sharon M.

    2018-05-01

    We investigate the detections with RXTE of the highest-frequency kHz QPOs previously reported in six neutron star (NS) low mass X-ray binaries. We find that the highest-frequency kHz QPO detected in 4U 0614+09 has a 1267 Hz 3σ confidence lower limit on its centroid frequency. This is the highest such limit reported to date, and of direct physical interest as it can be used to constrain QPO models and the supranuclear density equation of state (EoS). We compare our measured frequencies to maximum orbital frequencies predicted in full GR using models of rotating neutron stars with a number of different modern EoS and show that these can accommodate the observed QPO frequencies. Orbital motion constrained by NS and ISCO radii is therefore a viable explanation of these QPOs. In the most constraining case of 4U 0614+09 we find the NS mass must be M<2.1 M⊙. From our measured QPO frequencies we can constrain the NS radii for five of the six sources we studied to narrow ranges (±0.1-0.7 km) different for each source and each EoS.

  2. Construction of a small Mus musculus repetitive DNA library: identification of a new satellite sequence in Mus musculus.

    PubMed Central

    Pietras, D F; Bennett, K L; Siracusa, L D; Woodworth-Gutai, M; Chapman, V M; Gross, K W; Kane-Haas, C; Hastie, N D

    1983-01-01

    We report the construction of a small library of recombinant plasmids containing Mus musculus repetitive DNA inserts. The repetitive cloned fraction was derived from denatured genomic DNA by reassociation to a Cot value at which repetitive, but not unique, sequences have reannealed followed by exhaustive S1 nuclease treatment to degrade single stranded DNA. Initial characterizations of this library by colony filter hybridizations have led to the identification of a previously undetected M. musculus minor satellite as well as to clones containing M. musculus major satellite sequences. This new satellite is repeated 10-20 times less than the major satellite in the M. musculus genome. It has a repeat length of 130 nucleotides compared with the M. musculus major satellite with a repeat length of 234 nucleotides. Sequence analysis of the minor satellite has shown that it has a 29 base pair region with extensive homology to one of the major satellite repeating subunits. We also show by in situ hybridization that this minor satellite sequence is located at the centromeres and possibly the arms of at least half the M musculus chromosomes. Sequences related to the minor satellite have been found in the DNA of a related Mus species, Mus spretus, and may represent the major satellite of that species. Images PMID:6314268

  3. 50 CFR 665.14 - Reporting and recordkeeping.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... to the Regional Administrator within 7 days of each landing of coral reef ecosystem MUS. (d) Sales... immediately available for Federal inspection and copying upon request by an authorized officer. (4) Coral reef... maintain and submit records of catch and effort, landings and sales for coral reef ecosystem MUS by this...

  4. 50 CFR 665.14 - Reporting and recordkeeping.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... to the Regional Administrator within 7 days of each landing of coral reef ecosystem MUS. (d) Sales... immediately available for Federal inspection and copying upon request by an authorized officer. (4) Coral reef... maintain and submit records of catch and effort, landings and sales for coral reef ecosystem MUS by this...

  5. 77 FR 66 - Western Pacific Fisheries; 2012 Annual Catch Limits and Accountability Measures

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-03

    ... proposes annual catch limits for western Pacific bottomfish, crustacean, precious coral, and coral reef... specify ACLs for bottomfish, crustacean, precious coral, and coral reef ecosystem fishery MUS in American... bottomfish, crustacean, precious coral, or coral reef ecosystem MUS in the PRIA because commercial fishing is...

  6. 50 CFR 665.463 - Prohibitions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Mariana precious coral MUS in any Mariana precious coral permit area, unless a permit has been issued for..., take, or retain any species of Mariana precious coral MUS in any Mariana precious coral permit area: (1...) Take and retain, possess, or land any live pink coral or live black coral from any precious coral...

  7. 50 CFR 665.463 - Prohibitions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Mariana precious coral MUS in any Mariana precious coral permit area, unless a permit has been issued for..., take, or retain any species of Mariana precious coral MUS in any Mariana precious coral permit area: (1...) Take and retain, possess, or land any live pink coral or live black coral from any precious coral...

  8. 50 CFR 665.463 - Prohibitions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Mariana precious coral MUS in any Mariana precious coral permit area, unless a permit has been issued for..., take, or retain any species of Mariana precious coral MUS in any Mariana precious coral permit area: (1...) Take and retain, possess, or land any live pink coral or live black coral from any precious coral...

  9. 50 CFR 665.463 - Prohibitions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Mariana precious coral MUS in any Mariana precious coral permit area, unless a permit has been issued for..., take, or retain any species of Mariana precious coral MUS in any Mariana precious coral permit area: (1...) Take and retain, possess, or land any live pink coral or live black coral from any precious coral...

  10. 50 CFR 665.463 - Prohibitions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Mariana precious coral MUS in any Mariana precious coral permit area, unless a permit has been issued for..., take, or retain any species of Mariana precious coral MUS in any Mariana precious coral permit area: (1...) Take and retain, possess, or land any live pink coral or live black coral from any precious coral...

  11. Stop Stalling: Mus81 Required for Efficient Replication | Center for Cancer Research

    Cancer.gov

    DNA replication is precisely controlled to ensure that daughter cells receive intact, accurate genetic information. Each segment of DNA must be copied only once, and the rate of replication coordinated genome-wide. Mild replication stress slows DNA synthesis and activates a pathway involving the Mus81 endonuclease, which generates a series of DNA breaks that are rapidly repaired, allowing the cell to avoid activating the S-phase checkpoint and its potentially damaging outcomes of apoptosis or error-prone repair. Mirit Aladjem, Ph.D., of CCR’s Developmental Therapeutics Branch, and her colleagues wondered whether Mus81 also plays a role in regulating the replication rate during growth in the absence of stress.

  12. 50 CFR 665.124 - Permits and fees.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... retaining American Samoa coral reef ecosystem MUS must have a special permit if they, or a vessel which they operate, is used to fish for any: (i) American Samoa coral reef ecosystem MUS in low-use MPAs as defined in § 665.99; (ii) American Samoa Potentially Harvested Coral Reef Taxa in the coral reef ecosystem...

  13. 50 CFR 665.124 - Permits and fees.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... retaining American Samoa coral reef ecosystem MUS must have a special permit if they, or a vessel which they operate, is used to fish for any: (i) American Samoa coral reef ecosystem MUS in low-use MPAs as defined in § 665.99; (ii) American Samoa Potentially Harvested Coral Reef Taxa in the coral reef ecosystem...

  14. 50 CFR 665.424 - Permits and fees.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... retaining Mariana coral reef ecosystem MUS must have a special permit if they, or a vessel which they operate, is used to fish for any: (i) Mariana coral reef ecosystem MUS in low-use MPAs as defined in § 665.399; (ii) Mariana Potentially Harvested Coral Reef Taxa in the coral reef ecosystem management area...

  15. 50 CFR 665.124 - Permits and fees.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... retaining American Samoa coral reef ecosystem MUS must have a special permit if they, or a vessel which they operate, is used to fish for any: (i) American Samoa coral reef ecosystem MUS in low-use MPAs as defined in § 665.99; (ii) American Samoa Potentially Harvested Coral Reef Taxa in the coral reef ecosystem...

  16. 50 CFR 665.424 - Permits and fees.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... retaining Mariana coral reef ecosystem MUS must have a special permit if they, or a vessel which they operate, is used to fish for any: (i) Mariana coral reef ecosystem MUS in low-use MPAs as defined in § 665.399; (ii) Mariana Potentially Harvested Coral Reef Taxa in the coral reef ecosystem management area...

  17. 50 CFR 665.424 - Permits and fees.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... retaining Mariana coral reef ecosystem MUS must have a special permit if they, or a vessel which they operate, is used to fish for any: (i) Mariana coral reef ecosystem MUS in low-use MPAs as defined in § 665.399; (ii) Mariana Potentially Harvested Coral Reef Taxa in the coral reef ecosystem management area...

  18. 50 CFR 665.124 - Permits and fees.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... retaining American Samoa coral reef ecosystem MUS must have a special permit if they, or a vessel which they operate, is used to fish for any: (i) American Samoa coral reef ecosystem MUS in low-use MPAs as defined in § 665.99; (ii) American Samoa Potentially Harvested Coral Reef Taxa in the coral reef ecosystem...

  19. 50 CFR 665.424 - Permits and fees.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... retaining Mariana coral reef ecosystem MUS must have a special permit if they, or a vessel which they operate, is used to fish for any: (i) Mariana coral reef ecosystem MUS in low-use MPAs as defined in § 665.399; (ii) Mariana Potentially Harvested Coral Reef Taxa in the coral reef ecosystem management area...

  20. 50 CFR 665.424 - Permits and fees.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... retaining Mariana coral reef ecosystem MUS must have a special permit if they, or a vessel which they operate, is used to fish for any: (i) Mariana coral reef ecosystem MUS in low-use MPAs as defined in § 665.399; (ii) Mariana Potentially Harvested Coral Reef Taxa in the coral reef ecosystem management area...

  1. 50 CFR 665.124 - Permits and fees.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... retaining American Samoa coral reef ecosystem MUS must have a special permit if they, or a vessel which they operate, is used to fish for any: (i) American Samoa coral reef ecosystem MUS in low-use MPAs as defined in § 665.99; (ii) American Samoa Potentially Harvested Coral Reef Taxa in the coral reef ecosystem...

  2. 50 CFR 665.663 - Prohibitions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., possess or land PRIA precious coral MUS in any precious coral permit area, unless a permit has been issued..., take, or retain any species of PRIA precious coral MUS in any precious coral permit area: (1) By means... retain, possess, or land any live pink coral or live black coral from any precious coral permit area that...

  3. 50 CFR 665.663 - Prohibitions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ..., possess or land PRIA precious coral MUS in any precious coral permit area, unless a permit has been issued..., take, or retain any species of PRIA precious coral MUS in any precious coral permit area: (1) By means... retain, possess, or land any live pink coral or live black coral from any precious coral permit area that...

  4. 50 CFR 665.663 - Prohibitions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., possess or land PRIA precious coral MUS in any precious coral permit area, unless a permit has been issued..., take, or retain any species of PRIA precious coral MUS in any precious coral permit area: (1) By means... retain, possess, or land any live pink coral or live black coral from any precious coral permit area that...

  5. 50 CFR 665.663 - Prohibitions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., possess or land PRIA precious coral MUS in any precious coral permit area, unless a permit has been issued..., take, or retain any species of PRIA precious coral MUS in any precious coral permit area: (1) By means... retain, possess, or land any live pink coral or live black coral from any precious coral permit area that...

  6. 50 CFR 665.663 - Prohibitions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ..., possess or land PRIA precious coral MUS in any precious coral permit area, unless a permit has been issued..., take, or retain any species of PRIA precious coral MUS in any precious coral permit area: (1) By means... retain, possess, or land any live pink coral or live black coral from any precious coral permit area that...

  7. Detection of Highly-Absorbed X-rays from Nova Mus 2018 with Swift

    NASA Astrophysics Data System (ADS)

    Nelson, Thomas; Kuin, Paul; Mukai, Koji; Page, Kim; Chomiuk, Laura; Kawash, Adam; Sokoloski, J. L.; Linford, Justin; Rupen, Michael P.; Mioduszewski, Amy

    2018-03-01

    We report the detection of X-rays from Nova Mus 2018 with the Swift XRT instrument. We have been carrying out weekly monitoring of the nova with Swift since its discovery on 2018 Jan 15 (see ATel #11220), and observations up to 2018 Feb 24 yielded X-ray non-detections.

  8. Forensic STR loci reveal common genetic ancestry of the Thai-Malay Muslims and Thai Buddhists in the deep Southern region of Thailand.

    PubMed

    Kutanan, Wibhu; Kitpipit, Thitika; Phetpeng, Sukanya; Thanakiatkrai, Phuvadol

    2014-12-01

    Among the people living in the five deep Southern Thai provinces, Thai-Malay Muslims (MUS) constitute the majority, while the remaining are Thai Buddhists (BUD). Cultural, linguistic and religious differences between these two populations have been previously reported. However, their biological relationship has never been investigated. In this study, we aimed to reveal the genetic structure and genetic affinity between MUS and BUD by analyzing 15 autosomal short tandem repeats. Both distance and model-based clustering methods showed significant genetic homogeneity between these two populations, suggesting a common biological ancestry. After Islamization in this region during the fourteenth century AD, gradual albeit nonstatistically significant genetic changes occurred within these two populations. Cultural barriers possibly influenced these genetic changes. MUS have closer admixture to Malaysian-Malay Muslims than BUD countrywide. Admixture proportions also support certain degree of genetic dissimilarity between the two studied populations, as shown by the unequal genetic contribution from Malaysian-Malay Muslims. Cultural transformation and recent minor genetic admixture are the likely processes that shaped the genetic structure of both MUS and BUD.

  9. Host subspecific viral strains in European house mice: Murine cytomegalovirus in the Eastern (Mus musculus musculus) and Western house mouse (Mus musculus domesticus).

    PubMed

    Čížková, Dagmar; Baird, Stuart J E; Těšíková, Jana; Voigt, Sebastian; Ľudovít, Ďureje; Piálek, Jaroslav; Goüy de Bellocq, Joëlle

    2018-06-09

    Murine cytomegalovirus (MCMV) has been reported from house mice (Mus musculus) worldwide, but only recently from Eastern house mice (M. m. musculus), of particular interest because they form a semi-permeable species barrier in Europe with Western house mice, M. m. domesticus. Here we report genome sequences of EastMCMV (from Eastern mice), and set these in the context of MCMV genomes from genus Mus hosts. We show EastMCMV and WestMCMV are genetically distinct. Phylogeny splitting analyses show a genome wide (94%) pattern consistent with no West-East introgression, the major exception (3.8%) being a genome-terminal region of duplicated genes involved in host immune system evasion. As expected from its function, this is a region of maintenance of ancestral polymorphism: The lack of clear splitting signal cannot be interpreted as evidence of introgression. The EastMCMV genome sequences reported here can therefore serve as a well-described resource for exploration of murid MCMV diversity. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Randomized trial of reattribution on psychosocial talk between doctors and patients with medically unexplained symptoms.

    PubMed

    Morriss, R; Gask, L; Dowrick, C; Dunn, G; Peters, S; Ring, A; Davies, J; Salmon, P

    2010-02-01

    In reattribution, general practitioners (GPs) request psychosocial information directly and explain medically unexplained symptoms (MUS) using psychosocial information in the consultation. We explored whether reattribution training (RT) increased the communication of psychosocial information and decreased communication about somatic intervention between GPs and their MUS patients. A cluster randomized controlled trial (RCT) of RT versus usual treatment in GPs from 16 practices and 141 patients with MUS on audio-recorded and transcribed doctor-patient communication in an index consultation. In a secondary data analysis, the Liverpool Clinical Interaction Analysis Scheme (LCIAS) was applied by an experienced rater to each turn of speech in the transcript from the index consultation blind to treatment allocation. After RT, patients were more likely to disclose and discuss psychosocial problems, and propose psychosocial explanations for symptoms; around 25% of patients discussed psychosocial information extensively. In the RT group, GPs did not seek new psychosocial disclosure but they reduced advocacy for somatic intervention. After RT, GPs suggested, on average, two utterances of psychosocial explanation and six utterances of somatic intervention. After RT, some patients discussed psychosocial issues extensively but GPs did not probe underlying psychosocial issues. They gave mixed psychosocial and somatic messages about MUS, which may have increased patients' concerns about their health. GPs should actively seek the disclosure of underlying psychosocial problems and give clear, unambiguous messages to MUS patients when they are willing to discuss psychosocial issues.

  11. GABAergic regulation of REM sleep in reticularis pontis oralis and caudalis in rats.

    PubMed

    Sanford, Larry D; Tang, Xiangdong; Xiao, Jihua; Ross, Richard J; Morrison, Adrian R

    2003-08-01

    The nucleus reticularis pontis oralis (RPO) and nucleus reticularis pontis caudalis (RPC) are implicated in the generation of rapid eye movement sleep (REM). Work in cats has indicated that GABA in RPO plays a role in the regulation of REM. We assessed REM after local microinjections into RPO and RPC of the gamma-aminobutyric acid-A (GABA(A)) agonist, muscimol (MUS), and the GABA(A) antagonist, bicuculline (BIC). Rats (90-day-old male Sprague-Dawley) were implanted with electrodes for recording electroencephalographs (EEG) and electromyographs (EMG). Guide cannulae were aimed into RPO (n = 9) and RPC (n = 8) for microinjecting MUS (200, 1,000.0 microM) and BIC (0.056, 0.333, 1.0, 1,000.0, and 10,000.0 microM). Animals received bilateral microinjections of saline, MUS, and BIC (0.2 microl microinjected at 0.1 microl/min) into each region followed by 6-h sleep recordings. In RPO, MUS (1,000.0 microM) suppressed REM and BIC (1,000.0 microM) enhanced REM. In RPC, MUS (200, 1,000.0 microM) suppressed REM, but BIC (1,000.0 microM and less) did not significantly affect REM. Higher concentrations of BIC (10,000.0 microM) injected into RPO (n = 9) and RPC (n = 4) produced wakefulness and escape behavior. The results indicate that GABA in RPO/RPC is involved in the regulation of REM and suggest site-specific differences in this regulation.

  12. The influence of the way the muscle force is modeled on the predicted results obtained by solving indeterminate problems for a fast elbow flexion.

    PubMed

    Raikova, Rositsa; Aladjov, Hristo

    2003-06-01

    A critical point in models of the human limbs when the aim is to investigate the motor control is the muscle model. More often the mechanical output of a muscle is considered as one musculotendon force that is a design variable in optimization tasks solved predominantly by static optimization. For dynamic conditions, the relationship between the developed force, the length and the contraction velocity of a muscle becomes important and rheological muscle models can be incorporated in the optimization tasks. Here the muscle activation can be a design variable as well. Recently a new muscle model was proposed. A muscle is considered as a mixture of motor units (MUs) with different peculiarities and the muscle force is calculated as a sum of the MUs twitches. The aim of the paper is to compare these three ways for presenting the muscle force. Fast elbow flexion is investigated using a planar model with five muscles. It is concluded that the rheological models are suitable for calculation of the current maximal muscle forces that can be used as weight factors in the objective functions. The model based on MUs has many advantages for precise investigations of motor control. Such muscle presentation can explain the muscle co-contraction and the role of the fast and the slow MUs. The relationship between the MUs activation and the mechanical output is more clear and closer to the reality.

  13. The effect of an educational intervention in family phisicians on self-rated quality of life in patients with medically unexplained symptoms.

    PubMed

    Ivetić, Vojislav; Pašić, Klemen; Selič, Polona

    2017-06-01

    Medically unexplained symptoms (MUS) are very common in family medicine, despite being a poorly-defined clinical entity. This study aimed to evaluate the effect of an educational intervention (EI) on self-rated quality of life, treatment satisfaction, and the family physician-patient relationship in patients with MUS. In a multi-centre longitudinal intervention study, which was performed between 2012 and 2014, patients were asked to rate their quality of life, assess their depression, anxiety, stress and somatisation, complete the Hypochondriasis Index, the Medical Interview Satisfaction Scale and the Patient Enablement Instrument for assessing the physician-patient relationship, before and after the EI. The mean values before and after the intervention showed that after the EI, patients with MUS gave a lower (total) mean rating of their health issues and a higher rating of their quality of life, and they also had a more positive opinion of their relationship with the physician (p<0.05). However, there were no differences in the (total) rating of treatment satisfaction before and after the EI (p=0.423). Significant differences in the symptoms in patients with MUS before and after the intervention were confirmed for stress, somatisation and hypochondriasis (p<0.05). It could be beneficial to equip family physicians with the knowledge, skills and tools to reduce hypochondriasis and somatisation in MUS patients, which would improve patients' self-rated health status.

  14. Treatment with Riluzole Restores Normal Control of Soleus and Extensor Digitorum Longus Muscles during Locomotion in Adult Rats after Sciatic Nerve Crush at Birth

    PubMed Central

    Cabaj, Anna M.; Sławińska, Urszula

    2017-01-01

    The effects of sciatic nerve crush (SNC) and treatment with Riluzole on muscle activity during unrestrained locomotion were identified in an animal model by analysis of the EMG activity recorded from soleus (Sol) and extensor digitorum longus (EDL) muscles of both hindlimbs; in intact rats (IN) and in groups of rats treated for 14 days with saline (S) or Riluzole (R) after right limb nerve crush at the 1st (1S and 1R) or 2nd (2S and 2R) day after birth. Changes in the locomotor pattern of EMG activity were correlated with the numbers of survived motor units (MUs) identified in investigated muscles. S rats with 2–8 and 10–28 MUs that survived in Sol and EDL muscles respectively showed increases in the duration and duty factor of muscle EMG activity and a loss of correlation between the duty factors of muscle activity, and abnormal flexor-extensor co-activation 3 months after SNC. R rats with 5, 6 (Sol) and 15–29 MUs (EDL) developed almost normal EMG activity of both Sol and control EDL muscles, whereas EDL muscles with SNC showed a lack of recovery. R rats with 8 (Sol) and 23–33 (EDL) MUs developed almost normal EMG activities of all four muscles. A subgroup of S rats with a lack of recovery and R rats with almost complete recovery that had similar number of MUs (8 and 24–28 vs 8 and 23–26), showed that the number of MUs was not the only determinant of treatment effectiveness. The results demonstrated that rats with SNC failed to develop normal muscle activity due to malfunction of neuronal circuits attenuating EDL muscle activity during the stance phase, whereas treatment with Riluzole enabled almost normal EMG activity of Sol and EDL muscles during locomotor movement. PMID:28095499

  15. Does Mid-Urethral Sling Surgery in the Treatment of Stress Urinary Incontinence Affect Weight Changes in Women? A Retrospective Cohort Study Using Internal Controls.

    PubMed

    Gehrich, Alan P; Patzwald, Jason; Raby, Lauren; Lustik, Michael; Gruber, Daniel; Gonzalez, Hector

    2017-11-01

    Stress urinary incontinence (SUI) is a common disorder among women. This is particularly bothersome to physically active women, such as those who serve in the Armed Forces. With the documented success of the midurethral sling (MUS) in the treatment of SUI, more women are electing to undergo surgical treatment. Studies document that women have less inhibition about exercise as a result of decreased incontinence following MUS surgery. We sought to determine if MUS surgery is associated with a change in weight postoperatively resulting from increased levels of activity following surgery. We hypothesized that women, particularly active duty (AD) women, would experience a decrease in weight and body mass index (BMI) in the year following the MUS procedure. This retrospective cohort study used the military electronic medical record system. The subjects included AD military and civilian (CV) patients who underwent MUS surgery at tertiary care centers between July 2006 and March 2013. Weight and BMI were recorded for three distinct time periods: 1-year preoperatively, at time of surgery, and 1-year postoperatively. A total of 207 women met inclusion criteria, 76 of which were AD women in the U.S. military. For the group as a whole, we found no significant difference in mean weight or BMI among the three time points examined; however, decreases in BMI and weight were noted in the year following surgery for the subgroups of AD and obese women. Analysis of covariance showed that age, parity, preoperative weight, and concomitant hysterectomy were not significant determinants for change in weight postoperatively. Despite its effective treatment of SUI, MUS surgery did not significantly affect the weight of patients postoperatively in our retrospective cohort. Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.

  16. Treatment with Riluzole Restores Normal Control of Soleus and Extensor Digitorum Longus Muscles during Locomotion in Adult Rats after Sciatic Nerve Crush at Birth.

    PubMed

    Zmysłowski, Wojciech; Cabaj, Anna M; Sławińska, Urszula

    2017-01-01

    The effects of sciatic nerve crush (SNC) and treatment with Riluzole on muscle activity during unrestrained locomotion were identified in an animal model by analysis of the EMG activity recorded from soleus (Sol) and extensor digitorum longus (EDL) muscles of both hindlimbs; in intact rats (IN) and in groups of rats treated for 14 days with saline (S) or Riluzole (R) after right limb nerve crush at the 1st (1S and 1R) or 2nd (2S and 2R) day after birth. Changes in the locomotor pattern of EMG activity were correlated with the numbers of survived motor units (MUs) identified in investigated muscles. S rats with 2-8 and 10-28 MUs that survived in Sol and EDL muscles respectively showed increases in the duration and duty factor of muscle EMG activity and a loss of correlation between the duty factors of muscle activity, and abnormal flexor-extensor co-activation 3 months after SNC. R rats with 5, 6 (Sol) and 15-29 MUs (EDL) developed almost normal EMG activity of both Sol and control EDL muscles, whereas EDL muscles with SNC showed a lack of recovery. R rats with 8 (Sol) and 23-33 (EDL) MUs developed almost normal EMG activities of all four muscles. A subgroup of S rats with a lack of recovery and R rats with almost complete recovery that had similar number of MUs (8 and 24-28 vs 8 and 23-26), showed that the number of MUs was not the only determinant of treatment effectiveness. The results demonstrated that rats with SNC failed to develop normal muscle activity due to malfunction of neuronal circuits attenuating EDL muscle activity during the stance phase, whereas treatment with Riluzole enabled almost normal EMG activity of Sol and EDL muscles during locomotor movement.

  17. 50 CFR 665.224 - Permits and fees.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... retaining Hawaii coral reef ecosystem MUS must have a special permit if they, or a vessel which they operate, is used to fish for any: (i) Hawaii coral reef ecosystem MUS in low-use MPAs as defined in § 665.199; (ii) Hawaii Potentially Harvested Coral Reef Taxa in the coral reef ecosystem management area; or (iii...

  18. 50 CFR 665.625 - Prohibitions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., possess or land any PRIA coral reef ecosystem MUS in any low-use MPA as defined in § 665.599 unless: (1) A... applicable area of harvest; (2) A permit is not required, as outlined in § 665.624; (3) The PRIA coral reef..., take, or retain any PRIA coral reef ecosystem MUS species: (1) That is determined overfished with...

  19. 50 CFR 665.225 - Prohibitions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... land any Hawaii coral reef ecosystem MUS in any low-use MPA as defined in § 665.199 unless: (1) A valid..., take, or retain any Hawaii coral reef ecosystem MUS species: (1) That is determined overfished with... applicable area of harvest; (2) A permit is not required, as outlined in § 665.224; or (3) The Hawaii coral...

  20. 50 CFR 665.224 - Permits and fees.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... retaining Hawaii coral reef ecosystem MUS must have a special permit if they, or a vessel which they operate, is used to fish for any: (i) Hawaii coral reef ecosystem MUS in low-use MPAs as defined in § 665.199; (ii) Hawaii Potentially Harvested Coral Reef Taxa in the coral reef ecosystem management area; or (iii...

  1. 50 CFR 665.224 - Permits and fees.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... retaining Hawaii coral reef ecosystem MUS must have a special permit if they, or a vessel which they operate, is used to fish for any: (i) Hawaii coral reef ecosystem MUS in low-use MPAs as defined in § 665.199; (ii) Hawaii Potentially Harvested Coral Reef Taxa in the coral reef ecosystem management area; or (iii...

  2. 50 CFR 665.624 - Permits and fees.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... applies to coral reef ecosystem permits. (1) Special permit. Any person of the United States fishing for, taking or retaining PRIA coral reef ecosystem MUS must have a special permit if they, or a vessel which they operate, is used to fish for any: (i) PRIA Coral reef ecosystem MUS in low-use MPAs as defined in...

  3. 50 CFR 665.225 - Prohibitions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... land any Hawaii coral reef ecosystem MUS in any low-use MPA as defined in § 665.199 unless: (1) A valid..., take, or retain any Hawaii coral reef ecosystem MUS species: (1) That is determined overfished with... applicable area of harvest; (2) A permit is not required, as outlined in § 665.224; or (3) The Hawaii coral...

  4. 50 CFR 665.225 - Prohibitions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... land any Hawaii coral reef ecosystem MUS in any low-use MPA as defined in § 665.199 unless: (1) A valid..., take, or retain any Hawaii coral reef ecosystem MUS species: (1) That is determined overfished with... applicable area of harvest; (2) A permit is not required, as outlined in § 665.224; or (3) The Hawaii coral...

  5. 50 CFR 665.224 - Permits and fees.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... retaining Hawaii coral reef ecosystem MUS must have a special permit if they, or a vessel which they operate, is used to fish for any: (i) Hawaii coral reef ecosystem MUS in low-use MPAs as defined in § 665.199; (ii) Hawaii Potentially Harvested Coral Reef Taxa in the coral reef ecosystem management area; or (iii...

  6. 50 CFR 665.225 - Prohibitions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... land any Hawaii coral reef ecosystem MUS in any low-use MPA as defined in § 665.199 unless: (1) A valid..., take, or retain any Hawaii coral reef ecosystem MUS species: (1) That is determined overfished with... applicable area of harvest; (2) A permit is not required, as outlined in § 665.224; or (3) The Hawaii coral...

  7. 50 CFR 665.625 - Prohibitions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ..., possess or land any PRIA coral reef ecosystem MUS in any low-use MPA as defined in § 665.599 unless: (1) A... applicable area of harvest; (2) A permit is not required, as outlined in § 665.624; (3) The PRIA coral reef..., take, or retain any PRIA coral reef ecosystem MUS species: (1) That is determined overfished with...

  8. 50 CFR 665.624 - Permits and fees.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... applies to coral reef ecosystem permits. (1) Special permit. Any person of the United States fishing for, taking or retaining PRIA coral reef ecosystem MUS must have a special permit if they, or a vessel which they operate, is used to fish for any: (i) PRIA Coral reef ecosystem MUS in low-use MPAs as defined in...

  9. 50 CFR 665.625 - Prohibitions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., possess or land any PRIA coral reef ecosystem MUS in any low-use MPA as defined in § 665.599 unless: (1) A... applicable area of harvest; (2) A permit is not required, as outlined in § 665.624; (3) The PRIA coral reef..., take, or retain any PRIA coral reef ecosystem MUS species: (1) That is determined overfished with...

  10. 50 CFR 665.624 - Permits and fees.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... applies to coral reef ecosystem permits. (1) Special permit. Any person of the United States fishing for, taking or retaining PRIA coral reef ecosystem MUS must have a special permit if they, or a vessel which they operate, is used to fish for any: (i) PRIA Coral reef ecosystem MUS in low-use MPAs as defined in...

  11. 50 CFR 665.224 - Permits and fees.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... retaining Hawaii coral reef ecosystem MUS must have a special permit if they, or a vessel which they operate, is used to fish for any: (i) Hawaii coral reef ecosystem MUS in low-use MPAs as defined in § 665.199; (ii) Hawaii Potentially Harvested Coral Reef Taxa in the coral reef ecosystem management area; or (iii...

  12. 50 CFR 665.225 - Prohibitions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... land any Hawaii coral reef ecosystem MUS in any low-use MPA as defined in § 665.199 unless: (1) A valid..., take, or retain any Hawaii coral reef ecosystem MUS species: (1) That is determined overfished with... applicable area of harvest; (2) A permit is not required, as outlined in § 665.224; or (3) The Hawaii coral...

  13. OER on the Asian Mega Universities: Developments, Motives, Openness, and Sustainability

    ERIC Educational Resources Information Center

    Farisi, Mohammad Imam

    2013-01-01

    The OER movement originated and integrated into ODE developments. Mega Universities (MUs) are among the most important of ODE providers worldwide should be to be the primary organizations for providing access to OER. So far, however, in-depth studies on OER developments in the Asian MUs were very limited. This study focuses on the developments,…

  14. Board of Regents' Montana University System (MUS) Strategic Plan 2016

    ERIC Educational Resources Information Center

    Montana University System, 2016

    2016-01-01

    The Montana University System Strategic Plan is the primary planning document of the Board of Regents. The Plan sets forth an agenda for higher education in Montana by delineating the strategic directions, goals, and objectives that guide the Montana University System (MUS). In July 2006, after several years of study, public dialogue, and internal…

  15. Binary Systems as Test-Beds of Gravity Theories

    NASA Astrophysics Data System (ADS)

    Damour, Thibault

    The discovery of binary pulsars in 1974 [1] opened up a new testing ground for relativistic gravity. Before this discovery, the only available testing ground for relativistic gravity was the solar system. As Einstein's theory of General Relativity (GR) is one of the basic pillars of modern science, it deserves to be tested, with the highest possible accuracy, in all its aspects. In the solar sys tem, the gravitational field is slowly varying and represents only a very small deformation of a flat spacetime. As a consequence, solar system tests can only probe the quasi-stationary (non-radiative) weak-field limit of relativis tic gravity. By contrast binary systems containing compact objects (neutron stars or black holes) involve spacetime domains (inside and near the compact objects) where the gravitational field is strong. Indeed, the surface relativistic gravitational field h 00 ≈ 2 GM/c 2 R of a neutron star is of order 0.4, which is close to the one of a black hole (2GM/c 2 R = 1) and much larger than the surface gravitational fields of solar system bodies: (2GM/c 2 R)Sun ˜ 10-6, (2GM/c 2 R)Earth ˜ 10-9. In addition, the high stability of “pulsar clocks” has made it possible to monitor the dynamics of its orbital motion down to a precision allowing one to measure the small (˜ (v/c)5) orbital effects linked to the propagation of the gravitational field at the velocity of light between the pulsar and its companion.

  16. 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.

  17. Sleep/wake firing patterns of human genioglossus motor units.

    PubMed

    Bailey, E Fiona; Fridel, Keith W; Rice, Amber D

    2007-12-01

    Although studies of the principal tongue protrudor muscle genioglossus (GG) suggest that whole muscle GG electromyographic (EMG) activities are preserved in nonrapid eye movement (NREM) sleep, it is unclear what influence sleep exerts on individual GG motor unit (MU) activities. We characterized the firing patterns of human GG MUs in wakefulness and NREM sleep with the aim of determining 1) whether the range of MU discharge patterns evident in wakefulness is preserved in sleep and 2) what effect the removal of the "wakefulness" input has on the magnitude of the respiratory modulation of MU activities. Microelectrodes inserted into the extrinsic tongue protrudor muscle, the genioglossus, were used to follow the discharge of single MUs. We categorized MU activities on the basis of the temporal relationship between the spike train and the respiration cycle and quantified the magnitude of the respiratory modulation of each MU using the eta (eta(2)) index, in wakefulness and sleep. The majority of MUs exhibited subtle increases or decreases in respiratory modulation but were otherwise unaffected by NREM sleep. In contrast, 30% of MUs exhibited marked sleep-associated changes in discharge frequency and respiratory modulation. We suggest that GG MUs should not be considered exclusively tonic or phasic; rather, the discharge pattern appears to be a flexible feature of GG activities in healthy young adults. Whether such flexibility is important in the response to changes in the chemical and/or mechanical environment and whether it is preserved as a function of aging or in individuals with obstructive sleep apnea are critical questions for future research.

  18. Vitamin K epoxide reductase complex subunit 1 (Vkorc1) haplotype diversity in mouse priority strains

    PubMed Central

    Song, Ying; Vera, Nicole; Kohn, Michael H

    2008-01-01

    Background Polymorphisms in the vitamin K-epoxide reductase complex subunit 1 gene, Vkorc1, could affect blood coagulation and other vitamin K-dependent proteins, such as osteocalcin (bone Gla protein, BGP). Here we sequenced the Vkorc1 gene in 40 mouse priority strains. We analyzed Vkorc1 haplotypes with respect to prothrombin time (PT) and bone mineral density and composition (BMD and BMC); phenotypes expected to be vitamin K-dependent and represented by data in the Mouse Phenome Database (MPD). Findings In the commonly used laboratory strains of Mus musculus domesticus we identified only four haplotypes differing in the intron or 5' region sequence of the Vkorc1. Six haplotypes differing by coding and non-coding polymorphisms were identified in the other subspecies of Mus. We detected no significant association of Vkorc1 haplotypes with PT, BMD and BMC within each subspecies of Mus. Vkorc1 haplotype sequences divergence between subspecies was associated with PT, BMD and BMC. Conclusion Phenotypic variation in PT, BMD and BMC within subspecies of Mus, while substantial, appears to be dominated by genetic variation in genes other than the Vkorc1. This was particularly evident for M. m. domesticus, where a single haplotype was observed in conjunction with virtually the entire range of PT, BMD and BMC values of all 5 subspecies of Mus included in this study. Differences in these phenotypes between subspecies also should not be attributed to Vkorc1 variants, but should be viewed as a result of genome wide genetic divergence. PMID:19046458

  19. Torque decrease during submaximal evoked contractions of the quadriceps muscle is linked not only to muscle fatigue.

    PubMed

    Matkowski, Boris; Lepers, Romuald; Martin, Alain

    2015-05-01

    The aim of this study was to analyze the neuromuscular mechanisms involved in the torque decrease induced by submaximal electromyostimulation (EMS) of the quadriceps muscle. It was hypothesized that torque decrease after EMS would reflect the fatigability of the activated motor units (MUs), but also a reduction in the number of MUs recruited as a result of changes in axonal excitability threshold. Two experiments were performed on 20 men to analyze 1) the supramaximal twitch superimposed and evoked at rest during EMS (Experiment 1, n = 9) and 2) the twitch response and torque-frequency relation of the MUs activated by EMS (Experiment 2, n = 11). Torque loss was assessed by 15 EMS-evoked contractions (50 Hz; 6 s on/6 s off), elicited at a constant intensity that evoked 20% of the maximal voluntary contraction (MVC) torque. The same stimulation intensity delivered over the muscles was used to induce the torque-frequency relation and the single electrical pulse evoked after each EMS contraction (Experiment 2). In Experiment 1, supramaximal twitch was induced by femoral nerve stimulation. Torque decreased by ~60% during EMS-evoked contractions and by only ~18% during MVCs. This was accompanied by a rightward shift of the torque-frequency relation of MUs activated and an increase of the ratio between the superimposed and posttetanic maximal twitch evoked during EMS contraction. These findings suggest that the torque decrease observed during submaximal EMS-evoked contractions involved muscular mechanisms but also a reduction in the number of MUs recruited due to changes in axonal excitability. Copyright © 2015 the American Physiological Society.

  20. 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 maintenance of atrial mechanical function.

  1. Stop Stalling: Mus81 Required for Efficient Replication | Center for Cancer Research

    Cancer.gov

    DNA replication is precisely controlled to ensure that daughter cells receive intact, accurate genetic information. Each segment of DNA must be copied only once, and the rate of replication coordinated genome-wide. Mild replication stress slows DNA synthesis and activates a pathway involving the Mus81 endonuclease, which generates a series of DNA breaks that are rapidly

  2. An MBS-Assisted Femtocell Transmit Power Control Scheme with Mobile User QoS Guarantee in 2-Tier Heterogeneous Femtocell Networks

    PubMed Central

    Yang, Chih-Cheng; Sheu, Shiann-Tsong

    2013-01-01

    This study investigates how to adjust the transmit power of femto base station (FBS) to mitigate interference problems between the FBSs and mobile users (MUs) in the 2-tier heterogeneous femtocell networks. A common baseline of deploying the FBS to increase the indoor access bandwidth requires that the FBS operation will not affect outdoor MUs operation with their quality-of-service (QoS) requirements. To tackle this technical problem, an FBS transmit power adjustment (FTPA) algorithm is proposed to adjust the FBS transmit power (FTP) to avoid unwanted cochannel interference (CCI) with the neighboring MUs in downlink transmission. FTPA reduces the FTP to serve its femto users (FUs) according to the QoS requirements of the nearest neighboring MUs to the FBS so that the MU QoS requirement is guaranteed. Simulation results demonstrate that FTPA can achieve a low MU outage probability as well as serve FUs without violating the MU QoS requirements. Simulation results also reveal that FTPA has better performance on voice and video services which are the major trend of future multimedia communication in the NGN. PMID:24391461

  3. Mid-urethral slings in female incontinence: Current status

    PubMed Central

    Krlin, Ryan M.; Murphy, Alana M.; Ingber, Michael S.; Vasavada, Sandip P.

    2011-01-01

    The advent of the mid-urethral sling (MUS) 15 years ago has drastically changed the surgical management of stress urinary incontinence (SUI). Both retropubic and transobturator MUS can be placed in the ambulatory setting with excellent results. The tension-free vaginal tape (TVT) sling has the most robust and long-term data, but more recent literature suggests that the transobturator tape sling may offer comparable efficacy in appropriately selected patients. Single incision sling (SIS) is the newest addition to the MUS group and was developed in an attempt to minimize morbidity and create an anti-incontinence procedure that could be performed in the office. The efficacy of SIS remains unknown as the current literature regarding SIS lacks long-term results and comparative trials. The suprapubic arc sling appears to have equally effective outcomes in at least the short-term when compared with TVT. Although evolution of the SIS has led to a less invasive procedure with decreased post-op pain and reduced recovery time, durability of efficacy could be the endpoint we are sacrificing. Until longer-term data and more quality comparison trials are available, tailoring one's choice of MUS to the individual patient and her unique clinical parameters remains the best option. PMID:22022053

  4. An MBS-assisted femtocell transmit power control scheme with mobile user QoS guarantee in 2-tier heterogeneous femtocell networks.

    PubMed

    Chen, Jenhui; Yang, Chih-Cheng; Sheu, Shiann-Tsong

    2013-01-01

    This study investigates how to adjust the transmit power of femto base station (FBS) to mitigate interference problems between the FBSs and mobile users (MUs) in the 2-tier heterogeneous femtocell networks. A common baseline of deploying the FBS to increase the indoor access bandwidth requires that the FBS operation will not affect outdoor MUs operation with their quality-of-service (QoS) requirements. To tackle this technical problem, an FBS transmit power adjustment (FTPA) algorithm is proposed to adjust the FBS transmit power (FTP) to avoid unwanted cochannel interference (CCI) with the neighboring MUs in downlink transmission. FTPA reduces the FTP to serve its femto users (FUs) according to the QoS requirements of the nearest neighboring MUs to the FBS so that the MU QoS requirement is guaranteed. Simulation results demonstrate that FTPA can achieve a low MU outage probability as well as serve FUs without violating the MU QoS requirements. Simulation results also reveal that FTPA has better performance on voice and video services which are the major trend of future multimedia communication in the NGN.

  5. Localised task-dependent motor-unit recruitment in the masseter.

    PubMed

    Schindler, H J; Hellmann, D; Giannakopoulos, N N; Eiglsperger, U; van Dijk, J P; Lapatki, B G

    2014-07-01

    Localised motor-unit (MU) recruitment in the masseter was analysed in this study. We investigated whether differential activation behaviour, which has already been reported for distant masseter regions, can also be detected in small muscle subvolumes at the level of single MUs. Two bipolar fine-wire electrodes and an intra-oral 3D bite-force transmitter were used to record intra-muscular electromyograms (EMG) resulting from controlled bite-forces of 10 healthy human subjects (mean age 24.1 ± 1.2 years). Two-hundred and seventeen decomposed MUs were organised into localised MU task groups with different (P < 0.001) force-direction-specific behaviour. Proportions of MUs involved in one, two, three or four examined tasks were 46%, 31%, 18% and 5%, respectively. This study provides evidence of the ability of the neuromuscular system to modify the mechanical output of small masseter subvolumes by differential control of adjacent MUs belonging to distinct task groups. Localised differential activation behaviour of the masseter may be the crucial factor enabling highly flexible and efficient adjustment of the muscle activity in response to complex local biomechanical needs, for example, continually varying bite-forces during the demanding masticatory process. © 2014 John Wiley & Sons Ltd.

  6. Evolution of the Iga Heavy Chain Gene in the Genus Mus

    PubMed Central

    Osborne, B. A.; Golde, T. E.; Schwartz, R. L.; Rudikoff, S.

    1988-01-01

    To examine questions of immunoglobulin gene evolution, the IgA α heavy chain gene from Mus pahari, an evolutionarily distant relative to Mus musculus domesticus, was cloned and sequenced. The sequence, when compared to the IgA gene of BALB/c or human, demonstrated that the IgA gene is evolving in a mosaic fashion with the hinge region accumulating mutations most rapidly and the third domain at a considerably lower frequency. In spite of this pronounced accumulation of mutations, the hinge region appears to maintain the conformation of a random coil. A marked propensity to accumulate replacement over silent site changes in the coding regions was noted, as was a definite codon bias. The possibility that these two phenomena are interrelated is discussed. PMID:2842228

  7. 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.

  8. 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.

  9. Accounting Artifacts in High-Throughput Toxicity Assays.

    PubMed

    Hsieh, Jui-Hua

    2016-01-01

    Compound activity identification is the primary goal in high-throughput screening (HTS) assays. However, assay artifacts including both systematic (e.g., compound auto-fluorescence) and nonsystematic (e.g., noise) complicate activity interpretation. In addition, other than the traditional potency parameter, half-maximal effect concentration (EC50), additional activity parameters (e.g., point-of-departure, POD) could be derived from HTS data for activity profiling. A data analysis pipeline has been developed to handle the artifacts and to provide compound activity characterization with either binary or continuous metrics. This chapter outlines the steps in the pipeline using Tox21 glucocorticoid receptor (GR) β-lactamase assays, including the formats to identify either agonists or antagonists, as well as the counter-screen assays for identifying artifacts as examples. The steps can be applied to other lower-throughput assays with concentration-response data.

  10. Junior doctors' experiences of managing patients with medically unexplained symptoms: a qualitative study.

    PubMed

    Yon, Katherine; Nettleton, Sarah; Walters, Kate; Lamahewa, Kethakie; Buszewicz, Marta

    2015-12-01

    To explore junior doctors' knowledge about and experiences of managing patients with medically unexplained symptoms (MUS) and to seek their recommendations for improved future training on this important topic about which they currently receive little education. Qualitative study using in-depth interviews analysed using the framework method. Participants were recruited from three North Thames London hospitals within the UK. Twenty-two junior doctors undertaking the UK foundation two-year training programme (FY1/FY2). The junior doctors interviewed identified a significant gap in their training on the topic of MUS, particularly in relation to their awareness of the topic, the appropriate level of investigations, possible psychological comorbidities, the formulation of suitable explanations for patients' symptoms and longer term management strategies. Many junior doctors expressed feelings of anxiety, frustration and a self-perceived lack of competency in this area, and spoke of over-investigating patients or avoiding patient contact altogether due to the challenging nature of MUS and a difficulty in managing the accompanying uncertainty. They also identified the negative attitudes of some senior clinicians and potential role models towards patients with MUS as a factor contributing to their own attitudes and management choices. Most reported a need for more training during the foundation years, and recommended interactive case-based group discussions with a focus on providing meaningful explanations to patients for their symptoms. There is an urgent need to improve postgraduate training about the topics of MUS and avoiding over-investigation, as current training does not equip junior doctors with the necessary knowledge and skills to effectively and confidently manage patients in these areas. Training needs to focus on practical skill development to increase clinical knowledge in areas such as delivering suitable explanations, and to incorporate individual management strategies to help junior doctors tolerate the uncertainty associated with MUS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  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

    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

  12. Explanation and relations. How do general practitioners deal with patients with persistent medically unexplained symptoms: a focus group study

    PubMed Central

    olde Hartman, Tim C; Hassink-Franke, Lieke J; Lucassen, Peter L; van Spaendonck, Karel P; van Weel, Chris

    2009-01-01

    Background Persistent presentation of medically unexplained symptoms (MUS) is troublesome for general practitioners (GPs) and causes pressure on the doctor-patient relationship. As a consequence, GPs face the problem of establishing an ongoing, preferably effective relationship with these patients. This study aims at exploring GPs' perceptions about explaining MUS to patients and about how relationships with these patients evolve over time in daily practice. Methods A qualitative approach, interviewing a purposive sample of twenty-two Dutch GPs within five focus groups. Data were analyzed according to the principles of constant comparative analysis. Results GPs recognise the importance of an adequate explanation of the diagnosis of MUS but often feel incapable of being able to explain it clearly to their patients. GPs therefore indicate that they try to reassure patients in non-specific ways, for example by telling patients that there is no disease, by using metaphors and by normalizing the symptoms. When patients keep returning with MUS, GPs report the importance of maintaining the doctor-patient relationship. GPs describe three different models to do this; mutual alliance characterized by ritual care (e.g. regular physical examination, regular doctor visits) with approval of the patient and the doctor, ambivalent alliance characterized by ritual care without approval of the doctor and non-alliance characterized by cutting off all reasons for encounter in which symptoms are not of somatic origin. Conclusion GPs feel difficulties in explaining the symptoms. GPs report that, when patients keep presenting with MUS, they focus on maintaining the doctor-patient relationship by using ritual care. In this care they meticulously balance between maintaining a good doctor-patient relationship and the prevention of unintended consequences of unnecessary interventions. PMID:19775481

  13. Identification of Novel Rodent Herpesviruses, Including the First Gammaherpesvirus of Mus musculus▿

    PubMed Central

    Ehlers, Bernhard; Küchler, Judit; Yasmum, Nezlisah; Dural, Güzin; Voigt, Sebastian; Schmidt-Chanasit, Jonas; Jäkel, Thomas; Matuschka, Franz-Rainer; Richter, Dania; Essbauer, Sandra; Hughes, David J.; Summers, Candice; Bennett, Malcolm; Stewart, James P.; Ulrich, Rainer G.

    2007-01-01

    Rodent herpesviruses such as murine cytomegalovirus (host, Mus musculus), rat cytomegalovirus (host, Rattus norvegicus), and murine gammaherpesvirus 68 (hosts, Apodemus species) are important tools for the experimental study of human herpesvirus diseases. However, alphaherpesviruses, roseoloviruses, and lymphocryptoviruses, as well as rhadinoviruses, that naturally infect Mus musculus (house mouse) and other Old World mice are unknown. To identify hitherto-unknown rodent-associated herpesviruses, we captured M. musculus, R. norvegicus, and 14 other rodent species in several locations in Germany, the United Kingdom, and Thailand. Samples of trigeminal ganglia, dorsal root ganglia, brains, spleens, and other organs, as well as blood, were analyzed with a degenerate panherpesvirus PCR targeting the DNA polymerase (DPOL) gene. Herpesvirus-positive samples were subjected to a second degenerate PCR targeting the glycoprotein B (gB) gene. The sequences located between the partial DPOL and gB sequences were amplified by long-distance PCR and sequenced, resulting in a contiguous sequence of approximately 3.5 kbp. By DPOL PCR, we detected 17 novel betaherpesviruses and 21 novel gammaherpesviruses but no alphaherpesvirus. Of these 38 novel herpesviruses, 14 were successfully analyzed by the complete bigenic approach. Most importantly, the first gammaherpesvirus of Mus musculus was discovered (Mus musculus rhadinovirus 1 [MmusRHV1]). This virus is a member of a novel group of rodent gammaherpesviruses, which is clearly distinct from murine herpesvirus 68-like rodent gammaherpesviruses. Multigenic phylogenetic analysis, using an 8-kbp locus, revealed that MmusRHV1 diverged from the other gammaherpesviruses soon after the evolutionary separation of Epstein-Barr virus-like lymphocryptoviruses from human herpesvirus 8-like rhadinoviruses and alcelaphine herpesvirus 1-like macaviruses. PMID:17507487

  14. Small vertical changes in jaw relation affect motor unit recruitment in the masseter.

    PubMed

    Terebesi, S; Giannakopoulos, N N; Brüstle, F; Hellmann, D; Türp, J C; Schindler, H J

    2016-04-01

    Strategies for recruitment of masseter muscle motor units (MUs), provoked by constant bite force, for different vertical jaw relations have not previously been investigated. The objective of this study was to analyse the effect of small changes in vertical jaw relation on MU recruitment behaviour in different regions of the masseter during feedback-controlled submaximum biting tasks. Twenty healthy subjects (mean age: 24·6 ± 2·4 years) were involved in the investigation. Intra-muscular electromyographic (EMG) activity of the right masseter was recorded in different regions of the muscle. MUs were identified by the use of decomposition software, and root-mean-square (RMS) values were calculated for each experimental condition. Six hundred and eleven decomposed MUs with significantly (P < 0·001) different jaw relation-specific recruitment behaviour were organised into localised MU task groups. MUs with different task specificity in seven examined tasks were observed. The RMS EMG values obtained from the different recording sites were also significantly (P < 0·01) different between tasks. Overall MU recruitment was significantly (P < 0·05) greater in the deep masseter than in the superficial muscle. The number of recruited MUs and the RMS EMG values decreased significantly (P < 0·01) with increasing jaw separation. This investigation revealed differential MU recruitment behaviour in discrete subvolumes of the masseter in response to small changes in vertical jaw relations. These fine-motor skills might be responsible for its excellent functional adaptability and might also explain the successful management of temporomandibular disorder patients by somatic intervention, in particular by the use of oral splints. © 2015 John Wiley & Sons Ltd.

  15. 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.

  16. 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.

  17. The first linear polarization spectra of Wolf-Rayet stars in the ultraviolet - EZ Canis Majoris and Theta Muscae

    NASA Technical Reports Server (NTRS)

    Schulte-Ladbeck, R. E.; Nordsieck, K. H.; Code, A. D.; Anderson, C. M.; Babler, B. L.; Bjorkman, K. S.; Clayton, G. C.; Magalhaes, A. M.; Meade, M. R.; Shepherd, D.

    1992-01-01

    During the 1990 December Astro-1 Space Shuttle mission, spectropolarimetry was conducted in the wavelength region from 1400 to 3200 A of the Wolf-Rayet stars EZ CMa (WN5) and Theta Mus (WC6 + O9.5I) with the Wisconsin Ultraviolet Photo-Polarimeter Experiment. The UV polarization of EZ CMa displays features which correspond to emission lines. This indicates a large, about 0.8 percent, intrinsic UV-continuum polarization, and provides further evidence that the wind of EZ CMa is highly distorted. The polarization of Theta Mus does not change across emission lines, or the strong interstellar 2200 A feature. The polarization decreases smoothly to shorter wavelengths, at constant position angle. The combined UV-optical polarization spectrum of Theta Mus can be described well with interstellar polarization following a Serkowski law.

  18. 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.

  19. Corrected placement of Mus-Rattus fossil calibration forces precision in the molecular tree of rodents.

    PubMed

    Kimura, Yuri; Hawkins, Melissa T R; McDonough, Molly M; Jacobs, Louis L; Flynn, Lawrence J

    2015-09-28

    Time calibration derived from the fossil record is essential for molecular phylogenetic and evolutionary studies. Fossil mice and rats, discovered in the Siwalik Group of Pakistan, have served as one of the best-known fossil calibration points in molecular phylogenic studies. Although these fossils have been widely used as the 12 Ma date for the Mus/Rattus split or a more basal split, conclusive paleontological evidence for the nodal assignments has been absent. This study analyzes newly recognized characters that demonstrate lineage separation in the fossil record of Siwalik murines and examines the most reasonable nodal placement of the diverging lineages in a molecular phylogenetic tree by ancestral state reconstruction. Our specimen-based approach strongly indicates that Siwalik murines of the Karnimata clade are fossil members of the Arvicanthini-Otomyini-Millardini clade, which excludes Rattus and its relatives. Combining the new interpretation with the widely accepted hypothesis that the Progonomys clade includes Mus, the lineage separation event in the Siwalik fossil record represents the Mus/Arvicanthis split. Our test analysis on Bayesian age estimates shows that this new calibration point provides more accurate estimates of murine divergence than previous applications. Thus, we define this fossil calibration point and refine two other fossil-based points for molecular dating.

  20. Corrected placement of Mus-Rattus fossil calibration forces precision in the molecular tree of rodents

    PubMed Central

    Kimura, Yuri; Hawkins, Melissa T. R.; McDonough, Molly M.; Jacobs, Louis L.; Flynn, Lawrence J.

    2015-01-01

    Time calibration derived from the fossil record is essential for molecular phylogenetic and evolutionary studies. Fossil mice and rats, discovered in the Siwalik Group of Pakistan, have served as one of the best-known fossil calibration points in molecular phylogenic studies. Although these fossils have been widely used as the 12 Ma date for the Mus/Rattus split or a more basal split, conclusive paleontological evidence for the nodal assignments has been absent. This study analyzes newly recognized characters that demonstrate lineage separation in the fossil record of Siwalik murines and examines the most reasonable nodal placement of the diverging lineages in a molecular phylogenetic tree by ancestral state reconstruction. Our specimen-based approach strongly indicates that Siwalik murines of the Karnimata clade are fossil members of the Arvicanthini-Otomyini-Millardini clade, which excludes Rattus and its relatives. Combining the new interpretation with the widely accepted hypothesis that the Progonomys clade includes Mus, the lineage separation event in the Siwalik fossil record represents the Mus/Arvicanthis split. Our test analysis on Bayesian age estimates shows that this new calibration point provides more accurate estimates of murine divergence than previous applications. Thus, we define this fossil calibration point and refine two other fossil-based points for molecular dating. PMID:26411391

  1. Implementing a Psychotherapy Service for Medically Unexplained Symptoms in a Primary Care Setting

    PubMed Central

    Cooper, Angela; Abbass, Allan; Town, Joel

    2017-01-01

    Medically unexplained symptoms (MUS) are known to be costly, complex to manage and inadequately addressed in primary care settings. In many cases, there are unresolved psychological and emotional processes underlying these symptoms, leaving traditional medical approaches insufficient. This paper details the implementation of an evidence-based, emotion-focused psychotherapy service for MUS across two family medicine clinics. The theory and evidence-base for using Intensive Short-Term Dynamic Psychotherapy (ISTDP) with MUS is presented along with the key service components of assessment, treatment, education and research. Preliminary outcome indicators showed diverse benefits. Patients reported significantly decreased somatic symptoms in the Patient Health Questionnaire-15 (d = 0.4). A statistically significant (23%) decrease in family physicians’ visits was found in the 6 months after attending the MUS service compared to the 6 months prior. Both patients and primary care clinicians reported a high degree of satisfaction with the service. Whilst further research is needed, these findings suggest that a direct psychology service maintained within the family practice clinic may assist patient and clinician function while reducing healthcare utilization. Challenges and further service developments are discussed, including the potential benefits of re-branding the service to become a ‘Primary Care Psychological Consultation and Treatment Service’. PMID:29186054

  2. Implementing a Psychotherapy Service for Medically Unexplained Symptoms in a Primary Care Setting.

    PubMed

    Cooper, Angela; Abbass, Allan; Town, Joel

    2017-11-29

    Medically unexplained symptoms (MUS) are known to be costly, complex to manage and inadequately addressed in primary care settings. In many cases, there are unresolved psychological and emotional processes underlying these symptoms, leaving traditional medical approaches insufficient. This paper details the implementation of an evidence-based, emotion-focused psychotherapy service for MUS across two family medicine clinics. The theory and evidence-base for using Intensive Short-Term Dynamic Psychotherapy (ISTDP) with MUS is presented along with the key service components of assessment, treatment, education and research. Preliminary outcome indicators showed diverse benefits. Patients reported significantly decreased somatic symptoms in the Patient Health Questionnaire-15 ( d = 0.4). A statistically significant (23%) decrease in family physicians' visits was found in the 6 months after attending the MUS service compared to the 6 months prior. Both patients and primary care clinicians reported a high degree of satisfaction with the service. Whilst further research is needed, these findings suggest that a direct psychology service maintained within the family practice clinic may assist patient and clinician function while reducing healthcare utilization. Challenges and further service developments are discussed, including the potential benefits of re-branding the service to become a 'Primary Care Psychological Consultation and Treatment Service'.

  3. Effectiveness of midurethral slings in intrinsic sphincteric-related stress urinary incontinence.

    PubMed

    Lim, Yik N; Dwyer, Peter L

    2009-10-01

    Previous literature has shown that urodynamic evidence of intrinsic sphincter deficiency (ISD) decreases the surgical success of traditional antistress incontinence surgeries. The aim of this review is to assess recent evidence on the effectiveness of the increasingly popular midurethral slings (MUS) in women with ISD and stress urinary incontinence. Using the ISD definition of maximum urethral closure pressure of 20 cm H2O or less and/or abdominal/valsalva leak point pressure of 60 cm H2O or less, current literature would suggest that the effectiveness of retropubic MUS is reduced but remained acceptable in women with stress urinary incontinence and ISD. There are conflicting data on whether coexisting poor urethral mobility could further compromise surgical success. Of note, there is now emerging evidence to suggest that transobturator tapes are associated with much higher failure rates in this setting and retropubic MUS should be used instead. Currently, there is too little data on the new single-incision mini-slings for any recommendation of use in women with stress incontinence with good or poor intrinsic urethral function. MUS is an effective treatment for stress urinary incontinence. However, when urodynamic evidence of ISD is present, the retropubic approach may be preferable to the transobturator approach.

  4. Determinants of the number of mammography units in 31 countries with significant mammography screening

    PubMed Central

    Autier, P; Ouakrim, D A

    2008-01-01

    In the 2000s, most of the female population of industrialised countries had access to mammography breast cancer screening, but with variable modalities among the countries. We assessed the number of mammography units (MUs) in 31 European, North American and Asian countries where significant mammography activity has existed for over 10 years, collecting data on the number of such units and of radiologists by contacting institutions in each country likely to provide the relevant information. Around 2004, there were 32 324 MU in 31 countries, the number per million women ranging from less than 25 in Turkey, Denmark, the Netherlands, the United Kingdom, Norway, Poland and Hungary to more than 80 in Cyprus, Italy, France, the United States and Austria. In a multivariate analysis, the number of MUs was positively associated with the number of radiologists (P=0.0081), the number of women (P=0.0023) and somewhat with the country surface area (P=0.077). There is considerable variation in the density of MU across countries and the number of MUs in service are often well above what would be necessary according to local screening recommendations. High number of MUs in some countries may have undesirable consequences, such as unnecessarily high screening frequency and decreased age at which screening is started. PMID:18781176

  5. AAA and AXB algorithms for the treatment of nasopharyngeal carcinoma using IMRT and RapidArc techniques.

    PubMed

    Kamaleldin, Maha; Elsherbini, Nader A; Elshemey, Wael M

    2017-09-27

    The aim of this study is to evaluate the impact of anisotropic analytical algorithm (AAA) and 2 reporting systems (AXB-D m and AXB-D w ) of Acuros XB algorithm (AXB) on clinical plans of nasopharyngeal patients using intensity-modulated radiotherapy (IMRT) and RapidArc (RA) techniques. Six plans of different algorithm-technique combinations are performed for 10 patients to calculate dose-volume histogram (DVH) physical parameters for planning target volumes (PTVs) and organs at risk (OARs). The number of monitor units (MUs) and calculation time are also determined. Good coverage is reported for all algorithm-technique combination plans without exceeding the tolerance for OARs. Regardless of the algorithm, RA plans persistently reported higher D 2% values for PTV-70. All IMRT plans reported higher number of MUs (especially with AXB) than did RA plans. AAA-IMRT produced the minimum calculation time of all plans. Major differences between the investigated algorithm-technique combinations are reported only for the number of MUs and calculation time parameters. In terms of these 2 parameters, it is recommended to employ AXB in calculating RA plans and AAA in calculating IMRT plans to achieve minimum calculation times at reduced number of MUs. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

  6. Microstructure and properties of hard and optically transparent HfO2 films prepared by high-rate reactive high-power impulse magnetron sputtering

    NASA Astrophysics Data System (ADS)

    Patterson, Burkley Delesdernier

    Hafnium Dioxide (HfO2) has an extraordinary high bulk modulus, high hardness, high chemical stability, high melting point and high thermal stability. This material can be used as protective coatings for application involving high temperature environments. HfO2 films were fabricated on Si using high-rate reactive high-power impulse magnetron sputtering (HiPIMS) using different deposition-averaged target power density and voltage pulse durations t1. Five HfO2 films were prepared with (1) t1 = 25 mus, =7.6 Wcm-2 (T25S7), (2) t 1 = 100 mus, =7.2 Wcm-2 (T100S7), (3) t1 = 200 mus, =7.3 Wcm-2 (T200S7), (4) t1 = 200 mus, =18 Wcm-2 (T200S18) and (5) t1 = 200 mus, =54 Wcm-2 (T200S54). Atomic force microscopy (AFM) images of the T200S54, T200S18 and T200S7 films exhibit a coarser granular structure with a similar grain size varying from 25 nm to 120 nm in diameter and an average grain size of ˜70 nm. AFM images of the T25S7 and T100S7 films show smaller granular structures compared to the other three films. Transmission electron microscopy (TEM) studies show that all films are composed of an interlayer next to the Si interface followed by a nano-columnar structure layer. The interlayer structure of the films consists of a population of lower density nanoscale regions. A reduction in t1 and in films T200S54, T200S18, T200S7 and T100S7 caused an increase in the interlayer thickness and a decrease in the width of the nano-columnar structures from ˜46 nm to ˜21 nm. This microstructural change was accompanied by a concomitant change of the grain boundary structure from tight and interlocking in films T200S54 and T200S18, to rough and thicker (˜1 nm) boundaries in films T200S7 and T100S7. Film T25S7 exhibited an entirely different microstructure composed of a multilayered interlayer (˜3 nm) and nano-columnar (˜15 nm) structure. Films prepared with large t1 (200 mus) have a monoclinic HfO 2 structure and that with small t1 (25 mus) an orthorhombic HfO 2 structure. Film prepared with an intermediate t1 value (100 mus) exhibited a mixture of both monoclinic and orthorhombic phases. A high hardness of 17.6-17.0 GPa was shown for films with a monoclinic HfO2 structure. The films exhibited a refractive index of 2.02-2.11 and an extinction coefficient between ≥≤2x10-3 and 0.1x10-3 (both at a wavelength of 550 nm). High optical quality was achieved for films T200S54 and T200S18 owing to the presence of a dense microstructure with sharp and interlocking grain boundaries.

  7. 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 upregulated nine Arabidopsis genes involved in defense responses to various stresses, including chilling. These results strongly suggest CsGR-RBP3 plays a positive role in defense against chilling stress. PMID:29740470

  8. 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 ).

  9. Preliminary Characterization of Mus musculus–Derived Pathogenic Strains of Leptospira borgpetersenii Serogroup Ballum in a Hamster Model

    PubMed Central

    da Silva, Éverton F.; Félix, Samuel R.; Cerqueira, Gustavo M.; Fagundes, Michel Q.; Neto, Amilton C. P. S.; Grassmann, André A.; Amaral, Marta G.; Gallina, Tiago; Dellagostin, Odir A.

    2010-01-01

    Human and animal leptospirosis caused by Leptospira spp. belonging to serogroup Ballum has increased worldwide in the past decade. We report the isolation and serologic and molecular characterization of four L. borgpetersenii serogroup Ballum isolates obtained from Mus musculus, and preliminary virulence studies. These isolates are useful for diagnosis of leptospirosis and for epidemiologic studies of its virulence and pathogenic mechanisms. PMID:20682877

  10. 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

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. A magnetically driven origin for the low luminosity GRB 170817A associated with GW170817

    NASA Astrophysics Data System (ADS)

    Tong, Hao; Yu, Cong; Huang, Lei

    2018-06-01

    The gamma-ray burst GR170817A associated with GW170817 is subluminous and subenergetic compared with other typical short gamma-ray bursts. It may be due to a relativistic jet viewed off-axis, or a structured jet or cocoon emission. Giant flares from magnetars may possibly be ruled out. However, the luminosity and energetics of GRB 170817A are coincident with those of magnetar giant flares. After the coalescence of a binary neutron star, a hypermassive neutron star may be formed. The hypermassive neutron star may have a magnetar-strength magnetic field. During the collapse of this hypermassive neutron star, magnetic field energy will also be released. This giant-flare-like event may explain the luminosity and energetics of GRB 170817A. Bursts with similar luminosity and energetics are expected in future neutron star-neutron star or neutron star-black hole mergers.

  18. 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).

  19. 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

  20. Process for recovery of hydrogen and

    DOEpatents

    James, Brian R.; Li-Lee, Chung; Lilga, Michael A.; Nelson, David A.

    1987-01-01

    on of sulfur Abstract A process of abstracting sulfur from H.sub.2 S and generating hydrogen is disclosed comprising dissolving Pd.sub.2 X.sub.2 (.mu.-dppm).sub.2 in a solvent and then introducing H.sub.2 S. The palladium complex abstracts sulfur, forming hydrogen and a (.mu.-S) complex. The (.mu.-S) complex is readily oxidizable to a (.mu.-SO.sub.2) adduct which spontaneously loses SO.sub.2 and regenerates the palladium complex.

  1. Development of metaphors to explain cognitive behavioural principles for patients with medically unexplained symptoms in Sri Lanka.

    PubMed

    Sumathipala, Athula

    2014-03-01

    Medically unexplained symptoms (MUS) are common in primary care across cultures, accounting for high consultations with multiple providers and unnecessary investigations. Cognitive behavioural therapy (CBT) is efficacious for MUS and reduces physical symptoms, psychological distress and disability. Two intervention trials by the author and his group remain the only reported trials from the developing world. A treatment package was designed by modifying a CBT model. The modifications were innovative use of locally relevant appropriate language and strategies that were simple enough while conforming to the CBT principles. The aim was to convey the principles of CBT to people using simple techniques--using metaphor. These are described in the paper as generic metaphors that could be used to explain the CBT principles and specific ones for patients with MUS. Metaphor is an effective clinical tool. The author's clinical experience and patients' feedback suggest that these metaphors are helpful in conveying the CBT principles to patients. To develop metaphors appealing to the client and effective clinically, carrying out qualitative research among patients' explanatory model is an important prerequisite. The generic and MUS-specific metaphors reported here should be tried in other cultural and clinical settings and evaluated. Further systematic work including qualitative work for consensus evaluation among CBT experts as well as opinion on user-friendliness of these techniques tested among CBT practitioners will be needed.

  2. 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.

  3. 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

  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. DIANA-microT web server v5.0: service integration into miRNA functional analysis workflows.

    PubMed

    Paraskevopoulou, Maria D; Georgakilas, Georgios; Kostoulas, Nikos; Vlachos, Ioannis S; Vergoulis, Thanasis; Reczko, Martin; Filippidis, Christos; Dalamagas, Theodore; Hatzigeorgiou, A G

    2013-07-01

    MicroRNAs (miRNAs) are small endogenous RNA molecules that regulate gene expression through mRNA degradation and/or translation repression, affecting many biological processes. DIANA-microT web server (http://www.microrna.gr/webServer) is dedicated to miRNA target prediction/functional analysis, and it is being widely used from the scientific community, since its initial launch in 2009. DIANA-microT v5.0, the new version of the microT server, has been significantly enhanced with an improved target prediction algorithm, DIANA-microT-CDS. It has been updated to incorporate miRBase version 18 and Ensembl version 69. The in silico-predicted miRNA-gene interactions in Homo sapiens, Mus musculus, Drosophila melanogaster and Caenorhabditis elegans exceed 11 million in total. The web server was completely redesigned, to host a series of sophisticated workflows, which can be used directly from the on-line web interface, enabling users without the necessary bioinformatics infrastructure to perform advanced multi-step functional miRNA analyses. For instance, one available pipeline performs miRNA target prediction using different thresholds and meta-analysis statistics, followed by pathway enrichment analysis. DIANA-microT web server v5.0 also supports a complete integration with the Taverna Workflow Management System (WMS), using the in-house developed DIANA-Taverna Plug-in. This plug-in provides ready-to-use modules for miRNA target prediction and functional analysis, which can be used to form advanced high-throughput analysis pipelines.

  6. DIANA-microT web server v5.0: service integration into miRNA functional analysis workflows

    PubMed Central

    Paraskevopoulou, Maria D.; Georgakilas, Georgios; Kostoulas, Nikos; Vlachos, Ioannis S.; Vergoulis, Thanasis; Reczko, Martin; Filippidis, Christos; Dalamagas, Theodore; Hatzigeorgiou, A.G.

    2013-01-01

    MicroRNAs (miRNAs) are small endogenous RNA molecules that regulate gene expression through mRNA degradation and/or translation repression, affecting many biological processes. DIANA-microT web server (http://www.microrna.gr/webServer) is dedicated to miRNA target prediction/functional analysis, and it is being widely used from the scientific community, since its initial launch in 2009. DIANA-microT v5.0, the new version of the microT server, has been significantly enhanced with an improved target prediction algorithm, DIANA-microT-CDS. It has been updated to incorporate miRBase version 18 and Ensembl version 69. The in silico-predicted miRNA–gene interactions in Homo sapiens, Mus musculus, Drosophila melanogaster and Caenorhabditis elegans exceed 11 million in total. The web server was completely redesigned, to host a series of sophisticated workflows, which can be used directly from the on-line web interface, enabling users without the necessary bioinformatics infrastructure to perform advanced multi-step functional miRNA analyses. For instance, one available pipeline performs miRNA target prediction using different thresholds and meta-analysis statistics, followed by pathway enrichment analysis. DIANA-microT web server v5.0 also supports a complete integration with the Taverna Workflow Management System (WMS), using the in-house developed DIANA-Taverna Plug-in. This plug-in provides ready-to-use modules for miRNA target prediction and functional analysis, which can be used to form advanced high-throughput analysis pipelines. PMID:23680784

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. Diagnosing somatisation disorder (P75) in routine general practice using the International Classification of Primary Care.

    PubMed

    Schaefert, Rainer; Laux, Gunter; Kaufmann, Claudia; Schellberg, Dieter; Bölter, Regine; Szecsenyi, Joachim; Sauer, Nina; Herzog, Wolfgang; Kuehlein, Thomas

    2010-09-01

    (i) To analyze general practitioners' diagnosis of somatisation disorder (P75) using the International Classification of Primary Care (ICPC)-2-E in routine general practice. (ii) To validate the distinctiveness of the ICD-10 to ICPC-2 conversion rule which maps ICD-10 dissociative/conversion disorder (F44) as well as half of the somatoform categories (F45.0-2) to P75 and codes the other half of these disorders (F45.3-9), including autonomic organ dysfunctions and pain syndromes, as symptom diagnoses plus a psychosocial code in a multiaxial manner. Cross-sectional analysis of routine data from a German research database comprising the electronic patient records of 32 general practitioners from 22 practices. For each P75 patient, control subjects matched for age, gender, and practice were selected from the 2007 yearly contact group (YCG) without a P75 diagnosis using a propensity-score algorithm that resulted in eight controls per P75 patient. Of the 49,423 patients in the YCG, P75 was diagnosed in 0.6% (302) and F45.3-9 in 1.8% (883) of cases; overall, somatisation syndromes were diagnosed in 2.4% of patients. The P75 coding pattern coincided with typical characteristics of severe, persistent medically unexplained symptoms (MUS). F45.3-9 was found to indicate moderate MUS that otherwise showed little clinical difference from P75. Pain syndromes exhibited an unspecific coding pattern. Mild and moderate MUS were predominantly recorded as symptom diagnoses. Psychosocial codes were rarely documented. ICPC-2 P75 was mainly diagnosed in cases of severe MUS. Multiaxial coding appears to be too complicated for routine primary care. Instead of splitting P75 and F45.3-9 diagnoses, it is proposed that the whole MUS spectrum should be conceptualized as a continuum model comprising categorizations of uncomplicated (mild) and complicated (moderate and severe) courses. Psychosocial factors require more attention. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  12. Optically detected magnetic resonance studies on pi-conjugated polymers and novel carbon allotropes

    NASA Astrophysics Data System (ADS)

    Partee, Jonathan Farel

    1997-12-01

    The photophysics of poly(p-phenylene)-type ladder polymers (m-LPPP) and 2,5-dibutoxy poly(p-phenylene ethynylene) (DBO-PPE) films and solutions were studied by X-band photoluminescence detected magnetic resonance (PLDMR). Frequency resolved PLDMR measurements on LPPP, DBO-PPE, poly(3-hexylthiophene) (P3HT), poly(p-phenylene-vinylene) (PPV), and Csb{70} are also reported and discussed. All the polymer samples exhibit three distinct features when excited at wavelengths lambda≥ 458nm: (i) A narrow PL-enhancing spin-1/2 polaron resonance, (ii) broad full- and (iii) half-field spin-1 triplet exciton powder patterns due to the Deltamsbs = 1 and Deltamsbs = 2 transitions among the triplet sublevels, respectively. The full-width at half maximum (FWHM) of the spin-1/2 resonance in LPPP decreased from film to solution. However, the FWHM of that resonance in PPE was identical at all concentrations. This spin-1/2 resonance is assigned to the magnetic resonance enhancement of the recombination of both interchain and intrachain-intersegment polaron pairs which quench singlet exciton recombination. In solid m-LPPP samples, the aggregate PL gives rise to a proportionally higher magnetic resonance effect than other parts of the PL spectrum. In DBO-PPE and m-LPPP solutions, the triplet resonance decreased with decreasing concentration. This suggests that the triplet state is an intrinsic long-lived (˜30mus) trapped state localized on a phenylene ring and stabilized by coupling to a unit of an adjacent chain. Frequency resolved measurements of the lifetime of the species affected by the resonance conditions for all the polymers are described and discussed. The lifetimes appeared to include: (i) fast (9mus ≤ tausb1 ≤ 40mus) and (ii) slow (575mus\\ ≤ tausb2≤ 1868mus) components. The lifetimes increased with increasing concentration of the polymers in toluene solutions. These results can be interpreted to provide support for the interchain/intersegment polaron model or a distribution of lifetimes model.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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 Receptor. • Involvement of Glucocorticoid Receptor in multiple pathologies. • Novel xenobiotic ligands for Glucocorticoid Receptor. • Potential for multifaceted Glucocorticoid Receptor-targeted pharmacological interventions.« less

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. The negotiation of the sick role: general practitioners’ classification of patients with medically unexplained symptoms

    PubMed Central

    Mik-Meyer, Nanna; Obling, Anne Roelsgaard

    2012-01-01

    In encounters between general practitioners (GPs) and patients with medically unexplained symptoms (MUS), the negotiation of the sick role is a social process. In this process, GPs not only use traditional biomedical diagnostic tools but also rely on their own opinions and evaluations of a patient’s particular circumstances in deciding whether that patient is legitimately sick. The doctor is thus a gatekeeper of legitimacy. This article presents results from a qualitative interview study conducted in Denmark with GPs concerning their approach to patients with MUS. We employ a symbolic interaction approach that pays special attention to the external validation of the sick role, making GPs’ accounts of such patients particularly relevant. One of the article’s main findings is that GPs’ criteria for judging the legitimacy of claims by those patients that present with MUS are influenced by the extent to which GPs are able to constitute these patients as people with social problems and problematic personality traits. PMID:22384857

  6. Late stages in the evolution of classical novae

    NASA Technical Reports Server (NTRS)

    Starrfield, S.; Krautter, J.; Sonneborn, G.; Shore, S. N.; Wagner, R. M.; Austin, S.; Saizar, P.; Ferland, G.; Wade, R.; Gehrz, R. D.

    1990-01-01

    We have begun a study of the long term evolution of novae in outburst in order to determine the means by which they return in quiescence when nuclear burning has ended. This project involves both IUE and optical observations and theoretical predictions. Recently, in the initial observational part of this project, we have obtained IUE Short Wavelength Prime (SWP) spectra of GQ Mus 1983 and QU Vul 1984. Each spectrum was a 16 hour exposure using a combined US1 plus Vilspa shift. No novae have been studied in the UV for as long as QU Vul and GQ Mus and observations of their spectral evolution are providing unique data on the turn-off time scale. We have also obtained the spectra of old novae from the IUE archives in order to compare and contrast the existing spectra with those of GQ Mus and Qu Vul. The theoretical prediction is that a nova should be very hot just before turnoff but x ray observations from EXOSAT do not confirm this prediction.

  7. Dosimetric Accuracy of a Dual Photon Energy Linac at Low Monitor Setting for Various Pulse Repetition Frequencies

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

    Sharma, Anil Kumar; Supe, Sanjay S.; Anantha, N.

    2015-01-15

    Accuracy of dose delivery at low monitor unit setting is studied for a dual photon energy linear accelerator. Dose delivered per MU is found to be constant for both the photon beams for MU settings above 30. For lower MUs there is definite deviation from the calibrated value and the error is found to be increasing as fewer MUs are set for dose delivery. This dose/MU ratio at low MU setting is found to be dose-rate dependent, showing an increasing trend with pulse repetition frequency (PRF). Also, the dosimetric ratio is observed to be mode dependent; its value for anmore » 18 MV beam is almost double that observed in the case of a 6 MV beam at very low MU setting. The magnitude of this error should be determined for each energy so that appropriate corrections can be applied if very low MUs are to be used.« less

  8. Genomic resources for wild populations of the house mouse, Mus musculus and its close relative Mus spretus

    PubMed Central

    Harr, Bettina; Karakoc, Emre; Neme, Rafik; Teschke, Meike; Pfeifle, Christine; Pezer, Željka; Babiker, Hiba; Linnenbrink, Miriam; Montero, Inka; Scavetta, Rick; Abai, Mohammad Reza; Molins, Marta Puente; Schlegel, Mathias; Ulrich, Rainer G.; Altmüller, Janine; Franitza, Marek; Büntge, Anna; Künzel, Sven; Tautz, Diethard

    2016-01-01

    Wild populations of the house mouse (Mus musculus) represent the raw genetic material for the classical inbred strains in biomedical research and are a major model system for evolutionary biology. We provide whole genome sequencing data of individuals representing natural populations of M. m. domesticus (24 individuals from 3 populations), M. m. helgolandicus (3 individuals), M. m. musculus (22 individuals from 3 populations) and M. spretus (8 individuals from one population). We use a single pipeline to map and call variants for these individuals and also include 10 additional individuals of M. m. castaneus for which genomic data are publically available. In addition, RNAseq data were obtained from 10 tissues of up to eight adult individuals from each of the three M. m. domesticus populations for which genomic data were collected. Data and analyses are presented via tracks viewable in the UCSC or IGV genome browsers. We also provide information on available outbred stocks and instructions on how to keep them in the laboratory. PMID:27622383

  9. Successful Treatment of Intracranial Glioblastoma Xenografts With a Monoamine Oxidase B-Activated Pro-Drug.

    PubMed

    Sharpe, Martyn A; Livingston, Andrew D; Gist, Taylor L; Ghosh, Pardip; Han, Junyan; Baskin, David S

    2015-09-01

    The last major advance in the treatment of glioblastoma multiforme (GBM) was the introduction of temozolomide in 1999. Treatment with temozolomide following surgical debulking extends survival rate compared to radiotherapy and debulking alone. However, virtually all glioblastoma patients experience disease progression within 7 to 10 months. Although many salvage treatments, including bevacizumab, rechallenge with temozolomide, and other alkylating agents, have been evaluated, none of these clearly improves survival. Monoamine oxidase B (MAOB) is highly expressed in glioblastoma cell mitochondria, and mitochondrial function is intimately tied to treatment-resistant glioblastoma progression. These glioblastoma properties provide a strong rationale for pursuing a MAOB-selective pro-drug treatment approach that, upon drug activation, targets glioblastoma mitochondria, especially mitochondrial DNA. MP-MUS is the lead compound in a family of pro-drugs designed to treat GBM that is converted into the mature, mitochondria-targeting drug, P(+)-MUS, by MAOB. We show that MP-MUS can successfully kill primary gliomas in vitro and in vivo mouse xenograft models.

  10. Successful Treatment of Intracranial Glioblastoma Xenografts With a Monoamine Oxidase B-Activated Pro-Drug

    PubMed Central

    Sharpe, Martyn A.; Livingston, Andrew D.; Gist, Taylor L.; Ghosh, Pardip; Han, Junyan; Baskin, David S.

    2015-01-01

    The last major advance in the treatment of glioblastoma multiforme (GBM) was the introduction of temozolomide in 1999. Treatment with temozolomide following surgical debulking extends survival rate compared to radiotherapy and debulking alone. However, virtually all glioblastoma patients experience disease progression within 7 to 10 months. Although many salvage treatments, including bevacizumab, rechallenge with temozolomide, and other alkylating agents, have been evaluated, none of these clearly improves survival. Monoamine oxidase B (MAOB) is highly expressed in glioblastoma cell mitochondria, and mitochondrial function is intimately tied to treatment-resistant glioblastoma progression. These glioblastoma properties provide a strong rationale for pursuing a MAOB-selective pro-drug treatment approach that, upon drug activation, targets glioblastoma mitochondria, especially mitochondrial DNA. MP-MUS is the lead compound in a family of pro-drugs designed to treat GBM that is converted into the mature, mitochondria-targeting drug, P+-MUS, by MAOB. We show that MP-MUS can successfully kill primary gliomas in vitro and in vivo mouse xenograft models. PMID:26501110

  11. 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.

  12. 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.

  13. 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 results also reveal that GR ‾ / P ‾ in finer soils with smaller n values decreases more rapidly with decreasing P ‾ .

  14. 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.

  15. Joint Interference Alignment and Power Allocation for K-User Multicell MIMO Channel through Staggered Antenna Switching.

    PubMed

    Selvaprabhu, Poongundran; Chinnadurai, Sunil; Sarker, Md Abdul Latif; Lee, Moon Ho

    2018-01-28

    In this paper, we characterise the joint interference alignment (IA) and power allocation strategies for a K -user multicell multiple-input multiple-output (MIMO) Gaussian interference channel. We consider a MIMO interference channel with blind-IA through staggered antenna switching on the receiver. We explore the power allocation and feasibility condition for cooperative cell-edge (CE) mobile users (MUs) by assuming that the channel state information is unknown. The new insight behind the transmission strategy of the proposed scheme is premeditated (randomly generated transmission strategy) and partial cooperative CE MUs, where the transmitter is equipped with a conventional antenna, the receiver is equipped with a reconfigurable multimode antenna (staggered antenna switching pattern), and the receiver switches between preset T modes. Our proposed scheme assists and aligns the desired signals and interference signals to cancel the common interference signals because the received signal must have a corresponding independent signal subspace. The capacity for a K -user multicell MIMO Gaussian interference channel with reconfigurable multimode antennas is completely characterised. Furthermore, we show that the proposed K -user multicell MIMO scheduling and K -user L -cell CEUs partial cooperation algorithms elaborate the generalisation of K -user IA and power allocation strategies. The numerical results demonstrate that the proposed intercell interference scheme with partial-cooperative CE MUs achieves better capacity and signal-to-interference plus noise ratio (SINR) performance compared to noncooperative CE MUs and without intercell interference schemes.

  16. Illness explanations among patients with medically unexplained symptoms: different idioms for different contexts.

    PubMed

    Risør, Mette Bech

    2009-09-01

    Patients with medically unexplained symptoms (MUS) are often considered to be strictly confined to thinking about their symptoms as having only a physical etiology. However, several studies have shown, that the patients also apply other explanations for their sufferings. The aim of this study is to analyse the social construction of illness explanations among patients with MUS, and to illustrate the use of explanatory idioms as being dependent on space, time and setting, legitimizing each idiom. The study is based on repeated, semi-structured, qualitative interviews with nine informants during a period of 1.5 years. A thematic content analysis was performed on a pragmatic and phenomenological basis. We found, that patients with MUS employ at least four different explanatory idioms defined as: (1) the symptomatic idiom; (2) the personal idiom; (3) the social idiom; and (4) the moral idiom. All idioms play an important role in the process of creating meaning in the patients' everyday life. The symptomatic idiom is mainly used at clinical consultations in primary care, but it is not the only idiom of significance for the patients. Simultaneously other idioms exist and gradually become important for especially patients with MUS due to the lack of valid diagnoses and treatment opportunities. Clinical settings, however, call for the employment of the symptomatic idiom and a discrepancy is found between the general practitioners' notion of the bio-psycho-social model and the patients' everyday life idioms.

  17. Methylation status as a predictor of intravesical Bacillus Calmette-Guérin (BCG) immunotherapy response of high grade non-muscle invasive bladder tumor.

    PubMed

    Husek, Petr; Pacovsky, Jaroslav; Chmelarova, Marcela; Podhola, Miroslav; Brodak, Milos

    2017-06-01

    Genetic and epigenetic alterations play an important role in urothelial cancer pathogenesis. Deeper understanding of these processes could help us achieve better diagnosis and management of this life-threatening disease. The aim of this research was to evaluate the methylation status of selected tumor suppressor genes for predicting BCG response in patients with high grade non-muscle-invasive bladder tumor (NMIBC). We retrospectively evaluated 82 patients with high grade non-muscle-invasive bladder tumor (stage Ta, T1, CIS) who had undergone BCG instillation therapy. We compared epigenetic methylation status in BCG-responsive and BCG-failure groups. We used the MS-MLPA (Methylation-Specific Multiplex Ligation-Dependent Probe Amplification probe sets ME001 and ME004. The control group was 13 specimens of normal urotel (bladder tissue)). Newly identified methylations in high grade NMIBC were found in MUS81a, NTRK1 and PCCA. The methylation status of CDKN2B (P=0.00312 ** ) and MUS81a (P=0.0191 * ) is associated with clinical outcomes of BCG instillation therapy response. CDKN2B and MUS81a unmethylation was found in BCG failure patients. The results show that the methylation status of selected tumor suppressor genes (TSGs) has the potential for predicting BCG response in patients with NMIBC high grade tumors. Tumor suppressor genes such as CDKN2b, MUS81a, PFM-1, MSH6 and THBS1 are very promising for future research.

  18. Joint Interference Alignment and Power Allocation for K-User Multicell MIMO Channel through Staggered Antenna Switching

    PubMed Central

    2018-01-01

    In this paper, we characterise the joint interference alignment (IA) and power allocation strategies for a K-user multicell multiple-input multiple-output (MIMO) Gaussian interference channel. We consider a MIMO interference channel with blind-IA through staggered antenna switching on the receiver. We explore the power allocation and feasibility condition for cooperative cell-edge (CE) mobile users (MUs) by assuming that the channel state information is unknown. The new insight behind the transmission strategy of the proposed scheme is premeditated (randomly generated transmission strategy) and partial cooperative CE MUs, where the transmitter is equipped with a conventional antenna, the receiver is equipped with a reconfigurable multimode antenna (staggered antenna switching pattern), and the receiver switches between preset T modes. Our proposed scheme assists and aligns the desired signals and interference signals to cancel the common interference signals because the received signal must have a corresponding independent signal subspace. The capacity for a K-user multicell MIMO Gaussian interference channel with reconfigurable multimode antennas is completely characterised. Furthermore, we show that the proposed K-user multicell MIMO scheduling and K-user L-cell CEUs partial cooperation algorithms elaborate the generalisation of K-user IA and power allocation strategies. The numerical results demonstrate that the proposed intercell interference scheme with partial-cooperative CE MUs achieves better capacity and signal-to-interference plus noise ratio (SINR) performance compared to noncooperative CE MUs and without intercell interference schemes. PMID:29382100

  19. The identification in primary care of patients who have been repeatedly referred to hospital for medically unexplained symptoms: a pilot study.

    PubMed

    Smith, Benjamin J; McGorm, Kelly J; Weller, David; Burton, Christopher; Sharpe, Michael

    2009-09-01

    The study aimed (a) to test a method of identifying patients who have been repeatedly referred (RR) from primary care to medical outpatient clinics where they have received multiple diagnoses of medically unexplained symptoms (MUS) and (b) to describe the prevalence and characteristics of these patients. RR patients with MUS (RRMUS) were arbitrarily defined as those with (a) five or more referrals in a 5-year period and (b) a specialist final diagnosis of MUS for at least three of these referrals. A two-stage method of identifying these patients was piloted in one primary care practice: Stage 1 used computerized health service data to identify RR; Stage 2 used manual case note review to identify referrals that ended with specialist diagnoses of MUS. The RRMUS patients identified were asked to complete a questionnaire, a psychiatric diagnostic interview, and their GPs were asked to rate how "difficult to manage" they were. The process was feasible and reasonably accurate. From 6770 registered patients aged 18 to 65 years, 23 (0.3%) were identified as RRMUS. They accounted for 157 referrals over the 5-year period. Sixteen agreed to further assessment, and 8 (50%) had a current anxiety or depressive disorder. GPs rated only 8 (50%) as "difficult to manage." This two-stage procedure offers a practical method of identifying RRMUS patients in primary care as a first step in achieving more cost-effective care. These patients have substantial psychiatric morbidity.

  20. Functional Genomic Analysis of Cotton Genes with Agrobacterium-Mediated Virus-Induced Gene Silencing

    PubMed Central

    Gao, Xiquan; Shan, Libo

    2015-01-01

    Cotton (Gossypium spp.) is one of the most agronomically important crops worldwide for its unique textile fiber production and serving as food and feed stock. Molecular breeding and genetic engineering of useful genes into cotton have emerged as advanced approaches to improve cotton yield, fiber quality, and resistance to various stresses. However, the understanding of gene functions and regulations in cotton is largely hindered by the limited molecular and biochemical tools. Here, we describe the method of an Agrobacterium infiltration-based virus-induced gene silencing (VIGS) assay to transiently silence endogenous genes in cotton at 2-week-old seedling stage. The genes of interest could be readily silenced with a consistently high efficiency. To monitor gene silencing efficiency, we have cloned cotton GrCla1 from G. raimondii, a homolog gene of Arabidopsis Cloroplastos alterados 1 (AtCla1) involved in chloroplast development, and inserted into a tobacco rattle virus (TRV) binary vector pYL156. Silencing of GrCla1 results in albino phenotype on the newly emerging leaves, serving as a visual marker for silencing efficiency. To further explore the possibility of using VIGS assay to reveal the essential genes mediating disease resistance to Verticillium dahliae, a fungal pathogen causing severe Verticillium wilt in cotton, we developed a seedling infection assay to inoculate cotton seedlings when the genes of interest are silenced by VIGS. The method we describe here could be further explored for functional genomic analysis of cotton genes involved in development and various biotic and abiotic stresses. PMID:23386302

  1. Functional genomic analysis of cotton genes with agrobacterium-mediated virus-induced gene silencing.

    PubMed

    Gao, Xiquan; Shan, Libo

    2013-01-01

    Cotton (Gossypium spp.) is one of the most agronomically important crops worldwide for its unique textile fiber production and serving as food and feed stock. Molecular breeding and genetic engineering of useful genes into cotton have emerged as advanced approaches to improve cotton yield, fiber quality, and resistance to various stresses. However, the understanding of gene functions and regulations in cotton is largely hindered by the limited molecular and biochemical tools. Here, we describe the method of an Agrobacterium infiltration-based virus-induced gene silencing (VIGS) assay to transiently silence endogenous genes in cotton at 2-week-old seedling stage. The genes of interest could be readily silenced with a consistently high efficiency. To monitor gene silencing efficiency, we have cloned cotton GrCla1 from G. raimondii, a homolog gene of Arabidopsis Cloroplastos alterados 1 (AtCla1) involved in chloroplast development, and inserted into a tobacco rattle virus (TRV) binary vector pYL156. Silencing of GrCla1 results in albino phenotype on the newly emerging leaves, serving as a visual marker for silencing efficiency. To further explore the possibility of using VIGS assay to reveal the essential genes mediating disease resistance to Verticillium dahliae, a fungal pathogen causing severe Verticillium wilt in cotton, we developed a seedling infection assay to inoculate cotton seedlings when the genes of interest are silenced by VIGS. The method we describe here could be further explored for functional genomic analysis of cotton genes involved in development and various biotic and abiotic stresses.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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 these parameters. PMID:25558132

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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 elevated in Gr5 and Gr20, relative to Gr1. Pulmonary and systemic toxicity of graphite nanoplates may be dependent on lateral size and/or surface reactivity, with the graphite nanoplates > 5 μm laterally inducing greater toxicity which peaked at the early time points post-exposure relative to the 1-2 μm graphite nanoplate.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. Tracing the tracks of genotoxicity by trivalent and hexavalent chromium in Drosophila melanogaster.

    PubMed

    Mishra, Manish; Sharma, Anurag; Negi, M P S; Dwivedi, U N; Chowdhuri, D Kar

    2011-05-18

    Mutagen sensitive strains (mus) in Drosophila are known for their hypersensitivity to mutagens and environmental carcinogens. Accordingly, these mutants were grouped in pre- and post-replication repair pathways. However, studying mutants belonging to one particular repair pathway may not be adequate for examining chemical-induced genotoxicity when other repair pathways may neutralize its effect. To test whether both pre-and post-replication pathways are involved and effect of Cr(III)- and Cr(VI)-induced genotoxicity in absence or presence of others, we used double mutant approach in D. melanogaster. We observed DNA damage as evident by changes in Comet assay DNA migration in cells of larvae of Oregon R(+) and single mutants of pre- (mei-9, mus201 and mus210) and post- (mei-41, mus209 and mus309) replication repair pathways and also in double mutants of different combinations (pre-pre, pre-post and post-post replication repair) exposed to increasing concentrations of Cr(VI) (0.0, 5.0, 10.0 and 20.0 μg/ml) for 48 h. The damage was greater in pre-replication repair mutants after exposure to 5.0 μg/ml Cr(VI), while effects on Oregon R(+) and post replication repair mutants were insignificant. Post-replication repair mutants revealed significant DNA damage after exposure to 20.0 μg/ml Cr(VI). Further, double mutants generated in the above repair categories were examined for DNA damage following Cr(VI) exposure and a comparison of damage was studied between single and double mutants. Combinations of double mutants generated in the pre-pre replication repair pathways showed an indifferent interaction between the two mutants after Cr(VI) exposure while a synergistic interaction was evident in exposed post-post replication repair double mutants. Cr(III) (20.0 μg/ml) exposure to these strains did not induce any significant DNA damage in their cells. The study suggests that both pre- and post-replication pathways are affected in Drosophila by Cr(VI) leading to genotoxicity, which may have consequences for metal-induced carcinogenesis. 2011 Elsevier B.V. All rights reserved.

  7. Combinatorial Regulation of Meiotic Holliday Junction Resolution in C. elegans by HIM-6 (BLM) Helicase, SLX-4, and the SLX-1, MUS-81 and XPF-1 Nucleases

    PubMed Central

    Sonneville, Remi; Jagut, Marlène; Woglar, Alexander; Blow, Julian; Jantsch, Verena; Gartner, Anton

    2013-01-01

    Holliday junctions (HJs) are cruciform DNA structures that are created during recombination events. It is a matter of considerable importance to determine the resolvase(s) that promote resolution of these structures. We previously reported that C. elegans GEN-1 is a symmetrically cleaving HJ resolving enzyme required for recombinational repair, but we could not find an overt role in meiotic recombination. Here we identify C. elegans proteins involved in resolving meiotic HJs. We found no evidence for a redundant meiotic function of GEN-1. In contrast, we discovered two redundant HJ resolution pathways likely coordinated by the SLX-4 scaffold protein and also involving the HIM-6/BLM helicase. SLX-4 associates with the SLX-1, MUS-81 and XPF-1 nucleases and has been implicated in meiotic recombination in C. elegans. We found that C. elegans [mus-81; xpf-1], [slx-1; xpf-1], [mus-81; him-6] and [slx-1; him-6] double mutants showed a similar reduction in survival rates as slx-4. Analysis of meiotic diakinesis chromosomes revealed a distinct phenotype in these double mutants. Instead of wild-type bivalent chromosomes, pairs of “univalents” linked by chromatin bridges occur. These linkages depend on the conserved meiosis-specific transesterase SPO-11 and can be restored by ionizing radiation, suggesting that they represent unresolved meiotic HJs. This suggests the existence of two major resolvase activities, one provided by XPF-1 and HIM-6, the other by SLX-1 and MUS-81. In all double mutants crossover (CO) recombination is reduced but not abolished, indicative of further redundancy in meiotic HJ resolution. Real time imaging revealed extensive chromatin bridges during the first meiotic division that appear to be eventually resolved in meiosis II, suggesting back-up resolution activities acting at or after anaphase I. We also show that in HJ resolution mutants, the restructuring of chromosome arms distal and proximal to the CO still occurs, suggesting that CO initiation but not resolution is likely to be required for this process. PMID:23901331

  8. Combinatorial regulation of meiotic holliday junction resolution in C. elegans by HIM-6 (BLM) helicase, SLX-4, and the SLX-1, MUS-81 and XPF-1 nucleases.

    PubMed

    Agostinho, Ana; Meier, Bettina; Sonneville, Remi; Jagut, Marlène; Woglar, Alexander; Blow, Julian; Jantsch, Verena; Gartner, Anton

    2013-01-01

    Holliday junctions (HJs) are cruciform DNA structures that are created during recombination events. It is a matter of considerable importance to determine the resolvase(s) that promote resolution of these structures. We previously reported that C. elegans GEN-1 is a symmetrically cleaving HJ resolving enzyme required for recombinational repair, but we could not find an overt role in meiotic recombination. Here we identify C. elegans proteins involved in resolving meiotic HJs. We found no evidence for a redundant meiotic function of GEN-1. In contrast, we discovered two redundant HJ resolution pathways likely coordinated by the SLX-4 scaffold protein and also involving the HIM-6/BLM helicase. SLX-4 associates with the SLX-1, MUS-81 and XPF-1 nucleases and has been implicated in meiotic recombination in C. elegans. We found that C. elegans [mus-81; xpf-1], [slx-1; xpf-1], [mus-81; him-6] and [slx-1; him-6] double mutants showed a similar reduction in survival rates as slx-4. Analysis of meiotic diakinesis chromosomes revealed a distinct phenotype in these double mutants. Instead of wild-type bivalent chromosomes, pairs of "univalents" linked by chromatin bridges occur. These linkages depend on the conserved meiosis-specific transesterase SPO-11 and can be restored by ionizing radiation, suggesting that they represent unresolved meiotic HJs. This suggests the existence of two major resolvase activities, one provided by XPF-1 and HIM-6, the other by SLX-1 and MUS-81. In all double mutants crossover (CO) recombination is reduced but not abolished, indicative of further redundancy in meiotic HJ resolution. Real time imaging revealed extensive chromatin bridges during the first meiotic division that appear to be eventually resolved in meiosis II, suggesting back-up resolution activities acting at or after anaphase I. We also show that in HJ resolution mutants, the restructuring of chromosome arms distal and proximal to the CO still occurs, suggesting that CO initiation but not resolution is likely to be required for this process.

  9. 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.

  10. Postoperative Urinary Retention and Urinary Tract Infections Predict Midurethral Sling Mesh Complications.

    PubMed

    Punjani, Nahid; Winick-Ng, Jennifer; Welk, Blayne

    2017-01-01

    To determine if postoperative urinary retention and urinary tract infections (UTIs) were predictors of future mesh complications requiring surgical intervention after midurethral sling (MUS). Administrative data in Ontario, Canada, between 2002 and 2013 were used to identify all women who underwent a mesh-based MUS. The primary outcome was revision of the transvaginal mesh sling (including mesh removal/erosion/fistula, or urethrolysis). Two potential risk factors were analyzed: postoperative retention (within 30 days of procedure) and number of postoperative emergency room visits or hospital admissions for UTI symptoms. A total of 59,556 women had a MUS, of which 1598 (2.7%) required revision surgery. Of the 2025 women who presented to the emergency room or were admitted to hospital for postoperative retention, 212 (10.5%) required operative mesh revision. Of the 11,747 patients who had at least one postoperative UTI, 366 (3.1%) patients required operative mesh revision. In adjusted analysis, postoperative retention was significantly predictive of future reoperation (hazard ratio [HR] 3.46, 95% confidence interval [CI] 2.97-4.02), and this difference persisted when urethrolysis was excluded as a reason for sling revision (HR 3.08, 95% CI 2.62-3.63). Similarly, in adjusted analysis, each additional postoperative hospital visit for UTI symptoms increased the risk for surgical intervention for mesh complications (HR 1.74, 95% CI 1.61-1.87). Postoperative urinary retention and hospital presentation for UTI symptoms are associated with an increased risk of reoperation for MUS complications. These patients should be followed and investigated for mesh complications when appropriate. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. The interpretation of low mood and worry by high users of secondary care with medically unexplained symptoms.

    PubMed

    Burton, Christopher; McGorm, Kelly; Weller, David; Sharpe, Michael

    2011-10-02

    Around 1% of adults are repeatedly referred from primary to secondary care with medically unexplained symptoms (MUS); many of these patients have depression and anxiety disorders which are unrecognized or inadequately treated. We aimed to investigate the ways patients with MUS and their General Practitioners (GPs) interpret low mood and worry, whether they regard them as depressive or anxiety disorders and how they relate them causally to symptoms. We carried out semi-structured interviews with 27 patients who had been repeatedly referred to specialists for MUS and their GPs and analysed transcripts by qualitative comparison. The analysis examined themes relating to low mood and worry, and their influence on symptoms. It drew on the concept of "otherness", whereby mental phenomena can be located either within the self or as separate entities. Both patients and GPs acknowledged the presence of low mood and worry. They viewed low mood as either an individual's personal response to circumstances (including their physical symptoms) or as the illness called "depression"; only the latter was amenable to medical intervention. Worry was seen as a trait rather than as a symptom of an anxiety disorder. While low mood and worry were acknowledged to influence physical symptoms, they were considered insufficient to be the main cause by either the patients or their doctors. Patients with MUS who are high users of secondary care services interpret low mood and worry in ways which allow them to be discussed with professionals, but not as the cause of their physical symptoms.

  12. Effects of whole body vibration on motor unit recruitment and threshold

    PubMed Central

    Woledge, Roger C.; Martin, Finbarr C.; Newham, Di J.

    2012-01-01

    Whole body vibration (WBV) has been suggested to elicit reflex muscle contractions but this has never been verified. We recorded from 32 single motor units (MU) in the vastus lateralis of 7 healthy subjects (34 ± 15.4 yr) during five 1-min bouts of WBV (30 Hz, 3 mm peak to peak), and the vibration waveform was also recorded. Recruitment thresholds were recorded from 38 MUs before and after WBV. The phase angle distribution of all MUs during WBV was nonuniform (P < 0.001) and displayed a prominent peak phase angle of firing. There was a strong linear relationship (r = −0.68, P < 0.001) between the change in recruitment threshold after WBV and average recruitment threshold; the lowest threshold MUs increased recruitment threshold (P = 0.008) while reductions were observed in the higher threshold units (P = 0.031). We investigated one possible cause of changed thresholds. Presynaptic inhibition in the soleus was measured in 8 healthy subjects (29 ± 4.6 yr). A total of 30 H-reflexes (stimulation intensity 30% Mmax) were recorded before and after WBV: 15 conditioned by prior stimulation (60 ms) of the antagonist and 15 unconditioned. There were no significant changes in the relationship between the conditioned and unconditioned responses. The consistent phase angle at which each MU fired during WBV indicates the presence of reflex muscle activity similar to the tonic vibration reflex. The varying response in high- and low-threshold MUs may be due to the different contributions of the mono- and polysynaptic pathways but not presynaptic inhibition. PMID:22096119

  13. Analysis of Copy Number Variation in the Abp Gene Regions of Two House Mouse Subspecies Suggests Divergence during the Gene Family Expansions

    PubMed Central

    Pezer, Željka; Chung, Amanda G.; Karn, Robert C.

    2017-01-01

    Abstract The Androgen-binding protein (Abp) gene region of the mouse genome contains 64 genes, some encoding pheromones that influence assortative mating between mice from different subspecies. Using CNVnator and quantitative PCR, we explored copy number variation in this gene family in natural populations of Mus musculus domesticus (Mmd) and Mus musculus musculus (Mmm), two subspecies of house mice that form a narrow hybrid zone in Central Europe. We found that copy number variation in the center of the Abp gene region is very common in wild Mmd, primarily representing the presence/absence of the final duplications described for the mouse genome. Clustering of Mmd individuals based on this variation did not reflect their geographical origin, suggesting no population divergence in the Abp gene cluster. However, copy number variation patterns differ substantially between Mmd and other mouse taxa. Large blocks of Abp genes are absent in Mmm, Mus musculus castaneus and an outgroup, Mus spretus, although with differences in variation and breakpoint locations. Our analysis calls into question the reliance on a reference genome for interpreting the detailed organization of genes in taxa more distant from the Mmd reference genome. The polymorphic nature of the gene family expansion in all four taxa suggests that the number of Abp genes, especially in the central gene region, is not critical to the survival and reproduction of the mouse. However, Abp haplotypes of variable length may serve as a source of raw genetic material for new signals influencing reproductive communication and thus speciation of mice. PMID:28575204

  14. Recruitment order of quadriceps motor units: femoral nerve vs. direct quadriceps stimulation.

    PubMed

    Rodriguez-Falces, Javier; Place, Nicolas

    2013-12-01

    To investigate potential differences in the recruitment order of motor units (MUs) in the quadriceps femoris when electrical stimulation is applied over the quadriceps belly versus the femoral nerve. M-waves and mechanical twitches were evoked using femoral nerve stimulation and direct quadriceps stimulation of gradually increasing intensity from 20 young, healthy subjects. Recruitment order was investigated by analysing the time-to-peak twitch and the time interval from the stimulus artefact to the M-wave positive peak (M-wave latency) for the vastus medialis (VM) and vastus lateralis (VL) muscles. During femoral nerve stimulation, time-to-peak twitch and M-wave latency decreased consistently (P < 0.05) with increasing stimulus intensity, whereas, during graded direct quadriceps stimulation, time-to-peak twitch and VL M-wave latency did not show a clear trend (P > 0.05). For the VM muscle, M-wave latency decreased with increasing stimulation level for both femoral nerve and direct quadriceps stimulation, whereas, for the VL muscle, the variation of M-wave latency with stimulus intensity was different for the two stimulation geometries (P < 0.05). Femoral nerve stimulation activated MUs according to the size principle, whereas the recruitment order during direct quadriceps stimulation was more complex, depending ultimately on the architecture of the peripheral nerve and its terminal branches below the stimulating electrodes for each muscle. For the VM, MUs were orderly recruited for both stimulation geometries, whereas, for the VL muscle, MUs were orderly recruited for femoral nerve stimulation, but followed no particular order for direct quadriceps stimulation.

  15. Effects of whole body vibration on motor unit recruitment and threshold.

    PubMed

    Pollock, Ross D; Woledge, Roger C; Martin, Finbarr C; Newham, Di J

    2012-02-01

    Whole body vibration (WBV) has been suggested to elicit reflex muscle contractions but this has never been verified. We recorded from 32 single motor units (MU) in the vastus lateralis of 7 healthy subjects (34 ± 15.4 yr) during five 1-min bouts of WBV (30 Hz, 3 mm peak to peak), and the vibration waveform was also recorded. Recruitment thresholds were recorded from 38 MUs before and after WBV. The phase angle distribution of all MUs during WBV was nonuniform (P < 0.001) and displayed a prominent peak phase angle of firing. There was a strong linear relationship (r = -0.68, P < 0.001) between the change in recruitment threshold after WBV and average recruitment threshold; the lowest threshold MUs increased recruitment threshold (P = 0.008) while reductions were observed in the higher threshold units (P = 0.031). We investigated one possible cause of changed thresholds. Presynaptic inhibition in the soleus was measured in 8 healthy subjects (29 ± 4.6 yr). A total of 30 H-reflexes (stimulation intensity 30% Mmax) were recorded before and after WBV: 15 conditioned by prior stimulation (60 ms) of the antagonist and 15 unconditioned. There were no significant changes in the relationship between the conditioned and unconditioned responses. The consistent phase angle at which each MU fired during WBV indicates the presence of reflex muscle activity similar to the tonic vibration reflex. The varying response in high- and low-threshold MUs may be due to the different contributions of the mono- and polysynaptic pathways but not presynaptic inhibition.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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 related transcription factors. This review provides currently available information regarding the role of GR phosphorylation in its action, and highlights the possible underlying mechanisms of action.

  16. 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

  17. 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 (K-Gr1) consumed less of the foods they selected for their lunch meals, and wasted more than older elementary school students. Future studies should investigate why younger children wasted more food and potential strategies to reduce food waste by younger students. PMID:27637576

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

    Nguyen, Kham, E-mail: khamdiep@gmail.com; UT MD Anderson Cancer Center, School of Health Professions—Unit 2, Houston, TX; Cummings, David

    The purpose of this study was to evaluate the differences between volumetric modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) in the treatment of nasal cavity carcinomas. The treatment of 10 patients, who had completed IMRT treatment for resected tumors of the nasal cavity, was replanned with the Philips Pinnacle{sup 3} Version 9 treatment-planning system. The IMRT plans used a 9-beam technique whereas the VMAT (known as SmartArc) plans used a 3-arc technique. Both types of plans were optimized using Philips Pinnacle{sup 3} Direct Machine Parameter Optimization algorithm. IMRT and VMAT plans' quality was compared by evaluating the maximum,more » minimum, and mean doses to the target volumes and organs at risk, monitor units (MUs), and the treatment delivery time. Our results indicate that VMAT is capable of greatly reducing treatment delivery time and MUs compared with IMRT. The reduction of treatment delivery time and MUs can decrease the effects of intrafractional uncertainties that can occur because of patient movement during treatment delivery. VMAT's plans further reduce doses to critical structures that are in close proximity to the target volume.« less

  19. Whole Genome Sequence of Two Wild-Derived Mus musculus domesticus Inbred Strains, LEWES/EiJ and ZALENDE/EiJ, with Different Diploid Numbers

    PubMed Central

    Morgan, Andrew P.; Didion, John P.; Doran, Anthony G.; Holt, James M.; McMillan, Leonard; Keane, Thomas M.; de Villena, Fernando Pardo-Manuel

    2016-01-01

    Wild-derived mouse inbred strains are becoming increasingly popular for complex traits analysis, evolutionary studies, and systems genetics. Here, we report the whole-genome sequencing of two wild-derived mouse inbred strains, LEWES/EiJ and ZALENDE/EiJ, of Mus musculus domesticus origin. These two inbred strains were selected based on their geographic origin, karyotype, and use in ongoing research. We generated 14× and 18× coverage sequence, respectively, and discovered over 1.1 million novel variants, most of which are private to one of these strains. This report expands the number of wild-derived inbred genomes in the Mus genus from six to eight. The sequence variation can be accessed via an online query tool; variant calls (VCF format) and alignments (BAM format) are available for download from a dedicated ftp site. Finally, the sequencing data have also been stored in a lossless, compressed, and indexed format using the multi-string Burrows-Wheeler transform. All data can be used without restriction. PMID:27765810

  20. A polymorphic and hypervariable locus in the pseudoautosomal region of the CBA/H mouse sex chromosomes

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

    Fennelly, J.; Laval, S.; Wright, E.

    1996-04-01

    We have identified a genomic locus (DXYH1) that is polymorphic and hypervariable within the CBA/H colony. Using a panel of C57BL/6 x Mus spretus backcross offspring, it was mapped to the distal end of the X chromosome. Pseudoautosomal inheritance was demonstrated through three generations of CBA/H x CBA/H and CBA/H x C57BL/6 crosses and confirmed through linkage to the Sxr locus in X/Y Sxr x 3H1 crosses. Meiotic recombination frequencies place DXYH1 {approximately}28% into the pseudoautosomal region from the boundary. The de novo generation of CBA/H variant DXYH1 restriction fragment length polymorphisms during spermatogenesis is suggestive of the germline instabilitymore » associated with hypermutable human minisatellites. The absence of DXY1-related sequences in Mus spretus provides DNA sequence evidence to support the observed failure of X-Y pairing during meiosis and consequent hybrid infertility in C57BL/6 x Mus spretus male F1 offspring. 19 refs., 4 figs.« less

  1. IR luminescence of tellurium-doped silica-based optical fibre

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

    Dianov, Evgenii M; Alyshev, S V; Shubin, Aleksei V

    2012-03-31

    Tellurium-doped germanosilicate fibre has been fabricated by the MCVD process. In contrast to Te-containing glasses studied earlier, it has a broad luminescence band (full width at half maximum of {approx}350 nm) centred at 1500 nm, with a lifetime of {approx}2 {mu}s. The luminescence of the fibre has been studied before and after gamma irradiation in a {sup 60}Co source to 309 and 992 kGy. The irradiation produced a luminescence band around 1100 nm, with a full width at half maximum of {approx}400 nm and lifetime of {approx}5 {mu}s. (letters)

  2. Comparison of contraction times of a muscle and its motor units

    NASA Technical Reports Server (NTRS)

    Eldred, E.; Smith, L.; Edgerton, V. R.

    1992-01-01

    The twitch contraction time (CT) for each of 13 soleus (SOL) and 13 medial gastrocnemius (MG) muscles was compared with the mean CT from a sample of its motor units (MUs; 356 total) to see if the CT of a whole muscle when tested at its optimal length (Lo) differed systematically from that of its MUs tested at their individual Lo's. The CTs of the whole muscle were significantly longer in the ratio of 1.13. This is consistent with a hypothesis that electrical-field effects result in a more protracted contraction of the individual muscle fiber.

  3. Laboratory trials of three anticoagulant rodenticides for use against the Indian field mouse, Mus booduga Gray.

    PubMed Central

    Balasubramanyam, M.; Christopher, M. J.; Purushotham, K. R.

    1984-01-01

    The efficacy of three anticoagulant rodenticides for use against the Indian field mouse, Mus booduga, was evaluated in the laboratory. The poisons, namely warfarin, bromadiolone and brodifacoum, were all found to be toxic enough at the concentrations normally used against other commensal and field rodents. With brodifacoum (0.001 25%), bromadiolone (0.005%) and warfarin (0.025%), 83% of the animals died respectively after 1, 1 and 6 days' feeding. It is suggested that brodifacoum and bromadiolone might be more economical than warfarin for use in practical rodent control. PMID:6512257

  4. Relativistic Newtonian dynamics for objects and particles

    NASA Astrophysics Data System (ADS)

    Friedman, Y.

    2017-04-01

    Relativistic Newtonian Dynamics (RND) was introduced in a series of recent papers by the author, in partial cooperation with J. M. Steiner. RND was capable of describing non-classical behavior of motion under a central attracting force. RND incorporates the influence of potential energy on spacetime in Newtonian dynamics, treating gravity as a force in flat spacetime. It was shown that this dynamics predicts accurately gravitational time dilation, the anomalous precession of Mercury and the periastron advance of any binary. In this paper the model is further refined and extended to describe also the motion of both objects with non-zero mass and massless particles, under a conservative attracting force. It is shown that for any conservative force a properly defined energy is conserved on the trajectories and if this force is central, the angular momentum is also preserved. An RND equation of motion is derived for motion under a conservative force. As an application, it is shown that RND predicts accurately also the Shapiro time delay - the fourth test of GR.

  5. 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.

  6. 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.

  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. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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 GR programs either strongly agreed or agreed that GR are an essential component of any academic radiology department, and this opinion was shared by a majority of all respondents (68%). Almost all respondents (97%) either strongly agreed or agreed that general radiologic education of imaging subspecialists is valuable in an academic radiology department. A majority (65%) either strongly agreed or agreed that attendance at GR should be expected of all attending radiologists. GR programs among radiology residencies tend to have similar formats involving invited speakers, although the frequency, types of talks, and honoraria may vary slightly. Most programs value GR, and all programs integrate GR within resident education to some degree. The recent economic downturn has led to a decrease in the number of invited visiting speakers but not to a decrease in the amounts of honoraria. Copyright © 2011 AUR. Published by Elsevier Inc. All rights reserved.

  17. 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.

  18. 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

  19. 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.

  20. 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 transistor concepts with high operating speed and I(on)/I(off) ratio can be envisaged.

  1. [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

  2. 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.

  3. 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

  4. 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, are not clear at this time. PMID:23845513

  5. 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 PCEP-GR has proven to be a feasible, economic, valid and reliable tool for the assessment of UPCE that comprises self-efficacy expectation and relevant attitudes towards palliative care.

  6. 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.

  7. Temporal changes in artificial light exposure of marine turtle nesting areas.

    PubMed

    Kamrowski, Ruth L; Limpus, Col; Jones, Rhondda; Anderson, Sharolyn; Hamann, Mark

    2014-08-01

    Artificial light at night poses a significant threat to multiple taxa across the globe. In coastal regions, artificial lighting close to marine turtle nesting beaches is disruptive to their breeding success. Prioritizing effective management of light pollution requires an understanding of how the light exposure of nesting areas changes over time in response to changing temporal and spatial distributions of coastal development. We analyzed multitemporal, satellite night-light data, in combination with linear mixed model analysis, to determine broadscale changes in artificial light exposure at Australian marine turtle nesting areas between 1993 and 2010. We found seven marine turtle management units (MU), from five species, have experienced significant increases in light exposure over time, with flatback turtles nesting in east Australia experiencing the fastest increases. The remaining 12 MUs showed no significant change in light exposure. Unchanging MUs included those previously identified as having high exposure to light pollution (located in western Australia and southern Queensland), indicating that turtles in these areas have been potentially exposed to high light levels since at least the early nineties. At a finer geographic scale (within-MU), nine MUs contained nesting areas with significant increases in light exposure. These nesting areas predominantly occurred close to heavily industrialized coastal areas, thus emphasizing the importance of rigorous light management in industry. Within all MUs, nesting areas existed where light levels were extremely low and/or had not significantly increased since 1993. With continued coastal development, nesting females may shift to these darker/unchanging 'buffer' areas in the future. This is valuable information that informs our understanding of the capacity and resilience of marine turtles faced with coastal development: an understanding that is essential for effective marine turtle conservation. © 2013 John Wiley & Sons Ltd.

  8. GABAergic influences on ORX receptor-dependent abnormal motor behaviors and neurodegenerative events in fish

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

    Facciolo, Rosa Maria, E-mail: rm.facciolo@unical.i; Crudo, Michele; Giusi, Giuseppina

    2010-02-15

    At date the major neuroreceptors i.e. gamma-aminobutyric acid{sub A} (GABA{sub A}R) and orexin (ORXR) systems are beginning to be linked to homeostasis, neuroendocrine and emotional states. In this study, intraperitoneal treatment of the marine teleost Thalassoma pavo with the highly selective GABA{sub A}R agonist (muscimol, MUS; 0,1 mug/g body weight) and/or its antagonist bicuculline (BIC; 1 mug/g body weight) have corroborated a GABA{sub A}ergic role on motor behaviors. In particular, MUS induced moderate (p < 0.05) and great (p < 0.01) increases of swimming towards food sources and resting states after 24 (1 dose) and 96 (4 doses) h treatmentmore » sessions, respectively, when compared to controls. Conversely, BIC caused a very strong (p < 0.001) reduction of the former behavior and in some cases convulsive swimming. From the correlation of BIC-dependent behavioral changes to neuronal morphological and ORXR transcriptional variations, it appeared that the disinhibitory action of GABA{sub A}R was very likely responsible for very strong and strong ORXR mRNA reductions in cerebellum valvula and torus longitudinalis, respectively. Moreover these effects were linked to evident ultra-structural changes such as shrunken cell membranes and loss of cytoplasmic architecture. In contrast, MUS supplied a very low, if any, argyrophilic reaction in hypothalamic and mesencephalic regions plus a scarce level of ultra-structural damages. Interestingly, combined administrations of MUS + BIC were not related to consistent damages, aside mild neuronal alterations in motor-related areas such as optic tectum. Overall it is tempting to suggest, for the first time, a neuroprotective role of GABA{sub A}R inhibitory actions against the overexcitatory ORXR-dependent neurodegeneration and consequently abnormal swimming events in fish.« less

  9. Analysis of Copy Number Variation in the Abp Gene Regions of Two House Mouse Subspecies Suggests Divergence during the Gene Family Expansions.

    PubMed

    Pezer, Željka; Chung, Amanda G; Karn, Robert C; Laukaitis, Christina M

    2017-06-01

    The Androgen-binding protein ( Abp ) gene region of the mouse genome contains 64 genes, some encoding pheromones that influence assortative mating between mice from different subspecies. Using CNVnator and quantitative PCR, we explored copy number variation in this gene family in natural populations of Mus musculus domesticus ( Mmd ) and Mus musculus musculus ( Mmm ), two subspecies of house mice that form a narrow hybrid zone in Central Europe. We found that copy number variation in the center of the Abp gene region is very common in wild Mmd , primarily representing the presence/absence of the final duplications described for the mouse genome. Clustering of Mmd individuals based on this variation did not reflect their geographical origin, suggesting no population divergence in the Abp gene cluster. However, copy number variation patterns differ substantially between Mmd and other mouse taxa. Large blocks of Abp genes are absent in Mmm , Mus musculus castaneus and an outgroup, Mus spretus , although with differences in variation and breakpoint locations. Our analysis calls into question the reliance on a reference genome for interpreting the detailed organization of genes in taxa more distant from the Mmd reference genome. The polymorphic nature of the gene family expansion in all four taxa suggests that the number of Abp genes, especially in the central gene region, is not critical to the survival and reproduction of the mouse. However, Abp haplotypes of variable length may serve as a source of raw genetic material for new signals influencing reproductive communication and thus speciation of mice. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  10. Effect of Preoperative Low Maximal Flow Rate on Postoperative Voiding Trials after the Midurethral Sling Procedure in Women with Stress Urinary Incontinence.

    PubMed

    Chae, Ji Y; Bae, Jae H; Lee, Jeong G; Park, Hong S; Moon, Du G; Oh, Mi M

    2017-06-02

    To evaluate the effects of preoperative low maximal flow rate (Qmax) on voiding trials after the midurethral sling (MUS) procedure in women with stress urinary incontinence (SUI). One hundred and sixty-eight women who underwent MUS procedure were enrolled. Preoperative free uroflowmetry was performed and patients were divided by Qmax. Low Qmax was defined as a Qmax under 15 mL/sec with voided volume at least 150 mL. Surgical results, failure of voiding trial, and postoperative uroflowmetry parameters were compared between the groups. Failure of voiding trial was defined by a PVR more than 100 mL on postoperative uroflowmetry. At the discharge day, there were 42 cases showing failure of voiding trial and 33 cases requiring CIC, but only one patient showed failure of voiding trial at 12 months postoperatively. Overall, 48 patients had preoperative low Qmax. Low Qmax group showed lower Qmax in all of postoperative uroflowmetry, but there were no significant differences in the rate of postoperative voiding trial failure or CIC. The low Qmax group was then divided into two groups according to the preoperative detrusor pressure at Qmax over and under 20 cmH 2 O in pressure flow study. Comparing the two groups, no significant differences were observed in the cure rate, voiding trial failure or CIC. Our results suggest that women with preoperative low Qmax experienced no definite unfavorable voiding problem from the MUS procedure compared to those with normal voiding function. MUS procedure may be regarded as a safe and successful procedure in SUI women with low Qmax. © 2017 John Wiley & Sons Australia, Ltd.

  11. Influence of the contractile properties of muscle on motor unit firing rates during a moderate-intensity contraction in vivo.

    PubMed

    Trevino, Michael A; Herda, Trent J; Fry, Andrew C; Gallagher, Philip M; Vardiman, John P; Mosier, Eric M; Miller, Jonathan D

    2016-08-01

    It is suggested that firing rate characteristics of motor units (MUs) are influenced by the physical properties of the muscle. However, no study has correlated MU firing rates at recruitment, targeted force, or derecruitment with the contractile properties of the muscle in vivo. Twelve participants (age = 20.67 ± 2.35 yr) performed a 40% isometric maximal voluntary contraction of the leg extensors that included linearly increasing, steady force, and decreasing segments. Muscle biopsies were collected with myosin heavy chain (MHC) content quantified, and surface electromyography (EMG) was recorded from the vastus lateralis. The EMG signal was decomposed into the firing events of single MUs. Slopes and y-intercepts were calculated for 1) firing rates at recruitment vs. recruitment threshold, 2) mean firing rates at steady force vs. recruitment threshold, and 3) firing rates at derecruitment vs. derecruitment threshold relationships for each subject. Correlations among type I %MHC isoform content and the slopes and y-intercepts from the three relationships were examined. Type I %MHC isoform content was correlated with MU firing rates at recruitment (y-intercepts: r = -0.577; slopes: r = 0.741) and targeted force (slopes: r = 0.853) vs. recruitment threshold and MU firing rates at derecruitment (y-intercept: r = -0.597; slopes: r = 0.701) vs. derecruitment threshold relationships. However, the majority of the individual MU firing rates vs. recruitment and derecruitment relationships were not significant (P > 0.05) and, thus, revealed no systematic pattern. In contrast, MU firing rates during the steady force demonstrated a systematic pattern with higher firing rates for the lower- than higher-threshold MUs and were correlated with the physical properties of MUs in vivo. Copyright © 2016 the American Physiological Society.

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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 highly significant result (p<.001). GrD2 had a mean dentinal tubule diameter of 2.78μm and GrD3 of 1.09μm. Conclusion The present study revealed type I etching pattern after acid etching, while type III etching pattern in enamel after laser etching. The lased dentin showed preferential removal of intertubular dentin while acid etching had more effect on the peritubular dentin. No significant differences was observed in removal of smear layer between the acid etched and lased groups. Although diameter of the exposed dentinal tubules was lesser after lased treatment in comparison to acid etching, further long term in vivo studies are needed with different parameters to establish the usage of Er,Cr:YSGG as a sole etching agent. PMID:27437337

  8. 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 1.80 × 10 -10 mol m -2 s -1, g ≡ |Δ Gr|/R T is a dimensionless number, and n, m1, and m2 are adjustable fitted parameters ( n = 7.98 × 10 -5, m1 = 3.81 and m2 = 1.17). Based on measurements of the temporal evolution of RSi and RAl for each experiment, steady-state dissolution rates appear to be congruent at all Δ Gr. In contrast, non-steady-state dissolution is incongruent, and is related to Δ Gr. Scanning electron microscopy (SEM) images of post-reaction grain surfaces indicate that dissolution close to equilibrium (Δ Gr > -25 kJ mol -1) resulted in the precipitation of a secondary crystalline phase, but there are no indications that this altered the measured R-Δ Gr relation.

  9. Data Access Tools And Services At The Goddard Distributed Active Archive Center (GDAAC)

    NASA Technical Reports Server (NTRS)

    Pham, Long; Eng, Eunice; Sweatman, Paul

    2003-01-01

    As one of the largest providers of Earth Science data from the Earth Observing System, GDAAC provides the latest data from the Moderate Resolution Imaging Spectroradiometer (MODIS), Atmospheric Infrared Sounder (AIRS), Solar Radiation and Climate Experiment (SORCE) data products via GDAAC's data pool (50TB of disk cache). In order to make this huge volume of data more accessible to the public and science communities, the GDAAC offers multiple data access tools and services: Open Source Project for Network Data Access Protocol (OPeNDAP), Grid Analysis and Display System (GrADS/DODS) (GDS), Live Access Server (LAS), OpenGlS Web Map Server (WMS) and Near Archive Data Mining (NADM). The objective is to assist users in retrieving electronically a smaller, usable portion of data for further analysis. The OPeNDAP server, formerly known as the Distributed Oceanographic Data System (DODS), allows the user to retrieve data without worrying about the data format. OPeNDAP is capable of server-side subsetting of HDF, HDF-EOS, netCDF, JGOFS, ASCII, DSP, FITS and binary data formats. The GrADS/DODS server is capable of serving the same data formats as OPeNDAP. GDS has an additional feature of server-side analysis. Users can analyze the data on the server there by decreasing the computational load on their client's system. The LAS is a flexible server that allows user to graphically visualize data on the fly, to request different file formats and to compare variables from distributed locations. Users of LAS have options to use other available graphics viewers such as IDL, Matlab or GrADS. WMS is based on the OPeNDAP for serving geospatial information. WMS supports OpenGlS protocol to provide data in GIs-friendly formats for analysis and visualization. NADM is another access to the GDAAC's data pool. NADM gives users the capability to use a browser to upload their C, FORTRAN or IDL algorithms, test the algorithms, and mine data in the data pool. With NADM, the GDAAC provides an environment physically close to the data source. NADM will benefit users with mining or offer data reduction algorithms by reducing large volumes of data before transmission over the network to the user.

  10. Interaction between shock wave and single inertial bubbles near an elastic boundary.

    PubMed

    Sankin, G N; Zhong, P

    2006-10-01

    The interaction of laser-generated single inertial bubbles (collapse time = 121 mus) near a silicon rubber membrane with a shock wave (55 MPa in peak pressure and 1.7 mus in compressive pulse duration) is investigated. The interaction leads to directional, forced asymmetric collapse of the bubble with microjet formation toward the surface. Maximum jet penetration into the membrane is produced during the bubble collapse phase with optimal shock wave arrival time and stand-off distance. Such interaction may provide a unique acoustic means for in vivo microinjection, applicable to targeted delivery of macromolecules and gene vectors to biological tissues.

  11. Of Mice and ‘Convicts’: Origin of the Australian House Mouse, Mus musculus

    PubMed Central

    Gabriel, Sofia I.; Stevens, Mark I.; Mathias, Maria da Luz; Searle, Jeremy B.

    2011-01-01

    The house mouse, Mus musculus, is one of the most ubiquitous invasive species worldwide and in Australia is particularly common and widespread, but where it originally came from is still unknown. Here we investigated this origin through a phylogeographic analysis of mitochondrial DNA sequences (D-loop) comparing mouse populations from Australia with those from the likely regional source area in Western Europe. Our results agree with human historical associations, showing a strong link between Australia and the British Isles. This outcome is of intrinsic and applied interest and helps to validate the colonization history of mice as a proxy for human settlement history. PMID:22174847

  12. A new spontaneous allele at the pink-eyed dilution (p) locus discovered in Mus musculus castaneus.

    PubMed

    Tsuji, A; Wakayama, T; Ishikawa, A

    1995-10-01

    Mutant mice characterized by a cream coat and pink eyes were spontaneously discovered among the descendants of Indonesian wild mice (Mus musculus castaneus). This mutant phenotype was controlled by a single autosomal recessive gene that was allelic to the pink-eyed dilution (p) gene. The mutant mouse phenotypically resembled the original p mouse which was the first mutant identified at this locus. Nevertheless, these two alleles differed in origin, a previous report suggesting that the original p allele was derived from Japanese wild mice (M. m. molossinus). Thus the symbol pcas (pink-eyed castaneus) was proposed for the present mutation allele.

  13. Novel Arenavirus Sequences in Hylomyscus sp. and Mus (Nannomys) setulosus from Côte d'Ivoire: Implications for Evolution of Arenaviruses in Africa

    PubMed Central

    Kouassi, Stéphane K.; Fichet-Calvet, Elisabeth; Becker-Ziaja, Beate; Rieger, Toni; Ölschläger, Stephan; Dosso, Hernri; Denys, Christiane; ter Meulen, Jan; Akoua-Koffi, Chantal; Günther, Stephan

    2011-01-01

    This study aimed to identify new arenaviruses and gather insights in the evolution of arenaviruses in Africa. During 2003 through 2005, 1,228 small mammals representing 14 different genera were trapped in 9 villages in south, east, and middle west of Côte d'Ivoire. Specimens were screened by pan-Old World arenavirus RT-PCRs targeting S and L RNA segments as well as immunofluorescence assay. Sequences of two novel tentative species of the family Arenaviridae, Menekre and Gbagroube virus, were detected in Hylomyscus sp. and Mus (Nannomys) setulosus, respectively. Arenavirus infection of Mus (Nannomys) setulosus was also demonstrated by serological testing. Lassa virus was not found, although 60% of the captured animals were Mastomys natalensis. Complete S RNA and partial L RNA sequences of the novel viruses were recovered from the rodent specimens and subjected to phylogenetic analysis. Gbagroube virus is a closely related sister taxon of Lassa virus, while Menekre virus clusters with the Ippy/Mobala/Mopeia virus complex. Reconstruction of possible virus–host co-phylogeny scenarios suggests that, within the African continent, signatures of co-evolution might have been obliterated by multiple host-switching events. PMID:21695269

  14. [First evidence of lymphocytic choriomeningitis virus (Arenavirus) infection in Mus musculus rodents captured in the urban area of the municipality of Sincelejo, Sucre, Colombia].

    PubMed

    Castellar, Anais; Guevara, Marco; Rodas, Juan D; Londoño, Andrés F; Arroyave, Esteban; Díaz, Francisco J; Levis, Silvana; Blanco, Pedro J

    2017-04-01

    The lymphocytic choriomeningitis virus is an Old World arenavirus that infects Mus musculus, and can cause congenital hydrocephalus, chorioretinitis and multisystemic failure in transplant human recipients. Although the disease has not been clinically diagnosed in Colombia yet, there have been reports of infection with the Pichindé virus in rodents from Cauca and Valle del Cauca departments, and with the Guanarito virus in rodents from Córdoba department. To identify the lymphocytic choriomeningitis virus from Mus musculus captured in the municipality of Sincelejo. We evaluated 80 samples of plasma by ELISA using antigen from lymphocytic choriomeningitis virus. Additionally, a nested RT-PCR was performed to seropositive and seronegative samples for the S-segment. We found a 10% seroprevalence (8/80) and the viral genome was detected in 16 brain samples; the alignment (BLAST) and the phylogenetic analysis (MrBayes, version 3.2.2) confirmed the presence of the lymphocytic choriomeningitis virus. The results indicated that human infection with the lymphocytic choriomeningitis virus in humans could occur in the urban area of Sincelejo, although no cases have been reported so far.

  15. Differential expression of non-coding RNAs and continuous evolution of the X chromosome in testicular transcriptome of two mouse species.

    PubMed

    Homolka, David; Ivanek, Robert; Forejt, Jiri; Jansa, Petr

    2011-02-14

    Tight regulation of testicular gene expression is a prerequisite for male reproductive success, while differentiation of gene activity in spermatogenesis is important during speciation. Thus, comparison of testicular transcriptomes between closely related species can reveal unique regulatory patterns and shed light on evolutionary constraints separating the species. Here, we compared testicular transcriptomes of two closely related mouse species, Mus musculus and Mus spretus, which diverged more than one million years ago. We analyzed testicular expression using tiling arrays overlapping Chromosomes 2, X, Y and mitochondrial genome. An excess of differentially regulated non-coding RNAs was found on Chromosome 2 including the intronic antisense RNAs, intergenic RNAs and premature forms of Piwi-interacting RNAs (piRNAs). Moreover, striking difference was found in the expression of X-linked G6pdx gene, the parental gene of the autosomal retrogene G6pd2. The prevalence of non-coding RNAs among differentially expressed transcripts indicates their role in species-specific regulation of spermatogenesis. The postmeiotic expression of G6pdx in Mus spretus points towards the continuous evolution of X-chromosome silencing and provides an example of expression change accompanying the out-of-the X-chromosomal retroposition.

  16. Foraging activity of commensal Mus musculus in semi-captivity conditions. Effect of predator odours, previous experience and moonlight.

    PubMed

    Busch, María; Burroni, Nora E

    2015-12-01

    Mus musculus is a pest in urban and rural habitats where it consumes and contaminates food and may transmit diseases to human and domestic animals. Its control by anticoagulants is partially effective because of aversive behaviours and resistance. In this context, we wanted to assess the potential of the use of predator odours as repellents in experimental feeding trials using urine and faeces of domestic cats and faeces of geoffroyi cat, a wild small felid that is one of the main rodent predators in the study area. We also assessed the effect of previous experience and moonlight on foraging activity. We did not find an aversive response to cat odours in Mus musculus individuals. There was a trend to consume food in the same feeding stations over time, and the visit rate was lower in periods with high moonlight than in periods with low moonlight. Predator odours did not seem to be useful as rodent repellents, but maintaining illumination may lower rodent foraging activity. As rodents maintain their feeding sites over time, toxic baits may be more efficiently placed at sites previously known to be used by rodents. © 2014 Society of Chemical Industry.

  17. A 120kV IGBT modulator for driving a pierce electron gun

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

    Earley, L. M.; Brown, R. W.; Carlson, R. L.

    2004-01-01

    An IGBT modulator has been developed to drive a 120 kV, 23 A Pierce electron gun. The modulator is capable of producing pulses up to 10 {mu}s in width at repetition rates up to 10Hz with no active reset. The pulse rise time on the electron gun will be approximately 2 {mu}s and the remaining 8 {mu}s of flattop is tuned to have a ripple of less than 1 percent rms. The modulator technology was developed from a previous 50 kV prototype. The modulator consists of six boards, each with one EUPEC IGBT that drives a single common step-up transformermore » wound on METGLAS 2605SC cores. The six transformer cores share a common bi-filar output secondary winding. The modulator uses a fiber optic trigger system and has a high voltage cable output with an epoxy receptacle on the oil end and a ceramic receptacle on the vacuum end. The 120 kV electron gun was manufactured by MDS Co. and will be used to generate sheet electron beams from the standard pencil beam produced by the Pierce electron gun.« less

  18. Assessing altered motor unit recruitment patterns in paretic muscles of stroke survivors using surface electromyography.

    PubMed

    Hu, Xiaogang; Suresh, Aneesha K; Rymer, William Z; Suresh, Nina L

    2015-12-01

    The advancement of surface electromyogram (sEMG) recording and signal processing techniques has allowed us to characterize the recruitment properties of a substantial population of motor units (MUs) non-invasively. Here we seek to determine whether MU recruitment properties are modified in paretic muscles of hemispheric stroke survivors. Using an advanced EMG sensor array, we recorded sEMG during isometric contractions of the first dorsal interosseous muscle over a range of contraction levels, from 20% to 60% of maximum, in both paretic and contralateral muscles of stroke survivors. Using MU decomposition techniques, MU action potential amplitudes and recruitment thresholds were derived for simultaneously activated MUs in each isometric contraction. Our results show a significant disruption of recruitment organization in paretic muscles, in that the size principle describing recruitment rank order was materially distorted. MUs were recruited over a very narrow force range with increasing force output, generating a strong clustering effect, when referenced to recruitment force magnitude. Such disturbances in MU properties also correlated well with the impairment of voluntary force generation. Our findings provide direct evidence regarding MU recruitment modifications in paretic muscles of stroke survivors, and suggest that these modifications may contribute to weakness for voluntary contractions.

  19. Disruption of SLX4-MUS81 Function Increases the Relative Biological Effectiveness of Proton Radiation

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

    Liu, Qi; Underwood, Tracy S.A.; Kung, Jong

    2016-05-01

    Purpose: Clinical proton beam therapy has been based on the use of a generic relative biological effectiveness (RBE) of ∼1.1. However, emerging data have suggested that Fanconi anemia (FA) and homologous recombination pathway defects can lead to a variable RBE, at least in vitro. We investigated the role of SLX4 (FANCP), which acts as a docking platform for the assembly of multiple structure-specific endonucleases, in the response to proton irradiation. Methods and Materials: Isogenic cell pairs for the study of SLX4, XPF/ERCC1, MUS81, and SLX1 were irradiated at the mid-spread-out Bragg peak of a clinical proton beam (linear energy transfer 2.5 keV/μm)more » or with 250 kVp x-rays, and the clonogenic survival fractions were determined. To estimate the RBE of the protons relative to cobalt-60 photons (Co60Eq), we assigned a RBE(Co60Eq) of 1.1 to x-rays to correct the physical dose measured. Standard DNA repair foci assays were used to monitor the damage responses, and the cell cycle distributions were assessed by flow cytometry. The poly(ADP-ribose) polymerase inhibitor olaparib was used for comparison. Results: Loss of SLX4 function resulted in an enhanced proton RBE(Co60Eq) of 1.42 compared with 1.11 for wild-type cells (at a survival fraction of 0.1; P<.05), which correlated with increased persistent DNA double-strand breaks in cells in the S/G{sub 2} phase. Genetic analysis identified the SLX4-binding partner MUS81 as a mediator of resistance to proton radiation. Both proton irradiation and olaparib treatment resulted in a similar prolonged accumulation of RAD51 foci in SLX4/MUS81-deficient cells, suggesting a common defect in the repair of DNA replication fork-associated damage. Conclusions: A defect in the FA pathway at the level of SLX4 results in hypersensitivity to proton radiation, which is, at least in part, due to impaired MUS81-mediated processing of replication forks that stall at clustered DNA damage. In vivo and clinical studies are needed to confirm these findings in human cancers.« less

  20. Disruption of SLX4-MUS81 Function Increases the Relative Biological Effectiveness of Proton Radiation.

    PubMed

    Liu, Qi; Underwood, Tracy S A; Kung, Jong; Wang, Meng; Lu, Hsiao-Ming; Paganetti, Harald; Held, Kathryn D; Hong, Theodore S; Efstathiou, Jason A; Willers, Henning

    2016-05-01

    Clinical proton beam therapy has been based on the use of a generic relative biological effectiveness (RBE) of ∼1.1. However, emerging data have suggested that Fanconi anemia (FA) and homologous recombination pathway defects can lead to a variable RBE, at least in vitro. We investigated the role of SLX4 (FANCP), which acts as a docking platform for the assembly of multiple structure-specific endonucleases, in the response to proton irradiation. Isogenic cell pairs for the study of SLX4, XPF/ERCC1, MUS81, and SLX1 were irradiated at the mid-spread-out Bragg peak of a clinical proton beam (linear energy transfer 2.5 keV/μm) or with 250 kVp x-rays, and the clonogenic survival fractions were determined. To estimate the RBE of the protons relative to cobalt-60 photons (Co60Eq), we assigned a RBE(Co60Eq) of 1.1 to x-rays to correct the physical dose measured. Standard DNA repair foci assays were used to monitor the damage responses, and the cell cycle distributions were assessed by flow cytometry. The poly(ADP-ribose) polymerase inhibitor olaparib was used for comparison. Loss of SLX4 function resulted in an enhanced proton RBE(Co60Eq) of 1.42 compared with 1.11 for wild-type cells (at a survival fraction of 0.1; P<.05), which correlated with increased persistent DNA double-strand breaks in cells in the S/G2 phase. Genetic analysis identified the SLX4-binding partner MUS81 as a mediator of resistance to proton radiation. Both proton irradiation and olaparib treatment resulted in a similar prolonged accumulation of RAD51 foci in SLX4/MUS81-deficient cells, suggesting a common defect in the repair of DNA replication fork-associated damage. A defect in the FA pathway at the level of SLX4 results in hypersensitivity to proton radiation, which is, at least in part, due to impaired MUS81-mediated processing of replication forks that stall at clustered DNA damage. In vivo and clinical studies are needed to confirm these findings in human cancers. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. 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.

  2. 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.

  3. 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 samples were taken from high in the atmosphere. A significant difference in PR and GR reflectivity was found in convective cases, particularly in convective samples from the lower part of the atmosphere. In this case, the mean difference between PR and corrected GR reflectivity was -1.88 dBZ. The PR-GR bias was found to increase with the amount of PR attenuation correction applied, with the PR-GR bias reaching -3.07 dBZ in cases where the attenuation correction applied is greater than 6 dBZ. Additional analysis indicated that the version 6 TRMM PR retrieval algorithm underestimates rainfall in case of convective rain in the lower part of the atmosphere by 30%-40%.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. Results of a 10-year survey of workload for 10 treatment vaults at a high-throughput comprehensive cancer center.

    PubMed

    Saleh, Ziad H; Jeong, Jeho; Quinn, Brian; Mechalakos, James; St Germain, Jean; Dauer, Lawrence T

    2017-05-01

    The workload for shielding purposes of modern linear accelerators (linacs) consists of primary and scatter radiation which depends on the dose delivered to isocenter (cGy) and leakage radiation which depends on the monitor units (MUs). In this study, we report on the workload for 10 treatment vaults in terms of dose to isocenter (cGy), monitor units delivered (MUs), number of treatment sessions (Txs), as well as, use factors (U) and modulation factors (CI) for different treatment techniques. The survey was performed for the years between 2006 and 2015 and included 16 treatment machines which represent different generations of Varian linear accelerators (6EX, 600C, 2100C, 2100EX, and TrueBeam) operating at different electron and x-ray energies (6, 9, 12, 16 and 20 MeV electrons and, 6 and 15 MV x-rays). An institutional review board (IRB) approval was acquired to perform this study. Data regarding patient workload, dose to isocenter, number of monitor units delivered, beam energies, gantry angles, and treatment techniques were exported from an ARIA treatment management system (Varian Medical Systems, Palo Alto, Ca.) into Excel spreadsheets and data analysis was performed in Matlab. The average (± std-dev) number of treatment sessions, dose to isocenter, and number of monitor units delivered per week per machine in 2006 was 119 ± 39 Txs, (300 ± 116) × 10 2 cGys, and (78 ± 28) × 10 3 MUs respectively. In contrast, the workload in 2015 was 112 ± 40 Txs, (337 ± 124) × 10 2 cGys, and (111 ± 46) × 10 3 MUs. 60% of the workload (cGy) was delivered using 6 MV and 30% using 15 MV while the remaining 10% was delivered using electron beams. The modulation factors (MU/cGy) for IMRT and VMAT were 5.0 (± 3.4) and 4.6 (± 1.6) respectively. Use factors using 90° gantry angle intervals were equally distributed (~0.25) but varied considerably among different treatment techniques. The workload, in terms of dose to isocenter (cGy) and subsequently monitor units (MUs), has been steadily increasing over the past decade. This increase can be attributed to increased use of high dose hypo-fractionated regimens (SBRT, SRS) and the increase in use of IMRT and VMAT, which require higher MUs per cGy as compared to more conventional treatment (3DCRT). Meanwhile, the patient workload in terms of treatment sessions per week remained relatively constant. The findings of this report show that variables used for shielding purposes still fall within the recommendation of NCRP Report 151. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

  18. 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 globe, this study may have important applications in aiding water resources management in different regions.

  19. 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 changes in GR and egr-1 expression that arise early during postnatal developmental are reversible by chronic fluoxetine treatment during adolescence and adulthood. Copyright 2010 S. Karger AG, Basel.

  20. 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.

  1. Muscovite dissolution kinetics as a function of pH at elevated temperature

    DOE PAGES

    Lammers, Kristin; Smith, Megan M.; Carroll, Susan A.

    2017-06-07

    We report that mineral reactivity can play an important role in fracture-controlled fluid networks where maintaining or increasing permeability is a goal, such as enhanced geothermal systems. In these systems, dissolution generates new void space, removes cement and physically transports less reactive mineral grains, while secondary precipitation acts to narrow or seal off fluid pathways. Sheet silicate mineral reactivity is likely to affect permeability evolution at the elevated temperatures of geothermal reservoirs because of the high reactive surface area and prevalence of these minerals in hydrothermal zones. To better describe the reactivity of one common sheet silicate, muscovite, we conducted kinetic dissolution experiments using flow-through reactors at temperatures of 100–280 °C and a pH range of 2–9. Surface area-normalized muscovite dissolution rates ranged from 0.17–155 · 10 - 11 mol m - 2 s - 1 over this temperature range, but showed little variation with pH above 150 °C. Aluminum was released to solution nonstoichiometrically with respect to dissolved silica, most likely resulting from secondary precipitation of an aluminum oxy-hydroxide identified as boehmite (γ-AlO(OH)( s)) by X-ray diffraction in reaction products from experiments conducted at pH ≤ 6. Surface area-normalized muscovite dissolution rates, Rate mus (mol m - 2 s - 1), can be described from 25 to 280 °C with the following kinetic rate equation: Rate mus = ([3∙10 -3∙e -44 /R∙T∙amore » $$0.8\\atop{H+}$$] + [9∙10 -6∙e- 45/R∙T] + [5∙10 -1∙ e-61/R∙T ∙a$$0.6\\atop{OH-}$$] ∙ (1-e -ΔGr/RT) where the rate and pre-exponential factors are in mol m - 2 s - 1; the activation energies, E, are in kJ mol - 1; a H+ and a OH- represent the activities of H + and OH -, respectively; R (kJ mol - 1 K - 1) is the gas constant; T is the temperature in Kelvins; and ΔG r (kJ mol - 1) is a measure of how close the aqueous solution is to muscovite equilibrium. The rate equation is constrained by our new data literature rates and has been evaluated against previous formulations with varying dependence on reaction affinity. Although 150 °C muscovite rates from Oelkers et al. (2008) show a systematic dependence on reaction affinity, incorporating this dependence did not accurately reproduce the higher-temperature rates. In conclusion, we recommend the rate equation shown above, with an affinity term that slows reaction rates only when solutions are close to equilibrium, for simulating the dissolution of muscovite under geothermal conditions.« less

  2. Muscovite dissolution kinetics as a function of pH at elevated temperature

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

    Lammers, Kristin; Smith, Megan M.; Carroll, Susan A.

    We report that mineral reactivity can play an important role in fracture-controlled fluid networks where maintaining or increasing permeability is a goal, such as enhanced geothermal systems. In these systems, dissolution generates new void space, removes cement and physically transports less reactive mineral grains, while secondary precipitation acts to narrow or seal off fluid pathways. Sheet silicate mineral reactivity is likely to affect permeability evolution at the elevated temperatures of geothermal reservoirs because of the high reactive surface area and prevalence of these minerals in hydrothermal zones. To better describe the reactivity of one common sheet silicate, muscovite, we conducted kinetic dissolution experiments using flow-through reactors at temperatures of 100–280 °C and a pH range of 2–9. Surface area-normalized muscovite dissolution rates ranged from 0.17–155 · 10 - 11 mol m - 2 s - 1 over this temperature range, but showed little variation with pH above 150 °C. Aluminum was released to solution nonstoichiometrically with respect to dissolved silica, most likely resulting from secondary precipitation of an aluminum oxy-hydroxide identified as boehmite (γ-AlO(OH)( s)) by X-ray diffraction in reaction products from experiments conducted at pH ≤ 6. Surface area-normalized muscovite dissolution rates, Rate mus (mol m - 2 s - 1), can be described from 25 to 280 °C with the following kinetic rate equation: Rate mus = ([3∙10 -3∙e -44 /R∙T∙amore » $$0.8\\atop{H+}$$] + [9∙10 -6∙e- 45/R∙T] + [5∙10 -1∙ e-61/R∙T ∙a$$0.6\\atop{OH-}$$] ∙ (1-e -ΔGr/RT) where the rate and pre-exponential factors are in mol m - 2 s - 1; the activation energies, E, are in kJ mol - 1; a H+ and a OH- represent the activities of H + and OH -, respectively; R (kJ mol - 1 K - 1) is the gas constant; T is the temperature in Kelvins; and ΔG r (kJ mol - 1) is a measure of how close the aqueous solution is to muscovite equilibrium. The rate equation is constrained by our new data literature rates and has been evaluated against previous formulations with varying dependence on reaction affinity. Although 150 °C muscovite rates from Oelkers et al. (2008) show a systematic dependence on reaction affinity, incorporating this dependence did not accurately reproduce the higher-temperature rates. In conclusion, we recommend the rate equation shown above, with an affinity term that slows reaction rates only when solutions are close to equilibrium, for simulating the dissolution of muscovite under geothermal conditions.« less

  3. 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.

  4. 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.

  5. 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.

  6. [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.

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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...

  17. New Results on Cepheid Masses

    NASA Astrophysics Data System (ADS)

    Evans, N. R.; Bohm-Vitense, E.; Carpenter, K.; Robinson, R.; Beck-Winchatz, B.

    1996-12-01

    Masses for Cepheid variable stars can be measured by combining the orbital velocity amplitude for the Cepheid (from a ground-based orbit) with the orbital velocity amplitude of a hot main sequence companion (observed in the ultraviolet from satellites such as IUE and HST) and the mass of the companion (inferred from from the ultraviolet energy distribution). Observations of 5 binary systems are now completed or in progress with the Goddard High Resolution Spectrograph on the Hubble Space Telescope. Recently completed observations of U Aql lead to a mass of 5.1 +/- 1.1 Msun . We will discuss the results for S Mus, V350 Sgr, U Aql, and Y Car, and the constraints they place on stellar evolution calculations. As would be expected, some of the B companions have high rotational velocities, decreasing the accuracy with which their orbital velocities can be measured. The preliminary conclusion from the 4 HST targets and SU Cyg (mass from IUE observations) is that a weighted mean indicates no convective overshoot but the mode (which reflects the HST results better) agrees with the modest overshoot used in the Geneva evolutionary calculations. Financial Support was provided by a NASA grant GO-4541-01 to EB--V and GO-4541.02 to KGC, a grant from the Natural Sciences and Engineering Council, Canada to NRE, from the AXAF Science Center NASA Contract NAS8-39073.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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 maximum agonist response (apparent pKB values of 11.9, 11.2 and 11.1 respectively). 5. In anaesthetized rabbits, GR203040 antagonized reductions in carotid arterial vascular resistance evoked by SPOMe, injected via the lingual artery (DR10 (i.e. the dose producing a dose-ratio of 10) = 1.1 micrograms kg-1, i.v.). At a dose 20 fold greater than its DR10 value (i.e. 22 micrograms kg-1, i.v.), significant antagonism was evident more than 2 h after GR203040 administration. 6. In anaesthetized rats, GR203040 (3 and 10 mg kg-1, i.v.) produced a dose-dependent inhibition of plasma protein extravasation in dura mater, conjunctiva, eyelid and lip in response to electrical stimulation of the trigeminal ganglion. 7. It is concluded that GR203040 is one of the most potent and selective NK1 receptor antagonists yet described, and as such, has considerable potential as a pharmacological tool to characterize the physiological and pathological roles of substance P and NK1 receptors. GR203040 may also have potential as a novel therapeutic agent for the treatment of conditions such as migraine, emesis and pain. PMID:8719789

  3. Methylation patterns of repetitive DNA sequences in germ cells of Mus musculus.

    PubMed

    Sanford, J; Forrester, L; Chapman, V; Chandley, A; Hastie, N

    1984-03-26

    The major and the minor satellite sequences of Mus musculus were undermethylated in both sperm and oocyte DNAs relative to the amount of undermethylation observed in adult somatic tissue DNA. This hypomethylation was specific for satellite sequences in sperm DNA. Dispersed repetitive and low copy sequences show a high degree of methylation in sperm DNA; however, a dispersed repetitive sequence was undermethylated in oocyte DNA. This finding suggests a difference in the amount of total genomic DNA methylation between sperm and oocyte DNA. The methylation levels of the minor satellite sequences did not change during spermiogenesis, and were not associated with the onset of meiosis or a specific stage in sperm development.

  4. DNase I nick translation in situ on meiotic chromosomes of the mouse, Mus musculus.

    PubMed

    Raman, R; Singh, A P; Nanda, I

    1988-08-01

    DNase-I-sensitive sites have been located on the meiotic chromosomes of the mouse, Mus musculus, by the in situ DNase I nick-translation method. We find that: (1) of all the cell types studied, pachytene nuclei are the most sensitive to DNase I; (2) in diplotene the nicks occur preferentially in the vicinity of chiasmata; (3) the sex chromosomes are also sensitive to the enzyme despite their transcriptional quiescence; and (4) in the sex bivalent the nicks are primarily observed in the putative region of recombination. We conclude that, in addition to discriminating between the transcriptionally active and inactive states of chromatin, DNase I identifies recombination-specific chromatin changes in meiotic prophase.

  5. Optical Studies of Nd-doped benzil, a potential luminescent and laser material.

    PubMed

    Noginov, M A; Curley, M; Noginova, N; Wang, W S; Aggarwal, M D

    1998-08-20

    Neodymium-doped benzil crystals have been synthesized and characterized for their absorption, emission, and kinetics properties. From Judd-Ofelt analysis, the radiative decay time of Nd emission (peaking at 1055 nm) is estimated to be equal to 441 mus. The experimental Nd lifetime (under Ar+ laser excitation) is equal to 19 mus. The broad emission band centered at approximately 700 nm (tau(decay) approximately 15 ns) and the Raman scattering with characteristic frequency shift of 1600 cm(-1) have been observed at excitation of benzil with 532-nm Q-switched laser pulses. We show that rare-earth-doped benzil can be considered as a potential candidate for luminescent and solid-state laser material.

  6. 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 categorization applied to the data. In this paper, we will show results comparing the 3-D gridded analysis "black box" approach to the GPM prototype volume-matching approach, using matching TRMM PR and WSR-88D ground radar data. The affects of applying data constraints and data categorizations on the volume-matched data to the results will be shown, and explanations of the differences in terms of data and analysis algorithm characteristics will be presented. Implications of the differences to the determination of PR/DPR calibration differences and use of ground radar data to evaluate the PR and DPR attenuation correction algorithms will be discussed.

  7. 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 improvement related to fortified yogurt consumption; (2) an inversely baseline-dependent increase in s25OHD; and (3) a seasonal effect that highlights the importance of VitD3-fortified foods during winter, even at 5 µg/d, in healthy menopausal women. PMID:28976265

  8. 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 inversely baseline-dependent increase in s25OHD; and (3) a seasonal effect that highlights the importance of VitD 3 -fortified foods during winter, even at 5 µg/d, in healthy menopausal women.

  9. 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

  10. 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

  11. 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

  12. 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.

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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.

  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. [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), 1.45 vs 1.03 (p < 0.05); platelets - 0.09 vs 0.22 (p < 0.02), 0.24 vs 0.15 (NS). 3) Renal function (%pts): increased serum cre- atinine - 56% vs 56%, 55% vs 38% (p < 0.001); hemofiltration use - 1.1% vs 1.5% (NS), 1.5% vs 0.4% (NS). 4) Perioperative myocardial infarction - 21.6% vs 17.9% (NS), 17.6% vs 14.6% (NS); other ischemic events - 3.2% vs 3.0% (NS), 1.5% vs 1.2% (NS). 5) Hospital mortality: 4.8% vs 4.5% (NS), 4.4% vs 1.6% (NS). 1) TrAc does not reduce the risk of surgical re-exploration for bleeding. 2) Taking into account the differences between conv CABG and off-pump CABG, TrAc hemostatic effect seems to be inferior to that of Aprot, without offering a better safety profile in terms of lesser renal or ischemic risk as a counterpart.

  20. Quantitative muscle ultrasound is useful for evaluating secondary axonal degeneration in chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Hokkoku, Keiichi; Matsukura, Kiyoshi; Uchida, Yudai; Kuwabara, Midori; Furukawa, Yuichi; Tsukamoto, Hiroshi; Hatanaka, Yuki; Sonoo, Masahiro

    2017-10-01

    In chronic inflammatory demyelinating polyneuropathy (CIDP), exclusion of secondary axonal degeneration is challenging with conventional methods such as nerve conduction study (NCS), needle electromyography, and nerve biopsy. Increased echo intensity (EI) and decreased muscle thickness (MT) identified on muscle ultrasound (MUS) examination represent muscle denervation due to axonal degeneration in neurogenic disorders, suggesting MUS as a new tool to detect secondary axonal degeneration in patients with CIDP. EI and MT of abductor pollicis brevis, abductor digiti minimi, and first dorsal interosseous muscles were measured in 16 CIDP patients. Raw values were converted into z -scores using data from 60 normal controls (NCs). Six of 45 muscles showed abnormally high EI and low MT, suggesting denervation following secondary axonal degeneration. These six muscles belonged to two patients with long disease history, unresponsiveness to treatment, and long interval from onset to initial therapy. There were no significant differences in EI and MT ( p  = .23 and .67, respectively) between the CIDP and NC groups, although NCS results revealed obvious demyelinating abnormalities in all CIDP patients, suggesting the fact that muscle structures will be preserved, and EI and MT will not change unless secondary axonal degeneration occurs in CIDP. MUS is a promising tool for evaluating secondary axonal degeneration in patients with CIDP.

  1. A research coding method to evaluate medical clinicians conduct of behavioral health care in patients with unexplained symptoms.

    PubMed

    Grayson-Sneed, Katelyn A; Smith, Robert C

    2018-04-01

    Develop a reliable coding method of a Behavioral Health Treatment Model for patients with Medically Unexplained Symptoms (BHTM-MUS). Two undergraduates trained for 30h coded videotaped interviews from 161 resident-simulated patient (SP) interactions. Trained on 45 videotapes, coders coded 33 (20%) of 161 study set tapes for the BHTM-MUS. Guetzkow's U, Cohen's Kappa, and percent of agreement were used to measure coders' reliability in unitizing and coding residents' skills for eliciting: education and informing (4 yes/no items), motivating (2), treatment statements (5), commitment and goals (2), negotiates plan (8), non-emotion patient-centered skills (4), and patient-centered emotional skills (8). 60 items were dichotomized a priori from analysis of the BHTM-MUS and were reduced to 33 during training. Guetzkow's U ranged from .00 to .082. Kappa ranged from 0.76 to 0.97 for the 7 variables and 33 individual items. The overall kappa was 0.87, and percent of agreement was 95.7%. Percent of agreement by item ranged from 85 to 100%. A highly reliable coding method is recommended to evaluate medical clinicians' behavioral care skills in patients with unexplained symptoms. A way to rate behavioral care in patients with unexplained symptoms. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Test of Fruit Extract Pare (Momordica charantia L.) to Quality of Ejaculated Spermatozoa Mice (Mus musculus L.)

    NASA Astrophysics Data System (ADS)

    Fifendy, M.; Indriati, G.

    2018-04-01

    Pare (Momordica charantia L.) can be used in the treatment of various diseases, such as influenza, cancer, anti-inflammatory, anti-HIV, antimitotic and antifertilitas. This study aimed to determine the effect of the herbal bitter (Momordica charantia L.) to ejaculated sperm quality mice (Mus musculus L.). This research was conducted using Completely Randomized Design (CRD) with 4 treatments and 6 replications, water and fed adlibitum. First treatment is given solvent extract. Second treatments extract were given 0.2 gram, third treatment were given 0.4 gram of extracts and fourth treatment were treated exstrac 0.6 gram were orally for 30 days. After the mice decapitated, dissected and take sperm from vas deferens. Then, the sperm preparation determined using the improved Neubauer. Data were analyzed by ANOVA (Analysis of Varians). The results shoured at doses of 0,2 gram, the average sperm count was 19.89. decrease significant when compared with the control in which the average number of sperm 29.13. So with this research the effective doses to decrease sperm count and can be used as a contraception medication dosage was 0,2 gram. It can be conclude that the extract of bitter (Momordica charantia L.) can decrease the quality of the ejaculated sperm of mice (Mus musculus L.)

  3. Playing Super Mario 64 increases hippocampal grey matter in older adults.

    PubMed

    West, Greg L; Zendel, Benjamin Rich; Konishi, Kyoko; Benady-Chorney, Jessica; Bohbot, Veronique D; Peretz, Isabelle; Belleville, Sylvie

    2017-01-01

    Maintaining grey matter within the hippocampus is important for healthy cognition. Playing 3D-platform video games has previously been shown to promote grey matter in the hippocampus in younger adults. In the current study, we tested the impact of 3D-platform video game training (i.e., Super Mario 64) on grey matter in the hippocampus, cerebellum, and the dorsolateral prefrontal cortex (DLPFC) of older adults. Older adults who were 55 to 75 years of age were randomized into three groups. The video game experimental group (VID; n = 8) engaged in a 3D-platform video game training over a period of 6 months. Additionally, an active control group took a series of self-directed, computerized music (piano) lessons (MUS; n = 12), while a no-contact control group did not engage in any intervention (CON; n = 13). After training, a within-subject increase in grey matter within the hippocampus was significant only in the VID training group, replicating results observed in younger adults. Active control MUS training did, however, lead to a within-subject increase in the DLPFC, while both the VID and MUS training produced growth in the cerebellum. In contrast, the CON group displayed significant grey matter loss in the hippocampus, cerebellum and the DLPFC.

  4. Differential Expression of Non-Coding RNAs and Continuous Evolution of the X Chromosome in Testicular Transcriptome of Two Mouse Species

    PubMed Central

    Homolka, David; Ivanek, Robert; Forejt, Jiri; Jansa, Petr

    2011-01-01

    Background Tight regulation of testicular gene expression is a prerequisite for male reproductive success, while differentiation of gene activity in spermatogenesis is important during speciation. Thus, comparison of testicular transcriptomes between closely related species can reveal unique regulatory patterns and shed light on evolutionary constraints separating the species. Methodology/Principal Findings Here, we compared testicular transcriptomes of two closely related mouse species, Mus musculus and Mus spretus, which diverged more than one million years ago. We analyzed testicular expression using tiling arrays overlapping Chromosomes 2, X, Y and mitochondrial genome. An excess of differentially regulated non-coding RNAs was found on Chromosome 2 including the intronic antisense RNAs, intergenic RNAs and premature forms of Piwi-interacting RNAs (piRNAs). Moreover, striking difference was found in the expression of X-linked G6pdx gene, the parental gene of the autosomal retrogene G6pd2. Conclusions/Significance The prevalence of non-coding RNAs among differentially expressed transcripts indicates their role in species-specific regulation of spermatogenesis. The postmeiotic expression of G6pdx in Mus spretus points towards the continuous evolution of X-chromosome silencing and provides an example of expression change accompanying the out-of-the X-chromosomal retroposition. PMID:21347268

  5. Playing Super Mario 64 increases hippocampal grey matter in older adults

    PubMed Central

    Konishi, Kyoko; Benady-Chorney, Jessica; Bohbot, Veronique D.; Peretz, Isabelle; Belleville, Sylvie

    2017-01-01

    Maintaining grey matter within the hippocampus is important for healthy cognition. Playing 3D-platform video games has previously been shown to promote grey matter in the hippocampus in younger adults. In the current study, we tested the impact of 3D-platform video game training (i.e., Super Mario 64) on grey matter in the hippocampus, cerebellum, and the dorsolateral prefrontal cortex (DLPFC) of older adults. Older adults who were 55 to 75 years of age were randomized into three groups. The video game experimental group (VID; n = 8) engaged in a 3D-platform video game training over a period of 6 months. Additionally, an active control group took a series of self-directed, computerized music (piano) lessons (MUS; n = 12), while a no-contact control group did not engage in any intervention (CON; n = 13). After training, a within-subject increase in grey matter within the hippocampus was significant only in the VID training group, replicating results observed in younger adults. Active control MUS training did, however, lead to a within-subject increase in the DLPFC, while both the VID and MUS training produced growth in the cerebellum. In contrast, the CON group displayed significant grey matter loss in the hippocampus, cerebellum and the DLPFC. PMID:29211727

  6. Assessing altered motor unit recruitment patterns in paretic muscles of stroke survivors using surface electromyography

    NASA Astrophysics Data System (ADS)

    Hu, Xiaogang; Suresh, Aneesha K.; Rymer, William Z.; Suresh, Nina L.

    2015-12-01

    Objective. The advancement of surface electromyogram (sEMG) recording and signal processing techniques has allowed us to characterize the recruitment properties of a substantial population of motor units (MUs) non-invasively. Here we seek to determine whether MU recruitment properties are modified in paretic muscles of hemispheric stroke survivors. Approach. Using an advanced EMG sensor array, we recorded sEMG during isometric contractions of the first dorsal interosseous muscle over a range of contraction levels, from 20% to 60% of maximum, in both paretic and contralateral muscles of stroke survivors. Using MU decomposition techniques, MU action potential amplitudes and recruitment thresholds were derived for simultaneously activated MUs in each isometric contraction. Main results. Our results show a significant disruption of recruitment organization in paretic muscles, in that the size principle describing recruitment rank order was materially distorted. MUs were recruited over a very narrow force range with increasing force output, generating a strong clustering effect, when referenced to recruitment force magnitude. Such disturbances in MU properties also correlated well with the impairment of voluntary force generation. Significance. Our findings provide direct evidence regarding MU recruitment modifications in paretic muscles of stroke survivors, and suggest that these modifications may contribute to weakness for voluntary contractions.

  7. Assessing altered motor unit recruitment patterns in paretic muscles of stroke survivors using surface electromyography

    PubMed Central

    Hu, Xiaogang; Suresh, Aneesha K; Rymer, William Z; Suresh, Nina L

    2017-01-01

    Objective The advancement of surface electromyogram (sEMG) recording and signal processing techniques has allowed us to characterize the recruitment properties of a substantial population of motor units (MUs) non-invasively. Here we seek to determine whether MU recruitment properties are modified in paretic muscles of hemispheric stroke survivors. Approach Using an advanced EMG sensor array, we recorded sEMG during isometric contractions of the first dorsal interosseous muscle over a range of contraction levels, from 20% to 60% of maximum, in both paretic and contralateral muscles of stroke survivors. Using MU decomposition techniques, MU action potential amplitudes and recruitment thresholds were derived for simultaneously activated MUs in each isometric contraction. Main results Our results show a significant disruption of recruitment organization in paretic muscles, in that the size principle describing recruitment rank order was materially distorted. MUs were recruited over a very narrow force range with increasing force output, generating a strong clustering effect, when referenced to recruitment force magnitude. Such disturbances in MU properties also correlated well with the impairment of voluntary force generation. Significance Our findings provide direct evidence regarding MU recruitment modifications in paretic muscles of stroke survivors, and suggest that these modifications may contribute to weakness for voluntary contractions. PMID:26402920

  8. 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 responded sensitively to Holocene climate changes. Ongoing research will improve the chronological constraints on these fluctuations.

  9. 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 associated with GRα transcripts in SLE patients.

  10. 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 progression of diseases such as HIV-1. PMID:23658782

  11. 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 below 0.6°. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. [Physical and technical quality assurance in German breast cancer screening: progress report of the Reference Center Muenster after three years].

    PubMed

    Sommer, A; Girnus, R; Wendt, B; Czwoydzinski, J; Wüstenbecker, C; Heindel, W; Lenzen, H

    2009-05-01

    German breast cancer screening is monitored by a large physical quality assurance program. This report refers to the first experiences of the Reference Center (RC) Muenster after three years of the technical quality control of digital and analog mammography units (MU). This paper also shows whether the presently used quality assurance (QA) method is able to ensure that the MUs in the screening program are functioning without any serious problems. RC Muenster supervises 95 units (May 2008). The daily, weekly and monthly quality assurance of these units is controlled by web-based QA software named "MammoConrol" and developed by RC Muenster. The annual QA for the units must be conducted in the form of an on-site inspection by medical physics experts of the RC and is scored by an objective ranking system. The results of these QA routines were evaluated and analyzed for this paper. During the period from 3/1/2006 to 5/31/2008, 8 % of the analog systems and 1 % of the digital systems exhibited problems in the daily QA. For 9 % of the analog MUs and 17 % of the digital MUs, failures appeared in the monthly QA. In the annual control, 86.7 % of the analog units exhibited slight problems and 13.3 % had serious problems. With respect to the digital units, 12 % were without any defects, 58 % had slight problems, 27 % had serious failures and 3 % had to be reported to the responsible authorities and were temporarily shut down. The special quality control requirements for German breast cancer screening, including annual on-site checks of the units, have shown in the last three years that QA with a high monitoring standard can be ensured for a large number of decentralized MUs. The currently used QA method sufficiently ensures that the screening program is technically safe. Further studies must show whether the density and focus of the QA measures must be reconfigured.

  13. Mouse allergen, lung function, and atopy in Puerto Rican children.

    PubMed

    Forno, Erick; Cloutier, Michelle M; Datta, Soma; Paul, Kathryn; Sylvia, Jody; Calvert, Deanna; Thornton-Thompson, Sherell; Wakefield, Dorothy B; Brehm, John; Hamilton, Robert G; Alvarez, María; Colón-Semidey, Angel; Acosta-Pérez, Edna; Canino, Glorisa; Celedón, Juan C

    2012-01-01

    To examine the relation between mouse allergen exposure and asthma in Puerto Rican children. Mus m 1, Der p 1, Bla g 2, and Fel d 1 allergens were measured in dust samples from homes of Puerto Rican children with (cases) and without (controls) asthma in Hartford, CT (n = 449) and San Juan (SJ), Puerto Rico (n = 678). Linear or logistic regression was used for the multivariate analysis of mouse allergen (Mus m 1) and lung function (FEV(1) and FEV(1)/FVC) and allergy (total IgE and skin test reactivity (STR) to ≥1 allergen) measures. Homes in SJ had lower mouse allergen levels than those in Hartford. In multivariate analyses, mouse allergen was associated with higher FEV(1) in cases in Hartford (+70.6 ml, 95% confidence interval (CI) = 8.6-132.7 ml, P = 0.03) and SJ (+45.1 ml, 95% CI =  -0.5 to 90.6 ml, P = 0.05). In multivariate analyses of controls, mouse allergen was inversely associated with STR to ≥1 allergen in non-sensitized children (odds ratio [OR] for each log-unit increment in Mus m 1 = 0.7, 95% CI = 0.5-0.9, P<0.01). In a multivariate analysis including all children at both study sites, each log-increment in mouse allergen was positively associated with FEV(1) (+28.3 ml, 95% CI = 1.4-55.2 ml, P = 0.04) and inversely associated with STR to ≥1 allergen (OR for each log-unit increment in Mus m 1 = 0.8, 95% CI = 0.6-0.9, P<0.01). Mouse allergen is associated with a higher FEV(1) and lower odds of STR to ≥1 allergen in Puerto Rican children. This may be explained by the allergen itself or correlated microbial exposures.

  14. SU-E-T-216: TPS QC Supporting Program by a Third-Party Evaluation Agency in Japan.

    PubMed

    Fukata, K; Minemura, T; Kurokawa, C; Miyagishi, T; Itami, J

    2012-06-01

    To equalize the quality of radiation therapy in Japan by supporting quality control of radiation treatment planning system. Center for Cancer Control and Information Service in National Cancer Center supports the QA-QC of the cancer core hospitals in Japan as a third-party evaluation agency. Recently, a program for assessing the quality of treatment planning system (TPS) began as a part of our QA-QC supporting activities. In this program, a questionnaire about TPS was sent to 45 prefectural cancer core hospitals in Japan. The object of this questionnaire is to assess the proper commissioning, implement and applications of TPSs. The contents of the questionnaire are as follows; 1) calculate MUs which deliver 1000 cGy to the point of SSD = 100 cm, 10 cm depth with field sizes ranging from 5×5 to 30 × 30 cm 2 , and obtain doses at several depths for the calculated MUs, 2) calculate MUs which deliver 1000 cGy to the point of SSD = 100 cm, 10 cm depth for wedge fields whose angles are from 15 to 60 degrees, and obtain doses at several depths with the MUs, 3) calculate MU which deliver 1000 cGy to the point of STD = 100 cm, 10 cm depth with 10×10 cm 2 field size and obtain doses at several depths with the MU. In this program, 179 beam data from 44 facilities were collected. Data were compared in terms of dose per MU, output factor, wedge factor and TMR. It was found that 90% of the data agreed within 2%. The quality of the treatment planning system was investigated through the questionnaire including the information of essential beam data. We compared 179 beam data in TPSs sent from 44 facilities and 90% of the data showed good agreement. © 2012 American Association of Physicists in Medicine.

  15. Evaluation of clinically applied treatment beams with respect to bunker shielding parameters for a Cyberknife M6.

    PubMed

    Henzen, Dominik; Schmidhalter, Daniel; Zanella, Claudia Christina; Volken, Werner; Mackeprang, Paul-Henry; Malthaner, Marco; Fix, Michael Karl; Manser, Peter

    2018-01-01

    Compared to a conventional linear accelerator, the Cyberknife (CK) is a unique system with respect to radiation protection shielding and the variety and number of non-coplanar beams are two key components regarding this aspect. In this work, a framework to assess the direction distribution and modulation factor (MF) of clinically applied treatment beams of a CyberKnife M6 is developed. Database filtering options allow studying the influence of different parameters such as collimator types, treatment sites or different bunker sizes. A distribution of monitor units (MU) is generated by projecting treatment beams onto the walls, floor and ceiling of the CyberKnife bunker. This distribution is found to be highly heterogeneous and depending, among other parameters, on the bunker size. For our bunker design, 10%-13% of the MUs are delivered to the right and left wall, each. The floor receives more than 64% of the applied MUs, while the wall behind the patient's head is not hit by primary treatment beams. Between 0% and 5% of the total MUs are delivered to the wall at the patient's feet. This number highly depends on the treatment site, e.g., for extracranial patients no beams hit that wall. Collimator choice was found to have minor influence on the distribution of MUs. On the other hand, the MF depends on the collimator type as well as on the treatment site. The MFs (delivered MU/prescribed dose) for all treatments, all MLC treatments, cranial and extracranial treatments are 8.3, 6.4, 7.7, and 9.9 MU/cGy, respectively. The developed framework allows assessing and monitoring important parameters regarding radiation protection of a CK-M6 using the actually applied treatment beams. Furthermore, it enables evaluating different clinical and constructional situations using the filtering options. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

  16. Monosynaptic Ia projections from intrinsic hand muscles to forearm motoneurones in humans.

    PubMed

    Marchand-Pauvert, V; Nicolas, G; Pierrot-Deseilligny, E

    2000-05-15

    Heteronymous Ia excitatory projections from intrinsic hand muscles to human forearm motoneurones (MNs) were investigated. Changes in firing probability of single motor units (MUs) in the flexor carpi radialis (FCR), flexor carpi ulnaris (FCU), flexor digitorum superficialis (FDS), extensor carpi radialis (ECR), extensor carpi ulnaris (ECU) and extensor digitorum communis (EDC) were studied after electrical stimuli were applied to the median and ulnar nerve at wrist level and to the corresponding homonymous nerve at elbow level. Homonymous facilitation, occurring at the same latency as the H reflex, and therefore attributed to monosynaptic Ia EPSPs, was found in all the sampled units. In many MUs an early facilitation was also evoked by heteronymous low-threshold afferents from intrinsic hand muscles. The low threshold (between 0.5 and 0.6 times motor threshold (MT)) and the inability of a pure cutaneous stimulation to reproduce this effect indicate that it is due to stimulation of group I muscle afferents. Evidence for a similar central delay (monosynaptic) in heteronymous as in homonymous pathways was accepted when the difference in latencies of the homonymous and heteronymous peaks did not differ from the estimated supplementary afferent conduction time from wrist to elbow level by more than 0.5 ms (conduction velocity in the fastest Ia afferents between wrist and elbow levels being equal to 69 m s-1). A statistically significant heteronymous monosynaptic Ia excitation from intrinsic hand muscles supplied by both median and ulnar nerves was found in MUs belonging to all forearm motor nuclei tested (although not in ECU MUs after ulnar stimulation). It was, however, more often found in flexors than in extensors, in wrist than in finger muscles and in muscles operating in the radial than in the ulnar side. It is argued that the connections of Ia afferents from intrinsic hand muscles to forearm MNs, which are stronger and more widely distributed than in the cat, might be used to provide a support to the hand during manipulatory movements.

  17. Perirhinal cortical inactivation impairs object-in-place memory and disrupts task-dependent firing in hippocampal CA1, but not in CA3.

    PubMed

    Lee, Inah; Park, Seong-Beom

    2013-01-01

    Objects and their locations can associatively define an event and a conjoint representation of object-place can form an event memory. Remembering how to respond to a certain object in a spatial context is dependent on both hippocampus and perirhinal cortex (PER). However, the relative functional contributions of the two regions are largely unknown in object-place associative memory. We investigated the PER influence on hippocampal firing in a goal-directed object-place memory task by comparing the firing patterns of CA1 and CA3 of the dorsal hippocampus between conditions of PER muscimol inactivation and vehicle control infusions. Rats were required to choose one of the two objects in a specific spatial context (regardless of the object positions in the context), which was shown to be dependent on both hippocampus and PER. Inactivation of PER with muscimol (MUS) severely disrupted performance of well-trained rats, resulting in response bias (i.e., choosing any object on a particular side). MUS did not significantly alter the baseline firing rates of hippocampal neurons. We measured the similarity in firing patterns between two trial conditions in which the same target objects were chosen on opposite sides within the same arm [object-in-place (O-P) strategy] and compared the results with the similarity in firing between two trial conditions in which the rat chose any object encountered on a particular side [response-in-place (R-P) strategy]. We found that the similarity in firing patterns for O-P trials was significantly reduced with MUS compared to control conditions (CTs). Importantly, this was largely because MUS injections affected the O-P firing patterns in CA1 neurons, but not in CA3. The results suggest that PER is critical for goal-directed organization of object-place associative memory in the hippocampus presumably by influencing how object information is associated with spatial information in CA1 according to task demand.

  18. Variation in light intensity with height and time from subsequent lightning return strokes

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

    Jordan, D.M.; Uman, M.A.

    1983-08-20

    Relative light intensity has been measured photographically as a function of height and time for seven subsequent return strokes in two lightning flashes at ranges of 7.8 and 8.7 km. The film used was Kodak 5474 Shellburst, which has a roughly constant spectral response between 300 and 670 nm. The time resolution was about 1.0 ..mu..s, and the spatial resolution was about 4 m. The observed light signals consisted of a fast rise to peak, followed by a slower decrease to a relatively constant value. The amplitude of the initial light peak decreases exponentially with height with a decay constantmore » of about 0.6 to 0.8 km. The 20% to 80% rise time of the initial light signal is between 1 and 4 ..mu..s near ground and increases by an additional 1 to 2 ..mu..s by the time the return stroke reaches the cloud base, a height between 1 and 2 km. The light intensity 30 ..mu..s after the initial peak is relatively constant with height and has an amplitude that is 15% to 30% of the initial peak near the ground and 50% to 100% of the initial peak at cloud base. The logarithm of the peak light intensity near the ground is roughly proportional to the initial peak electric field intensity, and this in turn implies that the current decrease with height may be much slower than the light decrease. The absolute light intensity has been estimated by integrating the photographic signals from individual channel segments to simulate the calibrated all-sky photoelectric data of Guo and Krider (1982). Using this method, the authors find that the mean peak radiance near the ground is 8.3 x 10/sup 5/ W/m, with a total range from 1.4 x 10/sup 5/ to 3.8 x 10/sup 6/ W/m. 16 references, 11 figures.« less

  19. Mental health care use in medically unexplained and explained physical symptoms: findings from a general population study

    PubMed Central

    van Eck van der Sluijs, Jonna F; ten Have, Margreet; Rijnders, Cees A; van Marwijk, Harm WJ; de Graaf, Ron; van der Feltz-Cornelis, Christina M

    2016-01-01

    Objective The aim of this study was to explore mental health care utilization patterns in primary and specialized mental health care of people with unexplained or explained physical symptoms. Methods Data were derived from the first wave of the Netherlands Mental Health Survey and Incidence Study-2, a nationally representative face-to-face cohort study among the general population aged 18–64 years. We selected subjects with medically unexplained symptoms (MUS) only (MUSonly; n=177), explained physical symptoms only (PHYonly, n=1,952), combined MUS and explained physical symptoms (MUS + PHY, n=209), and controls without physical symptoms (NONE, n=4,168). We studied entry into mental health care and the number of treatment contacts for mental problems, in both primary care and specialized mental health care. Analyses were adjusted for sociodemographic characteristics and presence of any 12-month mental disorder assessed with the Composite International Diagnostic Interview 3.0. Results At the primary care level, all three groups of subjects with physical symptoms showed entry into care for mental health problems significantly more often than controls. The adjusted odds ratios were 2.29 (1.33, 3.95) for MUSonly, 1.55 (1.13, 2.12) for PHYonly, and 2.25 (1.41, 3.57) for MUS + PHY. At the specialized mental health care level, this was the case only for MUSonly subjects (adjusted odds ratio 1.65 [1.04, 2.61]). In both the primary and specialized mental health care, there were no significant differences between the four groups in the number of treatment contacts once they entered into treatment. Conclusion All sorts of physical symptoms, unexplained as well as explained, were associated with significant higher entry into primary care for mental problems. In specialized mental health care, this was true only for MUSonly. No differences were found in the number of treatment contacts. This warrants further research aimed at the content of the treatment contacts. PMID:27574433

  20. Mouse Allergen, Lung Function, and Atopy in Puerto Rican Children

    PubMed Central

    Forno, Erick; Cloutier, Michelle M.; Datta, Soma; Paul, Kathryn; Sylvia, Jody; Calvert, Deanna; Thornton-Thompson, Sherell; Wakefield, Dorothy B.; Brehm, John; Hamilton, Robert G.; Alvarez, María; Colón-Semidey, Angel; Acosta-Pérez, Edna; Canino, Glorisa; Celedón, Juan C.

    2012-01-01

    Objective To examine the relation between mouse allergen exposure and asthma in Puerto Rican children. Methods Mus m 1, Der p 1, Bla g 2, and Fel d 1 allergens were measured in dust samples from homes of Puerto Rican children with (cases) and without (controls) asthma in Hartford, CT (n = 449) and San Juan (SJ), Puerto Rico (n = 678). Linear or logistic regression was used for the multivariate analysis of mouse allergen (Mus m 1) and lung function (FEV1 and FEV1/FVC) and allergy (total IgE and skin test reactivity (STR) to ≥1 allergen) measures. Results Homes in SJ had lower mouse allergen levels than those in Hartford. In multivariate analyses, mouse allergen was associated with higher FEV1 in cases in Hartford (+70.6 ml, 95% confidence interval (CI) = 8.6–132.7 ml, P = 0.03) and SJ (+45.1 ml, 95% CI =  −0.5 to 90.6 ml, P = 0.05). In multivariate analyses of controls, mouse allergen was inversely associated with STR to ≥1 allergen in non-sensitized children (odds ratio [OR] for each log-unit increment in Mus m 1 = 0.7, 95% CI = 0.5–0.9, P<0.01). In a multivariate analysis including all children at both study sites, each log-increment in mouse allergen was positively associated with FEV1 (+28.3 ml, 95% CI = 1.4–55.2 ml, P = 0.04) and inversely associated with STR to ≥1 allergen (OR for each log-unit increment in Mus m 1 = 0.8, 95% CI = 0.6–0.9, P<0.01). Conclusions Mouse allergen is associated with a higher FEV1 and lower odds of STR to ≥1 allergen in Puerto Rican children. This may be explained by the allergen itself or correlated microbial exposures. PMID:22815744

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