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Sample records for jet mk ii

  1. Identification of the sites for CaMK-II-dependent phosphorylation of GABA(A) receptors.

    PubMed

    Houston, Catriona M; Lee, Henry H C; Hosie, Alastair M; Moss, Stephen J; Smart, Trevor G

    2007-06-15

    Phosphorylation can affect both the function and trafficking of GABA(A) receptors with significant consequences for neuronal excitability. Serine/threonine kinases can phosphorylate the intracellular loops between M3-4 of GABA(A) receptor beta and gamma subunits thereby modulating receptor function in heterologous expression systems and in neurons (1, 2). Specifically, CaMK-II has been demonstrated to phosphorylate the M3-4 loop of GABA(A) receptor subunits expressed as GST fusion proteins (3, 4). It also increases the amplitude of GABA(A) receptor-mediated currents in a number of neuronal cell types (5-7). To identify which substrate sites CaMK-II might phosphorylate and the consequent functional effects, we expressed recombinant GABA(A) receptors in NG108-15 cells, which have previously been shown to support CaMK-II modulation of GABA(A) receptors containing the beta3 subunit (8). We now demonstrate that CaMK-II mediates its effects on alpha1beta3 receptors via phosphorylation of Ser(383) within the M3-4 domain of the beta subunit. Ablation of beta3 subunit phosphorylation sites for CaMK-II revealed that for alphabetagamma receptors, CaMK-II has a residual effect on GABA currents that is not mediated by previously identified sites of CaMK-II phosphorylation. This residual effect is abolished by mutation of tyrosine phosphorylation sites, Tyr(365) and Tyr(367), on the gamma2S subunit, and by the tyrosine kinase inhibitor genistein. These results suggested that CaMK-II is capable of directly phosphorylating GABA(A) receptors and activating endogenous tyrosine kinases to phosphorylate the gamma2 subunit in NG108-15 cells. These findings were confirmed in a neuronal environment by expressing recombinant GABA(A) receptors in cerebellar granule neurons. PMID:17442679

  2. Differential expression of CaMK-II genes during early zebrafish embryogenesis.

    PubMed

    Rothschild, Sarah C; Lister, James A; Tombes, Robert M

    2007-01-01

    CaMK-II is a highly conserved Ca(2+)/calmodulin-dependent protein kinase expressed throughout the lifespan of all vertebrates. During early development, CaMK-II regulates cell cycle progression and "non-canonical" Wnt-dependent convergent extension. In the zebrafish, Danio rerio, CaMK-II activity rises within 2 hr after fertilization. At the time of somite formation, zygotic expression from six genes (camk2a1, camk2b1, camk2g1, camk2g2, camk2d1, camk2d2) results in a second phase of increased activity. Zebrafish CaMK-II genes are 92-95% identical to their human counterparts in the non-variable regions. During the first three days of development, alternative splicing yields at least 20 splice variants, many of which are unique. Whole-mount in situ hybridization reveals that camk2g1 comprises the majority of maternal expression. All six genes are expressed strongly in ventral regions at the 18-somite stage. Later, camk2a1 is expressed in anterior somites, heart, and then forebrain. Camk2b1 is expressed in somites, mid- and forebrain, gut, retina, and pectoral fins. Camk2g1 appears strongly along the midline and then in brain, gut, and pectoral fins. Camk2g2 is expressed early in the midbrain and trunk and exhibits the earliest retinal expression. Camk2d1 is elevated early at somite boundaries, then epidermal tissue, while camk2d2 is expressed in discrete anterior locations, steadily increasing along either side of the dorsal midline and then throughout the brain, including the retina. These findings reveal a complex pattern of CaMK-II gene expression consistent with pleiotropic roles during development. PMID:17103413

  3. Carbon-11 labeling of nonpeptide angiotensin-II antogonists: MK-996 and analogs

    SciTech Connect

    Mathews, W.B.; Burns, H.D.; Hamill, T.D.

    1994-05-01

    Our goal was to develop a tracer that can be used for imaging of angiotensin-II (ANG-II), AT{sub 1} receptors in vivo via PET. MK-996 is a potent, nonpeptide, benzamide-based, AT{sub 1} selective antagonist (IC{sub 50}=0.15 nM) in clinical trials for the treatment of hypertension. (C-11)MK-996 was prepared using (C-11)benzoyl chloride synthesized in two steps from (C-11) carbon dioxide via (C-11)benzoic acid. The labeled acid chloride was made by reacting the (C-11)benzoic acid with either phthaloyl dichloride or thionyl chloride. After HPLC purification, the (C-11)MK-996 with an average synthesis time of 38 minutes from EOB, a non-decay corrected radiochemical yield of 3%, and a specific activity of 1162 Ci/mmol at EOS. Although this route provided the radiotracer in sufficient quantities for imaging studies, the synthesis was cumbersome. Thus, a labeled tracer that could be prepared more conveniently was sought.

  4. Validating the Serpent Model of FiR 1 Triga Mk-II Reactor by Means of Reactor Dosimetry

    NASA Astrophysics Data System (ADS)

    Viitanen, Tuomas; Leppänen, Jaakko

    2016-02-01

    A model of the FiR 1 Triga Mk-II reactor has been previously generated for the Serpent Monte Carlo reactor physics and burnup calculation code. In the current article, this model is validated by comparing the predicted reaction rates of nickel and manganese at 9 different positions in the reactor to measurements. In addition, track-length estimators are implemented in Serpent 2.1.18 to increase its performance in dosimetry calculations. The usage of the track-length estimators is found to decrease the reaction rate calculation times by a factor of 7-8 compared to the standard estimator type in Serpent, the collision estimators. The differences in the reaction rates between the calculation and the measurement are below 20%.

  5. Jet Charge Tagging at CDF using Run II Data

    NASA Astrophysics Data System (ADS)

    Paus, Christoph

    2004-05-01

    We present a study of the jet charge tagging in Run II CDF. The jet charge tagging method is applied to determine the b/barb-quark flavor of B hadrons at the time of production in a sample of b arrow ℓ ν X decays collected in 2002-2003.

  6. Verification of MCNP simulation of neutron flux parameters at TRIGA MK II reactor of Malaysia.

    PubMed

    Yavar, A R; Khalafi, H; Kasesaz, Y; Sarmani, S; Yahaya, R; Wood, A K; Khoo, K S

    2012-10-01

    A 3-D model for 1 MW TRIGA Mark II research reactor was simulated. Neutron flux parameters were calculated using MCNP-4C code and were compared with experimental results obtained by k(0)-INAA and absolute method. The average values of φ(th),φ(epi), and φ(fast) by MCNP code were (2.19±0.03)×10(12) cm(-2)s(-1), (1.26±0.02)×10(11) cm(-2)s(-1) and (3.33±0.02)×10(10) cm(-2)s(-1), respectively. These average values were consistent with the experimental results obtained by k(0)-INAA. The findings show a good agreement between MCNP code results and experimental results. PMID:22885391

  7. Jet-intracluster medium interaction in Hydra A - II. The effect of jet precession

    NASA Astrophysics Data System (ADS)

    Nawaz, M. A.; Bicknell, G. V.; Wagner, A. Y.; Sutherland, R. S.; McNamara, B. R.

    2016-05-01

    We present three-dimensional relativistic hydrodynamical simulations of a precessing jet interacting with the intracluster medium and compare the simulated jet structure with the observed structure of the Hydra A northern jet. For the simulations, we use jet parameters obtained in the parameter space study of the first paper in this series and probe different values for the precession period and precession angle. We find that for a precession period P ≈ 1 Myr and a precession angle ψ ≈ 20°, the model reproduces (i) the curvature of the jet, (ii) the correct number of bright knots within 20 kpc at approximately correct locations and (iii) the turbulent transition of the jet to a plume. The Mach number of the advancing bow shock ≈1.85 is indicative of gentle cluster atmosphere heating during the early stages of the AGN's activity.

  8. HOT ELECTROMAGNETIC OUTFLOWS. II. JET BREAKOUT

    SciTech Connect

    Russo, Matthew; Thompson, Christopher

    2013-08-20

    We consider the interaction between radiation, matter, and a magnetic field in a compact, relativistic jet. The entrained matter accelerates outward as the jet breaks out of a star or other confining medium. In some circumstances, such as gamma-ray bursts (GRBs), the magnetization of the jet is greatly reduced by an advected radiation field while the jet is optically thick to scattering. Where magnetic flux surfaces diverge rapidly, a strong outward Lorentz force develops and radiation and matter begin to decouple. The increase in magnetization is coupled to a rapid growth in Lorentz factor. We take two approaches to this problem. The first examines the flow outside the fast magnetosonic critical surface, and calculates the flow speed and the angular distribution of the radiation field over a range of scattering depths. The second considers the flow structure on both sides of the critical surface in the optically thin regime, using a relaxation method. In both approaches, we find how the terminal Lorentz factor and radial profile of the outflow depend on the radiation intensity and optical depth at breakout. The effect of bulk Compton scattering on the radiation spectrum is calculated by a Monte Carlo method, while neglecting the effects of internal dissipation. The peak of the scattered spectrum sits near the seed peak if radiation pressure dominates the acceleration, but is pushed to a higher frequency if the Lorentz force dominates. The unscattered seed radiation can form a distinct, low-frequency component of the spectrum, especially if the magnetic Poynting flux dominates.

  9. BIPOLAR JETS LAUNCHED FROM ACCRETION DISKS. II. THE FORMATION OF ASYMMETRIC JETS AND COUNTER JETS

    SciTech Connect

    Fendt, Christian; Sheikhnezami, Somayeh E-mail: nezami@mpia.de

    2013-09-01

    We investigate the jet launching from accretion disks, in particular the formation of intrinsically asymmetric jet/counter jet systems. We perform axisymmetric MHD simulations of the disk-jet structure on a bipolar computational domain covering both hemispheres. We apply various models such as asymmetric disks with (initially) different scale heights in each hemisphere, symmetric disks into which a local disturbance is injected, and jets launched into an asymmetric disk corona. We consider both a standard global magnetic diffusivity distribution and a novel local diffusivity model. Typical disk evolution first shows substantial disk warping and then results in asymmetric outflows with a 10%-30% mass flux difference. We find that the magnetic diffusivity profile is essential for establishing a long-term outflow asymmetry. We conclude that bipolar asymmetry in protostellar and extragalactic jets can indeed be generated intrinsically and maintained over a long time by disk asymmetries and the standard jet launching mechanism.

  10. Turbulence measurements in axisymmetric jets of air and helium. I - Air jet. II - Helium jet

    NASA Astrophysics Data System (ADS)

    Panchapakesan, N. R.; Lumley, J. L.

    1993-01-01

    Results are presented of measurements on turbulent round jets of air and of helium of the same nozzle momentum efflux, using, for the air jets, x-wire hot-wire probes mounted on a moving shuttle and, for He jets, a composite probe consisting of an interference probe of the Way-Libby type and an x-probe. Current models for scalar triple moments were evaluated. It was found that the performance of the model termed the Full model, which includes all terms except advection, was very good for both the air and the He jets.

  11. MiR-152 May Silence Translation of CaMK II and Induce Spontaneous Immune Tolerance in Mouse Liver Transplantation

    PubMed Central

    Wang, Jingcheng; Yan, Sheng; Zhou, Lin; Xie, Haiyang; Chen, Hui; Li, Hui; Zhang, Jinhua; Zhao, Jiacong; Zheng, Shusen

    2014-01-01

    Spontaneous immune tolerance in mouse liver transplantation has always been a hotspot in transplantation-immune research. Recent studies revealed that regulatory T cells (Tregs), hepatic satellite cells and Kupffer cells play a potential role in spontaneous immune tolerance, however the precise mechanism of spontaneous immune tolerance is still undefined. By using Microarray Chips, we investigated different immune regulatory factors to decipher critical mechanisms of spontaneous tolerance after mouse liver transplantation. Allogeneic (C57BL/6-C3H) and syngeneic (C3H-C3H) liver transplantation were performed by 6-8 weeks old male C57BL/6 and C3H mice. Graft samples (N = 4 each group) were collected from 8 weeks post-operation mice. 11 differentially expressed miRNAs in allogeneic grafts (Allografts) vs. syngeneic grafts (Syngrafts) were identified using Agilent Mouse miRNA Chips. It was revealed that 185 genes were modified by the 11 miRNAs, furthermore, within the 185 target genes, 11 of them were tightly correlated with immune regulation after Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Genbank data cross-comparison. Verified by real-time PCR and western blot, our results indicated that mRNA expression levels of IL-6 and TAB2 were respectively down regulated following miR-142-3p and miR-155 augment. In addition, increased miR-152 just silenced mRNA of CaMK II and down-regulated translation of CaMK II in tolerated liver grafts, which may play a critical role in immune regulation and spontaneous tolerance induction of mouse liver transplantation. PMID:25133393

  12. A Protostellar Jet Emanating from a Hypercompact H ii Region

    NASA Astrophysics Data System (ADS)

    Guzmán, Andrés E.; Garay, Guido; Rodríguez, Luis F.; Contreras, Yanett; Dougados, Catherine; Cabrit, Sylvie

    2016-08-01

    We present radio continuum observations of the high-mass young stellar object (HMYSO) G345.4938+01.4677 obtained using the Australia Telescope Compact Array (ATCA) at 5, 9, 17, and 19 GHz. These observations provide definite evidence that the outer and inner pairs of radio lobes consist of shock-ionized material being excited by an underlying collimated and fast protostellar jet emanating from a hypercompact H ii region. By comparing with images taken 6 years earlier at 5 and 9 GHz using the same telescope, we assess the proper motions (PMs) of the radio sources. The outer west and east lobes exhibit PMs of 64 ± 12 and 48 ± 13 mas yr‑1, indicating velocities projected in the plane of the sky and receding from G345.4938+01.4677 of 520 and 390 {\\text{km s}}-1, respectively. The internal radio lobes also display PM signals consistently receding from the HMYSO with magnitudes of 17 ± 11 and 35 ± 10 mas yr‑1 for the inner west and east lobes, respectively. The morphology of the outer west lobe is that of a detached bow shock. At 17 and 19 GHz, the outer east lobe displays an arcuate morphology also suggesting a bow shock. These results show that disk accretion and jet acceleration—possibly occurring in a very similar way compared with low-mass protostars—is taking place in G345.4938+01.4677 despite the presence of ionizing radiation and the associated hypercompact H ii region.

  13. A large-volume high-pressure and high-temperature apparatus for in situ X-ray observation, ' SPEED-Mk.II'

    NASA Astrophysics Data System (ADS)

    Katsura, Tomoo; Funakoshi, Ken-ichi; Kubo, Atsushi; Nishiyama, Norimasa; Tange, Yoshinori; Sueda, Yu-ichiro; Kubo, Tomoaki; Utsumi, Wataru

    2004-06-01

    SPEED-Mk.II, the second KAWAI-type high P- T apparatus for in situ X-ray observation that was installed at the bending magnet beam line at SPring-8, is described. The guide block system was designed so that the change of the relative dimension of the cubic compression space with press load can be minimized by repeated adjustments. The hydraulic system was designed so as to enable smooth compression and decompression. These precise controls should be advantageous for high-pressure generation, especially when sintered diamond (SD) anvils are used. An oscillation system was equipped for the first time in a large volume press, making it possible to obtain high-quality diffraction patterns even when the number of sample grains is limited. The use of the oscillation system also reduces errors in pressure determination that may be caused by insufficient averaging of diffraction angles over grains in a limited diffraction volume, because the oscillating grains should sweep through the 2 θ range that is allowed by the finite widths of the optical slits.

  14. Observations of Chromospheric Anemone Jets with Hinode CaII Broadband Filtergraph and Hida CaII Spectroheliograph

    NASA Astrophysics Data System (ADS)

    Morita, Satoshi; Shibata, Kazunari; Ueno, Satoru; Ichimoto, Kiyoshi; Kitai, Reizaburo; Otsuji, Ken-Ichi

    2010-08-01

    We report on the first simultaneous observations of chromospheric ``anemone'' jets in solar active regions with the Hinode Solar Optical Telescope (SOT) CaII H broadband filtergraph and the CaII K spetroheliograph on the Domeless Solar Telescope (DST) at Hida Observatory. During the period of coordinated observations, nine chromospheric anemone jets were simultaneously observed with the two instruments. These observations revealed three important features: (1) the jets are generated in the lower chromosphere; i.e., these cannot be seen in CaII K3; (2) the length and lifetime of the jets are 0.4-5 Mm and 40-320 s, respectively; (3) the apparent velocity of the jets observed with the SOT is 3-24 km s-1, while the CaII K3 component at the jets shows a blueshift (in 5 events) in the range of 2-6 km s-1. The chromospheric anemone jets are associated with mixed polarity regions, which are either small emerging flux regions or moving magnetic features. It is found that the CaII K line often shows red or blue asymmetry in the K2/K1 component; the footpoint of the jets associated with emerging flux regions often shows a redshift (2-16 km s-1), while the one with moving magnetic features shows a blueshift (˜5 km s-1). A detailed analysis of the magnetic evolution of the jet-forming regions revealed that the reconnection rate (or canceling rate) of the total magnetic flux at the footpoint of the jets is on the order of 1016 Mx s-1, and the resulting magnetic energy release rate is (1.1-10) × 1024 erg s-1, with a total energy release of (1-13) × 1026 erg for the duration of the magnetic cancellation, ˜130 s. These are comparable to the estimated total energy, ˜1026 erg, in a single chromospheric anemone jet. In addition to the DST CaII K spectroheliogram and the SOT CaII H broadband filtergram, we also used for analysis an SOT magnetogram as well as a Hida Hα filtergram. We present a physical model of the jet based on the observation, and discuss the relation between

  15. Nerve-mediated antidiuresis and antinatriuresis after air-jet stress is modulated by angiotensin II.

    PubMed

    Veelken, R; Hilgers, K F; Stetter, A; Siebert, H G; Schmieder, R E; Mann, J F

    1996-11-01

    A putative interaction between angiotensin II (Ang II) and the sympathetic nervous system within the kidney has been reported. We tested the hypothesis in conscious rats that endogenous Ang II modulates the renal effects of a stress-induced increase in sympathetic nerve activity. We recorded mean arterial blood pressure, heart rate, renal sympathetic nerve activity, renal hemodynamics, urine volume, and urinary sodium content in conscious rats. We used the Ang II type 1 receptor blocker ZD 7155 to inhibit the effects of endogenous Ang II. Ten minutes of air-jet stress increased renal sympathetic nerve activity by 98 +/- 4% (n = 6) without changing systemic hemodynamics. Air-jet stress reduced urine volume (from 31 +/- 3 to 8 +/- 4 microL/min per gram kidney weight, P < .05, n = 12) and sodium excretion (from 4.3 +/- 0.9 to 1.2 +/- 0.3 mumol/min per gram kidney weight, P < .05, n = 12). After renal denervation, air-jet stress had no effect on either parameter. Six micrograms of the Ang II type 1 receptor inhibitor ZD 7155 blunted the decrease in urine volume and sodium excretion in response to air-jet stress, although the increase in renal sympathetic nerve activity during air-jet stress and the pressor response to exogenous Ang II were not affected. Glomerular filtration rate and renal plasma flow were also not affected. Higher doses of 30 and 60 micrograms ZD 7155 inhibited the pressor response to exogenous Ang II and abolished the changes in urine volume and sodium excretion in response to air-jet stress. None of the ZD 7155 doses affected urinary sodium excretion permanently. Hence, the Ang II type 1 receptor antagonist ZD 7155 impaired or abolished the renal nerve-mediated antinatriuresis and anitidiuresis in response to air-jet stress. We conclude that endogenous Ang II modulates the renal effects of centrally mediated changes of sympathetic nerve activity in conscious rats. PMID:8901830

  16. Chromospheric Anemone Jets Observed with Hinode/SOT and Hida Ca II Spectroheliograph

    NASA Astrophysics Data System (ADS)

    Morita, S.; Shibata, K.; Ueno, S.; Ichimoto, K.; Kitai, R.; Otsuji, K.

    2012-08-01

    We present the first simultaneous observations of chromospheric “anemone” jets in active regions with the Ca II H broadband filetergram on the Hinode/SOT and with the Ca II K spetroheliogram on the Domeless Solar Telescope (DST) at the Hida Observatory. During coordinated observation period, 9 chromospheric anemone jets were simultaneously observed with the two instruments. These observations revealed: (1) the jets are generated in the low chromosphere because these cannot be seen in Ca II K3, (2) these jets are associated with mixed polarity regions which are either small emerging flux regions or moving magnetic features, (3) the Ca II K line often show red or blue asymmetry in K2/K1 component; the footpoint of the jets associated with emerging flux regions often show red asymmetry (2-16 km s-1), while the one with moving magnetic features show blue asymmetry (˜5 km s-1). The magnetic cancellations were observed at the footpoint of the jets. The canceling rates are of order of 1016 Mx s-1, and the resulting magnetic energy release rate (1.1-10)×1024 erg s-1, with the total energy release (1-13)×1026 erg for the duration of the magnetic cancellations, ˜130 s. These are comparable to the estimated total energy, ˜1026 erg, in a single chromospheric anemone jet.

  17. Performance oriented packaging testing of nine Mk 3 Mod 0 signal containers in PPP-B-621 wood box for packing group II solid hazardous materials. Final report

    SciTech Connect

    Libbert, K.J.

    1992-10-01

    A PPP-B-621 wood box containing nine Mk 3 Mod 0 Signal containers was tested for conformance to Performance Oriented Packaging criteria established by Code of Federal Regulations Title 49 CFR. The container was tested with a gross weight of 123.3 pounds (56 kilograms) and met all requirements.

  18. Development and Testing of a Jet Assisted Polycrystalline Diamond Drilling Bit. Phase II Development Efforts

    SciTech Connect

    David S. Pixton

    1999-09-20

    Phase II efforts to develop a jet-assisted rotary-percussion drill bit are discussed. Key developments under this contract include: (1) a design for a more robust polycrystalline diamond drag cutter; (2) a new drilling mechanism which improves penetration and life of cutters; and (3) a means of creating a high-pressure mud jet inside of a percussion drill bit. Field tests of the new drill bit and the new robust cutter are forthcoming.

  19. [Fe II] Emission Tracing Massive, Irradiated Jets from Intermediate-Mass Protostars in the Carina Nebula

    NASA Astrophysics Data System (ADS)

    Reiter, Megan; Smith, Nathan

    2013-07-01

    We present new spectroscopy and HST and ground-based AO imaging of five protostellar jets in the Carina nebula. Near-IR [Fe II] emission traces dense gas in the jet that is self-shielded from Lyman continuum photons from nearby O-type stars, but is excited by non-ionizing FUV photons that penetrate the ionization front within the jet. New near-IR [Fe II] images reveal a substantial mass of dense, neutral gas that is not seen in Halpha emission from these jets, leading to densities and mass-loss rate estimates an order of magnitude higher than those derived from the Halpha emission measure. Higher jet mass-loss rates require higher accretion rates, implying that these jets are driven by intermediate-mass (~2-8 Msun) protostars. For two of the sources, mid-IR luminosities of the driving sources are clearly consistent with intermediate-mass protostars, while the other two driving sources are more deeply embedded and require imaging at longer wavelengths with high spatial resolution to confirm their luminosity. Tangential velocities from new proper motion measurements exceed velocities typical for lower-luminosity sources (100-200 km/s). In addition, these outflows are highly collimated, with opening angles of only a few degrees, similar to low-mass protostars. We propose that these jets reflect essentially the same outflow phenomenon seen in low-mass protostars, but that the collimated atomic jet core is irradiated and rendered observable. Thus, the jets in Carina constitute a new view of collimated jets from intermediate-mass protostars that exists in a feedback dominated environment, and offer strong additional evidence that stars up to ~8 Msun form by the same accretion mechanisms as low-mass stars.

  20. Measurement of the inclusive jet cross section using the midpoint algorithm in Run II at CDF

    SciTech Connect

    Group, Robert Craig; /Florida U.

    2006-12-01

    A measurement is presented of the inclusive jet cross section using the Midpoint jet clustering algorithm in five different rapidity regions. This is the first analysis which measures the inclusive jet cross section using the Midpoint algorithm in the forward region of the detector. The measurement is based on more than 1 fb{sup -1} of integrated luminosity of Run II data taken by the CDF experiment at the Fermi National Accelerator Laboratory. The results are consistent with the predictions of perturbative quantum chromodynamics.

  1. Dynamic characteristics of peripheral jet ACV. II - Pitching motion

    NASA Astrophysics Data System (ADS)

    Mori, T.; Maeda, H.

    The dynamic pitching characteristics of peripheral jet ACV (Air Cushion Vehicle) which have a stability curtain are investigated analytically and experimentally. The measured values of moment, lift and cushion pressure are compared with numerical results noting applicability to the pitching motion. The response of ACV to the sinusoidal pitching oscillation of the ground is also studied.

  2. Triggering on B-jets at CDF II

    SciTech Connect

    Amerio, Silvia; Casarsa, Massimo; Cortiana, Giorgio; Donini, Julien; Lucchesi, Donatella; Pagan Griso, Simone; /Padua U. /INFN, Padua

    2009-01-01

    In this paper we present a trigger algorithm able to select online events enriched of b-jets. This feature is of central interest in order to extend the physics reach for standard model and minimal super symmetric model Higgs decaying into a pair of b-quarks. The algorithm fully exploits the recently upgraded CDFII tracking system and Level 2 CALorimeter cluster finder. These upgrades are necessary to cope with Tevatron increasing luminosity and provide new and refined trigger primitives that are the key elements of our algorithm together with the already existing silicon vertex trigger. A b-hadron can travel some millimeters before decaying and the trigger algorithm exploits this characteristic by searching for tracks displaced with respect to the primary vertex and matched to energetic jets of particles. We discuss the study and the optimization of the algorithm, its technical implementation as well as its performance. The new trigger provides an efficient selection for Higgs decaying into a pair of b-quarks and runs up to high luminosity with an acceptable occupancy of the available bandwidth.

  3. Jet-gas interactions and hotspots in FR I/II transition sources

    NASA Astrophysics Data System (ADS)

    Worrall, Diana; Birkinshaw, Mark

    2016-07-01

    Sources with intermediate FR I/II morphologies, and with powers in the decade straddling the FR I/II boundary, provide an opportunity to understand triggers responsible for the different workings of the two classes. Illustrated by deep Chandra observations of several sources, this presentation will show evidence that the physics changes within the transition range, and the work done in driving shocks can exceed that in evacuating the cavities common in FR I sources. Hotspots can be absent, seen only on one side (jet-side or counter-jet-side), or both, in which case X-ray/radio correspondence can be very different on the two sides. Evidence will be shown for radio-emitting plasma running along boundaries between gas of different temperature, apparently lubricating the gas flows and inhibiting heat transfer.

  4. AGN jet power, formation of X-ray cavities, and FR I/II dichotomy in galaxy clusters

    NASA Astrophysics Data System (ADS)

    Fujita, Yutaka; Kawakatu, Nozomu; Shlosman, Isaac

    2016-04-01

    We investigate the ability of jets in active galactic nuclei to break out of the ambient gas with sufficiently large advance velocities. Using observationally estimated jet power, we analyze 28 bright elliptical galaxies in nearby galaxy clusters. Because the gas density profiles in the innermost regions of galaxies have not been resolved so far, we consider two extreme cases for temperature and density profiles. We also follow two types of evolution for the jet cocoons: being driven by the pressure inside the cocoon [Fanaroff-Riley (FR) type I], and being driven by the jet momentum (FR type II). Our main result is that regardless of the assumed form of the density profiles, jets with observed powers of ≲1044 erg s-1 are not powerful enough to evolve as FR II sources. Instead, they evolve as FR I sources and appear to be decelerated below the buoyant velocities of the cocoons when jets were propagating through the central dense regions of the host galaxies. This explains why FR I sources are more frequent than FR II sources in clusters. Furthermore, we predict the sizes of X-ray cavities from the observed jet powers and compare them with the observed ones-they are consistent within a factor of two if the FR I type evolution is realized. Finally, we find that the jets with a power ≳1044 erg s-1 are less affected by the ambient medium, and some of them, but not all, could serve as precursors of the FR II sources.

  5. A Phase II Dose-Ranging Study Evaluating the Efficacy and Safety of the Orexin Receptor Antagonist Filorexant (MK-6096) in Patients with Primary Insomnia

    PubMed Central

    Mahoney, Erin; Jackson, Saheeda; Hutzelmann, Jill; Zhao, Xin; Jia, Nan; Snyder, Ellen; Snavely, Duane; Michelson, David; Roth, Thomas; Herring, W. Joseph

    2016-01-01

    Background: Filorexant (MK-6096) is an orexin receptor antagonist; here, we evaluate the efficacy of filorexant in the treatment of insomnia in adults. Methods: A double-blind, placebo-controlled, randomized, two 4-week–period, adaptive crossover polysomnography study was conducted at 51 sites worldwide. Patients (18 to <65 years) with insomnia received 1 of 4 doses of oral filorexant (2.5, 5, 10, 20mg) once daily at bedtime during one period and matching placebo in the other period in 1 of 8 possible treatment sequences. Polysomnography was performed on night 1 and end of week 4 of each period. The primary endpoint was sleep efficiency at night 1 and end of week 4. Secondary endpoints included wakefulness after persistent sleep onset and latency to onset of persistent sleep. Results: A total of 324 patients received study treatment, 315 received ≥1 dose of placebo, and 318 ≥1 dose of filorexant (2.5mg, n=79; 5mg, n=78; 10mg, n=80; 20mg, n=81). All filorexant doses (2.5/5/10/20mg) were significantly superior to placebo in improving sleep among patients with insomnia as measured by sleep efficiency and wakefulness after persistent sleep onset on night 1 and end of week 4. The 2 higher filorexant doses (10/20mg) were also significantly more effective than placebo in improving sleep onset as measured by latency to onset of persistent sleep at night 1 and end of week 4. Filorexant was generally well tolerated. Conclusions: Orexin receptor antagonism by filorexant significantly improved sleep efficiency in nonelderly patients with insomnia. Dose-related improvements in sleep onset and maintenance outcomes were also observed with filorexant. PMID:26979830

  6. Precise measurement of the top quark mass in the lepton+jets topology at CDF II

    SciTech Connect

    Abulencia, A.; Adelman, J.; Affolder, T.; Akimoto, T.; Albrow, M.G.; Amerio, S.; Amidei, D.; Anastassov, A.; Anikeev, K.; Annovi, A.; Antos, J.; /Comenius U. /Tsukuba U.

    2007-03-01

    The authors present a measurement of the mass of the top quark from proton-antiproton collisions recorded at the CDF experiment in Run II of the Fermilab Tevatron. They analyze events from the single lepton plus jets final state (t{bar t} {yields} W{sup +}bW{sup -}{bar b} {yields} lvbq{bar q}{bar b}). The top quark mass is extracted using a direct calculation of the probability density that each event corresponds to the t{bar t} final state. The probability is a function of both the mass of the top quark and the energy scale of the calorimeter jets, which is constrained in situ by the hadronic W boson mass. Using 167 events observed in 955 pb{sup -1} of integrated luminosity, they achieve the single most precise measurement of the top quark mass, 170.8 {+-} 2.2(stat.) {+-} 1.4(syst.) GeV/c{sup 2}.

  7. HH 666: different kinematics from H α and [Fe II] emission provide a missing link between jets and outflows

    NASA Astrophysics Data System (ADS)

    Reiter, Megan; Smith, Nathan; Kiminki, Megan M.; Bally, John

    2015-06-01

    HH 666 is an externally irradiated protostellar outflow in the Carina nebula for which we present new near-IR [Fe II] spectra obtained with the Folded-Port Infrared Echellette spectrograph at Magellan Observatory. Earlier H α and near-IR [Fe II] imaging revealed that the two emission lines trace substantially different morphologies in the inner ˜40 arcsec of the outflow. H α traces a broad cocoon that surrounds the collimated [Fe II] jet that extends throughout the parent dust pillar. New spectra show that this discrepancy extends to their kinematics. Near-IR [Fe II] emission traces steady, fast velocities of ±200 km s-1 from the eastern and western limbs of the jet. We compare this to a previously published H α spectrum that reveals a Hubble-flow velocity structure near the jet-driving source. New, second-epoch Hubble Space Telescope (HST)/Advanced Camera for Surveys (ACS) H α images reveal the lateral spreading of the H α outflow lobe away from the jet axis. H α proper motions also indicate a sudden increase in the mass-loss rate ˜1000 yr ago, while steady [Fe II] emission throughout the inner jet suggest that the burst is ongoing. An accretion burst sustained for ˜1000 yr is an order of magnitude longer than expected for FU Orionis outbursts, but represents only a small fraction of the total age of the HH 666 outflow. Altogether, available data suggests that [Fe II] traces the highly collimated protostellar jet while H α traces the entrained and irradiated outflow. HH 666 appears to be a missing link between bare jets seen in H II regions and entrained molecular outflows seen from embedded protostars in more quiescent regions.

  8. HST/WFC3 imaging of protostellar jets in Carina: [Fe II] emission tracing massive jets from intermediate-mass protostars

    NASA Astrophysics Data System (ADS)

    Reiter, Megan; Smith, Nathan

    2013-08-01

    We present narrow-band Wide Field Camera 3 (WFC3)-UVIS and WFC3-IR images of four externally irradiated protostellar jets in the Carina nebula: HH 666, HH 901, HH 902 and HH 1066. These massive jets are unusual because they are bathed in UV radiation from dozens of nearby O-type stars, but despite the strong incident ionizing radiation, portions of the jet remain neutral. Near-IR [Fe II] images reveal dense, neutral gas that was not seen in previous studies of Hα emission. We show that near-IR [Fe II] emitting gas must be self-shielded from Lyman continuum photons, regardless of its excitation mechanism (shocks, far-ultraviolet radiation or both). High densities are required for the survival of Fe+ amid the strong Lyman continuum luminosity from Tr14, raising estimates of the mass-loss rates by an order of magnitude. Higher jet mass-loss rates require higher accretion rates on to their driving protostars, implying that these jets are driven by intermediate-mass (˜2-8 M⊙) stars. Indeed, the IR driving sources of two of these outflows have luminosities that require intermediate-mass protostars (the other two are so deeply embedded that their luminosity is uncertain). All four of these HH jets are highly collimated, with opening angles of only a few degrees, similar to those observed in low-mass protostars. We propose that these jets reflect essentially the same outflow phenomenon seen in wide-angle molecular outflows associated with intermediate- and high-mass protostars, but that the collimated atomic jet core is irradiated and rendered observable in the harsh radiative environment of the Carina nebula. In more quiescent environments, this atomic core remains invisible, and outflows traced by shock-excited molecules in the outflow cavity give the impression that these outflows have a wider opening angle. Thus, the externally irradiated jets in Carina constitute a new view of collimated jets from intermediate-mass protostars and offer strong additional evidence

  9. Polarized Atomic Hydrogen Beam Tests in the Mark-II Ultra-Cold Jet Target.

    NASA Astrophysics Data System (ADS)

    Luppov, V. G.; Blinov, B. B.; Gladycheva, S. E.; Kageya, T.; Kantsyrev, D. Yu.; Krisch, A. D.; Murray, J. R.; Neumann, J. J.; Raymond, R. S.; Borisov, N. S.; Kleppner, D.; Davidenko, A. M.; Grishin, V. N.

    2000-04-01

    To study spin effects in high energy collisions, we are developing an ultra-cold high-density jet target of proton-spin-polarized hydrogen atoms (Mark-II). The target uses a 12 Tesla magnetic field and a 0.3 K separation cell coated with superfluid helium-4 to produce a slow monochromatic electron-spin-polarized atomic hydrogen beam; an rf transition unit then converts this into a proton-spin-polarized beam, which is focused by a superconducting sextupole into the interaction region. Recently, the Jet produced a measured electron-spin-polarized atomic hydrogen beam of about 10^15 H s-1 into a 0.3 cm^2 area at the detector. This intensity corresponds to the free jet density of about 10^11 H cm-3 with a proton polarization of about 50%. So far, the intensity is limited by the high insulation vacuum pressure due to the evaporation of the separation cell's helium film. The beam's angular and radial distributions were measured. A test of a new superfluid-^4He-coated parabolic mirror, attached to the separation cell, appeared to increase the beam intensity by a factor of about 3, as expected.

  10. A Direct Top-Quark Width Measurement from Lepton + Jets Events at CDF II

    SciTech Connect

    Aaltonen, T.; Alvarez Gonzalez, B.; Amerio, S.; Amidei, D.; Anastassov, A.; Annovi, A.; Antos, J.; Apollinari, G.; Appel, J.A.; Apresyan, A.; Arisawa, T.; /Waseda U. /Dubna, JINR

    2010-08-01

    We present a measurement of the top-quark width using t{bar t} events produced in p{bar p} collisions at Fermilab's Tevatron collider and collected by the CDF II detector. In the mode where the top quark decays to a W boson and a bottom quark, we select events in which one W decays leptonically and the other hadronically (lepton + jets channel) . From a data sample corresponding to 4.3 fb{sup -1} of integrated luminosity, we identify 756 candidate events. The top-quark mass and the mass of W boson that decays hadronically are reconstructed for each event and compared with templates of different top-quark widths ({Lambda}{sub t}) and deviations from nominal jet energy scale ({Delta}{sub JES}) to perform a simultaneous fit for both parameters, where {Delta}{sub JES} is used for the in situ calibration of the jet energy scale. By applying a Feldman-Cousins approach, we establish an upper limit at 95% confidence level (CL) of {Lambda}{sub t} < 7.6 GeV and a two-sided 68% CL interval of 0.3 GeV < {Lambda}{sub t} < 4.4 GeV for a top-quark mass of 172.5 GeV/c{sup 2}, which are consistant with the standard model prediction. This is the first direct measurement of {Lambda}{sub t} to set a lower limit with 68% CL.

  11. SOLAR X-RAY JETS, TYPE-II SPICULES, GRANULE-SIZE EMERGING BIPOLES, AND THE GENESIS OF THE HELIOSPHERE

    SciTech Connect

    Moore, Ronald L.; Sterling, Alphonse C.; Cirtain, Jonathan W.; Falconer, David A.

    2011-04-10

    From Hinode observations of solar X-ray jets, Type-II spicules, and granule-size emerging bipolar magnetic fields in quiet regions and coronal holes, we advocate a scenario for powering coronal heating and the solar wind. In this scenario, Type-II spicules and Alfven waves are generated by the granule-size emerging bipoles (EBs) in the manner of the generation of X-ray jets by larger magnetic bipoles. From observations and this scenario, we estimate that Type-II spicules and their co-generated Alfven waves carry into the corona an area-average flux of mechanical energy of {approx}7 x 10{sup 5} erg cm{sup -2} s{sup -1}. This is enough to power the corona and solar wind in quiet regions and coronal holes, and therefore indicates that the granule-size EBs are the main engines that generate and sustain the entire heliosphere.

  12. Chandra Reveals Twin X-ray Jets in the Powerful FR-II Radio Galaxy 3C353

    SciTech Connect

    Kataoka, J.; Stawarz, L.; Harris, D.E.; Siemiginowska, A.; Ostrowski, M.; Swain, M.R.; Hardcastle, M.J.; Goodger, J.L.; Iwasawa, K.; Edwards, P.G.

    2008-06-13

    We report X-ray imaging of the powerful FR II radio galaxy 3C 353 using the Chandra X-ray Observatory. 3C 353's two 4-inch wide and 2-feet long jets allow us to study in detail the internal structure of the large-scale relativistic outflows at both radio and X-ray photon energies with the sub-arcsecond spatial resolution provided by the VLA and Chandra instruments. In a 90 ks Chandra observation, we have detected X-ray emission from most radio structures in 3C 353, including the nucleus, the jet and the counterjet, the terminal jet regions (hotspots), and one radio lobe. We show that the detection of the X-ray emission associated with the radio knots and counterknots, which is most likely non-thermal in origin, puts several crucial constraints on the X-ray emission mechanisms in powerful large-scale jets of quasars and FR II sources. In particular, we show that this detection is inconsistent with the inverse-Compton model proposed in the literature, and instead implies a synchrotron origin of the X-ray jet photons. We also find that the width of the X-ray counterjet is possibly narrower than that measured in radio bands, that the radio-to-X-ray flux ratio decreases systematically downstream along the jets, and that there are substantial (kpc-scale) offsets between the positions of the X-ray and radio intensity maxima within each knot, whose magnitudes increase away from the nucleus. We discuss all these findings in the wider context of the physics of extragalactic jets, proposing some particular though not definitive solutions or interpretations for each problem. In general, we find that the synchrotron X-ray emission of extragalactic large-scale jets is not only shaped by the global hydrodynamical configuration of the outflows, but is also likely to be very sensitive to the microscopic parameters of the jet plasma. A complete, self-consistent model for the X-ray emission of extragalactic jets still remains elusive.

  13. Chandra Reveals Twin X-ray Jets in the Powerful FR II Radio Galaxy 3C 353

    SciTech Connect

    Kataoka, Jun

    2008-12-24

    We report X-ray imaging of the powerful FR II radio galaxy 3C 353 using the Chandra X-ray Observatory. 3C 353's two 4''-wide and 2'-long jets allow us to study in detail the internal structure of the large-scale relativistic outflows at both radio and X-ray photon energies with the sub-arcsecond spatial resolution provided by the VLA and Chandra instruments. In a 90 ks Chandra observation, we have detected X-ray emission from most radio structures in 3C 353, including the nucleus, the jet and the counterjet, the terminal jet regions (hotspots), and one radio lobe. We show that the detection of the X-ray emission associated with the radio knots and counterknots, which is most likely non-thermal in origin, puts several crucial constraints on the X-ray emission mechanisms in powerful large-scale jets of quasars and FR II sources. In particular, we show that this detection is inconsistent with the inverse-Compton model proposed in the literature, and instead implies a synchrotron origin of the X-ray jet photons. We also find that the width of the X-ray counterjet is possibly narrower than that measured in radio bands, that the radio-to-X-ray flux ratio decreases systematically downstream along the jets, and that there are substantial (kpc-scale) offsets between the positions of the X-ray and radio intensity maxima within each knot, whose magnitudes increase away from the nucleus. We discuss all these findings in the wider context of the physics of extragalactic jets, proposing some particular though not definitive solutions or interpretations for each problem. In general, we find that the synchrotron X-ray emission of extragalactic large-scale jets is not only shaped by the global hydrodynamical configuration of the outflows, but is also likely to be very sensitive to the microscopic parameters of the jet plasma. A complete, self-consistent model for the X-ray emission of extragalactic jets still remains elusive.

  14. The First measurement of the top quark mass at CDF II in the lepton+jets and dilepton channels simultaneously

    SciTech Connect

    Aaltonen, T.; Adelman, J.; Akimoto, T.; Albrow, Michael G.; Alvarez Gonzalez, B.; Amerio, S.; Amidei, Dante E.; Anastassov, A.; Annovi, Alberto; Antos, J.; Apollinari, G.; /Fermilab /Purdue U.

    2008-09-01

    The authors present a measurement of the mass of the top quark using data corresponding to an integrated luminosity of 1.9 fb{sup -1} of p{bar p} collisions collected at {radical}s = 1.96 TeV with the CDF II detector at Fermilab's Tevatron. This is the first measurement of the top quark mass using top-antitop pair candidate events in the lepton + jets and dilepton decay channels simultaneously. They reconstruct two observables in each channel and use a non-parametric kernel density estimation technique to derive two-dimensional probability density functions from simulated signal and background samples. The observables are the top quark mass and the invariant mass of two jets from the W decay in the lepton + jets channel, and the top quark mass and the scalar sum of transverse energy of the event in the diletpon channel. They perform a simultaneous fit for the top quark mass and the jet energy scale, which is constrained in situ by the hadronic W boson mass. using 332 lepton + jets candidate events and 144 diletpon candidate events, they measure the top quark mass to be m{sub top} = 171.9 {+-} 1.7 (stat. + JES) {+-} 1.1 (other sys.) GeV/c{sup 2} = 171.9 {+-} 2.0 GeV/c{sup 2}.

  15. Measurement of the W Plus N Inclusive Jets Cross-Section at CDF Run II

    SciTech Connect

    Stentz, Dale James

    2012-01-01

    In this thesis we present the study of the production of the W boson in association with hadronic jets at the Collider Detector at Fermilab (CDF). Along with the electroweak properties the W boson, we examine jet kinematic variables with the aim of studying predictions of perturbative quantum chromodynamics. We derive several di erential crosssections as a function of the inclusive jet multiplicity and the transverse momenta of each jet. In this analysis, we are using 2.8 fb-1 of data and consider both the electron and muon lepton nal states for the W boson decay.

  16. Sub-arcsecond [Fe ii] spectro-imaging of the DG Tauri jet. Periodic bubbles and a dusty disk wind?

    NASA Astrophysics Data System (ADS)

    Agra-Amboage, V.; Dougados, C.; Cabrit, S.; Reunanen, J.

    2011-08-01

    Context. The origin of protostellar jets as well as their impact on the regulation of angular momentum and the inner disk physics are still crucial open questions in star formation. Aims: We aim to test the different proposed ejection processes in T Tauri stars through high-angular resolution observations of forbidden-line emission from the inner DG Tauri microjet. Methods: We present spectro-imaging observations of the DG Tauri jet obtained with SINFONI/VLT in the lines of [Fe ii]λ1.64 μm, 1.53 μm with 0.15 arcsec angular resolution and R = 3000 spectral resolution. We analyze the morphology and kinematics, derive electronic densities and mass-flux rates and discuss the implications for proposed jet launching models. Results: (1) We observe an onion-like velocity structure in [Fe ii] in the blueshifted jet, similar to that observed in optical lines. High-velocity (HV) gas at ≃ -200 km s-1 is collimated inside a half-opening angle of 4° and medium-velocity (MV) gas at ≃ -100 km s-1 in a cone with an half-opening angle 14° (2) Two new axial jet knots are detected in the blue jet, as well as a more distant bubble with corresponding counter-bubble. The periodic knot ejection timescale is revised downward to 2.5 yrs. (3) The redshifted jet is detected only beyond 0.7 arcsec from the star, yielding revised constraints on the disk surface density. (4) From comparison to [O i] data we infer iron depletion of a factor 3 at high velocities and a factor 10 at speeds below -100 km s-1. (5) The mass-fluxes in each of the medium and high-velocity components of the blueshifted lobe are ≃1.6 ± 0.8 × 10-8 M⊙ yr-1, representing 0.02 - 0.2 of the disk accretion rate. Conclusions: The medium-velocity conical [Fe ii] flow in the DG Tau jet is too fast and too narrow to trace photo-evaporated matter from the disk atmosphere. Both its kinematics and collimation cannot be reproduced by the X-wind, nor can the "conical magnetospheric wind". The level of Fe gas phase

  17. PAGaN II: The Evolution of AGN Jets on Sub-Parsec Scales

    NASA Astrophysics Data System (ADS)

    Oh, Junghwan; Trippe, Sascha; Kang, Sincheol; Kim, Jae-Young; Park, Jong-Ho; Lee, Taeseok; Kim, Daewon; Kino, Motoki; Lee, Sang-Sung; Sohn, Bong Won

    2015-10-01

    We report first results from KVN and VERA Array (KaVA) VLBI observations obtained in the frame of our Plasma-physics of Active Galactic Nuclei (PAGaN) project. We observed eight selected AGN at 22 and 43 GHz in single polarization (LCP) between March 2014 and April 2015. Each source was observed for 6 to 8 hours per observing run to maximize the uv coverage. We obtained a total of 15 deep high-resolution images permitting the identification of individual circular Gaussian jet components and three spectral index maps of BL Lac, 3C~111 and 3C~345 from simultaneous dual-frequency observations. The spectral index maps show trends in agreement with general expectations -- flat core and steep jets -- while the actual value of the spectral index for jets shows indications for a dependence on AGN type. We analyzed the kinematics of jet components of BL Lac and 3C~111, detecting superluminal proper motions with maximum apparent speeds of about 5c. This constrains the lower limits of the intrinsic component velocities to ˜0.98c and the upper limits of the angle between jet and line of sight to ˜20°. In agreement with global jet expansion, jet components show systematically larger diameters d at larger core distances r, following the global relation d≈0.2r, albeit within substantial scatter.

  18. Precise measurement of the top-quark mass in the lepton+jets topology at CDF II.

    PubMed

    Aaltonen, T; Abulencia, A; Adelman, J; Affolder, T; Akimoto, T; Albrow, M G; Amerio, S; Amidei, D; Anastassov, A; Anikeev, K; Annovi, A; Antos, J; Aoki, M; Apollinari, G; Arisawa, T; Artikov, A; Ashmanskas, W; Attal, A; Aurisano, A; Azfar, F; Azzi-Bacchetta, P; Azzurri, P; Bacchetta, N; Badgett, W; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Baroiant, S; Bartsch, V; Bauer, G; Beauchemin, P-H; Bedeschi, F; Behari, S; Bellettini, G; Bellinger, J; Belloni, A; Benjamin, D; Beretvas, A; Beringer, J; Berry, T; Bhatti, A; Binkley, M; Bisello, D; Bizjak, I; Blair, R E; Blocker, C; Blumenfeld, B; Bocci, A; Bodek, A; Boisvert, V; Bolla, G; Bolshov, A; Bortoletto, D; Boudreau, J; Boveia, A; Brau, B; Brigliadori, L; Bromberg, C; Brubaker, E; Budagov, J; Budd, H S; Budd, S; Burkett, K; Busetto, G; Bussey, P; Buzatu, A; Byrum, K L; Cabrera, S; Campanelli, M; Campbell, M; Canelli, F; Canepa, A; Carrillo, S; Carlsmith, D; Carosi, R; Carron, S; Casal, B; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chang, S H; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, I; Cho, K; Chokheli, D; Chou, J P; Choudalakis, G; Chuang, S H; Chung, K; Chung, W H; Chung, Y S; Cilijak, M; Ciobanu, C I; Ciocci, M A; Clark, A; Clark, D; Coca, M; Compostella, G; Convery, M E; Conway, J; Cooper, B; Copic, K; Cordelli, M; Cortiana, G; Crescioli, F; Cuenca Almenar, C; Cuevas, J; Culbertson, R; Cully, J C; DaRonco, S; Datta, M; D'Auria, S; Davies, T; Dagenhart, D; de Barbaro, P; De Cecco, S; Deisher, A; De Lentdecker, G; De Lorenzo, G; Dell'Orso, M; Delli Paoli, F; Demortier, L; Deng, J; Deninno, M; De Pedis, D; Derwent, P F; Di Giovanni, G P; Dionisi, C; Di Ruzza, B; Dittmann, J R; D'Onofrio, M; Dörr, C; Donati, S; Dong, P; Donini, J; Dorigo, T; Dube, S; Efron, J; Erbacher, R; Errede, D; Errede, S; Eusebi, R; Fang, H C; Farrington, S; Fedorko, I; Fedorko, W T; Feild, R G; Feindt, M; Fernandez, J P; Field, R; Flanagan, G; Forrest, R; Forrester, S; Franklin, M; Freeman, J C; Furic, I; Gallinaro, M; Galyardt, J; Garcia, J E; Garberson, F; Garfinkel, A F; Gay, C; Gerberich, H; Gerdes, D; Giagu, S; Giannetti, P; Gibson, K; Gimmell, J L; Ginsburg, C; Giokaris, N; Giordani, M; Giromini, P; Giunta, M; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldschmidt, N; Goldstein, J; Golossanov, A; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gresele, A; Grinstein, S; Grosso-Pilcher, C; Group, R C; Grundler, U; Guimaraes da Costa, J; Gunay-Unalan, Z; Haber, C; Hahn, K; Hahn, S R; Halkiadakis, E; Hamilton, A; Han, B-Y; Han, J Y; Handler, R; Happacher, F; Hara, K; Hare, D; Hare, M; Harper, S; Harr, R F; Harris, R M; Hartz, M; Hatakeyama, K; Hauser, J; Hays, C; Heck, M; Heijboer, A; Heinemann, B; Heinrich, J; Henderson, C; Herndon, M; Heuser, J; Hidas, D; Hill, C S; Hirschbuehl, D; Hocker, A; Holloway, A; Hou, S; Houlden, M; Hsu, S-C; Huffman, B T; Hughes, R E; Husemann, U; Huston, J; Incandela, J; Introzzi, G; Iori, M; Ivanov, A; Iyutin, B; James, E; Jang, D; Jayatilaka, B; Jeans, D; Jeon, E J; Jindariani, S; Johnson, W; Jones, M; Joo, K K; Jun, S Y; Jung, J E; Junk, T R; Kamon, T; Karchin, P E; Kato, Y; Kemp, Y; Kephart, R; Kerzel, U; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kimura, N; Kirsch, L; Klimenko, S; Klute, M; Knuteson, B; Ko, B R; Kondo, K; Kong, D J; Konigsberg, J; Korytov, A; Kotwal, A V; Kraan, A C; Kraus, J; Kreps, M; Kroll, J; Krumnack, N; Kruse, M; Krutelyov, V; Kubo, T; Kuhlmann, S E; Kuhr, T; Kulkarni, N P; Kusakabe, Y; Kwang, S; Laasanen, A T; Lai, S; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; Lazzizzera, I; LeCompte, T; Lee, J; Lee, J; Lee, Y J; Lee, S W; Lefèvre, R; Leonardo, N; Leone, S; Levy, S; Lewis, J D; Lin, C; Lin, C S; Lindgren, M; Lipeles, E; Lister, A; Litvintsev, D O; Liu, T; Lockyer, N S; Loginov, A; Loreti, M; Lu, R-S; Lucchesi, D; Lujan, P; Lukens, P; Lungu, G; Lyons, L; Lys, J; Lysak, R; Lytken, E; Mack, P; MacQueen, D; Madrak, R; Maeshima, K; Makhoul, K; Maki, T; Maksimovic, P; Malde, S; Malik, S; Manca, G; Manousakis, A; Margaroli, F; Marginean, R; Marino, C; Marino, C P; Martin, A; Martin, M; Martin, V; Martínez, M; Martínez-Ballarín, R; Maruyama, T; Mastrandrea, P; Masubuchi, T; Matsunaga, H; Mattson, M E; Mazini, R; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Menzemer, S; Menzione, A; Merkel, P; Mesropian, C; Messina, A; Miao, T; Miladinovic, N; Miles, J; Miller, R; Mills, C; Milnik, M; Mitra, A; Mitselmakher, G; Miyamoto, A; Moed, S; Moggi, N; Mohr, B; Moon, C S; Moore, R; Morello, M; Movilla Fernandez, P; Mülmenstädt, J; Mukherjee, A; Muller, Th; Mumford, R; Murat, P; Mussini, M; Nachtman, J; Nagano, A; Naganoma, J; Nakamura, K; Nakano, I; Napier, A; Necula, V; Neu, C; Neubauer, M S; Nielsen, J; Nodulman, L; Norniella, O; Nurse, E; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Oldeman, R; Orava, R; Osterberg, K; Pagliarone, C; Palencia, E; Papadimitriou, V; Papaikonomou, A; Paramonov, A A; Parks, B; Pashapour, S; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Piedra, J; Pinera, L; Pitts, K; Plager, C; Pondrom, L; Portell, X; Poukhov, O; Pounder, N; Prakoshyn, F; Pronko, A; Proudfoot, J; Ptohos, F; Punzi, G; Pursley, J; Rademacker, J; Rahaman, A; Ramakrishnan, V; Ranjan, N; Redondo, I; Reisert, B; Rekovic, V; Renton, P; Rescigno, M; Richter, S; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rogers, E; Rolli, S; Roser, R; Rossi, M; Rossin, R; Roy, P; Ruiz, A; Russ, J; Rusu, V; Saarikko, H; Safonov, A; Sakumoto, W K; Salamanna, G; Saltó, O; Santi, L; Sarkar, S; Sartori, L; Sato, K; Savard, P; Savoy-Navarro, A; Scheidle, T; Schlabach, P; Schmidt, E E; Schmidt, M P; Schmitt, M; Schwarz, T; Scodellaro, L; Scott, A L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semenov, A; Sexton-Kennedy, L; Sfyrla, A; Shalhout, S Z; Shapiro, M D; Shears, T; Shepard, P F; Sherman, D; Shimojima, M; Shochet, M; Shon, Y; Shreyber, I; Sidoti, A; Sinervo, P; Sisakyan, A; Slaughter, A J; Slaunwhite, J; Sliwa, K; Smith, J R; Snider, F D; Snihur, R; Soderberg, M; Soha, A; Somalwar, S; Sorin, V; Spalding, J; Spinella, F; Spreitzer, T; Squillacioti, P; Stanitzki, M; Staveris-Polykalas, A; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Stuart, D; Suh, J S; Sukhanov, A; Sun, H; Suslov, I; Suzuki, T; Taffard, A; Takashima, R; Takeuchi, Y; Tanaka, R; Tecchio, M; Teng, P K; Terashi, K; Thom, J; Thompson, A S; Thomson, E; Tipton, P; Tiwari, V; Tkaczyk, S; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Tourneur, S; Trischuk, W; Tsuno, S; Tu, Y; Turini, N; Ukegawa, F; Uozumi, S; Vallecorsa, S; van Remortel, N; Varganov, A; Vataga, E; Vazquez, F; Velev, G; Vellidis, C; Veramendi, G; Veszpremi, V; Vidal, M; Vidal, R; Vila, I; Vilar, R; Vine, T; Vogel, M; Vollrath, I; Volobouev, I; Volpi, G; Würthwein, F; Wagner, P; Wagner, R G; Wagner, R L; Wagner, J; Wagner, W; Wallny, R; Wang, S M; Warburton, A; Waters, D; Weinberger, M; Wester, W C; Whitehouse, B; Whiteson, D; Wicklund, A B; Wicklund, E; Williams, G; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, C; Wright, T; Wu, X; Wynne, S M; Yagil, A; Yamamoto, K; Yamaoka, J; Yamashita, T; Yang, C; Yang, U K; Yang, Y C; Yao, W M; Yeh, G P; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanello, L; Zanetti, A; Zaw, I; Zhang, X; Zhou, J; Zucchelli, S

    2007-11-01

    We present a measurement of the mass of the top quark from proton-antiproton collisions recorded at the CDF experiment in Run II of the Fermilab Tevatron. We analyze events from the single lepton plus jets final state (tt-->W(+)bW(-)b-->lnubqq'b). The top-quark mass is extracted using a direct calculation of the probability density that each event corresponds to the tt final state. The probability is a function of both the mass of the top quark and the energy scale of the calorimeter jets, which is constrained in situ by the hadronic W boson mass. Using 167 events observed in 955 pb(-1) of integrated luminosity, we achieve the single most precise measurement of the top-quark mass, 170.8+/-2.2(stat.)+/-1.4(syst.) GeV/c(2). PMID:17995397

  19. Neuroprotective effects of MK-801 against traumatic brain injury in immature rats.

    PubMed

    Sönmez, Ataç; Sayın, Oya; Gürgen, Seren Gülşen; Çalişir, Meryem

    2015-06-15

    Traumatic brain injury (TBI) is a major health problem in pediatric ages and also has major social, economic, and emotional outcomes, with diverse sequelae in many spheres of everyday life. We aimed to investigate the effect of MK-801, a competitive NMDA receptor antagonist, on hippocampal damage and behavioral deficits on 10-day-old rat pups subjected to contusion injury. The aims of the present study were to determine: (i) the short term effects of MK-801 on hippocampal BDNF, NGF and NMDA receptor immunoreactivity and neuron density in hippocampus (ii) long term effects of MK-801 on cognitive dysfunction following TBI in the immature rats. MK-801, was injected intraperitoneally at the doses of 1mg/kg of body weight immediately after induction of traumatic injury. Hippocampal damage was examined by cresyl violet staining, BDNF, NGF and NMDAR receptor immunohistochemistry on P10 day and behavioral alterations were evaluated using elevated plus maze and novel object recognition tests two months after the trauma. Histopathological and immunohistochemical evaluations showed that treatment with a single dose of 1mg/kg MK-801 (i.p.) significantly ameliorated the trauma induced hippocampal neuron loss and decreased BDNF, NGF and NMDAR expressions in CA1, CA3 and DG hippocampal brain regions. Additionally, treatment with MK-801 ameliorated anxiety and hippocampus dependent memory of animals subjected to trauma. These results show that acute treatment of MK-801 has a neuroprotective role against trauma induced hippocampal neuron loss and associated cognitive impairment in immature rats. PMID:25943283

  20. Contribution of NMDA, GABAA and GABAB receptors and l-arginine-NO-cGMP, MEK1/2 and CaMK-II pathways in the antidepressant-like effect of 7-fluoro-1,3-diphenylisoquinoline-1-amine in mice.

    PubMed

    Pesarico, Ana Paula; Stangherlin, Eluza Curte; Rosa, Suzan Gonçalves; Mantovani, Anderson C; Zeni, Gilson; Nogueira, Cristina Wayne

    2016-07-01

    It has been reported that the antidepressant-like effect of 7-fluoro-1,3-diphenylisoquinoline-1-amine (FDPI) may result from the modulation of brain monoaminergic systems. However, the mechanisms of FDPI action are not fully understood. The aim of this study was to investigate the contribution of N-methyl-d-aspartate (NMDA) and gamma-aminobutyric acid (GABA) systems as well as l-arginine-nitric oxide-(NO)-cyclic guanosine monophosphate-(cGMP), mitogen-activated protein/extracellular signal-regulated kinase (MEK1/2) and Ca(2+)/calmodulin-dependent protein kinase II (CaMK-II) signaling pathways in the antidepressant-like effect of FDPI in the mouse forced swimming test (FST). The levels of NO and uptake of [(3)H]glutamate and [(3)H]GABA were determined in prefrontal cortices of Swiss mice. Pretreatments with NMDA (0.1 pmol/site, i.c.v., a NMDA receptor agonist), bicuculline (1mg/kg, i.p., a GABAA receptor antagonist), phaclofen (2mg/kg, i.p., a GABAB receptor antagonist) and l-arginine (750mg/kg, i.p., a NO precursor), KN-62 (1μg/site, a CaMK-II inhibitor), U0126 (5μg/site, a MEK1/2 inhibitor) and PD09058 (5μg/site, a MEK1/2 inhibitor) blocked the antidepressant-like effect of FDPI, at a dose of 1mg/kg, in the FST. ODQ (30 pmol/site, i.c.v., a soluble guanylate cyclase (sGC) inhibitor) in combination with a sub-effective dose of FDPI (0.1mg/kg, i.g.) reduced the immobility time in the FST. The administration of FDPI (50mg/kg) to mice increased the glutamate uptake and reduced NO levels in the prefrontal cortex of mice. The results suggest a contribution of NMDA, GABAA and GABAB receptors and l-arginine-NO-cGMP pathway in the antidepressant-like action of FDPI in mice, and this effect is related to CaMK-II and MEK 1/2 activation. PMID:27112660

  1. Near Noise Field of a Jet-engine Exhaust II : Cross Correlation of Sound Pressures

    NASA Technical Reports Server (NTRS)

    Callaghan, Edmund E; Howes, Walton L; Coles, Willard D

    1956-01-01

    Pressure cross correlations were obtained over a range of jet velocities both longitudinally and laterally for the overall sound pressure and for several frequency bands. The region of positive correlation was found to increase with distance downstream of the nozzle exit and was greater for lateral than for longitudinal correlations. In general, little change in the correlation curves was found as a function of jet velocity or frequency band width. Measurements made with a fixed and a movable microphone in a plate showed correlations similar to the free-field results. The results are interpreted in terms of pressure loads on surfaces.

  2. Pilot study of MK-462 in migraine.

    PubMed

    Cutler, N R; Claghorn, J; Sramek, J J; Block, G; Panebianco, D; Cheng, H; Olah, T V; Reines, S A

    1996-04-01

    MK-462 is a potent, selective 5HT1D receptor agonist which may be useful in treating acute migraine. We conducted a double-blind placebo-controlled inpatient study to assess the preliminary efficacy and safety of oral doses of MK-462 20 mg (n = 8) and 40 mg (n = 36) vs placebo (n = 21), administered to 65 male and post-menopausal female migraine patients aged 22-51 with moderate or severe migraine headache. Headache severity and functional disability were measured at 0.5, 1, 1.5, and 2 h post-dose. The 20 mg dose was well tolerated and 4/8 patients obtained relief in headache severity at the 2 h time point. The 40 mg dose was well tolerated and was significantly (p < 0.05) superior to placebo at the 1.5 and 2 h time points (with 27/36 or 75% obtaining relief at 2 h compared to 7/21 or 33% for placebo). Adverse events occurred in 50% of patients on 20 mg MK-462, 72% of those on 40 mg MK-462, and in 52% of placebo-treated subjects. The most common adverse events associated with MK-462 were drowsiness (20 mg 12%; 40 mg 44%; placebo 24%), dry mouth (40 mg 36%; placebo 19%), and lightheadedness/dizziness (40 mg 17%; placebo 10%). Based on these preliminary results, MK-462 appears worthy of continued study for the treatment of acute migraine. PMID:8665577

  3. PERFORMANCE OF A HIGH-VELOCITY PULSE-JET FILTER, II

    EPA Science Inventory

    The report gives results of a study of the performance of a high-velocity pulse-jet filter. Such filtration has distinct advantages over low-velocity filtration in that the equipment required to clean a gas stream is reduced in size and initial cost as velocity increases. Althoug...

  4. Measurement of the Top Quark Mass at D0 Run II with the Matrix Element Method in the Lepton+Jets Final State

    SciTech Connect

    Schieferdecker, Philipp; /Munich U.

    2005-08-01

    The mass of the top quark is a fundamental parameter of the Standard Model. Its precise knowledge yields valuable insights into unresolved phenomena in and beyond the Standard Model. A measurement of the top quark mass with the matrix element method in the lepton+jets final state in D0 Run II is presented. Events are selected requiring an isolated energetic charged lepton (electron or muon), significant missing transverse energy, and exactly four calorimeter jets. For each event, the probabilities to originate from the signal and background processes are calculated based on the measured kinematics, the object resolutions and the respective matrix elements. The jet energy scale is known to be the dominant source of systematic uncertainty. The reference scale for the mass measurement is derived from Monte Carlo events. The matrix element likelihood is defined as a function of both, m{sub top} and jet energy scale JES, where the latter represents a scale factor with respect to the reference scale. The top mass is obtained from a two-dimensional correlated fit, and the likelihood yields both the statistical and jet energy scale uncertainty. Using a dataset of 320 pb{sup -1} of D0 Run II data, the mass of the top quark is measured to be: m{sub top}{sup {ell}+jets} = 169.5 {+-} 4.4(stat. + JES){sub -1.6}{sup +1.7}(syst.) GeV; m{sub top}{sup e+jets} = 168.8 {+-} 6.0(stat. + JES){sub -1.9}{sup +1.9}(syst.) GeV; m{sub top}{sup {mu}+jets} = 172.3 {+-} 9.6(stat.+JES){sub -3.3}{sup +3.4}(syst.) GeV. The jet energy scale measurement in the {ell}+jets sample yields JES = 1.034 {+-} 0.034, suggesting good consistency of the data with the simulation. The measurement forecasts significant improvements to the total top mass uncertainty during Run II before the startup of the LHC, as the data sample will grow by a factor of ten and D0's tracking capabilities will be employed in jet energy reconstruction and flavor identification.

  5. Altitude-chamber performance of British Rolls-Royce Nene II engine III : 18.00-inch-diameter jet nozzle

    NASA Technical Reports Server (NTRS)

    Grey, Ralph E; Brightwell, Virginia L; Barson, Zelmar; NACA

    1950-01-01

    An altitude-chamber investigation of British Rolls-Royce Nene II turbojet engine was conducted over range of altitudes from sea level to 65,000 feet and ram pressure ratios from 1.10 to 3.50, using an 18.00-inch-diameter jet nozzle. The 18.00-inch-diameter jet nozzle gave slightly lower values of net-thrust specific fuel consumption than either the 18.41- or the standard 18.75-inch-diameter jet nozzles at high flight speeds. At low flight speeds, the 18.41-inch-diameter jet nozzle gave the lowest value of net-thrust specific fuel consumption.

  6. The 5-6 December 1991 FIRE IFO II jet stream cirrus case study: Possible influences of volcanic aerosols

    SciTech Connect

    Sassen, K.; Starr, D.O.C.; Melfi, S.H.; Spinhirne, J.D.; Poellot, M.R.; Eberhard, W.L.; Eloranta, E.W.; Hagen, D.E.; Hallett, J.

    1995-01-01

    In presenting an overview of the cirrus clouds comprehensively studied by ground-based and airborne sensors from Coffeyville, Kansas, during the 5-6 December 1992 Project FIRE IFO II case study period, evidence is provided that volcanic aerosols from the June 1991 Pinatubo eruptions may have significantly influenced the formation and maintenance of the cirrus. Following the local appearance of a spur of stratospheric volcanic debris from the subtropics, a series of jet streaks subsequently conditioned the troposphere through tropopause foldings with sulfur-based particles that became effective cloud-forming nuclei in cirrus clouds. Aerosol and ozone measurements suggest a complicated history of stratospheric-tropospheric exchanges embedded within the upper-level flow, and cirrus cloud formation was noted to occur locally at the boundaries of stratospheric aerosol-enriched layers that became humidified through diffusion, precipitation, or advective processes. Apparent cirrus cloud alterations include abnormally high ice crystal concentrations (up to {approximately}600 L{sup {minus}1}), complex radial ice crystal types, and relatively large haze particles in cirrus uncinus cell heads at temperatures between {minus}40{degrees} and {minus}50{degrees}C. Implications for volcanic-cirrus cloud climate effects and usual (nonvolcanic aerosol) jet stream cirrus cloud formation are discussed. 42 refs., 25 figs., 3 tabs.

  7. Probing the disc wind-jet connection in black hole transients II

    NASA Astrophysics Data System (ADS)

    Diaz Trigo, Maria

    2013-10-01

    We propose six observations of one high inclination black hole low mass X-ray binary (LMXB) at different stages of its outburst. We will investigate the presence of X-ray narrow absorption/emission features in the XMM spectra, which are a signature of a disc wind, and their relation to the accreting regime. Such features, identified with ions like FeXXV and FeXXVI, have been observed in a number of LMXBs and give us information about the mass outflow rate and the launching mechanism of the wind. With simultaneous radio observations we will probe the jet power as a function of the wind properties and how the radio flux density correlates with the X-ray flux at different accretion regimes. We will also investigate the broadening mechanism of the FeK emission line detected up to now in several LMXBs.

  8. Measurement of the top-quark mass in the lepton+jets channel using a matrix element technique with the CDF II detector

    SciTech Connect

    Aaltonen, T.

    2011-10-14

    A measurement of the top-quark mass is presented using Tevatron data from proton-antiproton collisions at center-of-mass energy √s = 1.96 TeV collected with the CDF II detector. Events are selected from a sample of candidates for production of tt̄ pairs that decay into the lepton+jets channel. The top-quark mass is measured with an unbinned maximum likelihood method where the event probability density functions are calculated using signal and background matrix elements, as well as a set of parameterized jet-to-parton transfer functions. The likelihood function is maximized with respect to the top-quark mass, the signal fraction in the sample, and a correction to the jet energy scale (JES) calibration of the calorimeter jets. The simultaneous measurement of the JES correction ({Delta}{sub JES}) amounts to an additional in situ jet energy calibration based on the known mass of the hadronically decaying W boson. Using the data sample of 578 lepton+jets candidate events, corresponding to 3.2 fb-1 of integrated luminosity, the top-quark mass is measured to be mt = 172.4± 1.4 (stat + ΔJES) ± 1.3 (syst) GeV/c2.

  9. Measurement of the top-quark mass in the lepton+jets channel using a matrix element technique with the CDF II detector

    DOE PAGESBeta

    Aaltonen, T.

    2011-10-14

    A measurement of the top-quark mass is presented using Tevatron data from proton-antiproton collisions at center-of-mass energy √s = 1.96 TeV collected with the CDF II detector. Events are selected from a sample of candidates for production of tt̄ pairs that decay into the lepton+jets channel. The top-quark mass is measured with an unbinned maximum likelihood method where the event probability density functions are calculated using signal and background matrix elements, as well as a set of parameterized jet-to-parton transfer functions. The likelihood function is maximized with respect to the top-quark mass, the signal fraction in the sample, and amore » correction to the jet energy scale (JES) calibration of the calorimeter jets. The simultaneous measurement of the JES correction ({Delta}{sub JES}) amounts to an additional in situ jet energy calibration based on the known mass of the hadronically decaying W boson. Using the data sample of 578 lepton+jets candidate events, corresponding to 3.2 fb-1 of integrated luminosity, the top-quark mass is measured to be mt = 172.4± 1.4 (stat + ΔJES) ± 1.3 (syst) GeV/c2.« less

  10. DICHOTOMY OF SOLAR CORONAL JETS: STANDARD JETS AND BLOWOUT JETS

    SciTech Connect

    Moore, Ronald L.; Cirtain, Jonathan W.; Sterling, Alphonse C.; Falconer, David A.

    2010-09-01

    By examining many X-ray jets in Hinode/X-Ray Telescope coronal X-ray movies of the polar coronal holes, we found that there is a dichotomy of polar X-ray jets. About two thirds fit the standard reconnection picture for coronal jets, and about one third are another type. We present observations indicating that the non-standard jets are counterparts of erupting-loop H{alpha} macrospicules, jets in which the jet-base magnetic arch undergoes a miniature version of the blowout eruptions that produce major coronal mass ejections. From the coronal X-ray movies we present in detail two typical standard X-ray jets and two typical blowout X-ray jets that were also caught in He II 304 A snapshots from STEREO/EUVI. The distinguishing features of blowout X-ray jets are (1) X-ray brightening inside the base arch in addition to the outside bright point that standard jets have, (2) blowout eruption of the base arch's core field, often carrying a filament of cool (T {approx} 10{sup 4} - 10{sup 5} K) plasma, and (3) an extra jet-spire strand rooted close to the bright point. We present cartoons showing how reconnection during blowout eruption of the base arch could produce the observed features of blowout X-ray jets. We infer that (1) the standard-jet/blowout-jet dichotomy of coronal jets results from the dichotomy of base arches that do not have and base arches that do have enough shear and twist to erupt open, and (2) there is a large class of spicules that are standard jets and a comparably large class of spicules that are blowout jets.

  11. Dichotomy of Solar Coronal Jets: Standard Jets and Blowout Jets

    NASA Technical Reports Server (NTRS)

    Moore, R. L.; Cirtain, J. W.; Sterling, A. C.; Falconer, D. A.

    2010-01-01

    By examining many X-ray jets in Hinode/XRT coronal X-ray movies of the polar coronal holes, we found that there is a dichotomy of polar X-ray jets. About two thirds fit the standard reconnection picture for coronal jets, and about one third are another type. We present observations indicating that the non-standard jets are counterparts of erupting-loop H alpha macrospicules, jets in which the jet-base magnetic arch undergoes a miniature version of the blowout eruptions that produce major CMEs. From the coronal X-ray movies we present in detail two typical standard X-ray jets and two typical blowout X-ray jets that were also caught in He II 304 Angstrom snapshots from STEREO/EUVI. The distinguishing features of blowout X-ray jets are (1) X-ray brightening inside the base arch in addition to the outside bright point that standard jets have, (2) blowout eruption of the base arch's core field, often carrying a filament of cool (T 10(exp 4) - 10(exp 5) K) plasma, and (3) an extra jet-spire strand rooted close to the bright point. We present cartoons showing how reconnection during blowout eruption of the base arch could produce the observed features of blowout X-ray jets. We infer that (1) the standard-jet/blowout-jet dichotomy of coronal jets results from the dichotomy of base arches that do not have and base arches that do have enough shear and twist to erupt open, and (2) there is a large class of spicules that are standard jets and a comparably large class of spicules that are blowout jets.

  12. Discovery of MK-7655, a β-lactamase inhibitor for combination with Primaxin®.

    PubMed

    Blizzard, Timothy A; Chen, Helen; Kim, Seongkon; Wu, Jane; Bodner, Rena; Gude, Candido; Imbriglio, Jason; Young, Katherine; Park, Young-Whan; Ogawa, Aimie; Raghoobar, Susan; Hairston, Nichelle; Painter, Ronald E; Wisniewski, Doug; Scapin, Giovanna; Fitzgerald, Paula; Sharma, Nandini; Lu, Jun; Ha, Sookhee; Hermes, Jeff; Hammond, Milton L

    2014-02-01

    β-Lactamase inhibitors with a bicyclic urea core and a variety of heterocyclic side chains were prepared and evaluated as potential partners for combination with imipenem to overcome class A and C β-lactamase mediated antibiotic resistance. The piperidine analog 3 (MK-7655) inhibited both class A and C β-lactamases in vitro. It effectively restored imipenem's activity against imipenem-resistant Pseudomonas and Klebsiella strains at clinically achievable concentrations. A combination of MK-7655 and Primaxin® is currently in phase II clinical trials for the treatment of Gram-negative bacterial infections. PMID:24433862

  13. L-H power threshold studies in JET with Be/W and C wall

    NASA Astrophysics Data System (ADS)

    Maggi, C. F.; Delabie, E.; Biewer, T. M.; Groth, M.; Hawkes, N. C.; Lehnen, M.; de la Luna, E.; McCormick, K.; Reux, C.; Rimini, F.; Solano, E. R.; Andrew, Y.; Bourdelle, C.; Bobkov, V.; Brix, M.; Calabro, G.; Czarnecka, A.; Flanagan, J.; Lerche, E.; Marsen, S.; Nunes, I.; Van Eester, D.; Stamp, M. F.; EFDA Contributors, JET

    2014-02-01

    A comparison of the L-H power threshold (Pthr) in JET with all carbon, JET-C, and beryllium/tungsten wall (the ITER-like choice), JET-ILW, has been carried out in experiments with slow input power ramps and matched plasma shapes, divertor configuration and IP/BT pairs. The low density dependence of the L-H power threshold, namely an increase below a minimum density ne,min, which was first observed in JET with the MkII-GB divertor and C wall and subsequently not observed with the current MkII-HD geometry, is observed again with JET-ILW. At plasma densities above ne,min, Pthr is reduced by ˜30%, and by ˜40% when the radiation from the bulk plasma is subtracted (Psep), with JET-ILW compared to JET-C. At the L-H transition the electron temperature at the edge, where the pedestal later develops, is also lower with JET-ILW, for a given edge density. With JET-ILW the minimum density is found to increase roughly linearly with magnetic field, n_{e,min} \\sim B_{T}^{4/5} , while the power threshold at the minimum density scales as P_{sep,\\min} \\sim B_{T}^{5/2} . The H-mode power threshold in JET-ILW is found to be sensitive both to variations in main plasma shape (Psep decreases with increasing lower triangularity and increases with upper triangularity) and in divertor configuration. When the data are recast in terms of Psep and Zeff or subdivertor neutral pressure a linear correlation is found, pointing to a possible role of Zeff and/or subdivertor neutral pressure in the L-H transition physics. Depending on the chosen divertor configuration, Pthr can be up to a factor of two lower than the ITPA scaling law for densities above ne,min. A shallow edge radial electric field well is observed at the L-H transition. The edge impurity ion poloidal velocity remains low, close to its L-mode values, ⩽5 km s-1 ± 2-3 km s-1, at the L-H transition and throughout the H-mode phase, with no measureable increase within the experimental uncertainties. The edge toroidal rotation

  14. [Fe II] 1.64 μm FEATURES OF JETS AND OUTFLOWS FROM YOUNG STELLAR OBJECTS IN THE CARINA NEBULA

    SciTech Connect

    Shinn, Jong-Ho; Lee, Jae-Joon; Chun, Moo-Young; Lyo, A.-Ran; Moon, Dae-Sik; Kyeong, Jaemann; Park, Byeong-Gon; Pyo, Tae-Soo; Lee, Ho-Gyu; Kim, Hyun-Jeong; Koo, Bon-Chul; Lee, Yong-Hyun; Sung, Hwankyung; Hur, Hyeonoh

    2013-11-01

    We present [Fe II] 1.64 μm imaging observations for jets and outflows from young stellar objects (YSOs) over the northern part (∼24' × 45') of the Carina Nebula, a massive star-forming region. The observations were performed with IRIS2 of the Anglo-Australian Telescope and the seeing was ∼1.''5 ± 0.''5. Eleven jet and outflow features are detected at eight different regions and are termed ionized Fe objects (IFOs). One Herbig-Haro candidate that was missed in Hubble Space Telescope Hα observations is newly identified as HHc-16, referring to our [Fe II] images. IFOs have knotty or longish shapes, and the detection rate of IFOs against previously identified YSOs is 1.4%, which should be treated as a lower limit. Four IFOs show anti-correlated peak intensities in [Fe II] and Hα, where the ratio I([Fe II])/I(Hα) is higher for longish IFOs than for knotty IFOs. We estimate the outflow mass loss rate from the [Fe II] flux using two different methods. The jet-driving objects are identified for three IFOs (IFO-2, -4, and -7) for which we study the relations between the outflow mass loss rate and the YSO physical parameters from the radiative transfer model fitting. The ratios of the outflow mass loss rate over the disk accretion rate for IFO-4 and -7 are consistent with the previously reported values (10{sup –2}-10{sup +1}), while the ratio is higher for IFO-2. This excess may result from underestimating the disk accretion rate. The jet-driving objects are likely to be low- or intermediate-mass stars. Other YSO physical parameters, such as luminosity and age, show reasonable relations or trends.

  15. Emerging jets

    NASA Astrophysics Data System (ADS)

    Schwaller, Pedro; Stolarski, Daniel; Weiler, Andreas

    2015-05-01

    In this work, we propose a novel search strategy for new physics at the LHC that utilizes calorimeter jets that (i) are composed dominantly of displaced tracks and (ii) have many different vertices within the jet cone. Such emerging jet signatures are smoking guns for models with a composite dark sector where a parton shower in the dark sector is followed by displaced decays of dark pions back to SM jets. No current LHC searches are sensitive to this type of phenomenology. We perform a detailed simulation for a benchmark signal with two regular and two emerging jets, and present and implement strategies to suppress QCD backgrounds by up to six orders of magnitude. At the 14 TeV LHC, this signature can be probed with mediator masses as large as 1.5 TeV for a range of dark pion lifetimes, and the reach is increased further at the high-luminosity LHC. The emerging jet search is also sensitive to a broad class of long-lived phenomena, and we show this for a supersymmetric model with R-parity violation. Possibilities for discovery at LHCb are also discussed.

  16. Particle diffusion and localized acceleration in inhomogeneous AGN jets - II. Stochastic variation

    NASA Astrophysics Data System (ADS)

    Chen, Xuhui; Pohl, Martin; Böttcher, Markus; Gao, Shan

    2016-05-01

    We study the stochastic variation of blazar emission under a 2D spatially resolved leptonic jet model we previously developed. Random events of particle acceleration and injection in small zones within the emission region are assumed to be responsible for flux variations. In addition to producing spectral energy distributions that describe the observed flux of Mrk 421, we further analyse the timing properties of the simulated light curves, such as the power spectral density (PSD) at different bands, flux-flux correlations, as well as the cross-correlation function between X-rays and TeV γ-rays. We find spectral breaks in the PSD at a time-scale comparable to the dominant characteristic time-scale in the system, which is usually the pre-defined decay time-scale of an acceleration event. Cooling imposes a delay, and so PSDs taken at lower energy bands in each emission component (synchrotron or inverse Compton) generally break at longer time-scales. The flux-flux correlation between X-rays and TeV γ-rays can be either quadratic or linear, depending on whether or not there are large variation of the injection into the particle acceleration process. When the relationship is quadratic, the TeV flares lag the X-ray flares, and the optical and GeV flares are large enough to be comparable to the ones in X-ray. When the relationship is linear, the lags are insignificant, and the optical and GeV flares are small.

  17. ADAPTIVE OPTICS ECHELLE SPECTROSCOPY OF [Fe II] 1.644 mum IN THE RW AUR JET: A NARROW SLICE DOWN THE AXIS OF THE FLOW

    SciTech Connect

    Hartigan, Patrick; Hillenbrand, Lynne

    2009-11-10

    We present new adaptive optics echelle spectra of the near-infrared [Fe II] lines in the redshifted and blueshifted jets from the T Tauri star RW Aur. The spectra have an unprecedented combination of high spatial and spectral resolution that makes it possible to trace the dynamics of the flow to a projected distance of only 10 AU from the source. As noted by previous studies, the redshifted flow is much slower than its fainter blueshifted counterpart. Our observations clearly show that both the radial velocities and the emission line widths are larger closer to the source on both sides of the jet. The line widths are 20%-30% of the jet velocity on both sides of the flow, significantly larger than would be produced by a divergent constant velocity flow. The observed line widths could arise from a layered velocity structure in the jet or from magnetic waves. A bright knot in the redshifted jet has no concomitant increase in line width, implying that it is not heated by a bow shock. Alternate heating mechanisms include planar shocks, ambipolar diffusion, and magnetic reconnection.

  18. Effect of the Angiotensin I Converting Enzyme Inhibitor, MK-421, on Experimentally Induced Drinking

    NASA Technical Reports Server (NTRS)

    Fregley, Melvin J.; Fater, Dennis C.; Greenleaf, John E.

    1982-01-01

    MK-421, the ethyl ester maleate salt of N-(S)-1-(ethoxycarbonyl)-3-phenyl-propyl- Ala-L-Pro, is an angiotensin I converting enzyme inhibitor. An initial objective was to determine whether MK-421, administered at 0, 2.5, 5.0, 10.0, 20.0 and 40.0 mg/kg, ip to 96 female rats 15 min prior to administration of the beta-adrenergic agonist, isoproterenol (25 microgram/kg, ip), would inhibit the drinking induced by isoproterenol during 2 h after its administration. The water intake induced by isoproterenol was inhibited significantly by 2.5 mg MK-421/kg. When a similar experiment was performed using Angiotensin I (AI) (200 microgram/kg, ip) as the dipsogenic agent, MK-421 (5 mg/kg, ip), administered 15 min prior to AI, inhibited significantly both the dipsogenic and the diuretic effect of AI. However, administration of angiotensin II (AII, 200 microgram/kg, ip) 15 min after MK-421 (5mg/kg) was accompanied by a water intake that did not differ from AII alone. The drink induced by ip administration of 1.0 m NaCl solution (1% of body wt, ip) was not inhibited by administration of MK-421 (5 mg/kg) 15 min prior to allowing access to water while the drink induced by a 24 h dehydration was partially inhibited. Thus, the drinks induced by administraition of either isoproterenol or AI are dependent on formation of AII. That induced by dehydration is partially dependent, while that induced by hypertonic siilinc is independent of the formation of AII.

  19. A magnetohydrodynamic model of the M87 jet. II. Self-consistent quad-shock jet model for optical relativistic motions and particle acceleration

    SciTech Connect

    Nakamura, Masanori

    2014-04-20

    We describe a new paradigm for understanding both relativistic motions and particle acceleration in the M87 jet: a magnetically dominated relativistic flow that naturally produces four relativistic magnetohydrodynamic (MHD) shocks (forward/reverse fast and slow modes). We apply this model to a set of optical super- and subluminal motions discovered by Biretta and coworkers with the Hubble Space Telescope during 1994-1998. The model concept consists of ejection of a single relativistic Poynting jet, which possesses a coherent helical (poloidal + toroidal) magnetic component, at the remarkably flaring point HST-1. We are able to reproduce quantitatively proper motions of components seen in the optical observations of HST-1 with the same model we used previously to describe similar features in radio very long baseline interferometry observations in 2005-2006. This indicates that the quad relativistic MHD shock model can be applied generally to recurring pairs of super/subluminal knots ejected from the upstream edge of the HST-1 complex as observed from radio to optical wavelengths, with forward/reverse fast-mode MHD shocks then responsible for observed moving features. Moreover, we identify such intrinsic properties as the shock compression ratio, degree of magnetization, and magnetic obliquity and show that they are suitable to mediate diffusive shock acceleration of relativistic particles via the first-order Fermi process. We suggest that relativistic MHD shocks in Poynting-flux-dominated helical jets may play a role in explaining observed emission and proper motions in many active galactic nuclei.

  20. Relativistic Jets in the Radio Reference Frame Image Database. II. Blazar Jet Accelerations from the First 10 Years of Data (1994-2003)

    NASA Astrophysics Data System (ADS)

    Piner, B. G.; Pushkarev, A. B.; Kovalev, Y. Y.; Marvin, C. J.; Arenson, J. G.; Charlot, P.; Fey, A. L.; Collioud, A.; Voitsik, P. A.

    2012-10-01

    We analyze blazar jet apparent speeds and accelerations from the RDV series of astrometric and geodetic very long baseline interferometry (VLBI) experiments. From these experiments, we have produced and analyzed 2753 global VLBI images of 68 sources at 8 GHz with a median beam size of 0.9 milliarcseconds (mas) and a median of 43 epochs per source. From this sample, we analyze the motions of 225 jet components in 66 sources. The distribution of the fastest measured apparent speed in each source has a median of 8.3c and a maximum of 44c. Sources in the 2FGL Fermi LAT catalog display higher apparent speeds than those that have not been detected. On average, components farther from the core in a given source have significantly higher apparent speeds than components closer to the core; for example, for a typical source, components at ~3 mas from the core (~15 pc projected at z ~ 0.5) have apparent speeds about 50% higher than those of components at ~1 mas from the core (~5 pc projected at z ~ 0.5). We measure accelerations of components in orthogonal directions parallel and perpendicular to their average velocity vector. Parallel accelerations have significantly larger magnitudes than perpendicular accelerations, implying that observed accelerations are predominantly due to changes in the Lorentz factor (bulk or pattern) rather than projection effects from jet bending. Positive parallel accelerations are significantly more common than negative ones, so the Lorentz factor (bulk or pattern) tends to increase on the scales observed here. Observed parallel accelerations correspond to modest source frame increases in the bulk or pattern Lorentz factor.

  1. SU2C Phase Ib Study of Paclitaxel and MK-2206 in Advanced Solid Tumors and Metastatic Breast Cancer

    PubMed Central

    Gonzalez-Angulo, Ana M.; Krop, Ian; Akcakanat, Argun; Chen, Huiqin; Liu, Shuying; Li, Yisheng; Culotta, Kirk S.; Tarco, Emily; Piha-Paul, Sarina; Moulder-Thompson, Stacy; Velez-Bravo, Vivianne; Sahin, Aysegul A.; Doyle, Laurence A.; Do, Kim-Anh; Winer, Eric P.; Mills, Gordon B.; Kurzrock, Razelle

    2015-01-01

    Background: There is preclinical synergism between taxanes and MK-2206. We aim to determine the maximum tolerated dose, safety, and activity of combining MK-2206 and paclitaxel in metastatic cancer. Methods: Patients received weekly doses of paclitaxel at 80mg/m2 on day 1, followed by MK-2206 orally on day 2 escalated at 90mg, 135mg, and 200mg. Treatment continued until progression, excessive toxicity, or patient request. Blood and tissue were collected for pharmacokinetic and pharmacodynamics markers. A cycle consisted of three weeks of therapy. Dose-limiting toxicity (DLT) was defined as unacceptable toxicity during the first cycle. All statistical tests were two-sided. Results: Twenty-two patients were treated, nine in dose escalation and 13 in dose expansion. Median age was 55 years. Median number of cycles was four. Dose escalation was completed with no DLT. CTCAE Grade 3 or higher adverse events were fatigue (n = 2), rash (n = 2), hyperglycemia (n = 1), and neutropenia (n = 7). Four patients in the expansion phase required MK-2206 dose reduction. Phase II recommended dose was established as paclitaxel 80mg/m2 weekly on day 1, and MK-2206 135mg weekly on day 2. Paclitaxel systemic exposure was similar in the presence or absence of MK-2206. Plasma MK-2206 concentrations were similar to data from previous phase I monotherapy. There was a statistically significant decrease in expression of pAKT S473 (P = .01) and pAKT T308 (P = .002) after therapy. PI3K/AKT/mTOR downregulation in tumor tissues and circulating markers did not correlate with tumor response or clinical benefit. There were five objective responses, and nine patients had stable disease. Conclusion: MK-2206 was well tolerated with paclitaxel. Preliminary antitumor activity was documented. PMID:25688104

  2. In vitro cytokine release from rat type II pneumocytes and alveolar macrophages following exposure to JP-8 jet fuel in co-culture.

    PubMed

    Wang, Shengjun; Young, R Scotte; Sun, Nina N; Witten, Mark L

    2002-05-01

    Alveolar type II epithelial cells (AIIE) and pulmonary alveolar macrophages (PAM) are involved in pulmonary toxicity of JP-8 jet fuel exposure. To further elucidate their inflammatory mechanisms, the effect(s) of JP-8 jet fuel on cytokine secretion were examined in a transformed rat AIIE cell line (RLE-6TN) culture alone, primary PAM (from Fischer 344 rats) culture alone, and the co-culture of AIIE and primary PAM. A series of JP-8 jet fuel concentrations (0-0.8 microg/ml), which may actually be encountered in alveolar space of lungs exposed in vivo, were placed in cell culture for 24 h. Cultured AIIE alone secreted spontaneously interleukin (IL)-1beta and -6 [below detectable limits for IL-10 and tumor necrosis factor-alpha (TNF-alpha)], whereas cultured PAM alone secreted IL-1beta, -10, and TNF-alpha, in a concentration-dependent manner. These data suggest that the release of cytokines, not only from PAM but also from AIIE cells, may contribute to JP-8 jet fuel-induced inflammatory response in the alveolar space. However, the co-cultures of AIIE and PAM showed no significant changes in IL-1beta, -6, and TNF-alpha at any JP-8 jet fuel concentration compared to control values. These cytokine levels in co-cultures of AIIE and PAM were inversely related to these of cultured AIIE or PAM alone. Interestingly, IL-10 levels in the co-culture system were concentration-dependently increased up to 1058% at JP-8 concentrations of 0.8 microg/ml, although under detectable limits in cultured AIIE alone and no significant concentration change in cultured PAM alone. It appears that PAM may possibly act via paracrine and/or autocrine pathways to signal AIIE cells to regulate cytokine release. PMID:11960674

  3. [Fe II] 1.257 μm and He I 1.083 μm Emission in the Central Region of the Orion Nebula: H II Region, HH Flows, Jets, and Proplyds

    NASA Astrophysics Data System (ADS)

    Takami, Michihiro; Usuda, Tomonori; Sugai, Hajime; Suto, Hiroshi; Pyo, Tae-Soo; Takeyama, Norihide; Aoki, Tetsuo; Mizutani, Kohei; Tanaka, Masuo

    2002-02-01

    The [Fe II] 1.257 μm and He I 1.083 μm emission lines were observed in the central 6'×8' region of the Orion Nebula, and their excitation in the photoionized H II region, HH flows, jets, and proplyds is investigated. Observations were carried out using the imaging Fabry-Perot spectrometer MUSE at the National Astronomical Observatory of Japan 1.5 m infrared telescope, which provides a 4'×4' field of view and a spectral resolution λ/δλ of ~2000 at the observed wavelengths. The [Fe II] images exhibit (1) filamentary structures and diffuse emission, which presumably arise from ionization fronts of the photoionized H II region, and (2) a number of knots, some of which are newly identified. Centroidal velocities in most of the knots are negative relative to those in the ionization fronts by up to -60 km s-1, and observed line profiles in the bright knots exhibit blueshifted wings, agreeing with bow shock models. The He I 1.083 μm emission in the observed region is dominated by the photoionized H II region, and its distribution reflects the complicated nature of the excitation. The He I images also contain blueshifted emission from several HH flows and jets and redshifted emission associated with proplyds. Our results for the shocks suggest that the [Fe II] 1.257 μm and He I 1.083 μm emission reflects the ionization of the preshock gas: the [Fe II] 1.257 μm emission is prominent in shocks propagating in molecular/atomic gas, while the He I 1.083 μm is prominent in shocks in the photoionized H II region. Different line excitation in these shocks can be explained by the following physical properties and processes: (1) difference of the excitation energies from the ground state (1 and 20 eV for the [Fe II] and He I lines, respectively), (2) resonance scattering and collisional excitation from the metastable state, enhancing the He I 1.083 μm line in shocks in the photoionized H II region, (3) a large photoionization cross section of Fe+, causing the absence of

  4. MK2 Regulates Ras Oncogenesis through Stimulating ROS Production

    PubMed Central

    Kobayashi, Yusuke; Qi, Xiaomei

    2012-01-01

    Ras signals through both mitogenic and stress pathways and studies of Ras regulatory effects of stress pathways hold great promise to control Ras-dependent malignancies. Our previous work showed Ras activation of a stress kinase (MAPK-activated protein kinase 2 [MK2]), and here, we examine regulatory effects of MK2 on Ras oncogenesis. MK2 knockout was shown to increase Ras transformation in mouse embryonic fibroblasts (MEFs) in vitro and to enhance the resultant tumor growth in mice, indicating a tumor suppressor activity. In Ras-dependent and -independent human colon cancer, however, MK2-forced expression increases and MK2 depletion decreases the malignant growth, suggesting its oncogenic activity. The oncogenic activity of MK2 couples with its activation by both stress and mitogenic signals through extracellular signal–regulated kinase and p38α pathways, whereas its tumor-suppressing effect links to its stimulation only by stress downstream of p38α. Of interest, MK2 was shown to decrease intracellular levels of reactive oxygen species (ROS) in MEFs but increase its production in human colon cancer cells, and experiments with antioxidants revealed that ROS is required for Ras oncogenesis in both systems. These results indicate that MK2 can increase or decrease Ras oncogenesis dependent of its ROS regulatory activities. PMID:23264852

  5. ACS Chemical Neuroscience Molecule Spotlight on Telcagepant (MK-0974)

    PubMed Central

    2011-01-01

    Telcagepant (MK-0974) is a novel calcitonin gene-related peptide (CGRP) receptor antagonist currently undergoing clinical trials for migraine (http://www.merck.com/research/pipeline/home.html). MK-0974 is currently being studied in phase III clinical trials. PMID:22816019

  6. Measurement of the Inclusive Jet Cross Section using the k(T) algorithm in p anti-p collisions at s**(1/2) = 1.96-TeV with the CDF II Detector

    SciTech Connect

    Abulencia, A.; Adelman, J.; Affolder, Anthony Allen; Akimoto, T.; Albrow, Michael G.; Ambrose, D.; Amerio, S.; Amidei, Dante E.; Anastassov, A.; Anikeev, Konstantin; Annovi, A.; /Frascati /Comenius U.

    2007-01-01

    The authors report on measurements of the inclusive jet production cross section as a function of the jet transverse momentum in p{bar p} collisions at {radical}s = 1.96 TeV, using the k{sub T} algorithm and a data sample corresponding to 1.0 fb{sup -1} collected with the Collider Detector at Fermilab in Run II. The measurements are carried out in five different jet rapidity regions with |y{sup jet}| < 2.1 and transverse momentum in the range 54 < p{sub T}{sup jet} < 700 GeV/c. Next-to-leading order perturbative QCD predictions are in good agreement with the measured cross sections.

  7. Search for Anomalous Production of Photon + Jets + Missing Transverse Energy in $p\\bar{p}$ Collisions at $\\sqrt{s}=1.96$~TeV Using the CDF II Detector

    SciTech Connect

    Hewamanage, Samantha Kaushalya

    2011-01-01

    A model-independent signature-based search for physics beyond the Standard Model is performed in the photon~+ jets~+ missing transverse energy channel in \\ppbar collisions at a center of mass energy of 1.96 TeV using the CDF II detector. Events with a photon + jets are predicted by the Standard Model and also by many theoretical models beyond the Standard Model. In the Standard Model, the main mechanisms for photon~+ jets production include quark-antiquark annihilation and quark-gluon scattering. No intrinsic missing transverse energy is present in any of these Standard Model processes. In this search, photon~+ $\\geq$1 jet and photon~+ $\\geq$2 jet events are analyzed with and without a minimum requirement on the missing transverse energy. Numerous mass distributions and kinematic distributions are studied and no significant excess over the background prediction is found. All results indicate good agreement with expectations of the Standard Model.

  8. A DEEP CHANDRA ACIS STUDY OF NGC 4151. II. THE INNERMOST EMISSION LINE REGION AND STRONG EVIDENCE FOR RADIO JET-NLR CLOUD COLLISION

    SciTech Connect

    Wang Junfeng; Fabbiano, Giuseppina; Elvis, Martin; Risaliti, Guido; Karovska, Margarita; Zezas, Andreas; Mundell, Carole G.

    2011-07-20

    We have studied the X-ray emission within the inner {approx}150 pc radius of NGC 4151 by constructing high spatial resolution emission line images of blended O VII, O VIII, and Ne IX. These maps show extended structures that are spatially correlated with the radio outflow and optical [O III] emission. We find strong evidence for jet-gas cloud interaction, including morphological correspondences with regions of X-ray enhancement, peaks of near-infrared [Fe II] emission, and optical clouds. In these regions, moreover, we find evidence of elevated Ne IX/O VII ratios; the X-ray emission of these regions also exceeds that expected from nuclear photoionization. Spectral fitting reveals the presence of a collisionally ionized component. The thermal energy of the hot gas suggests that {approx}> 0.1% of the estimated jet power is deposited into the host interstellar medium through interaction between the radio jet and the dense medium of the circumnuclear region. We find possible pressure equilibrium between the collisionally ionized hot gas and the photoionized line-emitting cool clouds. We also obtain constraints on the extended iron and silicon fluorescent emission. Both lines are spatially unresolved. The upper limit on the contribution of an extended emission region to the Fe K{alpha} emission is {approx}< 5% of the total, in disagreement with a previous claim that 65% of the Fe K{alpha} emission originates in the extended narrow line region.

  9. Pharmacokinetics and food interaction of MK-462 in healthy males.

    PubMed

    Cheng, H; Polvino, W J; Sciberras, D; Yogendran, L; Cerchio, K A; Christie, K; Olah, T V; McLoughlin, D; James, I; Rogers, J D

    1996-01-01

    A study was conducted to assess the safety, tolerability, and pharmacokinetics of single intravenous (IV) doses of 5-90 micrograms kg-1 of MK-462, and the effect of food on the pharmacokinetics of MK-462 administered orally to healthy males. Results of this study indicate that IV doses of MK-462 from 5 to 90 micrograms kg-1 are well tolerated. The disposition kinetics of MK-462 were linear for IV doses up to and including 60 micrograms kg-1. The values of the plasma clearance (CL), steady-state volume of distribution (Vss), plasma terminal half-life (t1/2), and mean residence time in the body (MRT) of MK-462 averaged 1376 mL min-1, 140 L, 1.8 h, and 1.7 h, respectively, and remained essentially constant over the dosage range of 10-60 micrograms kg-1 of IV MK-462. However, as the dose increased from 60 to 90 micrograms kg-1, the mean value of the apparent CL decreased from 1376 to 807 mL min-1. Thus, elimination of MK-462 was dose dependent in this dosage range. Based on the disposition decomposition analysis (DDA), it was shown that the Vss value of MK-462 remained essentially constant over the dosage range of 10-90 micrograms kg-1 of IV MK-462. The following values of two dose-independent parameters were also calculated by using DDA: distribution clearance (CLd) = 2028 mL min-1, and mean transit time in the peripheral tissues (MTTT) = 0.74 h. The mean values of AUC, Cmax, tmax, and apparent t1/2 of MK-462 in 12 subjects each receiving a 40 mg tablet of MK-462 without breakfast were 330 ng.h mL-1, 77 ng mL-1, 1.6 h, and 1.8 h, respectively. Although administration of a standard breakfast prior to dosing increased the AUC value (by approximately 20%) of MK-462 and delayed its absorption, there were no significant effects of the meal on the values of Cmax and apparent t1/2 of MK-462. PMID:8991488

  10. In vitro time- and dose-effect response of JP-8 and S-8 jet fuel on alveolar type II epithelial cells of rats.

    PubMed

    Robb, Tiffany M; Rogers, Michael J; Woodward, Suann S; Wong, Simon S; Witten, Mark L

    2010-07-01

    This study was designed to characterize and compare the effects of jet propellant-8 (JP-8) fuel and synthetic-8 (S-8) on cell viability and nitric oxide synthesis in cultured alveolar type II epithelial cells of rats. Exposure times varied from 0.25, 0.5, 1, and 6 hours at the following concentrations of jet fuel: 0.0, 0.1, 0.4, and 2.0 microg/mL. Data indicate that JP-8 presents a gradual decline in cell viability and steady elevation in nitric oxide release as exposure concentrations increase. At a 2.0 microg/mL concentration of JP-8, nearly all of the cells are not viable. Moreover, S-8 exposure to rat type II lung cells demonstrated an abrupt fall in percentage cell viability and increases in nitric oxide measurement, particularly after the 2.0 microg/mL was reached at 1 and 6 hours. At 0.0, 0.2, and 0.4 microg/mL concentrations of S-8, percentage viability was sustained at steady concentrations. The results suggest different epithelial toxicity and mechanistic effects of S-8 and JP-8, providing further insight concerning the impairment imposed at specific levels of lung function and pathology induced by the different fuels. PMID:20504826

  11. Complete multiwavelength evolution of galactic black hole transients during outburst decay. II. Compact jets and X-ray variability properties

    SciTech Connect

    Dinçer, T.; Kalemci, E.; Tomsick, J. A.; Buxton, M. M.; Bailyn, C. D.

    2014-11-01

    We investigated the relation between compact jet emission and X-ray variability properties of all black hole transients with multiwavelength coverage during their outburst decays. We studied the evolution of all power spectral components (including low-frequency quasi-periodic oscillations; QPOs), and related this evolution to changes in jet properties tracked by radio and infrared observations. We grouped sources according to their tracks in the radio/X-ray luminosity relation and show that the standards show stronger broadband X-ray variability than outliers at a given X-ray luminosity when the compact jet turns on. This trend is consistent with the internal shock model and can be important for the understanding of the presence of tracks in the radio/X-ray luminosity relation. We also observed that the total and the QPO rms amplitudes increase together during the earlier part of the outburst decay, but after the compact jet turns, either the QPO disappears or its rms amplitude decreases significantly while the total rms amplitudes remain high. We discuss these results with a scenario including a variable corona and a non-variable disk with a mechanism for the QPO separate from the mechanism that creates broad components. Finally, we evaluated the timing predictions of the magnetically dominated accretion flow model that can explain the presence of tracks in the radio/X-ray luminosity relation.

  12. Twin Jet

    NASA Technical Reports Server (NTRS)

    Henderson, Brenda; Bozak, Rick

    2010-01-01

    Many subsonic and supersonic vehicles in the current fleet have multiple engines mounted near one another. Some future vehicle concepts may use innovative propulsion systems such as distributed propulsion which will result in multiple jets mounted in close proximity. Engine configurations with multiple jets have the ability to exploit jet-by-jet shielding which may significantly reduce noise. Jet-by-jet shielding is the ability of one jet to shield noise that is emitted by another jet. The sensitivity of jet-by-jet shielding to jet spacing and simulated flight stream Mach number are not well understood. The current experiment investigates the impact of jet spacing, jet operating condition, and flight stream Mach number on the noise radiated from subsonic and supersonic twin jets.

  13. Shock associated noise of inverted-profile coannular jets. II - Condition for minimum noise. III - Shock structure and noise characteristic

    NASA Technical Reports Server (NTRS)

    Tam, C. K. W.; Tanna, H. K.

    1985-01-01

    The generation of noise by the shock-turbulence interaction with shock cells in an inverted-profile coannular jet with nozzle exit velocity aligned with the jet axis is investigated analytically, interpreting the optical measurements of Tanna et al. (1985). The noise-intensity minimum at slightly supersonic primary-flow velocities is related to the weakness of the primary-stream shock-cell structure and the lack of such a pattern in the outer fan stream. The discrepancies between this finding and those of Dosanjh et al. (1977 and 1978) are attributed to nozzle design, the definition of minimum noise, and different interpretative approaches. A first-order shock-cell model is then developed to derive formulas for the peak frequencies and the scaling of noise intensity. The results of computations using these formulas are presented in graphs and found to be in good agreement with the experimental data.

  14. THE FERMI BUBBLES. II. THE POTENTIAL ROLES OF VISCOSITY AND COSMIC-RAY DIFFUSION IN JET MODELS

    SciTech Connect

    Guo Fulai; Mathews, William G.; Oh, S. Peng

    2012-09-10

    The origin of the Fermi bubbles recently detected by the Fermi Gamma-ray Space Telescope in the inner Galaxy is mysterious. In the companion paper Guo and Mathews (Paper I), we use hydrodynamic simulations to show that they could be produced by a recent powerful active galactic nucleus (AGN) jet event. Here, we further explore this scenario to study the potential roles of shear viscosity and cosmic-ray (CR) diffusion on the morphology and CR distribution of the bubbles. We show that even a relatively low level of viscosity ({mu}{sub visc} {approx}> 3 g cm{sup -1} s{sup -1}, or {approx}0.1%-1% of Braginskii viscosity in this context) could effectively suppress the development of Kelvin-Helmholtz instabilities at the bubble surface, resulting in smooth bubble edges as observed. Furthermore, viscosity reduces circulating motions within the bubbles, which would otherwise mix the CR-carrying jet backflow near bubble edges with the bubble interior. Thus viscosity naturally produces an edge-favored CR distribution, an important ingredient to produce the observed flat gamma-ray surface brightness distribution. Generically, such a CR distribution often produces a limb-brightened gamma-ray intensity distribution. However, we show that by incorporating CR diffusion that is strongly suppressed across the bubble surface (as inferred from sharp bubble edges) but is close to canonical values in the bubble interior, we obtain a reasonably flat gamma-ray intensity profile. The similarity of the resulting CR bubble with the observed Fermi bubbles strengthens our previous result in Paper I that the Fermi bubbles were produced by a recent AGN jet event. Studies of the nearby Fermi bubbles may provide a unique opportunity to study the potential roles of plasma viscosity and CR diffusion on the evolution of AGN jets and bubbles.

  15. Mk12A/W78 ground test project (u)

    SciTech Connect

    Stokes, Kyle R

    2010-12-01

    The slides present the scope, objectives and status of the Mk12A1W78 Ground Test Project for the purpose of updating the ICBM Project Officers Group. In addition, project constraints and risks are discussed.

  16. Nanoelectronic primary thermometry below 4 mK

    NASA Astrophysics Data System (ADS)

    Bradley, D. I.; George, R. E.; Gunnarsson, D.; Haley, R. P.; Heikkinen, H.; Pashkin, Yu. A.; Penttilä, J.; Prance, J. R.; Prunnila, M.; Roschier, L.; Sarsby, M.

    2016-01-01

    Cooling nanoelectronic structures to millikelvin temperatures presents extreme challenges in maintaining thermal contact between the electrons in the device and an external cold bath. It is typically found that when nanoscale devices are cooled to ~10 mK the electrons are significantly overheated. Here we report the cooling of electrons in nanoelectronic Coulomb blockade thermometers below 4 mK. The low operating temperature is attributed to an optimized design that incorporates cooling fins with a high electron-phonon coupling and on-chip electronic filters, combined with low-noise electronic measurements. By immersing a Coulomb blockade thermometer in the 3He/4He refrigerant of a dilution refrigerator, we measure a lowest electron temperature of 3.7 mK and a trend to a saturated electron temperature approaching 3 mK. This work demonstrates how nanoelectronic samples can be cooled further into the low-millikelvin range.

  17. Nanoelectronic primary thermometry below 4 mK.

    PubMed

    Bradley, D I; George, R E; Gunnarsson, D; Haley, R P; Heikkinen, H; Pashkin, Yu A; Penttilä, J; Prance, J R; Prunnila, M; Roschier, L; Sarsby, M

    2016-01-01

    Cooling nanoelectronic structures to millikelvin temperatures presents extreme challenges in maintaining thermal contact between the electrons in the device and an external cold bath. It is typically found that when nanoscale devices are cooled to ∼ 10 mK the electrons are significantly overheated. Here we report the cooling of electrons in nanoelectronic Coulomb blockade thermometers below 4 mK. The low operating temperature is attributed to an optimized design that incorporates cooling fins with a high electron-phonon coupling and on-chip electronic filters, combined with low-noise electronic measurements. By immersing a Coulomb blockade thermometer in the (3)He/(4)He refrigerant of a dilution refrigerator, we measure a lowest electron temperature of 3.7 mK and a trend to a saturated electron temperature approaching 3 mK. This work demonstrates how nanoelectronic samples can be cooled further into the low-millikelvin range. PMID:26816217

  18. Jet shielding of jet noise

    NASA Technical Reports Server (NTRS)

    Simonich, J. C.; Amiet, R. K.; Schlinker, R. H.

    1986-01-01

    An experimental and theoretical study was conducted to develop a validated first principle analysis for predicting the jet noise reduction achieved by shielding one jet exhaust flow with a second, closely spaced, identical jet flow. A generalized fuel jet noise analytical model was formulated in which the acoustic radiation from a source jet propagates through the velocity and temperature discontinuity of the adjacent shielding jet. Input variables to the prediction procedure include jet Mach number, spacing, temperature, diameter, and source frequency. Refraction, diffraction, and reflection effects, which control the dual jet directivity pattern, are incorporated in the theory. The analysis calculates the difference in sound pressure level between the dual jet configuration and the radiation field based on superimposing two independent jet noise directivity patterns. Jet shielding was found experimentally to reduce noise levels in the common plane of the dual jet system relative to the noise generated by two independent jets.

  19. Impulsive Heating of Solar Flare Ribbons Above 10 MK

    NASA Astrophysics Data System (ADS)

    Simões, P. J. A.; Graham, D. R.; Fletcher, L.

    2015-12-01

    The chromospheric response to the input of flare energy is marked by extended extreme ultraviolet (EUV) ribbons and hard X-ray (HXR) footpoints. These are usually explained as the result of heating and bremsstrahlung emission from accelerated electrons colliding in the dense chromospheric plasma. We present evidence of impulsive heating of flare ribbons above 10 MK in a two-ribbon flare. We analyse the impulsive phase of SOL2013-11-09T06:38, a C2.6 class event using data from Atmospheric Imaging Assembly (AIA) on board of the Solar Dynamics Observatory (SDO) and the Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI) to derive the temperature, emission measure and differential emission measure of the flaring regions and investigate the evolution of the plasma in the flaring ribbons. The ribbons were visible at all SDO/AIA EUV/UV wavelengths, in particular, at 94 and 131 Å filters, sensitive to temperatures of 8 MK and 12 MK. The time evolution of the emission measure of the plasma above 10 MK at the ribbons has a peak near the HXR peak time. The presence of hot plasma in the lower atmosphere is further confirmed by a RHESSI imaging spectroscopy analysis, which shows resolved sources at 11 - 13 MK that are associated with at least one ribbon. We found that collisional beam-heating can only marginally explain the power necessary to heat the 10 MK plasma at the ribbons.

  20. Interrogating two schedules of the AKT inhibitor MK-2206 in patients with advanced solid tumors incorporating novel pharmacodynamic and functional imaging biomarkers

    PubMed Central

    Yap, Timothy A.; Yan, Li; Patnaik, Amita; Tunariu, Nina; Biondo, Andrea; Fearen, Ivy; Papadopoulos, Kyriakos P.; Olmos, David; Baird, Richard; Delgado, Liliana; Tetteh, Ernestina; Beckman, Robert A.; Lupinacci, Lisa; Riisnaes, Ruth; Decordova, Shaun; Heaton, Simon P.; Swales, Karen; deSouza, Nandita M; Leach, Martin O.; Garrett, Michelle D.; Sullivan, Daniel M.; de Bono, Johann S.; Tolcher, Anthony W.

    2014-01-01

    Purpose Multiple cancers harbor genetic aberrations that impact AKT signaling. MK-2206 is a potent pan-AKT inhibitor with a maximum tolerated dose (MTD) previously established at 60mg on alternate days (QOD). Due to a long half-life (60-80h), a weekly (QW) MK-2206 schedule was pursued to compare intermittent QW and continuous QOD dosing. Experimental Design Patients with advanced cancers were enrolled onto a QW dose-escalation phase I study to investigate the safety and pharmacokinetic-pharmacodynamic profiles of tumor and platelet-rich plasma (PRP). The QOD MTD of MK-2206 was also assessed in patients with ovarian and castration-resistant prostate cancers, and patients with advanced cancers undergoing multiparametric functional magnetic resonance imaging (MRI) studies, including dynamic contrast-enhanced MRI, diffusion-weighted imaging, magnetic resonance spectroscopy and intrinsic susceptibility-weighted MRI. Results Seventy-one patients were enrolled; 38 patients had 60mg MK-2206 QOD, while 33 received MK-2206 at 90mg, 135mg, 150mg, 200mg, 250mg, and 300mg QW. The QW MK-2206 MTD was established at 200mg following dose-limiting rash at 250mg and 300mg. QW dosing appeared to be similarly tolerated to QOD, with toxicities including rash, gastrointestinal symptoms, fatigue, and hyperglycemia. Significant AKT pathway blockade was observed with both continuous QOD and intermittent QW dosing of MK-2206 in serially-obtained tumor and PRP specimens. The functional imaging studies demonstrated that complex multiparametric MRI protocols may be effectively implemented in a phase I trial. Conclusions MK-2206 safely results in significant AKT pathway blockade in QOD and QW schedules. The intermittent dose of 200mg QW is currently used in phase II MK-2206 monotherapy and combination studies. PMID:25239610

  1. The impact of dynamic data assimilation on the numerical simulations of the QE II cyclone and an analysis of the jet streak influencing the precyclogenetic environment

    NASA Technical Reports Server (NTRS)

    Manobianco, John; Uccellini, Louis W.; Brill, Keith F.; Kuo, Ying-Hwa

    1992-01-01

    A mesoscale numerical model is combined with a dynamic data assimilation via Newtonian relaxation, or 'nudging', to provide initial conditions for subsequent simulations of the QE II cyclone. Both the nudging technique and the inclusion of supplementary data are shown to have a large positive impact on the simulation of the QE II cyclone during the initial phase of rapid cyclone development. Within the initial development period (from 1200 to 1800 UTC 9 September 1978), the dynamic assimilation of operational and bogus data yields a coherent two-layer divergence pattern that is not well defined in the model run using only the operational data and static initialization. Diagnostic analysis based on the simulations show that the initial development of the QE II storm between 0000 UTC 9 September and 0000 UTC 10 September was embedded within an indirect circulation of an intense 300-hPa jet streak, was related to baroclinic processes extending throughout a deep portion of the troposphere, and was associated with a classic two-layer mass-divergence profile expected for an extratropical cyclone.

  2. Critical evaluation of Jet-A spray combustion using propane chemical kinetics in gas turbine combustion simulated by KIVA-II

    NASA Technical Reports Server (NTRS)

    Nguyen, H. L.; Ying, S.-J.

    1990-01-01

    Numerical solutions of the Jet-A spray combustion were obtained by means of the KIVA-II computer code after Jet-A properties were added to the 12 chemical species the program had initially contained. Three different reaction mechanism models are considered. The first model consists of 131 reactions and 45 species; it is evaluated by comparing calculated ignition delay times with available shock tube data, and it is used in the evaluation of the other two simplified models. The simplified mechanisms consider 45 reactions and 27 species and 5 reactions and 12 species, respectively. In the prediction of pollutants NOx and CO, the full mechanism of 131 reactions is considered to be more reliable. The numerical results indicate that the variation of the maximum flame temperature is within 20 percent as compared with that of the full mechanism of 131 reactions. The chemical compositions of major components such as C3H8, H2O, O2, CO2, and N2 are of the same order of magnitude. However, the concentrations of pollutants are quite different.

  3. Nocturnal Low-Level Jet in a Mountain Basin Complex. Part II: Transport and Diffusion of Tracer under Stable Conditions

    SciTech Connect

    Darby, Lisa S.; Allwine, K Jerry; Banta, Robert M.

    2006-05-01

    Differences in nighttime transport and diffusion of sulfur hexafluoride (SF6) tracer in an urban complex-terrain setting (Salt Lake City, Utah) are investigated using surface and Dopplerlidar wind data, and large-scale surface pressure differences. Interacting scales of motion, as studied through the URBAN 2000 field program combined with the Vertical Transport and Mixing Experiment (VTMX), explained the differences in the tracer behavior during three separate Intensive Operating Periods (IOPs). With an emphasis on nighttime stable boundary layer conditions, these field programs were designed to study flow features responsible for the nighttime transport of airborne substances. This transport has implications for air quality, homeland security, and emergency response issues if the airborne substances are hazardous. The important flow features investigated included thermally forced canyon and slope flows and a low-level jet (LLJ) that dominated the basin-scale winds when the surface pressure gradient was weak. The presence of thermally forced flows contributed to the complexity and hindered the predictability of the tracer motion within and beyond the city. When organized thermally forced flows were present, the tracer tended to stay closer to the city for longer periods of time, even though a strong basin-scale LLJ did develop. When thermally forced flows were short-lived or absent, the basin-scale low-level jet dominated the wind field and enhanced the transport of tracer material out of the city.

  4. Performance of a high-velocity pulse-jet filter, II. Final report Sep 76-Sep 79

    SciTech Connect

    Leith, D.; Ellenbecker, M.J.; First, M.W.; Price, J.M.; Martin, A.

    1980-03-01

    The report gives results of a study of the performance of a high-velocity pulse-jet filter. Such filtration has distinct advantages over low-velocity filtration in that the equipment required to clean a gas stream is reduced in size and initial cost as velocity increases. Although high filtration velocity causes a number of problems, many of them are dealt with in the report. Location of the gas inlet to the filter was found to affect penetration and pressure drop; both were higher for inlets near the bottom of the filter housing. Fabric type was also found to affect performance by affecting the amount and characteristics of the dust deposit accumulated. Fabric surface properties help explain the nature of this deposit. These ideas and others were used to develop a mathematical model for pressure drop in a pulse-jet cleaned filter. The model can be used to predict pressure drop under stable or variable operating conditions, and to predict operating conditions that cause unstable filter operation. An understanding of particle/fiber interactions is essential to understanding the collection characteristics of a felt fabric. Under certain conditions, particles bounce on impact with fibers. An adhesion probability was determined and found to depend on incident particle kinetic energy.

  5. Clinical physiology and mechanism of dizocilpine (MK-801)

    PubMed Central

    Somanathan, Ratnasamy

    2010-01-01

    Dizocilpine (MK-801), an extensively investigated drug possessing secondary amine and benzenoid functions, displays a wide array of biological properties, including anticonvulsant and anesthetic. There is scant discussion of biomechanism. A relevant, important finding is formation of oxidative metabolites in the hydroxylamine and phenolic categories. Analogy to cocaine metabolites suggests participation of redox entities, such as, hydroxylamine, nitroxide and nitrosonium, which can lead to electron transfer and radical formation. There is also similarity to metabolism by 3,3′-iminodipropionitrile and phencyclidine. Alternatively, the phenolic metabolites are well-known precursors of ET quinones. The review documents various physiological effects, mainly involving the central nervous system. Also of interest are the pro- and anti-oxidant properties. Considerable attention has been paid to MK-801 as an antagonist of the N-methyl-D-aspartate receptor in the glutamate category. This aspect is often associated with effects on the central nervous system. The review also provides recent literature dealing with MK-801/NMDA receptor in various areas of bioactivity. Studies were made of MK-801 involvement in working memory processing. Deficits in behavior were noted after administration of the drug. Treatment of mice with dizocilpine induced learning impairment. The influence of MK-801 on fear has been investigated. The substance is known to exert an analgesic effect in pain control. A number of reports deal with anesthetic properties. PMID:20716924

  6. Analysis of Performance of Jet Engine from Characteristics of Components II : Interaction of Components as Determined from Engine Operation

    NASA Technical Reports Server (NTRS)

    Goldstein, Arthur W; Alpert, Sumner; Beede, William; Kovach, Karl

    1949-01-01

    In order to understand the operation and the interaction of jet-engine components during engine operation and to determine how component characteristics may be used to compute engine performance, a method to analyze and to estimate performance of such engines was devised and applied to the study of the characteristics of a research turbojet engine built for this investigation. An attempt was made to correlate turbine performance obtained from engine experiments with that obtained by the simpler procedure of separately calibrating the turbine with cold air as a driving fluid in order to investigate the applicability of component calibration. The system of analysis was also applied to prediction of the engine and component performance with assumed modifications of the burner and bearing characteristics, to prediction of component and engine operation during engine acceleration, and to estimates of the performance of the engine and the components when the exhaust gas was used to drive a power turbine.

  7. Measurement of the WW+WZ Production Cross Section Using the Lepton+Jets Final State at CDF II

    SciTech Connect

    Aaltonen, T.; Adelman, J.; Alvarez Gonzalez, B.; Amerio, S.; Amidei, D.; Anastassov, A.; Annovi, A.; Antos, J.; Apollinari, G.; Apresyan, A.; Arisawa, T.; /Waseda U. /Dubna, JINR

    2009-11-01

    We report two complementary measurements of the diboson (WW + WZ) cross section in the final state consisting of an electron or muon, missing transverse energy, and jets, performed using p{bar p} collision data at {radical}s = 1.96 TeV collected by the Collider Detector at Fermilab. The first method uses the dijet invariant mass distribution while the second method uses more of the kinematic information in the event through matrix-element calculations of the signal and background processes and has a higher sensitivity. The result from the second method has a signal significance of 5.4{sigma} and is the first observation of WW + WZ production using this signature. Combining the results from both methods gives {sigma}{sub WW+WZ} = 16.0 {+-} 3.3 pb, in agreement with the standard model prediction.

  8. Sound generated by instability waves of supersonic flows. I Two-dimensional mixing layers. II - Axisymmetric jets

    NASA Technical Reports Server (NTRS)

    Tam, C. K. W.; Burton, D. E.

    1984-01-01

    An investigation is conducted of the phenomenon of sound generation by spatially growing instability waves in high-speed flows. It is pointed out that this process of noise generation is most effective when the flow is supersonic relative to the ambient speed of sound. The inner and outer asymptotic expansions corresponding to an excited instability wave in a two-dimensional mixing layer and its associated acoustic fields are constructed in terms of the inner and outer spatial variables. In matching the solutions, the intermediate matching principle of Van Dyke and Cole is followed. The validity of the theory is tested by applying it to an axisymmetric supersonic jet and comparing the calculated results with experimental measurements. Very favorable agreements are found both in the calculated instability-wave amplitude distribution (the inner solution) and the near pressure field level contours (the outer solution) in each case.

  9. SAFARI engineering model 50 mK cooler

    NASA Astrophysics Data System (ADS)

    Duband, L.; Duval, J. M.; Luchier, N.

    2014-11-01

    SAFARI is an infrared instrument developed by a European based consortium to be flown in SPICA, a Japanese led mission. The SAFARI detectors are transition edge sensors (TES) and require temperatures down to 50 mK for their operation. For that purpose we have developed a hybrid architecture based on the combination of a 300 mK sorption stage and a small adiabatic demagnetization stage. An engineering model has been designed to provide net heat lifts of 0.4 and 14 μW respectively at 50 and 300 mK, with an overall cycle duration of 48 h and a duty cycle objective of over 75%. The cooler is self-contained, fits in a volume of 156 × 312 × 182 mm and is expected to weigh 5.1 kg. It has been designed to withstand static loads of 120 g and a random vibration level of 21 g RMS.

  10. mkESA: enhanced suffix array construction tool

    PubMed Central

    Homann, Robert; Fleer, David; Giegerich, Robert; Rehmsmeier, Marc

    2009-01-01

    Summary: We introduce the tool mkESA, an open source program for constructing enhanced suffix arrays (ESAs), striving for low memory consumption, yet high practical speed. mkESA is a user-friendly program written in portable C99, based on a parallelized version of the Deep-Shallow suffix array construction algorithm, which is known for its high speed and small memory usage. The tool handles large FASTA files with multiple sequences, and computes suffix arrays and various additional tables, such as the LCP table (longest common prefix) or the inverse suffix array, from given sequence data. Availability: The source code of mkESA is freely available under the terms of the GNU General Public License (GPL) version 2 at http://bibiserv.techfak.uni-bielefeld.de/mkesa/. Contact: rhomann@techfak.uni-bielefeld.de PMID:19246510

  11. mkESA: enhanced suffix array construction tool.

    PubMed

    Homann, Robert; Fleer, David; Giegerich, Robert; Rehmsmeier, Marc

    2009-04-15

    We introduce the tool mkESA, an open source program for constructing enhanced suffix arrays (ESAs), striving for low memory consumption, yet high practical speed. mkESA is a user-friendly program written in portable C99, based on a parallelized version of the Deep-Shallow suffix array construction algorithm, which is known for its high speed and small memory usage. The tool handles large FASTA files with multiple sequences, and computes suffix arrays and various additional tables, such as the LCP table (longest common prefix) or the inverse suffix array, from given sequence data. PMID:19246510

  12. Testing of 100 mK bolometers for space applications

    NASA Technical Reports Server (NTRS)

    Murray, A. G.; Ade, P. A. R.; Bhatia, R. S.; Griffin, M. J.; Maffei, B.; Nartallo, R.; Beeman, J. W.; Bock, J.; Lange, A.; DelCastillo, H.

    1996-01-01

    Electrical and optical performance data are presented for a prototype 100 mK spider-web bolometer operating under very low photon backgrounds. These data are compared with the bolometer theory and are used to estimate the expected sensitivity of such a detector used for low background space astronomy. The results demonstrate that the sensitivity and speed of response requirements of the bolometer instruments proposed for these missions can be met by 100 mK spider-web bolometers using neutron transmutation doped germanium as the temperature sensitive element.

  13. [Air decontamination and the fine filtration system "Potok 150MK"].

    PubMed

    Kapustina, E A; Volodina, E V

    2004-01-01

    Longevity of space stations is dependent on efficiency and robustness of the life support systems. The article describes the principle of operation of air decontamination system Potok 150MK intended for providing microbial safety of the orbital station environment. High quality of air disinfection and decontamination has been demonstrated aboard SS Mir and the International space station. PMID:15233040

  14. Fuzzy jets

    NASA Astrophysics Data System (ADS)

    Mackey, Lester; Nachman, Benjamin; Schwartzman, Ariel; Stansbury, Conrad

    2016-06-01

    Collimated streams of particles produced in high energy physics experiments are organized using clustering algorithms to form jets. To construct jets, the experimental collaborations based at the Large Hadron Collider (LHC) primarily use agglomerative hierarchical clustering schemes known as sequential recombination. We propose a new class of algorithms for clustering jets that use infrared and collinear safe mixture models. These new algorithms, known as fuzzy jets, are clustered using maximum likelihood techniques and can dynamically determine various properties of jets like their size. We show that the fuzzy jet size adds additional information to conventional jet tagging variables in boosted topologies. Furthermore, we study the impact of pileup and show that with some slight modifications to the algorithm, fuzzy jets can be stable up to high pileup interaction multiplicities.

  15. Fuzzy jets

    DOE PAGESBeta

    Mackey, Lester; Nachman, Benjamin; Schwartzman, Ariel; Stansbury, Conrad

    2016-06-01

    Here, collimated streams of particles produced in high energy physics experiments are organized using clustering algorithms to form jets . To construct jets, the experimental collaborations based at the Large Hadron Collider (LHC) primarily use agglomerative hierarchical clustering schemes known as sequential recombination. We propose a new class of algorithms for clustering jets that use infrared and collinear safe mixture models. These new algorithms, known as fuzzy jets , are clustered using maximum likelihood techniques and can dynamically determine various properties of jets like their size. We show that the fuzzy jet size adds additional information to conventional jet taggingmore » variables in boosted topologies. Furthermore, we study the impact of pileup and show that with some slight modifications to the algorithm, fuzzy jets can be stable up to high pileup interaction multiplicities.« less

  16. Photon + jets at D0

    SciTech Connect

    Sonnenschein, Lars; /RWTH Aachen U.

    2009-06-01

    Photon plus jet production has been studied by the D0 experiment in Run II of the Fermilab Tevatron Collider at a centre of mass energy of {radical}s = 1.96 TeV. Measurements of the inclusive photon, inclusive photon plus jet, photon plus heavy flavour jet cross sections and double parton interactions in photon plus three jet events are presented. They are based on integrated luminosities between 0.4 fb{sup -1} and 1.0 fb{sup -1}. The results are compared to perturbative QCD calculations in various approximations.

  17. Search for vector-like quark production in the lepton+jets and dilepton+jets final states using 5.4 fb-1 of Run II data

    SciTech Connect

    Caughron, Seth

    2011-01-01

    The Standard Model of particle physics provides an excellent description of particle interactions at energies up to ~1 TeV, but it is expected to fail above that scale. Multiple models developed to describe phenomena above the TeV scale predict the existence of very massive, vector-like quarks. A search for single electroweak production of such particles in p$\\bar{p}$ collisions at a center-of-mass energy of 1.96 TeV is performed in the W+jets and Z+jets channels. The data were collected by the DØ detector at the Fermilab Tevatron Collider and correspond to an integrated luminosity of 5.4 fb-1. Events consistent with a heavy object decaying to a vector boson and a jet are selected. We observe no significant excess in comparison to the background prediction and set 95% confidence level upper limits on production cross sections for vector-like quarks decaying to W+jet and Z+jet. Assuming a vector-like quark -- standard model quark coupling parameter $\\tilde{κ}$qQ of unity, we exclude vector-like quarks with mass below 693 GeV for decays to W+jet and mass below 449 GeV for decays to Z+jet. These represent the most sensitive limits to date.

  18. Explosive Nucleosynthesis in Magnetohydrodynamical Jets from Collapsars. II --- Heavy-Element Nucleosynthesis of s, p, r-Processes

    NASA Astrophysics Data System (ADS)

    Ono, M.; Hashimoto, M.; Fujimoto, S.; Kotake, K.; Yamada, S.

    2012-10-01

    We investigate the nucleosynthesis in a massive star of 70 M_{⊙} with solar metallicity in the main sequence stage. The helium core mass after hydrogen burning corresponds to 32 M_{⊙}. Nucleosynthesis calculations have been performed during the stellar evolution and the jetlike supernova explosion of a collapsar model. We focus on the production of elements heavier than iron group nuclei. Nucleosynthesis calculations have been accomplished consistently from hydrostatic to dynamic stages by using large nuclear reaction networks, where the weak s-, p-, and r-processes are taken into account. We confirm that s-elements of 60 < A < 90 are highly overproduced relative to the solar abundances in the hydrostatic nucleosynthesis. During oxygen burning, p-elements of A > 90 are produced via photodisintegrations of seed s-elements. However, the produced p-elements are disintegrated in later stages except for ^{180}Ta. In the explosive nucleosynthesis, elements of 90 < A < 160 are significantly overproduced relative to the solar values owing to the r-process, which is very different from the results of spherical explosion models. Only heavy p-elements (N > 50) are overproduced via the p-process because of the low peak temperatures in the oxygen- and neon-rich layers. Compared with the previous study of r-process nucleosynthesis calculations in the collapsar model of 40 M_{⊙} by Fujimoto et al. [S. Fujimoto, M. Hashimoto, K. Kotake and S. Yamada, Astrophys. J. 656 (2007), 382; S. Fujimoto, N. Nishimura and M. Hashimoto, Astrophys. J. 680 (2008), 1350], our jet model cannot contribute to the third peak of the solar r-elements and intermediate p-elements, which have been much produced because of the distribution of the lowest part of electron fraction in the ejecta. Averaging the overproduction factors over the progenitor masses with the use of Salpeter's IMF, we suggest that the 70 M_{⊙} star could contribute to the solar weak s}-elements of 60 < A < 90 and neutron

  19. Falciparum malaria parasites invade erythrocytes that lack glycophorin A and B (MkMk). Strain differences indicate receptor heterogeneity and two pathways for invasion.

    PubMed Central

    Hadley, T J; Klotz, F W; Pasvol, G; Haynes, J D; McGinniss, M H; Okubo, Y; Miller, L H

    1987-01-01

    To determine the ligands on erythrocytes for invasion by Plasmodium falciparum, we tested invasion into MkMk erythrocytes that lack glycophorins A and B and enzyme-treated erythrocytes by parasites that differ in their requirement for erythrocyte sialic acid. The 7G8 strain invaded MkMk erythrocytes and neuraminidase-treated normal erythrocytes with greater than 50% the efficiency of normal erythrocytes. In contrast, the Camp strain invaded MkMk erythrocytes at 20% of control and neuraminidase-treated normal erythrocytes at only 1.8% of control. Invasion of MkMk erythrocytes by 7G8 parasites was unaffected by treatment with neuraminidase but was markedly reduced by treatment with trypsin. In contrast, invasion of MkMk cells by Camp parasites was markedly reduced by neuraminidase but was unaffected by trypsin. We conclude that the 7G8 and Camp strains differ in ligand requirements for invasion and that 7G8 requires a trypsin sensitive ligand distinct from glycophorins A and B. Images PMID:3308959

  20. Inclusive jet production at the Tevatron

    SciTech Connect

    Norniella, Olga; /Barcelona, IFAE

    2006-08-01

    Preliminary results on inclusive jet production in proton-antiproton collisions at {radical}s = 1.96 TeV based on 1 fb{sup -1} of CDF Run II data are presented. Measurements are preformed using different jet algorithms in a wide range of jet transverse momentum and jet rapidity. The measured cross sections are compared to next-to-leading order perturbative QCD calculations

  1. Triggering on electrons, jets and tau leptons with the CMS upgraded calorimeter trigger for the LHC RUN II

    NASA Astrophysics Data System (ADS)

    Zabi, A.; Beaudette, F.; Cadamuro, L.; Mastrolorenzo, L.; Romanteau, T.; Sauvan, J. B.; Strebler, T.; Marrouche, J.; Wardle, N.; Aggleton, R.; Ball, F.; Brooke, J.; Newbold, D.; Paramesvaran, S.; Smith, D.; Baber, M.; Bundock, A.; Citron, M.; Elwood, A.; Hall, G.; Iles, G.; Laner, C.; Penning, B.; Rose, A.; Tapper, A.; Durkin, T.; Harder, K.; Harper, S.; Shepherd-Themistocleous, C.; Thea, A.; Williams, T.

    2016-02-01

    The Compact Muon Solenoid (CMS) experiment has implemented a sophisticated two-level online selection system that achieves a rejection factor of nearly 105. During Run II, the LHC will increase its centre-of-mass energy up to 13 TeV and progressively reach an instantaneous luminosity of 2 × 1034 cm-2 s-1. In order to guarantee a successful and ambitious physics programme under this intense environment, the CMS Trigger and Data acquisition (DAQ) system has been upgraded. A novel concept for the L1 calorimeter trigger is introduced: the Time Multiplexed Trigger (TMT) . In this design, nine main processors receive each all of the calorimeter data from an entire event provided by 18 preprocessors. This design is not different from that of the CMS DAQ and HLT systems. The advantage of the TMT architecture is that a global view and full granularity of the calorimeters can be exploited by sophisticated algorithms. The goal is to maintain the current thresholds for calorimeter objects and improve the performance for their selection. The performance of these algorithms will be demonstrated, both in terms of efficiency and rate reduction. The callenging aspects of the pile-up mitigation and firmware design will be presented.

  2. Search for Third Generation Squarks in the Missing Transverse Energy plus Jet Sample at CDF Run II

    SciTech Connect

    Marono, Miguel Vidal

    2010-03-01

    lightest SUSY particle (LSP) which would provide a candidate for cold dark matter, that account for 23% of the universe content, as strongly suggested by recent astrophysical data [1]. The Tevatron is a hadron collider operating at Fermilab, USA. This accelerator provides proton-antiproton (p$\\bar{p}$) collisions with a center of mass energy of √s = 1.96 TeV. CDF and D0 are the detectors built to analyse the products of the collisions provided by the Tevatron. Both experiments have produced a very significant scientific output in the last few years, like the discovery of the top quark or the measurement of the Bs mixing. The Tevatron experiments are also reaching sensitivity to the SM Higgs boson. The scientific program of CDF includes a broad spectrum on searches for physics signatures beyond the Standard Model. Tevatron is still the energy frontier, what means an unique opportunity to produce a discovery in physic beyond the Standard Model. The analyses presented in this thesis focus on the search for third generation squarks in the missing transverse energy plus jets final state. The production of sbottom ($\\tilde{b}$) and stop ($\\tilde{t}$) quarks could be highly enhanced at the Tevatron, giving the possibility of discovering new physics or limiting the parameter space available in the theory. No signal is found over the predicted Standard Model background in both searches. Instead, 95% confidence level limits are set on the production cross section, and then translated into the mass plane of the hypothetical particles. This thesis sketches the basic theory concepts of the Standard Model and the Minimal Supersymmetric Extension in Chapter 2. Chapter 3, describes the Tevatron and CDF. Based on the CDF subsystems information, Chapter 4 and 5 describe the analysis objet reconstruction and the heavy flavor tagging tools. The development of the analyses is shown in Chapter 6 and Chapter 7. Finally, Chapter 8 is devoted to discuss the results and conclusions

  3. Discovery of MK-7246, a selective CRTH2 antagonist for the treatment of respiratory diseases.

    PubMed

    Gallant, Michel; Beaulieu, Christian; Berthelette, Carl; Colucci, John; Crackower, Michael A; Dalton, Chad; Denis, Danielle; Ducharme, Yves; Friesen, Richard W; Guay, Daniel; Gervais, François G; Hamel, Martine; Houle, Robert; Krawczyk, Connie M; Kosjek, Birgit; Lau, Stephen; Leblanc, Yves; Lee, Ernest E; Levesque, Jean-François; Mellon, Christophe; Molinaro, Carmela; Mullet, Wayne; O'Neill, Gary P; O'Shea, Paul; Sawyer, Nicole; Sillaots, Susan; Simard, Daniel; Slipetz, Deborah; Stocco, Rino; Sørensen, Dan; Truong, Vouy Linh; Wong, Elizabeth; Wu, Jin; Zaghdane, Helmi; Wang, Zhaoyin

    2011-01-01

    In this manuscript we wish to report the discovery of MK-7246 (4), a potent and selective CRTH2 (DP2) antagonist. SAR studies leading to MK-7246 along with two synthetic sequences enabling the preparation of this novel class of CRTH2 antagonist are reported. Finally, the pharmacokinetic and metabolic profile of MK-7246 is disclosed. PMID:21106375

  4. Cosmic jets

    SciTech Connect

    Blandford, R.D.; Begelman, M.C.; Rees, M.J.

    1982-05-01

    Observations with radio telescopes have revealed that the center of many galaxies is a place of violent activity. This activity is often manifested in the production of cosmic jets. Each jet is a narrow stream of plasma that appears to squirt out of the center of a galaxy emitting radiowaves as it does so. New techniques in radio astronomy have shown how common jets are in the universe. These jets take on many different forms. The discovery of radio jets has helped in the understanding of the double structure of the majority of extragalactic radio sources. The morphology of some jets and explanations of how jets are fueled are discussed. There are many difficulties plaguing the investigation of jets. Some of these difficulties are (1) it is not known how much power the jets are radiating, (2) it is hard to tell whether a jet delieated by radio emission is identical to the region where ionized gas is flowing, and (3) what makes them. (SC)

  5. MK3 Modulation Affects BMI1-Dependent and Independent Cell Cycle Check-Points

    PubMed Central

    Dahlmans, Vivian E. H.; Spaapen, Frank; Salvaing, Juliette; Vanhove, Jolien; Geijselaers, Claudia; Bartels, Stefanie J. J.; Partouns, Iris; Neumann, Dietbert; Speel, Ernst-Jan; Takihara, Yoshihiro; Wouters, Bradly G.; Voncken, Jan Willem

    2015-01-01

    Although the MK3 gene was originally found deleted in some cancers, it is highly expressed in others. The relevance of MK3 for oncogenesis is currently not clear. We recently reported that MK3 controls ERK activity via a negative feedback mechanism. This prompted us to investigate a potential role for MK3 in cell proliferation. We here show that overexpression of MK3 induces a proliferative arrest in normal diploid human fibroblasts, characterized by enhanced expression of replication stress- and senescence-associated markers. Surprisingly, MK3 depletion evokes similar senescence characteristics in the fibroblast model. We previously identified MK3 as a binding partner of Polycomb Repressive Complex 1 (PRC1) proteins. In the current study we show that MK3 overexpression results in reduced cellular EZH2 levels and concomitant loss of epigenetic H3K27me3-marking and PRC1/chromatin-occupation at the CDKN2A/INK4A locus. In agreement with this, the PRC1 oncoprotein BMI1, but not the PCR2 protein EZH2, bypasses MK3-induced senescence in fibroblasts and suppresses P16INK4A expression. In contrast, BMI1 does not rescue the MK3 loss-of-function phenotype, suggesting the involvement of multiple different checkpoints in gain and loss of MK3 function. Notably, MK3 ablation enhances proliferation in two different cancer cells. Finally, the fibroblast model was used to evaluate the effect of potential tumorigenic MK3 driver-mutations on cell proliferation and M/SAPK signaling imbalance. Taken together, our findings support a role for MK3 in control of proliferation and replicative life-span, in part through concerted action with BMI1, and suggest that the effect of MK3 modulation or mutation on M/SAPK signaling and, ultimately, proliferation, is cell context-dependent. PMID:25853770

  6. Jet maximization, axis minimization, and stable cone finding

    NASA Astrophysics Data System (ADS)

    Thaler, Jesse

    2015-10-01

    Jet finding is a type of optimization problem, where hadrons from a high-energy collision event are grouped into jets based on a clustering criterion. As three interesting examples, one can form a jet cluster that (i) optimizes the overall jet four-vector, (ii) optimizes the jet axis, or (iii) aligns the jet axis with the jet four-vector. In this paper, we show that these three approaches to jet finding, despite being philosophically quite different, can be regarded as descendants of a mother optimization problem. For the special case of finding a single cone jet of fixed opening angle, the three approaches are genuinely identical when defined appropriately, and the result is a stable cone jet with the largest value of a quantity J . This relationship is only approximate for cone jets in the rapidity-azimuth plane, as used at the Large Hadron Collider, though the differences are mild for small radius jets.

  7. Water Jetting

    NASA Technical Reports Server (NTRS)

    1985-01-01

    Hi-Tech Inc., a company which manufactures water jetting equipment, needed a high pressure rotating swivel, but found that available hardware for the system was unsatisfactory. They were assisted by Marshall, which had developed water jetting technology to clean the Space Shuttles. The result was a completely automatic water jetting system which cuts rock and granite and removes concrete. Labor costs have been reduced; dust is suppressed and production has been increased.

  8. Cosmic jets

    NASA Technical Reports Server (NTRS)

    Rees, M. J.

    1986-01-01

    The evidence that active galactic nuclei produce collimated plasma jets is summarised. The strongest radio galaxies are probably energised by relativistic plasma jets generated by spinning black holes interacting with magnetic fields attached to infalling matter. Such objects can produce e(+)-e(-) plasma, and may be relevant to the acceleration of the highest-energy cosmic ray primaries. Small-scale counterparts of the jet phenomenon within our own galaxy are briefly reviewed.

  9. Osmotic stress induces the phosphorylation of WNK4 Ser575 via the p38MAPK-MK pathway

    PubMed Central

    Maruyama, Junichi; Kobayashi, Yumie; Umeda, Tsuyoshi; Vandewalle, Alain; Takeda, Kohsuke; Ichijo, Hidenori; Naguro, Isao

    2016-01-01

    The With No lysine [K] (WNK)-Ste20-related proline/alanine-rich kinase (SPAK)/oxidative stress-responsive kinase 1 (OSR1) pathway has been reported to be a crucial signaling pathway for triggering pseudohypoaldosteronism type II (PHAII), an autosomal dominant hereditary disease that is characterized by hypertension. However, the molecular mechanism(s) by which the WNK-SPAK/OSR1 pathway is regulated remain unclear. In this report, we identified WNK4 as an interacting partner of a recently identified MAP3K, apoptosis signal-regulating kinase 3 (ASK3). We found that WNK4 is phosphorylated in an ASK3 kinase activity-dependent manner. By exploring the ASK3-dependent phosphorylation sites, we identified Ser575 as a novel phosphorylation site in WNK4 by LC-MS/MS analysis. ASK3-dependent WNK4 Ser575 phosphorylation was mediated by the p38MAPK-MAPK-activated protein kinase (MK) pathway. Osmotic stress, as well as hypotonic low-chloride stimulation, increased WNK4 Ser575 phosphorylation via the p38MAPK-MK pathway. ASK3 was required for the p38MAPK activation induced by hypotonic stimulation but was not required for that induced by hypertonic stimulation or hypotonic low-chloride stimulation. Our results suggest that the p38MAPK-MK pathway might regulate WNK4 in an osmotic stress-dependent manner but its upstream regulators might be divergent depending on the types of osmotic stimuli. PMID:26732173

  10. p38MAPK/MK2-mediated phosphorylation of RBM7 regulates the human nuclear exosome targeting complex

    PubMed Central

    Lubas, Michal; Tehrani, Mohammad; Menon, Manoj B.; Ronkina, Natalia; Rousseau, Simon; Cohen, Philip; Kotlyarov, Alexey

    2015-01-01

    The nuclear exosome targeting complex (NEXT) directs a major 3′–5′ exonuclease, the RNA exosome, for degradation of nuclear noncoding (nc) RNAs. We identified the RNA-binding component of the NEXT complex, RBM7, as a substrate of p38MAPK/MK2-mediated phosphorylation at residue S136. As a result of this phosphorylation, RBM7 displays a strongly decreased RNA-binding capacity, while inhibition of p38MAPK or mutation of S136A in RBM7 increases its RNA association. Interestingly, promoter-upstream transcripts (PROMPTs), such as proRBM39, proEXT1, proDNAJB4, accumulated upon stress stimulation in a p38MAPK/MK2-dependent manner, a process inhibited by overexpression of RBM7S136A. While there are no stress-dependent changes in RNA-polymerase II (RNAPII) occupation of PROMPT regions representing unchanged transcription, stability of PROMPTs is increased. Hence, we propose that phosphorylation of RBM7 by the p38MAPK/MK2 axis increases nuclear ncRNA stability by blocking their RBM7-binding and subsequent RNA exosome targeting to allow stress-dependent modulations of the noncoding transcriptome. PMID:25525152

  11. Unconditional jetting.

    PubMed

    Gañán-Calvo, Alfonso M

    2008-08-01

    Capillary jetting of a fluid dispersed into another immiscible phase is usually limited by a critical capillary number, a function of the Reynolds number and the fluid property ratios. Critical conditions are set when the minimum spreading velocity of small perturbations v_{-};{*} along the jet (marginal stability velocity) is zero. Here we identify and describe parametric regions of high technological relevance, where v_{-};{*}>0 and the jet flow is always supercritical independently of the dispersed liquid flow rate; within these relatively broad regions, the jet does not undergo the usual dripping-jetting transition, so that either the jet can be made arbitrarily thin (yielding droplets of any imaginably small size), or the issuing flow rate can be made arbitrarily small. In this work, we provide illustrative analytical studies of asymptotic cases for both negligible and dominant inertia forces. In this latter case, requiring a nonzero jet surface velocity, axisymmetric perturbation waves "surf" downstream for all given wave numbers, while the liquid bulk can remain static. In the former case (implying small Reynolds flow) we found that the jet profile small slope is limited by a critical value; different published experiments support our predictions. PMID:18850933

  12. Isolation of the Entomopathogenic Fungal Strain Cod-MK1201 from a Cicada Nymph and Assessment of Its Antibacterial Activities.

    PubMed

    Sangdee, Kusavadee; Nakbanpote, Woranan; Sangdee, Aphidech

    2015-01-01

    The entomopathogenic fungus Cod-MK1201 was isolated from a dead cicada nymph. Three regions of ribosomal nuclear DNA, the internal transcribed spacers of nuclear ribosomal DNA repeats (ITS), the partial small subunit of rDNA (nrSSU) , and the partial large subunit of rDNA (nrLSU), and two protein-coding regions, the elongation factor 1α (EF-1α), and the largest subunit of the RNA polymerase II (rpb1) gene, were sequenced and used for fungal identification. The phylogenetic analysis of the ITS and the combined data set of the five genes indicated that the fungal isolate Cod-MK1201 is a new strain of Cordyceps sp. that is closely related to Cordyceps nipponica and C. kanzashiana. Crude extracts of mycelium-cultured Cod-MK1201 were obtained using distilled water and 50% (v/v) ethanol, and the antibacterial activity of each was determined. Both extracts had activity against Gram-positive and Gram-negative bacteria, but the ethanol extract was the more potent of the two. The antibacterial activity of the protein fractions of these extracts was also determined. The protein fraction from the ethanol extract was more antibacterial than the protein fraction from the aqueous extract. Three antibacterial constituents including adenosine, the total phenolic content (TPC), and the total flavonoid content (TFC) was also determined. The results showed that the adenosine content, the TPC, and the TFC of the ethanol extract were more active than those of the aqueous extract. Moreover, synergism was detected between these antibacterial constituents. In conclusion, the entomopathogenic fungal isolate Cod-MK1201 represents a natural source of antibacterial agents. PMID:25746406

  13. Inclusive jet production using the kt algorithm

    SciTech Connect

    Norniella, Olga; /Barcelona, IFAE

    2006-05-01

    Results on inclusive jet production using the k{sub T} algorithm in proton-antiproton collisions at {radical}s = 1.96 TeV are presented, based on 1 fb{sup -1} of CDF Run II data. The measurements are carried out for jets with p{sub T}{sup jet} > 54 GeV/c in five different jet rapidity regions up to |y{sub jet}| = 2.1. The measured cross sections are corrected to the hadron level and compared to next-to-leading order perturbative QCD predictions (NLO pQCD).

  14. Hot Electrons and Energy Transport in Metals at MK Temperatures.

    NASA Astrophysics Data System (ADS)

    Roukes, Michael Lee

    Using a new technique involving the generation of hot carriers, we directly measure energy loss lifetimes for electrons in impure metals at mK temperatures. At these temperatures very weak inelastic scattering processes determine energy transport out of the electron gas. A temperature difference between the electron gas and the lattice can be induced by applying an extremely small electric field (of order 1 (mu)V/cm at 25 mK). This temperature difference reflects the rate at which electrons lose energy to the surroundings. The experiment is carried out using a pair of interdigitated thin film resistors mounted on a millidegree demagnetization cryostat: we obtain electron temperature directly by observing current fluctuations. Noise generated by the resistors is measured using an ultra-sensitive two -channel dc SQUID system, providing femtoamp resolution at KHz frequencies. A dc voltage applied across one resistor imposes the bias field causing electron heating. Phonon temperature in the metal lattice is obtained by measuring noise from a second (unbiased) resistor, which is tightly coupled thermally to the first (biased). Our measurements show that electron heating follows an E('2/5) power law in the regime where electron temperature is largely determined by the electric field, E. This implies a T('-3) law for the energy loss lifetime, suggesting electron -acoustic phonon processes dominate. In the mK temperature regime the conductivity is impurity limited and remains ohmic, even as the electrons heat. Assuming a T('3) dependence and extrapolating our measured rates to higher temperatures, we find agreement with electron-phonon rates measured above 1K in clean bulk metals. This contrasts with results from weak localization experiments showing a power law differing from T('3) and much faster rates. This difference arises because weak localization experiments measure the electron phase coherence lifetime; our electron heating experiments, however, measure an energy

  15. Investigation of rocket motors 3 inch number 1 Mk 4

    NASA Astrophysics Data System (ADS)

    Barrington, L. M.

    1994-05-01

    In 1992, Aircraft Research and Development Unit (ARDU), RAAF, experienced two misfires with Rocket Motors, 3 in., No. 1, Mk 4, during a series of firings at Woomera. These motors were sampled from a batch manufactured in 1957, and subsequent to the misfires this batch was withdrawn from use. An alternate batch of motors manufactured in 1966 was available to ARDU. Tests were conducted on a number of these motors to advise on their suitability for use, and as a result, a further five years life was assigned with a recommendation to retest after that period.

  16. Equilibrium shape of (4)He crystal under zero gravity below 200 mK.

    PubMed

    Takahashi, Takuya; Ohuchi, Haruka; Nomura, Ryuji; Okuda, Yuichi

    2015-10-01

    Equilibrium crystal shape is the lowest energy crystal shape that is hardly realized in ordinary crystals because of their slow relaxation. (4)He quantum crystals in a superfluid have been expected as unique exceptions that grow extremely fast at very low temperatures. However, on the ground, gravity considerably deforms the crystals and conceals the equilibrium crystal shape, and thus, gravity-free environment is needed to observe the equilibrium shape of (4)He. We report the relaxation processes of macroscopic (4)He crystals in a superfluid below 200 mK under zero gravity using a parabolic flight of a jet plane. When gravity was removed from a gravity-flattened (4)He crystal, the crystal rapidly transformed into a shape with flat surfaces. Although the relaxation processes were highly dependent on the initial condition, the crystals relaxed to a nearly homothetic shape in the end, indicating that they were truly in an equilibrium shape minimizing the interfacial free energy. Thanks to the equilibrium shape, we were able to determine the Wulff's origin and the size of the c-facet together with the vicinal surface profile next to the c-facet. The c-facet size was extremely small in the quantum crystals, and the facet-like flat surfaces were found to be the vicinal surfaces. At the same time, the interfacial free energy of the a-facet and s-facet was also obtained. PMID:26601315

  17. Equilibrium shape of 4He crystal under zero gravity below 200 mK

    PubMed Central

    Takahashi, Takuya; Ohuchi, Haruka; Nomura, Ryuji; Okuda, Yuichi

    2015-01-01

    Equilibrium crystal shape is the lowest energy crystal shape that is hardly realized in ordinary crystals because of their slow relaxation. 4He quantum crystals in a superfluid have been expected as unique exceptions that grow extremely fast at very low temperatures. However, on the ground, gravity considerably deforms the crystals and conceals the equilibrium crystal shape, and thus, gravity-free environment is needed to observe the equilibrium shape of 4He. We report the relaxation processes of macroscopic 4He crystals in a superfluid below 200 mK under zero gravity using a parabolic flight of a jet plane. When gravity was removed from a gravity-flattened 4He crystal, the crystal rapidly transformed into a shape with flat surfaces. Although the relaxation processes were highly dependent on the initial condition, the crystals relaxed to a nearly homothetic shape in the end, indicating that they were truly in an equilibrium shape minimizing the interfacial free energy. Thanks to the equilibrium shape, we were able to determine the Wulff’s origin and the size of the c-facet together with the vicinal surface profile next to the c-facet. The c-facet size was extremely small in the quantum crystals, and the facet-like flat surfaces were found to be the vicinal surfaces. At the same time, the interfacial free energy of the a-facet and s-facet was also obtained. PMID:26601315

  18. MK2 Deletion in Mice Prevents Diabetes-Induced Perturbations in Lipid Metabolism and Cardiac Dysfunction.

    PubMed

    Ruiz, Matthieu; Coderre, Lise; Lachance, Dominic; Houde, Valérie; Martel, Cécile; Thompson Legault, Julie; Gillis, Marc-Antoine; Bouchard, Bertrand; Daneault, Caroline; Carpentier, André C; Gaestel, Matthias; Allen, Bruce G; Des Rosiers, Christine

    2016-02-01

    Heart disease remains a major complication of diabetes, and the identification of new therapeutic targets is essential. This study investigates the role of the protein kinase MK2, a p38 mitogen-activated protein kinase downstream target, in the development of diabetes-induced cardiomyopathy. Diabetes was induced in control (MK2(+/+)) and MK2-null (MK2(-/-)) mice using repeated injections of a low dose of streptozotocin (STZ). This protocol generated in MK2(+/+) mice a model of diabetes characterized by a 50% decrease in plasma insulin, hyperglycemia, and insulin resistance (IR), as well as major contractile dysfunction, which was associated with alterations in proteins involved in calcium handling. While MK2(-/-)-STZ mice remained hyperglycemic, they showed improved IR and none of the cardiac functional or molecular alterations. Further analyses highlighted marked lipid perturbations in MK2(+/+)-STZ mice, which encompass increased 1) circulating levels of free fatty acid, ketone bodies, and long-chain acylcarnitines and 2) cardiac triglyceride accumulation and ex vivo palmitate β-oxidation. MK2(-/-)-STZ mice were also protected against all these diabetes-induced lipid alterations. Our results demonstrate the benefits of MK2 deletion on diabetes-induced cardiac molecular and lipid metabolic changes, as well as contractile dysfunction. As a result, MK2 represents a new potential therapeutic target to prevent diabetes-induced cardiac dysfunction. PMID:26558681

  19. Experiment on performance of adjustable jet pump

    NASA Astrophysics Data System (ADS)

    Zhu, J. M.; Long, X. P.; Zhang, S. B.; Lu, X.

    2012-11-01

    When the water level of upper or lower reaches of hydraulic power station changes, the adjustable jet pump which is different from traditional fixed jet pump can maintain stable pressure and flow rate for the system of technical water supply of hydraulic power plant. The model test indicates that the efficiency of the adjustable jet pump is slightly lower than fixed jet pump near rating operation point. With the decrease of opening degree, both efficiencies are more and more close to each other. The fundamental performance of I-type adjustable jet pump is better than II-type and the cavitation performance of I-type adjustable jet pump is worse than II-type. Test data also indicate that the performance of adjustable jet pump is very different from fixed jet pump, so the theory of fixed jet pump is not able to be copied to adjustable jet pump. It is necessary to farther study on the performance of the adjustable jet pump. This paper has reference value for analogous design of system of circulation water supply to turbine units in hydraulic power station.

  20. CaMK4 Gene Deletion Induces Hypertension

    PubMed Central

    Santulli, Gaetano; Cipolletta, Ersilia; Sorriento, Daniela; Del Giudice, Carmine; Anastasio, Antonio; Monaco, Sara; Maione, Angela Serena; Condorelli, Gianluigi; Puca, Annibale; Trimarco, Bruno; Illario, Maddalena; Iaccarino, Guido

    2012-01-01

    Background The expression of calcium/calmodulin-dependent kinase IV (CaMKIV) was hitherto thought to be confined to the nervous system. However, a recent genome-wide analysis indicated an association between hypertension and a single-nucleotide polymorphism (rs10491334) of the human CaMKIV gene (CaMK4), which suggests a role for this kinase in the regulation of vascular tone. Methods and Results To directly assess the role of CaMKIV in hypertension, we characterized the cardiovascular phenotype of CaMK4−/− mice. They displayed a typical hypertensive phenotype, including high blood pressure levels, cardiac hypertrophy, vascular and kidney damage, and reduced tolerance to chronic ischemia and myocardial infarction compared with wild-type littermates. Interestingly, in vitro experiments showed the ability of this kinase to activate endothelial nitric oxide synthase. Eventually, in a population study, we found that the rs10491334 variant associates with a reduction in the expression levels of CaMKIV in lymphocytes from hypertensive patients. Conclusions Taken together, our results provide evidence that CaMKIV plays a pivotal role in blood pressure regulation through the control of endothelial nitric oxide synthase activity. (J Am Heart Assoc. 2012;1:e001081 doi: 10.1161/JAHA.112.001081.) PMID:23130158

  1. Giant Radio Sources as a Probe of the Cosmological Evolution of the IGM. II. The Observational Constraint on the Model of Radio-Jets Propagation through the X-ray Halo-IGM Interface

    NASA Astrophysics Data System (ADS)

    Kuligowska, E.; Jamrozy, M.; Koziel-Wierzbowska, D.; Machalski, J.

    2009-12-01

    Three limited samples of high-redshift radio sources of FRII-type are used to constrain the dynamical model for the jets' propagation through the two-media environment: the X-ray emitting halo with the power-law density profile surrounding the parent galaxy and the much hotter intergalactic medium (IGM) of a constant density. The model, originally developed by Gopal-Krishna and Wiita, is modified adopting modern values of its free parameters taken from recent X-ray measurements with the XMM-Newton and Chandra Observatories. We find that (i) giant-sized radio sources (≍1 Mpc) exist at redshifts up to z≍2, (ii) all newly identified the largest radio sources with 1jets than peculiar environmental conditions (e.g., voids) in the IGM. The extreme powerful jets may testify to a dominant role of the accretion processes onto black holes in earlier cosmological epochs.

  2. MHD simulations of NSNS mergers in full GR: the role of the initial B field on the emergence of sGRB jets II

    NASA Astrophysics Data System (ADS)

    Lang, Ryan; Paschalidis, Vasileios; Ruiz, Milton; Shapiro, Stuart

    2016-03-01

    Mergers of neutron star-neutron star (NSNS) binaries are among the most promising candidates for the engines that power short gamma-ray bursts (sGRBs). The most likely sGRB model requires the presence of a highly relativistic jet. However, recent relativistic simulations of NSNS mergers have shown that it is difficult for such jets to emerge following the delayed collapse of the hypermassive neutron star (HMNS) remnant. Varying the initial NS magnetic field in an NSNS binary, we have performed magnetohydrodynamic simulations in full general relativity that explore the formation of jets from the black hole-disk system following the HMNS collapse. In this talk we focus on initial dipole magnetic fields which extend from the neutron star interior into the exterior.

  3. 2,4-Diaminopyrimidine MK2 inhibitors. Part I: Observation of an unexpected inhibitor binding mode

    SciTech Connect

    Argiriadi, Maria A.; Ericsson, Anna M.; Harris, Christopher M.; Banach, David L.; Borhani, David W.; Calderwood, David J.; Demers, Megan D.; DiMauro, Jennifer; Dixon, Richard W.; Hardman, Jennifer; Kwak, Silvia; Li, Biqin; Mankovich, John A.; Marcotte, Douglas; Mullen, Kelly D.; Ni, Baofu; Pietras, M.; Sadhukhan, Ramkrishna; Sousa, Silvino; Tomlinson, Medha J.; Wang, L.; Xiang, T.; Talanian, R.V.

    2010-09-17

    MK2 is a Ser/Thr kinase of significant interest as an anti-inflammatory drug discovery target. Here we describe the development of in vitro tools for the identification and characterization of MK2 inhibitors, including validation of inhibitor interactions with the crystallography construct and determination of the unique binding mode of 2,4-diaminopyrimidine inhibitors in the MK2 active site.

  4. Jet-Induced Star Formation

    SciTech Connect

    van Breugel, W; Fragile, C; Anninos, P; Murray, S

    2003-12-16

    Jets from radio galaxies can have dramatic effects on the medium through which they propagate. We review observational evidence for jet-induced star formation in low ('FR-I') and high ('FR-II') luminosity radio galaxies, at low and high redshifts respectively. We then discuss numerical simulations which are aimed to explain a jet-induced starburst ('Minkowski's Object') in the nearby FR-I type radio galaxy NGC 541. We conclude that jets can induce star formation in moderately dense (10 cm{sup -3}), warm (10{sup 4} K) gas; that this may be more common in the dense environments of forming, active galaxies; and that this may provide a mechanism for 'positive' feedback from AGN in the galaxy formation process.

  5. Synthetic Jets

    NASA Technical Reports Server (NTRS)

    Milanovic, Ivana M.

    2003-01-01

    Current investigation of synthetic jets and synthetic jets in cross-flow examined the effects of orifice geometry and dimensions, momentum-flux ratio, cluster of orifices, pitch and yaw angles as well as streamwise development of the flow field. This comprehensive study provided much needed experimental information related to the various control strategies. The results of the current investigation on isolated and clustered synthetic jets with and without cross-flow will be further analyzed and documented in detail. Presentations at national conferences and publication of peer- reviewed journal articles are also expected. Projected publications will present both the mean and turbulent properties of the flow field, comparisons made with the data available in an open literature, as well as recommendations for the future work.

  6. STS-42 Commander Grabe uses DTO 653 MK1 Rowing Machine on OV-103's middeck

    NASA Technical Reports Server (NTRS)

    1992-01-01

    STS-42 Commander Ronald J. Grabe exercises using MK1 Rowing Machine on the middeck of Discovery, Orbiter Vehicle (OV) 103. Grabe is using the exercise device as part of Development Test Objective (DTO) 653, Evaluation of MK1 Rowing Machine. The forward lockers appear at Grabe's right and the sleep station behind him.

  7. MK2 inhibitor reduces alkali burn-induced inflammation in rat cornea

    PubMed Central

    Chen, Yanfeng; Yang, Wenzhao; Zhang, Xiaobo; Yang, Shu; Peng, Gao; Wu, Ting; Zhou, Yueping; Huang, Caihong; Reinach, Peter S.; Li, Wei; Liu, Zuguo

    2016-01-01

    MK2 activation by p38 MAPK selectively induces inflammation in various diseases. We determined if a MK2 inhibitor (MK2i), improves cornea wound healing by inhibiting inflammation caused by burning rat corneas with alkali. Our study, for the first time, demonstrated that MK2i inhibited alkali burn-induced MK2 activation as well as rises in inflammation based on: a) blunting rises in inflammatory index, inflammatory cell infiltration, ED1+ macrophage and PMN+ neutrophil infiltration; b) suppressing IL-6 and IL-1β gene expression along with those of macrophage inflammatory protein-1α (MIP-1α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1); c) reducing angiogenic gene expression levels and neovascularization (NV) whereas anti-angiogenic PEDF levels increased. In addition, this study found that MK2i did not affect human corneal epithelial cell (HCEC) proliferation and migration and had no detectable side effects on ocular surface integrity. Taken together, MK2i selectively inhibited alkali burn-induced corneal inflammation by blocking MK2 activation, these effects have clinical relevance in the treatment of inflammation related ocular surface diseases. PMID:27329698

  8. Structure-based lead identification of ATP-competitive MK2 inhibitors.

    PubMed

    Barf, Tjeerd; Kaptein, Allard; de Wilde, Sander; van der Heijden, Ruud; van Someren, Richard; Demont, Dennis; Schultz-Fademrecht, Carsten; Versteegh, Judith; van Zeeland, Mario; Seegers, Nicole; Kazemier, Bert; van de Kar, Bas; van Hoek, Maaike; de Roos, Jeroen; Klop, Henri; Smeets, Ruben; Hofstra, Claudia; Hornberg, Jorrit; Oubrie, Arthur

    2011-06-15

    MK2 kinase is a promising drug discovery target for the treatment of inflammatory diseases. Here, we describe the discovery of novel MK2 inhibitors using X-ray crystallography and structure-based drug design. The lead has in vivo efficacy in a short-term preclinical model. PMID:21565500

  9. Benzothiophene inhibitors of MK2. Part 2: Improvements in kinase selectivity and cell potency

    SciTech Connect

    Anderson, David R.; Meyers, Marvin J.; Kurumbail, Ravi G.; Caspers, Nicole; Poda, Gennadiy I.; Long, Scott A.; Pierce, Betsy S.; Mahoney, Matthew W.; Mourey, Robert J.; Parikh, Mihir D.; Pfizer

    2010-10-01

    Optimization of kinase selectivity for a set of benzothiophene MK2 inhibitors provided analogs with potencies of less than 500 nM in a cell based assay. The selectivity of the inhibitors can be rationalized by examination of X-ray crystal structures of inhibitors bound to MK2.

  10. {sup 3}He melting pressure temperature scale below 25 mK

    SciTech Connect

    Adams, E.D.; Ni, W.; Xia, J.S.

    1995-04-01

    Using {sup 60}Co {gamma} ray anisotropy radiation as a primary thermometer, with a Pt NMR susceptibility secondary thermometer, the authors have made high precision measurements of the {sup 3}He melting pressure versus temperature from 500 {mu}K to 25 mK. Temperatures obtained for the fixed points on the melting curve are: the superfluid A transition T{sub A} = 2.505 mK, the A-B transition T{sub AB} = 1.948 mK, and the solid ordering temperature T{sub N} = 0.934 mK. The authors provide a functional form for P(T), which, with the fixed points, constitutes a convenient temperature scale, based on a primary thermometer, usable to well below 1 mK.

  11. Measurement of the top quark mass using the template method in the lepton plus jets channel with in situ W ---> j j calibration at CDF-II

    SciTech Connect

    Adelman, Jahred A.; Arguin, J.F.; Bellettini, G.; Brubaker, E.; Budagov, J.; Chlachidze, G.; Demortier, L.; Gibson, A.; Kim, S.; Kim, Y.K.; Maruyama, T.; Sato, K.; Shochet, M.; Sinervo, P.; Tomura, T.; Velev, G.; Xie, S.; Yang, U.K.; /Chicago U. /Toronto U. /INFN, Pisa /Dubna, JINR /Rockefeller U. /LBL, Berkeley /Tsukuba U. /Fermilab

    2006-05-01

    We report an updated measurement of the top quark mass in the lepton plus jets channel of t{bar t} events from p{bar p} collisions at {radical}s = 1.96 TeV. This measurement uses a dataset with integrated luminosity of 680 pb{sup -1}, containing 360 t{bar t} candidates separated into four subsamples. A top quark mass is reconstructed for each event by using energy and momentum constraints on the top quark pair decay products. We also employ the reconstructed mass of hadronic W boson decays W {yields} jj to constrain in situ the largest systematic uncertainty of the top quark mass measurement: the jet energy scale. Monte Carlo templates of the reconstructed top quark and W boson mass are produced as a function of the true top quark mass and the jet energy scale. The distribution of reconstructed top quark and W boson mass in the data are compared to the Monte Carlo templates using a likelihood fit to obtain: M{sub top} = 173.4 {+-} 2.8 GeV/c{sup 2}.

  12. CONSTRAINING THE PHYSICAL CONDITIONS IN THE JETS OF γ-RAY FLARING BLAZARS USING CENTIMETER-BAND POLARIMETRY AND RADIATIVE TRANSFER SIMULATIONS. II. EXPLORING PARAMETER SPACE AND IMPLICATIONS

    SciTech Connect

    Hughes, Philip A.; Aller, Margo F.; Aller, Hugh D. E-mail: mfa@umich.edu

    2015-02-01

    We analyze the shock-in-jet models for the γ-ray flaring blazars 0420-014, OJ 287, and 1156+295 presented in Paper I, quantifying how well the modeling constrains internal properties of the flow (low-energy spectral cutoff, partition between random and ordered magnetic field), the flow dynamics (quiescent flow speed and orientation), and the number and strength of the shocks responsible for radio-band flaring. We conclude that well-sampled, multifrequency polarized flux light curves are crucial for defining source properties. We argue for few, if any, low-energy particles in these flows, suggesting no entrainment and efficient energization of jet material, and for approximate energy equipartition between the random and ordered magnetic field components, suggesting that the ordered field is built by nontrivial dynamo action from the random component, or that the latter arises from a jet instability that preserves the larger-scale, ordered flow. We present evidence that the difference between orphan radio-band (no γ-ray counterpart) and non-orphan flares is due to more complex shock interactions in the latter case.

  13. Constraining the Physical Conditions in the Jets of γ-Ray Flaring Blazars Using Centimeter-band Polarimetry and Radiative Transfer Simulations. II. Exploring Parameter Space and Implications

    NASA Astrophysics Data System (ADS)

    Hughes, Philip A.; Aller, Margo F.; Aller, Hugh D.

    2015-02-01

    We analyze the shock-in-jet models for the γ-ray flaring blazars 0420-014, OJ 287, and 1156+295 presented in Paper I, quantifying how well the modeling constrains internal properties of the flow (low-energy spectral cutoff, partition between random and ordered magnetic field), the flow dynamics (quiescent flow speed and orientation), and the number and strength of the shocks responsible for radio-band flaring. We conclude that well-sampled, multifrequency polarized flux light curves are crucial for defining source properties. We argue for few, if any, low-energy particles in these flows, suggesting no entrainment and efficient energization of jet material, and for approximate energy equipartition between the random and ordered magnetic field components, suggesting that the ordered field is built by nontrivial dynamo action from the random component, or that the latter arises from a jet instability that preserves the larger-scale, ordered flow. We present evidence that the difference between orphan radio-band (no γ-ray counterpart) and non-orphan flares is due to more complex shock interactions in the latter case.

  14. Behavioural sensitisation to MK-801 is dose-dependent and independent of environmental context.

    PubMed

    Lefevre, Emilia M; Eyles, Darryl W; Burne, Thomas H J

    2016-02-01

    The pathophysiology of schizophrenia is associated with disturbed glutamate signalling, particularly via a dysfunction of the N-methyl-d-aspartate (NMDA) receptor. In rodents, behavioural sensitisation to the NMDA receptor antagonist MK-801 is proposed to recapitulate aspects of the NMDA receptor hypofunction hypothesis of schizophrenia. The aim of this study was to determine the modulatory role of MK-801 dose and environmental context on the development and expression of MK-801-induced behavioural sensitisation. Sprague Dawley rats were administered saline or varying doses of MK-801 (i.p.) once daily for 7 days and locomotor activity was recorded. After 5 days of withdrawal, rats were challenged with their respective dose to test for sensitisation. From this experiment a sensitising dose was obtained. In the second experiment the magnitude of sensitisation was compared between rats that were treated in either a home or test environmental context. Rats treated with 0.25mg/kg MK-801 developed robust sensitisation when challenged after withdrawal. Rats treated with lower (0.1mg/kg) or higher (0.5mg/kg) doses of MK-801 did not develop locomotor sensitisation. Sensitisation to 0.25mg/kg MK-801 developed equally between rats treated in the home or test context. The study shows that male Sprague Dawley rats develop behavioural sensitisation to repeated injections of MK-801. The development of sensitisation is selective to MK-801 dose in an inverted-U dose response fashion. In this paradigm MK-801 induced sensitisation was expressed similarly between groups treated in two distinct environmental contexts. PMID:26593108

  15. Normal cadmium uptake in microcytic anemia mk/mk mice suggests that DMT1 is not the only cadmium transporter in vivo

    SciTech Connect

    Suzuki, Tomohito; Momoi, Kanae; Hosoyamada, Makoto Kimura, Masaki; Shibasaki, Toshiaki

    2008-03-15

    Divalent metal transporter 1 (DMT1) is a mammalian iron (Fe) transporter and also transports Cadmium (Cd) in vitro. This study compared Cd absorption in DMT1-dysfunctional MK/Rej-{sup mk}/{sub mk} mice (mk/mk mice) and in DMT1-functional, Fe-deficient wild-type (WT) mice, to clarify the role of DMT1 in intestinal Cd absorption in vivo. Mice were given 1 ppm CdCl{sub 2} aq in drinking water for 2 weeks, and the concentrations of Cd and Fe in liver, kidney, and intestinal epithelium were subsequently determined. The Fe concentration in intestinal epithelia of WT mice was decreased in proportion to the level of dietary Fe limitation, while Cd accumulation under the same conditions was increased. DMT1 mRNA expression in the small intestine of Fe-deficient WT mice was clearly increased compared to that in Fe-sufficient WT mice. Iron deficiency resulted in up-regulation of Cd uptake in the intestine of Fe-deficient WT mice. The mk/mk mice have a mutation in DMT1 and loss of its function led to decreased intestinal Fe concentration. However, intestinal Cd accumulation was the same as in WT mice and it was also increased in Fe-deficient situation. There is the possibility that an unknown Cd pathway has taken a role on Cd intestinal absorption in vivo and that this pathway is regulated by food Fe concentrations. Therefore, DMT1 is not the sole transporter of intestinal cadmium absorption in vivo.

  16. Jet Dipolarity: Top Tagging with Color Flow

    SciTech Connect

    Hook, Anson; Jankowiak, Martin; Wacker, Jay G.; /SLAC

    2011-08-12

    A new jet observable, dipolarity, is introduced that can distinguish whether a pair of subjets arises from a color singlet source. This observable is incorporated into the HEPTopTagger and is shown to improve discrimination between top jets and QCD jets for moderate to high p{sub T}. The impressive resolution of the ATLAS and CMS detectors means that a typical QCD jet at the LHC deposits energy in {Omicron}(10-100) calorimeter cells. Such fine-grained calorimetry allows for jets to be studied in much greater detail than previously, with sophisticated versions of current techniques making it possible to measure more than just the bulk properties of jets (e.g. event jet multiplicities or jet masses). One goal of the LHC is to employ these techniques to extend the amount of information available from each jet, allowing for a broader probe of the properties of QCD. The past several years have seen significant progress in developing such jet substructure techniques. A number of general purpose tools have been developed, including: (i) top-tagging algorithms designed for use at both lower and higher p{sub T} as well as (ii) jet grooming techniques such as filtering, pruning, and trimming, which are designed to improve jet mass resolution. Jet substructure techniques have also been studied in the context of specific particle searches, where they have been shown to substantially extend the reach of traditional search techniques in a wide variety of scenarios, including for example boosted Higgses, neutral spin-one resonances, searches for supersymmetry, and many others. Despite these many successes, however, there is every reason to expect that there remains room for refinement of jet substructure techniques.

  17. The PIT MkV pulsed inductive thruster

    NASA Technical Reports Server (NTRS)

    Dailey, C. Lee; Lovberg, Ralph H.

    1993-01-01

    The pulsed inductive thruster (PIT) is an electrodeless, magnetic rocket engine that can operate with any gaseous propellant. A puff of gas injected against the face of a flat (spiral) coil is ionized and ejected by the magnetic field of a fast-rising current pulse from a capacitor bank discharge. Single shot operation on an impulse balance has provided efficiency and I(sub sp) data that characterize operation at any power level (pulse rate). The 1-m diameter MkV thruster concept offers low estimated engine mass at low powers, together with power capability up to more than 1 MW for the 1-m diameter design. A 20 kW design estimate indicates specific mass comparable to Ion Engine specific mass for 10,000 hour operation, while a 100,000 hour design would have a specific mass 1/3 that of the Ion Engine. Performance data are reported for ammonia and hydrazine. With ammonia, at 32 KV coil voltage, efficiency is a little more than 50 percent from 4000 to more than 8000 seconds I(sub sp). Comparison with data at 24 and 28 kV indicates that a wider I(sub sp) range could be achieved at higher coil voltages, if required for deep space missions.

  18. Identification of Statistical Invariance for Anodic Signals of Mk-IV Electrorefiner

    SciTech Connect

    Supathorn Phongikaroon; Tae-Sic Yoo

    2007-09-01

    A statistical invariance technique is proposed for an analysis of anodic signals from the Mk-IV electrorefiner (ER) currently used for treating spent EBR-II fuel. Voltage and applied current signals obtained from the Data Archival Software System (DASS) were used in this study. In general, the plots of these signals from different experimental runs present complex patterns to analyze—the currents were adjusted and shut-off due to limited ampere-hr or cut-off cell voltage; the voltage would increase showing a sign that uranium in the fuel elements had been depleted. Rather than directly analyzing these sets of time-series signals, a simple nonlinear function of these signal sequences and division were observed, which returned resistance series information. The primary idea deriving the methodology presented in this paper is that “anodic resistance time series should show intrinsic kinetic progress of anodic ER process.” A simple histogram-based analysis reveals notable statistical information, which may be invariant under ideal ER operating conditions. For instance, the results suggest that mostly uranium dissolution would be preferentially transferred around 0.00217 - 0.00354 ohm and other minor distribution peaks may possibly represent other transfers of fission species in the system.

  19. Decline in Age-dependent, MK801-induced Injury Coincides With Developmental Switch in Parvalbumin Expression: Somatosensory and Motor Cortex

    PubMed Central

    Tomé, Carla M Lema; Miller, Ryan; Bauer, Clayton; Smith, Chelsey; Blackstone, Kaitlin; Leigh, Adam; Busch, Jamie; Turner, Christopher P

    2009-01-01

    MK801-induced activation of caspase-3 is developmentally regulated, peaking at postnatal day (P) 7 and decreasing with increasing postnatal age thereafter. Further, at P7, cells displaying activation of caspase-3 lack expression of calcium binding proteins (CaBPs). To further explore this relationship, we investigated postnatal expression of calbindin (CB), calretinin (CR) and parvalbumin (PV) in two brain regions susceptible to MK801-induced injury, the somatosensory cortex (S1) and layer II/III of motor cortex (M1/M2). Expression of CB and especially PV was low to absent prior to P7 but substantially increased from P7 through to P21 and adulthood. In contrast, CR expression was more variable at early developmental ages, stabilized to lower levels after P7 and showed a marked decline by P21. The results suggest that not only does calcium buffering capacity increase developmentally but acquisition of enhanced buffering may be one mechanism by which neurons survive agent-induced alterations in calcium homeostasis. PMID:18688810

  20. The effect of high curing temperature on the reaction kinetics in MK/lime and MK-blended cement matrices at 60 deg. C

    SciTech Connect

    Rojas, Moises Frias; Sanchez de Rojas, M.I

    2003-05-01

    It is well known that the pozzolanic reaction between metakaolin (MK) and calcium hydroxide produces CSH, C{sub 2}ASH{sub 8} (stratlingite), C{sub 4}AH{sub 13} and C{sub 3}ASH{sub 6} (hydrogarnet). However, the presence or absence of these hydrated phases depends on different parameters, such as curing temperature, matrix used, etc. This paper shows the results of a study in order to know the effect of high curing temperature (60 deg. C) on the kinetics of the pozzolanic reaction in different matrices. MK/lime (calcium hydroxide) and MK-blended cement matrices were studied in samples stored and cured at 60 deg. C and up to 123 days of hydration. The nature, sequence and crystallinity of the hydrated phases were analysed using differential thermal analysis (DTA) and X-ray diffraction (XRD) techniques. Results showed that the sequence and formation of the hydrated phases was different in both matrices cured at 60 deg. C. In an MK/lime matrix, C{sub 2}ASH{sub 8}, C{sub 4}AH{sub 13} and C{sub 3}ASH{sub 6} were the main hydrated phases; while in an MK-blended cement, stratlingite was the sole hydrated phase issued from pozzolanic reaction. The DTA and XRD data also reveal an important fact: there is no evidence of the presence of hydrogarnet in blended cements.

  1. Reactive Transformation and Increased BDNF Signaling by Hippocampal Astrocytes in Response to MK-801

    PubMed Central

    Wang, Yueming; Li, Guanjun; Wang, Lihua; Li, Huafang

    2015-01-01

    MK-801, also known as dizocilpine, is a noncompetitive N-methyl-D-aspartic acid (NMDA) receptor antagonist that induces schizophrenia-like symptoms. While astrocytes have been implicated in the pathophysiology of psychiatric disorders, including schizophrenia, astrocytic responses to MK-801 and their significance to schizotypic symptoms are unclear. Changes in the expression levels of glial fibrillary acid protein (GFAP), a marker of astrocyte activation in response to a variety of pathogenic stimuli, were examined in the hippocampus of rats treated with the repeated MK-801 injection (0.5 mg/10ml/kg body weight for 6 days) and in primary cultured hippocampal astrocytes incubated with MK-801 (5 or 20 μM for 24 h). Moreover, the expression levels of BDNF and its receptors TrkB and p75 were examined in MK-801-treated astrocyte cultures. MK-801 treatment enhanced GFAP expression in the rat hippocampus and also increased the levels of GFAP protein and mRNA in hippocampal astrocytes in vitro. Treatment of cultured hippocampal astrocytes with MK-801 enhanced protein and mRNA levels of BDNF, TrkB, and p75. Collectively, our results suggest that hippocampal astrocytes may contribute to the pathophysiology of schizophrenia symptoms associated with NMDA receptor hypofunction by reactive transformation and altered BDNF signaling. PMID:26700309

  2. Effects of MK-467 on the antinociceptive and sedative actions and pharmacokinetics of medetomidine in dogs.

    PubMed

    Bennett, R C; Salla, K M; Raekallio, M R; Hänninen, L; Rinne, V M; Scheinin, M; Vainio, O M

    2016-08-01

    We investigated the influence of the peripherally acting α2 -adrenoceptor antagonist MK-467 on the sedative and antinociceptive actions and plasma drug concentrations of medetomidine, an α2 -adrenoceptor agonist that is used in veterinary medicine as a sedative and analgesic agent. Eight healthy beagle dogs received intravenous medetomidine (10 μg/kg) or medetomidine with MK-467 (250 μg/kg) in a randomized crossover design. A standardized nociceptive pressure stimulus was applied to a nail bed of a hindlimb. Times for withdrawal of the limb and for head lift were measured, and sedation was scored. EEG data were collected prior to and after stimulation. Plasma drug concentrations were measured. Co-administration of MK-467 significantly attenuated medetomidine analgesia, as assessed with limb withdrawal, and also shortened the duration of sedation. The apparent plasma clearance of both enantiomers of medetomidine, dexmedetomidine and levomedetomidine, was more than doubled in the presence of MK-467. Antagonism by MK-467 of medetomidine-evoked vasoconstriction is seen as the mechanism behind this pharmacokinetic drug interaction. Thus, MK-467 attenuated the antinociceptive and sedative effects of medetomidine. This can probably be explained by increased clearance and decreased concentrations of dexmedetomidine in plasma after co-administration of MK-467 with racemic medetomidine. PMID:26763145

  3. New insights into the activation, interaction partners and possible functions of MK5/PRAK.

    PubMed

    Perander, Maria; Keyse, Stephen M; Seternes, Ole-Morten

    2016-01-01

    MAP kinase-activated protein kinase 5 (MK5) was first described as a downstream target of the p38 MAP kinase pathway leading to its alternative acronym of p38-regulated/activated protein kinase (PRAK). However, since the discovery that MK5 is a bona fide interaction partner of the atypical MAP kinases ERK3 and ERK4 and that this interaction leads to both the activation and subcellular relocalisation of MK5, there has been considerable debate as to the relative roles of these MAPK pathways in mediating the activation and biological functions of MK5. Here we discuss recent progress in defining novel upstream components of the ERK3/ERK4 signalling pathway, our increased understanding of the mechanism by which MK5 interacts with and is activated by ERK3 and ERK4, and the discovery of novel interaction partners for MK5. Finally, we review recent literature that suggests novel biological functions for MK5 in a range of physiological and pathophysiological conditions including neuronal function and cancer. PMID:26709779

  4. Differential Effects of Olanzapine and Haloperidol on MK-801-induced Memory Impairment in Mice

    PubMed Central

    Song, Jae Chun; Seo, Mi Kyoung; Park, Sung Woo; Lee, Jung Goo; Kim, Young Hoon

    2016-01-01

    Objective We investigated the differential effects of the antipsychotic drugs olanzapine and haloperidol on MK-801-induced memory impairment and neurogenesis in mice. Methods MK-801 (0.1 mg/kg) was administered 20 minutes prior to behavioral testing over 9 days. Beginning on the sixth day of MK-801 treatment, either olanzapine (0.05 mg/kg) or haloperidol (0.05 mg/kg) was administered 40 minutes prior to MK-801 for the final 4 days. Spatial memory performance was measured using a Morris water maze (MWM) test for 9 days (four trials/day). Immunohistochemistry with bromodeoxyuridine (BrdU) was used to identify newborn cells labeled in tissue sections from the dentate gyrus of the hippocampus. Results MK-801 administration over 9 days significantly impaired memory performance in the MWM test compared to untreated controls (p<0.05) and these deficits were blocked by treatment with olanzapine (p<0.05) but not haloperidol. The administration of MK-801 also resulted in a decrease in the number of BrdU-labeled cells in the dentate gyrus (28.6%; p<0.01), which was prevented by treatment with olanzapine (p<0.05) but not haloperidol. Conclusion These results suggest that olanzapine has a protective effect against cognitive impairments induced by MK-801 in mice via the stimulating effects of neurogenesis. PMID:27489382

  5. MK2: an unrecognized regulator of tumor promoting macrophages in colorectal cancer?

    PubMed Central

    Castillo, Eliseo F.; Ray, Anita L.; Beswick, Ellen J.

    2016-01-01

    Colorectal cancer (CRC) is one of the most common malignancies and is associated closely with inflammation before and after development. Macrophages promote colitis and colitis-associated CRC. M1 macrophages contribute to colitis directly through the production of proinflammatory cytokines and through activation of proinflammatory immune cell phenotypes. In cancer, both M1 and M2 macrophages participate in tumor development and progression through cytokine production, changes in cell signaling and activation of T cells. We have identified the mitogen-activated protein kinase-activated protein kinase 2 (MK2) as a regulator of macrophages during colitis-associated CRC (CAC). MK2 is a proinflammatory kinase that promotes production of IL-1α, IL-1β, IL-6 and TNF-α. MK2−/− mice have decreases in macrophages, macrophage-associated chemokines, and proinflammatory cytokines. Most significantly, MK2−/− mice do not develop neoplasms in an inflammatory model of CRC. However, addition of MK2+/+ macrophages to MK2−/− mice increases production of proinflammatory cytokines. In wild type mice, both cytokines and tumor burdens increase upon addition of additional macrophages. These data support the importance of MK2 in macrophage regulation during inflammation-associated CRC. PMID:26998523

  6. Interaction of the NMDA receptor noncompetitive antagonist MK-801 with model and native membranes.

    PubMed Central

    Moring, J; Niego, L A; Ganley, L M; Trumbore, M W; Herbette, L G

    1994-01-01

    MK-801, a noncompetitive antagonist of the NMDA (N-methyl-D-aspartate) receptor, has protective effects against excitotoxicity and ethanol withdrawal seizures. We have determined membrane/buffer partition coefficients (Kp[mem]) of MK-801 and its rates of association with and dissociation from membranes. Kp[mem] (+/- SD) = 1137 (+/- 320) in DOPC membranes and 485 (+/- 99) in synaptoneurosomal (SNM) lipid membranes from rat cerebral cortex (unilamellar vesicles). In multilamellar vesicles, Kp[mem] was higher: 3374 (+/- 253) in DOPC and 6879 (+/- 947) in SNM. In cholesterol/DOPC membranes, Kp[mem] decreased as the cholesterol content increased. MK-801 associated with and dissociated from membranes rapidly. Addition of ethanol to SNM did not affect Kp[mem]. MK-801 decreased the cooperative unit size of DMPC membranes. The decrease was smaller than that caused by 1,4-dihydropyridine drugs, indicating a weaker interaction with the hydrocarbon core. Small angle x-ray diffraction, with multilayer autocorrelation difference function modeling, indicated that MK-801 in a cholesterol/DOPC membrane (mole ratio = 0.6) causes a perturbation at approximately 16.0 A from the bilayer center. In bilayers of cholesterol/DOPC = 0.15 (mole ratio) or pure DOPC, the perturbation caused by MK-801 was more complex. The physical chemical interactions of MK-801 with membranes in vitro are consistent with a fast onset and short duration of action in vivo. PMID:7696477

  7. NAAG peptidase inhibitors block cognitive deficit induced by MK-801 and motor activation induced by d-amphetamine in animal models of schizophrenia.

    PubMed

    Olszewski, R T; Janczura, K J; Ball, S R; Madore, J C; Lavin, K M; Lee, J C-M; Lee, M J; Der, E K; Hark, T J; Farago, P R; Profaci, C P; Bzdega, T; Neale, J H

    2012-01-01

    The most widely validated animal models of the positive, negative and cognitive symptoms of schizophrenia involve administration of d-amphetamine or the open channel NMDA receptor blockers, dizocilpine (MK-801), phencyclidine (PCP) and ketamine. The drug ZJ43 potently inhibits glutamate carboxypeptidase II (GCPII), an enzyme that inactivates the peptide transmitter N-acetylaspartylglutamate (NAAG) and reduces positive and negative behaviors induced by PCP in several of these models. NAAG is an agonist at the metabotropic glutamate receptor 3 (mGluR3). Polymorphisms in this receptor have been associated with expression of schizophrenia. This study aimed to determine whether two different NAAG peptidase inhibitors are effective in dopamine models, whether their efficacy was eliminated in GCPII knockout mice and whether the efficacy of these inhibitors extended to MK-801-induced cognitive deficits as assessed using the novel object recognition test. ZJ43 blocked motor activation when given before or after d-amphetamine treatment. (R,S)-2-phosphono-methylpentanedioic acid (2-PMPA), another potent NAAG peptidase inhibitor, also reduced motor activation induced by PCP or d-amphetamine. 2-PMPA was not effective in GCPII knockout mice. ZJ43 and 2-PMPA also blocked MK-801-induced deficits in novel object recognition when given before, but not after, the acquisition trial. The group II mGluR antagonist LY341495 blocked the effects of NAAG peptidase inhibition in these studies. 2-PMPA was more potent than ZJ43 in a test of NAAG peptidase inhibition in vivo. By bridging the dopamine and glutamate theories of schizophrenia with two structurally different NAAG peptidase inhibitors and demonstrating their efficacy in blocking MK-801-induced memory deficits, these data advance the concept that NAAG peptidase inhibition represents a potentially novel antipsychotic therapy. PMID:22850437

  8. In Vitro Characterization of MK-1439, a Novel HIV-1 Nonnucleoside Reverse Transcriptase Inhibitor

    PubMed Central

    Feng, Meizhen; Falgueyret, Jean-Pierre; Tawa, Paul; Witmer, Marc; DiStefano, Daniel; Li, Yuan; Burch, Jason; Sachs, Nancy; Lu, Meiqing; Cauchon, Elizabeth; Campeau, Louis-Charles; Grobler, Jay; Yan, Youwei; Ducharme, Yves; Côté, Bernard; Asante-Appiah, Ernest; Hazuda, Daria J.; Miller, Michael D.

    2014-01-01

    Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are a mainstay of therapy for treating human immunodeficiency type 1 virus (HIV-1)-infected patients. MK-1439 is a novel NNRTI with a 50% inhibitory concentration (IC50) of 12, 9.7, and 9.7 nM against the wild type (WT) and K103N and Y181C reverse transcriptase (RT) mutants, respectively, in a biochemical assay. Selectivity and cytotoxicity studies confirmed that MK-1439 is a highly specific NNRTI with minimum off-target activities. In the presence of 50% normal human serum (NHS), MK-1439 showed excellent potency in suppressing the replication of WT virus, with a 95% effective concentration (EC95) of 20 nM, as well as K103N, Y181C, and K103N/Y181C mutant viruses with EC95 of 43, 27, and 55 nM, respectively. MK-1439 exhibited similar antiviral activities against 10 different HIV-1 subtype viruses (a total of 93 viruses). In addition, the susceptibility of a broader array of clinical NNRTI-associated mutant viruses (a total of 96 viruses) to MK-1439 and other benchmark NNRTIs was investigated. The results showed that the mutant profile of MK-1439 was superior overall to that of efavirenz (EFV) and comparable to that of etravirine (ETR) and rilpivirine (RPV). Furthermore, E138K, Y181C, and K101E mutant viruses that are associated with ETR and RPV were susceptible to MK-1439 with a fold change (FC) of <3. A two-drug in vitro combination study indicated that MK-1439 acts nonantagonistically in the antiviral activity with each of 18 FDA-licensed drugs for HIV infection. Taken together, these in vitro data suggest that MK-1439 possesses the desired properties for further development as a new antiviral agent. PMID:24379202

  9. Jets in air-jet family

    NASA Technical Reports Server (NTRS)

    Navia, C. E.; Sawayanagi, K.

    1985-01-01

    The A-jet families on Chacaltaya emulsion chamber experiments were analyzed by the study of jets which are reconstructed by a grouping procedure. It is demonstrated that large-E sub J R sub J events are characterized by small number of jets and two-jet like asymmetric shape, binocular events and the other type. This type has a larger number of jets and more symmetrical shape in the P sub t plane.

  10. Marine Jet

    NASA Technical Reports Server (NTRS)

    1978-01-01

    The marine turbine pump pictured is the Jacuzzi 12YJ, a jet propulsion system for pleasure or commercial boating. Its development was aided by a NASA computer program made available by the Computer Software Management and Information Center (COSMIC) at the University of Georgia. The manufacturer, Jacuzzi Brothers, Incorporated, Little Rock, Arkansas, used COSMIC'S Computer Program for Predicting Turbopump Inducer Loading, which enabled substantial savings in development time and money through reduction of repetitive testing.

  11. Weak-value thermostat with 0.2 mK precision.

    PubMed

    Egan, Patrick; Stone, Jack A

    2012-12-01

    A new laser-based thermostat sensitive to 0.2 mK at room temperature is reported. The method utilizes a fluid-filled prism and interferometric weak-value amplification to sense nanoradian deviations of a laser beam: due to the high thermo-optic coefficient of the fluid (colorless fluorocarbon), the deviation angle through the prism is sensitive to temperature. We estimate the daily stability of our device to be 0.2 mK, which is limited by drifts in the apparatus, and the narrow 20 mK capture range is the price paid for the weak measurement. PMID:23202114

  12. The role of purinergic and dopaminergic systems on MK-801-induced antidepressant effects in zebrafish.

    PubMed

    da Silva, Raquel Bohrer; Siebel, Anna Maria; Bonan, Carla Denise

    2015-12-01

    Depression is a serious disease characterized by low mood, anhedonia, loss of interest in daily activities, appetite and sleep disturbances, reduced concentration, and psychomotor agitation. There is a growing interest in NMDA antagonists as a promising target for the development of new antidepressants. Considering that purinergic and dopaminergic systems are involved in depression and anxiety states, we characterized the role of these signaling pathways on MK-801-induced antidepressant effects in zebrafish. Animals treated with MK-801 at the doses of 5, 10, 15, or 20μM during 15, 30, or 60min spent longer time in the top area of aquariums in comparison to control group, indicating an anxiolytic/antidepressant effect induced by this drug. Animals treated with MK-801 spent longer time period at top area until 2 (5μM MK-801) and 4 (20μM MK-801) hours after treatment, returning to basal levels from 24h to 7days after exposure. Repeated MK-801 treatment did not induce cumulative effects, since animals treated daily during 7days had the same behavioral response pattern observed since the first until the 7th day. In order to investigate the effects of adenosine A1 and A2A receptor antagonist and agonist and the influence of modulation of adenosine levels on MK-801 effects, we treated zebrafish with caffeine, DPCPX, CPA, ZM 241385, CGS 21680, AMPCP, EHNA, dipyridamole, and NBTI during 30min before MK-801 exposure. The non-specific adenosine receptor antagonist caffeine (50mg/kg) and the selective A1 receptor antagonist DPCPX (15mg/kg) prevented the behavioral changes induced by MK-801. The non-specific nucleoside transporter (NT) inhibitor dipyridamole (10mg/kg) exacerbated the behavioral changes induced by MK-801. Dopamine receptor antagonists (sulpiride and SCH 23390) did not change the behavioral alterations induced by MK-801. Our findings demonstrated that antidepressant-like effects of MK-801 in zebrafish are mediated through adenosine A1 receptor activation. PMID

  13. Filament Eruptions, Jets, and Space Weather

    NASA Technical Reports Server (NTRS)

    Moore, Ronald; Sterling, Alphonse; Robe, Nick; Falconer, David; Cirtain, Jonathan

    2013-01-01

    Previously, from chromospheric H alpha and coronal X-ray movies of the Sun's polar coronal holes, it was found that nearly all coronal jets (greater than 90%) are one or the other of two roughly equally common different kinds, different in how they erupt: standard jets and blowout jets (Yamauchi et al 2004, Apl, 605, 5ll: Moore et all 2010, Apj, 720, 757). Here, from inspection of SDO/AIA He II 304 A movies of 54 polar x-ray jets observed in Hinode/XRT movies, we report, as Moore et al (2010) anticipated, that (1) most standard x-ray jets (greater than 80%) show no ejected plasma that is cool enough (T is less than or approximately 10(exp 5K) to be seen in the He II 304 A movies; (2) nearly all blownout X-ray jets (greater than 90%) show obvious ejection of such cool plasma; (3) whereas when cool plasma is ejected in standard X-ray jets, it shows no lateral expansion, the cool plasma ejected in blowout X-ray jets shows strong lateral expansion; and (4) in many blowout X-ray jets, the cool plasma ejection displays the erupting-magnetic-rope form of clasic filament eruptions and is thereby seen to be a miniature filament eruption. The XRT movies also showed most blowout X-ray jets to be larger and brighter, and hence to apparently have more energy, than most standard X-ray jets. These observations (1) confirm the dichotomy of coronal jets, (2) agree with the Shibata model for standard jets, and (3) support the conclusion of Moore et al (2010) that in blowout jets the magnetic-arch base of the jet erupts in the manner of the much larger magnetic arcades in which the core field, the field rooted along the arcade's polarity inversion line, is sheared and twisted (sigmoid), often carries a cool-plasma filament, and erupts to blowout the arcade, producing a CME. From Hinode/SOT Ca II movies of the polar limb, Sterling et al (2010, ApJ, 714, L1) found that chromospheric Type-II spicules show a dichotomy of eruption dynamics similar to that found here for the cool

  14. DAG/PKCδ and IP3/Ca2+/CaMK IIβ Operate in Parallel to Each Other in PLCγ1-Driven Cell Proliferation and Migration of Human Gastric Adenocarcinoma Cells, through Akt/mTOR/S6 Pathway

    PubMed Central

    Dai, Lianzhi; Zhuang, Luhua; Zhang, Bingchang; Wang, Fen; Chen, Xiaolei; Xia, Chun; Zhang, Bing

    2015-01-01

    Phosphoinositide specific phospholipase Cγ (PLCγ) activates diacylglycerol (DAG)/protein kinase C (PKC) and inositol 1,4,5-trisphosphate (IP3)/Ca2+/calmodulin-dependent protein kinase II (CaMK II) axes to regulate import events in some cancer cells, including gastric adenocarcinoma cells. However, whether DAG/PKCδ and IP3/Ca2+/CaMK IIβ axes are simultaneously involved in PLCγ1-driven cell proliferation and migration of human gastric adenocarcinoma cells and the underlying mechanism are not elucidated. Here, we investigated the role of DAG/PKCδ or CaMK IIβ in PLCγ1-driven cell proliferation and migration of human gastric adenocarcinoma cells, using the BGC-823 cell line. The results indicated that the inhibition of PKCδ and CaMK IIβ could block cell proliferation and migration of BGC-823 cells as well as the effect of inhibiting PLCγ1, including the decrease of cell viability, the increase of apoptotic index, the down-regulation of matrix metalloproteinase (MMP) 9 expression level, and the decrease of cell migration rate. Both DAG/PKCδ and CaMK IIβ triggered protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/S6 pathway to regulate protein synthesis. The data indicate that DAG/PKCδ and IP3/Ca2+/CaMK IIβ operate in parallel to each other in PLCγ1-driven cell proliferation and migration of human gastric adenocarcinoma cells through Akt/mTOR/S6 pathway, with important implication for validating PLCγ1 as a molecular biomarker in early gastric cancer diagnosis and disease surveillance. PMID:26633375

  15. Top Jets at the LHC

    SciTech Connect

    Almeida, L.G.; Lee, S.J.; Perez, G.; Sung, I.; Virzi, J.

    2008-10-06

    We investigatethe reconstruction of high pT hadronically-decaying top quarksat the Large Hadron Collider. One of the main challenges in identifying energetictop quarks is that the decay products become increasingly collimated. This reducesthe efficacy of conventional reconstruction methods that exploit the topology of thetop quark decay chain. We focus on the cases where the decay products of the topquark are reconstructed as a single jet, a"top-jet." The most basic"top-tag" methodbased on jet mass measurement is considered in detail. To analyze the feasibility ofthe top-tagging method, both theoretical and experimental aspects of the large QCDjet background contribution are examined. Based on a factorization approach, wederive a simple analytic approximation for the shape of the QCD jet mass spectrum.We observe very good agreement with the Monte Carlo simulation. We consider high pT tt bar production in the Standard Model as an example, and show that our theoretical QCD jet mass distributions can efficiently characterize the background via sideband analyses. We show that with 25 fb-1 of data, our approach allows us to resolve top-jets with pT _> 1 TeV, from the QCD background, and about 1.5 TeV top-jets with 100 fb-1, without relying on b-tagging. To further improve the significancewe consider jet shapes (recently analyzed in 0807.0234 [hep-ph]), which resolve thesubstructure of energy flow inside cone jets. A method of measuring the top quarkpolarization by using the transverse momentum of the bottom quark is also presented.The main advantages of our approach are: (i) the mass distributions are driven byfirst principle calculations, instead of relying solely on Monte Carlo simulation; (ii) for high pT jets (pT _> 1 TeV), IR-safe jet shape variables are robust against detectorresolution effects. Our analysis can be applied to other boosted massive particlessuch as the electroweak gauge bosons and the Higgs.

  16. Rapid single-flux-quantum circuits for low noise mK operation

    NASA Astrophysics Data System (ADS)

    Intiso, Samuel; Pekola, Jukka; Savin, Alexander; Devyatov, Ygor; Kidiyarova-Shevchenko, Anna

    2006-05-01

    Rapid single-flux-quantum (RSFQ) technology has been proposed as control electronics for superconducting quantum bits because of the material and working temperature compatibility. In this work, we consider practical aspects of RSFQ circuit design for low noise low power operation. At the working temperature of 20 mK and operational frequency of 2 GHz, dissipated power per junction is reduced to 25 pW by using 6 µA critical current junctions available at the Hypres and VTT low Jc fabrication process. To limit phonon temperature to 30 mK, a maximum of 40 junctions can be placed on a 5 mm × 5 mm chip. Electron temperature in resistive shunts of Josephson junctions is minimized by use of cooling fins, giving minimum electron temperatures of about 150 mK for the Hypres process and 70 mK for the VTT process.

  17. Pyrroloquinoline quinone prevents MK-801-induced stereotypical behavior and cognitive deficits in mice.

    PubMed

    Zhou, Xingqin; Chen, Quancheng; Hu, Xindai; Mao, Shishi; Kong, Yanyan

    2014-01-01

    Pyrroloquinoline quinone (PQQ), an essential nutrient, antioxidant, redox modulator, and nerve growth factor, prevents cognitive deficits associated with oxidative stress-induced neurodegeneration. Previous molecular imaging studies also demonstrate that PQQ binds to N-methyl D-aspartate (NMDA) receptors. In this study, we investigated the effects of PQQ on stereotypical behaviors and cognitive deficits induced by MK-801, a non-competitive NMDA antagonist used to model schizophrenia. Mice were given repeated injections of MK-801 (0.5mg/kg/d) and PQQ (0.2, 2.0, or 20 μg/kg/d) for 60 days. Behavior was evaluated using a variety of motor, social, and cognitive tests. We found that PQQ administration significantly attenuated MK-801-induced increases in stereotypical behavior and ataxia, suggesting a protective role of PQQ against MK-801-induced neuronal dysfunction and psychiatric disorders. Future studies are necessary to elucidate the underlying mechanisms of PQQ. PMID:24149067

  18. Mechanism of action of MK-401 against Fasciola hepatica: inhibition of phosphoglycerate kinase.

    PubMed

    Schulman, M D; Ostlind, D A; Valentino, D

    1982-03-01

    The effect of MK-401 (4-amino-6-trichloroethenyl 1,3-benzenedisulfonamide) on Fasciola hepatica phosphoglycerate kinase (EC 2.7.2.3) was investigated. MK-401 was a competitive inhibitor of both 3-phosphoglycerate and ATP and had a Ki of 0.29 mM. ATP, 1,3-diphosphoglycerate and MK-401 protected the Fasciola enzyme from inhibition by N-ethylmaleimide. Analogues of MK-401 with different substituents at the 6 position (R = Cl, CF3, C2 F3, C3 F7) were competitive inhibitors of both 3-phosphoglycerate and ATP and a good correlation between the Ki and in vivo activity of these analogues was observed. PMID:7088033

  19. Altitude Test Chamber Investigation of Performance of a 28-inch Ram-jet Engine II : Effects of Gutter Width and Blocked Area on Operating Range and Combustion Efficiency

    NASA Technical Reports Server (NTRS)

    Shillito, T B; Jones, W L; Kahn, R W

    1950-01-01

    Altitude-test-chamber investigation of effects of flame-holder blocked area and gutter width on performance of 28-inch diameter ram jet at simulated flight Mach number of 2.0 for altitudes from 40,000 to 55,000 feet was conducted at NACA Lewis laboratory. Ten flame holders investigated covered gutter widths from 1.00 to 2.50 inches and blocked areas from 40.5 to 62.0 percent of combustion-chamber area. Gutter width did not appreciably affect combustion efficiency. Increase in blocked area from 40 to 62 percent resulted in 5- to 10-percent increase in combustion efficiency. Increasing gutter width resulted in improvement in fuel-air-ratio operating range.

  20. Identification of peptides in wheat germ hydrolysate that demonstrate calmodulin-dependent protein kinase II inhibitory activity.

    PubMed

    Kumrungsee, Thanutchaporn; Akiyama, Sayaka; Guo, Jian; Tanaka, Mitsuru; Matsui, Toshiro

    2016-12-15

    Hydrolysis of wheat germ by proteases resulted in bioactive peptides that demonstrated an inhibitory effect against the vasoconstrictive Ca(2+)-calmodulin (CaM)-dependent protein kinase II (CaMK II). The hydrolysate by thermolysin (1.0wt%, 5h) showed a particularly potent CaMK II inhibition. As a result of mixed mode high-performance liquid chromatography of thermolysin hydrolysate with pH elution gradient ranging between 4.8 and 8.9, the fraction eluted at pH 8.9 was the most potent CaMK II inhibitor. From this fraction, Trp-Val and Trp-Ile were identified as CaMK II inhibitors. In Sprague-Dawley rats, an enhanced aortic CaMK II activity by 1μM phenylephrine was significantly (p<0.05) suppressed by 15-min incubation with 300μM Trp-Val or Trp-Ile. On the basis of Ca(2+)-chelating fluorescence and CaMK II activity assays, it was concluded that Trp-Val and Trp-Ile competed with Ca(2+)-CaM complex to bind to CaMK II with Ki values of 5.4 and 3.6μM, respectively. PMID:27451188

  1. Jet Propulsion Laboratory/NASA Lewis Research Center space qualified hybrid high temperature superconducting/semiconducting 7.4 GHz low-noise downconverter for NRL HTSSE-II program

    SciTech Connect

    Javadi, H.H.S.; Bowen, J.G.; Rascoe, D.L.; Romanofsky, R.R.; Bhasin, K.B.; Chorey, C.M.

    1996-07-01

    A deep space satellite downconverter receiver was proposed by Jet Propulsion Laboratory (JPL) and NASA Lewis Research Center (LeRC) for the Naval Research Laboratory`s (NRL) high temperature superconductivity space experiment, phase-II (HTSSE-II) program. Space qualified low-noise cryogenic downconverter receivers utilizing thin-film high temperature superconducting (HTS) passive circuitry and semiconductor active devices were developed and delivered to NRL. The downconverter consists of an HTS preselect filter, a cryogenic low-noise amplifier, a cryogenic mixer, and a cryogenic oscillator with an HTS resonator. HTS components were inserted as the front-end filter and the local oscillator resonator for their superior 77 K performance over the conventional components. The semiconducting low noise amplifier also benefited from cooling to 77 K. The mixer was designed specifically for cryogenic applications and provided low conversion loss and low power consumption. In addition to an engineering model, two space qualified units (qualification, flight) were built and delivered to NRL. Manufacturing, integration and test of the space qualified downconverters adhered to the requirements of JPL class-D space instruments and partially to MIL-STD-883D specifications. The qualification unit has {approximately}50 K system noise temperature which is a factor of three better than a conventional downconverter at room temperature.

  2. The effect of ghrelin on MK-801 induced memory impairment in rats.

    PubMed

    Goshadrou, Fatemeh; Kermani, Mojtaba; Ronaghi, Abdolaziz; Sajjadi, Samad

    2013-06-01

    Accumulating evidence indicates that the brain-gut peptide ghrelin which is expressed in hippocampus improves memory and learning processes. The MK-801, a noncompetitive NMDA receptor antagonist, has also shown amnesic properties in animal model. The current study was to find out whether intracerebroventricular administration of ghrelin can prevent amnesia induced by MK-801 in rats. A week after the surgery, during which cannuals were implanted in the lateral ventricular, the animals were trained and tested in a step-through type passive avoidance task. Memory retrieval was measured by step-through latency (STL) and total time in dark compartments (TDC). In the first series of experiments, we established a dose-response relationship for ghrelin on the passive avoidance paradigm. In the second set of experiments, animals were divided to two groups. In the first group, MK-801 (0.075, 0.15 and 0.3mg/kg) was injected intraperitoneally (i.p.) immediately after the acquisition session and in the second group MK-801 (same doses) was injected (i.p.) 30 min before the retention session. Analysis of data showed that in both groups, MK-801 impaired learning and memory. In the third set of experiments, administration of ghrelin (200 ng/rat) right after the acquisition session (i.e. before MK-801 injection) improved the MK-801 induced memory impairment, but administration of ghrelin before retrieval session did not affect the MK-801 induced memory impairment. These results show an interaction between ghrelin and glutamatergic system. A novel finding in this study is that ghrelin can prevent amnesia produced by NMDA antagonist in rats when injected in post-training phase. PMID:23538209

  3. Cholinesterase inhibitors ameliorate behavioral deficits induced by MK-801 in mice.

    PubMed

    Csernansky, John G; Martin, Maureen; Shah, Renu; Bertchume, Amy; Colvin, Jenny; Dong, Hongxin

    2005-12-01

    Enhancing cholinergic function has been suggested as a possible strategy for ameliorating the cognitive deficits of schizophrenia. The purpose of this study was to examine the effects of acetylcholinesterase (AChE) inhibitors in mice treated with the noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, MK-801, which has been suggested as an animal model of the cognitive deficits of schizophrenia. Three separate experiments were conducted to test the effects of physostigmine, donepezil, or galantamine on deficits in learning and memory induced by MK-801. In each experiment, MK-801 (0.05 or 0.10 mg/kg) or saline was administered i.p. 20 min prior to behavioral testing over a total of 12 days. At 30 min prior to administration of MK-801 or saline, one of three doses of the AChE inhibitor (ie physostigmine-0.03, 0.10, or 0.30 mg/kg; donepezil-0.10, 0.30, or 1.00 mg/kg; or galantamine-0.25, 0.50, or 1.00 mg/kg) or saline was administered s.c. Behavioral testing was performed in all experimental animals using the following sequence: (1) spatial reversal learning, (2) locomotion, (3) fear conditioning, and (4) shock sensitivity. Both doses of MK-801 produced impairments in spatial reversal learning and in contextual and cued memory, as well as hyperlocomotion. Physostigmine and donepezil, but not galantamine, ameliorated MK-801-induced deficits in spatial reversal learning and in contextual and cued memory in a dose-dependent manner. Also, physostigmine, but not donepezil or galantamine, reversed MK-801-induced hyperlocomotion. Galantamine, but not physostigmine or donepezil, altered shock sensitivity. These results suggest that AChE inhibitors may differ in their capacity to ameliorate learning and memory deficits produced by MK-801 in mice, which may have relevance for the cognitive effects of cholinomimetic drugs in patients with schizophrenia. PMID:15956997

  4. Magnetic Untwisting in Most Solar X-Ray Jets

    NASA Technical Reports Server (NTRS)

    Moore, Ronald; Sterling, Alphonse; Falconer, David; Robe, Dominic

    2013-01-01

    From 54 X-ray jets observed in the polar coronal holes by Hinode's X-Ray Telescope (XRT) during coverage in movies from Solar Dynamic Observatory's Atmospheric Imaging Assembly (AIA) taken in its He II 304 Å band at a cadence of 12 s, we have established a basic characteristic of solar X-ray jets: untwisting motion in the spire. In this presentation, we show the progression of few of these X-ray jets in XRT images and track their untwisting in AIA He II images. From their structure displayed in their XRT movies, 19 jets were evidently standard jets made by interchange reconnection of the magnetic-arcade base with ambient open field, 32 were evidently blowout jets made by blowout eruption of the base arcade, and 3 were of ambiguous form. As was anticipated from the >10,000 km span of the base arcade in most polar X-ray jets and from the disparity of standard jets and blowout jets in their magnetic production, few of the standard X-ray jets (3 of 19) but nearly all of the blowout X-ray jets (29 of 32) carried enough cool (T is approximately 105 K) plasma to be seen in their He II movies. In the 32 X-ray jets that showed a cool component, the He II movies show 10-100 km/s untwisting motions about the axis of the spire in all 3 standard jets and in 26 of the 29 blowout jets. Evidently, the open magnetic field in nearly all blowout X-ray jets and probably in most standard X-ray jets carries transient twist. This twist apparently relaxes by propagating out along the open field as a torsional wave. High-resolution spectrograms and Dopplergrams have shown that most Type-II spicules have torsional motions of 10-30 km/s. Our observation of similar torsional motion in X-ray jets strengthens the case for Type-II spicules being made in the same way as X-ray jets, by blowout eruption of a twisted magnetic arcade in the spicule base and/or by interchange reconnection of the twisted base arcade with the ambient open field. This work was funded by NASA's Heliophysics Division

  5. The quiet Sun average Doppler shift of coronal lines up to 2 MK

    NASA Astrophysics Data System (ADS)

    Dadashi, N.; Teriaca, L.; Solanki, S. K.

    2011-10-01

    Context. The average Doppler shift shown by spectral lines formed from the chromosphere to the corona reveals important information on the mass and energy balance of the solar atmosphere, providing an important observational constraint to any models of the solar corona. Previous spectroscopic observations of vacuum ultra-violet (VUV) lines have revealed a persistent average wavelength shift of lines formed at temperatures up to 1 MK. At higher temperatures, the behaviour is still essentially unknown. Aims: Here we analyse combined SUMER (Solar Ultraviolet Measurements of Emitted Radiation)/SoHO (Solar and Heliospheric Observatory) and EIS (EUV Imaging Spectrometer)/Hinode observations of the quiet Sun around disk centre to determine, for the first time, the average Doppler shift of several spectral lines formed between 1 and 2 MK, where the largest part of the quiet coronal emission is formed. Methods: The measurements are based on a novel technique applied to EIS spectra to measure the difference in Doppler shift between lines formed at different temperatures. Simultaneous wavelength-calibrated SUMER spectra allow establishing the absolute value at the reference temperature of T ≈ 1 MK. Results: The average line shifts at 1 MK < T < 1.8 MK are modestly, but clearly bluer than those observed at 1 MK. By accepting an average blue shift of about (-1.8 ± 0.6) km s-1 at 1 MK (as provided by SUMER measurements), this translates into a maximum Doppler shift of (-4.4 ± 2.2) km s-1 around 1.8 MK. The measured value appears to decrease to about (-1.3 ± 2.6) km s-1 at the Fe xv formation temperature of 2.1 MK. Conclusions: The measured average Doppler shift between 0.01 and 2.1 MK, for which we provide a parametrisation, appears to be qualitatively and roughly quantitatively consistent with what foreseen by 3D coronal models where heating is produced by dissipation of currents induced by photospheric motions and by reconnection with emerging magnetic flux.

  6. Inclusive Jets in PHP

    NASA Astrophysics Data System (ADS)

    Roloff, P.

    Differential inclusive-jet cross sections have been measured in photoproduction for boson virtualities Q^2 < 1 GeV^2 with the ZEUS detector at HERA using an integrated luminosity of 300 pb^-1. Jets were identified in the laboratory frame using the k_T, anti-k_T or SIScone jet algorithms. Cross sections are presented as functions of the jet pseudorapidity, eta(jet), and the jet transverse energy, E_T(jet). Next-to-leading-order QCD calculations give a good description of the measurements, except for jets with low E_T(jet) and high eta(jet). The cross sections have the potential to improve the determination of the PDFs in future QCD fits. Values of alpha_s(M_Z) have been extracted from the measurements based on different jet algorithms. In addition, the energy-scale dependence of the strong coupling was determined.

  7. MK2206 in Treating Patients With Stage I, Stage II, or Stage III Breast Cancer

    ClinicalTrials.gov

    2015-03-16

    Estrogen Receptor Negative; Estrogen Receptor Positive; HER2/Neu Negative; HER2/Neu Positive; Progesterone Receptor Negative; Progesterone Receptor Positive; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-Negative Breast Carcinoma

  8. New results on jet fragmentation at CDF

    SciTech Connect

    Jindariani, Sergo; /Florida U.

    2006-12-01

    Presented are the latest results of jet fragmentation studies at the Tevatron using the CDF Run II detector. Studies include the distribution of transverse momenta (Kt) of particles jets, two-particle momentum correlations, and indirectly global event shapes in p{bar p} collisions. Results are discussed within the context of recent Next-to-Leading Log calculations as well as earlier experimental results from the Tevatron and e{sup +}e{sup -} colliders.

  9. A deep Chandra observation of the poor cluster AWM 4 - II. The role of the radio jets in enriching the intracluster medium

    NASA Astrophysics Data System (ADS)

    O'Sullivan, Ewan; Giacintucci, Simona; David, Laurence P.; Vrtilek, Jan M.; Raychaudhury, Somak

    2011-03-01

    We use a Chandra observation of the poor cluster AWM 4 to map the temperature and abundance of the intracluster medium, so as to examine the influence of the central radio galaxy on its environment. While the cluster core is generally enriched to near-solar abundances, we find evidence of supersolar abundances correlated with the radio jets, extending ˜35 kpc from the core of the central dominant galaxy NGC 6051 along its minor-axis. We conclude that the enriched gas has been transported out of the central galaxy through the action of the radio source. We estimate the excess mass of iron in the entrained gas to be ˜1.4 × 106 M⊙ and find that this can be produced in the core of NGC 6051 within the time-scale of the active galactic nucleus (AGN) outburst. The energy required to transport this gas to its current location is ˜4.5 × 1057 erg, a significant fraction of the estimated total mechanical energy output of the AGN, though this estimate is dependent on the degree of enrichment of the uplifted gas. The larger near-solar abundance region is also compatible with enrichment by metals mixed outwards from NGC 6051 over a much longer time-scale.

  10. Antiviral Activity of MK-4965, a Novel Nonnucleoside Reverse Transcriptase Inhibitor▿

    PubMed Central

    Lai, Ming-Tain; Munshi, Vandna; Touch, Sinoeun; Tynebor, Robert M.; Tucker, Thomas J.; McKenna, Philip M.; Williams, Theresa M.; DiStefano, Daniel J.; Hazuda, Daria J.; Miller, Michael D.

    2009-01-01

    Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are the mainstays of therapy for the treatment of human immunodeficiency virus type 1 (HIV-1) infections. However, the effectiveness of NNRTIs can be hampered by the development of resistance mutations which confer cross-resistance to drugs in the same class. Extensive efforts have been made to identify new NNRTIs that can suppress the replication of the prevalent NNRTI-resistant viruses. MK-4965 is a novel NNRTI that possesses both diaryl ether and indazole moieties. The compound displays potency at subnanomolar concentrations against wild-type (WT), K103N, and Y181C reverse transcriptase (RT) in biochemical assays. MK-4965 is also highly potent against the WT virus and two most prevalent NNRTI-resistant viruses (viruses that harbor the K103N or the Y181C mutation), against which it had 95% effective concentrations (EC95s) of <30 nM in the presence of 10% fetal bovine serum. The antiviral EC95 of MK-4965 was reduced approximately four- to sixfold when it was tested in 50% human serum. Moreover, MK-4965 was evaluated with a panel of 15 viruses with NNRTI resistance-associated mutations and showed a superior mutant profile to that of efavirenz but not to that of etravirine. MK-4965 was similarly effective against various HIV-1 subtypes and viruses containing nucleoside reverse transcriptase inhibitor or protease inhibitor resistance-conferring mutations. A two-drug combination study showed that the antiviral activity of MK-4965 was nonantagonistic with each of the 18 FDA-licensed drugs tested vice versa in the present study. Taken together, these in vitro data show that MK-4965 possesses the desired properties for further development as a new NNRTI for the treatment of HIV-1 infection. PMID:19289522

  11. Fast apoptosis and erythroid differentiation induced by imatinib mesylate in JURL-MK1 cells.

    PubMed

    Kuzelová, Katerina; Grebenová, Dana; Marinov, Iuri; Hrkal, Zbynek

    2005-05-15

    We compare the effects of Imatinib mesylate (Glivec) on chronic myeloid leukemia derived cell lines K562 and JURL-MK1. In both cell lines, the cell cycle arrests in G(1)/G(0) phase within 24 h after the addition of 1 microM Imatinib. This is followed by a decrease of Ki-67 expression and the induction of apoptosis. In JURL-MK1 cells, the apoptosis is faster in comparison with K562 cells: the caspase-3 activity reaches the peak value (20 to 30 fold of the control) after about 40 h and the apoptosis proceeds to its culmination point, the DNA fragmentation, within 48 h following 1 microM Imatinib addition. Unlike K562 cells, JURL-MK1 cells possess a probably functional p53 protein inducible by TPA (tetradecanoyl phorbol acetate) or UV-B irradiation. However, no increase in p53 expression was observed in Imatinib-treated JURL-MK1 cells indicating that the difference in the apoptosis rate between the two cell lines is not due to the lack of p53 in K562 cells. Imatinib also triggers erythroid differentiation both in JURL-MK1 and K562 cells. Glycophorin A expression occurred simultaneously with the apoptosis, even at the single cell level. In K562 cells, but not in JURL-MK1 cells, the differentiation process involved increased hemoglobin synthesis. However, during spontaneous evolution of JURL-MK1 cells in culture, the effects produced by Imatinib progressively changed from the fast apoptosis to the more complete erythroid differentiation. We suggest that the apoptosis and the erythroid differentiation are parallel effects of Imatinib and their relative contributions, kinetics and completeness are related to the differentiation stage of the treated cells. PMID:15770664

  12. Blockade of voltage-gated K⁺ currents in rat mesenteric arterial smooth muscle cells by MK801.

    PubMed

    Kim, Jeong Min; Park, Sang Woong; Lin, Hai Yue; Shin, Kyung Chul; Sung, Dong Jun; Kim, Jae Gon; Cho, Hana; Kim, Bokyung; Bae, Young Min

    2015-01-01

    MK801 (dizocilpine), a phencyclidine (PCP) derivative, is a potent noncompetitive antagonist of the N-Methyl-D-aspartate receptor (NMDAr). Another PCP derivative, ketamine, was reported to block voltage-gated K(+) (Kv) channels, which was independent of NMDAr function. Kv currents are major regulators of the membrane potential (Em) and excitability of muscles and neurons. Here, we investigated the effect of MK801 on the Kv channels and Em in rat mesenteric arterial smooth muscle cells (RMASMCs). We used the whole-cell patch clamp technique to analyze the effect of MK801 enantiomers on Kv channels and Em. (+)MK801 inhibited Kv channels in a concentration-dependent manner (IC50 of 89.1 ± 13.1 μM, Hill coefficient of 1.05 ± 0.08). The inhibition was voltage- and state- independent. (+)MK801 didn't influence steady-state activation and inactivation of Kv channels. (+)MK801 treatment depolarized Em in a concentration-dependent manner and concomitantly decreased membrane conductance. (-)MK801 also similarly inhibited the Kv channels (IC50 of 134.0 ± 17.5 μM, Hill coefficient of 0.87 ± 0.09). These results indicate that MK801 directly inhibits the Kv channel in a state-independent manner in RMASMCs. This MK801-mediated inhibition of Kv channels should be considered when assessing the various pharmacological effects produced by MK801, such as schizophrenia, neuroprotection, and hypertension. PMID:25704024

  13. Corporate Jet

    NASA Technical Reports Server (NTRS)

    1991-01-01

    Gulfstream Aerospace Corporation, Savannah, GA, used a version of a NASA program called WIBCO to design a wing for the Gulfstream IV (G-IV) which will help to reduce transonic drag (created by shock waves that develop as an airplane approaches the speed of sound). The G-IV cruises at 88 percent of the speed of sound, and holds the international record in its class for round-the-world flight. They also used the STANS5 and Profile programs in the design. They will use the NASA program GASP to help determine the gross weight, range, speed, payload and optimum wing area of an intercontinental supersonic business jet being developed in cooperation with Sukhoi Design Bureau, a Soviet organization.

  14. Jet inclusive cross sections

    SciTech Connect

    Del Duca, V.

    1992-11-01

    Minijet production in jet inclusive cross sections at hadron colliders, with large rapidity intervals between the tagged jets, is evaluated by using the BFKL pomeron. We describe the jet inclusive cross section for an arbitrary number of tagged jets, and show that it behaves like a system of coupled pomerons.

  15. Supersonic gas jets

    NASA Astrophysics Data System (ADS)

    Dulov, V. G.

    The papers presented in this volume provide an overview of the current state of research in the gas dynamics of jet flows. In particular, attention is given to free supersonic jets and to the interaction of supersonic jets with one another and with obstacles under stationary and nonstationary flow conditions. Papers are presented on a method for calculating a weakly anisotropic supersonic turbulent jet in a subsonic slipstream; composite supersonic jets; the principal gas-dynamic characteristics of the processes occurring in gas-jet-driven shock-wave generators; and the construction of models for supersonic jet flows. For individual items see A84-16902 to A84-16918

  16. Inverse agonist and pharmacochaperone properties of MK-0524 on the prostanoid DP1 receptor.

    PubMed

    Labrecque, Pascale; Roy, Sébastien J; Fréchette, Louis; Iorio-Morin, Christian; Gallant, Maxime A; Parent, Jean-Luc

    2013-01-01

    Prostaglandin D₂ (PGD₂) acts through two G protein-coupled receptors (GPCRs), the prostanoid DP receptor and CRTH2 also known as DP1 and DP2, respectively. Several previously characterized GPCR antagonists are now classified as inverse agonists and a number of GPCR ligands are known to display pharmacochaperone activity towards a given receptor. Here, we demonstrate that a DP1 specific antagonist, MK-0524 (also known as laropiprant), decreased basal levels of intracellular cAMP produced by DP1, a Gα(s)-coupled receptor, in HEK293 cells. This reduction in cAMP levels was not altered by pertussis toxin treatment, indicating that MK-0524 did not induce coupling of DP1 to Gα(i/o) proteins and that this ligand is a DP1 inverse agonist. Basal ERK1/2 activation by DP1 was not modulated by MK-0524. Interestingly, treatment of HEK293 cells expressing Flag-tagged DP1 with MK-0524 promoted DP1 cell surface expression time-dependently to reach a maximum increase of 50% compared to control after 24 h. In contrast, PGD₂ induced the internalization of 75% of cell surface DP1 after the same time of stimulation. The increase in DP1 cell surface targeting by MK-0524 was inhibited by Brefeldin A, an inhibitor of transport from the endoplasmic reticulum-Golgi to the plasma membrane. Confocal microscopy confirmed that a large population of DP1 remained trapped intracellularly and co-localized with calnexin, an endoplasmic reticulum marker. Redistribution of DP1 from intracellular compartments to the plasma membrane was observed following treatment with MK-0524 for 24 h. Furthermore, MK-0524 promoted the interaction between DP1 and the ANKRD13C protein, which we showed previously to display chaperone-like effects towards the receptor. We thus report that MK-0524 is an inverse agonist and a pharmacochaperone of DP1. Our findings may have important implications during therapeutic treatments with MK-0524 and for the development of new molecules targeting DP1. PMID:23762421

  17. "Waveguidability" of idealized jets

    NASA Astrophysics Data System (ADS)

    Manola, Iris; Selten, Frank; Vries, Hylke; Hazeleger, Wilco

    2013-09-01

    It is known that strong zonal jets can act as waveguides for Rossby waves. In this study we use the European Center for Medium-Range Weather Forecasts (ECMWF) reanalysis data to analyze the connection between jets and zonal waves at timescales beyond 10 days. Moreover, a barotropic model is used to systematically study the ability of idealized jets to trap Rossby wave energy ("waveguidability") as a function of jet strength, jet width, and jet location. In general, strongest waveguidability is found for narrow, fast jets. In addition, when the stationary wave number is integer, a resonant response is found through constructive interference. In Austral summer, the Southern Hemispheric jet is closest to the idealized jets considered and it is for this season that similar jet-zonal wave relationships are identified in the ECMWF reanalysis data.

  18. A natural therapeutic approach for the treatment of periodontitis by MK615.

    PubMed

    Morimoto-Yamashita, Yoko; Kawakami, Yoshiko; Tatsuyama, Syoko; Miyashita, Keiko; Emoto, Makiko; Kikuchi, Kiyoshi; Kawahara, Ko-ichi; Tokuda, Masayuki

    2015-11-01

    Periodontitis is a chronic inflammatory disease that affects the tooth-supporting tissues. Gingival fibroblasts are the most abundant cells in periodontal tissues and they participate actively in the host inflammatory response to periodontal pathogens that is known to mediate local tissue destruction in periodontitis. The Japanese apricot, known as Ume in Japanese, has been a traditional Japanese medicine for centuries and is a familiar and commonly consumed food. The health benefits of Ume are widely recognized and have been confirmed in recent studies showing that MK615, an extract of compounds from Ume, has strong anticancer and anti-inflammatory effects. However, the potential role of MK615 in oral health is unknown. We hypothesized that the anti-inflammatory activities of MK615 could be exploited to inhibit the effects of lipopolysaccharide (LPS) produced by periodontal bacterial pathogens, such as Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis. Here, we show that LPS-induced interleukin (IL)-6 and IL-8 production by gingival fibroblasts was dose-dependently inhibited by MK615. As a potent inhibitor of the inflammatory responses induced by periodontal pathogens, MK615 merits further testing as a therapeutic agent in inflammatory diseases such as periodontitis. PMID:26305447

  19. Properties of Mlso MK3 White-Light CMEs from 1989-1996

    NASA Astrophysics Data System (ADS)

    St Cyr, O. C.; Flint, Q.; Xie, H.; Webb, D. F.; Burkepile, J.; Lecinski, A. R.

    2014-12-01

    Observations low in the solar corona are key to understanding the initiation and propagation of coronal mass ejections (CMEs). Similar to solar magnetographs and total solar irradiance measurements, white-light coronagraph observations are another aspect of Heliophysics that have followed a path comparable to that found in Earth science, where longevity and continuity of measurements lead to new understanding through modeling. Previously we have reported on our efforts to fill the only remaining data gap since 1973 in the CME rate using the Mauna Loa Solar Observatory's MK3 K-coronameter observations from 1989-1996. The MK3 instrument observed routinely several hours most days beginning in 1980 until it was upgraded to MK4 in 1998. MK3 CMEs detected from 1980-1989 were compared with Solwind and SMM and reported by St. Cyr et al. (1999). Here we provide a preliminary report on the statistical properties of CMEs detected during 1989-1996. Since this period began in solar maximum activity conditions and descended into minimum, we can compare the properties of MLSO MK3 events with CMEs detected by other coronagraphs during similar activity phases.

  20. GM1 ganglioside reverses the cognitive deficits induced by MK801 in mice.

    PubMed

    Ni, Yu-Fei; Zhang, Wei; Bao, Xiao-Feng; Wang, Wei; Song, Lu; Jiang, Bo

    2016-08-01

    Cognitive deficits are core symptoms of schizophrenia, but effective treatments are still lacking. Previous studies have reported that the brain-derived neurotrophic factor (BDNF) signaling is closely involved in learning and memory. Monosialotetrahexosylganglioside (GM1) is a ganglioside with wide-ranging pharmacologic effects that enhances the BDNF signaling cascade. This study aimed to assess the effects of GM1 on schizophrenia-related cognitive impairments. A brief disruption of N-methyl-D-aspartate receptors with MK801 was used to generate the animal model for cognitive deficits in schizophrenia. It was found that MK801-treated mice showed significant deficits in memory ability compared with control mice in different behavior tests, and this was accompanied by decreased hippocampal BDNF signaling pathway. Consecutive administration of GM1 fully restored the MK801-induced cognitive deficits and the impaired BDNF signaling in the hippocampus. Furthermore, a BDNF system inhibitor abolished the effects of GM1 in the MK801 model. Taken together, our results show that GM1 could reverse the MK801-induced cognitive deficits, suggesting a potential usefulness of GM1 in treating the schizophrenia-related cognitive impairments. PMID:26960162

  1. Effect of MK-801 and Clozapine on the Proteome of Cultured Human Oligodendrocytes

    PubMed Central

    Cassoli, Juliana S.; Iwata, Keiko; Steiner, Johann; Guest, Paul C.; Turck, Christoph W.; Nascimento, Juliana M.; Martins-de-Souza, Daniel

    2016-01-01

    Separate lines of evidence have demonstrated the involvement of N-methyl-D-aspartate (NMDA) receptor and oligodendrocyte dysfunctions in schizophrenia. Here, we have carried out shotgun mass spectrometry proteome analysis of oligodendrocytes treated with the NMDA receptor antagonist MK-801 to gain potential insights into these effects at the molecular level. The MK-801 treatment led to alterations in the levels of 68 proteins, which are associated with seven distinct biological processes. Most of these proteins are involved in energy metabolism and many have been found to be dysregulated in previous proteomic studies of post-mortem brain tissues from schizophrenia patients. Finally, addition of the antipsychotic clozapine to MK-801-treated oligodendrocyte cultures resulted in changes in the levels of 45 proteins and treatment with clozapine alone altered 122 proteins and many of these showed opposite changes to the MK-801 effects. Therefore, these proteins and the associated energy metabolism pathways should be explored as potential biomarkers of antipsychotic efficacy. In conclusion, MK-801 treatment of oligodendrocytes may provide a useful model for testing the efficacy of novel treatment approaches. PMID:26973466

  2. MK615: a new therapeutic approach for the treatment of oral disease.

    PubMed

    Morimoto-Yamashita, Yoko; Matsuo, Miki; Komatsuzawa, Hitoshi; Kawahara, Ko-ichi; Kikuchi, Kiyoshi; Torii, Mitsuo; Tokuda, Masayuki

    2011-08-01

    The oral cavity is inhabited by over 500 different bacterial species. Dental caries and periodontitis are major bacterial infectious diseases in the oral cavity. Prunus mume Sieb. et Zucc., which is a variety of Japanese apricot known as Ume in Japanese, has been a traditional Japanese medicine for centuries, and is a familiar and commonly consumed food. The health benefits of Ume are now being widely recognized. Recent studies showed that MK615, an extract of compounds from Ume, has strong anticancer and anti-inflammatory effects. However, the potential role of MK615 in the antimicrobial field remains unknown. Therefore, we hypothesize that MK615 has antimicrobial activities against a range of oral bacterial pathogens. Here, we show that MK615 may be a potent inhibitor of the growth of some oral bacteria and an inhibitor of biofilm formation by Streptococcus mutans, the principal etiological agent of human dental caries. Our findings suggest that MK615 has potential as a therapeutic agent for treating and preventing oral diseases such as dental caries and periodontitis. PMID:21565449

  3. Agmatine enhances antidepressant potency of MK-801 and conventional antidepressants in mice.

    PubMed

    Neis, Vivian Binder; Moretti, Morgana; Manosso, Luana Meller; Lopes, Mark W; Leal, Rodrigo Bainy; Rodrigues, Ana Lúcia S

    2015-03-01

    Agmatine, an endogenous guanidine amine, has been shown to produce antidepressant-like effects in animal studies. This study investigated the effects of the combined administration of agmatine with either conventional monoaminergic antidepressants or the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 in the tail suspension test (TST) in mice. The aim was to evaluate the extent of the antidepressant synergism by examining the ability of a fixed dose of agmatine to shift the antidepressant potency of fluoxetine, imipramine, bupropion and MK-801. A sub-effective dose of agmatine (0.0001 mg/kg, p.o.) significantly increased the potency by which fluoxetine, imipramine, bupropion and MK-801 decreased immobility time in the TST by 2-fold (fluoxetine), 10-fold (imipramine and bupropion) and 100-fold (MK-801). Combined with previous evidence indicating a role of monoaminergic systems in the effect of agmatine, the current data suggest that agmatine may modulate monoaminergic neurotransmission and augment the activity of conventional antidepressants. Moreover, this study found that agmatine substantially augmented the antidepressant-like effect of MK-801, reinforcing the notion that this compound modulates NMDA receptor activation. These preclinical data may stimulate future clinical studies testing the effects of augmentation therapy with agmatine for the management of depressive disorders. PMID:25553821

  4. Decreased hyperthermic effect of MK-801 in selectively bred hypercholinergic rats.

    PubMed

    Pucilowski, O; Danysz, W; Overstreet, D H; Rezvani, A H; Eichelman, B; Janowsky, D S

    1991-04-01

    The Flinders Sensitive Line (FSL) of rats has been selectively bred to have increased sensitivity to cholinergic agonists. However, these rats exhibit altered responsiveness to a number of noncholinergic agents, such as apomorphine, buspirone and ethanol. This study compared the FSL and control Flinders Resistant Line (FRL) rats in terms of their hyperthermic response to the phencyclidine (PCP) receptor agonist, MK-801 (0.2 mg/kg SC) and their MK-801 binding characteristics. We have found that FSL rats react with a delayed hyperthermia, having a significantly lower hyperthermia for the first 120 min of observation. Thereafter the response does not differ in FSL and FRL rats. Both groups had similar affinities and numbers of [3H]MK-801 binding sites in the hippocampus/cerebral cortex. Pretreatment with scopolamine (1 mg/kg SC) failed to affect MK-801-induced hyperthermia in either line of rats. These findings suggest that selective breeding of FSL rats attenuated the secondary mechanisms involved in the PCP receptor-mediated hyperthermic response. However, by itself cholinergic supersensitivity does not appear to be a major factor in the blunted responsiveness of FSL rats to MK-801. PMID:1868361

  5. Sensorimotor gating impairments induced by MK-801 treatment may be reduced by tolerance effect and by familiarization in monkeys

    PubMed Central

    Saletti, Patricia G.; Maior, Rafael S.; Hori, Etsuro; Nishijo, Hisao; Tomaz, Carlos

    2015-01-01

    Dizocilpine (MK-801) is a non-competitive NMDA antagonist that induces schizophreniclike effects. It is therefore widely used in experimental models of schizophrenia including prepulse inhibition (PPI) impairments in rodents. Nevertheless, MK-801 has never been tested in monkeys on a PPI paradigm. In order to evaluate MK-801 effects on monkeys’ PPI, we tested eight capuchin monkeys (Sapajus spp.) using three different doses of MK-801 (0.01; 0.02; 0.03 mg/kg). Results show PPI impairment in acute administration of the highest dose (0.03 mg/kg). PPI impairment induced by MK-801 was reversed by re-exposure to the PPI test throughout treatment trials, in contrast with rodent studies. These results indicate that tolerance effect and familiarization with PPI test may reduce the sensorimotor gating deficits induced by MK-801 in monkeys, suggesting a drug-training interaction. PMID:26441660

  6. Age-related differential sensitivity to MK-801-induced locomotion and stereotypy in C57BL/6 mice

    PubMed Central

    Qi, Chunting; Zou, Hong; Zhang, Ruizhong; Zhao, Guoping; Jin, Meilei; Yu, Lei

    2009-01-01

    Psychomotor effects elicited by systemic administration of the noncompetitive NMDA (N-methyl-D-aspartate) receptor antagonist MK-801 (dizocilpine maleate) represent perturbation of glutamatergic pathways, providing an animal model for psychotic symptoms of schizophrenia. Hyperlocomotion and stereotypy are the two main psychomotor behaviors induced by MK-801. This study compared MK-801-induced hyperlocomotion and stereotypy in young (1-month old) and aged mice (12-month old), in order to determine how the aging process may influence these behaviors. The tested MK-801 doses ranged from 0.015 to 1 mg/kg. The data indicated that MK-801 impacted the aged mice more pronouncedly than the young mice, as both hyperlocomotion and stereotypy were increased significantly more in the aged mice relative to the young mice. These results suggest an age-related increase in MK-801 sensitivity in mice. PMID:18053981

  7. Inhibitory effects of KN-93, an inhibitor of Ca2+ calmodulin-dependent protein kinase II, on light-regulated root gravitropism in maize

    NASA Technical Reports Server (NTRS)

    Feldman, L. J.; Hidaka, H.

    1993-01-01

    Light is essential for root gravitropism in Zea mays L., cultivar Merit. It is hypothesized that calcium mediates this light-regulated response. KN-93, an inhibitor of calcium/calmodulin kinase II (CaMK II), inhibits light-regulated root gravitropism but does not affect light perception. We hypothesize that CaMK II, or a homologue, operates late in the light/gravity signal transduction chain. Here we provide evidence suggesting a possible physiological involvement of CaMK II in root gravitropism in plants.

  8. MK5 activates Rag transcription via Foxo1 in developing B cells

    PubMed Central

    Chow, Kwan T.; Timblin, Greg A.; McWhirter, Sarah M.

    2013-01-01

    Foxo1 is a critical, direct regulator of Rag (recombination activating gene) transcription during B cell development and is thus essential for the generation of a diverse repertoire of antigen receptors. Although Foxo1 regulation has been widely studied in many cell types, pathways regulating Foxo1 in B cells have not been fully elucidated. By screening a panel of Foxo1 mutants, we identified serine 215 on Foxo1 as a novel phosphorylation site that is essential for the activation of Rag transcription. Mutation of S215 strongly attenuated transactivation of Rag but did not affect most other Foxo1 target genes. We show that MK5, a MAPK-activated protein kinase, is a previously unidentified upstream regulator of Foxo1. MK5 was necessary and sufficient to activate Rag transcription in transformed and primary pro–B cells. Together, our experiments show that MK5 positively regulates Rag transcription via phosphorylation of Foxo1 in developing B cells. PMID:23878308

  9. Akt inhibitor MK2206 prevents influenza pH1N1 virus infection in vitro.

    PubMed

    Denisova, Oxana V; Söderholm, Sandra; Virtanen, Salla; Von Schantz, Carina; Bychkov, Dmitrii; Vashchinkina, Elena; Desloovere, Jens; Tynell, Janne; Ikonen, Niina; Theisen, Linda L; Nyman, Tuula A; Matikainen, Sampsa; Kallioniemi, Olli; Julkunen, Ilkka; Muller, Claude P; Saelens, Xavier; Verkhusha, Vladislav V; Kainov, Denis E

    2014-07-01

    The influenza pH1N1 virus caused a global flu pandemic in 2009 and continues manifestation as a seasonal virus. Better understanding of the virus-host cell interaction could result in development of better prevention and treatment options. Here we show that the Akt inhibitor MK2206 blocks influenza pH1N1 virus infection in vitro. In particular, at noncytotoxic concentrations, MK2206 alters Akt signaling and inhibits endocytic uptake of the virus. Interestingly, MK2206 is unable to inhibit H3N2, H7N9, and H5N1 viruses, indicating that pH1N1 evolved specific requirements for efficient infection. Thus, Akt signaling could be exploited further for development of better therapeutics against pH1N1 virus. PMID:24752266

  10. Discovery of selective and orally available spiro-3-piperidyl ATP-competitive MK2 inhibitors.

    PubMed

    Kaptein, Allard; Oubrie, Arthur; de Zwart, Edwin; Hoogenboom, Niels; de Wit, Joeri; van de Kar, Bas; van Hoek, Maaike; Vogel, Gerard; de Kimpe, Vera; Schultz-Fademrecht, Carsten; Borsboom, Judith; van Zeeland, Mario; Versteegh, Judith; Kazemier, Bert; de Roos, Jeroen; Wijnands, Frank; Dulos, John; Jaeger, Martin; Leandro-Garcia, Paula; Barf, Tjeerd

    2011-06-15

    The identification of a potent, selective, and orally available MK2 inhibitor series is described. The initial absence of oral bioavailability was successfully tackled by moving the basic nitrogen of the spiro-4-piperidyl moiety towards the electron-deficient pyrrolepyridinedione core, thereby reducing the pK(a) and improving Caco-2 permeability. The resulting racemic spiro-3-piperidyl analogues were separated by chiral preparative HPLC, and the activity towards MK2 inhibition was shown to reside mostly in the first eluting stereoisomer. This led to the identification of new MK2 inhibitors, such as (S)-23, with low nanomolar biochemical inhibition (EC(50) 7.4 nM) and submicromolar cellular target engagement activity (EC(50) 0.5 μM). PMID:21565498

  11. Akt Inhibitor MK2206 Prevents Influenza pH1N1 Virus Infection In Vitro

    PubMed Central

    Denisova, Oxana V.; Söderholm, Sandra; Virtanen, Salla; Von Schantz, Carina; Bychkov, Dmitrii; Vashchinkina, Elena; Desloovere, Jens; Tynell, Janne; Ikonen, Niina; Theisen, Linda L.; Nyman, Tuula A.; Matikainen, Sampsa; Kallioniemi, Olli; Julkunen, Ilkka; Muller, Claude P.; Saelens, Xavier; Verkhusha, Vladislav V.

    2014-01-01

    The influenza pH1N1 virus caused a global flu pandemic in 2009 and continues manifestation as a seasonal virus. Better understanding of the virus-host cell interaction could result in development of better prevention and treatment options. Here we show that the Akt inhibitor MK2206 blocks influenza pH1N1 virus infection in vitro. In particular, at noncytotoxic concentrations, MK2206 alters Akt signaling and inhibits endocytic uptake of the virus. Interestingly, MK2206 is unable to inhibit H3N2, H7N9, and H5N1 viruses, indicating that pH1N1 evolved specific requirements for efficient infection. Thus, Akt signaling could be exploited further for development of better therapeutics against pH1N1 virus. PMID:24752266

  12. Evolution of the Jet Opening Angle Distribution in Holographic Plasma

    NASA Astrophysics Data System (ADS)

    Rajagopal, Krishna; Sadofyev, Andrey V.; van der Schee, Wilke

    2016-05-01

    We use holography to analyze the evolution of an ensemble of jets, with an initial probability distribution for their energy and opening angle as in proton-proton (p p ) collisions, as they propagate through an expanding cooling droplet of strongly coupled plasma as in heavy ion collisions. We identify two competing effects: (i) each individual jet widens as it propagates and (ii) because wide-angle jets lose more energy, energy loss combined with the steeply falling perturbative spectrum serves to filter wide jets out of the ensemble at any given energy. Even though every jet widens, jets with a given energy can have a smaller mean opening angle after passage through the plasma than jets with that energy would have had in vacuum, as experimental data may indicate.

  13. Evolution of the Jet Opening Angle Distribution in Holographic Plasma.

    PubMed

    Rajagopal, Krishna; Sadofyev, Andrey V; van der Schee, Wilke

    2016-05-27

    We use holography to analyze the evolution of an ensemble of jets, with an initial probability distribution for their energy and opening angle as in proton-proton (pp) collisions, as they propagate through an expanding cooling droplet of strongly coupled plasma as in heavy ion collisions. We identify two competing effects: (i) each individual jet widens as it propagates and (ii) because wide-angle jets lose more energy, energy loss combined with the steeply falling perturbative spectrum serves to filter wide jets out of the ensemble at any given energy. Even though every jet widens, jets with a given energy can have a smaller mean opening angle after passage through the plasma than jets with that energy would have had in vacuum, as experimental data may indicate. PMID:27284647

  14. MK-4827, a PARP-1/-2 inhibitor, strongly enhances response of human lung and breast cancer xenografts to radiation.

    PubMed

    Wang, Li; Mason, Kathy A; Ang, K Kian; Buchholz, Thomas; Valdecanas, David; Mathur, Anjili; Buser-Doepner, Carolyn; Toniatti, Carlo; Milas, Luka

    2012-12-01

    The poly-(ADP-ribose) polymerase (PARP) inhibitor, MK-4827, is a novel potent, orally bioavailable PARP-1 and PARP-2 inhibitor currently in phase I clinical trials for cancer treatment. No preclinical data currently exist on the combination of MK-4827 with radiotherapy. The current study examined combined treatment efficacy of MK-4827 and fractionated radiotherapy using a variety of human tumor xenografts of differing p53 status: Calu-6 (p53 null), A549 (p53 wild-type [wt]) and H-460 (p53 wt) lung cancers and triple negative MDA-MB-231 human breast carcinoma. To mimic clinical application of radiotherapy, fractionated radiation (2 Gy per fraction) schedules given once or twice daily for 1 to 2 weeks combined with MK-4827, 50 mg/kg once daily or 25 mg/kg twice daily, were used. MK-4827 was found to be highly and similarly effective in both radiation schedules but maximum radiation enhancement was observed when MK-4827 was given at a dose of 50 mg/kg once daily (EF = 2.2). MK-4827 radiosensitized all four tumors studied regardless of their p53 status. MK-4827 reduced PAR levels in tumors by 1 h after administration which persisted for up to 24 h. This long period of PARP inhibition potentially adds to the flexibility of design of future clinical trials. Thus, MK-4827 shows high potential to improve the efficacy of radiotherapy. PMID:22127459

  15. Attenuation of MK-801-induced behavioral perseveration by typical and atypical antipsychotic pretreatment in rats.

    PubMed

    Tuplin, Erin W; Stocco, Marlaina R; Holahan, Matthew R

    2015-08-01

    The noncompetitive NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5-10-imine maleate (MK-801) has been shown to increase the probability of operant responding during extinction and reduce infralimbic prefrontal cortical activation, possibly modeling the cognitive dysfunction symptomology, and underlying cause, in patients with schizophrenia. The present study sought to determine if typical and/or atypical antipsychotics would attenuate the MK-801-induced behavioral perseveration and whether this would be associated with concomitant changes in phosphorylated ERK1/2 (pERK1/2) labeling in the infralimbic cortex (IL). Male, Long Evans rats were pretreated with the typical antipsychotic, Flupenthixol (0, 0.125, 0.25 or 0.5 mg/kg) or the atypical antipsychotic, aripiprazole (0, 0.3, 1.0, 3.0 mg/kg), then given 0.1 mg/kg MK-801 followed by a 60-min appetitive operant extinction session. Flupenthixol produced a dose-dependent decrease in MK-801-induced bar pressing behavior and locomotor activity and a dose-dependent increase in IL pERK1/2 labeling. Aripiprazole produced a U-shaped dose-response curve on MK-801-induced bar pressing behavior, a dose-dependent decrease in locomotor activity but no changes in IL pERK1/2 labeling. The attenuation of the MK-801-induced behavioral (bar pressing, locomotion) profile by Flupenthixol indicates a clear dopaminergic contribution to this behavior. The behavioral effect of aripiprazole may be due to its a) binding to presynaptic dopamine receptors at the midrange dose decreasing dopamine output and b) binding to postsynaptic dopamine receptors at the higher dose increasing dopamine tone. While both classes of antipsychotics can normalize perseverative behavioral symptoms, the underlying prefrontal cortical dysregulation seems to persist. PMID:26052791

  16. Supplemental Reactor Physics Calculations and Analysis of ELF Mk 1A Fuel

    SciTech Connect

    Michael A. Pope

    2014-10-01

    These calculations supplement previous the reactor physics work evaluating the Enhanced Low Enriched Uranium (LEU) Fuel (ELF) Mk 1A element. This includes various additional comparisons between the current Highly Enriched Uranium (HEU) and LEU along with further characterization of the performance of the ELF fuel. The excess reactivity to be held down at BOC for ELF Mk 1A fuel is estimated to be approximately $2.75 greater than with HEU for a typical cycle. This is a combined effect of the absence of burnable poison in the ELF fuel and the reduced neck shim worth in LEU fuel compared to HEU. Burnable poison rods were conceptualized for use in the small B positions containing Gd2O3 absorber. These were shown to provide $2.37 of negative reactivity at BOC and to burn out in less than half of a cycle. The worth of OSCCs is approximately the same between HEU and ELF Mk 1A (LEU) fuels in the representative loading evaluated. This was evaluated by rotating all banks simultaneously. The safety rod worth is relatively unchanged between HEU and ELF Mk 1A (LEU) fuels in the representative loading evaluated. However, this should be reevaluated with different loadings. Neutron flux, both total and fast (>1 MeV), is either the same or reduced upon changing from HEU to ELF Mk 1A (LEU) fuels in the representative loading evaluated. This is consistent with the well-established trend of lower neutron fluxes for a given power in LEU than HEU.The IPT loop void reactivity is approximately the same or less positive with ELF Mk 1A (LEU) fuel than HEU in the representative loading evaluated.

  17. Therapeutic effect of the NMDA antagonist MK-801 on low-level laser induced retinal injury

    NASA Astrophysics Data System (ADS)

    Yan, W.-H.; Wu, J.; Chen, P.; Dou, J.-T.; Pan, C.-Y.; Mu, Y.-M.; Lu, J.-M.

    2009-03-01

    The aim of this article was to explore the mechanism of injury in rat retina after constant low-level helium-neon (He-Ne) laser exposure and therapeutic effects of MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, on laser-induced retinal injury. He-Ne laser lesions were created in the central retina of adult Wistar Kyoto rats and were followed immediately by intraperitoneal injection of MK-801 (2 mg/kg) or saline, macroscopical and microscopical lesion were observed by funduscope and light microscope. Ultrastructural changes of the degenerating cells were examined by electron microscopy. Photoreceptor apoptosis was evaluated by TdT-mediated dUTP nick end-labeling (TUNEL). mRNA levels were measured by in situ hybridization and NMDA receptor expression was determined by immunohistochemistry. Laser induced damage was histologically quantified by image-analysis morphometry. Electroretinograms (ERGs) were recorded at different time point after the cessation of exposure to constant irradiation. There was no visible bleeding, exudation or necrosis under funduscope. TUNEL and electron microscopy showed photoreceptor apoptosis after irradiation. MK-801-treated animals had significantly fewer TUNEL-positive cells in the photoreceptors than saline-treated animals after exposure to laser. In situ hybridization (ISH) showed that the NMDAR mRNA level of MK-801-treated rats decreased in the inner plexiform layer 6 h after the cessation of exposure to constant irradiation when compared with that of saline-treated rats. So did Immunohistochemistry (IHC). Electroretinogram showed that b-wave amplitudes of MK-801-treated group were higher than that of saline-treated group after laser exposure. These findings suggest that Low level laser may cause the retinal pathological changes under given conditions. High expression of NMDAR is one of the possible mechanisms causing experimental retinal laser injury of rats. MK-801 exhibits the therapeutic effect due to promote the

  18. Effects of Dipeptidyl Peptidase-4 Inhibition with MK-0431 on Syngeneic Mouse Islet Transplantation

    PubMed Central

    Juang, Jyuhn-Huarng; Kuo, Chien-Hung; Liu, Ying-Hsiu; Chang, Han-Ying; Chen, Chiung-Tong

    2014-01-01

    Dipeptidyl peptidase (DPP)-4 inhibitors increase circulating levels of glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide which may promote β-cell proliferation and survival. This study tested if DPP-4 inhibition with MK-0431 is beneficial for diabetic mice syngeneically transplanted with a marginal number of islets. We syngeneically transplanted 150 C57BL/6 mouse islets under the kidney capsule of each streptozotocin-diabetic mouse and then treated recipients with (n = 21) or without (n = 17) MK-0431 (30 mg/kg/day, po) for 6 weeks. After islet transplantation, blood glucose levels decreased in both MK-0431-treated and control groups. However, the blood glucose and area under the curve of the intraperitoneal glucose tolerance test at 2, 4, and 6 weeks were not significantly different between MK-0431-treated mice and controls. During 6 weeks, both groups exhibited increased body weights over time. However, the weight between two groups did not differ throughout the study period. At 6 weeks after transplantation, the graft beta-cell mass (0.024 ± 0.005 versus 0.023 ± 0.007 mg, P = 0.8793) and insulin content (140 ± 48 versus 231 ± 63 ng, P = 0.2939) were comparable in the MK-0431-treated group and controls. Our results indicate posttransplant DPP-4 inhibition with MK-0431 in the diabetic recipient with a marginal number of islets is not beneficial to transplantation outcome or islet grafts. PMID:25165473

  19. The HH 24 Jet Complex: Collimated and Colliding Jets from a Newborn Multiple Stellar System

    NASA Astrophysics Data System (ADS)

    Reipurth, Bo

    2013-10-01

    The HH 24 complex constitutes the richest concentration of collimated bright Herbig-Haro jets known, and they originate from a small grouping of newborn binary and multiple systems. At least 6 jets are identified in deep groundbased optical interference images, and a similar number of sources in infrared images. We propose to do the first HST study of this complex, using H-alpha and [SII] filters. HST 0.05" to 0.1" angular resolution {20 to 40 AU at d 400 pc} is needed to resolve the shocks and their post-shock cooling layers for comparison with advanced numerical modeling. Our emphasis here is to explore outflows from a multiple system of newborn stars. Many of the jets show clear evidence of wiggling. The theory of jet motion from binary systems coupled with disk precession is now understood, and we will interpret the jet wiggles in this framework. Additionally, two of the HH 24 jets are showing evidence for a collision, a unique situation not seen anywhere else, and HST resolution is needed for comparison with gas-dynamic studies of jet-jet collisions. Two of the HH 24 jets are bright in the infrared [FeII] 1.644 line. In this line the main jet can be traced all the way to the source, which is the most important region for understanding the effects of binarity on the jet structure. We also apply for a second-epoch [SII] image in Cycle 23. This allows us, in addition to deriving the bulk motion, to determine such processes as expansion of the jet beam, sideways ejection in a working surface, turbulent and chaotic motions, and the effect of instabilities.

  20. Stretched Inertial Jets

    NASA Astrophysics Data System (ADS)

    Ghabache, Elisabeth; Antkowiak, Arnaud; Seon, Thomas; Villermaux, Emmanuel

    2015-11-01

    Liquid jets often arise as short-lived bursting liquid flows. Cavitation or impact-driven jets, bursting champagne bubbles, shaped-charge jets, ballistospores or drop-on-demand inkjet printing are a few examples where liquid jets are suddenly released. The trademark of all these discharge jets is the property of being stretched, due to the quenching injection. the present theoretical and experimental investigation, the structure of the jet flow field will be unraveled experimentally for a few emblematic occurrences of discharge jets. Though the injection markedly depends on each flow configuration, the jet velocity field will be shown to be systematically and rapidly attracted to the universal stretching flow z/t. The emergence of this inertial attractor actually only relies on simple kinematic ingredients, and as such is fairly generic. The universality of the jet velocity structure will be discussed.

  1. The impact of medetomidine on the protein-binding characteristics of MK-467 in canine plasma.

    PubMed

    Bennett, R C; Hokkanen, J; Raekallio, M R; Vainio, O M

    2016-08-01

    This study determined the unbound fraction of the peripheral α2 -adrenoceptor antagonist MK-467 alone and combined with medetomidine. MK-467 (0.1, 1 and 10 μm) was incubated in canine plasma with and without medetomidine (molar ratio 20:1), with human serum albumin (HSA) and with α1-acid glycoprotein (AGP). Rapid equilibrium dialysis was used for the measurement of protein binding. All samples were analysed by liquid chromatography and tandem mass spectrometry to obtain the unbound fraction (fu ) of MK-467. Unbound fractions (fu ) of MK-467 in canine plasma (mean ± standard deviation) were 27.6 ± 3.5%, 26.6 ± 0.9% and 42.4 ± 1.2% at 0.1, 1.0 and 10 μm concentrations, respectively. In the presence of medetomidine, fu were 27.5 ± 0.4%, 26.6 ± 0.9% and 41.0 ± 2.4%. The fu of MK-467 in HSA were 50.1 ± 2.5% at 0.1 μm, 49.4 ± 1.2% at 1.0 μm and 56.7 ± 0.5% at 10 μm. fu of MK-467 in AGP was 56.3 ± 3.7% at 0.1 μm, 54.6 ± 5.6% at 1.0 μm and 65.3 ± 0.4% at 10 μm. Protein binding of MK-467 was approximately 70% between 0.1 and 1.0 μm. Medetomidine had no apparent effect on the protein binding of MK-467. PMID:26763140

  2. A continuous dry 300 mK cooler for THz sensing applications

    NASA Astrophysics Data System (ADS)

    Klemencic, G. M.; Ade, P. A. R.; Chase, S.; Sudiwala, R.; Woodcraft, A. L.

    2016-04-01

    We describe and demonstrate the automated operation of a novel cryostat design that is capable of maintaining an unloaded base temperature of less than 300 mK continuously, without the need to recycle the gases within the final cold head, as is the case for conventional single shot sorption pumped 3He cooling systems. This closed dry system uses only 5 l of 3He gas, making this an economical alternative to traditional systems where a long hold time is required. During testing, a temperature of 365 mK was maintained with a constant 20 μW load, simulating the cooling requirement of a far infrared camera.

  3. Inhibition of Morphine Tolerance and Dependence by the NMDA Receptor Antagonist MK-801

    NASA Astrophysics Data System (ADS)

    Trujillo, Keith A.; Akil, Huda

    1991-01-01

    The N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor is an important mediator of several forms of neural and behavioral plasticity. The present studies examined whether NMDA receptors might be involved in the development of opiate tolerance and dependence, two examples of behavioral plasticity. The noncompetitive NMDA receptor antagonist MK-801 attenuated the development of tolerance to the analgesic effect of morphine without affecting acute morphine analgesia. In addition, MK-801 attenuated the development of morphine dependence as assessed by naloxone-precipitated withdrawal. These results suggest that NMDA receptors may be important in the development of opiate tolerance and dependence.

  4. A continuous dry 300 mK cooler for THz sensing applications.

    PubMed

    Klemencic, G M; Ade, P A R; Chase, S; Sudiwala, R; Woodcraft, A L

    2016-04-01

    We describe and demonstrate the automated operation of a novel cryostat design that is capable of maintaining an unloaded base temperature of less than 300 mK continuously, without the need to recycle the gases within the final cold head, as is the case for conventional single shot sorption pumped (3)He cooling systems. This closed dry system uses only 5 l of (3)He gas, making this an economical alternative to traditional systems where a long hold time is required. During testing, a temperature of 365 mK was maintained with a constant 20 μW load, simulating the cooling requirement of a far infrared camera. PMID:27131707

  5. On-Chip ESR Measurements of DPPH at mK Temperatures

    NASA Astrophysics Data System (ADS)

    Voesch, Wolfgang; Thiemann, Markus; Bothner, Daniel; Dressel, Martin; Scheffler, Marc

    We study electron spin resonance (ESR) of DPPH at mK temperatures. Here we employ a superconducting coplanar microwave resonator that allows convenient implementation in a dilution refrigerator as well as operation at multiple ESR frequencies, in this case 1.5 GHz, 3.0 GHz, and 4.5 GHz. We find a strong temperature and magnetic field dependence of the ESR of DPPH below 1 K, which is consistent with an antiferromagnetic transition. Our study documents the potential of this on-chip ESR technique for mK experiments and elucidates the possibility to use DPPH as an ESR reference material in this regime.

  6. Preliminary animal pharmacokinetics of the parenteral antifungal agent MK-0991 (L-743,872).

    PubMed

    Hajdu, R; Thompson, R; Sundelof, J G; Pelak, B A; Bouffard, F A; Dropinski, J F; Kropp, H

    1997-11-01

    MK-0991 (L-743,872) is a potent antifungal agent featuring long half-life pharmacokinetics. The pharmacokinetics of MK-0991 administered intravenously to mice, rats, rhesus monkeys, and chimpanzees is presented. Unique to MK-0991 is its consistent cross-species performance. The range of values for the pharmacokinetic parameters were as follows: clearance, 0.26 to 0.51 ml/min/kg; half-life, 5.2 to 7.6 h; and distributive volume, 0.11 to 0.27 liters/kg. The level of protein binding of MK-0991 was determined to be 96% in mouse and human serum. The compound exhibited high affinities for human serum albumin and at least two lipid components. The rationale for the selection of MK-0991 as a drug development candidate was based on its two- to threefold superior pharmacokinetic performance in chimpanzees over the performance of an otherwise equivalent analog, L-733,560. Once-daily dosing for MK-0991 is indicated by a graphical comparison of levels in the circulations of chimpanzees and mice. In a study of the pharmacokinetics of MK-0991 in mouse tissue, the organs were assayed following intraperitoneal administration. The area under the concentration-versus-time curves (AUC) segregated the tissues into three exposure categories relative to plasma. The tissues with greater exposure than that for plasma were liver (16 times), kidney (3 times), and large intestine (2 times). The exposure for small intestine, lung, and spleen were equivalent to that for plasma. Organs with lower levels of exposure were the heart (0.3 times that for plasma), thigh (0.2 times), and brain (0.06 times). Kinetically, drug was cleared more slowly from all tissues than from plasma, indicating that terminal-phase equilibrium had not been achieved by 24 h. Thus, some measure of accumulation is predicted for all tissues. Single daily doses of MK-0991 should provide adequate systemic levels of fungicidal activity as a result of its long half-life pharmacokinetics, wide distribution, and slowly

  7. Electric jets following the occurrence of sprites

    NASA Astrophysics Data System (ADS)

    Lee, L.; Chou, J.; Huang, S.; Chang, S.; Wu, Y.; Lee, Y.; Kuo, C.; Chen, A. B.; Su, H.; Hsu, R.; Frey, H. U.; Mende, S. B.; Takahashi, Y.; Lee, L.

    2010-12-01

    Sprites are discharges occurring at the altitudes ~40 to 90 km, which are usually associated with positive cloud-to-ground lightning (+CGs). Electric jets, which include blue jets (BJs) with the terminal altitude of ~40km and gigantic jets (GJs) emanating to the lower ionosphere, are upward discharges from the cloud tops toward the upper atmosphere. From previous ground observations, it has been reported that the secondary discharges (“palm-tree” [Heavner, 2000] or “sprite-initiated secondary TLEs” [Marshall and Inan, 2007]) following sprites occurred in altitudes between the cloud top and the bottom of the sprite. From July 2004 to June 2010, ISUAL has recorded dozens of events which resemble the secondary TLEs. From image and photometric data recorded by ISUAL, all these secondary TLEs have the characteristics of jets, so we call these events “secondary jets”. These secondary jets are categorized into two groups according to their emanating horizontal positions in relative to the sprites. Group-I secondary jets occurred in the cloud top region which is directly below the sprites. The terminal altitude is ~ 40-50km for most of group-I secondary jets. Several group-I secondary jets appear to originate from the cloud top region below the symmetric center of the clustering sprites and then propagate toward the lower ionosphere. While the group-II secondary jets originate from region outside the shielding area of the clustering sprites. In this paper, the image and the photometric characteristics of the secondary jets will be presented and the possible generating mechanisms will be discussed.

  8. A Coronal Hole Jet Observed with Hinode and the Solar Dynamics Observatory

    NASA Technical Reports Server (NTRS)

    Young, Peter H.; Muglach, Karin

    2014-01-01

    A small blowout jet was observed at the boundary of the south coronal hole on 2011 February 8 at around 21:00 UT. Images from the Atmospheric Imaging Assembly (AIA) on board the Solar Dynamics Observatory (SDO) revealed an expanding loop rising from one footpoint of a compact, bipolar bright point. Magnetograms from the Helioseismic Magnetic Imager (HMI) on board SDO showed that the jet was triggered by the cancelation of a parasitic positive polarity feature near the negative pole of the bright point. The jet emission was present for 25 mins and it extended 30 Mm from the bright point. Spectra from the EUV Imaging Spectrometer on board Hinode yielded a temperature and density of 1.6 MK and 0.9-1.7 × 10( exp 8) cu cm for the ejected plasma. Line-of-sight velocities reached up to 250 km/s. The density of the bright point was 7.6 × 10(exp 8) cu cm, and the peak of the bright point's emission measure occurred at 1.3 MK, with no plasma above 3 MK.

  9. Discovery of MK-8718, an HIV Protease Inhibitor Containing a Novel Morpholine Aspartate Binding Group.

    PubMed

    Bungard, Christopher J; Williams, Peter D; Ballard, Jeanine E; Bennett, David J; Beaulieu, Christian; Bahnck-Teets, Carolyn; Carroll, Steve S; Chang, Ronald K; Dubost, David C; Fay, John F; Diamond, Tracy L; Greshock, Thomas J; Hao, Li; Holloway, M Katharine; Felock, Peter J; Gesell, Jennifer J; Su, Hua-Poo; Manikowski, Jesse J; McKay, Daniel J; Miller, Mike; Min, Xu; Molinaro, Carmela; Moradei, Oscar M; Nantermet, Philippe G; Nadeau, Christian; Sanchez, Rosa I; Satyanarayana, Tummanapalli; Shipe, William D; Singh, Sanjay K; Truong, Vouy Linh; Vijayasaradhi, Sivalenka; Wiscount, Catherine M; Vacca, Joseph P; Crane, Sheldon N; McCauley, John A

    2016-07-14

    A novel HIV protease inhibitor was designed using a morpholine core as the aspartate binding group. Analysis of the crystal structure of the initial lead bound to HIV protease enabled optimization of enzyme potency and antiviral activity. This afforded a series of potent orally bioavailable inhibitors of which MK-8718 was identified as a compound with a favorable overall profile. PMID:27437081

  10. Plasma Heating to Super-Hot Temperatures (>30 MK) in the August 9, 2011 Solar Flare

    NASA Astrophysics Data System (ADS)

    Sharykin, Ivan; Struminsky, Alexei; Zimovets, Ivan

    2015-08-01

    We investigate the August 9, 2011 solar flare of X-ray class X6.9, the "hottest" flare from 2000 to 2012, with a peak plasma temperature according to GOES data of 33 MK. Our goal is to determine the cause of such an anomalously high plasma temperature and to investigate the energy balance in the flare region with allowance made for the presence of a super-hot plasma (>30 MK). We analyze the RHESSI, GOES, AIA/SDO, and EVE/SDO data and discuss the spatial structure of the flare region and the results of our spectral analysis of its X-ray emission. Our analysis of the RHESSI X-ray spectra is performed in the one-temperature and two-temperature approximations by taking into account the emission of hot (20 MK) and super-hot (45 MK) plasmas. The hard X-ray spectrum in both models is fitted by power laws. The observed peculiarities of the flare are shown to be better explained in terms of the two-temperature model, in which the super-hot plasma is located at the flare loop tops (or in the magnetic cusp region). The formation of the super-hot plasma can be associated with its heating through primary energy release and with the suppression of thermal conduction.

  11. Au-Ge film thermometers for temperature range 30 mK-300 K

    NASA Astrophysics Data System (ADS)

    Béthoux, O.; Brusetti, R.; Lasjaunias, J. C.; Sahling, S.

    After optmization of the Au concentration and the annealing temperature, highly sensitive Au-Ge film thermometers for the temperature range 30 mK-300 K were obtained. The thermometers show good reproducibility, a very short relaxation time constant at low temperatures and are quite insensitive to magnetic field.

  12. MK3 controls Polycomb target gene expression via negative feedback on ERK

    PubMed Central

    2012-01-01

    Background Gene-environment interactions are mediated by epigenetic mechanisms. Polycomb Group proteins constitute part of an epigenetic cellular transcriptional memory system that is subject to dynamic modulation during differentiation. Molecular insight in processes that control dynamic chromatin association and dissociation of Polycomb repressive complexes during and beyond development is limited. We recently showed that MK3 interacts with Polycomb repressive complex 1 (PRC1). The functional relevance of this interaction, however, remained poorly understood. MK3 is activated downstream of mitogen- and stress-activated protein kinases (M/SAPKs), all of which fulfill crucial roles during development. We here use activation of the immediate-early response gene ATF3, a bona fide PRC1 target gene, as a model to study how MK3 and its effector kinases MAPK/ERK and SAPK/P38 are involved in regulation of PRC1-dependent ATF3 transcription. Results Our current data show that mitogenic signaling through ERK, P38 and MK3 regulates ATF3 expression by PRC1/chromatin dissociation and epigenetic modulation. Mitogenic stimulation results in transient P38-dependent H3S28 phosphorylation and ERK-driven PRC1/chromatin dissociation at PRC1 targets. H3S28 phosphorylation by itself appears not sufficient to induce PRC1/chromatin dissociation, nor ATF3 transcription, as inhibition of MEK/ERK signaling blocks BMI1/chromatin dissociation and ATF3 expression, despite induced H3S28 phosphorylation. In addition, we establish that concomitant loss of local H3K27me3 promoter marking is not required for ATF3 activation. We identify pERK as a novel signaling-induced binding partner of PRC1, and provide evidence that MK3 controls ATF3 expression in cultured cells via negative regulatory feedback on M/SAPKs. Dramatically increased ectopic wing vein formation in the absence of Drosophila MK in a Drosophila ERK gain-of-function wing vein patterning model, supports the existence of MK

  13. Jets of incipient liquids

    NASA Astrophysics Data System (ADS)

    Reshetnikov, A. V.; Mazheiko, N. A.; Skripov, V. P.

    2000-05-01

    Jets of incipient water escaping into the atmosphere through a short channel are photographed. In some experiments. complete disintegration of the jet is observed. The relationship of this phenomenon with intense volume incipience is considered. The role of the Coanda effect upon complete opening of the jet is revealed. Measurement results of the recoil force R of the jets of incipient liquids are presented. Cases of negative thrust caused by the Coanda effect are noted. Generalization of experimental data is proposed.

  14. NASA Jet Noise Research

    NASA Technical Reports Server (NTRS)

    Henderson, Brenda

    2012-01-01

    The presentation highlights jet-noise research conducted in the Subsonic Fixed Wing, Supersonics, and Environmentally Responsible Aviation Projects in the Fundamental Aeronautics Program at NASA. The research efforts discussed include NASA's updated Aircraft NOise Prediction Program (ANOPP2), acoustic-analogy-based prediction tools, jet-surface-interaction studies, plasma-actuator investigations, N+2 Supersonics Validation studies, rectangular-jet experiments, twin-jet experiments, and Hybrid Wind Body (HWB) activities.

  15. Study of Jet Transverse Momentum and Jet Rapidity Dependence on Dijet Azimuthal Decorrelations

    SciTech Connect

    Chakravarthula, Kiran

    2012-01-01

    In a collision experiment involving highly energetic particles such as hadrons, processes at high momentum transfers can provide information useful for many studies involving Quantum Chromodynamics (QCD). One way of analyzing these interactions is through angular distributions. In hadron-hadron collisions, the angular distribution between the two leading jets with the largest transverse momentum (pT ) is affected by the production of additional jets. While soft radiation causes small differences in the azimuthal angular distribution of the two leading jets produced in a collision event, additional hard jets produced in the event have more pronounced influence on the distribution of the two leading jets produced in the collision. Thus, the dijet azimuthal angular distribution can serve as a variable that can be used to study the transition from soft to hard QCD processes in a collision event. This dissertation presents a triple-differential study involving the azimuthal angular distribution and the jet transverse momenta, and jet rapidities of the first two leading jets. The data used for this research are obtained from proton-antiproton (p$\\bar{p}$) collisions occurring at a center of mass energy of 1.96TeV, using the DØ detector in Run II of the Tevatron Collider at the Fermi National Accelerator Laboratory (FNAL) in Illinois, USA. Comparisons are made to perturbative QCD (pQCD) predictions at next-to-leading order (NLO).

  16. Magnetic jets in long GRBs: jet stability, energy dissipation & the connection with the magnetar model

    NASA Astrophysics Data System (ADS)

    Bromberg, Omer

    2016-07-01

    It is commonly accepted that jets in long GRBs are powered by the magnetized rotation of a compact object: a BH or a fastly rotating magnetar. Such jets are intrinsically unstable to disruptive kink modes, yet they maintain their shape over many orders of magnitude as they propagate through the star and beyond, while converting their electromagnetic energy into radiation and kinetic energy. This calls for an efficient dissipation mechanism to work within the jet, without causing its disruption. In this talk I will present results from a 3D study of relativistic magnetized GRB jets propagating in stellar envelopes. The collimation of the jet leads to two types of instabilities: i) a local kink mode that causes internal dissipation of the magnetic energy to a state of equipartition with the thermal energy, ii) a global kink mode, which bodily deforms the jet, causing it to slow down may lead to jet stalling. I will discuss the interesting implications from these results on the energy emission in long GRBs and on the type of compact objects that power them. In particular I will show that within the framework of the magnetar model, the jet is expected to become highly kinked unstable and fail to breakout of the star. Instead it inflates a bubble with ~10^52 erg of energy at the center of the star leading to a highly energetic supernova.

  17. Measurement of sigma(p anti-p -> t anti-t) in the tau + jets channel by the D� experiment at Run II of the Tevatron Collider

    SciTech Connect

    Arov, Mikhail; /Northern Illinois U.

    2008-07-01

    The top quark is the heaviest and most mysterious of the known elementary particles. Therefore, careful study of its production rate and other properties is of utmost importance for modern particle physics. The Tevatron is the only facility currently capable of studying top quark properties by on-shell production. Measurement of the top quark pair production cross section is one of the major goals of the Tevatron Run II physics program. It provides an excellent test of QCD at energies exceeding 100 GeV. We report on a new measurement of p{bar p} {yields} t{bar t} production at {radical} = 1.96 TeV using 350 pb{sup -1} of data collected with the D0 detector between 2002 and 2005. We focus on the final state where a W boson from one of the top quarks decays into a {tau} lepton and its associated neutrino, while the other decays into a quark-antiquark pair. We aim to select those events in which the {tau} lepton subsequently decays to one or three charged hadrons, zero or more neutral hadrons and a tau neutrino (the charge conjugate processes are implied in all of the above). The observable signature thus consists of a narrow calorimeter shower with associated track(s) characteristic of a hadronic tau decay, four or more jets, of which two are initiated by b quarks accompanying the W's in the top quark decays, and a large net missing momentum in the transverse plane due to the energetic neutrino-antineutrino pair that leave no trace in the detector media. The preliminary result for the measured cross section is: {sigma}(t{bar t}) = 5.1{sub -3.5}{sup +4.3}(stat){sub -0.7}{sup +0.7}(syst) {+-} 0.3 (lumi.) pb.

  18. DNA microarray unravels rapid changes in transcriptome of MK-801 treated rat brain

    PubMed Central

    Kobayashi, Yuka; Kulikova, Sofya P; Shibato, Junko; Rakwal, Randeep; Satoh, Hiroyuki; Pinault, Didier; Masuo, Yoshinori

    2015-01-01

    AIM: To investigate the impact of MK-801 on gene expression patterns genome wide in rat brain regions. METHODS: Rats were treated with an intraperitoneal injection of MK-801 [0.08 (low-dose) and 0.16 (high-dose) mg/kg] or NaCl (vehicle control). In a first series of experiment, the frontoparietal electrocorticogram was recorded 15 min before and 60 min after injection. In a second series of experiments, the whole brain of each animal was rapidly removed at 40 min post-injection, and different regions were separated: amygdala, cerebral cortex, hippocampus, hypothalamus, midbrain and ventral striatum on ice followed by DNA microarray (4 × 44 K whole rat genome chip) analysis. RESULTS: Spectral analysis revealed that a single systemic injection of MK-801 significantly and selectively augmented the power of baseline gamma frequency (30-80 Hz) oscillations in the frontoparietal electroencephalogram. DNA microarray analysis showed the largest number (up- and down- regulations) of gene expressions in the cerebral cortex (378), midbrain (376), hippocampus (375), ventral striatum (353), amygdala (301), and hypothalamus (201) under low-dose (0.08 mg/kg) of MK-801. Under high-dose (0.16 mg/kg), ventral striatum (811) showed the largest number of gene expression changes. Gene expression changes were functionally categorized to reveal expression of genes and function varies with each brain region. CONCLUSION: Acute MK-801 treatment increases synchrony of baseline gamma oscillations, and causes very early changes in gene expressions in six individual rat brain regions, a first report. PMID:26629322

  19. Oxytocin reversed MK-801-induced social interaction and aggression deficits in zebrafish.

    PubMed

    Zimmermann, Fernanda Francine; Gaspary, Karina Vidarte; Siebel, Anna Maria; Bonan, Carla Denise

    2016-09-15

    Changes in social behavior occur in several neuropsychiatric disorders such as schizophrenia and autism. The interaction between individuals is an essential aspect and an adaptive response of several species, among them the zebrafish. Oxytocin is a neuroendocrine hormone associated with social behavior. The aim of the present study was to investigate the effects of MK-801, a non-competitive antagonist of glutamate NMDA receptors, on social interaction and aggression in zebrafish. We also examined the modulation of those effects by oxytocin, the oxytocin receptor agonist carbetocin and the oxytocin receptor antagonist L-368,899. Our results showed that MK-801 induced a decrease in the time spent in the segment closest to the conspecific school and in the time spent in the segment nearest to the mirror image, suggesting an effect on social behavior. The treatment with oxytocin after the exposure to MK-801 was able to reestablish the time spent in the segment closest to the conspecific school, as well as the time spent in the segment nearest to the mirror image. In addition, in support of the role of the oxytocin pathway in modulating those responses, we showed that the oxytocin receptor agonist carbetocin reestablished the social and aggressive behavioral deficits induced by MK-801. However, the oxytocin receptor antagonist L-368,899 was not able to reverse the behavioral changes induced by MK-801. This study supports the critical role for NMDA receptors and the oxytocinergic system in the regulation of social behavior and aggression which may be relevant for the mechanisms associated to autism and schizophrenia. PMID:27247142

  20. Prewhirl Jet Model

    NASA Technical Reports Server (NTRS)

    Meng, S. Y.; Jensen, M.; Jackson, E. D.

    1985-01-01

    Simple accurate model of centrifugal or rocket engine pumps provides information necessary to design inducer backflow deflector, backflow eliminator and prewhirl jet in jet mixing zones. Jet design based on this model shows improvement in inducer suction performance and reduced cavitation damage.

  1. Deficiency of MAPK-activated protein kinase 2 (MK2) prevents adverse remodelling and promotes endothelial healing after arterial injury.

    PubMed

    Kapopara, P R; von Felden, J; Soehnlein, O; Wang, Y; Napp, L C; Sonnenschein, K; Wollert, K C; Schieffer, B; Gaestel, M; Bauersachs, J; Bavendiek, U

    2014-12-01

    Maladaptive remodelling of the arterial wall after mechanical injury (e. g. angioplasty) is characterised by inflammation, neointima formation and media hypertrophy, resulting in narrowing of the affected artery. Moreover, mechanical injury of the arterial wall causes loss of the vessel protecting endothelial cell monolayer. Mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2), a major downstream target of p38 MAPK, regulates inflammation, cell migration and proliferation, essential processes for vascular remodelling and re-endothelialisation. Therefore, we investigated the role of MK2 in remodelling and re-endothelialisation after arterial injury in genetically modified mice in vivo. Hypercholesterolaemic low-density-lipoprotein-receptor-deficient mice (ldlr-/-) were subjected to wire injury of the common carotid artery. MK2-deficiency (ldlr-/-/mk2-/-) nearly completely prevented neointima formation, media hypertrophy, and lumen loss after injury. This was accompanied by reduced proliferation and migration of MK2-deficient smooth muscle cells. In addition, MK2-deficiency severely reduced monocyte adhesion to the arterial wall (day 3 after injury, intravital microscopy), which may be attributed to reduced expression of the chemokine ligands CCL2 and CCL5. In line, MK2-deficiency significantly reduced the content of monocytes, neutrophiles and lymphocytes of the arterial wall (day 7 after injury, flow cytometry). In conclusion, in a model of endothelial injury (electric injury), MK2-deficiency strongly increased proliferation of endothelial cells and improved re-endothelialisation of the arterial wall after injury. Deficiency of MK2 prevents adverse remodelling and promotes endothelial healing of the arterial wall after injury, suggesting that MK2-inhibition is a very attractive intervention to prevent restenosis after percutaneous therapeutic angioplasty. PMID:25120198

  2. New antineoplastic agent, MK615, from UME (a Variety of) Japanese apricot inhibits growth of breast cancer cells in vitro.

    PubMed

    Nakagawa, Aya; Sawada, Tokihiko; Okada, Toshie; Ohsawa, Tatsushi; Adachi, Masakazu; Kubota, Keiichi

    2007-01-01

    MK615 is an extract mixture containing hydrophobic substances from Japanese apricot. In this study, the antineoplastic effects of MK615 against breast cancer cells were investigated. Two breast cancer cell lines, MDA-MB-468 (MDA) and MCF7, were cultured with (600, 300, and 150 mug/mL) or without MK615. After 72 hours of incubation, growth inhibition was evaluated by MTT assay. The cells were then cultured with MK615 (300 mug/mL) and morphological changes were studied by light and electron microscopy. Finally, the mechanism of the antineoplastic effect of MK615 was evaluated by cell cycle and apoptosis assay. MK615 inhibited the growth of MDA and MCF7 in a dose-dependent manner. The percentage growth inhibition of MDA at dosages of 600, 300, and 150 mug/mL was 59.2%, 52.4%, and 23.3%, respectively, and that for MCF7 was 83.5%, 52.7%, and 16.6%, respectively. Morphological changes after MK615 treatment included massive vacuolization in the cytoplasm and apoptotic changes in the nucleus. These changes began to be apparent after at least 6 hours of incubation. Cell cycle analysis showed that MK615 increased the proportion of cells in the G2-M phase in both MDA (7.8-11.7%) and MCF7 (8.1-18.7%), and finally both cell lines became apoptotic. The proportion of apoptotic cells increased with incubation time. MK615 effectively inhibits the growth of breast cancer cells in vitro, possibly by cell cycle modification and apotosis induction. MK615 should be further investigated as a promising anti-breast cancer agent. PMID:17214792

  3. Aeroacoustics of hot jets

    NASA Astrophysics Data System (ADS)

    Viswanathan, K.

    2004-10-01

    A systematic study has been undertaken to quantify the effect of jet temperature on the noise radiated by subsonic jets. Nozzles of different diameters were tested to uncover the effects of Reynolds number. All the tests were carried out at Boeing's Low Speed Aeroacoustic Facility, with simultaneous measurement of thrust and noise. It is concluded that the change in spectral shape at high jet temperatures, normally attributed to the contribution from dipoles, is due to Reynolds number effects and not dipoles. This effect has not been identified before. A critical value of the Reynolds number that would need to be maintained to avoid the effects associated with low Reynolds number has been estimated to be {˜}400 000. It is well-known that large-scale structures are the dominant generators of noise in the peak radiation direction for high-speed jets. Experimental evidence is presented that shows the spectral shape at angles close to the jet axis from unheated low subsonic jets to be the same as from heated supersonic jets. A possible mechanism for the observed trend is proposed. When a subsonic jet is heated with the Mach number held constant, there is a broadening of the angular sector in which peak radiation occurs. Furthermore, there is a broadening of the spectral peak. Similar trends have been observed at supersonic Mach numbers. The spectral shapes in the forward quadrant and in the near-normal angles from unheated and heated subsonic jets also conform to the universal shape obtained from supersonic jet data. Just as for unheated jets, the peak frequency at angles close to the jet axis is independent of jet velocity as long as the acoustic Mach number is less than unity. The extensive database generated in the current test programme is intended to provide test cases with high-quality data that could be used for the evaluation of theoretical/semi-theoretical jet noise prediction methodologies.

  4. Z boson production in association with heavy quark jets at D0

    SciTech Connect

    Joseph Anthony Zennamo, III

    2013-10-28

    The dominant background in searches for a Higgs boson decaying into b-quarks at the Tevatron is production of a Z boson in association with either b- or c-quark initiated jets (b or c jets). This thesis describes the first measurements of the ratio of differential cross sections σ (Z + b jet)/ σ(Z + jet), and the first measurements of the ratio of cross sections σ (Z + c jet)/ σ(Z + jet) and σ (Z + c jet)/ σ(Z + b jet). These measurements are performed using the full D0 Run II data set corresponding to an integrated luminosity of 9.7 fb-1. The ratio of differential cross sections σ(Z + b jet)/σ (Z + jet) have been measured as a function of jet and Z boson pT , jet η , and Δφ(Z, jet). The Z+c jet ratios of differential cross sections are measured as a function of jet and Z boson pT .

  5. A search for ionized jets towards massive young stellar objects

    NASA Astrophysics Data System (ADS)

    Purser, S. J. D.; Lumsden, S. L.; Hoare, M. G.; Urquhart, J. S.; Cunningham, N.; Purcell, C. R.; Brooks, K. J.; Garay, G.; Gúzman, A. E.; Voronkov, M. A.

    2016-07-01

    Radio continuum observations using the Australia telescope compact array at 5.5, 9.0, 17.0 and 22.8 GHz have detected free-free emission associated with 45 of 49 massive young stellar objects and H II regions. Of these, 26 sources are classified as ionized jets (12 of which are candidates), 2 as ambiguous jets or disc winds, 1 as a disc-wind, 14 as H II regions and 2 were unable to be categorized. Classification as ionized jets is based upon morphology, radio flux and spectral index, in conjunction with previous observational results at other wavelengths. Radio luminosity and momentum are found to scale with bolometric luminosity in the same way as low-mass jets, indicating a common mechanism for jet production across all masses. In 13 of the jets, we see associated non-thermal/optically thin lobes resulting from shocks either internal to the jet and/or at working surfaces. 10 jets display non-thermal (synchrotron emission) spectra in their lobes, with an average spectral index of α = -0.55 consistent with Fermi acceleration in shocks. This shows that magnetic fields are present, in agreement with models of jet formation incorporating magnetic fields. Since the production of collimated radio jets is associated with accretion processes, the results presented in this paper support the picture of disc-mediated accretion for the formation of massive stars with an upper limit on the jet phase lasting approximately 6.5 × 104 yr. Typical mass-loss rates in the jet are found to be 1.4 × 10-5 M⊙ yr-1 with associated momentum rates of the order of (1-2) × 10-2 M⊙ km s-1 yr-1.

  6. Causality and stability of cosmic jets

    NASA Astrophysics Data System (ADS)

    Porth, Oliver; Komissarov, Serguei S.

    2015-09-01

    In stark contrast to their laboratory and terrestrial counterparts, cosmic jets appear to be very stable. They are able to penetrate vast spaces, which exceed by up to a billion times the size of their central engines. We propose that the reason behind this remarkable property is the loss of causal connectivity across these jets, caused by their rapid expansion in response to fast decline of external pressure with the distance from the `jet engine'. In atmospheres with power-law pressure distribution, pext ∝ z-κ, the total loss of causal connectivity occurs, when κ > 2 - the steepness which is expected to be quite common for many astrophysical environments. This conclusion does not seem to depend on the physical nature of jets - it applies both to relativistic and non-relativistic flows, both magnetically dominated and unmagnetized jets. In order to verify it, we have carried out numerical simulations of moderately magnetized and moderately relativistic jets. The results give strong support to our hypothesis and provide with valuable insights. In particular, we find that the z-pinched inner cores of magnetic jets expand slower than their envelopes and become susceptible to instabilities even when the whole jet is stable. This may result in local dissipation and emission without global disintegration of the flow. Cosmic jets may become globally unstable when they enter flat sections of external atmospheres. We propose that the Fanaroff-Riley (FR) morphological division of extragalactic radio sources into two classes is related to this issue. In particular, we argue that the low power FR-I jets become reconfined, causally connected and globally unstable on the scale of galactic X-ray coronas, whereas more powerful FR-II jets reconfine much further out, already on the scale of radio lobes and remain largely intact until they terminate at hotspots. Using this idea, we derived the relationship between the critical jet power and the optical luminosity of the host

  7. Theory of laminar viscous jets

    NASA Astrophysics Data System (ADS)

    Martynenko, O. G.; Korovkin, V. N.; Sokovishin, Iu. A.

    Results of recent theoretical studies of laminar jet flows of a viscous incompressible fluid are reviewed. In particular, attention is given to plane, fan-shaped, axisymmetric, and swirling jet flows; jet flows behind bodies; and slipstream jet flows. The discussion also covers dissipation of mechanical energy in jet flows, jet flows with a zero excess momentum, and asymptotic series expansions in the theory of jet flows.

  8. Evaluation of the ocean technology system's MK 1-S wireless surface unit, MK 1 DCI two diver air radio, MK 1-D-A wireless diver unit, MK 1-D-H hardwire diver unit and MK 1-D/S unit

    NASA Astrophysics Data System (ADS)

    Reyle, B. E.

    1985-05-01

    The OTS was evaluated for intelligibility, reliability and human engineering. The test subjects possessed various levels of experience with wireless or hardwire communication and SCUBA. The conditions under which the equipment was tested varied. Surface air temperatures ranged from 37 to 85 F; water temperatures from 65 to 80 F; and water depths from 8 feet of seawater (FSW) to greater than 60 FSW. The tests were conducted inside a circular 30 foot deep ascent tower, in shallow open bay water, and finally in an open ocean environment. The equipment was evaluated in areas of both high and low noise levels on the surface as well as in water. The OTS produced an overall intelligibility of 89.24% during manned open water testing using the Modified Rhyme Test (MRT) as the evaluation criteria, with a minimum effective range of 330 yards at 12 FSW and at least 875 yards, although it appears that the range of the MK 1-D-A is somewhat greater. Human engineering aspects of the OTS were found to be more than satisfactory, with no material failures encountered during testing. It is interesting to note that whenever the equipment required minor adjustments, these could be effected by the diver in the water (on the surface) and in most cases in less than 5 minutes. The amount of maintenance required on the OTS was minimal.

  9. Search for WW and WZ production in lepton, neutrino plus jets final states at CDF Run II and Silicon module production and detector control system for the ATLAS SemiConductor Tracker

    SciTech Connect

    Sfyrla, Anna; /Geneva U.

    2008-03-01

    In the first part of this work, we present a search for WW and WZ production in charged lepton, neutrino plus jets final states produced in p{bar p} collisions with {radical}s = 1.96 TeV at the Fermilab Tevatron, using 1.2 fb{sup -1} of data accumulated with the CDF II detector. This channel is yet to be observed in hadron colliders due to the large singleWplus jets background. However, this decay mode has a much larger branching fraction than the cleaner fully leptonic mode making it more sensitive to anomalous triple gauge couplings that manifest themselves at higher transverse W momentum. Because the final state is topologically similar to associated production of a Higgs boson with a W, the techniques developed in this analysis are also applicable in that search. An Artificial Neural Network has been used for the event selection optimization. The theoretical prediction for the cross section is {sigma}{sub WW/WZ}{sup theory} x Br(W {yields} {ell}{nu}; W/Z {yields} jj) = 2.09 {+-} 0.14 pb. They measured N{sub Signal} = 410 {+-} 212(stat) {+-} 102(sys) signal events that correspond to a cross section {sigma}{sub WW/WZ} x Br(W {yields} {ell}{nu}; W/Z {yields} jj) = 1.47 {+-} 0.77(stat) {+-} 0.38(sys) pb. The 95% CL upper limit to the cross section is estimated to be {sigma} x Br(W {yields} {ell}{nu}; W/Z {yields} jj) < 2.88 pb. The second part of the present work is technical and concerns the ATLAS SemiConductor Tracker (SCT) assembly phase. Although technical, the work in the SCT assembly phase is of prime importance for the good performance of the detector during data taking. The production at the University of Geneva of approximately one third of the silicon microstrip end-cap modules is presented. This collaborative effort of the university of Geneva group that lasted two years, resulted in 655 produced modules, 97% of which were good modules, constructed within the mechanical and electrical specifications and delivered in the SCT collaboration for assembly on

  10. MMI-0100 inhibits cardiac fibrosis in myocardial infarction by direct actions on cardiomyocytes and fibroblasts via MK2 inhibition

    PubMed Central

    Xu, Lei; Yates, Cecelia C.; Lockyer, Pamela; Xie, Liang; Bevilacqua, Ariana; He, Jun; Lander, Cynthia; Patterson, Cam; Willis, Monte

    2014-01-01

    The cell-permeant peptide inhibitor of MAPKAP kinase 2 (MK2), MMI-0100, inhibits MK2 and downstream fibrosis and inflammation. Recent studies have demonstrated that MMI-0100 reduces intimal hyperplasia in a mouse vein graft model, pulmonary fibrosis in a murine bleomycin-induced model and development of adhesions in conjunction with abdominal surgery. MK2 is critical to the pathogenesis of ischemic heart injury as MK2 −/− mice are resistant to ischemic remodeling. Therefore, we tested the hypothesis that inhibiting MK2 with MMI-0100 would protect the heart after acute myocardial infarction (AMI) in vivo. AMI was induced by placing a permanent LAD coronary ligation. When MMI-0100 peptide was given 30 minutes after permanent LAD coronary artery ligation, the resulting fibrosis was reduced/prevented ~50% at a 2 week time point, with a corresponding improvement in cardiac function and decrease in left ventricular dilation. In cultured cardiomyocytes and fibroblasts, MMI-0100 inhibited MK2 to reduce cardiomyocyte caspase 3/7 activity, while enhancing primary cardiac fibroblast caspase 3/7 activity, which may explain MMI-0100’s salvage of cardiac function and anti-fibrotic effects in vivo. These findings suggest that therapeutic inhibition of MK2 after acute MI, using rationally-designed cell-permeant peptides, inhibits cardiac fibrosis and maintains cardiac function by mechanisms that involve inhibiting cardiomyocyte apoptosis, while enhancing primary cardiac fibroblast cell death. PMID:25257914

  11. Targeting of Carbon Ion-Induced G2 Checkpoint Activation in Lung Cancer Cells Using Wee-1 Inhibitor MK-1775.

    PubMed

    Ma, Hongyu; Takahashi, Akihisa; Sejimo, Yukihiko; Adachi, Akiko; Kubo, Nobuteru; Isono, Mayu; Yoshida, Yukari; Kanai, Tatsuaki; Ohno, Tatsuya; Nakano, Takashi

    2015-12-01

    The potent inhibitor of the cell cycle checkpoint regulatory factor Wee-1, MK-1775, has been reported to enhance non-small cell lung cancer (NSCLC) cell sensitivity to photon radiation by abrogating radiation-induced G2 arrest. However, little is known about the effects of this sensitizer after exposure to carbon (C)-ion radiation. The purpose of this study was therefore to investigate the effects of C ions in combination with MK-1775 on the killing of NSCLC cells. Human NSCLC H1299 cells were exposed to X rays or C ions (290 MeV/n, 50 keV/μm at the center of a 6 cm spread-out Bragg peak) in the presence of MK-1775. The cell cycle was analyzed using flow cytometry and Western blotting. Radiosensitivity was determined using clonogenic survival assays. The mechanisms underlying MK-1775 radiosensitization were studied by observing H2AX phosphorylation and mitotic catastrophe. G2 checkpoint arrest was enhanced 2.3-fold by C-ion exposure compared with X-ray exposure. Radiation-induced G2 checkpoint arrest was abrogated by MK-1775. Exposure to radiation resulted in a significant reduction in the mitotic ratio and increased phosphorylation of cyclin-dependent kinase 1 (Cdk1), the primary downstream mediator of Wee-1-induced G2 arrest. The Wee-1 inhibitor, MK-1775 restored the mitotic ratio and suppressed Cdk1 phosphorylation. In addition, MK-1775 increased H1299 cell sensitivity to C ions and X rays independent of TP53 status. MK-1775 also significantly increased H2AX phosphorylation and mitotic catastrophe in irradiated cells. These results suggest that the G2 checkpoint inhibitor MK-1775 can enhance the sensitivity of human NSCLC cells to C ions as well as X rays. PMID:26645158

  12. Jet Substructure Without Trees

    SciTech Connect

    Jankowiak, Martin; Larkoski, Andrew J.; /SLAC /Stanford U., ITP

    2011-08-19

    We present an alternative approach to identifying and characterizing jet substructure. An angular correlation function is introduced that can be used to extract angular and mass scales within a jet without reference to a clustering algorithm. This procedure gives rise to a number of useful jet observables. As an application, we construct a top quark tagging algorithm that is competitive with existing methods. In preparation for the LHC, the past several years have seen extensive work on various aspects of collider searches. With the excellent resolution of the ATLAS and CMS detectors as a catalyst, one area that has undergone significant development is jet substructure physics. The use of jet substructure techniques, which probe the fine-grained details of how energy is distributed in jets, has two broad goals. First, measuring more than just the bulk properties of jets allows for additional probes of QCD. For example, jet substructure measurements can be compared against precision perturbative QCD calculations or used to tune Monte Carlo event generators. Second, jet substructure allows for additional handles in event discrimination. These handles could play an important role at the LHC in discriminating between signal and background events in a wide variety of particle searches. For example, Monte Carlo studies indicate that jet substructure techniques allow for efficient reconstruction of boosted heavy objects such as the W{sup {+-}} and Z{sup 0} gauge bosons, the top quark, and the Higgs boson.

  13. Thermoregulator and helium-level indicator using MK-64 pocket calculator

    SciTech Connect

    Bogdanov, S.V.; Donchenko, N.Ya.

    1987-08-01

    A thermoregulator for a helium cryostat and helium-level indicator are described that are based on an MK-64 programmable picket calculator with a built-in analog-digital converter. The temperature and helium-level sensors are TVO carbon resistors. The MK-64 makes it possible to maintain or change by program a temperature in the range of 1.2-77/sup 0/K with an accuracy of 0.05-0.5/sup 0/K and also to output to the calculator display and peripheral devices the temperature and any function of temperature. The calculator display indicates the presence of helium in the cryostat and the level of the helium tank.

  14. Reflectometry measurements of 1/f noise in SQUID phase qubits at mK temperatures

    NASA Astrophysics Data System (ADS)

    Cooper, B. K.; Lewis, R. M.; Palmer, B. S.; Zaretskey, V.; Przybysz, A. J.; Kwon, H.; Anderson, J. R.; Lobb, C. J.; Wellstood, F. C.

    2009-03-01

    We measure 1/f noise spectra in dc SQUID phase qubits using a microwave reflectometry technique. One of the SQUID junctions is shunted by a large capacitor, forming a microwave frequency resonator biased and driven to show nonlinear response, typically at 1.5 GHz. This nonlinearity means small current or flux fluctuations produce large changes in reflected phase which we can measure using homodyne detection. Measurements from aluminum qubits on sapphire are compared to previous measurements of 1/f flux noise in SQUIDs and a similarly designed Nb/AlOx/Nb on silicon dc SQUID qubit fabricated by Hypres; data was taken at temperatures ranging from 50 mK to 500 mK.

  15. Monitoring Excitations of the N =1 Landau Level by Optical Emission at mK Temperatures

    NASA Astrophysics Data System (ADS)

    Levy, Antonio; Wurstbauer, Ursula; Fields, Dov; Pinczuk, Aron; Watson, John; Mondal, Sumit; Manfra, Michael J.; West, Ken W.; Pfeiffer, Loren N.

    2013-03-01

    Optical emission experiments have proven to be powerful contactless probe of collective states of electrons in the second (N =1) Landau Level (LL). We report the emission spectrum from optical recombination in the N =0 and N =1 LL's the second LL. The 2DEG is confined in ultra-high-mobility GaAs quantum well structures. Optical emission red-shifted from the main luminescence of the N =0 and N =1 LL are interpreted as shakeup processes of quasiparticles in the N =1 LL. Results of two samples with different carrier densities measured in the temperature range of 42mK <=T <=650mK will be compared. The experimental observations will be discussed taking into account the striking quantum phases dominating the second LL. Supported by NSF and AvH

  16. Targeting p38 or MK2 Enhances the Anti-Leukemic Activity of Smac-Mimetics.

    PubMed

    Lalaoui, Najoua; Hänggi, Kay; Brumatti, Gabriela; Chau, Diep; Nguyen, Nhu-Y N; Vasilikos, Lazaros; Spilgies, Lisanne M; Heckmann, Denise A; Ma, Chunyan; Ghisi, Margherita; Salmon, Jessica M; Matthews, Geoffrey M; de Valle, Elisha; Moujalled, Donia M; Menon, Manoj B; Spall, Sukhdeep Kaur; Glaser, Stefan P; Richmond, Jennifer; Lock, Richard B; Condon, Stephen M; Gugasyan, Raffi; Gaestel, Matthias; Guthridge, Mark; Johnstone, Ricky W; Munoz, Lenka; Wei, Andrew; Ekert, Paul G; Vaux, David L; Wong, W Wei-Lynn; Silke, John

    2016-02-01

    Birinapant is a smac-mimetic (SM) in clinical trials for treating cancer. SM antagonize inhibitor of apoptosis (IAP) proteins and simultaneously induce tumor necrosis factor (TNF) secretion to render cancers sensitive to TNF-induced killing. To enhance SM efficacy, we screened kinase inhibitors for their ability to increase TNF production of SM-treated cells. We showed that p38 inhibitors increased TNF induced by SM. Unexpectedly, even though p38 is required for Toll-like receptors to induce TNF, loss of p38 or its downstream kinase MK2 increased induction of TNF by SM. Hence, we show that the p38/MK2 axis can inhibit or promote TNF production, depending on the stimulus. Importantly, clinical p38 inhibitors overcame resistance of primary acute myeloid leukemia to birinapant. PMID:26859455

  17. On size tripartite Ramsey numbers of P3 versus mK1,n

    NASA Astrophysics Data System (ADS)

    Lusiani, Anie; Baskoro, Edy Tri; Saputro, Suhadi Wido

    2016-02-01

    Let Kl×t be a complete, balanced, multipartite graph consisting of l partite sets and t vertices in each partite set. For simple graphs G and H, the size multipartite Ramsey number mj (G, H) is the smallest natural number t such that any arbitrary red-blue coloring on the edges of Kl×t contains a red G or a blue H as a subgraph. In particular, if j = 3 then m3(G, H) is called the size tripartite Ramsey number of G and H. In this paper, we determine the exact values of the size tripartite numbers m3(P3, mK1,n) for all integers m ≥ 1 and n ≥ 3, where P3 is a path of order 3 and mK1,n is a disjoint union of m copies of a star K1,n.

  18. MK Classification and Dynamical Masses for Late-Type Visual Binaries

    NASA Astrophysics Data System (ADS)

    Tamazian, Vakhtang S.; Docobo, José A.; Melikian, Norair D.; Karapetian, Arthur A.

    2006-06-01

    On the basis of slit spectra obtained with the SCORPIO spectral camera attached to the 2.6 m telescope of the V. Ambartsumian Byurakan Astrophysical Observatory (Armenia), MK classifications for 30 visual binaries comprising mostly late K and M type stars are presented. Comparison with other determinations shows that this configuration provides a reliable MK classification. Dynamical masses for 25 systems are computed. Using standard mass-luminosity calibrations, individual mass sums for 11 pairs consisting of virtually single, nonvariable dwarfs are calculated, showing a good agreement with corresponding dynamical masses. The dynamical parallax of HIP 112354 is closer to the trigonometric parallax given in the Yale General Catalogue of Trigonometric Stellar Parallaxes (van Altena et al.) than to the Hipparcos parallax.

  19. Sub-50-mK Electronic Cooling with Large-Area Superconducting Tunnel Junctions

    NASA Astrophysics Data System (ADS)

    Nguyen, H. Q.; Meschke, M.; Courtois, H.; Pekola, J. P.

    2014-11-01

    In electronic cooling with superconducting tunnel junctions, the cooling power is counterbalanced by the interaction with phonons and by the heat flow from the overheated leads. We study aluminum-based coolers that are equipped with a suspended normal metal and an efficient quasiparticle drain. At intermediate temperatures, the phonon bath of the suspended normal metal is cooled. By adjusting the junction transparency, we control the injection current and, thus, the temperature of the superconducting lead at the optimum cooling point. The best device shows remarkable cooling from 150 mK down to about 30 mK, a factor of 5 in temperature at a power of 40 pW. We discuss heat transport in our device and the reasons for cooling saturation at the low-temperature end.

  20. Hydrodynamics of pulsed jetting in juvenile and adult brief squid Lolliguncula brevis: evidence of multiple jet 'modes' and their implications for propulsive efficiency.

    PubMed

    Bartol, Ian K; Krueger, Paul S; Stewart, William J; Thompson, Joseph T

    2009-06-01

    The dynamics of pulsed jetting in squids throughout ontogeny is not well understood, especially with regard to the development of vortex rings, which are common features of mechanically generated jet pulses (also known as starting jets). Studies of mechanically generated starting jets have revealed a limiting principle for vortex ring formation characterized in terms of a ;formation number' (F), which delineates the transition between the formation of isolated vortex rings and vortex rings that have; pinched off' from the generating jet. Near F, there exists an optimum in pulse-averaged thrust with (potentially) low energetic cost, raising the question: do squids produce vortex rings and if so, do they fall near F, where propulsive benefits presumably occur? To better understand vortex ring dynamics and propulsive jet efficiency throughout ontogeny, brief squid Lolliguncula brevis ranging from 3.3 to 9.1 cm dorsal mantle length (DML) and swimming at speeds of 2.43-22.2 cms(-1) (0.54-3.50 DMLs(-1)) were studied using digital particle image velocimetry (DPIV). A range of jet structures were observed but most structures could be classified as variations of two principal jet modes: (1) jet mode I, where the ejected fluid rolled up into an isolated vortex ring; and (2) jet mode II, where the ejected fluid developed into a leading vortex ring that separated or ;pinched off' from a long trailing jet. The ratio of jet length [based on the vorticity extent (L(omega))] to jet diameter [based on peak vorticity locations (D(omega))] was <3.0 for jet mode I and >3.0 for jet mode II, placing the transition between modes in rough agreement with F determined in mechanical jet studies. Jet mode II produced greater time-averaged thrust and lift forces and was the jet mode most heavily used whereas jet mode I had higher propulsive efficiency, lower slip, shorter jet periods and a higher frequency of fin activity associated with it. No relationship between L(omega)/D(omega) and speed

  1. Upregulation of AKT3 Confers Resistance to the AKT Inhibitor MK2206 in Breast Cancer.

    PubMed

    Stottrup, Casey; Tsang, Tiffany; Chin, Y Rebecca

    2016-08-01

    Acquired resistance to molecular targeted therapy represents a major challenge for the effective treatment of cancer. Hyperactivation of the PI3K/AKT pathway is frequently observed in virtually all human malignancies, and numerous PI3K and AKT inhibitors are currently under clinical evaluation. However, mechanisms of acquired resistance to AKT inhibitors have yet to be described. Here, we use a breast cancer preclinical model to identify resistance mechanisms to a small molecule allosteric AKT inhibitor, MK2206. Using a step-wise and chronic high-dose exposure, breast cancer cell lines harboring oncogenic PI3K resistant to MK2206 were established. Using this model, we reveal that AKT3 expression is markedly upregulated in AKT inhibitor-resistant cells. Induction of AKT3 is regulated epigenetically by the bromodomain and extra terminal domain proteins. Importantly, knockdown of AKT3, but not AKT1 or AKT2, in resistant cells restores sensitivity to MK2206. AKT inhibitor-resistant cells also display an epithelial to mesenchymal transition phenotype as assessed by alterations in the levels of E-Cadherin, N-Cadherin, and vimentin, as well as enhanced invasiveness of tumor spheroids. Notably, the invasive morphology of resistant spheroids is diminished upon AKT3 depletion. We also show that resistance to MK2206 is reversible because upon drug removal resistant cells regain sensitivity to AKT inhibition, accompanied by reexpression of epithelial markers and reduction of AKT3 expression, implying that epigenetic reprogramming contributes to acquisition of resistance. These findings provide a rationale for developing therapeutics targeting AKT3 to circumvent acquired resistance in breast cancer. Mol Cancer Ther; 15(8); 1964-74. ©2016 AACR. PMID:27297869

  2. Structural and Thermodynamic Effects of Macrocyclization in HCV NS3/4A Inhibitor MK-5172.

    PubMed

    Soumana, Djadé I; Kurt Yilmaz, Nese; Prachanronarong, Kristina L; Aydin, Cihan; Ali, Akbar; Schiffer, Celia A

    2016-04-15

    Recent advances in direct-acting antivirals against Hepatitis C Virus (HCV) have led to the development of potent inhibitors, including MK-5172, that target the viral NS3/4A protease with relatively low susceptibility to resistance. MK-5172 has a P2-P4 macrocycle and a unique binding mode among current protease inhibitors where the P2 quinoxaline packs against the catalytic residues H57 and D81. However, the effect of macrocyclization on this binding mode is not clear, as is the relation between macrocyclization, thermodynamic stabilization, and susceptibility to the resistance mutation A156T. We have determined high-resolution crystal structures of linear and P1-P3 macrocyclic analogs of MK-5172 bound to WT and A156T protease and compared these structures, their molecular dynamics, and experimental binding thermodynamics to the parent compound. We find that the "unique" binding mode of MK-5172 is conserved even when the P2-P4 macrocycle is removed or replaced with a P1-P3 macrocycle. While beneficial to decreasing the entropic penalty associated with binding, the constraint exerted by the P2-P4 macrocycle prevents efficient rearrangement to accommodate the A156T mutation, a deficit alleviated in the linear and P1-P3 analogs. Design of macrocyclic inhibitors against NS3/4A needs to achieve the best balance between exerting optimal conformational constraint for enhancing potency, fitting within the substrate envelope and allowing adaptability to be robust against resistance mutations. PMID:26682473

  3. An Expert System for Classifying Stars on the MK Spectral Classification System

    NASA Astrophysics Data System (ADS)

    Corbally, Christopher J.; Gray, R. O.

    2013-01-01

    We will describe an expert computer system designed to classify stellar spectra on the MK Spectral Classification system employing methods similar to those of humans who make direct comparison with the MK classification standards. Like an expert human classifier, MKCLASS first comes up with a rough spectral type, and then refines that type by direct comparison with MK standards drawn from a standards library using spectral criteria appropriate to the spectral class. Certain common spectral-type peculiarities can also be detected by the program. The program is also capable of identifying WD spectra and carbon stars and giving appropriate (but currently approximate) spectral types on the relevant systems. We will show comparisons between spectral types (including luminosity types) performed by MKCLASS and humans. The program currently is capable of competent classifications in the violet-green region, but plans are underway to extend the spectral criteria into the red and near-infrared regions. Two standard libraries with resolutions of 1.8 and 3.6Å are now available, but a higher-resolution standard library, using the new spectrograph on the Vatican Advanced Technology Telescope, is currently under preparation. Once that library is available, MKCLASS and the spectral libraries will be made available to the astronomical community.

  4. An Expert Computer Program for Classifying Stars on the MK Spectral Classification System

    NASA Astrophysics Data System (ADS)

    Gray, R. O.; Corbally, C. J.

    2014-04-01

    This paper describes an expert computer program (MKCLASS) designed to classify stellar spectra on the MK Spectral Classification system in a way similar to humans—by direct comparison with the MK classification standards. Like an expert human classifier, the program first comes up with a rough spectral type, and then refines that spectral type by direct comparison with MK standards drawn from a standards library. A number of spectral peculiarities, including barium stars, Ap and Am stars, λ Bootis stars, carbon-rich giants, etc., can be detected and classified by the program. The program also evaluates the quality of the delivered spectral type. The program currently is capable of classifying spectra in the violet-green region in either the rectified or flux-calibrated format, although the accuracy of the flux calibration is not important. We report on tests of MKCLASS on spectra classified by human classifiers; those tests suggest that over the entire HR diagram, MKCLASS will classify in the temperature dimension with a precision of 0.6 spectral subclass, and in the luminosity dimension with a precision of about one half of a luminosity class. These results compare well with human classifiers.

  5. CRTH2 antagonist MK-7246: a synthetic evolution from discovery through development.

    PubMed

    Molinaro, Carmela; Bulger, Paul G; Lee, Ernest E; Kosjek, Birgit; Lau, Stephen; Gauvreau, Danny; Howard, Melissa E; Wallace, Debra J; O'Shea, Paul D

    2012-03-01

    In this paper, we report the development of different synthetic routes to MK-7246 (1) designed by the Process Chemistry group. The syntheses were initially designed as an enabling tool for Medicinal Chemistry colleagues in order to rapidly explore structure-activity relationships (SAR) and to procure the first milligrams of diverse target molecules for in vitro evaluation. The initial aziridine opening/cyclodehydration strategy was also directly amenable to the first GMP deliveries of MK-7246 (1), streamlining the transition from milligram to kilogram-scale production needed to support early preclinical and clinical evaluation of this compound. Subsequently a more scalable and cost-effective manufacturing route to MK-7246 (1) was engineered. Highlights of the manufacturing route include an Ir-catalyzed intramolecular N-H insertion of sulfoxonium ylide 41 and conversion of ketone 32 to amine 31 in a single step with excellent enantioselectivity through a transaminase process. Reactions such as these illustrate the enabling impact and efficiency gains that innovative developments in chemo- and biocatalysis can have on the synthesis of pharmaceutically relevant target molecules. PMID:22335767

  6. A 30 mK, 13.5 T scanning tunneling microscope with two independent tips.

    PubMed

    Roychowdhury, Anita; Gubrud, M A; Dana, R; Anderson, J R; Lobb, C J; Wellstood, F C; Dreyer, M

    2014-04-01

    We describe the design, construction, and performance of an ultra-low temperature, high-field scanning tunneling microscope (STM) with two independent tips. The STM is mounted on a dilution refrigerator and operates at a base temperature of 30 mK with magnetic fields of up to 13.5 T. We focus on the design of the two-tip STM head, as well as the sample transfer mechanism, which allows in situ transfer from an ultra high vacuum preparation chamber while the STM is at 1.5 K. Other design details such as the vibration isolation and rf-filtered wiring are also described. Their effectiveness is demonstrated via spectral current noise characteristics and the root mean square roughness of atomic resolution images. The high-field capability is shown by the magnetic field dependence of the superconducting gap of CuxBi2Se3. Finally, we present images and spectroscopy taken with superconducting Nb tips with the refrigerator at 35 mK that indicate that the effective temperature of our tips/sample is approximately 184 mK, corresponding to an energy resolution of 16 μeV. PMID:24784617

  7. A 30 mK, 13.5 T scanning tunneling microscope with two independent tips

    SciTech Connect

    Roychowdhury, Anita; Gubrud, M. A.; Dana, R.; Dreyer, M.; Anderson, J. R.; Lobb, C. J.; Wellstood, F. C.

    2014-04-15

    We describe the design, construction, and performance of an ultra-low temperature, high-field scanning tunneling microscope (STM) with two independent tips. The STM is mounted on a dilution refrigerator and operates at a base temperature of 30 mK with magnetic fields of up to 13.5 T. We focus on the design of the two-tip STM head, as well as the sample transfer mechanism, which allows in situ transfer from an ultra high vacuum preparation chamber while the STM is at 1.5 K. Other design details such as the vibration isolation and rf-filtered wiring are also described. Their effectiveness is demonstrated via spectral current noise characteristics and the root mean square roughness of atomic resolution images. The high-field capability is shown by the magnetic field dependence of the superconducting gap of Cu{sub x}Bi{sub 2}Se{sub 3}. Finally, we present images and spectroscopy taken with superconducting Nb tips with the refrigerator at 35 mK that indicate that the effective temperature of our tips/sample is approximately 184 mK, corresponding to an energy resolution of 16 μeV.

  8. Thrombin Maybe Plays an Important Role in MK Differentiation into Platelets

    PubMed Central

    Yang, Xiao-Lei; Ge, Meng-Kai; Mao, De-Kui; Lv, Ying-Tao; Sun, Shu-Yan; Yu, Ai-Ping

    2016-01-01

    Objectives. After development and differentiation, megakaryocytes (MKs) can produce platelets. As is well known, thrombopoietin (TPO) can induce MKs to differentiate. The effect of thrombin on MKs differentiation is not clear. In this study, we used a human megakaryoblastic leukemia cell line (Meg-01) to assess the effect of thrombin on MKs differentiation. Methods. In order to interrogate the role of thrombin in Meg-01 cells differentiation, the changes of morphology, cellular function, and expression of diverse factors were analyzed. Results. The results show that thrombin suppresses Meg-01 cells proliferation and induces apoptosis and cell cycle arrest. Thrombin upregulates the expression of CD41b, which is one of the most important MK markers. Globin transcription factor 1 (GATA-1), an important transcriptional regulator, controls MK development and maturation. The expression of GATA-1 is also upregulated by thrombin in Meg-01 cells. The expression of B-cell lymphoma 2 (Bcl-2), an apoptosis-inhibitory protein, is downregulated by thrombin. Phosphorylated protein kinase B (p-AKT) and phosphorylated extracellular signal-regulated kinase (p-ERK) were upregulated by thrombin in Meg-01 cells. All the results are consistent with Meg-01 cells treated with TPO. Discussion and Conclusion. In conclusion, all these data indicate that thrombin maybe plays an important role in MK differentiation into platelets. However, whether the platelet-like particles are certainly platelets remains unknown. PMID:27064425

  9. Effects of MK-801, ketamine and alaptide on quinolinate models in the maturing hippocampus.

    PubMed

    Keilhoff, G; Wolf, G; Stastný, F

    1991-01-01

    The ability of the N-methyl-D-aspartate receptor antagonists, MK-801, ketamine and alaptide [a newly synthesized cyclo(1-amino-1-cyclopentane-carbonyl-L-alanyl) with protective properties in models of hypoxia], to prevent neuronal degeneration caused by intracerebroventricular application of quinolinic acid was investigated. Neurodegenerative effects of quinolinate in the hippocampal formation were found to increase with the degree of maturity of glutamatergic target structures. A protective potency of the N-methyl-D-aspartate receptor antagonists was observed at all developmental stages studied (12- and 30-day-old and adult rats). MK-801 showed the highest efficacy, alaptide the lowest. These findings suggest a parallelism in maturity of glutamatergic transmission processes as one prerequisite of quinolinate vulnerability and postnatal increases of target fields of the protectives. Application of MK-801 or ketamine after quinolinate injection intensified their protective effects when compared to simultaneous or preadministration. This observation is interpreted as indicating that quinolinate is a prompter of a delayed neurodegenerative process rather than acting immediately as a toxicant. PMID:1832751

  10. Discovery of MK-8742: an HCV NS5A inhibitor with broad genotype activity.

    PubMed

    Coburn, Craig A; Meinke, Peter T; Chang, Wei; Fandozzi, Christine M; Graham, Donald J; Hu, Bin; Huang, Qian; Kargman, Stacia; Kozlowski, Joseph; Liu, Rong; McCauley, John A; Nomeir, Amin A; Soll, Richard M; Vacca, Joseph P; Wang, Dahai; Wu, Hao; Zhong, Bin; Olsen, David B; Ludmerer, Steven W

    2013-12-01

    The NS5A protein plays a critical role in the replication of HCV and has been the focus of numerous research efforts over the past few years. NS5A inhibitors have shown impressive in vitro potency profiles in HCV replicon assays, making them attractive components for inclusion in all oral combination regimens. Early work in the NS5A arena led to the discovery of our first clinical candidate, MK-4882 [2-((S)-pyrrolidin-2-yl)-5-(2-(4-(5-((S)-pyrrolidin-2-yl)-1H-imidazol-2-yl)phenyl)benzofuran-5-yl)-1H-imidazole]. While preclinical proof-of-concept studies in HCV-infected chimpanzees harboring chronic genotype 1 infections resulted in significant decreases in viral load after both single- and multiple-dose treatments, viral breakthrough proved to be a concern, thus necessitating the development of compounds with increased potency against a number of genotypes and NS5A resistance mutations. Modification of the MK-4882 core scaffold by introduction of a cyclic constraint afforded a series of tetracyclic inhibitors, which showed improved virologic profiles. Herein we describe the research efforts that led to the discovery of MK-8742, a tetracyclic indole-based NS5A inhibitor, which is currently in phase 2b clinical trials as part of an all-oral, interferon-free regimen for the treatment of HCV infection. PMID:24127258