Science.gov

Sample records for 10-6 m2 s-1

  1. Accurate and stable equal-pressure measurements of water vapor transmission rate reaching the 10(-6) g m(-2) day(-1) range.

    PubMed

    Nakano, Yoichiro; Yanase, Takashi; Nagahama, Taro; Yoshida, Hajime; Shimada, Toshihiro

    2016-10-17

    The water vapor transmission rate (WVTR) of a gas barrier coating is a critically important parameter for flexible organic device packaging, but its accurate measurement without mechanical stress to ultrathin films has been a significant challenge in instrumental analysis. At the current stage, no reliable results have been reported in the range of 10(-6) g m(-2) day(-1) that is required for organic light emitting diodes (OLEDs). In this article, we describe a solution for this difficult, but important measurement, involving enhanced sensitivity by a cold trap, stabilized temperature system, pumped sealing and calibration by a standard conductance element.

  2. Differential S1P Receptor Profiles on M1- and M2-Polarized Macrophages Affect Macrophage Cytokine Production and Migration

    PubMed Central

    Müller, Jan; von Bernstorff, Wolfram; Heidecke, Claus-Dieter

    2017-01-01

    Introduction. Macrophages are key players in complex biological processes. In response to environmental signals, macrophages undergo polarization towards a proinflammatory (M1) or anti-inflammatory (M2) phenotype. Sphingosine 1-phosphate (S1P) is a bioactive lysophospholipid that acts via 5 G-protein coupled receptors (S1P1–5) in order to influence a broad spectrum of biological processes. This study assesses S1P receptor expression on macrophages before and after M1 and M2 polarization and performs a comparative analysis of S1P signalling in the two activational states of macrophages. Methods. Bone marrow derived macrophages (BMDM) from C57 BL/6 mice were cultured under either M1- or M2-polarizing conditions. S1P-receptor expression was determined by quantitative RT-PCR. Influence of S1P on macrophage activation, migration, phagocytosis, and cytokine secretion was assessed in vitro. Results. All 5 S1P receptor subclasses were expressed in macrophages. Culture under both M1- and M2-polarizing conditions led to significant downregulation of S1P1. In contrast, M1-polarized macrophages significantly downregulated S1P4. The expression of the remaining three S1P receptors did not change. S1P increased expression of iNOS under M2-polarizing conditions. Furthermore, S1P induced chemotaxis in M1 macrophages and changed cytokine production in M2 macrophages. Phagocytosis was not affected by S1P-signalling. Discussion. The expression of different specific S1P receptor profiles may provide a possibility to selectively influence M1- or M2-polarized macrophages. PMID:28367448

  3. Form factors of descendant operators: reduction to perturbed M (2 , 2 s + 1) models

    NASA Astrophysics Data System (ADS)

    Lashkevich, Michael; Pugai, Yaroslav

    2015-04-01

    In the framework of the algebraic approach to form factors in two-dimensional integrable models of quantum field theory we consider the reduction of the sine-Gordon model to the Φ13-perturbation of minimal conformal models of the M (2 , 2 s + 1) series. We find in an algebraic form the condition of compatibility of local operators with the reduction. We propose a construction that make it possible to obtain reduction compatible local operators in terms of screening currents. As an application we obtain exact multiparticle form factors for the compatible with the reduction conserved currents T ±2 k , Θ±(2 k-2), which correspond to the spin ±(2 k - 1) integrals of motion, for any positive integer k. Furthermore, we obtain all form factors of the operators T 2 k T -2 l , which generalize the famous operator. The construction is analytic in the s parameter and, therefore, makes sense in the sine-Gordon theory.

  4. High Frequency of vacA s1m2 Genotypes Among Helicobacter pylori Isolates From Patients With Gastroduodenal Disorders in Kermanshah, Iran

    PubMed Central

    Pajavand, Hamid; Alvandi, Amirhooshang; Mohajeri, Parviz; Bakhtyari, Somaye; Bashiri, Homayoon; Kalali, Behnam; Gerhard, Markus; Najafi, Farid; Abiri, Ramin

    2015-01-01

    Background: Helicobacter pylori infection and related diseases outcome are mediated by a complex interplay between bacterial, host and environmental factors. Several distinct virulence factors of H. pylori have been shown to be associated with different clinical outcomes. Here we focused on vacA and cagA genotypes of H. pylori strains isolated from patients with gastric disorder. Objectives: The aim of this study was to determine the frequency of two toxins and genotypes of VacA toxin in patients referred to a central hospital in the west of Iran (Imam Reza hospital, Kermanshah) during 2011 - 2012. Patients and Methods: Samples were collected from patients infected with H. pylori. Gastric biopsy specimens from the stomach antrum and corpus were cultured. PCR analysis was performed for genotyping H. pylori vacA and cagA genes. Results: Helicobacter pylori was isolated from 48% (96/200) of patients with gastroduodenal disorders. In 81/96 (84%) cases, the cagA gene was present. Among different genotypes of vacA, two s1m2 and s2m2 genotypes were dominant with frequency of 39.5% and 50%, respectively. The frequency of the s1m1 genotype was 7.2% (7/96), which is much lower than elsewhere. H. pylori isolates with positive results for cagA gene and vacA s1m2 genotypes showed statistically significant correlation with peptic ulcer (s1m2 13/34 [38.2%] P = 0.003). However, isolates of H. pylori infection with cagA gene and vacA s2m2 genotypes were significantly associated with development of gastritis (s2m2 41/42 [97.6%] P = 0.000). Conclusions: About 90% of H. pylori strains potentially contained vacA s2m2 and s1m2 genotypes. Infection with H. pylori strain containing the cagA gene or the vacA s1m1 and s1m2 genotypes was associated with increased incidence of peptic ulcer disease (PUD). PMID:26862378

  5. The diffusion of cesium in the graphitic matrix A3-3 under irradiation by a fast neutron flux of 2 × 10 17 m -2 s -1

    NASA Astrophysics Data System (ADS)

    Hensel, W.; Hoinkis, E.

    1995-09-01

    The 137Cs core release rate of High Temperature Reactors (HTR) is effected by the interactions of cesium with the graphitic material used as a matrix for the coated fuel particles. The migration of 137Cs in the graphitic matrix A3-3 at a fast neutron flux of 2 × 10 17 m -2 s -1 was studied in short-term experiments using the thin-film technique. The penetration profiles did not satisfy Fick's second law. The diffusion/trapping/re-emission model was applied to determine the diffusion coefficient D and the trapping coefficient μ for four profiles produced at 1088 and 1166 K. D, μ and the reemission coefficient b at 1293 K were determined for two profiles. Compared to laboratory conditions no effect of the fast neutron irradiation on the 137Cs migration in matrix A3-3 was observed.

  6. Expansion and Evolution of a Virulent, Extensively Drug-Resistant (Polymyxin B-Resistant), QnrS1-, CTX-M-2-, and KPC-2-Producing Klebsiella pneumoniae ST11 International High-Risk Clone

    PubMed Central

    Vitali, Lúcia; Gaspar, Gilberto Gambero; Bellissimo-Rodrigues, Fernando; Martinez, Roberto; Darini, Ana Lúcia Costa

    2014-01-01

    In this study, we report the early expansion, evolution, and characterization of a multiresistant Klebsiella pneumoniae clone that was isolated with increasing frequency from inpatients in a tertiary-care university hospital in Brazil. Seven carbapenem- and quinolone-resistant and polymyxin B-susceptible or -resistant K. pneumoniae isolates isolated between December 2012 and February 2013 were investigated. Beta-lactamase- and plasmid-mediated quinolone resistance (PMQR)-encoding genes and the genetic environment were investigated using PCR, sequencing, and restriction fragment length polymorphism (RFLP). Clonal relatedness was established using XbaI–pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and phylogenetic group characterization. Plasmid analyses included PCR-based replicon typing (PBRT) and hybridization of the S1-PFGE product, plasmid MLST, and conjugation experiments. Virulence potential was assessed by PCR by searching for 10 virulence factor-encoding genes (ureA, fimH, kfuBC, uge, wabG, magA, mrkD, allS, rmpA, and cf29a) and by phenotypic tests to analyze the hypermucoviscous phenotype. The genetic context of a multidrug-resistant and extensively drug-resistant K. pneumoniae ST11-KpI clone harboring IncFIIk-Tn4401a-blaKPC-2, qnrS1, and blaCTX-M-2 was found. Moreover, three isolates displayed high resistance to polymyxin B (MICs = 32, 32, and 128 mg/liter) as well as mucous and hypermucoviscous phenotypes. These bacteria also harbored ureA, fimH, uge, wabG, and mrkD, which code for virulence factors associated with binding, biofilm formation, and the ability to colonize and escape from phagocytosis. Our study describes the association of important coresistance and virulence factors in the K. pneumoniae ST11 international high-risk clone, which makes this pathogen successful at infections and points to the quick expansion and evolution of this multiresistant and virulent clone, leading to a pandrug-resistant phenotype and

  7. 43 CFR 10.6 - Custody.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 1 2011-10-01 2011-10-01 false Custody. 10.6 Section 10.6 Public Lands: Interior Office of the Secretary of the Interior NATIVE AMERICAN GRAVES PROTECTION AND REPATRIATION REGULATIONS Human Remains, Funerary Objects, Sacred Objects, or Objects of Cultural Patrimony From Federal...

  8. 43 CFR 10.6 - Custody.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Custody. 10.6 Section 10.6 Public Lands: Interior Office of the Secretary of the Interior NATIVE AMERICAN GRAVES PROTECTION AND REPATRIATION REGULATIONS Human Remains, Funerary Objects, Sacred Objects, or Objects of Cultural Patrimony From Federal...

  9. 43 CFR 10.6 - Custody.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 1 2013-10-01 2013-10-01 false Custody. 10.6 Section 10.6 Public Lands: Interior Office of the Secretary of the Interior NATIVE AMERICAN GRAVES PROTECTION AND REPATRIATION REGULATIONS Human Remains, Funerary Objects, Sacred Objects, or Objects of Cultural Patrimony From Federal...

  10. 43 CFR 10.6 - Custody.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 1 2014-10-01 2014-10-01 false Custody. 10.6 Section 10.6 Public Lands: Interior Office of the Secretary of the Interior NATIVE AMERICAN GRAVES PROTECTION AND REPATRIATION REGULATIONS Human Remains, Funerary Objects, Sacred Objects, or Objects of Cultural Patrimony From Federal...

  11. 43 CFR 10.6 - Custody.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 1 2012-10-01 2011-10-01 true Custody. 10.6 Section 10.6 Public Lands: Interior Office of the Secretary of the Interior NATIVE AMERICAN GRAVES PROTECTION AND REPATRIATION REGULATIONS Human Remains, Funerary Objects, Sacred Objects, or Objects of Cultural Patrimony From Federal...

  12. 27 CFR 10.6 - Administrative provisions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Administrative provisions..., DEPARTMENT OF THE TREASURY LIQUORS COMMERCIAL BRIBERY Scope of Regulations § 10.6 Administrative provisions. (a) General. The Act makes applicable the provisions including penalties of sections 49 and 50...

  13. 24 CFR 10.6 - Initiation of rulemaking.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Initiation of rulemaking. 10.6 Section 10.6 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development RULEMAKING: POLICY AND PROCEDURES Procedures § 10.6 Initiation of rulemaking....

  14. 46 CFR 188.10-6 - Captain of the Port.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Captain of the Port. 188.10-6 Section 188.10-6 Shipping... PROVISIONS Definition of Terms Used in This Subchapter § 188.10-6 Captain of the Port. This term means an... activities within his assigned area. In addition, the District Commander shall be the Captain of the...

  15. 46 CFR 188.10-6 - Captain of the Port.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Captain of the Port. 188.10-6 Section 188.10-6 Shipping... PROVISIONS Definition of Terms Used in This Subchapter § 188.10-6 Captain of the Port. This term means an... activities within his assigned area. In addition, the District Commander shall be the Captain of the...

  16. 46 CFR 188.10-6 - Captain of the Port.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Captain of the Port. 188.10-6 Section 188.10-6 Shipping... PROVISIONS Definition of Terms Used in This Subchapter § 188.10-6 Captain of the Port. This term means an... activities within his assigned area. In addition, the District Commander shall be the Captain of the...

  17. 46 CFR 188.10-6 - Captain of the Port.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Captain of the Port. 188.10-6 Section 188.10-6 Shipping... PROVISIONS Definition of Terms Used in This Subchapter § 188.10-6 Captain of the Port. This term means an... activities within his assigned area. In addition, the District Commander shall be the Captain of the...

  18. 46 CFR 188.10-6 - Captain of the Port.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Captain of the Port. 188.10-6 Section 188.10-6 Shipping... PROVISIONS Definition of Terms Used in This Subchapter § 188.10-6 Captain of the Port. This term means an... activities within his assigned area. In addition, the District Commander shall be the Captain of the...

  19. 28 CFR 10.6 - Necessity for further registration.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 1 2013-07-01 2013-07-01 false Necessity for further registration. 10.6 Section 10.6 Judicial Administration DEPARTMENT OF JUSTICE REGISTRATION OF CERTAIN ORGANIZATIONS CARRYING ON ACTIVITIES WITHIN THE UNITED STATES Registration Statement § 10.6 Necessity for...

  20. 32 CFR 10.6 - Non-creation of right.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 1 2012-07-01 2012-07-01 false Non-creation of right. 10.6 Section 10.6 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE MILITARY COMMISSIONS MILITARY COMMISSION INSTRUCTIONS § 10.6 Non-creation of right. Neither this part nor any Military...

  1. 32 CFR 10.6 - Non-creation of right.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false Non-creation of right. 10.6 Section 10.6 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE MILITARY COMMISSIONS MILITARY COMMISSION INSTRUCTIONS § 10.6 Non-creation of right. Neither this part nor any Military...

  2. 32 CFR 10.6 - Non-creation of right.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 1 2014-07-01 2014-07-01 false Non-creation of right. 10.6 Section 10.6 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE MILITARY COMMISSIONS MILITARY COMMISSION INSTRUCTIONS § 10.6 Non-creation of right. Neither this part nor any Military...

  3. 32 CFR 10.6 - Non-creation of right.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 1 2013-07-01 2013-07-01 false Non-creation of right. 10.6 Section 10.6 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE MILITARY COMMISSIONS MILITARY COMMISSION INSTRUCTIONS § 10.6 Non-creation of right. Neither this part nor any Military...

  4. 32 CFR 10.6 - Non-creation of right.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 1 2011-07-01 2011-07-01 false Non-creation of right. 10.6 Section 10.6 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE MILITARY COMMISSIONS MILITARY COMMISSION INSTRUCTIONS § 10.6 Non-creation of right. Neither this part nor any Military...

  5. M2-F1 cockpit

    NASA Technical Reports Server (NTRS)

    1963-01-01

    This photo shows the cockpit configuration of the M2-F1 wingless lifting body. With a top speed of about 120 knots, the M2-F1 had a simple instrument panel. Besides the panel itself, the ribs of the wooden shell (left) and the control stick (center) are also visible. The wingless, lifting body aircraft design was initially conceived as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop near Long Beach for modification. With a special gearbox and racing slicks, the Pontiac could tow the 1,000-pound M2-F1 110 miles per hour in 30 seconds. It proved adequate for the roughly 400 car tows that got the M2-F1 airborne to prove it could fly safely and to train pilots before they were towed behind a C-47

  6. Mitsubishi A6M2

    NASA Technical Reports Server (NTRS)

    1943-01-01

    Captured at Akutan Island, Alaska, in August 1942. This Mitsubishi A6M2 fighter was the first 'Zero' to fall intact into Allied hands during WW II. After limited flying on the West Coast, the 'Zero' arrived at Langley for installation of test equipment prior to in-depth flight testing by the Navy at Patuxent River, Maryland.

  7. High sensitivity infrared 10.6 micrometer heterodyne receiver development

    NASA Technical Reports Server (NTRS)

    1972-01-01

    The results are presented for a study on the design of an infrared 10.6-micrometer quantum-noise-limited optical receiver subsystem. Performance measurements of the HgCdTe photomixer preamplifier combination were carried out for photomixer temperatures up to 152 K and a photomixer frequency response of up to 420 MHz was obtained. Results of temperature and bias cycling of HgCdTe photomixers are reported. Design considerations for an operational 10.6 micrometer heterodyne receiver are presented. These consist of design data on required laser LO illumination, heat load levels for photomixer cooler, photomixer uniformity and the effects of photomixer impedance match on receiver sensitivity. Analysis and measurements of 10.6 micrometer heterodyne detection in an extrinsic photoconductive (p-type) HgCdTe photomixer are also presented.

  8. Draft genome sequence of Phomopsis longicolla MSPL 10-6

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Phomopsis longicolla T.W. Hobbs is the primary cause of Phomopsis seed decay in soybean. We report the de novo assembled draft genome sequence of P. longicolla isolate MSPL10-6 with a 54.8-fold depth of coverage. The resulting draft genome was estimated to be approximately 64 Mb in size with an over...

  9. Rough surface interferometry at 10.6 microm.

    PubMed

    Kwon, O; Wyant, J C; Hayslett, C R

    1980-06-01

    An IR Twyman-Green interferometer is described. It uses a cw CO(2) laser as a light source operating at a 10.6-microm wavelength. Theoretical analysis and experimental measurements of the relationship between the contrast of the interference fringes and the rms roughness of test surfaces are discussed. Interferometric testing results and special alignment methods are shown for rough surface optics.

  10. Laser Induced EMP (Electromagnetic Pulse) at 10.6 Microns

    DTIC Science & Technology

    1987-05-01

    they are returned to the target by the potential barrier ( Barkhausen and Kurz, 1920), radiation is also produced by the oscillations of the position...34Self-Focusing of 10.6 um Radiation in an Underdense Plasma," Phys. Rev. Lett. 45, 1260 (1980). Barkhausen , V. H. and Kurz, K., "Die KUlrzesten mit

  11. Experiment definition phase shuttle laboratory. LDRL-10.6 experiment

    NASA Technical Reports Server (NTRS)

    1976-01-01

    The work completed on the experiment definition phase of the shuttle laboratory LDRL 10.6 micrometers experiment from 27 September 1975 to 26 January 1976 was reported. This work included progress in the following areas: (1) optomechanical system: completion of detail drawings, completion of the beryllium subassembly, fabrication, checking, and weighing of approximately 95% of the detailed parts, dry film lubrication of the bearings and gears, and initiation of assembly of the gimbals; (2) optics: update of the detailed optical layout, receipt of nine mirrors and the pre-expander; (3) miscellaneous: delivery of draft material for the final report, completion of optical testing of the 10.6 micrometers receiver, and receipt, assembly, and checkout of NASA test console.

  12. Experiment definition phase shuttle laboratory LDRL-10.6 experiment

    NASA Technical Reports Server (NTRS)

    1975-01-01

    This report for the Experiment Definition Phase of the Shuttle Laboratory LDRL 10.6 Micrometer Experiment covers period 27 June through 26 September 1975. Activities during the fifth quarter included: (1) reevaluation of system obscuration ratio with a subsequent reduction of this ratio from 0.417 to 0.362, (2) completion of detail drawings for the 6X pre-expander, (3) completion of detail drawings for the nine mirrors that comprise pointing and tracking optomechanical subsystem, (4) continuation of detailing of mechanical portions of CMSS and modifications to accommodate new obscuration ratio, (5) qualitative operation of the optomechanical subsystem of the 10.6 um receiver achieved under experiment measurement task; receiver fully integrated and operation demonstrated over a 10 km experimental link, and (6) data collection task initiated to begin preparation of link analysis volumes.

  13. Faraday Rotation Optical Isolator for 10.6-microm Radiation.

    PubMed

    Jacobs, S D; Teegarden, K J; Ahrenkiel, R K

    1974-10-01

    Measurements that have been performed indicate that hot-pressed ferromagnetic CdCr(2)S(4) would be a useful Faraday optical isolator material for laser systems at 10.6 microm. A large-aperture, liquid-nitrogen-cooled isolator, requiring modest magnetic fields with material of optimum thickness, would provide isolation in excess of 30 dB with insertion loss due to optical absorption in the active element of less than 3 dB. Consideration of its figure of merit indicates that hot-pressed CdCr(2)S(4) could be used as an isolator at 1.06 microm, introducing less than 2 dB insertion loss due to optical absorption at that wavelength.

  14. Absorption of thin film materials at 10.6 microm.

    PubMed

    Gibbs, W E; Butterfield, A W

    1975-12-01

    Absorption indices at a wavelength of 10.6 mum for thin films of As(2)S(3), GeSe, BaF(2), ZnSe, and CdTe were measured by calorimetric techniques with a CO(2) laser. The values obtained, 4.6 x 10(-4), 1.4 x 10(-3), 2.8 x 10(-3), 2.8 x 10(-3), and 5.0 x 10(-3), respectively, were significantly greater than the corresponding values for the bulk materials. This difference was least for the vitreous films, As(2)S(3) and GeSe, which also had a lower absorption than the remaining polycrystalline films. Details are presented of the microstructure of the films as determined by scanning electron microscopy and k-ray diffraction.

  15. Absorptivity of water vapor for 10.6 micron radiation

    NASA Technical Reports Server (NTRS)

    Pugh, E. R.; Krech, R. H.

    1982-01-01

    Attention is called to recent measurements of the absorptivity of water vapor to 10.6-micron laser radiation made using shock-heated H2O/H2 and H2O/Ar mixtures and a probe CO2 laser. It is noted that these measurements give values about a factor of 2 lower than Ludwig's (1971) low resolution values. It is also argued that Fowler's (1981) high values are not likely to be caused by excited water molecules. It is shown that very intense laser radiation would be required to obtain any appreciable vibrational nonequilibrium. Within the narrow spectral range of 944-948/cm, no significant variation in absorption coefficient (suitably normalized) is observed as a function of laser line, water vapor concentration, total pressure, or diluent gas.

  16. Magellan/M2FS Spectroscopy of Tucana 2 and Grus 1

    NASA Astrophysics Data System (ADS)

    Walker, Matthew G.; Mateo, Mario; Olszewski, Edward W.; Koposov, Sergey; Belokurov, Vasily; Jethwa, Prashin; Nidever, David L.; Bonnivard, Vincent; Bailey, John I., III; Bell, Eric F.; Loebman, Sarah R.

    2016-03-01

    We present results from spectroscopic observations with the Michigan/Magellan Fiber System (M2FS) of 147 stellar targets along the line of sight to the newly discovered “ultrafaint” stellar systems Tucana 2 (Tuc 2) and Grus 1 (Gru 1). Based on simultaneous estimates of line of sight velocity and stellar-atmospheric parameters, we identify 8 and 7 stars as probable members of Tuc 2 and and Gru 1, respectively. Our sample for Tuc 2 is sufficient to resolve an internal velocity dispersion of {8.6}-2.7+4.4 km s-1 about a mean of -{129.1}-3.5+3.5 km s-1 (solar rest frame), and to estimate a mean metallicity of [Fe/H] = -{2.23}-0.12+0.18. These results place Tuc 2 on chemodynamical scaling relations followed by dwarf galaxies, suggesting a dominant dark matter component with dynamical mass {2.7}-1.3+3.1× {10}6 {M}⊙ enclosed within the central ˜160 pc, and dynamical mass-to-light ratio {1913}-950+2234 {M}⊙ /{L}V,⊙ . For Gru 1 we estimate a mean velocity of -{140.5}-1.6+2.4 km s-1 and a mean metallicity of [Fe/H] = -{1.42}-0.42+0.55 but our sample does not resolve Gru 1's velocity dispersion. The radial coordinates of Tuc 2 and Gru 1 in Galactic phase space suggest that their orbits are among the most energetic within a distance of ≲ 300 {{kpc}}. Moreover, their proximity to each other in this space arises naturally if both objects are trailing the Large Magellanic Cloud. This paper presents data gathered with the Magellan Telescopes at Las Campanas Observatory, Chile.

  17. Hofbauer cells of M2a, M2b and M2c polarization may regulate feto-placental angiogenesis.

    PubMed

    Loegl, J; Hiden, U; Nussbaumer, E; Schliefsteiner, C; Cvitic, S; Lang, I; Wadsack, C; Huppertz, B; Desoye, G

    2016-11-01

    The human placenta comprises a special type of tissue macrophages, the Hofbauer cells (HBC), which exhibit M2 macrophage phenotype. Several subtypes of M2-polarized macrophages (M2a, M2b and M2c) exist in almost all tissues. Macrophage polarization depends on the way of macrophage activation and leads to the expression of specific cell surface markers and the acquisition of specific functions, including tissue remodeling and the promotion of angiogenesis. The placenta is a highly vascularized and rapidly growing organ, suggesting a role of HBC in feto-placental angiogenesis. We here aimed to characterize the specific polarization and phenotype of HBC and investigated the role of HBC in feto-placental angiogenesis. Therefore, HBC were isolated from third trimester placentas and their phenotype was determined by the presence of cell surface markers (FACS analysis) and secretion of cytokines (ELISA). HBC conditioned medium (CM) was analyzed for pro-angiogenic factors, and the effect of HBC CM on angiogenesis, proliferation and chemoattraction of isolated primary feto-placental endothelial cells (fpEC) was determined in vitro Our results revealed that isolated HBC possess an M2 polarization, with M2a, M2b and M2c characteristics. HBC secreted the pro-angiogenic molecules VEGF and FGF2. Furthermore, HBC CM stimulated the in vitro angiogenesis of fpEC. However, compared with control medium, chemoattraction of fpEC toward HBC CM was reduced. Proliferation of fpEC was not affected by HBC CM. These findings demonstrate a paracrine regulation of feto-placental angiogenesis by HBC in vitro Based on our collective results, we propose that the changes in HBC number or phenotype may affect feto-placental angiogenesis.

  18. Present and Future of M2M

    NASA Astrophysics Data System (ADS)

    Ono, Satoru; Watanabe, Takashi

    In recent years, the rapid progress in the development of hardware and software technologies enables tiny and low cost information devices hereinafter referred to as Machine to be widely available. M2M (Machine to Machine) has been of much attention where many tiny machines are connected to each other through networks with minimal human intervention to provide smooth and intelligent management. M2M is a promising core technology providing timely, flexible, efficient and comprehensive service at low cost. M2M has wide variety of applications including energy management system, environmental monitoring system, intelligent transport system, industrial automation system and other applications. M2M consists of terminals and networks that connect them. In this paper, we mainly focus on M2M networking and mention the future direction of the technology.

  19. Understanding Laser Beam Quality Beyond M2

    NASA Astrophysics Data System (ADS)

    Soskind, Y. G.; Soskind, M. G.

    2016-09-01

    The laser beam M2 quality parameter is based on the second moments' theory, as defined by ISO standards, and provides a common approach for defining the propagation characteristics of laser beams as a whole. At the same time, the M2 parameter fails to quantitatively distinguish the quality of laser beams with different spatial characteristics. For example, several laser beams with very different spatial profiles may have the same M2 value. To overcome this ambiguity, a different beam quality criterion is introduced, allowing for a quantitative definition of both the structured laser beam shape and its propagation characteristics. This criterion, called the encircled power M2 (EPM2), bridges the gap between the M2 quality parameter and the structured laser beam shape. Based on several examples we demonstrate the utility of EPM2 as applied to characterization of several structured laser beam types.

  20. Moving M2 mirror without pointing offset.

    NASA Astrophysics Data System (ADS)

    Ragazzoni, R.; Bortoletto, F.

    1991-09-01

    Moving the secondary mirror M2 to introduce an amount of decentering coma is one of the tasks of active optics. The authors show that this target is accomplished with high accuracy rotating the mirror around a point located near, but not exactly at the center of curvature of M2. Ray tracing results are compared to analytical ones in the case of the Italian Galileo telescope, that will be equipped with an high precision M2 driving device; the close matching with the analytical calculations is demonstrated.

  1. Serum Stability and Affinity Optimization of an M2 Macrophage-Targeting Peptide (M2pep)

    PubMed Central

    Ngambenjawong, Chayanon; Gustafson, Heather H.; Pineda, Julio M.; Kacherovsky, Nataly A.; Cieslewicz, Maryelise; Pun, Suzie H.

    2016-01-01

    Tumor associated macrophages (TAMs) are a major stromal component of the tumor microenvironment in several cancers. TAMs are a potential target for adjuvant cancer therapies due to their established roles in promoting proliferation of cancer cells, angiogenesis, and metastasis. We previously discovered an M2 macrophage-targeting peptide (M2pep) which was successfully used to target and deliver a pro-apoptotic KLA peptide to M2-like TAMs in a CT-26 colon carcinoma model. However, the effectiveness of in vivo TAM-targeting using M2pep is limited by its poor serum stability and low binding affinity. In this study, we synthesized M2pep derivatives with the goals of increasing serum stability and binding affinity. Serum stability evaluation of M2pepBiotin confirmed its rapid degradation attributed to exolytic cleavage from the N-terminus and endolytic cleavages at the W10/W11 and S16/K17 sites. N-terminal acetylation of M2pepBiotin protected the peptide against the exolytic degradation while W10w and K(17,18,19)k substitutions were able to effectively protect endolytic degradation at their respective cleavage sites. However, no tested amino acid changes at the W10 position resulted in both protease resistance at that site and retention of binding activity. Therefore, cyclization of M2pep was investigated. Cyclized M2pep better resisted serum degradation without compromising binding activity to M2 macrophages. During the serum stability optimization process, we also discovered that K9R and W10Y substitutions significantly enhanced binding affinity of M2pep. In an in vitro binding study of different M2pep analogs pre-incubated in mouse serum, cyclic M2pep with K9R and W10Y modifications (cyclic M2pep(RY)) retained the highest binding activity to M2 macrophages over time due to its improved serum stability. Finally, we evaluated the in vivo accumulation of sulfo-Cy5-labeled M2pep and cyclic M2pep(RY) in both the CT-26 and 4T1 breast carcinoma models. Cyclic M2pep

  2. Mitsubishi A6M2 'Zero'

    NASA Technical Reports Server (NTRS)

    1943-01-01

    Mitsubishi A6M2 'Zero': Captured at Akutan Island, Alaska, in August 1942, this Mitsubishi A6M2 fighter was the first 'Zero' to fall intact into Allied hands during WW II. After limited flying on the West Coast, the 'Zero' arrived at Langley for installation of test equipment prior to in-depth flight testing by the Navy at Patuxent River, Maryland.

  3. 46 CFR 30.10-6 - Cargo handling room-TB/ALL.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 1 2011-10-01 2011-10-01 false Cargo handling room-TB/ALL. 30.10-6 Section 30.10-6 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS GENERAL PROVISIONS Definitions § 30.10-6 Cargo handling room—TB/ALL. The term cargo handling room means any enclosed space where cargo is...

  4. 46 CFR 30.10-6 - Cargo handling room-TB/ALL.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Cargo handling room-TB/ALL. 30.10-6 Section 30.10-6 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS GENERAL PROVISIONS Definitions § 30.10-6 Cargo handling room—TB/ALL. The term cargo handling room means any enclosed space where cargo is...

  5. M2-F1 in flight

    NASA Technical Reports Server (NTRS)

    1965-01-01

    The M2-F1 Lifting Body is seen here under tow, high above Rogers Dry Lake near the Flight Research Center (later redesignated the Dryden Flight Research Center), Edwards, California. R. Dale Reed effectively advocated the project with the support of NASA research pilot Milt Thompson. Together, they gained the support of Flight Research Center Director Paul Bikle. After a six-month feasibility study, Bikle gave approval in the fall of 1962 for the M2-F1 to be built. The wingless, lifting body aircraft design was initially concieved as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Flight Research Center management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. These initial tests produced enough flight data about the M2-F1 to proceed with flights behind a NASA C-47 tow plane at greater altitudes. The C-47 took the craft to an altitude of 12,000 where free flights back to Rogers Dry Lake began. Pilot for the first series of flights of the M2-F1 was NASA research pilot Milt Thompson. Typical glide flights with the M2-F1 lasted about two minutes and reached speeds of 110 to l20 mph. More than 400 ground tows and 77 aircraft tow flights were carried out with the M2-F1. The success of Dryden's M2-F1 program led to NASA's development and construction of two heavyweight lifting bodies based on studies at NASA's Ames and Langley research centers--the M2-F2 and the HL

  6. Anti-influenza M2e antibody

    SciTech Connect

    Bradbury, Andrew M.

    2013-04-16

    Humanized recombinant and monoclonal antibodies specific for the ectodomain of the influenza virus M2 ion channel protein are disclosed. The antibodies of the invention have anti-viral activity and may be useful as anti-viral therapeutics and/or prophylactic/vaccine agents for inhibiting influenza virus replication and for treating individuals infected with influenza.

  7. Anti-influenza M2e antibody

    SciTech Connect

    Bradbury, Andrew M

    2011-12-20

    Humanized recombinant and monoclonal antibodies specific for the ectodomain of the influenza virus M2 ion channel protein are disclosed. The antibodies of the invention have anti-viral activity and may be useful as anti-viral therapeutics and/or prophylactic/vaccine agents for inhibiting influenza virus replication and for treating individuals infected with influenza.

  8. M2-F1 simulator cockpit

    NASA Technical Reports Server (NTRS)

    1963-01-01

    This early simulator of the M2-F1 lifting body was used for pilot training, to test landing techniques before the first ground tow attempts, and to test new control configurations after the first tow attempts and wind-tunnel tests. The M2-F1 simulator was limited in some ways by its analog simulator. It had only limited visual display for the pilot, as well. The wingless, lifting body aircraft design was initially conceived as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop near Long Beach for modification. With a special gearbox and racing slicks, the Pontiac could tow the 1,000-pound M2-F1 110 miles per hour in 30 seconds. It proved adequate for the roughly 400 car tows that got the M2-F1 airborne

  9. M2-F1 in flight

    NASA Technical Reports Server (NTRS)

    1964-01-01

    The M2-F1 Lifting Body is seen here under tow by an unseen C-47 at the NASA Flight Research Center (later redesignated the Dryden Flight Research Center), Edwards, California. The low-cost vehicle was the first piloted lifting body to be test flown. The lifting-body concept originated in the mid-1950s at the National Advisory Committee for Aeronautics' Ames Aeronautical Laboratory, Mountain View California. By February 1962, a series of possible shapes had been developed, and R. Dale Reed was working to gain support for a research vehicle. The wingless, lifting body aircraft design was initially concieved as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. These initial tests produced enough flight data about the M2-F1 to proceed with flights behind a NASA C-47 tow plane at greater altitudes. The C-47 took the craft to an altitude of 12,000 where free flights back to Rogers Dry Lake began. Pilot for the first series of flights of the M2-F1 was NASA research pilot Milt Thompson. Typical glide flights with the M2-F1 lasted about two minutes and reached speeds of 110 to l20 mph. More than 400 ground tows and 77 aircraft tow flights were carried out with the M2-F1. The success of Dryden's M2-F1 program led to NASA's development and construction of two heavyweight lifting bodies based on studies at

  10. What is $$\\Delta m^2_{ee}$$ ?

    DOE PAGES

    Parke, Stephen

    2016-03-09

    Here, the current short baseline reactor experiments, Daya Bay and RENO (Double Chooz) have measured (or are capable of measuring) an effective Δm2 associated with the atmospheric oscillation scale of 0.5 km/MeV in electron antineutrino disappearance. In this paper, I compare and contrast the different definitions of such an effective Δm2 and argue that the simple, L/E independent definition given by Δmee2≡cos2θ12Δm312+sin2θ12Δm322, i.e. “the νe weighted average of Δm312 and Δm322,” is superior to all other definitions and is useful for both short baseline experiments mentioned above and for the future medium baseline experiments JUNO and RENO-50.

  11. M2-F1 in flight

    NASA Technical Reports Server (NTRS)

    1963-01-01

    This 25-second clip shows Milt Thompson being towed in the M2-F1 behind a C-47 aircraft. The M2-F1 lifting body, dubbed the 'flying bathtub' by the media, was the precursor of a remarkable series of wingless flying vehicles that contributed data used in the Space Shuttles, the X-33 Advanced Technology Demonstrator for the next century's Reusable Launch Vehicle, and the X-38 Technology Demonstrator for crew return from the International Space Station. Based on the ideas and basic design of Alfred J. Eggers and others at the Ames Aeronautical Laboratory (now the Ames Research Center), Mountain View, California, in the mid-1950's, the M2-F1 was built in 1962-63 over a four-month period for a cost of only about $30,000, plus an additional $8,000-$10,000 for an ejection seat. Engineers and technicians at the NASA Flight Research Center (now NASA Dryden) kept costs low by designing and fabricating it partly in-house, with the plywood shell constructed by a local sailplane builder. Someone at the time estimated that it would have cost a major aircraft company $150,000 to build the same vehicle. Unlike the later lifting bodies, the M2-F1 was unpowered and was initially towed by a souped-up Pontiac convertible until it was airborne. Later a C-47 took over the towing duties. Flown by such famous research pilots as Milt Thompson, Bruce Peterson, Chuck Yeager, and Bill Dana, the lightweight flying bathtub demonstrated that a wingless vehicle shaped for reentry into the Earth's atmosphere from space could be flown and landed safely. Flown from 1963 to 1966, the lightweight M2-F1 paved the way for the heavyweight M2-F2, M2-F3, HL-10, X-24A, and X-24B lifting bodies that flew under rocket power after launch from a B-52 mothership. The heavyweights flew from 1966 to 1975, demonstrating the viability and versatility of the wingless configuration and the ability of a vehicle with low lift-over-drag characteristics to fly to high altitudes and then to land precisely with their rocket

  12. Newly Installed S-1 Truss

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Launched October 7, 2002 aboard the Space Shuttle Orbiter Atlantis, the STS-112 mission lasted 11 days and performed three sessions of Extra Vehicular Activity (EVA). Its primary mission was to install the Starboard (S1) Integrated Truss Structure and Equipment Translation Aid (CETA) Cart to the International Space Station (ISS). The S1 truss provides structural support for the orbiting research facility's radiator panels, which use ammonia to cool the Station's complex power system. The S1 truss, attached to the S0 (S Zero) truss installed by the previous STS-110 mission, flows 637 pounds of anhydrous ammonia through three heat rejection radiators. The truss is 45-feet long, 15-feet wide, 10-feet tall, and weighs approximately 32,000 pounds. The CETA is the first of two human-powered carts that will ride along the International Space Station's railway providing a mobile work platform for future extravehicular activities by astronauts. This is a view of the newly installed S1 Truss as photographed during the mission's first scheduled EVA. The Station's Canadarm2 is in the foreground. Visible are astronauts Piers J. Sellers (lower left) and David A. Wolf (upper right), both STS-112 mission specialists.

  13. LOSA-M2 aerosol Raman lidar

    SciTech Connect

    Balin, Yu S; Bairashin, G S; Kokhanenko, G P; Penner, I E; Samoilova, S V

    2011-10-31

    The scanning LOSA-M2 aerosol Raman lidar, which is aimed at probing atmosphere at wavelengths of 532 and 1064 nm, is described. The backscattered light is received simultaneously in two regimes: analogue and photon-counting. Along with the signals of elastic light scattering at the initial wavelengths, a 607-nm Raman signal from molecular nitrogen is also recorded. It is shown that the height range of atmosphere probing can be expanded from the near-Earth layer to stratosphere using two (near- and far-field) receiving telescopes, and analogue and photon-counting lidar signals can be combined into one signal. Examples of natural measurements of aerosol stratification in atmosphere along vertical and horizontal paths during the expeditions to the Gobi Desert (Mongolia) and Lake Baikal areas are presented.

  14. Evidence of paired M2 muscarinic receptors

    SciTech Connect

    Potter, L.T.; Ballesteros, L.A.; Bichajian, L.H.; Ferrendelli, C.A.; Fisher, A.; Hanchett, H.E.; Zhang, R. )

    1991-02-01

    Binding assays involving various antagonists, including N-(3H) methylscopolamine, (3H)quinuclidinyl benzilate, AFDX-116, pirenzepine, and propylbenzilylcholine mustard, disclosed only a single population of M2 muscarinic receptors in membranes from the rat brainstem (medulla, pons, and colliculi). However, competition curves between N-(3H)methylscopolamine and various agonists, including oxotremorine, cis-dioxolane, and acetylethylcholine mustard, showed approximately equal numbers of guanine nucleotide-sensitive high affinity (H) sites and guanine nucleotide-insensitive low affinity (L) sites. This 50% H phenomenon persisted in different buffers, at different temperatures, after the number of receptors was halved (and, thus, the remaining receptor to guanine nucleotide-binding protein ratio was doubled), after membrane solubilization with digitonin, and when rabbit cardiac membranes were used instead of rat brainstem membranes. Preferential occupation of H sites with acetylethylcholine mustard, and of L sites with quinuclidinyl benzilate or either mustard, yielded residual free receptor populations showing predominantly L and H sites, respectively. Low concentrations of (3H)-oxotremorine-M labeled only H sites, and the Bmax for these sites was 49% of the Bmax found with (3H)quinuclidinyl benzilate plus guanine nucleotide. These and other results are most consistent with the idea that H and L receptor sites exist on separate but dimeric receptor molecules and with the hypothesis that only the H receptors cycle between high and low affinity, depending upon interactions between this receptor molecule and a guanine nucleotide-binding protein.

  15. Interpreting observations of edge-on gravitationally unstable accretion flows. The case of G10.6-0.4

    NASA Astrophysics Data System (ADS)

    Liu, Hauyu Baobab

    2017-01-01

    Context. Gravitational collapse of molecular cloud or cloud core/clump may lead to the formation of geometrically flattened, rotating accretion flow surrounding the new born star or star cluster. Gravitational instability may occur in such accretion flow when the gas to stellar mass ratio is high (e.g., over 10%). Aims: This paper takes the OB cluster-forming region G10.6-0.4 as an example. We introduce the enclosed gas mass around its central ultra compact (UC) Hii region, address the gravitational stability of the accreting gas, and outline the observed potential signatures of gravitational instability. Methods: The dense gas accretion flow around the central UC Hii region in G10.6-0.4 is geometrically flattened, and is in an approximately edge-on projection. The position-velocity (PV) diagrams of various molecular gas tracers on G10.6-0.4 consistently show asymmetry in the spatial- and the velocity domain. We deduce the morphology of the dense gas accretion flow by modeling velocity distribution of the azimuthally asymmetric gas structures, and by directly de-projecting the PV diagrams. Results: We find that within the 0.3 pc radius, an infall velocity of 1-2 km s-1 may be required to explain the observed PV diagrams. In addition, the velocity distribution traced in the PV diagrams can be interpreted by spiral arm-like structures, which may be connected with exterior infalling gas filaments. We propose that the morphology of dense gas structures appears very similar to the spatially resolved gas structures around the OB cluster-forming region G33.92+0.11 with similar gas mass and size, which is likely, however, to be in an approximately face-on projection. Conclusions: The dense gas accretion flow around G10.6-0.4 appears to be Toomre-unstable, which is consistent with the existence of large-scale spiral arm-like structures, and the formation of localized gas condensations. The proposed approaches for data analyses may be applied to the observations of Class 0/I

  16. Optical response at 10.6 microns in tungsten silicide Schottky barrier diodes

    NASA Technical Reports Server (NTRS)

    Kumar, Sandeep; Boyd, Joseph T.; Jackson, Howard E.

    1987-01-01

    Optical response to radiation at a wavelength of 10.6 microns in tungsten silicide-silicon Schottky barrier diodes has been observed. Incident photons excite electrons by means of junction plasmon assisted inelastic electron tunneling. At 78 K, a peak in the second derivative of current versus junction bias voltage was observed at a voltage corresponding to the energy of photons having a wavelength of 10.6 microns. This peak increased with increasing incident laser power, saturating at the highest laser powers investigated.

  17. Acousto-Optic Beam Sampler, Part III: Diffraction Experiments at 10.6 micrometers.

    DTIC Science & Technology

    This report deals with the results of acousto - optic diffraction experiments in air at 10.6 micron. The laser used for the experiments was operated...fields. Detailed experiments were performed to investigate the dependence of the acousto - optic diffraction on incident laser power, acoustic drive voltage and angle of incidence.

  18. Motion-to-Energy (M2E) Power Generation Technology

    SciTech Connect

    INL

    2008-05-30

    INL researchers developed M2E, a new technology that converts motion to energy. M2E uses an innovative, optimized microgenerator with power management circuitry that kinetically charges mobile batteries from natural motion such as walking.

  19. Motion-to-Energy (M2E) Power Generation Technology

    ScienceCinema

    INL

    2016-07-12

    INL researchers developed M2E, a new technology that converts motion to energy. M2E uses an innovative, optimized microgenerator with power management circuitry that kinetically charges mobile batteries from natural motion such as walking.

  20. Coupling characteristics of thin-film metal-oxide-metal diodes at 10.6 microns

    NASA Technical Reports Server (NTRS)

    Wang, S. Y.; Gustafson, T. K.; Izawa, T.

    1975-01-01

    Direct detection experiments have demonstrated the coherent coupling of 10.6 micrometer radiation into photolithographically fabricated metal-oxide-metal tunnel junctions. A CO2 laser beam mechanically chopped at 1 KHz was focused at a variable angle of incidence with a power density of about 10 W/sq cm at the diodes. Diodes in which the junction resistance was much greater than the lead resistance displayed angular characteristics dominated by coherent antenna coupling.

  1. Radiation effects on beta 10.6 of pure and europium doped KCl

    NASA Technical Reports Server (NTRS)

    Grimes, H. H.; Maisel, J. E.; Hartford, R. H.

    1975-01-01

    Changes in the optical absorption coefficient as a result of X-ray and electron bombardment of pure KCl (monocrystalline and polycrystalline), and divalent europium doped polycrystalline KCl were determined. The optical absorption coefficients were measured by a constant heat flow calorimetric method. Both 300 KV X-irradiation and 2 MeV electron irradiation produced significant increases in beta 10.6, measured at room temperature. The X-irradiation of pure moncrystalline KCl increased beta 10.6 by 0.005/cm for a 113 MR dose. For an equivalent dose, 2 MeV electrons were found less efficient in changing beta 10.6. However, electron irradiation of pure and Eu-doped polycrystalline KCl produced marked increases in adsorption. Beta increased to over 0.25/cm in Eu-doped material for a 30 x 10 to the 14th power electrons/sq cm dose, a factor of 20 increase over unirradiated material. Moreover, bleaching the electron irradiated doped KCl with 649 m light produced and additional factor of 1.5 increase. These findings will be discussed in light of known defect-center properties in KCl.

  2. ABJ(M) and fractional M2's with fractional M2 charge

    NASA Astrophysics Data System (ADS)

    Evslin, Jarah; Kuperstein, Stanislav

    2009-12-01

    Recently Aharony, Bergman and Jafferis (ABJ) have argued that a 3d U(N+M)k × U(N)-k Chern-Simons gauge theory may have a vacuum with Script N = 6 supersymmetry only if M<=k and if a certain period of the B-field in a IIA background is quantized. We use a braneology argument to argue that Script N = 3 supersymmetry may be preserved under the weaker condition that 2Nk>=M(M-k) with no restriction on the B-field. IIB brane cartoons and 11d supergravity solutions corresponding to Script N = 3 vacua that do not preserve Script N = 6 supersymmetry are argued to represent cascading gauge theories, generalizing the Script N = 2 Seiberg duality conjectured by Giveon and Kutasov. While as usual the M2-brane charge runs as a result of the twisted Bianchi identity for *G4, the M5-brane charge running relies on the fact that it wraps a torsion homology cycle.

  3. Infrared (10.6-mum) scattering and extinction in laboratory water and ice clouds.

    PubMed

    Sassen, K

    1981-01-15

    Measurements of the angular scattering and extinction of IR (10.6-mum) laser radiation in laboratory water and ice clouds are reported and compared to theoretical predictions for spheres and visible (0.633-mum) light scattering data. Randomly oriented cloud particles with dimensions ranging from several times smaller to larger than the incident wavelength generated phase functions span the Rayleigh and Mie scattering domains and illustrate the effects caused by strong internal energy absorption. Dual-wavelength extinction measurements reveal information on the growth and dissipation of laboratory water clouds and the effects of cloud seeding. The remote sensing significance of the findings is discussed.

  4. S1P control of endothelial integrity.

    PubMed

    Xiong, Yuquan; Hla, Timothy

    2014-01-01

    Sphingosine 1-phosphate (S1P), a lipid mediator produced by sphingolipid metabolism, promotes endothelial cell spreading, vascular maturation/stabilization, and barrier function. S1P is present at high concentrations in the circulatory system, whereas in tissues its levels are low. This so-called vascular S1P gradient is essential for S1P to regulate much physiological and pathophysiological progress such as the modulation of vascular permeability. Cellular sources of S1P in blood has only recently begun to be identified. In this review, we summarize the current understanding of S1P in regulating vascular integrity. In particular, we discuss the recent discovery of the endothelium-protective functions of HDL-bound S1P which is chaperoned by apolipoprotein M.

  5. 26 CFR 1.401(m)-2 - ACP test.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 5 2013-04-01 2013-04-01 false ACP test. 1.401(m)-2 Section 1.401(m)-2 Internal... TAXES (CONTINUED) Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.401(m)-2 ACP test. (a) Actual contribution percentage (ACP) test—(1) In general—(i) ACP test formula. A plan satisfies the ACP test for...

  6. 26 CFR 1.401(m)-2 - ACP test.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 5 2011-04-01 2011-04-01 false ACP test. 1.401(m)-2 Section 1.401(m)-2 Internal... TAXES (CONTINUED) Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.401(m)-2 ACP test. (a) Actual... under paragraph (a)(1) of this section either— (A) Pursuant to section 401(m)(5)(C), the ACP test...

  7. Dry/wet wire reflectivities at 10.6 μm

    NASA Astrophysics Data System (ADS)

    Young, Donald S.; Osche, Gregory R.; Fisher, Kirk L.; Lok, Yuchoi F.

    1991-08-01

    Power cable reflectivities have been measured for both dry and wet conditions using a 10.6 micrometers coherent CO2 laser radar. Measurements were made at a range of 620 m using two types of cable: 1-in.-diameter Grosbeak and 3/8-in. Grouse, at +/- 60 degree(s) aspect angles relative to the normal in increments of 10 degree(s). The cables were both artificially sprayed, in an effort to simulate realistic rainfall rates, as well as being exposed to light rain. Results show that the drop in reflectivity of wet cables compared to dry cables is a function of aspect angle with a mean drop for the Grosbeak and Grouse cables of -5 dB and -1.3 dB, respectively. Measurements of the drying rates of the cables showed a return to the dry state reflectivity in approximately 100 sec after being liberally doused.

  8. 10.6% Certified Colloidal Quantum Dot Solar Cells via Solvent-Polarity-Engineered Halide Passivation.

    PubMed

    Lan, Xinzheng; Voznyy, Oleksandr; García de Arquer, F Pelayo; Liu, Mengxia; Xu, Jixian; Proppe, Andrew H; Walters, Grant; Fan, Fengjia; Tan, Hairen; Liu, Min; Yang, Zhenyu; Hoogland, Sjoerd; Sargent, Edward H

    2016-07-13

    Colloidal quantum dot (CQD) solar cells are solution-processed photovoltaics with broad spectral absorption tunability. Major advances in their efficiency have been made via improved CQD surface passivation and device architectures with enhanced charge carrier collection. Herein, we demonstrate a new strategy to improve further the passivation of CQDs starting from the solution phase. A cosolvent system is employed to tune the solvent polarity in order to achieve the solvation of methylammonium iodide (MAI) and the dispersion of hydrophobic PbS CQDs simultaneously in a homogeneous phase, otherwise not achieved in a single solvent. This process enables MAI to access the CQDs to confer improved passivation. This, in turn, allows for efficient charge extraction from a thicker photoactive layer device, leading to a certified solar cell power conversion efficiency of 10.6%, a new certified record in CQD photovoltaics.

  9. Testing the Wavelength Dependence of Cosmological Redshift Down to Δz ˜ 10-6

    NASA Astrophysics Data System (ADS)

    Ferreras, Ignacio; Trujillo, Ignacio

    2016-07-01

    At the core of the standard cosmological model lies the assumption that the redshift of distant galaxies is independent of photon wavelength. This invariance of cosmological redshift with wavelength is routinely found in all galaxy spectra with a precision of Δz ˜ 10-4. The combined use of approximately half a million high-quality galaxy spectra from the Sloan Digital Sky Survey (SDSS) allows us to explore this invariance down to a nominal precision in redshift of 10-6 (statistical). Our analysis is performed over the redshift interval 0.02 < z < 0.25. We use the centroids of spectral lines over the 3700-6800 Å rest-frame optical window. We do not find any difference in redshift between the blue and red sides down to a precision of 10-6 at z ≲ 0.1 and 10-5 at 0.1 ≲ z ≲ 0.25 (i.e., at least an order of magnitude better than with single galaxy spectra). This is the first time the wavelength-independence of the (1 + z) redshift law is confirmed over a wide spectral window at this precision level. This result holds independently of the stellar population of the galaxies and their kinematical properties. This result is also robust against wavelength calibration issues. The limited spectral resolution (R ˜ 2000) of the SDSS data, combined with the asymmetric wavelength sampling of the spectral features in the observed restframe due to the (1 + z) stretching of the lines, prevent our methodology from achieving a precision higher than 10-5, at z > 0.1. Future attempts to constrain this law will require high quality galaxy spectra at higher resolution (R ≳ 10,000).

  10. Secure Data Aggregation Protocol for M2M Communications

    DTIC Science & Technology

    2015-03-24

    smart grid communications, which precisely meets the requirement of periodically collecting users’ electricity consumption while preserving privacy...address: rxlu@ntu.edu.sg - Institution: School of Electrical and Electronics Engineering, Nanyang Technological University - Mailing Address: 50...surveillance, smart metering, environmental monitoring, industrial automation and military scenarios [1][2]. Despite various M2M applications, the basic M2M

  11. CYP2S1: A short review

    SciTech Connect

    Saarikoski, Sirkku T. . E-mail: sirkku.saarikoski@ktl.fi; Rivera, Steven P.; Hankinson, Oliver; Husgafvel-Pursiainen, Kirsti

    2005-09-01

    A new member of the cytochrome P450 superfamily, CYP2S1, has recently been identified in human and mouse. In this paper, we review the data currently available for CYP2S1. The human CYP2S1 gene is located in chromosome 19q13.2 within a cluster including CYP2 family members CYP2A6, CYP2A13, CYP2B6, and CYP2F1. These genes also show the highest homology to the human CYP2S1. The gene has recently been found to harbor genetic polymorphism. CYP2S1 is inducible by dioxin, the induction being mediated by the Aryl Hydrocarbon Receptor (AHR) and Aryl Hydrocarbon Nuclear Translocator (ARNT) in a manner typical for CYP1 family members. In line with this, CYP2S1 has been shown to be inducible by coal tar, an abundant source of PAHs, and it was recently reported to metabolize naphthalene. This points to the involvement of CYP2S1 in the metabolism of toxic and carcinogenic compounds, similar to other dioxin-inducible CYPs. CYP2S1 is expressed in epithelial cells of a wide variety of extrahepatic tissues. The highest expression levels have been observed in the epithelial tissues frequently exposed to xenobiotics, e.g., the respiratory, gastrointestinal, and urinary tracts, and in the skin. The observed ubiquitous tissue distribution, as well as the expression of CYP2S1 throughout embryogenesis suggest that CYP2S1 is likely to metabolize important endogenous substrates; thus far, retinoic acid has been identified. In conclusion, CYP2S1 exhibits many features of interest for human health and thus warrants further investigation.

  12. Safety assessment for the S-1 Spheromak

    SciTech Connect

    Ellis, R. Jr.; Stencel, J.R.

    1984-02-01

    The S-1 machine is part of the Magnetic Fusion Program. The goal of the Magnetic Fusion Program is to develop and demonstrate the practical application of fusion. S-1 is an experimental device which will provide an essential link in the research effort aiming at the realization of fusion power.

  13. Microsecond enamel ablation with 10.6μm CO2 laser radiation

    NASA Astrophysics Data System (ADS)

    Góra, W. S.; McDonald, A.; Hand, D. P.; Shephard, J. D.

    2016-02-01

    Lasers have been previously been used for dental applications, however there remain issues with thermally-induced cracking. In this paper we investigate the impact of pulse length on CO2 laser ablation of human dental enamel. Experiments were carried in vitro on molar teeth without any modification to the enamel surface, such as grinding or polishing. In addition to varying the pulse length, we also varied pulse energy and focal position, to determine the most efficient ablation of dental hard tissue and more importantly to minimize or eradicate cracking. The maximum temperature rise during the multi pulse ablation process was monitored using a set of thermocouples embedded into the pulpal chamber. The application of a laser device in dental surgery allows removal of tissue with higher precision, which results in minimal loss of healthy dental tissue. In this study we use an RF discharge excited CO2 laser operating at 10.6μm. The wavelength of 10.6 μm overlaps with a phosphate band (PO3-4) absorption in dental hard tissue hence the CO2 laser radiation has been selected as a potential source for modification of the tissue. This research describes an in-depth analysis of single pulse laser ablation. To determine the parameters that are best suited for the ablation of hard dental tissue without thermal cracking, a range of pulse lengths (10-200 μs), and fluences (0-100 J/cm2) are tested. In addition, different laser focusing approaches are investigated to select the most beneficial way of delivering laser radiation to the surface (divergent/convergent beam). To ensure that these processes do not increase the temperature above the critical threshold and cause the necrosis of the tissue a set of thermocouples was placed into the pulpal chambers. Intermittent laser radiation was investigated with and without application of a water spray to cool down the ablation site and the adjacent area. Results show that the temperature can be kept below the critical threshold

  14. Development of ferromagnetic spinels for optical isolation at 10. 6. mu. m

    SciTech Connect

    Teegarden, K.J.

    1980-05-01

    Vacuum hot pressing was used to fabricate CdCr/sub 2/S/sub 4/, CdCr/sub 2/Se/sub 4/ and (1-x) CdCr/sub 2/S/sub 4/.x CdCr/sub 2/Se/sub 4/ discs with diameters of 1.25 cm from fine powders and small single crystals to relative densities as high as 99.6%. Optical attenuation coefficients of approx. 1.0 cm/sup -1/ at 10.6 m were obtained for CdCr/sub 2/S/sub 4/, and values of 12.1 cm/sup -1/ and 14.9 cm/sup -1/ for the selenide and sulfur-selenide mixture. Two-and-three-phonon absorption bands were found to limit the transmission of CdCr/sub 2/S/sub 4/ at lambda > 10 ..mu..m. Extrinsic absorption mechanisms caused the higher attenuation coefficients in CdCr/sub 2/Se/sub 4/ and the mixture. The main extrinsic mechanisms at long wavelengths were free carrier absorption (in CdCr/sub 2/Se/sub 4/) and an impurity absorption band at 16.3 ..mu..m due to Cr/sub 2/O/sub 3/. At short wavelengths the attenuation coefficient was dominated by scattering from pores and second phases. Free carrier absorption was found to be induced by free selenium present in the starting powders. Suppression of this absorption was achieved by optimizing the hot-pressing procedure in order to remove free selenium. The presence of pores was attributed to incomplete densification arising from the presence of second phases (CdSe and Cr/sub 2/Se/sub 3/) and the absence of plastic deformation as a densification mechanism. Laser damage thresholds of 250 MWcm/sup -2/ and 100 MWcm/sup -2/ were measured at 10.6 ..mu..m for CdCr/sub 2/S/sub 4/ and CdCr/sub 2/Se/sub 4/, respectively.

  15. Genome-wide functional annotation of Phomopsis longicolla isolate MSPL 10-6.

    PubMed

    Darwish, Omar; Li, Shuxian; Matthews, Benjamin; Alkharouf, Nadim

    2016-06-01

    Phomopsis seed decay of soybean is caused primarily by the seed-borne fungal pathogen Phomopsis longicolla (syn. Diaporthe longicolla). This disease severely decreases soybean seed quality, reduces seedling vigor and stand establishment, and suppresses yield. It is one of the most economically important soybean diseases. In this study we annotated the entire genome of P. longicolla isolate MSPL 10-6, which was isolated from field-grown soybean seed in Mississippi, USA. This study represents the first reported genome-wide functional annotation of a seed borne fungal pathogen in the Diaporthe-Phomopsis complex. The P. longicolla genome annotation will enable research into the genetic basis of fungal infection of soybean seed and provide information for the study of soybean-fungal interactions. The genome annotation will also be a valuable resource for the research and agricultural communities. It will aid in the development of new control strategies for this pathogen. The annotations can be found from: http://bioinformatics.towson.edu/phomopsis_longicolla/download.html. NCBI accession number is: AYRD00000000.

  16. A polymer tandem solar cell with 10.6% power conversion efficiency.

    PubMed

    You, Jingbi; Dou, Letian; Yoshimura, Ken; Kato, Takehito; Ohya, Kenichiro; Moriarty, Tom; Emery, Keith; Chen, Chun-Chao; Gao, Jing; Li, Gang; Yang, Yang

    2013-01-01

    An effective way to improve polymer solar cell efficiency is to use a tandem structure, as a broader part of the spectrum of solar radiation is used and the thermalization loss of photon energy is minimized. In the past, the lack of high-performance low-bandgap polymers was the major limiting factor for achieving high-performance tandem solar cell. Here we report the development of a high-performance low bandgap polymer (bandgap <1.4 eV), poly[2,7-(5,5-bis-(3,7-dimethyloctyl)-5H-dithieno[3,2-b:2',3'-d]pyran)-alt-4,7-(5,6-difluoro-2,1,3-benzothia diazole)] with a bandgap of 1.38 eV, high mobility, deep highest occupied molecular orbital. As a result, a single-junction device shows high external quantum efficiency of >60% and spectral response that extends to 900 nm, with a power conversion efficiency of 7.9%. The polymer enables a solution processed tandem solar cell with certified 10.6% power conversion efficiency under standard reporting conditions (25 °C, 1,000 Wm(-2), IEC 60904-3 global), which is the first certified polymer solar cell efficiency over 10%.

  17. A searchable database for the genome of Phomopsis longicolla (isolate MSPL 10-6).

    PubMed

    Darwish, Omar; Li, Shuxian; May, Zane; Matthews, Benjamin; Alkharouf, Nadim W

    2016-01-01

    Phomopsis longicolla (syn. Diaporthe longicolla) is an important seed-borne fungal pathogen that primarily causes Phomopsis seed decay (PSD) in most soybean production areas worldwide. This disease severely decreases soybean seed quality by reducing seed viability and oil quality, altering seed composition, and increasing frequencies of moldy and/or split beans. To facilitate investigation of the genetic base of fungal virulence factors and understand the mechanism of disease development, we designed and developed a database for P. longicolla isolate MSPL 10-6 that contains information about the genome assemblies (contigs), gene models, gene descriptions and GO functional ontologies. A web-based front end to the database was built using ASP.NET, which allows researchers to search and mine the genome of this important fungus. This database represents the first reported genome database for a seed borne fungal pathogen in the Diaporthe- Phomopsis complex. The database will also be a valuable resource for research and agricultural communities. It will aid in the development of new control strategies for this pathogen.

  18. Standard sources at 10.6 GHz and variability in 3C147

    NASA Astrophysics Data System (ADS)

    Andrew, B. H.; MacLeod, J. M.; Feldman, P. A.

    1981-06-01

    It is pointed out that the work of Baars et al. (1977), referred to as BGPW, is among the most recent on the subject of the calibration of radio telescopes. BGPW provides flux densities for a set of secondary calibrators. Observations made at the Algonquin Radio Observatory (ARO) provide very accurate relative flux densities for the BGPW calibrators. Attention is given to questions of data derivation, variability, and absolute flux densities. The ARO relative flux densities are converted to the BGPW scale by means of the 'semi-absolute' 3C274. If the obtained values are adopted at 10.6 GHz, the BGPW scale can be used more efficiently in the 10 GHz range. Flux densities at other frequencies in the 10 GHz range can be obtained by using the spectral indices implied by Table 5 of BGPW. In view of the variability of 3C147, and the hints of variability in the observations of several other sources, observers should also bear in mind that any 'absolute' calibration scale may be ephemeral if it is tied to 'standard' sources that are assumed to be constant.

  19. TNF counterbalances the emergence of M2 tumor macrophages

    PubMed Central

    Kratochvill, Franz; Neale, Geoffrey; Haverkamp, Jessica M.; de Velde, Lee-Ann Van; Smith, Amber M.; Kawauchi, Daisuke; McEvoy, Justina; Roussel, Martine F.; Dyer, Michael A.; Qualls, Joseph E.; Murray, Peter J.

    2015-01-01

    Cancer is a form of non-resolving, persistent inflammation where varying numbers of tumor-associated macrophages (TAMs) infiltrate and adopt different activation states between anti-tumor M1 and pro-tumor M2 phenotypes. Here we resolve a cascade causing differential macrophage phenotypes in the tumor microenvironment. Reduction in TNF mRNA production or loss of Type I TNF receptor signaling resulted in a striking pattern of enhanced M2 mRNA expression. M2 gene expression was driven in part by IL-13 from eosinophils co-recruited with inflammatory monocytes, a pathway that was suppressed by TNF. Our data define regulatory nodes within the tumor microenvironment that balance M1 and M2 populations. Our results show macrophage polarization in cancer is dynamic and dependent on the balance between TNF and IL-13, thus providing a strategy for manipulating TAMs. PMID:26365184

  20. A model of the human M2 muscarinic acetylcholine receptor

    NASA Astrophysics Data System (ADS)

    Jöhren, Kirstin; Höltje, Hans-Dieter

    2002-11-01

    The M2 muscarinic acetylcholine receptor belongs to the family of rhodopsin like G-Protein Coupled Receptors. This subtype of muscarinic receptors is of special interest because it bears, aside from an orthosteric binding site, also an allosteric binding site. Based on the X-ray structure of bovine rhodopsin a complete homology model of the human M2 receptor was developed. For the orthosteric binding site point mutations and binding studies with different agonists and antagonists are available. This knowledge was utilized for an initial verification of the M2 model. Allosteric modulation of activity is mediated by structurally different ligands such as gallamine, caracurine V salts or W84 (a hexamethonium-derivative). Caracurine V derivatives with different affinities to M2 were docked using GRID-fields. Subsequent molecular dynamics simulations yielded different binding energies based on diverse electrostatic and lipophilic interactions. The calculated affinities are in good agreement to experimentally determined affinities.

  1. Theoretical Assessment of 178m2Hf De-Excitation

    SciTech Connect

    Hartouni, E P; Chen, M; Descalle, M A; Escher, J E; Loshak, A; Navratil, P; Ormand, W E; Pruet, J; Thompson, I J; Wang, T F

    2008-10-06

    This document contains a comprehensive literature review in support of the theoretical assessment of the {sup 178m2}Hf de-excitation, as well as a rigorous description of controlled energy release from an isomeric nuclear state.

  2. Comet C/2012 S1 (Ison)

    NASA Astrophysics Data System (ADS)

    Granslo, B. H.; Nakano, S.

    2013-12-01

    16.88 16 11 31.6 +19 45 05 0.07+ 0.14+ 15.5 Unsuccessful visual searches for the comet, with estimated limiting magnitudes: Dec. 4.26 UT, [8.0 (B. H. Granslo, Roverkollen, Oslo, Norway, 0.08-m refractor; altitude 5 degrees in twilight); Dec. 8.8, [10.6 (Akie Hashimoto, Chichibu, Saitama-ken, Japan, 25x150 binoculars; communicated by S. Nakano, Sumoto, Japan).

  3. Microbial metabolite butyrate facilitates M2 macrophage polarization and function.

    PubMed

    Ji, Jian; Shu, Dingming; Zheng, Mingzhu; Wang, Jie; Luo, Chenglong; Wang, Yan; Guo, Fuyou; Zou, Xian; Lv, Xiaohui; Li, Ying; Liu, Tianfei; Qu, Hao

    2016-04-20

    Metabolites from intestinal microbes modulate the mucosal immune system by regulating the polarization and expansion of T cells. Whether the microbial metabolites influence macrophage polarization, however, is poorly understood. Here, we show that the large bowel microbial fermentation product, butyrate, facilitates M2 macrophage polarization, in vitro and in vivo. The supernatant from butyrate-treated M2 macrophage increased the migration and enhanced the wound closure rate of MLE-12 cells. Butyrate attenuated intestinal inflammation in mice with dextran sulfate sodium (DSS)-induced colitis, with a significant increase in colonic expression of the M2 macrophage-associated protein, Arg1. M2 macrophage treated with butyrate, had increased activation of the H3K9/STAT6 signaling pathway, suggesting a mechanism for butyrate facilitated M2 macrophage polarization. Collectively, our study indicated that commensal microbe-derived butyrate is a novel activator of STAT6-mediated transcription through H3K9 acetylation driving M2 macrophage polarization, and delineated new insights into the immune interplay underlying inflammatory bowel disease.

  4. Revisiting the endocytosis of the m2 muscarinic acetylcholine receptor.

    PubMed

    Ockenga, Wymke; Tikkanen, Ritva

    2015-05-12

    The agonist-induced endocytosis of the muscarinic acetylcholine receptor M2 is different from that of the other members of the muscarinic receptor family. The uptake of the M2 receptor involves the adapter proteins of the β-arrestin family and the small GTPase ADP-ribosylation factor 6. However, it has remained inconclusive if M2 endocytosis is dependent on clathrin or the large GTPase dynamin. We here show by means of knocking down the clathrin heavy chain that M2 uptake upon agonist stimulation requires clathrin. The expression of various dominant-negative dynamin-2 mutants and the use of chemical inhibitors of dynamin function revealed that dynamin expression and membrane localization as such appear to be necessary for M2 endocytosis, whereas dynamin GTPase activity is not required for this process. Based on the data from the present and from previous studies, we propose that M2 endocytosis takes place by means of an atypical clathrin-mediated pathway that may involve a specific subset of clathrin-coated pits/vesicles.

  5. Revisiting the Endocytosis of the M2 Muscarinic Acetylcholine Receptor

    PubMed Central

    Ockenga, Wymke; Tikkanen, Ritva

    2015-01-01

    The agonist-induced endocytosis of the muscarinic acetylcholine receptor M2 is different from that of the other members of the muscarinic receptor family. The uptake of the M2 receptor involves the adapter proteins of the β-arrestin family and the small GTPase ADP-ribosylation factor 6. However, it has remained inconclusive if M2 endocytosis is dependent on clathrin or the large GTPase dynamin. We here show by means of knocking down the clathrin heavy chain that M2 uptake upon agonist stimulation requires clathrin. The expression of various dominant-negative dynamin-2 mutants and the use of chemical inhibitors of dynamin function revealed that dynamin expression and membrane localization as such appear to be necessary for M2 endocytosis, whereas dynamin GTPase activity is not required for this process. Based on the data from the present and from previous studies, we propose that M2 endocytosis takes place by means of an atypical clathrin-mediated pathway that may involve a specific subset of clathrin-coated pits/vesicles. PMID:25985102

  6. Internalization and down-regulation of human muscarinic acetylcholine receptor m2 subtypes. Role of third intracellular m2 loop and G protein-coupled receptor kinase 2.

    PubMed

    Tsuga, H; Kameyama, K; Haga, T; Honma, T; Lameh, J; Sadée, W

    1998-02-27

    Internalization and down-regulation of human muscarinic acetylcholine m2 receptors (hm2 receptors) and a hm2 receptor mutant lacking a central part of the third intracellular loop (I3-del m2 receptor) were examined in Chinese hamster ovary (CHO-K1) cells stably expressing these receptors and G protein-coupled receptor kinase 2 (GRK2). Agonist-induced internalization of up to 80-90% of hm2 receptors was demonstrated by measuring loss of [3H]N-methylscopolamine binding sites from the cell surface, and transfer of [3H]quinuclidinyl benzilate binding sites from the plasma membrane into the light-vesicle fractions separated by sucrose density gradient centrifugation. Additionally, translocation of hm2 receptors with endocytic vesicles were visualized by immunofluorescence confocal microscopy. Agonist-induced down-regulation of up to 60-70% of hm2 receptors was demonstrated by determining the loss of [3H]quinuclidinyl benzilate binding sites in the cells. The half-time (t1/2) of internalization and down-regulation in the presence of 10(-4) M carbamylcholine was estimated to be 9.5 min and 2.3 h, respectively. The rates of both internalization and down-regulation of hm2 receptors in the presence of 10(-6) M or lower concentrations of carbamylcholine were markedly increased by coexpression of GRK2. Agonist-induced internalization of I3-del m2 receptors was barely detectable upon incubation of cells for 1 h, but agonist-induced down-regulation of up to 40-50% of I3-del m2 receptors occurred upon incubation with 10(-4) M carbamylcholine for 16 h. However, the rate of down-regulation was lower compared with wild type receptors (t1/2 = 9.9 versus 2.3 h). These results indicate that rapid internalization of hm2 receptors is facilitated by their phosphorylation with GRK2 and does not occur in the absence of the third intracellular loop, but down-regulation of hm2 receptors may occur through both GRK2-facilitating pathway and third intracellular loop-independent pathways.

  7. Multi-wavelength view of an M2.2 solar flare on 26 november 2000

    NASA Astrophysics Data System (ADS)

    Chandra, R.; Verma, V. K.; Rani, S.; Maurya, R. A.

    2017-02-01

    In this paper, we present a study of an M2.2 class solar flare of 26 November 2000 from NOAA AR 9236. The flare was well observed by various ground based observatories (ARIES, Learmonths Solar Observatory) and space borne instruments (SOHO, HXRS, GOES) in time interval between 02:30 UT to 04:00 UT. The flare started with long arc-shape outer flare ribbon. Afterwards the main flare starts with two main ribbons. Initially the outer ribbons start to expand with an average speed (∼20 km s-1) and later it shows contraction. The flare was associated with partial halo coronal mass ejection (CMEs) which has average speed of 495 km s-1. The SOHO/MDI observations show that the active region was in quadrupolar magnetic configuration. The flux cancellation was observed before the flare onset close to flare site. Our analysis indicate the flare was initiated by the magnetic breakout mechanism.

  8. A Study of the DsJ(2317) and DsJ(2460) Mesons in Inclusive ccbar Production near sqrt(s) = 10.6 GeV

    SciTech Connect

    Aubert, B.

    2006-04-19

    A study of the D*{sub sJ}(2317){sup +} and D{sub sJ}(2460){sup +} mesons in inclusive c{bar c} production is presented using 232 fb{sup -1} of data collected by the BABAR experiment near {radical}s = 10.6 GeV. Final states consisting of a D{sub s}{sup +} meson along with one or more {pi}{sup 0}, {pi}{sup {+-}}, or {gamma} particles are considered. Estimates of the mass and limits on the width are provided for both mesons and for the D{sub s1}(2536){sup +} meson. A search is also performed for neutral and doubly-charged partners of the D*{sub sJ}(2317){sup +} meson.

  9. Anatomy of a Discovery: M1 and M2 Macrophages

    PubMed Central

    Mills, Charles Dudley

    2015-01-01

    M1 and M2 macrophage-type responses kill or repair in vivo. The unique ability of macrophages to make these polar opposite type of responses provides primary host protection and maintains tissue homeostasis throughout the animal kingdom. In humans and other higher animals, M1 and M2-type macrophage responses also initiate and direct T cells/adaptive immunity to provide additional protection such as Th1 (cytotoxic) or Th2 (antibody-mediated) type responses. Hence, macrophages were renamed M1 and M2 to indicate the central role of macrophages/innate immunity in immune systems. These findings indicate that the long held notion that adaptive immunity controls innate immunity was backward: a sea change in understanding how immune responses occur. The clinical impact of M1/kill and M2/repair responses is immense playing pivotal roles in curing (or causing) many diseases including infections, cancer, autoimmunity, and atherosclerosis. How M1/M2 came to be is an interesting story that, like life, involved Direction, Determination, Discouragement, and Discovery. PMID:25999950

  10. Computational discovery of stable M2A X phases

    NASA Astrophysics Data System (ADS)

    Ashton, Michael; Hennig, Richard G.; Broderick, Scott R.; Rajan, Krishna; Sinnott, Susan B.

    2016-08-01

    The family of layered Mn +1A Xn compounds provides a large class of materials with applications ranging from magnets to high-temperature coatings to nuclear cladding. In this work, we employ a density-functional-theory-based discovery approach to identify a large number of thermodynamically stable Mn +1A Xn compounds, where n =1 , M =Sc, Ti, V, Cr, Zr, Nb, Mo, Hf, Ta; A =Al, Si, P, S, Ga, Ge, As, Cd, In, Sn, Tl, Pb; and X =C, N. We calculate the formation energy for 216 pure M2A X compounds and 10 314 solid solutions, (MM') 2(A A') (X X') , relative to their competing phases. We find that the 49 experimentally known M2A X phases exhibit formation energies of less than 30 meV/atom. Among the 10 530 compositions considered, 3140 exhibit formation energies below 30 meV/atom, most of which have yet to be experimentally synthesized. A significant subset of 301 compositions exhibits strong exothermic stability in excess of 100 meV/atom, indicating favorable synthesis conditions. We identify empirical design rules for stable M2A X compounds. Among the metastable M2A X compounds are two Cr-based compounds with ferromagnetic ordering and expected Curie temperatures around 75 K. These results can serve as a map for the experimental design and synthesis of different M2A X compounds.

  11. The Global S$_1$ Ocean Tide

    NASA Technical Reports Server (NTRS)

    Ray, Richard D.; Egbert, G. D.

    2003-01-01

    The small S$_1$ ocean tide is caused primarily by diurnal atmospheric pressure loading. Its excitation is therefore unlike any other diurnal tide. The global character of $S-1$ is here determined by numerical modeling and by analysis of Topex/Poseidon satellite altimeter data. The two approaches yield reasonably consistent results, and large ( $ greater than $l\\cm) amplitudes in several regions are further confirmed by comparison with coastal tide gauges. Notwithstanding their excitation differences, S$-1$ and other diurnal tides are found to share several common features, such as relatively large amplitudes in the Arabian Sea, the Sea of Okhotsk, and the Gulf of Alaska. The most noticeable difference is the lack of an S$-1$ Antarctic Kelvin wave. These similarities and differences can be explained in terms of the coherences between near-diurnal oceanic normal modes and the underlying tidal forcings. While gravitational diurnal tidal forces excite primarily a 28-hour Antarctic-Pacific mode, the S$_1$ air tide excites several other near-diurnal modes, none of which has large amplitudes near Antarctica.

  12. M2-F1 in flight on tow line

    NASA Technical Reports Server (NTRS)

    1964-01-01

    The M2-F1 Lifting Body is seen here under tow at the Flight Research Center (later redesignated the Dryden Flight Research Center), Edwards, California. The wingless, lifting-body aircraft design was initially concieved as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Flight Research Center management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The M2-F1 project had limited goals. They were to show that a piloted lifting body could be built, that it could not only fly but be controlled in flight, and that it could make a successful landing. While the M2-F1 did prove the concept, with a wooden fuselage and fixed landing gear, it was far from an operational spacecraft. The next step in the lifting-body development was to build a heavyweight, rocket-powered vehicle that was more like an operational lifting body, albeit one without the thermal protection system that would be needed for reentry into the atmosphere from space at near-orbital speeds. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. These initial tests produced enough flight data about the M2-F1 to proceed with flights behind a NASA C-47 tow plane at greater altitudes. The C-47 took the craft to an altitude of 12,000 where free flights back to Rogers Dry Lake began. Pilot for the first series of flights of the M2-F1 was NASA research pilot Milt Thompson. Typical glide flights with the M2-F1 lasted about two minutes and reached speeds of 110 to

  13. M2-F1 on lakebed with pilot Milt Thompson

    NASA Technical Reports Server (NTRS)

    1963-01-01

    NASA Flight Research Pilot Milt Thompson, shown here on the lakebed with the M2-F1 lifting body, was an early backer of R. Dale Reed's lifting-body proposal. He urged Flight Research Center director Paul Bikle to approve the M2-F1's construction. Thompson also made the first glide flights in both the M2-F1 and its successor, the heavyweight M2-F2. The wingless, lifting body aircraft design was initially conceived as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, NASA Flight Research Center (later Dryden Flight Research Center, Edwards, CA) management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop near Long Beach for modification. With a special gearbox and racing slicks, the Pontiac could tow the 1,000-pound M2-F1 110 miles per hour in 30 seconds. It proved

  14. Mini Magnetospheric Plasma Propulsion (M2P2)

    NASA Technical Reports Server (NTRS)

    Gallagher, Dennis; Winglee, Robert

    2000-01-01

    The M2P2 concept is based on the transfer of momentum from the solar wind to an artificial magnetic field structure like that naturally occurs at all magnetized planets in the Solar System, called the magnetosphere. The objectives of this program include the following: (1) Demonstrate artificial magnetospheric inflation through cold plasma filling in vacuum; (2) Demonstrate deflection of a surrogate solar wind by an artificial magnetosphere in the laboratory vacuum chamber; (3) Compare theoretical calculations for thrust forces with laboratory measurements; (4) Develop flight control algorithms for planning mission specific trajectories; and (5) Develop M2P2 system concept.

  15. Comparisons of absolute gravimeters (COOMET.M.G-S1)

    NASA Astrophysics Data System (ADS)

    Vinnichenko, Mr Alexander; Germak, Alessandro, Dr

    2017-01-01

    This report describes the results of the RMO supplementary comparison COOMET.M.G-S1 (also known as bilateral comparison COOMET 634/UA/14). The comparison measurements between the two participants NSC 'IM' (pilot laboratory) and INRIM were started in December 2015 and finished in January 2016. Participants of comparisons were conducted at their national standards the measurements of the free fall acceleration in gravimetric point laboratory of absolute gravimetry of INRIM named INRiM.2. Absolute measurements of gravimetric acceleration were conducted by ballistic gravimeters. The agreement between the two participants is good. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  16. M2-F1 ejection seat test at South Edwards

    NASA Technical Reports Server (NTRS)

    1963-01-01

    The M2-F1 was fitted with an ejection seat before the airtow flights began. The project selected the seat used in the T-37 as modified by the Weber Company to use a rocket rather than a ballistic charge for ejection. To test the ejection seat, the Flight Research Center's Dick Klein constructed a plywood mockup of the M2-F1's top deck and canopy. On the first firings, the test was unsuccessful, but on the final test the dummy in the seat landed safely. The M2-F1 ejection seat was later used in the two Lunar Landing Research Vehicles and the three Lunar Landing Training Vehicles. Three of them crashed, but in each case the pilot ejected from the vehicle successfully. The wingless, lifting body aircraft design was initially conceived as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with

  17. M2FS: the Michigan/Magellan Fiber System

    NASA Astrophysics Data System (ADS)

    Mateo, Mario; Bailey, John I.; Crane, Jeffrey; Shectman, Stephen; Thompson, Ian; Roederer, Ian; Bigelow, Bruce; Gunnels, Steve

    2012-09-01

    We describe the Michigan/Magellan Fiber System (M2FS) under construction for use on the Magellan/Clay telescope. M2FS consists of four primary components including: (1) A fiber-fed double spectrograph (MSPec) in which each spectrograph is fed by 128 fibers (for a total multiplexing factor of 256) and each is optimized in to operate from 370- 950 nm; (2) A fiber mounting system (MFib) that supports the fibers and fiber plug plates at the telescope f/11 Nasmyth focal surface and organizes the fibers into `shoes' that are used to place the fibers at the image surface of the MSpec spectrographs;, (3) A new wide-field corrector (WFC) that produces high-quality images over a 30 arcmin diameter field; (4) A unit (MCal) mounted near the telescope secondary that provides wavelength and continuum calibration and that supports a key component in a novel automated fiber identification system. We describe the opto-mechanical properties of M2FS, its modes of operation, and its anticipated performance, as well as potential upgrades including the development of a robotic fiber positioner and an atmospheric dispersion corrector. We describe how the M2FS design could serve as the basis of a powerful wide-field, massively multiplexed spectroscopic survey facility.

  18. PK-M2 Makes Cells Sweeter on HIF1.

    PubMed

    Tennant, Daniel A

    2011-05-27

    The transcription factor hypoxia-inducible factor 1 (HIF1) facilitates the induction of enzymes necessary for anaerobic glycolysis. Luo et al. (2011) now identify pyruvate kinase (PK)-M2 as an intriguing new interacting partner for HIF1, revealing a potential mechanism for the Warburg effect, an elevation in aerobic glycolytic metabolism frequently observed in cancer.

  19. M2-F1 in hangar with Pontiac tow vehicle

    NASA Technical Reports Server (NTRS)

    1963-01-01

    The M2-F1 Lifting Body is seen here in a hangar with its hotrod Pontiac convertible tow vehicle at the Flight Research Center (later the Dryden Flight Research Center), Edwards, California. The car was a 1963 Pontiac Catalina convertible, fitted with a 421-cubic-inch tripower engine like those being run at the Daytona 500 auto race. The vehicle also had a four-speed transmission and a heavy-duty suspension and cooling system. A roll bar was also added and the passenger seat turned around so an observer could watch the M2-F1 while it was being towed. The rear seat was removed and a second, side-facing seat installed. The lifting-body team used the Pontiac for all the ground-tow flights over the next three years. The wingless, lifting body aircraft design was initially conceived as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey

  20. M2e-Based Universal Influenza A Vaccines.

    PubMed

    Deng, Lei; Cho, Ki Joon; Fiers, Walter; Saelens, Xavier

    2015-02-13

    The successful isolation of a human influenza virus in 1933 was soon followed by the first attempts to develop an influenza vaccine. Nowadays, vaccination is still the most effective method to prevent human influenza disease. However, licensed influenza vaccines offer protection against antigenically matching viruses, and the composition of these vaccines needs to be updated nearly every year. Vaccines that target conserved epitopes of influenza viruses would in principle not require such updating and would probably have a considerable positive impact on global human health in case of a pandemic outbreak. The extracellular domain of Matrix 2 (M2e) protein is an evolutionarily conserved region in influenza A viruses and a promising epitope for designing a universal influenza vaccine. Here we review the seminal and recent studies that focused on M2e as a vaccine antigen. We address the mechanism of action and the clinical development of M2e-vaccines. Finally, we try to foresee how M2e-based vaccines could be implemented clinically in the future.

  1. Progress On 58m2 Passive Resonant Ring Laser Gyroscope

    NASA Astrophysics Data System (ADS)

    Shaw, G. L.; Rotge, J.; Simmons, B. J.

    1986-01-01

    An update of the large area (now 60m2) Passive Resonant Ring Laser Gyro (PRRLG) is given. Some aspects of last year's design have changed; but performance is still predicted to be in the 10-10 earth rate unit (ERU) range. This is of interest for a number of geophysical applications.

  2. M2e-Based Universal Influenza A Vaccines

    PubMed Central

    Deng, Lei; Cho, Ki Joon; Fiers, Walter; Saelens, Xavier

    2015-01-01

    The successful isolation of a human influenza virus in 1933 was soon followed by the first attempts to develop an influenza vaccine. Nowadays, vaccination is still the most effective method to prevent human influenza disease. However, licensed influenza vaccines offer protection against antigenically matching viruses, and the composition of these vaccines needs to be updated nearly every year. Vaccines that target conserved epitopes of influenza viruses would in principle not require such updating and would probably have a considerable positive impact on global human health in case of a pandemic outbreak. The extracellular domain of Matrix 2 (M2e) protein is an evolutionarily conserved region in influenza A viruses and a promising epitope for designing a universal influenza vaccine. Here we review the seminal and recent studies that focused on M2e as a vaccine antigen. We address the mechanism of action and the clinical development of M2e-vaccines. Finally, we try to foresee how M2e-based vaccines could be implemented clinically in the future. PMID:26344949

  3. Defective transient endogenous spleen colony formation in S1/S1d mice.

    PubMed

    Wiktor-Jedrzejczak, W; Ahmed, A; Sharkis, S J; McKee, A; Sell, K W

    1979-04-01

    WCB6F1 mice of the genotype S1/S1d did not form transient 5-day endogenous spleen colonies following midlethal irradiation, either spontaneously or in response to postirradiation bleeding. Their hematologically normal (+/+) littermates produced colonies equivalent in number and morphologic type to a normal strain (D2B6F1), as evaluated by both macroscopic and microscopic criteria. Bone marrow cells from S1/S1d mice, when transplanted into lethally irradiated +/+ mice, were able to generate equivalent numbers of transient endogenous spleen colonies (TE-CFUs), as compared to that obtained when syngeneic +/+ marrow cells were injected into lethally irradiated +/+ recipients. A defective growth of an early class of hematopoietic progenitor cells, resulting in the clinical course of the S1/S1d anemia is suggested and confirms previous reports on the microenvironmental nature of this abnormality.

  4. Internal steel structure of M2-F1

    NASA Technical Reports Server (NTRS)

    1963-01-01

    The internal steel structure for the M2-F1 was built at the Flight Research Center (predecessor of the Dryden Flight Research Center, Edwards, CA) in a section of the calibration hangar dubbed 'Wright Bicycle Shop.' Visible are the stick, rudder pedals, and ejection seat. The external wooden shell was attached to the steel structure. The wingless, lifting body aircraft design was initially conceived as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop near Long Beach for modification. With a special gearbox and racing slicks, the Pontiac could tow the 1,000-pound M2-F1 110 miles per hour in 30 seconds. It proved adequate for the roughly 400 car tows that got the M2-F1 airborne to prove it could fly

  5. M2-F2 flight preparation and launch

    NASA Technical Reports Server (NTRS)

    1969-01-01

    This movie clip runs about 27 seconds and shows the cockpit canopy close-out by the ground crew, the aircraft hanging from the NB-52B wing pylon, and the M2-F2 being dropped away from the mothership. A fleet of lifting bodies flown at the NASA Flight Research Center (FRC), Edwards, California, from 1963 to l975 demonstrated the ability of pilots to maneuver (in the atmosphere) and safely land a wingless vehicle. These lifting bodies were basically designed so they could fly back to Earth from space and be landed like an aircraft at a pre-determined site. They served as precursors of today's Space Shuttle, the X-33, and the X-38, providing technical and operational engineering data that shaped all three space vehicles. (In 1976 NASA renamed the FRC as the NASA Dryden Flight Research Center (DFRC) in honor of Hugh L. Dryden.) In 1962, FRC Director Paul Bikle approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1. Built by Gus Briegleb, a sailplane builder from El Mirage, California, it featured a plywood shell, placed over a tubular steel frame crafted at the FRC. Construction was completed in 1963. The success of Dryden's M2-F1 program led to NASA's development and construction of two heavyweight lifting bodies based on studies at NASA Ames Research Center and NASA and Langley Research Center -- the M2-F2 and the HL-10, both built by the Northrop Corporation, Los Angeles, California. The 'M' refers to 'manned' and 'F' refers to 'flight' version. 'HL' comes from 'horizontal landing' and '10' is for the tenth lifting body model to be investigated by Langley. The first flight of the M2-F2 -- which looked much like the M2-F1 -- occurred on July 12, 1966. Thompson was the pilot. By then, the same B-52 used to air launch the famed X-15 rocket research aircraft had been modified to also carry the lifting bodies into the air and Thompson was

  6. IUE observations of the 'Butterfly' Nebula M2-9

    NASA Technical Reports Server (NTRS)

    Feibelman, W. A.

    1984-01-01

    IUE observations of the peculiar 'Butterfy' nebula M2-9 indicate that it is not a normal planetary nebula. The ultraviolet spectrum is characterized by few emission lines and a weak continuum. Mg II 2800 A is the strongest emission line present and may be indicative of a binary nucleus. Lines of N v, Q I, N III, N IV, Si III, and C III are seen, but C IV and O III are conspicuous by their absence. T(e) = 10,250 + or - 400 K was determined for the core. Nitrogen in the core is found to be overabundant by about a factor of 5 over the solar value. M2-9 may be an object in the early stages of becoming a planetary nebula.

  7. Fractional power in the bucket, beam quality and M2

    NASA Astrophysics Data System (ADS)

    Basu, Santanu; Gutheinz, Lee M.

    2010-02-01

    This paper gives expressions to calculate the fraction of power, fPIB, from a given multimode gaussian laser beam that can be deposited within a bucket of radius, rT, on a target at a range, zT, using a focusing optic of diameter, Df. We relate the power in the bucket, fPIB, to the M2 parameter, both of which can be experimentally measured. In this paper, we have also presented relationships between these two parameters and BQ and Strehl, which have not been unambiguously defined for a multimode laser beam in the literature. We propose fPIB and M2 to be used as standard design parameters instead of BQ and Strehl for laser-target interaction tests with multimode laser beams from stable resonators.

  8. M2 world ocean tide from tide gauge measurements

    SciTech Connect

    Francis, O.; Mazzega, P. )

    1991-06-01

    An empirical model of the M2 oceanic tide has been computed form the harmonic constants of a subset of deep sea and coastal tide gauge measurements. The optimal interpolation of these data based on inverse theory' uses a priori covariance functions deduced from a global hydrodynamical model. The inverse solution, produced with its associated error maps and samples of error spectra, is surprisingly good when compared to in situ data and to a hydrodynamical model.

  9. State-of-the-art Model M-2 Maintenance System

    SciTech Connect

    Herndon, J.N.; Martin, H.L.; Satterlee, P.E. Jr.; Jelatis, D.G.; Jennrich, C.E.

    1984-04-01

    The Model M-2 Maintenance System is part of an ongoing program within the Consolidated Fuel Reprocessing Program (CFRP) at Oak Ridge National Laboratory (ORNL) to improve remote manipulation technology for future nuclear fuel reprocessing and other remote applications. Techniques, equipment, and guidelines which can improve the efficiency of remote maintenance are being developed. The Model M-2 Maintenance System, installed in the Integrated Equipment Test (IET) Facility at ORNL, provides a complete, integrated remote maintenance system for the demonstration and development of remote maintenance techniques. The system comprises a pair of force-reflecting servomanipulator arms, television viewing, lighting, and auxiliary lifting capabilities, thereby allowing manlike maintenance operations to be executed remotely within the remote cell mockup area in the IET. The Model M-2 Maintenance System incorporates an upgraded version of the proven Central Research Laboratories' Model M servomanipulator. Included are state-of-the-art brushless dc servomotors for improved performance, remotely removable wrist assemblies, geared azimuth drive, and a distributed microprocessor-based digital control system. 5 references, 8 figures.

  10. Heme oxygenase-1 and anti-inflammatory M2 macrophages.

    PubMed

    Naito, Yuji; Takagi, Tomohisa; Higashimura, Yasuki

    2014-12-15

    Heme oxygenase-1 (HO-1) catalyzes the first and rate-limiting enzymatic step of heme degradation and produces carbon monoxide, free iron, and biliverdin. HO-1, a stress-inducible protein, is induced by various oxidative and inflammatory signals. Consequently, HO-1 expression has been regarded as an adaptive cellular response against inflammatory response and oxidative injury. Although several transcriptional factors and signaling cascades are involved in HO-1 regulation, the two main pathways of Nrf2/Bach1 system and IL-10/HO-1 axis exist in monocyte/macrophage. Macrophages are broadly divisible into two groups: pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages. More recently, several novel macrophage subsets have been identified including Mhem, Mox, and M4 macrophages. Of these, M2 macrophages, Mhem, and Mox are HO-1 highly expressing macrophages. HO-1 has been recognized as having major immunomodulatory and anti-inflammatory properties, which have been demonstrated in HO-1 deficient mice and human cases of genetic HO-1 deficiency. However, the mechanism underlying the immunomodulatory actions of HO-1 remains poorly defined. This review specifically addresses macrophage polarization. The present current evidence indicates that HO-1 induction mediated by multiple pathways can drive the phenotypic shift to M2 macrophages and suggests that HO-1 induction in macrophages is a potential therapeutic approach to immunomodulation in widely diverse human diseases.

  11. Flux-driven algebraic damping of m=2 diocotron mode

    NASA Astrophysics Data System (ADS)

    Chim, C. Y.; O'Neil, T. M.

    2016-10-01

    Recent experiments with pure electron plasmas in a Malmberg-Penning trap have observed the algebraic damping of m = 2 diocotron modes. Due to small field asymmetries a low density halo of electrons is transported radially outward from the plasma core, and the mode damping begins when the halo reaches the resonant radius rres, where f = mfE × B (rres) . The damping rate is proportional to the flux of halo particles through the resonant layer. The damping is related to, but distinct from the exponential spatial Landau damping in a linear wave-particle resonance. This poster uses analytic theory and simulations to explain the new flux-driven algebraic damping of the mode. As electrons are swept around the nonlinear ``cat's eye'' orbits of the resonant wave-particle interaction, they form a quadrupole (m = 2) density distribution, which sets up an electric field that acts back on the plasma core. The field causes an E × B drift motion that symmetrizes the core, i.e. damps the m = 2 mode. Supported by NSF Grant PHY-1414570, and DOE Grants DE-SC0002451.

  12. M2-F1 under tow across lakebed by car

    NASA Technical Reports Server (NTRS)

    1963-01-01

    This 20-second clip shows the M2-F1 being towed by the Pontiac across Rogers Dry Lakebed. The M2-F1 lifting body, dubbed the 'flying bathtub' by the media, was the precursor of a remarkable series of wingless flying vehicles that contributed data used in the Space Shuttles, the X-33 Advanced Technology Demonstrator for the next century's Reusable Launch Vehicle, and the X-38 Technology Demonstrator for crew return from the International Space Station. Based on the ideas and basic design of Alfred J. Eggers and others at the Ames Aeronautical Laboratory (now the Ames Research Center), Mountain View, California, in the mid-1950's, the M2-F1 was built in 1962-63 over a four-month period for a cost of only about $30,000, plus an additional $8,000-$10,000 for an ejection seat. Engineers and technicians at the NASA Flight Research Center (now NASA Dryden) kept costs low by designing and fabricating it partly in-house, with the plywood shell constructed by a local sailplane builder. Someone at the time estimated that it would have cost a major aircraft company $150,000 to build the same vehicle. Unlike the later lifting bodies, the M2-F1 was unpowered and was initially towed by a souped-up Pontiac convertible until it was airborne. Later a C-47 took over the towing duties. Flown by such famous research pilots as Milt Thompson, Bruce Peterson, Chuck Yeager, and Bill Dana, the lightweight flying bathtub demonstrated that a wingless vehicle shaped for reentry into the Earth's atmosphere from space could be flown and landed safely. Flown from 1963 to 1966, the lightweight M2-F1 paved the way for the heavyweight M2-F2, M2`F3, HL-10, X-24A, and X-24B lifting bodies that flew under rocket power after launch from a B-52 mothership. The heavyweights flew from 1966 to 1975, demonstrating the viability and versatility of the wingless configuration and the ability of a vehicle with low lift-over-drag characteristics to fly to high altitudes and then to land precisely with their

  13. M2A and M2C Macrophage Subsets Ameliorate Inflammation and Fibroproliferation in Acute Lung Injury Through Interleukin 10 Pathway.

    PubMed

    Tang, Lunxian; Zhang, Hua; Wang, Chunmei; Li, Hongqiang; Zhang, Qian; Bai, Jianwen

    2016-12-09

    The role of M2 macrophages in the resolution and fibroproliferation of acute lung injury (ALI) is poorly understood. In this study, we investigated the effects of two M2 macrophage subtypes, M2a induced by interleukin (IL)-4/IL-13 and M2c induced by IL-10/transforming growth factor (TGF)-β, on the pathogenesis of ALI. M2a and M2c were adoptively transferred into LPS-induced ALI mice model. Data showed that Vybrant-labeled macrophages appeared in the lungs of ALI mice. Subsequently, we observed that both subsets significantly reduced lung inflammation and injury including a reduction of neutrophil influx into the lung and an augmentation of apoptosis. Interestingly, M2c macrophages more effectively suppressed indices of lung injury than M2a macrophages. M2c macrophages were also more effective than M2a in reduction of lung fibrosis. In addition, we found that M2c but not M2a macrophages increased IL-10 level in lung tissues of the recipient ALI mice partially mediated by activating the JAK1/STAT3/SOCS3 signaling pathway. After blocking IL-10, these superior effects of M2c over M2a were abolished. These data imply that M2c are more potent than M2a macrophages in protecting against lung injury and subsequent fibrosis due to their ability to produce IL-10. Therefore, reprogramming macrophages to M2c subset may be a novel treatment modality with transitional potential.

  14. Restless legs syndrome mimicking S1 radiculopathy.

    PubMed

    Zambelis, Th; Wolgamuth, B R; Papoutsi, S N; Economou, N T

    2016-01-01

    Α case of a chronic idiopathic form of a severe type of Restless Legs Syndrome (RLS), which developed during pregnancy and persisted after this, misdiagnosed for 34 years as radiculopathy S1, is reported. In spite of the thorough clinical and laboratory investigation, in addition to constant changes of the therapeutic approach, the diagnosis of S1 radiculopathy could not be confirmed, resulting in a chronic clinical course; the latter was characterized by relapses and remissions not attributed or linked in any way to the treatment (various types of). In fact, it was due to a routine workup in a sleep clinic, where the patient was referred because of a coincident chronic insomnia (Restless Legs Syndrome is a known and important cause of insomnia/chronic insomnia), which resulted in a proper diagnosis and treatment of this case. With the use of Restless Legs Syndrome appropriate treatment (Pramipexole 0.18 mg taken at bedtime, a dopaminergic agent and Level A recommended drug for Restless Legs Syndrome) an excellent response and immediate elimination of symptoms was achieved. Restless Legs Syndrome may present with a variety of symptoms (with the most prominent shortly being reported with the acronym URGE: Urge to move the legs usually associated with unpleasant leg sensations, Rest induces symptoms, Getting active brings relief, Evening and night deteriorate symptoms); given the fact that Restless Legs Syndrome presents with a great variety and heterogeneity of symptoms (mostly pain, dysesthesia and paresthesia), which may occur in several other diseases (the so called "RLS mimics"), proper diagnosis of Restless Legs Syndrome usually fails. Restless Legs Syndrome misinterpreted as S1 radiculopathy, to the best of our knowledge, has not been reported yet in the literature. Here, case history, clinical course and common RLS mimics are presented. Different forms of Restless Legs Syndrome manifestations, which are commonly -as in this case- misinterpreted due to their

  15. Light-cone M5 and multiple M2-branes

    NASA Astrophysics Data System (ADS)

    Bandos, Igor A.; Townsend, Paul K.

    2008-12-01

    We present the light-cone gauge fixed Lagrangian for the M5-brane; it has a residual 'exotic' gauge invariance with the group of 5-volume preserving diffeomorphisms, SDiff5, as gauge group. For an M5-brane of topology \\bb{R}^2\\times M_3 , for closed 3-manifold M3, we find an infinite tension limit that yields an SO(8)-invariant (1 + 2)-dimensional field theory with 'exotic' SDiff3 gauge invariance. We show that this field theory is the Carrollian limit of the Nambu bracket realization of the 'BLG' model for multiple M2-branes.

  16. Sphingosine-1-phosphate (S1P) displays sustained S1P1 receptor agonism and signaling through S1P lyase-dependent receptor recycling.

    PubMed

    Gatfield, John; Monnier, Lucile; Studer, Rolf; Bolli, Martin H; Steiner, Beat; Nayler, Oliver

    2014-07-01

    The sphingosine-1-phosphate (S1P) type 1 receptor (S1P1R) is a novel therapeutic target in lymphocyte-mediated autoimmune diseases. S1P1 receptor desensitization caused by synthetic S1P1 receptor agonists prevents T-lymphocyte egress from secondary lymphoid organs into the circulation. The selective S1P1 receptor agonist ponesimod, which is in development for the treatment of autoimmune diseases, efficiently reduces peripheral lymphocyte counts and displays efficacy in animal models of autoimmune disease. Using ponesimod and the natural ligand S1P, we investigated the molecular mechanisms leading to different signaling, desensitization and trafficking behavior of S1P1 receptors. In recombinant S1P1 receptor-expressing cells, ponesimod and S1P triggered Gαi protein-mediated signaling and β-arrestin recruitment with comparable potency and efficiency, but only ponesimod efficiently induced intracellular receptor accumulation. In human umbilical vein endothelial cells (HUVEC), ponesimod and S1P triggered translocation of the endogenous S1P1 receptor to the Golgi compartment. However, only ponesimod treatment caused efficient surface receptor depletion, receptor accumulation in the Golgi and degradation. Impedance measurements in HUVEC showed that ponesimod induced only short-lived Gαi protein-mediated signaling followed by resistance to further stimulation, whereas S1P induced sustained Gαi protein-mediated signaling without desensitization. Inhibition of S1P lyase activity in HUVEC rendered S1P an efficient S1P1 receptor internalizing compound and abrogated S1P-mediated sustained signaling. This suggests that S1P lyase - by facilitating S1P1 receptor recycling - is essential for S1P-mediated sustained signaling, and that synthetic agonists are functional antagonists because they are not S1P lyase substrates.

  17. M2K Planet Search: Spectroscopic Screening and Transit Photometry

    NASA Astrophysics Data System (ADS)

    Mann, Andrew; Gaidos, E.; Fischer, D.; Lepine, S.

    2010-10-01

    The M2K project is a search for planets orbiting nearby early M and late K dwarf drawn from the SUPERBLINK catalog. M and K dwarfs are highly attractive targets for finding low-mass and habitable planets because (1) close-in planets are more likely to orbit within their habitable zone, (2) planets orbiting them induce a larger Doppler signal and have deeper transits than similar planets around F, G, and early K type stars, (3) planet formation models predict they hold an abundance of super-Earth sized planets, and (4) they represent the vast majority of the stars close enough for direct imaging techniques. In spite of this, only 10% of late K and early M dwarfs are being monitored by current Doppler surveys. As part of the M2K project we have obtained low-resolution spectra for more than 2000 of our sample of 10,000 M and K dwarfs. We vet our sample by screening these stars for high metallicity and low chromospheric activity. We search for transits on targets showing high RMS Doppler signal and photometry candidates provided by SuperWASP project. By using "snapshot” photometry have been able to achieve sub-millimag photometry on numerous transit targets in the same night. With further follow-up observations we will be able to detect planets smaller than 10 Earth masses.

  18. Marginal fluctuations as instantons on M2/D2-branes

    NASA Astrophysics Data System (ADS)

    Naghdi, M.

    2014-03-01

    We introduce some (anti-) M/D-branes through turning on the corresponding field strengths of the 11- and 10-dimensional supergravity theories over spaces, where we use and for the internal spaces. Indeed, when we add M2/D2-branes on the same directions with the near horizon branes of the Aharony-Bergman-Jafferis-Maldacena model, all symmetries and supersymmetries are preserved trivially. In this case, we obtain a localized object just in the horizon. This normalizable bulk massless scalar mode is a singlet of and , and it agrees with a marginal boundary operator of the conformal dimension of . However, after performing a special conformal transformation, we see that the solution is localized in the Euclideanized space and is attributable to the included anti-M2/D2-branes, which are also necessary to ensure that there is no back-reaction. The resultant theory now breaks all supersymmetries to , while the other symmetries are so preserved. The dual boundary operator is then set up from the skew-whiffing of the representations and for the supercharges and scalars, respectively, while the fermions remain fixed in of the original theory. Besides, we also address another alternate bulk to boundary matching procedure through turning on one of the gauge fields of the full gauge group along the same lines with a similar situation to the one faced in the AdS/CFT correspondence. The latter approach covers the difficulty already faced with in the bulk-boundary matching procedure for as well.

  19. The iron dispersion of the globular cluster M2, revised.

    PubMed

    Lardo, C; Mucciarelli, A; Bastian, N

    2016-03-21

    M2 has been claimed to possess three distinct stellar components that are enhanced in iron relative to each other. We use equivalent width measurements from 14 red giant branch stars from which Yong et al. detect a ∼0.8 dex wide, trimodal iron distribution to redetermine the metallicity of the cluster. In contrast to Yong et al., which derive atmospheric parameters following only the classical spectroscopic approach, we perform the chemical analysis using three different methods to constrain effective temperatures and surface gravities. When atmospheric parameters are derived spectroscopically, we measure a trimodal metallicity distribution, that well resembles that by Yong et al. We find that the metallicity distribution from Fe ii lines strongly differs from the distribution obtained from Fe i features when photometric gravities are adopted. The Fe i distribution mimics the metallicity distribution obtained using spectroscopic parameters, while the Fe ii shows the presence of only two stellar groups with metallicity [Fe/H] ≃ -1.5 and -1.1 dex, which are internally homogeneous in iron. This finding, when coupled with the high-resolution photometric evidence, demonstrates that M2 is composed by a dominant population (∼99 per cent) homogeneous in iron and a minority component (∼1 per cent) enriched in iron with respect to the main cluster population.

  20. The functional roles of S1P in immunity.

    PubMed

    Hisano, Yu; Nishi, Tsuyoshi; Kawahara, Atsuo

    2012-10-01

    The lipid mediator sphingosine-1-phosphate (S1P) is generated within cells from sphingosine by two sphingosine kinases (SPHK1 and SPHK2). Intracellularly synthesized S1P is released into the extracellular fluid by S1P transporters, including SPNS2. Released S1P binds specifically to the G protein-coupled S1P receptors (S1PR1/S1P(1)-S1PR5/S1P(5)), which activate a diverse range of downstream signalling pathways. Recent studies have proposed that one of the central physiological functions of intercellular S1P signalling is in lymphocyte trafficking in vivo because genetic disruption of SPHK1/2, SPNS2 or S1PR1/S1P(1) in mice induces a lymphopenia phenotype. In this review, we discuss the current understanding of intercellular S1P signalling in the context of immunity.

  1. Neutron detection on the Foton-M2 satellite by a track etch detector stack.

    PubMed

    Pálfalvi, J K; Szabó, J; Dudás, B

    2007-01-01

    In the frame of a European Space Agency (ESA) project called 'Biology and Physics in Space', a returning satellite, Foton-M2, was orbiting a container, the BIOPAN-5, loaded with biological experiments and facilities for radiation dosimetry (RADO) in the open space. One of the RADO experiments was dedicated to the detection of the primary cosmic rays and secondary neutrons by a track etch detector stack. The system was calibrated at high-energy particle accelerators and neutron generators. The developed detectors were investigated by an image analyser, and from the track parameters the linear energy transfer spectra and the absorbed dose were determined (26 microGy/d). Also, the neutron flux was estimated below 5 MeV and found to be 2.4 cm(-2) s(-1) directly from the space. The construction of the stack allowed to investigate the neutrons also from the direction of the carrying satellite, where the flux was found somewhat higher.

  2. A 10.6mm3 Fully-Integrated, Wireless Sensor Node with 8GHz UWB Transmitter

    PubMed Central

    Kim, Hyeongseok; Kim, Gyouho; Lee, Yoonmyung; Foo, Zhiyoong; Sylvester, Dennis; Blaauw, David; Wentzloff, David

    2015-01-01

    This paper presents a complete, autonomous, wireless temperature sensor, fully encapsulated in a 10.6mm3 volume. The sensor includes solar energy harvesting with an integrated 2 μAh battery, optical receiver for programming, microcontroller and memory, 8GHz UWB transmitter, and miniaturized custom antennas with a wireless range of 7 meters. Full, stand-alone operation was demonstrated for the first time for a system of this size and functionality. PMID:26855848

  3. Polarimetry of R Aqr and PN M2-9

    NASA Astrophysics Data System (ADS)

    Navarro, Silvana G.; Sabin, Laurence; Ramírez Vélez; , Julio; Hiriart, David

    2014-08-01

    The bipolar or more complex morphology observed in planetary nebulae have been explained by two principal hypothesis: by the existence of a companion and an accreting disk or by the effects of magnetic field, (or a combination of both). Symbiotics are binary systems and some of them show morphologies similar to those observed on planetary nebulae. This fact could support the binary hypothesis for PNe. We have therefore performed polarimetric observations of symbiotic systems and some planetary nebulae in order, first to detect linear polarisation with POLIMA at the San Pedro Mártir observatory, and ultimately to prove the existence and physical properties of those disks. We present here the first results of a project dedicated to the analysis of the polarisation observed in evolved objects starting with the PN M2-9 and R Aqr.

  4. The discovery of an anomalous RGB in M 2.

    NASA Astrophysics Data System (ADS)

    Lardo, C.; Pancino, E.; Mucciarelli, A.; Milone, A. P.

    Using UV images taken with the Telescopio Nazionale Galileo, we discovered an anomalous sequence in the color-magnitude diagram of M 2. This feature appears as a narrow poor-populated red giant branch, which extends down to the sub giant branch region. We speculate that this new feature could be the extension of the faint component of the split sub giant branch recently discovered by Piotto et al. We identified in our U,V images two CH stars detected in previous studies. These stars, which are both cluster members, fall on this redder sequence, suggesting indeed that the anomalous RGB should have a peculiar chemical pattern. Unfortunately, no additional spectra were obtained for stars in this previously unknown substructure.

  5. M2 tidal effects in greater cook strait, New Zealand

    NASA Astrophysics Data System (ADS)

    Kibblewhite, Alick C.; Ash, David E.

    1980-05-01

    The application of a M2 nonlinear numerical tidal model to the shelf seas of central New Zealand (~38.500 km2 area) is described. It has provided a preliminary assessment of tidal and residual currents, bottom stress, energy dissipation, and the stratification index. The existence of a permanent, tidally driven mesoscale eddy (~75 km diameter) is predicted nort of D'Urville Island. Large spatial gradients in bottom stress qualitatively agree with many features of the surficial sediment distribution. A comparison of all available bulk stratification data with the h/u3 stratification index clearly demonstrates the dominance of tidal versus wind mixing over the control of summer stratification. A potential application of the model to fisheries science is suggested through a comparison of the stratification index contour map and some observations of squid fishing vessel locations.

  6. Parkin Regulates the Activity of Pyruvate Kinase M2*

    PubMed Central

    Liu, Kun; Li, Fanzhou; Han, Haichao; Chen, Yue; Mao, Zebin; Luo, Jianyuan; Zhao, Yingming; Zheng, Bin; Gu, Wei; Zhao, Wenhui

    2016-01-01

    Parkin, a ubiquitin E3 ligase, is mutated in most cases of autosomal recessive early onset Parkinson disease. It was discovered that Parkin is also mutated in glioblastoma and other human malignancies and that it inhibits tumor cell growth. Here, we identified pyruvate kinase M2 (PKM2) as a unique substrate for parkin through biochemical purification. We found that parkin interacts with PKM2 both in vitro and in vivo, and this interaction dramatically increases during glucose starvation. Ubiquitylation of PKM2 by parkin does not affect its stability but decreases its enzymatic activity. Parkin regulates the glycolysis pathway and affects the cell metabolism. Our studies revealed the novel important roles of parkin in tumor cell metabolism and provided new insight for therapy of Parkinson disease. PMID:26975375

  7. Phase 1 study on S-1 and oxaliplatin therapy as an adjuvant after hepatectomy for colorectal liver metastases.

    PubMed

    Takahashi, Michiro; Hasegawa, Kiyoshi; Oba, Masaru; Saiura, Akio; Arita, Junichi; Sakamoto, Yoshihiro; Shinozaki, Eiji; Mizunuma, Nobuyuki; Matsuyama, Yutaka; Kokudo, Norihiro

    2016-08-01

    of Background Data The effectiveness of adjuvant chemotherapy in patients with stage II/III colorectal cancer has been confirmed in various studies. However, no adjuvant chemotherapy for colorectal liver metastasis (CLM) classified to stage IV has been established. Objectives We conducted a phase 1 study of S-1 and oxaliplatin to determine the recommended dose (RD) in patients with CLM as adjuvant therapy in two institutes. Methods S-1 and oxaliplatin were administered from day 1 to day 14 of a 3-week cycle as a 2-h infusion every 3 weeks, respectively. The initial doses of S-1 and oxaliplatin were fixed to 80 mg/m(2) and 100 mg/m(2), respectively (level 1). We scheduled in the protocol a dose change of S-1 and oxaliplatin to level 2 (S-1: 80 mg/m(2) and oxaliplatin: 130 mg/m(2)) or level 0 (S-1: 65 mg/m(2) and oxaliplatin: 100 mg/m(2)) depending on the incidence of dose-limiting toxicity (DLT) at level 1 in six patients. Results Because DLT occurred in one among the initial six patients at level 1, the doses were increased to level 2 in the next six patients. At level 2, grade 3 leukopenia and neutropenia occurred in one (16.7 %) and two (33.3 %) patients, respectively, in the absence of non-hematological event. Because no DLT occurred at level 2, we suggest that the RD can be set to the level 2 dose. The median number of cycles delivered at RD was 8. The mean relative dose intensity of S-1 and oxaliplatin at RD was 0.90 and 0.63, respectively. Conclusion In a patient undergoing hepatectomy for CLM, 80 mg/m(2) of S-1 and 130 mg/m(2) of oxaliplatin are recommended as adjuvant therapy. A further study is required to confirm the efficacy and safety of this regimen on a larger scale.

  8. Biophysical characterization of the interaction between M2-1 protein of hRSV and quercetin.

    PubMed

    Teixeira, Thiago Salem Pançonato; Caruso, Ícaro Putinhon; Lopes, Bruno Rafael Pereira; Regasini, Luis Octávio; Toledo, Karina Alves de; Fossey, Marcelo Andrés; Souza, Fátima Pereira de

    2017-02-01

    hRSV is the major causative agent of acute respiratory infections. Among its eleven proteins, M2-1 is a transcription antiterminator, making it an interesting target for antivirals. Quercetin is a flavonol which inhibits some virus infectivity and replication. In the present work, the M2-1 gene was cloned, expressed and the protein was purified. Thermal stability and secondary structure were analyzed by circular dichroism and the interaction with Quercetin was evaluated by fluorescence spectroscopy. Molecular docking experiments were performed to understand this mechanism of interaction. The purified protein is mainly composed of α-helix, with a melting temperature of 328.6K (≈55°C). M2-1 titration with Quercetin showed it interacts with two sites, one with a strong constant association K1 (site 1≈1.5×10(6)M(-1)) by electrostatic interactions, and another with a weak constant association K2 (site 2≈1.1×10(5)M(-1)) by a hydrophobic interaction. Ligand's docking shows it interacts with the N-terminus face in a more polar pocket and, between the domains of oligomerization and RNA and P protein interaction, in a more hydrophobic pocket, as predicted by experimental data. Therefore, we postulated this ligand could be interacting with important domains of the protein, avoiding viral replication and budding.

  9. Discrete functions of M2a and M2c macrophage subsets determine their relative efficacy in treating chronic kidney disease.

    PubMed

    Lu, Junyu; Cao, Qi; Zheng, Dong; Sun, Yan; Wang, Changqi; Yu, Xiao; Wang, Ya; Lee, Vincent W S; Zheng, Guoping; Tan, Thian K; Wang, Xin; Alexander, Stephen I; Harris, David C H; Wang, Yiping

    2013-10-01

    Two types of alternatively activated macrophages, M(2a) induced by IL-4/IL-13 and M(2c) by IL-10/TGF-β, exhibit anti-inflammatory functions in vitro and protect against renal injury in vivo. Since their relative therapeutic efficacy is unclear, we compared the effects of these two macrophage subsets in murine adriamycin nephrosis. Both subsets significantly reduced renal inflammation and renal injury; however, M(2c) macrophages more effectively reduced glomerulosclerosis, tubular atrophy, interstitial expansion, and proteinuria than M(2a) macrophages. The M(2c) macrophages were also more effective than M(2a) in reduction of macrophage and CD4(+) T-cell infiltration in kidney. Moreover, nephrotic mice treated with M(2c) had a greater reduction in renal fibrosis than those treated with M(2a). M(2c) but not M(2a) macrophages induced regulatory T cells (Tregs) from CD4(+)CD25(-) T cells in vitro, and increased Treg numbers in local draining lymph nodes of nephrotic mice. To determine whether the greater protection with M(2c) was due to their capability to induce Tregs, the Tregs were depleted by PC61 antibody in nephrotic mice treated with M(2a) or M(2c). Treg depletion diminished the superior effects of M(2c) compared to M(2a) in protection against renal injury, inflammatory infiltrates, and renal fibrosis. Thus, M(2c) are more potent than M(2a) macrophages in protecting against renal injury due to their ability to induce Tregs.

  10. Multiple heterologous M2 extracellular domains presented on virus-like particles confer broader and stronger M2 immunity than live influenza A virus infection.

    PubMed

    Kim, Min-Chul; Lee, Jong-Seok; Kwon, Young-Man; O, Eunju; Lee, Youn-Jeong; Choi, Jun-Gu; Wang, Bao-Zhong; Compans, Richard W; Kang, Sang-Moo

    2013-09-01

    The influenza M2 ectodomain (M2e) is poorly immunogenic and has some amino acid changes among isolates from different host species. We expressed a tandem repeat construct of heterologous M2e sequences (M2e5x) derived from human, swine, and avian origin influenza A viruses on virus-like particles (M2e5x VLPs) in a membrane-anchored form. Immunization of mice with M2e5x VLPs induced protective antibodies cross-reactive to antigenically different influenza A viruses and conferred cross protection. Anti-M2e antibodies induced by heterologous M2e5x VLPs showed a wider range of cross reactivity to influenza A viruses at higher levels than those by live virus infection, homologous M2e VLPs, or M2e monoclonal antibody 14C2. Fc receptors were found to be important for mediating protection by immune sera from M2e5x VLP vaccination. The present study provides evidence that heterologous recombinant M2e5x VLPs can be more effective in inducing protective M2e immunity than natural virus infection and further supports an approach for developing an effective universal influenza vaccine.

  11. Pyruvate kinase M2 is a phosphotyrosine-binding protein

    SciTech Connect

    Christofk, H.R.; Vander Heiden, M.G.; Wu, N.; Asara, J.M.; Cantley, L.C.

    2008-06-03

    Growth factors stimulate cells to take up excess nutrients and to use them for anabolic processes. The biochemical mechanism by which this is accomplished is not fully understood but it is initiated by phosphorylation of signalling proteins on tyrosine residues. Using a novel proteomic screen for phosphotyrosine-binding proteins, we have made the observation that an enzyme involved in glycolysis, the human M2 (fetal) isoform of pyruvate kinase (PKM2), binds directly and selectively to tyrosine-phosphorylated peptides. We show that binding of phosphotyrosine peptides to PKM2 results in release of the allosteric activator fructose-1,6-bisphosphate, leading to inhibition of PKM2 enzymatic activity. We also provide evidence that this regulation of PKM2 by phosphotyrosine signalling diverts glucose metabolites from energy production to anabolic processes when cells are stimulated by certain growth factors. Collectively, our results indicate that expression of this phosphotyrosine-binding form of pyruvate kinase is critical for rapid growth in cancer cells.

  12. Fermi surface behavior in the ABJM M2-brane theory

    NASA Astrophysics Data System (ADS)

    DeWolfe, Oliver; Henriksson, Oscar; Rosen, Christopher

    2015-06-01

    We calculate fermionic Green's functions for states of the three-dimensional Aharony-Bergman-Jafferis-Maldacena M2-brane theory at large N using the gauge-gravity correspondence. We embed extremal black brane solutions in four-dimensional maximally supersymmetric gauged supergravity, obtain the linearized Dirac equations for each spin-1 /2 mode that cannot mix with a gravitino, and solve these equations with infalling boundary conditions to calculate retarded Green's functions. For generic values of the chemical potentials, we find Fermi surfaces with universally non-Fermi liquid behavior, matching the situation for four-dimensional N =4 super-Yang-Mills. Fermi surface singularities appear and disappear discontinuously at the point where all chemical potentials are equal, reminiscent of a quantum critical point. One limit of parameter space has zero entropy at zero temperature, and fermionic fluctuations are perfectly stable inside an energy region around the Fermi surface. An ambiguity in the quantization of the fermions is resolved by supersymmetry.

  13. Optical spectrum of the planetary nebula M 2-24

    NASA Astrophysics Data System (ADS)

    Zhang, Y.; Liu, X.-W.

    2003-06-01

    We have obtained medium-resolution, deep optical long-slit spectra of the bulge planetary nebula (PN) M 2-24. The spectrum covers the wavelength range from 3610-7330 Å. Over two hundred emission lines have been detected. The spectra show a variety of optical recombination lines (ORLs) from C, N, O and Ne ions. The diagnostic diagram shows significant density and temperature variations across the nebula. Our analysis suggests that the nebula has a dense central emission core. The nebula was thus studied by dividing it into two regions: 1) a high ionization region characterized by an electron temperature of Te=16 300 K and a density of log Ne(cm-3) = 6.3; and 2) a low ionization region represented by Te=11 400 K and log Ne(cm-3) = 3.7. A large number of ORLs from C, N, O and Ne ions have been used to determine the abundances of these elements relative to hydrogen. In general, the resultant abundances are found to be higher than the corresponding values deduced from collisionally excited lines (CELs). This bulge PN is found to have large enhancements in two alpha -elements, magnesium and neon. Full Table 2 is available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.126.5) or via http://cdsweb.u-strasbg.fr/cgi-bin/qcat?J/A+A/404/545

  14. Isolation of new Stenotrophomonas bacteriophages and genomic characterization of temperate phage S1.

    PubMed

    García, Pilar; Monjardín, Cristina; Martín, Rebeca; Madera, Carmen; Soberón, Nora; Garcia, Eva; Meana, Alvaro; Suárez, Juan E

    2008-12-01

    Twenty-two phages that infect Stenotrophomonas species were isolated through sewage enrichment and prophage induction. Of them, S1, S3, and S4 were selected due to their wide host ranges compared to those of the other phages. S1 and S4 are temperate siphoviruses, while S3 is a virulent myovirus. The genomes of S3 and S4, about 33 and 200 kb, were resistant to restriction digestion. The lytic cycles lasted 30 min for S3 and about 75 min for S1 and S4. The burst size for S3 was 100 virions/cell, while S1 and S4 produced about 75 virus particles/cell. The frequency of bacteriophage-insensitive host mutants, calculated by dividing the number of surviving colonies by the bacterial titer of a parallel, uninfected culture, ranged between 10(-5) and 10(-6) for S3 and 10(-3) and 10(-4) for S1 and S4. The 40,287-bp genome of S1 contains 48 open reading frames (ORFs) and 12-bp 5' protruding cohesive ends. By using a combination of bioinformatics and experimental evidence, functions were ascribed to 21 ORFs. The morphogenetic and lysis modules are well-conserved, but no lysis-lysogeny switch or DNA replication gene clusters were recognized. Two major clusters of genes with respect to transcriptional orientation were observed. Interspersed among them were lysogenic conversion genes encoding phosphoadenosine phosphosulfate reductase and GspM, a protein involved in the general secretion system II. The attP site of S1 may be located within a gene that presents over 75% homology to a Stenotrophomonas chromosomal determinant.

  15. Comparison of cloud boundaries measured with 8.6 mm radar and 10.6 micrometer lidar

    NASA Technical Reports Server (NTRS)

    Uttal, Taneil; Intrieri, Janet M.

    1993-01-01

    One of the most basic cloud properties is location; the height of cloud base and the height of cloud top. The glossary of meteorology defines cloud base (top) as follows: 'For a given cloud or cloud layer, that lowest (highest) level in the atmosphere at which the air contains a perceptible quantity of cloud particles.' Our studies show that for a 8.66 mm radar, and a 10.6 micrometer lidar, the level at which cloud hydrometers become 'perceptible' can vary significantly as a function of the different wavelengths, powers, beamwidths and sampling rates of the two remote sensors.

  16. Electronic speckle pattern interferometry and digital holographic interferometry with microbolometer arrays at 10.6 {mu}m

    SciTech Connect

    Vandenrijt, Jean-Francois; Georges, Marc P.

    2010-09-20

    Electronic speckle pattern interferometry and digital holographic interferometry are investigated at long infrared wavelengths. Using such wavelengths allows one to extend the measurement range and decrease the sensitivity of the techniques to external perturbations. We discuss the behavior of reflection by the object surfaces due to the long wavelength. We have developed different experimental configurations associating a CO2 laser emitting at 10.6{mu}m and microbolometer arrays. Phase-shifting in-plane and out-of-plane electronic speckle pattern interferometry and lensless digital holographic interferometry are demonstrated on rotation measurements of a solid object.

  17. Development of a (Hg, Cd)Te photodiode detector, Phase 2. [for 10.6 micron spectral region

    NASA Technical Reports Server (NTRS)

    1972-01-01

    High speed sensitive (Hg,Cd)Te photodiode detectors operating in the 77 to 90 K temperature range have been developed for the 10.6 micron spectral region. P-N junctions formed by impurity (gold) diffusion in p-type (Hg, Cd) Te have been investigated. It is shown that the bandwidth and quantum efficiency of a diode are a constant for a fixed ratio of mobility/lifetime ratio of minority carriers. The minority carrier mobility and lifetime uniquely determine the bandwidth and quantum efficiency and indicate the shallow n on p (Hg,Cd) Te diodes are preferable as high performance, high frequency devices.

  18. Conversion therapy for pancreatic cancer with peritoneal metastases using intravenous and intraperitoneal paclitaxel with S-1

    PubMed Central

    Kitayama, Hiromitsu; Tsuji, Yasushi; Kondo, Tomohiro; Sugiyama, Junko; Hirayama, Michiaki; Yamamoto, Kazuyuki; Kawarada, You; Oyamada, Yumiko; Hirano, Satoshi

    2016-01-01

    Combination chemotherapy consisting of systemic and intraperitoneal agents against peritoneal metastases from several types of cancer has shown promising results. We herein report a case in which combination therapy with intravenous and intraperitoneal paclitaxel with S-1 converted an unresectable pancreatic cancer with peritoneal metastases into a resectable one. The patient was a 65-year old woman with recurrent pancreatitis for 5 months. Endoscopic ultrasonography-guided fine-needle aspiration revealed minute epithelial masses composed of cells with irregular nuclei in the pancreatic body. The patient underwent abdominal surgery, but no excision was performed, as two peritoneal metastases in the bursa omentalis were detected. Combination therapy was initiated, consisting of intravenous and intraperitoneal paclitaxel with S-1 as a single-center clinical trial. The regimen consisted with 2-week administration of S-1 (80 mg per day) followed by 1 week of rest, intravenous paclitaxel 50 mg/m2, and intraperitoneal paclitaxel 20 mg/m2 by a peritoneal access device on days 1 and 8. Over the seven cycles of the chemotherapy, the primary lesion did not change in size, and peritoneal lavage cytology remained negative. After confirming the disappearance of the peritoneal lesions by exploratory laparoscopy, the patient underwent distal pancreatectomy combined with resection of the transverse mesocolon and stomach wall. Thus, the 2-way chemotherapy of intravenous and intraperitoneal paclitaxel with S-1 was well-tolerated and was able to convert pancreatic cancer with peritoneal metastases to resectable disease. PMID:28105356

  19. Albumin modulates S1P delivery from red blood cells in perfused microvessels: mechanism of the protein effect.

    PubMed

    Adamson, R H; Clark, J F; Radeva, M; Kheirolomoom, A; Ferrara, K W; Curry, F E

    2014-04-01

    Removal of plasma proteins from perfusates increases vascular permeability. The common interpretation of the action of albumin is that it forms part of the permeability barrier by electrostatic binding to the endothelial glycocalyx. We tested the alternate hypothesis that removal of perfusate albumin in rat venular microvessels decreased the availability of sphingosine-1-phosphate (S1P), which is normally carried in plasma bound to albumin and lipoproteins and is required to maintain stable baseline endothelial barriers (Am J Physiol Heart Circ Physiol 303: H825-H834, 2012). Red blood cells (RBCs) are a primary source of S1P in the normal circulation. We compared apparent albumin permeability coefficients [solute permeability (Ps)] measured using perfusates containing albumin (10 mg/ml, control) and conditioned by 20-min exposure to rat RBCs with Ps when test perfusates were in RBC-conditioned protein-free Ringer solution. The control perfusate S1P concentration (439 ± 46 nM) was near the normal plasma value at 37 °C and established a stable baseline Ps (0.9 ± 0.4 × 10(-6) cm/s). Ringer solution perfusate contained 52 ± 8 nM S1P and increased Ps more than 10-fold (16.1 ± 3.9 × 10(-6) cm/s). Consistent with albumin-dependent transport of S1P from RBCs, S1P concentrations in RBC-conditioned solutions decreased as albumin concentration, hematocrit, and temperature decreased. Protein-free Ringer solution perfusates that used liposomes instead of RBCs as flow markers failed to maintain normal permeability, reproducing the "albumin effect" in these mammalian microvessels. We conclude that the albumin effect depends on the action of albumin to facilitate the release and transport of S1P from RBCs that normally provide a significant amount of S1P to the endothelium.

  20. Characterization of inhibition of M2 ion channel activity by BL-1743, an inhibitor of influenza A virus.

    PubMed Central

    Tu, Q; Pinto, L H; Luo, G; Shaughnessy, M A; Mullaney, D; Kurtz, S; Krystal, M; Lamb, R A

    1996-01-01

    The influenza A virus M2 integral membrane protein has ion channel activity that can be inhibited by the antiviral drug amantadine. Recently, a spirene-containing compound, BL-1743 (2-[3-azaspiro (5,5)undecanol]-2-imidazoline), that inhibits influenza virus growth was identified (S. Kurtz, G. Lao, K. M. Hahnenberger, C. Brooks, O. Gecha, K. Ingalls, K.-I. Numata, and M. Krystal, Antimicrob. Agents Chemother. 39:2204-2209, 1995). We have examined the ability of BL-1743 to inhibit the M2 ion channel when expressed in oocytes of Xenopus laevis. BL-1743 inhibition is complete as far as can be measured by electrophysiological methods and is reversible, with a reverse reaction rate constant of 4.0 x 10(-3) s(-1). In contrast, amantadine inhibition is irreversible within the time frame of the experiment. However, BL-1743 inhibition and amantadine inhibition have similar properties. The majority of isolated influenza viruses resistant to BL-1743 are also amantadine resistant. In addition, all known amino acid changes which result in amantadine resistance also confer BL-1743 resistance. However, one BL-1743-resistant virus isolated, designated M2-I35T, contained the change Ile-35-->Thr. This virus is >70-fold more resistant to BL-1743 and only 10-fold more resistant to amantadine than the wild-type virus. When the ion channel activity of M2-I35T was examined in oocytes, it was found that M2-I35T is BL-1743 resistant but is reversibly inhibited by amantadine. These findings suggest that these two drugs interact differently with the M2 protein transmembrane pore region. PMID:8676445

  1. RBP-J is required for M2 macrophage polarization in response to chitin and mediates expression of a subset of M2 genes.

    PubMed

    Foldi, Julia; Shang, Yingli; Zhao, Baohong; Ivashkiv, Lionel B; Hu, Xiaoyu

    2016-03-01

    Development of alternatively activated (M2) macrophage phenotypes is a complex process that is coordinately regulated by a plethora of pathways and factors. Here, we report that RBP-J, a DNA-binding protein that integrates signals from multiple pathways including the Notch pathway, is critically involved in polarization of M2 macrophages. Mice deficient in RBP-J in the myeloid compartment exhibited impaired M2 phenotypes in vivo in a chitin-induced model of M2 polarization. Consistent with the in vivo findings, M2 polarization was partially compromised in vitro in Rbpj-deficient macrophages as demonstrated by reduced expression of a subset of M2 effector molecules including arginase 1. Functionally, myeloid Rbpj deficiency impaired M2 effector functions including recruitment of eosinophils and suppression of T cell proliferation. Collectively, we have identified RBP-J as an essential regulator of differentiation and function of alternatively activated macrophages.

  2. Exit Strategies: S1P Signaling and T Cell Migration.

    PubMed

    Baeyens, Audrey; Fang, Victoria; Chen, Cynthia; Schwab, Susan R

    2015-12-01

    Whereas the role of sphingosine 1-phosphate receptor 1 (S1PR1) in T cell egress and the regulation of S1P gradients between lymphoid organs and circulatory fluids in homeostasis are increasingly well understood, much remains to be learned about S1P signaling and distribution during an immune response. Recent data suggest that the role of S1PR1 in directing cells from tissues into circulatory fluids is reprised again and again, particularly in guiding activated T cells from non-lymphoid tissues into lymphatics. Conversely, S1P receptor 2 (S1PR2), which antagonizes migration towards chemokines, confines cells within tissues. Here we review the current understanding of the roles of S1P signaling in activated T cell migration. In this context, we outline open questions, particularly regarding the shape of S1P gradients in different tissues in homeostasis and inflammation, and discuss recent strategies to measure S1P.

  3. Doubled haploid versus S1 family recurrent selection for testcross performance in a maize population.

    PubMed

    Bordes, J; Charmet, G; de Vaulx, R Dumas; Pollacsek, M; Beckert, M; Gallais, A

    2006-04-01

    Theoretically, in a recurrent selection program, the use of doubled haploids (DH) can increase genetic advance per unit of time. To evaluate the efficiency expected from the use of DH for the improvement of grain yield in a maize (Zea mays L.) population, two recurrent selection programs for testcross performance were initiated using testcross progenies from DH lines and S1 families. In 4 years one selection cycle using DH and two selection cycles using S1 families were carried out with the same selection intensity for both methods. As expected, testcross genetic variance was twice as high among DH lines as among S1 families. The predicted genetic gain was 8.2% for the DH selection cycle, and 10.6% for the two S1 selection cycles, giving a per year advantage of 29% for the S1 family method over the DH method with a cycle of 4 years. With a 3-year cycle for the DH method, both methods were expected to be equivalent. Using a tester related to the one used for selection, the genetic gains obtained were equivalent for both methods: 6.6% for the DH cycle and 7.0% for the two S1 cycles. With a 3-year cycle for the DH method, the advantage would have been in favor of DH method. Furthermore, the DH method has the advantage of simultaneously producing lines that are directly usable as parents of a hybrid. Thus, if the genetic advance per unit of time is evaluated at the level of developed varieties even with the same or with a lower genetic advance in population improvement, the DH method appears to be the most efficient.

  4. Exogenous S1P Exposure Potentiates Ischemic Stroke Damage That Is Reduced Possibly by Inhibiting S1P Receptor Signaling.

    PubMed

    Moon, Eunjung; Han, Jeong Eun; Jeon, Sejin; Ryu, Jong Hoon; Choi, Ji Woong; Chun, Jerold

    2015-01-01

    Initial and recurrent stroke produces central nervous system (CNS) damage, involving neuroinflammation. Receptor-mediated S1P signaling can influence neuroinflammation and has been implicated in cerebral ischemia through effects on the immune system. However, S1P-mediated events also occur within the brain itself where its roles during stroke have been less well studied. Here we investigated the involvement of S1P signaling in initial and recurrent stroke by using a transient middle cerebral artery occlusion/reperfusion (M/R) model combined with analyses of S1P signaling. Gene expression for S1P receptors and involved enzymes was altered during M/R, supporting changes in S1P signaling. Direct S1P microinjection into the normal CNS induced neuroglial activation, implicating S1P-initiated neuroinflammatory responses that resembled CNS changes seen during initial M/R challenge. Moreover, S1P microinjection combined with M/R potentiated brain damage, approximating a model for recurrent stroke dependent on S1P and suggesting that reduction in S1P signaling could ameliorate stroke damage. Delivery of FTY720 that removes S1P signaling with chronic exposure reduced damage in both initial and S1P-potentiated M/R-challenged brain, while reducing stroke markers like TNF-α. These results implicate direct S1P CNS signaling in the etiology of initial and recurrent stroke that can be therapeutically accessed by S1P modulators acting within the brain.

  5. S1-equivariant Chern-Weil constructions on loop space

    NASA Astrophysics Data System (ADS)

    McCauley, Thomas

    2017-02-01

    We study the existence of S1-equivariant characteristic classes on certain natural infinite rank bundles over the loop space LM of a manifold M. We discuss the different S1-equivariant cohomology theories in the literature and clarify their relationships. We attempt to use S1-equivariant Chern-Weil techniques to construct S1-equivariant characteristic classes. The main result is the construction of a sequence of S1-equivariant characteristic classes on the total space of the bundles, but these classes do not descend to the base LM. Nevertheless, we conclude by identifying a class of bundles for which the S1-equivariant first Chern class does descend to LM.

  6. [Response in a case of inoperable bile duct cancer treated by combined chemotherapy of S-1 and gemcitabine].

    PubMed

    Akiyama, Nobuhiro; Ayata, Sakura; Maruyama, Yuzuru; Tsukada, Yoshihisa

    2010-08-01

    A 60-year-old male patient was diagnosed as bile duct cancer with left neck and abdominal para-aortic lymph node metastasis. He was treated by combined chemotherapy of S-1 and gemcitabine(GEM). S-1 (120 mg/day) was administered 14 days followed by 14 days rest as one course. GEM (1,000 mg/m2) was administered at 8 and 15 days after the start of S-1. Combined therapy could be continued, though S-1 and GEM were reduced for neutropemia. After 5 courses of treatment, CT and MRCP revealed a partial response. S-1/GEM combined therapy was effective for inoperable biliary tract carcinoma.

  7. Blocking S1P interaction with S1P{sub 1} receptor by a novel competitive S1P{sub 1}-selective antagonist inhibits angiogenesis

    SciTech Connect

    Fujii, Yasuyuki; Ueda, Yasuji; Ohtake, Hidenori; Ono, Naoya; Takayama, Tetsuo; Nakazawa, Kiyoshi; Igarashi, Yasuyuki; Goitsuka, Ryo

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer The effect of a newly developed S1P{sub 1}-selective antagonist on angiogenic responses. Black-Right-Pointing-Pointer S1P{sub 1} is a critical component of VEGF-related angiogenic responses. Black-Right-Pointing-Pointer S1P{sub 1}-selective antagonist showed in vitro activity to inhibit angiogenesis. Black-Right-Pointing-Pointer S1P{sub 1}-selective antagonist showed in vivo activity to inhibit angiogenesis. Black-Right-Pointing-Pointer The efficacy of S1P{sub 1}-selective antagonist for anti-cancer therapies. -- Abstract: Sphingosine 1-phosphate receptor type 1 (S1P{sub 1}) was shown to be essential for vascular maturation during embryonic development and it has been demonstrated that substantial crosstalk exists between S1P{sub 1} and other pro-angiogenic growth factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor. We developed a novel S1P{sub 1}-selective antagonist, TASP0277308, which is structurally unrelated to S1P as well as previously described S1P{sub 1} antagonists. TASP0277308 inhibited S1P- as well as VEGF-induced cellular responses, including migration and proliferation of human umbilical vein endothelial cells. Furthermore, TASP0277308 effectively blocked a VEGF-induced tube formation in vitro and significantly suppressed tumor cell-induced angiogenesis in vivo. These findings revealed that S1P{sub 1} is a critical component of VEGF-related angiogenic responses and also provide evidence for the efficacy of TASP0277308 for anti-cancer therapies.

  8. Pulsed-laser-induced damage in semiconductors Ge, ZnS, and ZnSe at 10.6um

    NASA Astrophysics Data System (ADS)

    Lefranc, Sebastian; Kudriavtsev, Eugene M.; Autric, Michel L.

    1998-04-01

    Laser irradiation induced damage to several materials of interest for use as 10.6 micrometers laser system windows is investigated in this paper. The irradiation source in these single shot experiments was a pulsed TEA CO2 laser. Damage initiation in semiconductors has been studied during the interaction by measuring the variation of the transmitted intensity of a He- Ne and a CO2 cw lasers through the samples. Results show that damages appear at the beginning of the laser-matter interaction process on both surfaces and in the bulk of the materials. The damaged materials have been characterized for various incident fluences by means of optical microscopy and scanning electron microscopy in terms of topography and morphology. The modified surface chemical analysis and the structural analysis have been carried out using energy dispersive x-ray and Raman spectroscopy.

  9. Synthesis of silicon-based nanoparticles by 10.6 μm nanosecond CO2 laser ablation in liquid

    NASA Astrophysics Data System (ADS)

    Popovic, D. M.; Chai, J. S.; Zekic, A. A.; Trtica, M.; Momcilovic, M.; Maletic, S.

    2013-02-01

    Silicon-based nanoparticles were produced by irradiating a single-crystal silicon target with 10.6 μm nanosecond transverse excited atmospheric (TEA) pulsed CO2 laser in de-ionized water. The effects of the laser pulse energies and repetition rate were studied. To reveal the role of thermal effects, a low laser repetition rate has been applied, excluding the interaction of the laser beam with the previously generated cavitation bubble. The analysis of the influence of the laser pulse energies and the laser repetition rate showed that the increase of the laser pulse energies leads to an increase of the nanoparticle size. An explanation of such results was proposed and the importance of the role of the target surface temperature in the ablation process is discussed.

  10. Conformationally Constrained, Stable, Triplet Ground State (S = 1) Nitroxide Diradicals. Antiferromagnetic Chains of S = 1 Diradicals

    SciTech Connect

    Rajca, Andrzej; Takahashi, Masahiro; Pink, Maren; Spagnol, Gaelle; Rajca, Suchada

    2008-06-30

    Nitroxide diradicals, in which nitroxides are annelated to m-phenylene forming tricyclic benzobisoxazine-like structures, have been synthesized and characterized by X-ray crystallography, magnetic resonance (EPR and {sup 1}H NMR) spectroscopy, as well as magnetic studies in solution and in solid state. For the octamethyl derivative of benzobisoxazine nitroxide diradical, the conformationally constrained nitroxide moieties are coplanar with the m-phenylene, leading to large values of 2J (2J/k > 200 K in solution and 2J/k >> 300 K in the solid state). For the diradical, in which all ortho and para positions of the m-phenylene are sterically shielded, distortion of the nitroxide moieties from coplanarity is moderate, such that the singlet-triplet gaps remain large in both solution (2J/k > 200 K) and the solid state (2J/k {approx} 400-800 K), though an onset of thermal depopulation of the triplet ground state is detectable near room temperature. These diradicals have robust triplet ground states with strong ferromagnetic coupling and good stability at ambient conditions. Magnetic behavior of the nitroxide diradicals at low temperature is best fit to the model of one-dimensional S = 1 Heisenberg chains with intrachain antiferromagnetic coupling. The antiferromagnetic coupling between the S = 1 diradicals may be associated with the methyl nitroxide C-H {hor_ellipsis} O contacts, including nonclassical hydrogen bonds. These unprecedented organic S = 1 antiferromagnetic chains are highly isotropic, compared to those of the extensively studied Ni(II)-based chains.

  11. S1P in HDL promotes interaction between SR-BI and S1PR1 and activates S1PR1-mediated biological functions: calcium flux and S1PR1 internalization.

    PubMed

    Lee, Mi-Hye; Appleton, Kathryn M; El-Shewy, Hesham M; Sorci-Thomas, Mary G; Thomas, Michael J; Lopes-Virella, Maria F; Luttrell, Louis M; Hammad, Samar M; Klein, Richard L

    2017-02-01

    HDL normally transports about 50-70% of plasma sphingosine 1-phosphate (S1P), and the S1P in HDL reportedly mediates several HDL-associated biological effects and signaling pathways. The HDL receptor, SR-BI, as well as the cell surface receptors for S1P (S1PRs) may be involved partially and/or completely in these HDL-induced processes. Here we investigate the nature of the HDL-stimulated interaction between the HDL receptor, SR-BI, and S1PR1 using a protein-fragment complementation assay and confocal microscopy. In both primary rat aortic vascular smooth muscle cells and HEK293 cells, the S1P content in HDL particles increased intracellular calcium concentration, which was mediated by S1PR1. Mechanistic studies performed in HEK293 cells showed that incubation of cells with HDL led to an increase in the physical interaction between the SR-BI and S1PR1 receptors that mainly occurred on the plasma membrane. Model recombinant HDL (rHDL) particles formed in vitro with S1P incorporated into the particle initiated the internalization of S1PR1, whereas rHDL without supplemented S1P did not, suggesting that S1P transported in HDL can selectively activate S1PR1. In conclusion, these data suggest that S1P in HDL stimulates the transient interaction between SR-BI and S1PRs that can activate S1PRs and induce an elevation in intracellular calcium concentration.

  12. Chemical and genetic tools to explore S1P biology.

    PubMed

    Cahalan, Stuart M

    2014-01-01

    The zwitterionic lysophospholipid Sphingosine 1-Phosphate (S1P) is a pleiotropic mediator of physiology and pathology. The synthesis, transport, and degradation of S1P are tightly regulated to ensure that S1P is present in the proper concentrations in the proper location. The binding of S1P to five G protein-coupled S1P receptors regulates many physiological systems, particularly the immune and vascular systems. Our understanding of the functions of S1P has been aided by the tractability of the system to both chemical and genetic manipulation. Chemical modulators have been generated to affect most of the known components of S1P biology, including agonists of S1P receptors and inhibitors of enzymes regulating S1P production and degradation. Genetic knockouts and manipulations have been similarly engineered to disrupt the functions of individual S1P receptors or enzymes involved in S1P metabolism. This chapter will focus on the development and utilization of these chemical and genetic tools to explore the complex biology surrounding S1P and its receptors, with particular attention paid to the in vivo findings that these tools have allowed for.

  13. 26 CFR 1.414(s)-1 - Definition of compensation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Definition of compensation. 1.414(s)-1 Section 1.414(s)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.414(s)-1 Definition...

  14. Mitochondrial Ultrastructural Alterations and Declined M2 Receptor Density Were Involved in Cardiac Dysfunction in Rats after Long Term Treatment with Autoantibodies against M2 Muscarinic Receptor

    PubMed Central

    Wang, Jin; Wang, Li; Wu, Ye; Wang, Jie; Lv, Tingting; Liu, Huirong

    2015-01-01

    Background Previous studies showed that autoantibodies (M2-AA) against the second extracellular loop of M2 muscarinic receptor (M2AChR-el2) from dilated cardiomyopathy (DCM) serum could induce DCM-like morphological changes in mice hearts. However, the effects of M2-AA on the cardiac function during the process of DCM and the potential mechanisms are not fully known. The present study was designed to dynamically observe the cardiac function, mitochondrial changes, and M2 receptor binding characteristics in rats long-term stimulated with M2-AA in vivo. Methods M2-AA-positive model was established by actively immunizing healthy male Wistar rats with synthetic M2AChR-el2 peptide for 18 months. Meanwhile, vehicle group rats were administrated with physiological saline. The change of mitochondrial membrane potential (ΔΨm) was detected by radionuclide imaging. The ultrastructure of mitochondria was observed under electron microscopy. The M2 receptor binding characteristics were determined by radioactive ligand binding assay. Results After immunization for 12 months, compared with vehicle group, M2AChR-el2-immunized rats showed decreased myocardial contractility and cardiac diastolic function evidenced by declined maximal rate of rise of ventricular pressure and increased left ventricular end-diastolic pressure, respectively. Additionally, mitochondrial swelling and vacuolation were observed. At 18 months, M2AChR-el2-immunized rats manifested significant decreased cardiac systolic and diastolic function and pathological changes such as enlargement of right ventricular cavity and wall thinning; and the mitochondrial damage was aggravated. Furthermore, the M2 receptor maximum binding capacity (Bmax) of the M2AChR-el2-immunized rats significantly decreased, while the M2 receptor dissociation constant (Kd) was increased. Conclusions Our study suggested that long-term stimulation with M2-AA leaded to the ventricular dilatation and gradual deterioration of cardiac dysfunction

  15. 41 CFR 302-10.6 - Are the allowances for transporting a mobile home in addition to the allowances for per diem...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 41 Public Contracts and Property Management 4 2012-07-01 2012-07-01 false Are the allowances for transporting a mobile home in addition to the allowances for per diem, mileage, and transportation expenses, for me and my immediate family member(s)? 302-10.6 Section 302-10.6 Public Contracts and...

  16. Sphingosine-1-Phosphate (S1P) Lyase Inhibition Causes Increased Cardiac S1P Levels and Bradycardia in Rats.

    PubMed

    Harris, Christopher M; Mittelstadt, Scott; Banfor, Patricia; Bousquet, Peter; Duignan, David B; Gintant, Gary; Hart, Michelle; Kim, Youngjae; Segreti, Jason

    2016-10-01

    Inhibition of the sphingosine-1-phosphate (S1P)-catabolizing enzyme S1P lyase (S1PL) elevates the native ligand of S1P receptors and provides an alternative mechanism for immune suppression to synthetic S1P receptor agonists. S1PL inhibition is reported to preferentially elevate S1P in lymphoid organs. Tissue selectivity could potentially differentiate S1PL inhibitors from S1P receptor agonists, the use of which also results in bradycardia, atrioventricular block, and hypertension. But it is unknown if S1PL inhibition would also modulate cardiac S1P levels or cardiovascular function. The S1PL inhibitor 6-[(2R)-4-(4-benzyl-7-chlorophthalazin-1-yl)-2-methylpiperazin-1-yl]pyridine-3-carbonitrile was used to determine the relationship in rats between drug concentration, S1P levels in select tissues, and circulating lymphocytes. Repeated oral doses of the S1PL inhibitor fully depleted circulating lymphocytes after 3 to 4 days of treatment in rats. Full lymphopenia corresponded to increased levels of S1P of 100- to 1000-fold in lymph nodes, 3-fold in blood (but with no change in plasma), and 9-fold in cardiac tissue. Repeated oral dosing of the S1PL inhibitor in telemeterized, conscious rats resulted in significant bradycardia within 48 hours of drug treatment, comparable in magnitude to the bradycardia induced by 3 mg/kg fingolimod. These results suggest that S1PL inhibition modulates cardiac function and does not provide immune suppression with an improved cardiovascular safety profile over fingolimod in rats.

  17. M2b monocytes predominated in peripheral blood of severely burned patients.

    PubMed

    Kobayashi, Makiko; Jeschke, Marc G; Shigematsu, Kenji; Asai, Akira; Yoshida, Shohei; Herndon, David N; Suzuki, Fujio

    2010-12-15

    Severely burned patients were shown to be carriers of M2 monocytes, and all of the monocytes isolated from peripheral blood of severely burned patients (19 of 19 patients) were demonstrated as M2b monocytes (IL-12(-)IL-10(+)CCL1(+) monocytes). Low levels of M2a (IL-12(-)IL-10(+)CCL17(+) monocytes) and M2c monocytes (IL-12(-)IL-10(+)CXCL13(+) monocytes) were demonstrated in peripheral blood of severely burned patients (M2a, 2 of 19 patients; M2c, 5 of 19 patients). M2b, M2a, and M2c monocytes were not detected in peripheral blood of healthy donors. However, M2b monocytes appeared when healthy donor monocytes were cultured in media supplemented with burn patient serum (15%). CCL2 was detected in sera of all burn patients, and M2b monocytes were not generated from healthy donor monocytes cultured with media containing 15% burn patient sera that were previously treated with anti-CCL2 mAb. In addition, M2b monocytes were generated from healthy donor monocytes in cultures supplemented with rCCL2. These results indicate that M2b monocytes are predominant in peripheral blood of severely burned patients who are carriers of CCL2 that functions to stimulate monocyte conversion from resident monocytes to M2b monocytes.

  18. Host Cellular Protein TRAPPC6AΔ Interacts with Influenza A Virus M2 Protein and Regulates Viral Propagation by Modulating M2 Trafficking

    PubMed Central

    Zhu, Pengyang; Liang, Libin; Shao, Xinyuan; Luo, Weiyu; Jiang, Shuitao; Zhao, Qingqing; Sun, Nan; Zhao, Yuhui; Li, Junping; Wang, Jinguang; Zhou, Yuan; Zhang, Jie; Wang, Guangwen; Jiang, Li

    2016-01-01

    ABSTRACT Influenza A virus (IAV) matrix protein 2 (M2) plays multiple roles in the early and late phases of viral infection. Once synthesized, M2 is translocated to the endoplasmic reticulum (ER), travels to the Golgi apparatus, and is sorted at the trans-Golgi network (TGN) for transport to the apical plasma membrane, where it functions in virus budding. We hypothesized that M2 trafficking along with its secretory pathway must be finely regulated, and host factors could be involved in this process. However, no studies examining the role of host factors in M2 posttranslational transport have been reported. Here, we used a yeast two-hybrid (Y2H) system to screen for host proteins that interact with the M2 protein and identified transport protein particle complex 6A (TRAPPC6A) as a potential binding partner. We found that both TRAPPC6A and its N-terminal internal-deletion isoform, TRAPPC6A delta (TRAPPC6AΔ), interact with M2. Truncation and mutation analyses showed that the highly conserved leucine residue at position 96 of M2 is critical for mediating this interaction. The role of TRAPPC6AΔ in the viral life cycle was investigated by the knockdown of endogenous TRAPPC6AΔ with small interfering RNA (siRNA) and by generating a recombinant virus that was unable to interact with TRAPPC6A/TRAPPC6AΔ. The results indicated that TRAPPC6AΔ, through its interaction with M2, slows M2 trafficking to the apical plasma membrane, favors viral replication in vitro, and positively modulates virus virulence in mice. IMPORTANCE The influenza A virus M2 protein regulates the trafficking of not only other proteins but also itself along the secretory pathway. However, the host factors involved in the regulation of the posttranslational transport of M2 are largely unknown. In this study, we identified TRAPPC6A and its N-terminal internal-deletion isoform, TRAPPC6AΔ, as interacting partners of M2. We found that the leucine (L) residue at position 96 of M2 is critical for mediating

  19. Targeting sphingosine 1-phosphate (S1P) levels and S1P receptor functions for therapeutic immune interventions.

    PubMed

    Gräler, Markus H

    2010-01-01

    Sphingosine 1-phosphate (S1P) is an important regulator of many different immune functions including lymphocyte circulation, antigen presentation, and T cell development. It stimulates five G protein-coupled receptors designated S1P(1-5), which are also expressed by immune cells. S1P receptors couple to different heterotrimeric G proteins including G alpha i, q, and 12/13, and elicit cellular signalling events by activating the small GTPases Rac and Rho and protein kinases Akt, ERK, and JNK, and by inducing cellular calcium flux and inhibiting cAMP accumulation, amongst others. S1P is the exit signal for lymphocytes leaving lymphoid organs and present in blood and lymph at high nanomolar concentrations due to the S1P-producing activity of sphingosine kinases (SK). The S1P-degrading enzyme S1P-lyase maintains low amounts of S1P in lymphoid organs. Disrupting this concentration difference by S1P receptor agonists and antagonists like FTY720, SEW2871, and VPC23019, by an anti-S1P antibody, or by inhibiting the S1P-lyase has therapeutic potential for autoimmune diseases like multiple sclerosis (MS) and rheumatoid arthritis and for many other disorders like cancer, fibrosis, inflammation, macular degeneration, diabetic retinopathy, and glaucoma. This report aims to provide a brief overview of concepts, approaches, pharmaceutical compounds, and targets that are currently used to modulate S1P-driven immune functions.

  20. The structure of the third intracellular loop of the muscarinic acetylcholine receptor M2 subtype.

    PubMed

    Ichiyama, Susumu; Oka, Yoshiaki; Haga, Kazuko; Kojima, Shuichi; Tateishi, Yukihiro; Shirakawa, Masahiro; Haga, Tatsuya

    2006-01-09

    We have examined whether the long third intracellular loop (i3) of the muscarinic acetylcholine receptor M2 subtype has a rigid structure. Circular dichroism (CD) and nuclear magnetic resonance spectra of M2i3 expressed in and purified from Escherichia coli indicated that M2i3 consists mostly of random coil. In addition, the differential CD spectrum between the M2 and M2deltai3 receptors, the latter of which lacks most of i3 except N- and C-terminal ends, gave no indication of secondary structure. These results suggest that the central part of i3 of the M2 receptor has a flexible structure.

  1. Measurement of Double Charmonium Production in$e^+e^-$ Annihilations at $\\sqrt{s}=10.6$ GeV

    SciTech Connect

    Aubert, B.; Barate, R.; Boutigny, D.; Couderc, F.; Karyotakis, Y.; Lees, J.P.; Poireau, V.; Tisserand, V.; Zghiche, A.; Grauges, E.; Palano, A.; Pappagallo, M.; Pompili, A.; Chen, J.C.; Qi, N.D.; Rong, G.; Wang, P.; Zhu, Y.S.; Eigen, G.; Ofte, I.; Stugu, B. /Bergen U. /LBL, Berkeley /UC, Berkeley /Birmingham U. /Ruhr U., Bochum /Bristol U. /British Columbia U. /Brunel U. /Novosibirsk, IYF /UC, Irvine /UCLA /UC, Riverside /UC, San Diego /UC, Santa Barbara /UC, Santa Cruz /Caltech /Cincinnati U. /Colorado U. /Colorado State U. /Dortmund U. /Dresden, Tech. U. /Ecole Polytechnique /Edinburgh U. /Ferrara U. /INFN, Ferrara /Frascati /Genoa U. /INFN, Genoa /Harvard U. /Heidelberg U. /Imperial Coll., London /Iowa U. /Iowa State U. /Orsay, LAL /LLNL, Livermore /Liverpool U. /Queen Mary, U. of London /Royal Holloway, U. of London /Louisville U. /Manchester U. /Maryland U. /Massachusetts U., Amherst /MIT, LNS /McGill U. /Milan U. /INFN, Milan /Mississippi U. /Montreal U. /Mt. Holyoke Coll. /Naples U. /INFN, Naples /NIKHEF, Amsterdam /Notre Dame U. /Ohio State U. /Oregon U. /Padua U. /INFN, Padua /Paris U., VI-VII /Pennsylvania U. /Perugia U. /INFN, Perugia /Pisa U. /INFN, Pisa /Prairie View A-M /Princeton U. /Rome U. /INFN, Rome /Rostock U. /Rutherford /DAPNIA, Saclay /South Carolina U. /SLAC /Stanford U., Phys. Dept. /SUNY, Stony Brook /Tennessee U. /Texas U. /Texas U., Dallas /Turin U. /INFN, Turin /Trieste U. /INFN, Trieste /Valencia U., IFIC /Vanderbilt U. /Victoria U. /Warwick U. /Wisconsin U., Madison /Yale U.

    2005-06-29

    The authors study e{sup +}e{sup -} {yields} J/{psi} c{bar c} by measuring the invariant mass distribution recoiling against fully reconstructed J/{psi} decays, using 124.4 fb{sup -1} of data collected with a center-of-mass energy of 10.6 GeV with the BABAR detector. They observe signals for {eta}{sub c}(1S), {chi}{sub c0}, and {eta}{sub c}(2S) in the recoil mass distribution, thus confirming previous measurements. The authors measure {sigma}(e{sup +}e{sup -} {yields} J/{psi} + c{bar c}){Beta}(c{bar c} {yields} > 2 charged) to be 17.6 {+-} 2.8(stat){sub -2.1}{sup +1.5}(syst) fb, 10.3 {+-} 2.5(stat){sub -1.8}{sup +1.4}(syst) fb, and 16.4 {+-} 3.7(stat){sub -3.0}{sup +2.4}(syst) fb with c{bar c} = {eta}{sub c}(1S), {chi}{sub c0}, and {eta}{sub c}(2S), respectively.

  2. THE HIGH-VELOCITY MOLECULAR OUTFLOWS IN MASSIVE CLUSTER-FORMING REGION G10.6-0.4

    SciTech Connect

    Liu Hauyu Baobab; Ho, Paul T. P.; Zhang Qizhou E-mail: pho@asiaa.sinica.edu.t

    2010-12-20

    We report the arcsecond resolution Submillimeter Array observations of the {sup 12}CO (2-1) transition in the massive cluster-forming region G10.6-0.4. In these observations, the high-velocity {sup 12}CO emission is resolved into individual outflow systems, which have a typical size scale of a few arcseconds. These molecular outflows are energetic and are interacting with the ambient molecular gas. By inspecting the shock signatures traced by CH{sub 3}OH, SiO, and HCN emissions, we suggest that abundant star formation activities are distributed over the entire 0.5 pc scale dense molecular envelope. The star formation efficiency over one global free-fall timescale (of the 0.5 pc molecular envelope, {approx}10{sup 5} years) is about a few percent. The total energy feedback of these high-velocity outflows is higher than 10{sup 47} erg, which is comparable to the total kinetic energy in the rotational motion of the dense molecular envelope. From order-of-magnitude estimations, we suggest that the energy injected from the protostellar outflows is capable of balancing the turbulent energy dissipation. No high-velocity bipolar molecular outflow associated with the central OB cluster is directly detected, which can be due to the photoionization.

  3. Sphingosine-1-Phosphate (S1P) and S1P Signaling Pathway: Therapeutic Targets in Autoimmunity and Inflammation.

    PubMed

    Tsai, Hsing-Chuan; Han, May H

    2016-07-01

    Sphingosine-1-phosphate (S1P) and S1P receptors (S1PR) are ubiquitously expressed. S1P-S1PR signaling has been well characterized in immune trafficking and activation in innate and adaptive immune systems. However, the full extent of its involvement in the pathogenesis of autoimmune diseases is not well understood. FTY720 (fingolimod), a non-selective S1PR modulator, significantly decreased annualized relapse rates in relapsing-remitting multiple sclerosis (MS). FTY720, which primarily targets S1P receptor 1 as a functional antagonist, arrests lymphocyte egress from secondary lymphoid tissues and reduces neuroinflammation in the central nervous system (CNS). Recent studies suggest that FTY720 also decreases astrogliosis and promotes oligodendrocyte differentiation within the CNS and may have therapeutic benefit to prevent brain atrophy. Since S1P signaling is involved in multiple immune functions, therapies targeting S1P axis may be applicable to treat autoimmune diseases other than MS. Currently, over a dozen selective S1PR and S1P pathway modulators with potentially superior therapeutic efficacy and better side-effect profiles are in the pipeline of drug development. Furthermore, newly characterized molecules such as apolipoprotein M (ApoM) (S1P chaperon) and SPNS2 (S1P transporter) are also potential targets for treatment of autoimmune diseases. Finally, the application of therapies targeting S1P and S1P signaling pathways may be expanded to treat several other immune-mediated disorders (such as post-infectious diseases, post-stroke and post-stroke dementia) and inflammatory conditions beyond their application in primary autoimmune diseases.

  4. The cytoplasmic domain of influenza M2 protein interacts with caveolin-1.

    PubMed

    Zou, Peng; Wu, Fan; Lu, Lu; Huang, Jing-He; Chen, Ying-Hua

    2009-06-15

    The cytoplasmic domain of influenza M2 protein (M2c) consists of 54 amino acid (aa) residues from aa44 to aa97. In this paper, M2c and its deletion mutant M2c(delta47-55) were expressed using prokaryotic expression system. First, glutaraldehyde crosslinking assay showed that M2c had multimerization potential mediated by aa47-55. Then, M2c, instead of M2c(delta47-55), directed eGFP from the whole cell localization to a predominately perinuclear region in CHO cells, which indicated that aa47-55 of M2c mediated the localization. Moreover, M2c colocalized with caveolin-1 (Cav) when CHO cells were cotransfected with Cav. A caveolin-1 binding motif phixxxxphixxphi (phi represents aromatic amino acid residues) in aa47-55 of M2c was found by sequence alignment and analysis. Further overlay ELISA result showed that M2c, but not M2c(delta47-55), bound to prokaryotically expressed cholesterol-free Cav(2-101), which illustrated the interaction could be cholesterol-independent. That was the first report of cellular protein bound to M2c.

  5. Ising Model Spin S = 1 ON Directed BARABÁSI-ALBERT Networks

    NASA Astrophysics Data System (ADS)

    Lima, F. W. S.

    On directed Barabási-Albert networks with two and seven neighbours selected by each added site, the Ising model with spin S = 1/2 was seen not to show a spontaneous magnetisation. Instead, the decay time for flipping of the magnetisation followed an Arrhenius law for Metropolis and Glauber algorithms, but for Wolff cluster flipping the magnetisation decayed exponentially with time. On these networks the Ising model spin S = 1 is now studied through Monte Carlo simulations. However, in this model, the order-disorder phase transition is well defined in this system. We have obtained a first-order phase transition for values of connectivity m = 2 and m = 7 of the directed Barabási-Albert network.

  6. Motion-to-Energy (M2Eâ„¢) Power Generation Technology

    SciTech Connect

    Idaho National Laboratory

    2008-05-30

    INL researchers developed M2E, a new technology that converts motion to energy. M2E uses an innovative, optimized microgenerator with power management circuitry that kinetically charges mobile batteries from natural motion such as walking. To learn more,

  7. Potential of CO2 lasers (10.6 µm) associated with fluorides in inhibiting human enamel erosion.

    PubMed

    Ramos-Oliveira, Thayanne Monteiro; Ramos, Thaysa Monteiro; Esteves-Oliveira, Marcela; Apel, Christian; Fischer, Horst; Eduardo, Carlos de Paula; Steagall, Washington; Freitas, Patricia Moreira de

    2014-01-01

    This in vitro study aimed to investigate the potential of CO2 lasers associated with different fluoride agents in inhibiting enamel erosion. Human enamel samples were randomly divided into 9 groups (n = 12): G1-eroded enamel; G2-APF gel; G3-AmF/NaF gel; G4-AmF/SnF2 solution; G5-CO2 laser (λ = 10.6 µm)+APF gel; G6-CO2 laser+AmF/NaF gel; G7-CO2laser+AmF/SnF2solution; G8-CO2 laser; and G9-sound enamel. The CO2 laser parameters were: 0.45 J/cm2; 6 μs; and 128 Hz. After surface treatment, the samples (except from G9) were immersed in 1% citric acid (pH 4.0, 3 min). Surface microhardness was measured at baseline and after surface softening. The data were statistically analyzed by one-way ANOVA and Tukey's tests (p < 0.05). G2 (407.6 ± 37.3) presented the highest mean SMH after softening, followed by G3 (407.5 ± 29.8) and G5 (399.7 ± 32.9). Within the fluoride-treated groups, G4 (309.0 ± 24.4) had a significantly lower mean SMH than G3 and G2, which were statistically similar to each other. AmF/NaF and APF application showed potential to protect and control erosion progression in dental enamel, and CO2 laser irradiation at 0.45J/cm2 did not influence its efficacy. CO2 laser irradiation alone under the same conditions could also significantly decrease enamel erosive mineral loss, although at lower levels.

  8. Kinematic Structure of H2 and [Fe II] in the Bipolar Planetary Nebula M2-9

    NASA Astrophysics Data System (ADS)

    Smith, Nathan; Balick, Bruce; Gehrz, Robert D.

    2005-08-01

    We present new high-dispersion, long-slit, infrared (IR) spectra of the double-shell bipolar planetary nebula M2-9 in the emission lines [Fe II] λ16435 and H2v=1-0 S(1) λ21218. H2 spectra reveal for the first time the kinematic structure of the outer shell in M2-9. Kinematics of the inner shell, traced by [Fe II], resemble those of optical forbidden lines like [N II] λ6583, although we note subtle differences. [Fe II] and H2 shells have expansion speeds roughly proportional to distance from the star (``Hubble'' flows) and share the same dynamical age of 1200-2000 yr, depending on the distance to M2-9. Thus, the inner ionized lobes and outer molecular lobes, as well as the molecular torus and ``outer loops'' measured by other observers, were all formed around the same time. Consequently, their nested structure likely arises from an excitation gradient rather than independent ejections. H2 and [Fe II] emission is distributed more uniformly than [N II], and IR lines are not dominated by the moving ionization pattern like visual-wavelength lines. We suggest that this is because IR lines of [Fe II] and H2 are excited by relatively isotropic far-UV radiation (Balmer continuum), whereas optical lines respond to a directed rotating beam of Lyman continuum. Finally, we highlight intriguing similarities between M2-9 and the Homunculus of η Car, despite the different central engines powering the two nebulae.

  9. S1P and the birth of platelets.

    PubMed

    Hla, Timothy; Galvani, Sylvain; Rafii, Shahin; Nachman, Ralph

    2012-11-19

    Recent work has highlighted the multitude of biological functions of sphingosine 1-phosphate (S1P), which include roles in hematopoietic cell trafficking, organization of immune organs, vascular development, and neuroinflammation. Indeed, a functional antagonist of S1P(1) receptor, FTY720/Gilenya, has entered the clinic as a novel therapeutic for multiple sclerosis. In this issue of the JEM, Zhang et al. highlight yet another function of this lipid mediator: thrombopoiesis. The S1P(1) receptor is required for the growth of proplatelet strings in the bloodstream and the shedding of platelets into the circulation. Notably, the sharp gradient of S1P between blood and the interstitial fluids seems to be essential to ensure the production of platelets, and S1P appears to cooperate with the CXCL12-CXCR4 axis. Pharmacologic modulation of the S1P(1) receptor altered circulating platelet numbers acutely, suggesting a potential therapeutic strategy for controlling thrombocytopenic states. However, the S1P(4) receptor may also regulate thrombopoiesis during stress-induced accelerated platelet production. This work reveals a novel physiological action of the S1P/S1P(1) duet that could potentially be harnessed for clinical translation.

  10. Direct Interaction of GABAB Receptors with M2 Muscarinic Receptors Enhances Muscarinic Signaling

    PubMed Central

    Boyer, Stephanie B.; Clancy, Sinead M.; Terunuma, Miho; Revilla-Sanchez, Raquel; Thomas, Steven M.; Moss, Stephen J.; Slesinger, Paul A.

    2009-01-01

    Down-regulation of G protein coupled receptors (GPCR) provides an important mechanism for reducing neurotransmitter signaling during sustained stimulation. Chronic stimulation of M2 muscarinic receptors (M2R) causes internalization of M2R and G protein-activated inwardly rectifying potassium (GIRK) channels in neuronal PC12 cells, resulting in loss of function. Here, we show that co-expression of GABAB R2 receptors (GBR2) rescues both surface expression and function of M2R, including M2R-induced activation of GIRKs and inhibition of cAMP production. GBR2 showed significant association with M2R at the plasma membrane but not other GPCRs (M1R, μOR), as detected by FRET measured with TIRF microscopy. Unique regions of the proximal C-terminal domains of GBR2 and M2R mediate specific binding between M2R and GBR2. In the brain, GBR2, but not GBR1, biochemically coprecipitates with M2R and overlaps with M2R expression in cortical neurons. This novel heteromeric association between M2R and GBR2 provides a possible mechanism for altering muscarinic signaling in the brain and represents a previously unrecognized role for GBR2. PMID:20016095

  11. Understanding the Mysterious M2 Macrophage through Activation Markers and Effector Mechanisms

    PubMed Central

    Rőszer, Tamás

    2015-01-01

    The alternatively activated or M2 macrophages are immune cells with high phenotypic heterogeneity and are governing functions at the interface of immunity, tissue homeostasis, metabolism, and endocrine signaling. Today the M2 macrophages are identified based on the expression pattern of a set of M2 markers. These markers are transmembrane glycoproteins, scavenger receptors, enzymes, growth factors, hormones, cytokines, and cytokine receptors with diverse and often yet unexplored functions. This review discusses whether these M2 markers can be reliably used to identify M2 macrophages and define their functional subdivisions. Also, it provides an update on the novel signals of the tissue environment and the neuroendocrine system which shape the M2 activation. The possible evolutionary roots of the M2 macrophage functions are also discussed. PMID:26089604

  12. Transcriptome analysis of IL-10-stimulated (M2c) macrophages by next-generation sequencing.

    PubMed

    Lurier, Emily B; Dalton, Donald; Dampier, Will; Raman, Pichai; Nassiri, Sina; Ferraro, Nicole M; Rajagopalan, Ramakrishan; Sarmady, Mahdi; Spiller, Kara L

    2017-02-20

    Alternatively activated "M2" macrophages are believed to function during late stages of wound healing, behaving in an anti-inflammatory manner to mediate the resolution of the pro-inflammatory response caused by "M1" macrophages. However, the differences between two main subtypes of M2 macrophages, namely interleukin-4 (IL-4)-stimulated "M2a" macrophages and IL-10-stimulated "M2c" macrophages, are not well understood. M2a macrophages are characterized by their ability to inhibit inflammation and contribute to the stabilization of angiogenesis. However, the role and temporal profile of M2c macrophages in wound healing are not known. Therefore, we performed next generation sequencing (RNA-seq) to identify biological functions and gene expression signatures of macrophages polarized in vitro with IL-10 to the M2c phenotype in comparison to M1 and M2a macrophages and an unactivated control (M0). We then explored the expression of these gene signatures in a publicly available data set of human wound healing. RNA-seq analysis showed that hundreds of genes were upregulated in M2c macrophages compared to the M0 control, with thousands of alternative splicing events. Following validation by Nanostring, 39 genes were found to be upregulated by M2c macrophages compared to the M0 control, and 17 genes were significantly upregulated relative to the M0, M1, and M2a phenotypes (using an adjusted p-value cutoff of 0.05 and fold change cutoff of 1.5). Many of the identified M2c-specific genes are associated with angiogenesis, matrix remodeling, and phagocytosis, including CD163, MMP8, TIMP1, VCAN, SERPINA1, MARCO, PLOD2, PCOCLE2 and F5. Analysis of the macrophage-conditioned media for secretion of matrix-remodeling proteins showed that M2c macrophages secreted higher levels of MMP7, MMP8, and TIMP1 compared to the other phenotypes. Interestingly, temporal gene expression analysis of a publicly available microarray data set of human wound healing showed that M2c-related genes were

  13. Novel Markers to Delineate Murine M1 and M2 Macrophages

    PubMed Central

    Jablonski, Kyle A.; Amici, Stephanie A.; Webb, Lindsay M.; Ruiz-Rosado, Juan de Dios; Popovich, Phillip G.; Partida-Sanchez, Santiago; Guerau-de-Arellano, Mireia

    2015-01-01

    Classically (M1) and alternatively activated (M2) macrophages exhibit distinct phenotypes and functions. It has been difficult to dissect macrophage phenotypes in vivo, where a spectrum of macrophage phenotypes exists, and also in vitro, where low or non-selective M2 marker protein expression is observed. To provide a foundation for the complexity of in vivo macrophage phenotypes, we performed a comprehensive analysis of the transcriptional signature of murine M0, M1 and M2 macrophages and identified genes common or exclusive to either subset. We validated by real-time PCR an M1-exclusive pattern of expression for CD38, G-protein coupled receptor 18 (Gpr18) and Formyl peptide receptor 2 (Fpr2) whereas Early growth response protein 2 (Egr2) and c-Myc were M2-exclusive. We further confirmed these data by flow cytometry and show that M1 and M2 macrophages can be distinguished by their relative expression of CD38 and Egr2. Egr2 labeled more M2 macrophages (~70%) than the canonical M2 macrophage marker Arginase-1, which labels 24% of M2 macrophages. Conversely, CD38 labeled most (71%) in vitro M1 macrophages. In vivo, a similar CD38+ population greatly increased after LPS exposure. Overall, this work defines exclusive and common M1 and M2 signatures and provides novel and improved tools to distinguish M1 and M2 murine macrophages. PMID:26699615

  14. M2e-immobilized gold nanoparticles as influenza A vaccine: role of soluble M2e and longevity of protection

    PubMed Central

    Tao, Wenqian; Gill, Harvinder S.

    2015-01-01

    Influenza virus causes seasonal epidemics and also poses a high risk for pandemics. To develop a broadly cross-protective influenza vaccine we have previously shown that a formulation consisting of the extracellular domain of M2 membrane protein (M2e) immobilized on gold nanoparticles (AuNPs) and soluble CpG as an adjuvant can elicit protective immunity against different influenza A subtypes. The vaccine formulation contains M2e that is immobilized on AuNPs, and an excess amount that is freely dissolved in solution, whose role in inducing protective immunity against virus infection is unclear. Using a mouse model, the current study shows that inclusion of excess soluble M2e antigen along with M2e immobilized on AuNPs is vital for inducing high levels of antibody response, and in providing complete protection against lethal influenza virus challenge. We also show that the vaccine induces long-lasting protection against mortality and morbidity upon lethal challenge with influenza A virus. PMID:25842219

  15. Effects of 2.1 and 3.5x10(6) sex-sorted sperm dosages on conception rates of Holstein cows and heifers.

    PubMed

    DeJarnette, J M; McCleary, C R; Leach, M A; Moreno, J F; Nebel, R L; Marshall, C E

    2010-09-01

    The objective was to compare conceptions rates of Holstein cows and heifers after artificial insemination (AI) with 2.1 or 3.5x10(6) sex-sorted sperm or 15x10(6) conventional sperm. Ejaculates collected from 7 Holstein sires were cryopreserved conventionally at 15x10(6) sperm per dose or sorted to 90% purity for X-chromosome-bearing spermatozoa using flow cytometry and cryopreserved at either 2.1 or 3.5x10(6) sperm per dose. All treatments were processed in an egg-yolk (20%), Tris, glycerol (7%) extender and packaged in color-coded 0.25-mL French straws. Straws (n=700 straws/dosage per sire) were packaged and distributed in aliquots of 12 (4 straws/sperm dosage) to 69 Holstein herds with an across-herd goal of achieving approximately 50% use in heifers and cows. Straw color was recorded in the on-farm recordkeeping system at the time of AI and retrieved by electronic download. Data for cows and heifers were analyzed separately. Among heifers, 6,268 services were retrieved from 45 herds (298+/-4.2 services/sperm dose per sire; range: 244 to 344). Conception rate of heifers was influenced by the sire by treatment interaction. Conception rate of the 2.1 and 3.5x10(6) sex-sorted sperm dosages were comparable in 6 of 7 sires. Conception rate of both sex-sorted dosages were less than those of conventional semen for 6 of 7 sires. Across sires, heifer conception rates for 2.1 and 3.5x10(6) sex-sorted sperm dosages and 15x10(6) conventional dosages were 44, 46, and 61%, respectively. Among cows, 5,466 services were retrieved from 52 herds (260+/-3.3 services/sperm dose per sire; range: 236 to 289). Conception rates of cows were influenced by herd, sire, and sperm dosage. Conception rates of the 2.1 and 3.5x10(6) sex-sorted sperm dosage were comparable for all 7 sires. Conception rates of 2.1x10(6) sex-sorted sperm dosage were less than those of conventional semen for 4 of 7 sires and conception rates of the 3.5x10(6) sex-sorted sperm dosage were less than those of

  16. Current Development of Anti-Cancer Drug S-1

    PubMed Central

    Giri, Anil; Shakya, Suraj; Shakya, Sujana; Sapkota, Binaya; Pramod, KC

    2016-01-01

    S-1 is a novel oral fluoropyrimidine derivative, widely used for treating gastric, pancreatic, lung, head, neck and breast carcinomas. It is designed to enhance the clinical utility of an oral fluoropyrimidine and is associated with low gastrointestinal toxicity. S-1 consists of three pharmacological agents (at a molar ratio of 1:0.4:1)-Tegafur (FT), a prodrug of 5-Fluorouracil (5-FU), 5-Chloro-2-4-Dihydroxypyridine (CDHP), which inhibits the activity of Dihydropyrimidine Dehydrogenase (DPD) and Oxonic Acid (Oxo), which reduces Gastrointestinal (GI) toxicity of 5-FU. The present article reviews the current development of clinical study of S-1. PMID:28050491

  17. Serum from patients with systemic vasculitis induces alternatively activated macrophage M2c polarization.

    PubMed

    Ohlsson, Susanne M; Linge, Carl Petrus; Gullstrand, Birgitta; Lood, Christian; Johansson, Asa; Ohlsson, Sophie; Lundqvist, Andrea; Bengtsson, Anders A; Carlsson, Fredric; Hellmark, Thomas

    2014-01-01

    Anti-neutrophil cytoplasmic antibody associated vasculitides (AAV) are conditions defined by an autoimmune small vessel inflammation. Dying neutrophils are found around the inflamed vessels and the balance between infiltrating neutrophils and macrophages is important to prevent autoimmunity. Here we investigate how sera from AAV patients may regulate macrophage polarization and function. Macrophages from healthy individuals were differentiated into M0, M1, M2a, M2b or M2c macrophages using a standardized protocol, and phenotyped according to their expression surface markers and cytokine production. These phenotypes were compared with those of macrophages stimulated with serum from AAV patients or healthy controls. While the healthy control sera induced a M0 macrophage, AAV serum promoted polarization towards the M2c subtype. No sera induced M1, M2a or M2b macrophages. The M2c subtype showed increased phagocytosis capacity compared with the other subtypes. The M2c polarization found in AAV is consistent with previous reports of increased levels of M2c-associated cytokines.

  18. Roles of alternatively activated M2 macrophages in allergic contact dermatitis.

    PubMed

    Suzuki, Kotaro; Meguro, Kazuyuki; Nakagomi, Daiki; Nakajima, Hiroshi

    2017-03-17

    Alternatively activated macrophages (M2 macrophages) play key roles in the suppression of Th1 cell responses and the orchestration of tissue repair. However, recent studies have shown that M2 macrophages have potentials to produce high levels of proinflammatory cytokines such as IL-1β, IL-6, and TNF-α, suggesting that M2 macrophages may exacerbate inflammation in some settings. In this regard, we have recently shown that large numbers of M2 macrophages accumulate in the sites of hapten-induced contact hypersensitivity (CHS), an animal model of allergic contact dermatitis, and that M2 macrophages exacerbate hapten-induced CHS by producing matrix metalloproteinase 12 (MMP12). We have also shown that suppressor of cytokine signaling-3 (SOCS3), a member of SOCS family proteins that are cytokine-inducible negative regulators of the JAK/STAT signaling pathways, is highly and preferentially expressed in M2 macrophages in hapten-induced CHS and that SOCS3 expressed in M2 macrophages is involved in the attenuation of CHS by suppressing MMP12 production. These findings underscore the importance of M2 macrophage-derived MMP12 in the development of CHS, and suggest that inhibition of M2 macrophages or MMP12 could be a potential therapeutic strategy for the treatment of allergic contact dermatitis.

  19. A Novel Vaccine Using Nanoparticle Platform to Present Immunogenic M2e against Avian Influenza Infection

    PubMed Central

    Babapoor, Sankhiros; Neef, Tobias; Mittelholzer, Christian; Girshick, Theodore; Garmendia, Antonio; Shang, Hongwei; Khan, Mazhar I.; Burkhard, Peter

    2011-01-01

    Using peptide nanoparticle technology, we have designed two novel vaccine constructs representing M2e in monomeric (Mono-M2e) and tetrameric (Tetra-M2e) forms. Groups of specific pathogen free (SPF) chickens were immunized intramuscularly with Mono-M2e or Tetra-M2e with and without an adjuvant. Two weeks after the second boost, chickens were challenged with 107.2 EID50 of H5N2 low pathogenicity avian influenza (LPAI) virus. M2e-specific antibody responses to each of the vaccine constructs were tested by ELISA. Vaccinated chickens exhibited increased M2e-specific IgG responses for each of the constructs as compared to a non-vaccinated group. However, the vaccine construct Tetra-M2e elicited a significantly higher antibody response when it was used with an adjuvant. On the other hand, virus neutralization assays indicated that immune protection is not by way of neutralizing antibodies. The level of protection was evaluated using quantitative real time PCR at 4, 6, and 8 days post-challenge with H5N2 LPAI by measuring virus shedding from trachea and cloaca. The Tetra-M2e with adjuvant offered statistically significant (P < 0.05) protection against subtype H5N2 LPAI by reduction of the AI virus shedding. The results suggest that the self-assembling polypeptide nanoparticle shows promise as a potential platform for a development of a vaccine against AI. PMID:23074652

  20. Roles of the PVM M2-1, M2-2 and P gene ORF 2 (P-2) proteins in viral replication.

    PubMed

    Dibben, Oliver; Thorpe, Lindsay C; Easton, Andrew J

    2008-01-01

    A plasmid-based reverse genetics system for pneumonia virus of mice (PVM) using a synthetic minigenome is described. The system was used to investigate the functions of several viral proteins. The M2-1 protein of PVM was shown to enhance reporter gene expression when present at low levels, similar to the situation for the equivalent respiratory syncytial virus (RSV) M2-1 protein, but at high levels was shown to reduce gene expression from the minigenome activity, which differs significantly form the situation with RSV. Analysis of levels of nucleocapsid complex RNA showed that high levels of the PVM M2-1 protein inhibits RNA replication rather than transcription. In contrast, expression of the PVM M2-2 protein in conjunction with the polymerase proteins in a minigenome assay greatly reduced the levels of CAT reporter protein. This is similar to the situation with the RSV M2-2 protein although there is no significant sequence identity between the M2-2 proteins of the pneumoviruses. A significant difference between the genome organisations of RSV and PVM is that the P gene of PVM contains a second open reading frame, encoding the P-2 protein, which has no counterpart in the RSV P gene. Co-expression of the PVM P-2 protein with the minigenome inhibited virus gene expression. This resembles the situation seen with the accessory proteins expressed from alternate reading frames of the P gene of other paramyxoviruses. Analysis of levels of antigenome RNA and CAT mRNA produced by the minigenome in the presence of the P2 protein indicated that the protein inhibits viral transcription in a dose-dependent fashion.

  1. Characterization of the gene and protein of the common alpha 1-antitrypsin normal M2 allele.

    PubMed Central

    Nukiwa, T; Brantly, M L; Ogushi, F; Fells, G A; Crystal, R G

    1988-01-01

    The normal M2 variant of alpha 1-antitrypsin (alpha 1AT) was cloned from a genomic DNA library of an individual homozygous for this allele. Sequencing of all coding exons of the M2 gene revealed it was identical to the common M1(Val213) gene except for two bases (M1(Val213) CGT Arg101, M2 CAT His101; M1(Val213) GAA Glu376 M2 GAC Asp376). Analysis of the sequence of the M1(Val213) and M2 genes around residue 101 revealed the M1 Arg101----M2 His101 caused a loss of the cutting site for the restriction endonuclease RsaI. Using this enzyme, as well as 19-mer oligonucleotides probes centered at residues 101 and 376, evaluation of genomic DNA from 22 M1 alleles and 14 M2 alleles revealed that residue 101 was Arg in all M1 alleles and His in all M2 alleles, while residue 376 was Glu in all M1 alleles and Asp in all M2 alleles. Despite the differences in sequence at two amino acids, the M1(Val213) and M2 proteins function similarly as assessed by quantification of the association rate constant of each for their natural substrate neutrophil elastase. In the context that there are two mutations separating the M1(Val213) and M2 alleles, it is likely that there is another alpha 1AT variant that was an intermediate in the evolution of these genes. Images Figure 2 Figure 4 Figure 1 Figure 3 PMID:2901226

  2. 7S(1/2) ? 9S(1/2) two-photon spectroscopy of trapped francium.

    PubMed

    Simsarian, J E; Shi, W; Orozco, L A; Sprouse, G D; Zhao, W Z

    1996-12-01

    We report on the spectroscopic measurement of the (210)Fr 9S(1/2) energy obtained by two-photon excitation of atoms confined and cooled in a magneto-optic trap. The resonant intermediate level 7P(3/2) is the upper state of the trapping transition. We have measured the energy difference between the 9S(1/2) state and the 7S(1/2) ground state to be 25 671.021 +/- 0.006 cm(-1).

  3. Phonological Substitution Errors in L2 ASL Sentence Processing by Hearing M2L2 Learners

    ERIC Educational Resources Information Center

    Williams, Joshua; Newman, Sharlene

    2016-01-01

    In the present study we aimed to investigate phonological substitution errors made by hearing second language (M2L2) learners of American Sign Language (ASL) during a sentence translation task. Learners saw sentences in ASL that were signed by either a native signer or a M2L2 learner. Learners were to simply translate the sentence from ASL to…

  4. Postsynaptic muscarinic m2 receptors at cholinergic and glutamatergic synapses of mouse brainstem motoneurons.

    PubMed

    Csaba, Zsolt; Krejci, Eric; Bernard, Véronique

    2013-06-15

    In many brain areas, few cholinergic synapses are identified. Acetylcholine is released into the extracellular space and acts through diffuse transmission. Motoneurons, however, are contacted by numerous cholinergic terminals, indicating synaptic cholinergic transmission on them. The muscarinic m2 receptor is the major acetylcholine receptor subtype of motoneurons; therefore, we analyzed the localization of the m2 receptor in correlation with synapses by electron microscopic immunohistochemistry in the mouse trigeminal, facial, and hypoglossal motor nuclei. In all nuclei, m2 receptors were localized at the membrane of motoneuronal perikarya and dendrites. The m2 receptors were concentrated at cholinergic synapses located on the perikarya and most proximal dendrites. However, m2 receptors at cholinergic synapses represented only a minority (<10%) of surface m2 receptors. The m2 receptors were also enriched at glutamatergic synapses in both motoneuronal perikarya and dendrites. A relatively large proportion (20-30%) of plasma membrane-associated m2 receptors were located at glutamatergic synapses. In conclusion, the effect of acetylcholine on motoneuron populations might be mediated through a synaptic as well as diffuse type of transmission.

  5. Wound administration of M2-polarized macrophages does not improve murine cutaneous healing responses.

    PubMed

    Jetten, Nadine; Roumans, Nadia; Gijbels, Marion J; Romano, Andrea; Post, Mark J; de Winther, Menno P J; van der Hulst, Rene R W J; Xanthoulea, Sofia

    2014-01-01

    Macrophages play a crucial role in all stages of cutaneous wound healing responses and dysregulation of macrophage function can result in derailed wound repair. The phenotype of macrophages is influenced by the wound microenvironment and evolves during healing from a more pro-inflammatory (M1) profile in early stages, to a less inflammatory pro-healing (M2) phenotype in later stages of repair. The aim of the current study was to investigate the potential of exogenous administration of M2 macrophages to promote wound healing in an experimental mouse model of cutaneous injury. Bone marrow derived macrophages were stimulated in-vitro with IL-4 or IL-10 to obtain two different subsets of M2-polarized cells, M2a or M2c respectively. Polarized macrophages were injected into full-thickness excisional skin wounds of either C57BL/6 or diabetic db/db mice. Control groups were injected with non-polarized (M0) macrophages or saline. Our data indicate that despite M2 macrophages exhibit an anti-inflammatory phenotype in-vitro, they do not improve wound closure in wild type mice while they delay healing in diabetic mice. Examination of wounds on day 15 post-injury indicated delayed re-epithelialization and persistence of neutrophils in M2 macrophage treated diabetic wounds. Therefore, topical application of ex-vivo generated M2 macrophages is not beneficial and contraindicated for cell therapy of skin wounds.

  6. Orosomucoid 1 drives opportunistic infections through the polarization of monocytes to the M2b phenotype.

    PubMed

    Nakamura, Kiwamu; Ito, Ichiaki; Kobayashi, Makiko; Herndon, David N; Suzuki, Fujio

    2015-05-01

    Orosomucoid (ORM, composed of two isoforms, ORM1 and ORM2) has been described as an inducer of M2 macrophages, which are cells that decrease host antibacterial innate immunities. However, it is unknown which phenotypes of M2 macrophages are induced by ORM. In this study, healthy donor monocytes stimulated with ORM (ORM-monocytes) were characterized phenotypically and biologically. CCL1 (a biomarker of M2b macrophages) and IL-10 were detected in monocyte cultures supplemented with ORM1; however, CCL17 (a biomarker of M2a macrophages) and CXCL13 (a biomarker of M2c macrophages) were not produced in these cultures. All of these soluble factors were not detected in the culture fluids of monocytes stimulated with ORM2. Monocytes stimulated with ORM1 were characterized as CD64(-)CD209(-)CD163(+)CCL1(+) cells. MRSA and Enterococcus faecalis infections were accelerated in chimeras (NOD/scid IL-2Rγ(null) mice reconstituted with white blood cells) after inoculation with monocytes stimulated with ORM1 or treatment with ORM1; however, the infections were greatly mitigated in both chimeras inoculated with ORM1-stimulated monocytes and treated with ORM1, after an additional treatment with an inhibitor of M2b macrophages (CCL1 antisense ODN). These results indicate that ORM1 stimulates quiescent monocytes to polarize to M2b monocytes. The regulation of M2b macrophages may be beneficial in controlling opportunistic infections in patients with a large amount of plasma ORM1.

  7. Establishing a Research Center: The Minority Male Community College Collaborative (M2C3)

    ERIC Educational Resources Information Center

    Wood, J. Luke; Urias, Marissa Vasquez; Harris, Frank, III

    2016-01-01

    This chapter describes the establishment of the Minority Male Community College Collaborative (M2C3), a research and practice center at San Diego State University. M2C3 partners with community colleges across the United States to enhance access, achievement, and success among men of color. This chapter begins with a description of the national…

  8. 12 CFR Appendix M2 to Part 226 - Actual Repayment Disclosures

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Actual Repayment Disclosures M2 Appendix M2 to Part 226 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE... nearest whole year if the estimate contains a fractional year less than 0.5, and rounded up to the...

  9. EspM2 is a RhoA guanine nucleotide exchange factor

    PubMed Central

    Arbeloa, Ana; Garnett, James; Lillington, James; Bulgin, Richard R; Berger, Cedric N; Lea, Susan M; Matthews, Steve; Frankel, Gad

    2010-01-01

    We investigated how the type III secretion system WxxxE effectors EspM2 of enterohaemorrhagic Escherichia coli, which triggers stress fibre formation, and SifA of Salmonella enterica serovar Typhimurium, which is involved in intracellular survival, modulate Rho GTPases. We identified a direct interaction between EspM2 or SifA and nucleotide-free RhoA. Nuclear Magnetic Resonance Spectroscopy revealed that EspM2 has a similar fold to SifA and the guanine nucleotide exchange factor (GEF) effector SopE. EspM2 induced nucleotide exchange in RhoA but not in Rac1 or H-Ras, while SifA induced nucleotide exchange in none of them. Mutating W70 of the WxxxE motif or L118 and I127 residues, which surround the catalytic loop, affected the stability of EspM2. Substitution of Q124, located within the catalytic loop of EspM2, with alanine, greatly attenuated the RhoA GEF activity in vitro and the ability of EspM2 to induce stress fibres upon ectopic expression. These results suggest that binding of SifA to RhoA does not trigger nucleotide exchange while EspM2 is a unique Rho GTPase GEF. PMID:20039879

  10. Pilot Milt Thompson and the M2-F2 Lifting Body

    NASA Technical Reports Server (NTRS)

    1966-01-01

    Jay L. King, Joseph D. Huxman and Orion D. Billeter assist NASA research pilot Milt Thompson (on the ladder) into the cockpit of the M2-F2 lifting body research aircraft at the NASA Flight Research Center (now the Dryden Flight Research Center). The M2-F2 is attached to a wing pylon under the wing of NASA's B-52 mothership.

  11. Draft Genome Sequence of Bacillus ginsengihumi Strain M2.11 with Phytase Activity

    PubMed Central

    Suleimanova, Aliya D.; Boulygina, Eugenia A.; Kazakov, Sergey V.; Baranova, Daria S.; Akhmetova, Alina I.; Mardanova, Ayslu M.

    2015-01-01

    This paper announces the genome sequence of Bacillus ginsengihumi strain M2.11, which has been characterized as a strain which produces the enzyme with the ability to degrade phytase. The genome of the strain M2.11 is 3.7 Mb and harbors 3,082 coding sequences. PMID:26272561

  12. Performance oriented packaging report for charge, demolition, shaped, 15 pound, M2A4. Final report

    SciTech Connect

    Sniezek, F.M.

    1992-11-02

    This POP report is for the Charge, Demolition, Shaped, 15 Pound, M2A4 which is packaged 4 charges/Mil-B-2427 wood box. This report describes the results of testing conducted. Performance Oriented Packaging, POP, Charge, Demolition, Shaped, 15 Pound, M2A4, Mil-B-2427 Wood box.

  13. Regional distribution of M1, M2 and non-M1, non-M2 subtypes of muscarinic binding sites in rat brain

    SciTech Connect

    Ehlert, F.J.; Tran, L.P. )

    1990-12-01

    The distribution of subtypes of the muscarinic receptor in homogenates of the rat brain was investigated by measuring the competitive inhibition of the binding (3H)N-methylscopolamine by pirenzepine and AF-DX 116 (11((2-((diethylamino)methyl)-1-piperidinyl)acetyl)-5, 11-dihydro-6H-pyrido(2,3-b)(1,4)benzodiazepine-6-one). In most brain regions, the competitive binding curves for AF-DX 116 and pirenzepine were consistent with a two-site model. The dissociation constant of pirenzepine for its high-affinity site (M1 receptor) was approximately 10(-8) M, whereas the dissociation constant of AF-DX 116 for its high affinity site (M2 receptor) was approximately 10(-7) M. In many regions, particularly those in the forebrain, the sum of the densities of the M1 and M2 binding sites was substantially less than 100% of the total sites, indicating the existence of a third population of sites lacking high affinity for both pirenzepine and AF-DX 116. We have designated these latter sites as non-M1, non-M2 muscarinic receptors. In general, the densities of the M1 and non-M1, non-M2 binding sites were highest in cerebral cortex, corpus striatum and hippocampus, intermediate in thalamus and hypothalamus, and lowest in midbrain, medulla-pons and cerebellum, whereas the M2 binding site had a relatively low, uniform density throughout the brain. The binding capacity of (3H)N-methylquinuclidinyl benzilate was estimated to be 20 to 30% lower than that of (3H)quinuclidinyl benzilate in various regions of the forebrain, but not in more caudal regions of the brain where the two radioligands had approximately the same binding capacities.

  14. [Evaluation of Drug Interaction between S-1 and Warfarin].

    PubMed

    Yamamoto, Kaori; Suzuki, Shinya; Ikegawa, Kiwako; Nomura, Hisanaga; Fuse, Nozomu; Saito, Shinichiro

    2016-01-01

    Prolonged prothrombin time is observed in patients taking warfarin (WF) with a fluoropyrimidine, such as S-1. When WF is combined with S-1, the prothrombin time-international normalized ratio (PT-INR) and dose adjustment of WF should be closely monitored. To date, no clinical data have been reported in terms of the relation between temporal variation of PT-INR and its therapeutic range. In this study, we retrospectively collected patients' clinical data including PT-INR. We identified 21 patients receiving WF therapy before the start of S-1 treatment. Patient characteristics were male/female: 18/3, median age: 69 (range 48-81) years old, cancer of gastric/lung/pancreatic/other: 8/5/4/4, and history of deep vein thrombosis (DVT)/atrial fibrillation (AF)/cerebral infarction (CI)/other: 11/6/2/2. The PT-INR of 16 patients exceeded normal upper limits after taking S-1 with WF. The median time to exceed the PT-INR upper therapeutic range is 25 (range 3-77) days. Patients receiving WF anticoagulant therapy concomitant with S-1 should have their PT-INR closely monitored and WF doses adjusted accordingly.

  15. Degradation of G(M1) and G(M2) by mammalian sialidases.

    PubMed Central

    Li, S C; Li, Y T; Moriya, S; Miyagi, T

    2001-01-01

    In mammalian tissues, the pathway known for the catabolism of G(M1) [Galbeta3GalNAcbeta4(Neu5Acalpha3)Galbeta4GlcCer; where Cer is ceramide] is the conversion of this ganglioside into G(M2) [GalNAcbeta4(Neu5Acalpha3)Galbeta4GlcbetaCer] by beta-galactosidase followed by the conversion of G(M2) into G(M3) (Neu5Acalpha3Galbeta4GlcbetaCer) by beta-N-acetylhexosaminidase A (Hex A). However, the question of whether or not G(M1) and G(M2) can also be respectively converted into asialo-G(M1) (Galbeta3GalNAcbeta4Galbeta4GlcCer; G(A1)) and asialo-G(M2) (GalNAcbeta4Galbeta4GlcbetaCer, G(A2)) by mammalian sialidases has not been resolved. This is due to the fact that sialidases purified from mammalian tissues always contained detergents that interfered with the in vitro hydrolysis of G(M1) and G(M2) in the presence of an activator protein. The mouse model of human type B Tay-Sachs disease created by the disruption of the Hexa gene showed no neurological abnormalities, with milder clinical symptoms than the human counterpart, and the accumulation of G(M2) in the brains of affected mice was only limited to certain regions [Sango, Yamanaka, Hoffmann, Okuda, Grinberg, Westphal, McDonald, Crawley, Sandhoff, Suzuki and Proia (1995) Nat. Genet. 11, 170-176]. These results suggest the possible presence of an alternative catabolic pathway (the G(A2) pathway) in mouse to convert G(M2) into G(A2) by sialidase. To show the existence of this pathway, we have used recombinant mammalian cytosolic sialidase and membrane-associated sialidase to study the desialylation of G(M1) and G(M2). We found that the mouse membrane-bound sialidase was able to convert G(M1) and G(M2) into their respective asialo-derivatives in the presence of human or mouse G(M2) activator protein. The cytosolic sialidase did not exhibit this activity. Our results suggest that, in vivo, the stable NeuAc of G(M1) and G(M2) may be removed by the mammalian membrane-associated sialidase in the presence of G(M2) activator

  16. M2muscarinic receptors inhibit cell proliferation and migration in urothelial bladder cancer cells

    PubMed Central

    Pacini, Luca; De Falco, Elena; Di Bari, Maria; Coccia, Andrea; Siciliano, Camilla; Ponti, Donatella; Pastore, Antonio Luigi; Petrozza, Vincenzo; Carbone, Antonio; Tata, Ada Maria; Calogero, Antonella

    2014-01-01

    The role of muscarinic receptors in several diseases including cancer has recently emerged. To evaluate the hypothesis that muscarinic acetylcholine receptors may play a role in bladder cancer as well as in other tumor types, we investigated their expression in bladder tumor specimens. All examined samples expressed the M1, M2 and M3 receptor subtypes. We also found that the level of M2 transcripts, but not those of M1 or M3, significantly increased with the tumor histologic grade. In view of these results, we proceeded to investigate whether the M2 agonist Arecaidine had any effect on in vitro cell growth and migration of T24 cells, a bladder tumor cell line expressing the muscarinic receptors, including the M2 subtype. We observed that Arecaidine significantly reduced T24 and 5637 cell proliferation and migration in a concentration dependent manner. The silencing of M2 receptor by siRNA in T24 and 5637 cell lines showed the inability of Arecaidine (100 μM) to inhibit cell proliferation after 48 hours, whereas the use of M1 and M3 antagonists in T24 appeared not to counteract the Arecaidine effect, suggesting that the inhibition of cell proliferation was directly dependent on M2 receptor activation. These data suggest that M2 muscarinic receptors may play a relevant role in bladder cancer and represent a new attractive therapeutic target. PMID:25482946

  17. Respiratory syncytial virus M2-1 protein induces the activation of nuclear factor kappa B

    SciTech Connect

    Reimers, Kerstin . E-mail: reimers.kerstin@mh-hannover.de; Buchholz, Katja; Werchau, Hermann

    2005-01-20

    Respiratory syncytial virus (RSV) induces the production of a number of cytokines and chemokines by activation of nuclear factor kappa B (NF-{kappa}B). The activation of NF-{kappa}B has been shown to depend on viral replication in the infected cells. In this study, we demonstrate that expression of RSV M2-1 protein, a transcriptional processivity and anti-termination factor, is sufficient to activate NF-{kappa}B in A549 cells. Electromobility shift assays show increased NF-{kappa}B complexes in the nuclei of M2-1-expressing cells. M2-1 protein is found in nuclei of M2-1-expressing cells and in RSV-infected cells. Co-immunoprecipitations of nuclear extracts of M2-1-expressing cells and of RSV-infected cells revealed an association of M2-1 with Rel A protein. Furthermore, the activation of NF-{kappa}B depends on the C-terminus of the RSV M2-1 protein, as shown by NF-{kappa}B-induced gene expression of a reporter gene construct.

  18. Solidification Microstructure of AISI M2 High Speed Steel Manufactured by the Horizontal Continuous Casting Process

    NASA Astrophysics Data System (ADS)

    Zhou, X. F.; Fang, F.; Jiang, J. Q.

    2011-01-01

    In the present work, AISI M2 high speed steel is produced by the horizontal continuous casting process. The difference of solidification microstructure in ingots by mould casting and continuous casting has been examined by means of scanning electron microscope (SEM), electron back-scatter diffraction (EBSD), transmission electron microscope (TEM) and high resolution electron microscope (HREM). The results show that the as-cast structure consists of iron matrix and networks of M2C eutectic carbides, which are greatly refined in the continuous casting ingot compared to the case of ingot by mould casting. Meanwhile, the morphology of M2C eutectic carbides changes from the plate-like shape into the fibrous one. Micro-twining and stacking faults are observed in the plate-like M2C, whereas they are rarely identified in the fibrous M2C. Based on the characteristic of morphology and microstructure, it is expected that the plate-like M2C is a faceted phase while the fibrous M2C is a non-faceted phase.

  19. Kinked structures of isolated nicotinic receptor M2 helices: a molecular dynamics study.

    PubMed

    Sankararamakrishnan, R; Samsom, M S

    1994-12-01

    The pore-lining M2 helix of the nicotinic acetylcholine receptor exhibits a pronounced kink when the corresponding ion channel is in a closed conformation [N. Unwin (1993) Journal of Molecular Biology, Vol. 229, pp. 1101-1124]. We have performed molecular dynamics simulations of isolated 22-residue M2 helices in order to identify a possible molecular origin of this kink. In order to sample a wide range of conformational space, a simulated annealing protocol was used to generate five initial M2 helix structures, each of which was subsequently used as the basis of 300 ps MD simulations. Two helix sequences (M2 alpha and M2 delta) were studied in this manner, resulting in a total of ten 300 ps trajectories. Kinked helices present in the trajectories were identified and energy minimized to yield a total of five different stable kinked structures. For comparison, a similar molecular dynamics simulation of a Leu23 helix yielded no stable kinked structures. In four of the five kinked helices, the kink was stabilized by H bonds between the helix backbone and polar side-chain atoms. Comparison with data from the literature on site-directed mutagenesis of M2 residues suggests that such polar side-chain to main-chain H bonds may also contribute to kinking of M2 helices in the intact channel protein.

  20. M2BP inhibits HIV-1 virion production in a vimentin filaments-dependent manner

    PubMed Central

    Wang, Qin; Zhang, Xiaolin; Han, Yuling; Wang, Xinlu; Gao, Guangxia

    2016-01-01

    M2BP (also called 90K) is an interferon-stimulated gene product that is upregulated in HIV-1 infection. A recent study revealed that M2BP reduces the infectivity of HIV-1 by inhibiting the processing of the viral envelope protein. Here we report that in addition to reducing viral infectivity, M2BP inhibits HIV-1 virion production. We provide evidence showing that M2BP inhibits HIV-1 Gag trafficking to the plasma membrane in a vimentin-dependent manner. When vimentin filaments were collapsed by treating cells with acrylamide or by overexpression of a dominant-negative mutant of vimentin, M2BP inhibition of HIV-1 virion production was significantly relieved. We further show that M2BP interacts with both HIV-1 Gag and vimentin and thereby mediates their interactions. We propose that M2BP traps HIV-1 Gag to vimentin filaments to inhibit the transportation of HIV-1 Gag to the plasma membrane. These findings uncover a novel mechanism by which a host antiviral factor inhibits HIV-1 virion production. PMID:27604950

  1. HMGB1 enhances the protumoral activities of M2 macrophages by a RAGE-dependent mechanism.

    PubMed

    Rojas, Armando; Delgado-López, Fernando; Perez-Castro, Ramón; Gonzalez, Ileana; Romero, Jacqueline; Rojas, Israel; Araya, Paulina; Añazco, Carolina; Morales, Erik; Llanos, Jorge

    2016-03-01

    The monocyte-macrophage lineage shows a high degree of diversity and plasticity. Once they infiltrate tissues, they may acquire two main functional phenotypes, being known as the classically activated type 1 macrophages (M1) and the alternative activated type 2 macrophages (M2). The M1 phenotype can be induced by bacterial products and interferon-γ and exerts a cytotoxic effect on cancer cells. Conversely, the alternatively activated M2 phenotype is induced by Il-4/IL13 and promotes tumor cell growth and vascularization. Although receptor for advanced glycation end-products (RAGE) engagement in M1 macrophages has been reported by several groups to promote inflammation, nothing is known about the functionality of RAGE in M2 macrophages. In the current study, we demonstrate that RAGE is equally expressed in both macrophage phenotypes and that RAGE activation by high-mobility group protein box1 (HMGB1) promotes protumoral activities of M2 macrophages. MKN45 cells co-cultured with M2 macrophages treated with HMGB1 at different times displayed higher invasive abilities. Additionally, conditioned medium from HMGB1-treated M2 macrophages promotes angiogenesis in vitro. RAGE-targeting knockdown abrogates these activities. Overall, the present findings suggest that HMGB1 may contribute, by a RAGE-dependent mechanism, to the protumoral activities of the M2 phenotype.

  2. The chemotaxis of M1 and M2 macrophages is regulated by different chemokines.

    PubMed

    Xuan, Wenjuan; Qu, Qing; Zheng, Biao; Xiong, Sidong; Fan, Guo-Huang

    2015-01-01

    The homing of proinflammatory (M1) and the "alternatively activated" anti-inflammatory (M2) macrophages plays a different role in the process of inflammation. Chemokines are the major mediators of macrophage chemotaxis, but how they differentially regulate M1 and M2 macrophages remains largely unclear. In the present study, we attempted to screen chemokines that differentially induce chemotaxis of M1 and M2 macrophages and to explore the underlying mechanism. Among the 41 chemokines that specifically bind to 20 chemokine receptors, CCL19, CCL21, CCL24, CCL25, CXCL8, CXCL10, and XCL2 specifically induced M1 macrophage chemotaxis, whereas CCL7 induced chemotaxis of both M1 and M2 macrophages. Whereas the differential effects of these chemokines on M1/M2 macrophage chemotaxis could be attributable to the predominant expression of their cognate receptors on the macrophage subsets, CCR7, the receptor for CCL19/CCL21, appeared to be an exception. Immunoblot analysis indicated an equivalent level of CCR7 in the whole cell lysate of M1 and M2 macrophages, but CCL19 and CCL21 only induced M1 macrophage chemotaxis. Both immunoblot and confocal microscopy analyses demonstrated that CCR7 was predominantly expressed on the cell surface of M1 but in the cytosol of M2 macrophages before ligand stimulation. As a result, CCL19 or CCL21 induced activation of both MEK1-ERK1/2 and PI3K-AKT cascades in M1 but not in M2 macrophages. Intriguingly, CCL19/CCL21-mediated M1 macrophage chemotaxis was blocked by specific inhibition of PI3K rather than MEK1. Together, these findings suggest that recruitment of M1 and M2 macrophages is fine tuned by different chemokines with the involvement of specific signaling pathways.

  3. The S=1 Underscreened Anderson Lattice model for Uranium compounds

    NASA Astrophysics Data System (ADS)

    Thomas, C.; Simões, A. S. R.; Iglesias, J. R.; Lacroix, C.; Perkins, N. B.; Coqblin, B.

    2011-01-01

    Magnetic properties of uranium and neptunium compounds showing coexistence of the Kondo effect and ferromagnetic order are investigated within the degenerate Anderson Lattice Hamiltonian, describing a 5f2 electronic configuration with S = 1 spins. Through the Schrieffer-Wolff transformation, both an exchange Kondo interaction for the S = 1 f-spins and an effective f-band term are obtained, allowing to describe the coexistence of Kondo effect and ferromagnetic ordering and a weak delocalization of the 5f-electrons. We calculate the Kondo and Curie temperatures and we can account for the pressure dependence of the Curie temperature of UTe.

  4. Expression of the human muscarinic receptor gene m2 in Dictyostelium discoideum

    SciTech Connect

    Voith, G.; Dingermann, T.

    1995-11-01

    We have expressed a functional human muscarinic M2 receptor, under the control of the homologous discoidin I{gamma} promoter, in the cellular slime mold Dictyostelium discoideum. The use of a contact site A leader peptide ensured insertion of the newly synthesized receptor protein into the plasma membrane. Due to the characteristics of the discoidin I{gamma} promoter, the M2 receptor is expressed during late growth and early development. The heterologously expressed M2 receptors show binding characteristics similar to authentic receptors. Membranes as well as whole cells can be used in ligand binding assays. 36 refs., 4 figs.

  5. A humanized anti-M2 scFv shows protective in vitro activity against influenza

    SciTech Connect

    Bradbury, Andrew M; Velappan, Nileena; Schmidt, Jurgen G

    2008-01-01

    M2 is one of the most conserved influenza proteins, and has been widely prospected as a potential universal vaccine target, with protection predominantly mediated by antibodies. In this paper we describe the creation of a humanized single chain Fv from 14C2, a potent monoclonal antibody against M2. We show that the humanized scFv demonstrates similar activity to the parental mAb: it is able to recognize M2 in its native context on cell surfaces and is able to show protective in vitro activity against influenza, and so represents a potential lead antibody candidate for universal prophylactic or therapeutic intervention in influenza.

  6. Studies on Nanoparticle Based Avian Influenza Vaccines to Present Immunogenic Epitopes of the Virus with Concentration on Ectodomain of Matrix 2 (M2e) Protein

    NASA Astrophysics Data System (ADS)

    Babapoor Dighaleh, Sankhiros

    2011-12-01

    Avian influenza is an infectious disease of avian species caused by type A influenza viruses with a significant economic impact on the poultry industry. Vaccination is the main prevention strategy in many countries worldwide. However, available vaccines elicit antibodies against two major surface protein of the virus hemagglutinin (HA) and neuraminidase (NA), where they constantly change by point mutations. Influenza viruses can also easily undergo gene reassortment. Therefore, to protect chickens against new strain of avian influenza virus, as well as control and prevent virus spread among farms, new vaccines needed to be designed which is a tedious, time consuming and expensive. Recently, conserved regions of the influenza genome have been evaluated as possible universal vaccines to eliminate constant vaccine updates based on circulating virus. In this study, peptide nanotechnology was used to generate vaccine nanoparticles that carry the highly conserved external domain of matrix 2 protein (M2e). These nanoparticles presented M2e in monomeric or tetrameric forms, designated as PSC-M2e-CH and BNSC-M2eN-CH. respectively. First, to demonstrate immunogenicity of these nanoparticles, we measured anti-M2e antibody in chickens, particularly when a high dose was applied. Prior to vaccination-challenge study, the challenge dose were determined by oculonasal inoculation of 10 6 EID50 or 107.7 EID50 of low pathogenicity AI virus HSN2 followed by measuring cloacal and tracheal virus shedding. A biphasic virus shedding pattern was observed with two peaks of virus shedding at days 4 and 8 for both tracheal and cloacal swabs. The chickens infected with 107.7 EID50 had significant virus shedding as compared with 106 EID50. Based on results of mentioned studies, a vaccination-challenge study was conducted by using 75mug of each vaccine construct per inoculation (with and without adjuvant) and higher dose of virus for challenge. BN5C-M2e-CH with adjuvant significantly reduced the

  7. L5 – S1 Segmental Kinematics After Facet Arthroplasty

    PubMed Central

    Voronov, Leonard I.; Havey, Robert M.; Rosler, David M.; Sjovold, Simon G.; Rogers, Susan L.; Carandang, Gerard; Ochoa, Jorge A.; Yuan, Hansen; Webb, Scott

    2009-01-01

    Background Facet arthroplasty is a motion restoring procedure. It is normally suggested as an alternative to rigid fixation after destabilizing decompression procedures in the posterior lumbar spine. While previous studies have reported successful results in reproducing normal spine kinematics after facet replacement at L4-5 and L3-4, there are no data on the viability of facet replacement at the lumbosacral joint. The anatomy of posterior elements and the resulting kinematics at L5-S1 are distinctly different from those at superior levels, making the task of facet replacement at the lumbosacral level challenging. This study evaluated the kinematics of facet replacement at L5-S1. Methods Six human cadaveric lumbar spines (L1-S1, 46.7 ± 13.0 years) were tested in the following sequence: (1) intact (L1-S1), (2) complete laminectomy and bilateral facetectomy at L5-S1, and (3) implantation of TFAS-LS (Lumbosacral Total Facet Arthroplasty System, Archus Orthopedics, Redmond, Washington) at L5-S1 using pedicle screws. Specimens were tested in flexion (8Nm), extension (6Nm), lateral bending (LB, ± 6Nm), and axial rotation (AR, ± 5Nm). The level of significance was α = .017 after Bonferroni correction for three comparisons: (1) intact vs. destabilized, (2) destabilized vs. reconstructed, and (3) intact vs. reconstructed. Results Laminectomy-facetectomy at L5-S1 increased the L5-S1 angular range of motion (ROM) in all directions. Flexion-extension (F-E) ROM increased from 15.3 ± 2.9 to 18.7 ± 3.5 degrees (P < .017), LB from 8.2 ± 1.8 to 9.3 ± 1.6 degrees (P < .017), and AR from 3.7 ± 2.0 to 5.9 ± 1.8 degrees (P < .017). The facet arthroplasty system decreased ROM compared to the laminectomy-facetectomy condition in all tested directions (P < .017). The facet arthroplasty system restored the L5-S1 ROM to its intact levels in LB and AR (P > .017). F-E ROM after the facet arthroplasty system implantation was smaller than the intact value (10.1 ± 2.2 vs. 15.3 ± 2

  8. Development of transgenic lines of Eimeria tenella expressing M2e-enhanced yellow fluorescent protein (M2e-EYFP).

    PubMed

    Liu, Xianyong; Zou, Jun; Yin, Guangwen; Su, Huali; Huang, Xiaoxi; Li, Jianan; Xie, Li; Cao, Yingqiong; Cui, Yujuan; Suo, Xun

    2013-03-31

    Eimeria parasites are obligate intracellular apicomplexan protists that can cause coccidiosis, resulting in substantial economic losses in the poultry industry annually. As the component of anticoccidial vaccines, seven Eimeria spp. of chickens are characterized with potent immunogenicity. Whether genetically modified Eimeria spp. maintains this property or not needs to be verified. In this study, two identical transgenic lines of Eimeria tenella were developed by virtue of single sporocyst isolation from a stably transfected population expressing fused protein of M2 ectodomain of avian influenza virus (M2e) and enhanced yellow fluorescent protein (EYFP). The chromosomal integration and expression of M2e-EYFP were confirmed by Southern blot, plasmid rescue and Western blot analysis. We found that the reproduction of transgenic parasites was higher than that of the parental strain. Chickens challenged with wild type E. tenella after immunization with 200 oocysts of transgenic parasites had similar performance compared to those in non-immunized and non-challenged group. In another trial, the performance of transgenic parasite-immunized birds was also comparable to that of the Decoquinate Premix-treated chickens. These results suggest that this transgenic line of E. tenella is capable of inducing potent protection against homologous challenge as a live anticoccidial vaccine. Taking together, our study indicates that transgenic eimerian parasites have the potential to be developed as a vaccine vehicle for animal use in the future.

  9. Gut dysbiosis promotes M2 macrophage polarization and allergic airway inflammation via fungi-induced PGE₂.

    PubMed

    Kim, Yun-Gi; Udayanga, Kankanam Gamage Sanath; Totsuka, Naoya; Weinberg, Jason B; Núñez, Gabriel; Shibuya, Akira

    2014-01-15

    Although imbalances in gut microbiota composition, or "dysbiosis," are associated with many diseases, the effects of gut dysbiosis on host systemic physiology are less well characterized. We report that gut dysbiosis induced by antibiotic (Abx) treatment promotes allergic airway inflammation by shifting macrophage polarization in the lung toward the alternatively activated M2 phenotype. Adoptive transfer of alveolar macrophages derived from Abx-treated mice was sufficient to increase allergic airway inflammation. Abx treatment resulted in the overgrowth of a commensal fungal Candida species in the gut and increased plasma concentrations of prostaglandin E₂ (PGE₂), which induced M2 macrophage polarization in the lung. Suppression of PGE₂ synthesis by the cyclooxygenase inhibitors aspirin and celecoxib suppressed M2 macrophage polarization and decreased allergic airway inflammatory cell infiltration in Abx-treated mice. Thus, Abx treatment can cause overgrowth of particular fungal species in the gut and promote M2 macrophage activation at distant sites to influence systemic responses including allergic inflammation.

  10. Effects of orbital and spin current interference in E1 and M2 nuclear excitations

    SciTech Connect

    Goncharova, N. G.

    2015-12-15

    The interference of contributions from the orbital and spin currents to the E1 and M2 resonances is investigated. The results of the current interference analysis within the shell model are compared with the experimental data.

  11. MIS M2 initiation and termination link to the shallow CAS open and close?

    NASA Astrophysics Data System (ADS)

    Tan, Ning; Ramstein, Gilles; Dumas, Christophe; Contoux, Camille

    2016-04-01

    The Marine Isotope Stage M2 (3.264 -3.312 Ma) occurred just prior to the well documented warm mid-Pliocene (mPWP). With a 0.5‰ benthic foraminiferal δ180 shift (Lisiecki and Raymo, 2005), MIS M2 is thought to be a glacial comparable period associated with huge but uncertain sea-level records of 20-60m below present levels (Naish et al. 2009; Miller et al. 2012; Dwyer et al. 2009). However, the mechanism of M2 initiation and termination are still an enigma, since CO2 records were relatively higher than the Quaternary glaciation period and the minima summer insolation during M2 was stronger than other glacial periods. By inferring from data records, De Schepper (2013) proposed that the shallow open Central American Seaway (CAS) observed during M2 could play as a trigger in M2 initiation, then the closure of this shallow CAS resulted from M2 large ice sheet build-up terminates this glacial period. But this assumption has not been test by the model. In this study, we apply IPSL-CM5A Atmosphere-Ocean coupled General Circulation Model (AOGCM) and GRISLI ice sheet model to investigate mechanisms of M2 initiation and termination. We firstly investigate the role of "shallow open CAS" (De Schepper et al. 2013) on M2 initiation. In the mean time we also take into account the main forcing during M2, which includes astronomical parameters, Greenhouse gases and vegetation. Our results show that shallow open CAS plays an important role in reducing northward heat transport in Atlantic low latitudes by 0.05 - 0.1 PW, but it is not a key factor in NH ice sheet build-up; Astronomical parameters and CO2 concentration are essential to create a basic global cooling environment for M2 (cooling by ~3.65 K than mPWP); Cold vegetation replacement amplifies the cooling in north high latitudes by ~ 8 K, which finally allows large ice sheet building up in Northern Hemisphere (12.25 m sea level drop is simulated with considering ice sheet feedback on the climate). The simulated ice sheet

  12. Inhibition of Notch Signaling Attenuates Schistosomiasis Hepatic Fibrosis via Blocking Macrophage M2 Polarization

    PubMed Central

    Chen, Yixiong; Zheng, Shaojiang; Zheng, Liping; Weng, Zhihong

    2016-01-01

    Macrophages play a key role in the pathogenesis of liver granuloma and fibrosis in schistosomiasis. However, the underlying mechanisms have not been fully characterized. This study revealed that the macrophages infiltrating the liver tissues in a murine model of Schistosoma japonica infection exhibited M2 functional polarization, and Notch1/Jagged1 signaling was significantly upregulated in the M2 polarized macrophages in vivo and in vitro. Furthermore, the blockade of Notch signaling pathway by a γ–secretase inhibitor could reverse macrophage M2 polarization in vitro and alleviate liver granuloma and fibrosis in the murine model of schistosomiasis. These results implied that the Notch1/Jagged1 signaling-dependent M2 polarization of macrophages might play an important role in liver granuloma and fibrosis in schistosomiasis, and the inhibition of Notch1/Jagged1 signaling might provide a novel therapeutic approach to administrate patients with schistosomiasis. PMID:27875565

  13. Direct observation of the M2 phase with its Mott transition in a VO2 film

    NASA Astrophysics Data System (ADS)

    Kim, Hoon; Slusar, Tetiana V.; Wulferding, Dirk; Yang, Ilkyu; Cho, Jin-Cheol; Lee, Minkyung; Choi, Hee Cheul; Jeong, Yoon Hee; Kim, Hyun-Tak; Kim, Jeehoon

    2016-12-01

    In VO2, the explicit origin of the insulator-to-metal transition is still disputable between Peierls and Mott insulators. Along with the controversy, its second monoclinic (M2) phase has received considerable attention due to the presence of electron correlation in undimerized vanadium ions. However, the origin of the M2 phase is still obscure. Here, we study a granular VO2 film using conductive atomic force microscopy and Raman scattering. Upon the structural transition from monoclinic to rutile, we observe directly an intermediate state showing the coexistence of monoclinic M1 and M2 phases. The conductivity near the grain boundary in this regime is six times larger than that of the grain core, producing a donut-like landscape. Our results reveal an intra-grain percolation process, indicating that VO2 with the M2 phase is a Mott insulator.

  14. Secular changes of the M2 tide in the Gulf of Maine

    NASA Technical Reports Server (NTRS)

    Ray, Richard D.

    2005-01-01

    Analyses of long time series of hourly tide-gauge data at four stations in the Gulf of Maine reveal that the amplitude of the M2 tide underwent a nearly linear secular increase throughout most of the twentieth century. In the early 1980s, however, the amplitude of M2 abruptly dropped. Sea level changes alone appear inadequate to explain either the long-term trend or the recent trend discontinuity. Tidal models that account for Holocene sea level rise do predict an amplification of M2, but much smaller than the currently observed trends. Nor do recent annual mean sea levels correlate with the recent trend discontinuity. Some unknown fraction of the open Atlantic may be similarly affected, since the M2 discontinuity, but not the long-term secular increase in the tide, is evident also at Halifax.

  15. Excitation of nutation by the global radiational S1 tide

    NASA Astrophysics Data System (ADS)

    Schindelegger, M.; Salstein, D. A.; Einspigel, D.; Boehm, J.

    2014-12-01

    Cyclic mass redistributions in the atmosphere and oceans related to the global radiational S1 tide elicit seasonal perturbations of Earth's nutation at a level of 0.1 mas (milliarcseconds). The present study provides an up-to-date assessment of these excitation effects on the basis of 10-year surface and isobaric level data from three, previously unavailable global atmospheric reanalysis systems. We retrieve numerical values of in- and out-of-phase nutation corrections for seasonally modulated S1 variations and indicate how model improvements, specifically in terms of the representation of tidal oscillations, lead to different estimates with respect to earlier reanalyses. Motion term signals in nutation display a close agreement across all probed datasets, whereas larger disparities remain among mass term excitation estimates due to their dependency on small-scale diurnal surface pressure oscillations. A simple time-stepping model for barotropic ocean dynamics, based on the shallow water equations and driven by air pressure tide climatologies, represents an appropriate means to determine global S1 estimates of sea level heights and currents that are consistent with the respective forcing fields from each reanalysis. We address the intricacies of constructing such a model and compare our preliminary oceanic angular momentum solutions to those from more established hydrodynamic forward integrations. The combined influence of the S1 tide on Earth's nutation, associated with both atmosphere and ocean dynamics, is found to yield a rough agreement with observations from geodetic VLBI (Very Long Baseline Interferometry) measurements.

  16. Continuation maintenance therapy with S-1 in chemotherapy-naïve patients with advanced squamous cell lung cancer.

    PubMed

    Suzuki, Seiichiro; Karayama, Masato; Inui, Naoki; Fujisawa, Tomoyuki; Enomoto, Noriyuki; Nakamura, Yutaro; Kuroishi, Shigeki; Matsuda, Hiroyuki; Yokomura, Koshi; Koshimizu, Naoki; Toyoshima, Mikio; Imokawa, Shiro; Asada, Kazuhiro; Masuda, Masafumi; Yamada, Takashi; Watanabe, Hiroshi; Suda, Takafumi

    2016-08-01

    Objectives Maintenance therapy is a standard therapeutic strategy in non-squamous non-small-cell lung cancer. However, there is no consensus regarding the benefit of maintenance therapy for patients with squamous cell lung cancer. We assessed maintenance therapy with S-1, an oral fluoropyrimidine agent, following induction therapy with carboplatin and S-1 in patients with squamous cell lung cancer. Methods In this phase II trial, chemotherapy-naïve patients with squamous cell lung cancer were enrolled to induction therapy with four cycles of carboplatin (at an area under the curve of 5 on day 1) and S-1 (80 mg/m(2)/day on days 1-14) in a 28-day cycle. Patients who achieved disease control after induction therapy received maintenance therapy with S-1 in a 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival after administration of maintenance therapy. Results Fifty-one patients were enrolled in the study. The median progression-free survival from the start of maintenance therapy was 3.0 months (95 % confidence interval, 2.5-3.5). The most common toxicities associated with maintenance therapy were anemia, thrombocytopenia, and fatigue, but they were not severe. Conclusion S-1 maintenance therapy might be a feasible treatment option in patients with squamous cell lung cancer.

  17. Presenting Influenza A M2e Antigen on Recombinant Spores of Bacillus subtilis

    PubMed Central

    Obuchowski, Michał; Nidzworski, Dawid

    2016-01-01

    Effective vaccination against influenza virus infection is a serious problem mainly due to antigenic variability of the virus. Among many of investigated antigens, the extracellular domain of the M2 protein (M2e) features high homology in all strains of influenza A viruses and antibodies against M2e and is protective in animal models; this makes it a potential candidate for generation of a universal influenza vaccine. However, due to the low immunogenicity of the M2e, formulation of a vaccine based on this antigen requires some modification to induce effective immune responses. In this work we evaluated the possible use of Bacillus subtilis spores as a carrier of the Influenza A M2e antigen in mucosal vaccination. A tandem repeat of 4 consensus sequences coding for human—avian—swine—human M2e (M2eH-A-S-H) peptide was fused to spore coat proteins and stably exposed on the spore surface, as demonstrated by the immunostaining of intact, recombinant spores. Oral immunization of mice with recombinant endospores carrying M2eH-A-S-H elicited specific antibody production without the addition of adjuvants. Bacillus subtilis endospores can serve as influenza antigen carriers. Recombinant spores constructed in this work showed low immunogenicity although were able to induce antibody production. The System of influenza antigen administration presented in this work is attractive mainly due to the omitting time-consuming and cost-intensive immunogen production and purification. Therefore modification should be made to increase the immunogenicity of the presented system. PMID:27902762

  18. M1/M2-macrophage phenotypes regulate renal calcium oxalate crystal development

    PubMed Central

    Taguchi, Kazumi; Okada, Atsushi; Hamamoto, Shuzo; Unno, Rei; Moritoki, Yoshinobu; Ando, Ryosuke; Mizuno, Kentaro; Tozawa, Keiichi; Kohri, Kenjiro; Yasui, Takahiro

    2016-01-01

    In our previous report, M2-macrophage (Mφs) deficient mice showed increased renal calcium oxalate (CaOx) crystal formation; however, the role of Mφs-related-cytokines and chemokines that affect kidney stone formation remains unknown. Here, we investigated the role of M1/M2s in crystal development by using in vitro and in vivo approaches. The crystal phagocytic rate of bone marrow-derived M2Mφs was higher than that of bone marrow-derived Mφs and M1Mφs and increased on co-culture with renal tubular cells (RTCs). However, the amount of crystal attachment on RTCs reduced on co-culture with M2Mφs. In six hyperoxaluric C57BL/6J mice, M1Mφ transfusion and induction by LPS and IFN-γ facilitated renal crystal formation, whereas M2Mφ transfusion and induction by IL-4 and IL-13 suppressed renal crystal formation compared with the control. These M2Mφ treatments reduced the expression of crystal-related genes, such as osteopontin and CD44, whereas M1Mφ treatment increased the expression of pro-inflammatory and adhesion-related genes such as IL-6, inducible NOS, TNF-α, C3, and VCAM-1. The expression of M2Mφ-related genes was lower whereas that of M1Mφ-related genes was higher in papillary tissue of CaOx stone formers. Overall, our results suggest that renal crystal development is facilitated by M1Mφs, but suppressed by M2Mφs. PMID:27731368

  19. Enhanced M1/M2 macrophage ratio promotes orthodontic root resorption.

    PubMed

    He, D; Kou, X; Luo, Q; Yang, R; Liu, D; Wang, X; Song, Y; Cao, H; Zeng, M; Gan, Y; Zhou, Y

    2015-01-01

    Mechanical force-induced orthodontic root resorption is a major clinical challenge in orthodontic treatment. Macrophages play an important role in orthodontic root resorption, but the underlying mechanism remains unclear. In this study, we examined the mechanism by which the ratio of M1 to M2 macrophage polarization affects root resorption during orthodontic tooth movement. Root resorption occurred when nickel-titanium coil springs were applied on the upper first molars of rats for 3 to 14 d. Positively stained odontoclasts or osteoclasts with tartrate-resistant acid phosphatase were found in resorption areas. Meanwhile, M1-like macrophages positive for CD68 and inducible nitric oxide synthase (iNOS) persistently accumulated on the compression side of periodontal tissues. In addition, the expressions of the M1 activator interferon-γ and the M1-associated pro-inflammatory cytokine tumor necrosis factor (TNF)-α were upregulated on the compression side of periodontal tissues. When the coil springs were removed at the 14th day after orthodontic force application, root resorption was partially rescued. The number of CD68(+)CD163(+) M2-like macrophages gradually increased on the compression side of periodontal tissues. The levels of M2 activator interleukin (IL)-4 and the M2-associated anti-inflammatory cytokine IL-10 also increased. Systemic injection of the TNF-α inhibitor etanercept or IL-4 attenuated the severity of root resorption and decreased the ratio of M1 to M2 macrophages. These data imply that the balance between M1 and M2 macrophages affects orthodontic root resorption. Root resorption was aggravated by an enhanced M1/M2 ratio but was partially rescued by a reduced M1/M2 ratio.

  20. Late-stage optimization of a tercyclic class of S1P3-sparing, S1P1 receptor agonists.

    PubMed

    Horan, Joshua C; Kuzmich, Daniel; Liu, Pingrong; DiSalvo, Darren; Lord, John; Mao, Can; Hopkins, Tamara D; Yu, Hui; Harcken, Christian; Betageri, Raj; Hill-Drzewi, Melissa; Patenaude, Lori; Patel, Monica; Fletcher, Kimberly; Terenzzio, Donna; Linehan, Brian; Xia, Heather; Patel, Mita; Studwell, Debbie; Miller, Craig; Hickey, Eugene; Levin, Jeremy I; Smith, Dustin; Kemper, Raymond A; Modis, Louise K; Bannen, Lynne C; Chan, Diva S; Mac, Morrison B; Ng, Stephanie; Wang, Yong; Xu, Wei; Lemieux, René M

    2016-01-15

    Poor solubility and cationic amphiphilic drug-likeness were liabilities identified for a lead series of S1P3-sparing, S1P1 agonists originally developed from a high-throughput screening campaign. This work describes the subsequent optimization of these leads by balancing potency, selectivity, solubility and overall molecular charge. Focused SAR studies revealed favorable structural modifications that, when combined, produced compounds with overall balanced profiles. The low brain exposure observed in rat suggests that these compounds would be best suited for the potential treatment of peripheral autoimmune disorders.

  1. Opposite Effects of M1 and M2 Macrophage Subtypes on Lung Cancer Progression.

    PubMed

    Yuan, Ang; Hsiao, Yi-Jing; Chen, Hsuan-Yu; Chen, Huei-Wen; Ho, Chao-Chi; Chen, Yu-Yun; Liu, Yi-Chia; Hong, Tsai-Hsia; Yu, Sung-Liang; Chen, Jeremy J W; Yang, Pan-Chyr

    2015-09-24

    Macrophages in a tumor microenvironment have been characterized as M1- and M2-polarized subtypes. Here, we discovered the different macrophages' impacts on lung cancer cell A549. The M2a/M2c subtypes promoted A549 invasion and xenograft tumor growth. The M1 subtype suppressed angiogenesis. M1 enhanced the sensitivity of A549 to cisplatin and decreased the tube formation activity and cell viability of A549 cells by inducing apoptosis and senescence. Different macrophage subtypes regulated genes involved in the immune response, cytoskeletal remodeling, coagulation, cell adhesion, and apoptosis pathways in A549 cells, which was a pattern that correlated with the altered behaviors of the A549 cells. Furthermore, we found that the identified M1/M2 gene signatures were significantly correlated with the extended overall survival of lung cancer patients. These results suggest that M1/M2 gene expression signature may be used as a prognostic indicator for lung cancer patients, and M1/M2 polarization may be a target of investigation of immune-modulating therapies for lung cancer in the future.

  2. Muscarinic cholinergic receptor (M2) plays a crucial role in the development of myopia in mice.

    PubMed

    Barathi, Veluchamy A; Kwan, Jia Lin; Tan, Queenie S W; Weon, Sung Rhan; Seet, Li Fong; Goh, Liang Kee; Vithana, Eranga N; Beuerman, Roger W

    2013-09-01

    Myopia is a huge public health problem worldwide, reaching the highest incidence in Asia. Identification of susceptible genes is crucial for understanding the biological basis of myopia. In this paper, we have identified and characterized a functional myopia-associated gene using a specific mouse-knockout model. Mice lacking the muscarinic cholinergic receptor gene (M2; also known as Chrm2) were less susceptible to lens-induced myopia compared with wild-type mice, which showed significantly increased axial length and vitreous chamber depth when undergoing experimental induction of myopia. The key findings of this present study are that the sclera of M2 mutant mice has higher expression of collagen type I and lower expression of collagen type V than do wild-type mice and mice that are mutant for other muscarinic subtypes, and, therefore, M2 mutant mice were resistant to the development of experimental myopia. Pharmacological blockade of M2 muscarinic receptor proteins retarded myopia progression in the mouse. These results suggest for the first time a role of M2 in growth-related changes in extracellular matrix genes during myopia development in a mammalian model. M2 receptor antagonists might thus provide a targeted therapeutic approach to the management of this refractive error.

  3. Influenza M2 envelope protein augments avian influenza hemagglutinin pseudotyping of lentiviral vectors.

    PubMed

    McKay, T; Patel, M; Pickles, R J; Johnson, L G; Olsen, J C

    2006-04-01

    Lentivirus-based gene transfer has the potential to efficiently deliver DNA-based therapies into non-dividing epithelial cells of the airway for the treatment of lung diseases such as cystic fibrosis. However, significant barriers both to lung-specific gene transfer and to production of lentivirus vectors must be overcome before these vectors can be routinely used for applications to the lung. In this study, we investigated whether the ability to produce lentiviral vectors pseudotyped with fowl plague virus hemagglutinin (HA) could be improved by co-expression of influenza virus M2 in vector-producing cells. We found that M2 expression led to a 10-30-fold increase in production of HA-pseudotyped lentivirus vectors based upon equine infectious anemia virus (EIAV) or human immunodeficiency virus type 1 (HIV-1). Experiments using the M2 inhibitor amantadine and a drug-resistant mutant of M2 established that the ion channel activity of M2 was important for M2-dependent augmentation of vector production. Furthermore, the neuraminidase activity necessary for particle release from producer cells could also be incorporated into producer cells by co-expression of influenza NA cDNA. Lentiviral vectors pseudotyped with influenza envelope proteins were able to efficiently transduce via the apical membrane of polarized mouse tracheal cultures in vitro as well as mouse tracheal epithelia in vivo.

  4. Monocyte Differentiation towards Protumor Activity Does Not Correlate with M1 or M2 Phenotypes

    PubMed Central

    Chimal-Ramírez, G. Karina; Espinoza-Sánchez, Nancy Adriana; Chávez-Sánchez, Luis; Arriaga-Pizano, Lourdes

    2016-01-01

    Macrophages facilitate breast cancer progression. Macrophages were initially classified as M1 or M2 based on their distinct metabolic programs and then expanded to include antitumoral (M1) and protumoral (M2) activities. However, it is still uncertain what markers define the pro- and antitumoral phenotypes and what conditions lead to their formation. In this study, monocytic cell lines and primary monocytes were subjected to commonly reported protocols of M1/M2 polarization and conditions known to engage monocytes into protumoral functions. The results showed that only IDO enzyme and CD86 M1 markers were upregulated correlating with M1 polarization. TNF-α, CCR7, IL-10, arginase I, CD36, and CD163 were expressed indistinguishably from M1 or M2 polarization. Similarly, protumoral engaging resulted in upregulation of both M1 and M2 markers, with conditioned media from the most aggressive breast cancer cell line promoting the greatest changes. In spite of the mixed phenotype, M1-polarized macrophages exhibited the highest expression/secretion of inflammatory mediators, many of which have previously been associated with breast cancer aggressiveness. These data argue that although the existence of protumoral macrophages is unquestionable, their associated phenotypes and the precise conditions driving their formation are still unclear, and those conditions may need both M1 and M2 stimuli. PMID:27376091

  5. Mechanism of influenza A M2 transmembrane domain assembly in lipid membranes

    PubMed Central

    Georgieva, Elka R.; Borbat, Peter P.; Norman, Haley D.; Freed, Jack H.

    2015-01-01

    M2 from influenza A virus functions as an oligomeric proton channel essential for the viral cycle, hence it is a high-priority pharmacological target whose structure and functions require better understanding. We studied the mechanism of M2 transmembrane domain (M2TMD) assembly in lipid membranes by the powerful biophysical technique of double electron-electron resonance (DEER) spectroscopy. By varying the M2TMD-to-lipid molar ratio over a wide range from 1:18,800 to 1:160, we found that M2TMD exists as monomers, dimers, and tetramers whose relative populations shift to tetramers with the increase of peptide-to-lipid (P/L) molar ratio. Our results strongly support the tandem mechanism of M2 assembly that is monomers-to-dimer then dimers-to-tetramer, since tight dimers are abundant at small P/L’s, and thereafter they assemble as dimers of dimers in weaker tetramers. The stepwise mechanism found for a single-pass membrane protein oligomeric assembly should contribute to the knowledge of the association steps in membrane protein folding. PMID:26190831

  6. [Combination Chemotherapy Using Oxaliplatin plus S-1 for Well-Advanced Gastric Cancer].

    PubMed

    Saito, Hiroyuki; Suematsu, Yuki; Yamagishi, Shunsuke; Takahashi, Miyuki; Nakayama, Mao; Fukabori, Michiko; Morita, Akihiko; Wakabayashi, Kazuhiko; Itoh, Yutaka

    2016-11-01

    We studied the clinical efficacy of pre-operative combination chemotherapy using S-1 plus oxaliplatin for advanced gastric cancer. Four patients hadclinical Stage IV disease, 1 patient had clinical Stage III C disease, 2 patients had clinical Stage III B disease, and 1 patient had clinical Stage III A disease. The patients received 2-8 courses of oxaliplatin(130mg/m2)on day 1, andS -1 on days 1-14 every 3 weeks. The response rate was 56%(5 PR, 1 PD, and2 SD), andthe disease control rate was 88%. Toxicities were Grade 2 anemia, Grade 1 peripheral neuropathy, Grade 1 fatigue, and anorexia. Five of the 8 patients underwent R0 surgery after SOX chemotherapy, and no severe complications occurred. Histological responses were Grade 3 for 2 cases, Grade 2 for 2 cases, andGrad e 1a for 1 case. The SOX regimen showeda high objective tumor response, andis one of the promising regimens in the neoadjuvant setting for well-advanced gastric cancer.

  7. Efficacy and safety of oxaliplatin, bevacizumab and oral S-1 for advanced recurrent colorectal cancer.

    PubMed

    Suzuki, Shuji; Shimazaki, Jiro; Morishita, Keiichi; Koike, Nobusada; Harada, Nobuhiko; Hayashi, Tsuneo; Suzuki, Mamoru

    2016-10-01

    The aim of this study was to evaluate the efficacy and safety of co-administration of oral S-1 and oxaliplatin (SOX) in combination with bevacizumab (bev) in patients with advanced recurrent colorectal cancer. A retrospective study of 36 patients with advanced recurrent colorectal cancer was performed, of whom 27 received first-line and 9 received second-line SOX+bev chemotherapy between 2010 and 2013 at the Hachioji Digestive Disease Hospital (Hachioji, Japan). The SOX+bev regimen consisted of administration of intravenous oxaliplatin (85 mg/m(2)) on days 1 and 14, bevacizumab (5 mg/kg) on day 1, and co-administration of oral S-1 twice daily on days 1-14. The drug regimen was repeated every 4 weeks. SOX+bev treatment was associated with a response rate of 45.2%, a disease control rate of 71%, and a median progression-free survival (PFS) and overall survival (OS) of 9.9 and 21.9 months, respectively. Patients who received first-line chemotherapy benefited from treatment in terms of prolonged PFS (13.8 months) and OS (28.2 months). Grade 3/4 adverse events were infrequent and included anaemia, thrombocytopenia, anorexia, diarrhea, sensory neuropathy, increased aspartate aminotransferase level and skin rash. In conclusion, SOX+bev therapy was found to be feasible and safe for patients with advanced and recurrent colorectal cancer.

  8. Extinction of 10.6 μm laser radiation by free electrons in an argon filamentary discharge at atmospheric pressure

    NASA Astrophysics Data System (ADS)

    Park, S. H.; Yang, H. J.; Mironov, A. E.; Park, S.-J.; Eden, J. G.

    2016-09-01

    Experiments will be described in which the extinction of 10.6 μm photons by free electrons in a single filamentary discharge is being studied. The extinction ranges from 3 to 10 percent over a path length of 1 cm, depending on the argon flow rate. The temporally- and spatially-averaged electron density in the filament is approximately 1015 cm-3, as determined by Stark broadening of the hydrogen alpha (656.28 nm) and argon I (696.54 nm) lines. Calculations indicate that the observed extinction of 10.6 μm is attributable to a combination of inverse bremsstrahlung and a negative lens effect, and experimental results will be compared to theoretical calculations based on Boltzmann's equation. The potential application of such high electron density plasmas to studies of fundamental plasma phenomena, as well as optical applications will be discussed.

  9. Constitutive Activation of an Anthocyanin Regulatory Gene PcMYB10.6 Is Related to Red Coloration in Purple-Foliage Plum

    PubMed Central

    Zhou, Hui; Wang, Lu; Deng, Xianbao; Han, Yuepeng

    2015-01-01

    Cherry plum is a popular ornamental tree worldwide and most cultivars are selected for purple foliage. Here, we report the investigation of molecular mechanism underlying red pigmentation in purple-leaf plum ‘Ziyeli’ (Prunus cerasifera Ehrhar f. atropurpurea (Jacq.) Rehd.), which shows red color pigmentation in fruit (flesh and skin) and foliage. Six anthocyanin-activating MYB genes, designated PcMYB10.1 to PcMYB10.6, were isolated based on RNA-Seq data from leaves of cv. Ziyeli. Of these PcMYB10 genes, five (PcMYB10.1 through PcMYB10.5) show distinct spatial and temporal expression patterns, while the PcMYB10.6 gene is highly expressed in all the purple-coloured organs of cv. Ziyeli. Constitutive activation of PcMYB10.6 is closely related to red pigmentation in the leaf, fruit (flesh and skin), and sepal. However, the PcMYB10.6 activation cannot induce red pigmentation in the petal of cv. Ziyeli during late stages of flower development due to due to a lack of expression of PcUFGT. The inhibition of red pigmentation in the petal of cherry plum could be attributed to the high-level expression of PcANR that directs anthocyanidin flux to proanthocyanidin biosynthesis. In addition, PcMYB10.2 is highly expressed in fruit and sepal, but its expression cannot induce red pigmentation. This suggests the PcMYB10 gene family in cherry plum may have diverged in function and PcMYB10.2 plays little role in the regulation of red pigmentation. Our study provides for the first time an example of constitutive activation of an anthocyanin-activating MYB gene in Prunus although its underlying mechanism remains unclear. PMID:26247780

  10. Constitutive Activation of an Anthocyanin Regulatory Gene PcMYB10.6 Is Related to Red Coloration in Purple-Foliage Plum.

    PubMed

    Gu, Chao; Liao, Liao; Zhou, Hui; Wang, Lu; Deng, Xianbao; Han, Yuepeng

    2015-01-01

    Cherry plum is a popular ornamental tree worldwide and most cultivars are selected for purple foliage. Here, we report the investigation of molecular mechanism underlying red pigmentation in purple-leaf plum 'Ziyeli' (Prunus cerasifera Ehrhar f. atropurpurea (Jacq.) Rehd.), which shows red color pigmentation in fruit (flesh and skin) and foliage. Six anthocyanin-activating MYB genes, designated PcMYB10.1 to PcMYB10.6, were isolated based on RNA-Seq data from leaves of cv. Ziyeli. Of these PcMYB10 genes, five (PcMYB10.1 through PcMYB10.5) show distinct spatial and temporal expression patterns, while the PcMYB10.6 gene is highly expressed in all the purple-coloured organs of cv. Ziyeli. Constitutive activation of PcMYB10.6 is closely related to red pigmentation in the leaf, fruit (flesh and skin), and sepal. However, the PcMYB10.6 activation cannot induce red pigmentation in the petal of cv. Ziyeli during late stages of flower development due to due to a lack of expression of PcUFGT. The inhibition of red pigmentation in the petal of cherry plum could be attributed to the high-level expression of PcANR that directs anthocyanidin flux to proanthocyanidin biosynthesis. In addition, PcMYB10.2 is highly expressed in fruit and sepal, but its expression cannot induce red pigmentation. This suggests the PcMYB10 gene family in cherry plum may have diverged in function and PcMYB10.2 plays little role in the regulation of red pigmentation. Our study provides for the first time an example of constitutive activation of an anthocyanin-activating MYB gene in Prunus although its underlying mechanism remains unclear.

  11. Prediction of M2 tidal surface currents by a global baroclinic ocean model and evaluation using observed drifter trajectories

    NASA Astrophysics Data System (ADS)

    Kodaira, Tsubasa; Thompson, Keith R.; Bernier, Natacha B.

    2016-08-01

    Global M2 tidal surface currents are predicted using a global baroclinic ocean model with horizontal grid spacing of 1/12° and 19 z-levels in the vertical. After first showing the predicted tidal elevations are in reasonable agreement with observations made by bottom pressure recorders and altimeters, the predicted tidal surface currents are evaluated by comparing them with independent estimates based on observed drifter trajectories. Both predicted and observed tidal surface currents can exceed 0.1 m s-1 in the deep ocean. Internal tides are shown to make a significant contribution to the predicted tidal surface currents. Phase locking of the surface and internal tides causes spatial changes in the predicted tidal surface currents that vary with approximately the same wavenumber as that of the lowest mode internal tide. Qualitatively similar, small-scale variations are also detected in the observed estimates but the variations do not line up exactly with the predictions. Possible explanations for the mismatch are given. The seasonal variation of M2 tidal surface currents, and the energy conversion rate from surface to internal tides, is also predicted by initializing, and restoring, the model to an observed seasonal climatology of temperature and salinity. Compared to tidal elevation, the seasonal change of tidal surface current can be large (order 10% for each hemisphere). It is caused by seasonal variations in the vertical structure of the baroclinic modes and the energy conversion rate. In the vicinity of major bathymetric features, the seasonal variation of second and higher order modes can be much larger (up to 50%).

  12. Comparing the use of 4.6 um lasers versus 10.6 um lasers for mitigating damage site growth on fused silica surfaces

    SciTech Connect

    Yang, S T; Matthews, M J; Elhadj, S; Cooke, D; Guss, G M; Draggoo, V G; Wegner, P J

    2010-10-21

    The advantage of using mid-infrared (IR) 4.6 {micro}m lasers, versus far-infrared 10.6 {micro}m lasers, for mitigating damage growth on fused silica is investigated. In contrast to fused silica's high absorption at 10.6 {micro}m, silica absorption at 4.6 {micro}m is two orders of magnitude less. The much reduced absorption at 4.6 {micro}m enables deep heat penetration into fused silica when it is heated using the mid-IR laser, which in turn leads to more effective mitigation of damage sites with deep cracks. The advantage of using mid-IR versus far-IR laser for damage growth mitigation under non-evaporative condition is quantified by defining a figure of merit (FOM) that relates the crack healing depth to laser power required. Based on our FOM, we show that for damage cracks up to at least 500 {micro}m in depth, mitigation using a 4.6 {micro}m mid-IR laser is more efficient than mitigation using a 10.6 {micro}m far-IR laser.

  13. Lipopolysaccharide preconditioning facilitates M2 activation of resident microglia after spinal cord injury.

    PubMed

    Hayakawa, Kentaro; Okazaki, Rentaro; Morioka, Kazuhito; Nakamura, Kozo; Tanaka, Sakae; Ogata, Toru

    2014-12-01

    The inflammatory response following spinal cord injury (SCI) has both harmful and beneficial effects; however, it can be modulated for therapeutic benefit. Endotoxin/lipopolysaccharide (LPS) preconditioning, a well-established method for modifying the immune reaction, has been shown to attenuate damage induced by stroke and brain trauma in rodent models. Although such effects likely are conveyed by tissue-repairing functions of the inflammatory response, the mechanisms that control the effects have not yet been elucidated. The present study preconditioned C57BL6/J mice with 0.05 mg/kg of LPS 48 hr before inducing contusion SCI to investigate the effect of LPS preconditioning on the activation of macrophages/microglia. We found that LPS preconditioning promotes the polarization of M1/M2 macrophages/microglia toward an M2 phenotype in the injured spinal cord on quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemical analyses. Flow cytometric analyses reveal that LPS preconditioning facilitates M2 activation in resident microglia but not in infiltrating macrophages. Augmented M2 activation was accompanied by vascularization around the injured lesion, resulting in improvement in both tissue reorganization and functional recovery. Furthermore, we found that M2 activation induced by LPS preconditioning is regulated by interleukin-10 gene expression, which was preceded by the transcriptional activation of interferon regulatory factor (IRF)-3, as demonstrated by Western blotting and an IRF-3 binding assay. Altogether, our findings demonstrate that LPS preconditioning has a therapeutic effect on SCI through the modulation of M1/M2 polarization of resident microglia. The present study suggests that controlling M1/M2 polarization through endotoxin signal transduction could become a promising therapeutic strategy for various central nervous system diseases. © 2014 Wiley Periodicals, Inc.

  14. Expression patterns of ubiquitin conjugating enzyme UbcM2 during mouse embryonic development.

    PubMed

    Yanjiang, Xing; Hongjuan, He; Tiantian, Gu; Yan, Zhang; Zhijun, Huang; Qiong, Wu

    2012-01-01

    Ubiquitin conjugating enzyme UbcM2 (Ubiquitin-conjugating enzymes from Mice, the number reveals the identification order) has been implicated in many critical processes, such like growth-inhibiting, mediating cell proliferation and regulation of some transcription factor, but the expression profile during mouse embryo development remains unclear. Hereby, during mid-later embryonic stage, the expression patterns of UbcM2 were examined using in situ hybridization and quantitative real-time PCR (qRT-PCR). The signals were significantly intense in central nervous system and skeletal system, weak in tongue, heart, lung, liver, and kidney. In the central nervous system, UbcM2 was principally expressed in thalamus, external germinal layer of cerebellum (EGL), mitral cell layer of olfactory bulb, hippocampus, marginal zone and ventricular zone of cerebral cortex, and spinal cord. In the skeletal system, UbcM2 was primarily expressed in proliferating cartilage. Furthermore, qRT-PCR analysis displayed that the expression of UbcM2 was ubiquitous at E15.5, most prominent in brain, weaker in lung liver and kidney, accompanied by the lowest level in tongue and heart. During brain development, the expression level of UbcM2 first ascended and then decreased from E12.5 to E18.5, the peak of which sustained starting at E14.5 until E16.5. Together, these results suggest that UbcM2 may play potential roles in the development of mouse diverse tissues and organs, particularly in the development of brain and skeleton.

  15. The Global S_1 Tide in Earth's Nutation

    NASA Astrophysics Data System (ADS)

    Schindelegger, Michael; Einšpigel, David; Salstein, David; Böhm, Johannes

    2016-05-01

    Diurnal S_1 tidal oscillations in the coupled atmosphere-ocean system induce small perturbations of Earth's prograde annual nutation, but matching geophysical model estimates of this Sun-synchronous rotation signal with the observed effect in geodetic Very Long Baseline Interferometry (VLBI) data has thus far been elusive. The present study assesses the problem from a geophysical model perspective, using four modern-day atmospheric assimilation systems and a consistently forced barotropic ocean model that dissipates its energy excess in the global abyssal ocean through a parameterized tidal conversion scheme. The use of contemporary meteorological data does, however, not guarantee accurate nutation estimates per se; two of the probed datasets produce atmosphere-ocean-driven S_1 terms that deviate by more than 30 μ as (microarcseconds) from the VLBI-observed harmonic of -16.2+i113.4 μ as. Partial deficiencies of these models in the diurnal band are also borne out by a validation of the air pressure tide against barometric in situ estimates as well as comparisons of simulated sea surface elevations with a global network of S_1 tide gauge determinations. Credence is lent to the global S_1 tide derived from the Modern-Era Retrospective Analysis for Research and Applications (MERRA) and the operational model of the European Centre for Medium-Range Weather Forecasts (ECMWF). When averaged over a temporal range of 2004 to 2013, their nutation contributions are estimated to be -8.0+i106.0 μ as (MERRA) and -9.4+i121.8 μ as (ECMWF operational), thus being virtually equivalent with the VLBI estimate. This remarkably close agreement will likely aid forthcoming nutation theories in their unambiguous a priori account of Earth's prograde annual celestial motion.

  16. The global S1 tide and Earth's nutation

    NASA Astrophysics Data System (ADS)

    Schindelegger, M.; Böhm, J.; Salstein, D. A.

    2015-08-01

    Diurnal S1 tidal atmospheric oscillations induced by the cyclic heating of air masses through solar radiation elicit a small contribution to Earth's prograde annual nutation at a level of 100 μas (microarcseconds). Previously published estimates of this Sun-synchronous perturbation based on angular momentum series from global geophysical fluid models have however diverged, and within the present conventional nutation theory, the effect has been instead accounted for in an empirical manner based on analyzing residual spectra of observed celestial pole offsets. This study constitutes a first, tentative reassessment of the S1 signal in nutation by resorting to modern-day atmospheric reanalyses as well as available hydrodynamic solutions for diurnal oceanic angular momentum changes that are driven by daily air pressure variations at the water surface. We elucidate the global character of the S1 tide with particular regard to Earth rotation variations and investigate to which extent atmospheric and oceanic excitation terms from various sources can be superimposed. The combined influence of the principal diurnal tide on Earth's nutation, associated with both atmosphere and ocean dynamics, is found to yield a sound agreement with its observational evidence from geodetic VLBI (Very Long Baseline Interferometry) measurements.

  17. Angular momentum budget of the radiational S1 ocean tide

    NASA Astrophysics Data System (ADS)

    Schindelegger, Michael; Dobslaw, Henryk; Poropat, Lea; Salstein, David; Böhm, Johannes

    2016-04-01

    The balance of diurnal S1 oceanic angular momentum (OAM) variations through torques at the sea surface and the bottom topography is validated using both a barotropic and a baroclinic numerical tide model. This analysis discloses the extent to which atmosphere-driven S1 forward simulations are reliable for use in studies of high-frequency polar motion and changes in length-of-day. Viscous and dissipative torques associated with wind stress, bottom friction, as well as internal tidal energy conversion are shown to be small, and they are overshadowed by gravitational and pressure-related interaction forces. In particular, the zonal OAM variability of S1 is almost completely balanced by the water pressure torque on the local bathymetry, whereas in the prograde equatorial case also the air pressure torque on the seafloor as well as ellipsoidal contributions from the non-spherical atmosphere and solid Earth must be taken into account. Overall, the OAM budget is well closed in both the axial and the equatorial directions, thus allowing for an identification of the main diurnal angular momentum sinks in the ocean. The physical interaction forces are found to be largest at shelf breaks and continental slopes in low latitudes, with the most dominant contribution coming from the Indonesian archipelago.

  18. Search for ammonia in comet C/2012 S1 (ISON)

    NASA Astrophysics Data System (ADS)

    Faggi, S.; Codella, C.; Tozzi, G. P.; Comoretto, G.; Crovisier, J.; Nesti, R.; Panella, D.; Boissier, J.; Brucato, J. R.; Bolli, P.; Massi, F.; Tofani, G.

    2015-12-01

    Comets are uniquely pristine bodies providing unique insights about the formation of our Solar System. In this work, we focus on a dynamically new comet as it enters the inner Solar System for the first time after residing for billion of years in the Oort Cloud. Such comets are particularly important because they are thought to be not differentiated by solar radiation and they are supposed to have a large quantity of organic matter close to the surface. Here we report the results of a search for NH3(1,1) emission at 23.7 GHz towards comet C/2012 S1 (ISON) using a new dual-feed K band receiver mounted on the Medicina 32-m antenna. We observed the comet close to its perihelion, from 25 to 29 November 2013, when its heliocentric distance changed from 0.25 AU to 0.03 AU. We derive an upper limit of Q(NH3) of about 2.5×1029 mol s-1 on 26 November, that is consistent with the last peak of water production rate of ∼2×1030 mol s-1 within the last few days before the perihelion.

  19. Osmo-, Thermo- and Ethanol- Tolerances of Saccharomyces cerevisiae S1

    PubMed Central

    Balakumar, Sandrasegarampillai; Arasaratnam, Vasanthy

    2012-01-01

    Saccharomyces cerevisiae S1, which is a locally isolated and improved strain showed viability at 40, 45 and 50°C and produced ethanol at 40, 43 and 45°C. When the cells were given heat shock at 45°C for 30min and grown at 40°C, 100% viability was observed for 60h, and addition of 200gL−1 ethanol has led to complete cell death at 30h. Heat shock given at 45°C (for 30min) has improved the tolerance to temperature induced ethanol shock leading to 37% viability at 30h. When the cells were subjected to ethanol (200gL−1 for 30 min) and osmotic shock (sorbitol 300gL−1), trehalose contents in the cells were increased. The heat shocked cells showed better viability in presence of added ethanol. Soy flour supplementation has improved the viability of S. cerevisiae S1 to 80% in presence of 100gL−1 added ethanol and to 60% in presence of 300gL−1sorbitol. In presence of sorbitol (200gL−1) and ethanol (50gL−1) at 40°C, 46% viability was retained by S. cerevisiae S1 at 48h and it was improved to 80% by soy flour supplementation. PMID:24031814

  20. [[sup 3]H]QNB displays in vivo selectivity for the m2 subtype

    SciTech Connect

    Gitler, M.S.; De La Cruz, R.; Zeeberg, B.R. ); Reba, R.C. Univ. of Chicago Hospital, Chicago, IL )

    1994-01-01

    Alzheimer's disease (AD) involves selective loss of muscarinic m2, but not m1, subtype neuroreceptors in the posterior parietal cortex of the human brain. Emission tomographic study of the loss of m2 receptors in AD is limited by the fact that there is currently no available m2-selective radioligand which can penetrate the blood-brain barrier. [[sup 3]H](R)-3-quinuclidinylbenzilate ([[sup 3]H]QNB) is commonly used for performing in vitro studies of the muscarinic acetylcholine receptor (mAChR), either with membrane homogenates or with autoradiographic slices, in which [[sup 3]H]QNB is nonsubtype-selective. We report here the results of in vivo studies, using both carrier-free and low specific activity [[sup 3]H]QNB, which show that [[sup 3]H]QNB exhibits a substantial in vivo m2-selectivity. Previously reported in vivo (R)-3-quinuclidinyl (R)-4-iodobenzilate ((R,R)-[[sup 125]I]lQNB) binding appears to be nonsubtype-selective. Apparently the bulky iodine substitution in the 4 position reduces the subtype selectivity of QNB. It is possible that a less bulky fluorine substitution might permit retention of the selectivity exhibited by QNB itself. We conclude that a suitably radiolabeled derivative of QNB, possibly labeled with [sup 18]F, may be of potential use in positron emission tomographic (PET) study of the loss of m2 receptors in AD. 39 refs., 8 figs., 2 tab.

  1. Differences in forward angular light scattering distributions between M1 and M2 macrophages.

    PubMed

    Halaney, David L; Zahedivash, Aydin; Phipps, Jennifer E; Wang, Tianyi; Dwelle, Jordan; Saux, Claude Jourdan Le; Asmis, Reto; Milner, Thomas E; Feldman, Marc D

    2015-11-01

    The ability to distinguish macrophage subtypes noninvasively could have diagnostic potential in cancer, atherosclerosis, and diabetes, where polarized M1 and M2 macrophages play critical and often opposing roles. Current methods to distinguish macrophage subtypes rely on tissue biopsy. Optical imaging techniques based on light scattering are of interest as they can be translated into biopsy-free strategies. Because mitochondria are relatively strong subcellular light scattering centers, and M2 macrophages are known to have enhanced mitochondrial biogenesis compared to M1, we hypothesized that M1 and M2 macrophages may have different angular light scattering profiles. To test this, we developed an in vitro angle-resolved forward light scattering measurement system. We found that M1 and M2 macrophage monolayers scatter relatively unequal amounts of light in the forward direction between 1.6 deg and 3.2 deg with M2 forward scattering significantly more light than M1 at increasing angles. The ratio of forward scattering can be used to identify the polarization state of macrophage populations in culture.

  2. ICAM-1 suppresses tumor metastasis by inhibiting macrophage M2 polarization through blockade of efferocytosis

    PubMed Central

    Yang, M; Liu, J; Piao, C; Shao, J; Du, J

    2015-01-01

    Efficient clearance of apoptotic cells (efferocytosis) can profoundly influence tumor-specific immunity. Tumor-associated macrophages are M2-polarized macrophages that promote key processes in tumor progression. Efferocytosis stimulates M2 macrophage polarization and contributes to cancer metastasis, but the signaling mechanism underlying this process is unclear. Intercellular cell adhesion molecule-1 (ICAM-1) is a transmembrane glycoprotein member of the immunoglobulin superfamily, which has been implicated in mediating cell–cell interaction and outside-in cell signaling during the immune response. We report that ICAM-1 expression is inversely associated with macrophage infiltration and the metastasis index in human colon tumors by combining Oncomine database analysis and immunohistochemistry for ICAM-1. Using a colon cancer liver metastasis model in ICAM-1-deficient (ICAM-1−/−) mice and their wild-type littermates, we found that loss of ICAM-1 accelerated liver metastasis of colon carcinoma cells. Moreover, ICAM-1 deficiency increased M2 macrophage polarization during tumor progression. We further demonstrated that ICAM-1 deficiency in macrophages led to promotion of efferocytosis of apoptotic tumor cells through activation of the phosphatidylinositol 3 kinase/Akt signaling pathway. More importantly, coculture of ICAM-1−/− macrophages with apoptotic cancer cells resulted in an increase of M2-like macrophages, which was blocked by an efferocytosis inhibitor. Our findings demonstrate a novel role for ICAM-1 in suppressing M2 macrophage polarization via downregulation of efferocytosis in the tumor microenvironment, thereby inhibiting metastatic tumor progression. PMID:26068788

  3. Endoplasmic Reticulum Stress Controls M2 Macrophage Differentiation and Foam Cell Formation*

    PubMed Central

    Oh, Jisu; Riek, Amy E.; Weng, Sherry; Petty, Marvin; Kim, David; Colonna, Marco; Cella, Marina; Bernal-Mizrachi, Carlos

    2012-01-01

    Macrophages are essential in atherosclerosis progression, but regulation of the M1 versus M2 phenotype and their role in cholesterol deposition are unclear. We demonstrate that endoplasmic reticulum (ER) stress is a key regulator of macrophage differentiation and cholesterol deposition. Macrophages from diabetic patients were classically or alternatively stimulated and then exposed to oxidized LDL. Alternative stimulation into M2 macrophages lead to increased foam cell formation by inducing scavenger receptor CD36 and SR-A1 expression. ER stress induced by alternative stimulation was necessary to generate the M2 phenotype through JNK activation and increased PPARγ expression. The absence of CD36 or SR-A1 signaling independently of modified cholesterol uptake decreased ER stress and prevented the M2 differentiation typically induced by alternative stimulation. Moreover, suppression of ER stress shifted differentiated M2 macrophages toward an M1 phenotype and subsequently suppressed foam cell formation by increasing HDL- and apoA-1-induced cholesterol efflux indicating suppression of macrophage ER stress as a potential therapy for atherosclerosis. PMID:22356914

  4. RGS4 regulates partial agonism of the M2 muscarinic receptor-activated K+ currents

    PubMed Central

    Chen, I-Shan; Furutani, Kazuharu; Inanobe, Atsushi; Kurachi, Yoshihisa

    2014-01-01

    Partial agonists are used clinically to avoid overstimulation of receptor-mediated signalling, as they produce a submaximal response even at 100% receptor occupancy. The submaximal efficacy of partial agonists is due to conformational change of the agonist–receptor complex, which reduces effector activation. In addition to signalling activators, several regulators help control intracellular signal transductions. However, it remains unclear whether these signalling regulators contribute to partial agonism. Here we show that regulator of G-protein signalling (RGS) 4 is a determinant for partial agonism of the M2 muscarinic receptor (M2R). In rat atrial myocytes, pilocarpine evoked smaller G-protein-gated K+ inwardly rectifying (KG) currents than those evoked by ACh. In a Xenopus oocyte expression system, pilocarpine acted as a partial agonist in the presence of RGS4 as it did in atrial myocytes, while it acted like a full agonist in the absence of RGS4. Functional couplings within the agonist–receptor complex/G-protein/RGS4 system controlled the efficacy of pilocarpine relative to ACh. The pilocarpine–M2R complex suppressed G-protein-mediated activation of KG currents via RGS4. Our results demonstrate that partial agonism of M2R is regulated by the RGS4-mediated inhibition of G-protein signalling. This finding helps us to understand the molecular components and mechanism underlying the partial agonism of M2R-mediated physiological responses. PMID:24421355

  5. Modelling packing interactions in parallel helix bundles: pentameric bundles of nicotinic receptor M2 helices.

    PubMed

    Sankararamakrishnan, R; Sansom, M S

    1995-11-01

    The transbilayer pore of the nicotinic acetylcholine receptor (nAChR) is formed by a pentameric bundle of M2 helices. Models of pentameric bundles of M2 helices have been generated using simulated annealing via restrained molecular dynamics. The influence of: (a) the initial C alpha template; and (b) screening of sidechain electrostatic interactions on the geometry of the resultant M2 helix bundles is explored. Parallel M2 helices, in the absence of sidechain electrostatic interactions, pack in accordance with simple ridges-in-grooves considerations. This results in a helix crossing angle of ca. +12 degrees, corresponding to a left-handed coiled coil structure for the bundle as a whole. Tilting of M2 helices away from the central pore axis at their C-termini and/or inclusion of sidechain electrostatic interactions may perturb such ridges-in-grooves packing. In the most extreme cases right-handed coiled coils are formed. An interplay between inter-helix H-bonding and helix bundle geometry is revealed. The effects of changes in electrostatic screening on the dimensions of the pore mouth are described and the significance of these changes in the context of models for the nAChR pore domain is discussed.

  6. Unraveling a molecular determinant for clathrin-independent internalization of the M2 muscarinic acetylcholine receptor

    PubMed Central

    Wan, Min; Zhang, Wenhua; Tian, Yangli; Xu, Chanjuan; Xu, Tao; Liu, Jianfeng; Zhang, Rongying

    2015-01-01

    Endocytosis and postendocytic sorting of G-protein-coupled receptors (GPCRs) is important for the regulation of both their cell surface density and signaling profile. Unlike the mechanisms of clathrin-dependent endocytosis (CDE), the mechanisms underlying the control of GPCR signaling by clathrin-independent endocytosis (CIE) remain largely unknown. Among the muscarinic acetylcholine receptors (mAChRs), the M4 mAChR undergoes CDE and recycling, whereas the M2 mAChR is internalized through CIE and targeted to lysosomes. Here we investigated the endocytosis and postendocytic trafficking of M2 mAChR based on a comparative analysis of the third cytoplasmic domain in M2 and M4 mAChRs. For the first time, we identified that the sequence 374KKKPPPS380 servers as a sorting signal for the clathrin-independent internalization of M2 mAChR. Switching 374KKKPPPS380 to the i3 loop of the M4 mAChR shifted the receptor into lysosomes through the CIE pathway; and therefore away from CDE and recycling. We also found another previously unidentified sequence that guides CDE of the M2 mAChR, 361VARKIVKMTKQPA373, which is normally masked in the presence of the downstream sequence 374KKKPPPS380. Taken together, our data indicate that endocytosis and postendocytic sorting of GPCRs that undergo CIE could be sequence-dependent. PMID:26094760

  7. Structural environment built by AKAP12+ colon mesenchymal cells drives M2 macrophages during inflammation recovery.

    PubMed

    Yang, Jun-Mo; Lee, Hye Shin; Seo, Ji Hae; Park, Ji-Hyeon; Gelman, Irwin H; Lo, Eng H; Kim, Kyu-Won

    2017-02-16

    Macrophages exhibit phenotypic plasticity, as they have the ability to switch their functional phenotypes during inflammation and recovery. Simultaneously, the mechanical environment actively changes. However, how these dynamic alterations affect the macrophage phenotype is unknown. Here, we observed that the extracellular matrix (ECM) constructed by AKAP12+ colon mesenchymal cells (CMCs) generated M2 macrophages by regulating their shape during recovery. Notably, rounded macrophages were present in the linear and loose ECM of inflamed colons and polarized to the M1 phenotype. In contrast, ramified macrophages emerged in the contracted ECM of recovering colons and mainly expressed M2 macrophage markers. These contracted structures were not observed in the inflamed colons of AKAP12 knockout (KO) mice. Consequently, the proportion of M2 macrophages in inflamed colons was lower in AKAP12 KO mice than in WT mice. In addition, clinical symptoms and histological damage were more severe in AKAP12 KO mice than in WT mice. In experimentally remodeled collagen gels, WT CMCs drove the formation of a more compacted structure than AKAP12 KO CMCs, which promoted the polarization of macrophages toward an M2 phenotype. These results demonstrated that tissue contraction during recovery provides macrophages with the physical cues that drive M2 polarization.

  8. Free-Energy Profiles for Ions in the Influenza M2-TMD Channel

    PubMed Central

    Mustafa, Morad; Henderson, Douglas J.; Busath, David D.

    2009-01-01

    M2 transmembrane domain channel (M2-TMD) permeation properties are studied using molecular dynamics simulations of M2-TMD (1NYJ) embedded in a lipid bilayer (DMPC) with 1 mol/kg NaCl or KCl saline solution. This study allows examination of spontaneous cation and anion entry into the selectivity filter. Three titration states of the M2-TMD tetramer are modeled for which the four His37 residues, forming the selectivity filter, are net uncharged, +2 charged, or +3 charged. M2-TMD structural properties from our simulations are compared with the properties of other models extracted from NMR and X-ray studies. During 10 ns simulations, chloride ions rarely occupy the positively-charged selectivity filter, whereas from umbrella sampling simulations, Cl− has a lower free-energy barrier in the selectivity-filter region than either Na+ or NH4+, and NH4+ has a lower free-energy barrier than Na+. For Na+ and Cl−, the free-energy barriers are less than 5 kcal/mol, suggesting that the 1NYJ conformation would probably not be exquisitely proton selective. We also point out a rotameric configuration of Trp41 that could fully occlude the channel. PMID:19296508

  9. Structural environment built by AKAP12+ colon mesenchymal cells drives M2 macrophages during inflammation recovery

    PubMed Central

    Yang, Jun-Mo; Lee, Hye Shin; Seo, Ji Hae; Park, Ji-Hyeon; Gelman, Irwin H.; Lo, Eng H.; Kim, Kyu-Won

    2017-01-01

    Macrophages exhibit phenotypic plasticity, as they have the ability to switch their functional phenotypes during inflammation and recovery. Simultaneously, the mechanical environment actively changes. However, how these dynamic alterations affect the macrophage phenotype is unknown. Here, we observed that the extracellular matrix (ECM) constructed by AKAP12+ colon mesenchymal cells (CMCs) generated M2 macrophages by regulating their shape during recovery. Notably, rounded macrophages were present in the linear and loose ECM of inflamed colons and polarized to the M1 phenotype. In contrast, ramified macrophages emerged in the contracted ECM of recovering colons and mainly expressed M2 macrophage markers. These contracted structures were not observed in the inflamed colons of AKAP12 knockout (KO) mice. Consequently, the proportion of M2 macrophages in inflamed colons was lower in AKAP12 KO mice than in WT mice. In addition, clinical symptoms and histological damage were more severe in AKAP12 KO mice than in WT mice. In experimentally remodeled collagen gels, WT CMCs drove the formation of a more compacted structure than AKAP12 KO CMCs, which promoted the polarization of macrophages toward an M2 phenotype. These results demonstrated that tissue contraction during recovery provides macrophages with the physical cues that drive M2 polarization. PMID:28205544

  10. Large-Scale Mini-Magnetosphere Plasma Propulsion (M2P2) Experiments

    NASA Technical Reports Server (NTRS)

    Winglee, R. M.; Slough, J.; Ziemba, T.; Euripides, P.; Adrian, M. L.; Gallagher, D.; Craven, P.; Tomlinson, W.; Cravens, J.; Burch, J.; Whitaker, Ann F. (Technical Monitor)

    2001-01-01

    Mini-Magnetosphere Plasma Propulsion (M2P2) is an innovative plasma propulsion system that has the potential to propel spacecraft at unprecedented speeds of 50 to 80 km per second with a low-power requirement of approx. 1 kW per 100 kg of payload and approx. 1 kg of neutral gas [fuel] consumption per day of acceleration. Acceleration periods from several days to a few months are envisioned. High specific impulse and efficiency are achieved through coupling of the spacecraft to the 400 km per second solar wind through an artificial magnetosphere. The mini-magnetosphere or inflated magnetic bubble is produced by the injection of cold dense plasma into a spacecraft-generated magnetic field envelope. Magnetic bubble inflation is driven by electromagnetic processes thereby avoiding the material and deployment problems faced by mechanical solar sail designs, Here, we present the theoretical design of M2P2 as well as initial results from experimental testing of an M2P2 prototype demonstrating: 1) inflation of the dipole magnetic field geometry through the internal injection of cold plasma; and 2) deflection of and artificial solar wind by the prototype M2P2 system. In addition, we present plans for direct laboratory measurement of thrust imparted to a prototype M2P2 by an artificial solar wind during the summer of 2001.

  11. Large-Scale Mini-Magnetosphere Plasma Propulsion (M2P2) Experiments

    NASA Technical Reports Server (NTRS)

    Winglee, R. M.; Slough, J.; Ziemba, T.; Euripides, P.; Gallagher, D.; Craven, P.; Adrian, M. L.; Tomlinson, W.; Cravens, J.; Burch, J.; Rose, M. Franklin (Technical Monitor)

    2001-01-01

    Mini-Magnetosphere Plasma Propulsion (M2P2) is an innovative plasma propulsion system that has the potential to propel spacecraft at unprecedented speeds of 50 to 80 km/s, with a low power requirement of approx. 1 kW per 100 kg of payload and -1 kg of neutral gas [fuel] consumption per day of acceleration. Acceleration periods from several days to a few months are envisioned. High specific impulse and efficiency are achieved through coupling of the spacecraft to the 400 km/s. solar wind through an artificial magnetosphere. The mini-magnetosphere or inflated magnetic bubble is produced by the injection of cold dense plasma into a spacecraft-generated magnetic field envelope. Magnetic bubble inflation is driven by electromagnetic processes thereby avoiding the material and deployment problems faced by mechanical solar sail designs. Here, we present the theoretical design of M2P2 as well as initial results from experimental testing of an M2P2 prototype demonstrating: 1) inflation of the dipole magnetic field geometry through the internal injection of cold plasma; and 2) deflection of and artificial solar wind by the prototype M2P2 system. In addition, we present plans for direct laboratory measurement of thrust imparted to a prototype M2P2 by an artificial solar wind during the summer of 2001.

  12. Differences in forward angular light scattering distributions between M1 and M2 macrophages

    NASA Astrophysics Data System (ADS)

    Halaney, David L.; Zahedivash, Aydin; Phipps, Jennifer E.; Wang, Tianyi; Dwelle, Jordan; Saux, Claude Jourdan Le; Asmis, Reto; Milner, Thomas E.; Feldman, Marc D.

    2015-11-01

    The ability to distinguish macrophage subtypes noninvasively could have diagnostic potential in cancer, atherosclerosis, and diabetes, where polarized M1 and M2 macrophages play critical and often opposing roles. Current methods to distinguish macrophage subtypes rely on tissue biopsy. Optical imaging techniques based on light scattering are of interest as they can be translated into biopsy-free strategies. Because mitochondria are relatively strong subcellular light scattering centers, and M2 macrophages are known to have enhanced mitochondrial biogenesis compared to M1, we hypothesized that M1 and M2 macrophages may have different angular light scattering profiles. To test this, we developed an in vitro angle-resolved forward light scattering measurement system. We found that M1 and M2 macrophage monolayers scatter relatively unequal amounts of light in the forward direction between 1.6 deg and 3.2 deg with M2 forward scattering significantly more light than M1 at increasing angles. The ratio of forward scattering can be used to identify the polarization state of macrophage populations in culture.

  13. Unraveling a molecular determinant for clathrin-independent internalization of the M2 muscarinic acetylcholine receptor.

    PubMed

    Wan, Min; Zhang, Wenhua; Tian, Yangli; Xu, Chanjuan; Xu, Tao; Liu, Jianfeng; Zhang, Rongying

    2015-06-22

    Endocytosis and postendocytic sorting of G-protein-coupled receptors (GPCRs) is important for the regulation of both their cell surface density and signaling profile. Unlike the mechanisms of clathrin-dependent endocytosis (CDE), the mechanisms underlying the control of GPCR signaling by clathrin-independent endocytosis (CIE) remain largely unknown. Among the muscarinic acetylcholine receptors (mAChRs), the M4 mAChR undergoes CDE and recycling, whereas the M2 mAChR is internalized through CIE and targeted to lysosomes. Here we investigated the endocytosis and postendocytic trafficking of M2 mAChR based on a comparative analysis of the third cytoplasmic domain in M2 and M4 mAChRs. For the first time, we identified that the sequence (374)KKKPPPS(380) servers as a sorting signal for the clathrin-independent internalization of M2 mAChR. Switching (374)KKKPPPS(380) to the i3 loop of the M4 mAChR shifted the receptor into lysosomes through the CIE pathway; and therefore away from CDE and recycling. We also found another previously unidentified sequence that guides CDE of the M2 mAChR, (361)VARKIVKMTKQPA(373), which is normally masked in the presence of the downstream sequence (374)KKKPPPS(380). Taken together, our data indicate that endocytosis and postendocytic sorting of GPCRs that undergo CIE could be sequence-dependent.

  14. Differences in forward angular light scattering distributions between M1 and M2 macrophages

    PubMed Central

    Halaney, David L.; Zahedivash, Aydin; Phipps, Jennifer E.; Wang, Tianyi; Dwelle, Jordan; Saux, Claude Jourdan Le; Asmis, Reto; Milner, Thomas E.; Feldman, Marc D.

    2015-01-01

    Abstract. The ability to distinguish macrophage subtypes noninvasively could have diagnostic potential in cancer, atherosclerosis, and diabetes, where polarized M1 and M2 macrophages play critical and often opposing roles. Current methods to distinguish macrophage subtypes rely on tissue biopsy. Optical imaging techniques based on light scattering are of interest as they can be translated into biopsy-free strategies. Because mitochondria are relatively strong subcellular light scattering centers, and M2 macrophages are known to have enhanced mitochondrial biogenesis compared to M1, we hypothesized that M1 and M2 macrophages may have different angular light scattering profiles. To test this, we developed an in vitro angle-resolved forward light scattering measurement system. We found that M1 and M2 macrophage monolayers scatter relatively unequal amounts of light in the forward direction between 1.6 deg and 3.2 deg with M2 forward scattering significantly more light than M1 at increasing angles. The ratio of forward scattering can be used to identify the polarization state of macrophage populations in culture. PMID:26538329

  15. Beam quality M 2 factor matrix for non-circular symmetric laser beams

    NASA Astrophysics Data System (ADS)

    Du, Yongzhao; Fu, Yuqing; Zheng, Chaoying

    2017-02-01

    It is standard to use Mx2 and My2 to characterize the beam quality of a non-circular symmetrical beam on its x-axis and y-axis orientation. However, we knew that the values of Mx2 and My2 are inconsistent if one selects a different coordinate system or measures beam quality with different experimental conditionals, even when analyzing the same beam. To overcome this, a new beam quality characterization method, the M 2 factor matrix, is developed. It not only contains the beam quality terms, Mx2 and My2 , to characterize the beam quality along x-axis and y-axis orientation for the non-symmetric beam, but also introduces two additional cross terms, M xy and M yx , which are used to characterize the location relationship between the principal axis of the test beam and coordinate system in experiment. Moreover, M 2 factor matrix can be measured with a similar procedure to the traditional M 2 factor whose measurement instructions are described in ISO11146 by adding some additional image and signal processing procedure. The measurement principle and method is present and the experiment system for beam quality M 2 factor matrix is built to demonstrate the performance of M 2 factor matrix with real experiments.

  16. Interaction of integrin β4 with S1P receptors in S1P- and HGF-induced endothelial barrier enhancement.

    PubMed

    Ni, Xiuqin; Epshtein, Yulia; Chen, Weiguo; Zhou, Tingting; Xie, Lishi; Garcia, Joe G N; Jacobson, Jeffrey R

    2014-06-01

    We previously reported sphingosine 1-phosphate (S1P) and hepatocyte growth factor (HGF) augment endothelial cell (EC) barrier function and attenuate murine acute lung inury (ALI). While the mechanisms underlying these effects are not fully understood, S1P and HGF both transactivate the S1P receptor, S1PR1 and integrin β4 (ITGB4) at membrane caveolin-enriched microdomains (CEMs). In the current study, we investigated the roles of S1PR2 and S1PR3 in S1P/HGF-mediated EC signaling and their associations with ITGB4. Our studies confirmed ITGB4 and S1PR2/3 are recruited to CEMs in human lung EC in response to either S1P (1 µM, 5 min) or HGF (25 ng/ml, 5 min). Co-immunoprecipitation experiments identified an S1P/HGF-mediated interaction of ITGB4 with both S1PR2 and S1PR3. We then employed an in situ proximity ligation assay (PLA) to confirm a direct ITGB4-S1PR3 association induced by S1P/HGF although a direct association was not detectable between S1PR2 and ITGB4. S1PR1 knockdown (siRNA), however, abrogated S1P/HGF-induced ITGB4-S1PR2 associations while there was no effect on ITGB4-S1PR3 associations. Moreover, PLA confirmed a direct association between S1PR1 and S1PR2 induced by S1P and HGF. Finally, silencing of S1PR2 significantly attenuated S1P/HGF-induced EC barrier enhancement as measured by transendothelial resistance while silencing of S1PR3 significantly augmented S1P/HGF-induced barrier enhancement. These results confirm an important role for S1PR2 and S1PR3 in S1P/HGF-mediated EC barrier responses that are associated with their complex formation with ITGB4. Our findings elucidate novel mechanisms of EC barrier regulation that may ultimately lead to new therapeutic targets for disorders characterized by increased vascular permeability including ALI.

  17. Membrane remodeling by the M2 amphipathic helix drives influenza virus membrane scission

    PubMed Central

    Martyna, Agnieszka; Bahsoun, Basma; Badham, Matthew D.; Srinivasan, Saipraveen; Howard, Mark J.; Rossman, Jeremy S.

    2017-01-01

    Membrane scission is a crucial step in all budding processes, from endocytosis to viral budding. Many proteins have been associated with scission, though the underlying molecular details of how scission is accomplished often remain unknown. Here, we investigate the process of M2-mediated membrane scission during the budding of influenza viruses. Residues 50–61 of the viral M2 protein bind membrane and form an amphipathic α-helix (AH). Membrane binding requires hydrophobic interactions with the lipid tails but not charged interactions with the lipid headgroups. Upon binding, the M2AH induces membrane curvature and lipid ordering, constricting and destabilizing the membrane neck, causing scission. We further show that AHs in the cellular proteins Arf1 and Epsin1 behave in a similar manner. Together, they represent a class of membrane-induced AH domains that alter membrane curvature and fluidity, mediating the scission of constricted membrane necks in multiple biological pathways. PMID:28317901

  18. The M2&M3 positioning control systems of a 2.5m telescope

    NASA Astrophysics Data System (ADS)

    Ye, Yu; Pei, Chong; Zhang, Zhiyong; Gu, Bozhong

    2012-09-01

    The 2.5m optical/infrared telescope is an F/8 telescope comprising one Cassegrain foci, two Nasmyth foci and two student Nasmyth foci. This paper presents a brief description of the physical structure, conceptual design, hardware implementing measure and software structure in the positioning control system of M2&M3. The graphical user interface application (Qt) is adopted to design the software. During the full working range the M2 focus and decenter achieve the positioning repeatability is better than +/-4μm and the M2 tilt is better than 10 μrad. The M3 angular positioning and locking accuracy is better than 10 arcsec and repeatability is better than 2 arcsec RMS.

  19. A Novel Voltage Sensor in the Orthosteric Binding Site of the M2 Muscarinic Receptor.

    PubMed

    Barchad-Avitzur, Ofra; Priest, Michael F; Dekel, Noa; Bezanilla, Francisco; Parnas, Hanna; Ben-Chaim, Yair

    2016-10-04

    G protein-coupled receptors (GPCRs) mediate many signal transduction processes in the body. The discovery that these receptors are voltage-sensitive has changed our understanding of their behavior. The M2 muscarinic acetylcholine receptor (M2R) was found to exhibit depolarization-induced charge movement-associated currents, implying that this prototypical GPCR possesses a voltage sensor. However, the typical domain that serves as a voltage sensor in voltage-gated channels is not present in GPCRs, making the search for the voltage sensor in the latter challenging. Here, we examine the M2R and describe a voltage sensor that is comprised of tyrosine residues. This voltage sensor is crucial for the voltage dependence of agonist binding to the receptor. The tyrosine-based voltage sensor discovered here constitutes a noncanonical by which membrane proteins may sense voltage.

  20. Holographic cosmology from a system of M2-M5 branes

    NASA Astrophysics Data System (ADS)

    Sepehri, Alireza; Faizal, Mir; Setare, Mohammad Reza; Ali, Ahmed Farag

    2016-05-01

    In this paper, we analyze the holographic cosmology using a M2-M5 brane configuration. In this configuration, a M2-brane will be placed in between a M5-brane and an anti-M5-brane. The M2-brane will act as a channel for energy to flow from an anti-M5-brane to a M5-brane, and this will increase the degrees of freedom on the M5-brane causing inflation. The inflation will end when the M5-brane and anti-M5-brane get separated. However, at a later stage the distance between the M5-brane and the anti-M5-bran can reduce and this will cause the formation of tachyonic states. These tachyonic states will again open a bridge between the M5-branes and the anti-M5-branes, which will cause further acceleration of the universe.

  1. M2-F1 in flight being towed by a C-47

    NASA Technical Reports Server (NTRS)

    1964-01-01

    The M2-F1 Lifting Body is seen here being towed behind a C-47 at the Flight Research Center (later redesignated the Dryden Flight Research Center), Edwards, California. In this rear view, the M2-F1 is flying above and to one side of the C-47. This was done to avoid wake turbulence from the towplane. Lacking wings, the M2-F1 used an unusual configuration for its control surfaces. It had two rudders on the fins, two elevons (called 'elephant ears') mounted on the outsides of the fins, and two body flaps on the upper rear fuselage. The wingless, lifting body aircraft design was initially concieved as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. These initial tests produced enough flight data about the M2-F1 to proceed with flights behind the C-47 tow plane at greater altitudes. The C-47 took the craft to an altitude of 12,000 where free flights back to Rogers Dry Lake began. Pilot for the first series of flights of the M2-F1 was NASA research pilot Milt Thompson. Typical glide flights with the M2-F1 lasted about two minutes and reached speeds of 110 to l20 mph. More than 400 ground tows and 77 aircraft tow flights were carried out with the M2-F1. The success of Dryden's M2-F1 program led to NASA's development and construction of two heavyweight lifting bodies based on studies at NASA's Ames and

  2. Water-mediated conformational transitions in nicotinic receptor M2 helix bundles: a molecular dynamics study.

    PubMed

    Sankararamakrishnan, R; Sansom, M S

    1995-12-27

    The ion channel of the nicotinic acetylcholine receptor is a water-filled pore formed by five M2 helix segments, one from each subunit. Molecular dynamics simulations on bundles of five M2 alpha 7 helices surrounding a central column of water and with caps of water molecules at either end of the pore have been used to explore the effects of intrapore water on helix packing. Interactions of water molecules with the N-terminal polar sidechains lead to a conformational transition from right- to left-handed supercoils during these stimulations. These studies reveal that the pore formed by the bundle of M2 helices is flexible. A structural role is proposed for water molecules in determining the geometry of bundles of isolated pore-forming helices.

  3. A model of the closed form of the nicotinic acetylcholine receptor m2 channel pore.

    PubMed

    Kim, Sanguk; Chamberlain, Aaron K; Bowie, James U

    2004-08-01

    The nicotinic acetylcholine receptor is a neurotransmitter-gated ion channel in the postsynaptic membrane. It is composed of five homologous subunits, each of which contributes one transmembrane helix--the M2 helix--to create the channel pore. The M2 helix from the delta subunit is capable of forming a channel by itself. Although a model of the receptor was recently proposed based on a low-resolution, cryo-electron microscopy density map, we found that the model does not explain much of the other available experimental data. Here we propose a new model of the M2 channel derived solely from helix packing and symmetry constraints. This model agrees well with experimental results from solid-state NMR, chemical reactivity, and mutagenesis experiments. The model depicts the channel pore, the channel gate, and the residues responsible for cation specificity.

  4. Holographic cosmology from a system of M2–M5 branes

    SciTech Connect

    Sepehri, Alireza; Faizal, Mir; Setare, Mohammad Reza; Ali, Ahmed Farag

    2016-05-15

    In this paper, we analyze the holographic cosmology using a M2–M5 brane configuration. In this configuration, a M2-brane will be placed in between a M5-brane and an anti-M5-brane. The M2-brane will act as a channel for energy to flow from an anti-M5-brane to a M5-brane, and this will increase the degrees of freedom on the M5-brane causing inflation. The inflation will end when the M5-brane and anti-M5-brane get separated. However, at a later stage the distance between the M5-brane and the anti-M5-bran can reduce and this will cause the formation of tachyonic states. These tachyonic states will again open a bridge between the M5-branes and the anti-M5-branes, which will cause further acceleration of the universe.

  5. Most general spherically symmetric M2-branes and type-IIB strings

    SciTech Connect

    Wang Zhaolong; Lue, H.

    2009-09-15

    We obtain the most general spherically symmetric M2-branes and type-IIB strings, with R{sup 1,2}xSO(8) and R{sup 1,1}xSO(8) isometries, respectively. We find that there are 12 different classes of M2-branes, and we study their curvature properties. In particular, we obtain new smooth M2-brane wormholes that connect two asymptotic regions: one is flat and the other can be either flat or AdS{sub 4}xS{sup 7}. We find that these wormholes are traversable with certain timelike trajectories. We also obtain the most general Ricci-flat solutions in five dimensions with R{sup 1,1}xSO(3) isometries.

  6. Mechanism of the Pseudoirreversible Binding of Amantadine to the M2 Proton Channel.

    PubMed

    Llabrés, Salomé; Juárez-Jiménez, Jordi; Masetti, Matteo; Leiva, Rosana; Vázquez, Santiago; Gazzarrini, Sabrina; Moroni, Anna; Cavalli, Andrea; Luque, F Javier

    2016-11-30

    The M2 proton channel of influenza A virus is an integral membrane protein involved in the acidification of the viral interior, a step necessary for the release of the viral genetic material and replication of new virions. The aim of this study is to explore the mechanism of drug (un)binding to the M2 channel in order to gain insight into the structural and energetic features relevant for the development of novel inhibitors. To this end, we have investigated the binding of amantadine (Amt) to the wild type (wt) M2 channel and its V27A variant using multiple independent molecular dynamics simulations, exploratory conventional metadynamics, and multiple-walkers well-tempered metadynamics calculations. The results allow us to propose a sequential mechanism for the (un)binding of Amt to the wt M2 channel, which involves the adoption of a transiently populated intermediate (up state) leading to the thermodynamically favored down binding mode in the channel pore. Furthermore, they suggest that chloride anions play a relevant role in stabilizing the down binding mode of Amt to the wt channel, giving rise to a kinetic trapping that explains the experimentally observed pseudoirreversible inhibition of the wt channel by Amt. We propose that this trapping mechanism underlies the inhibitory activity of potent M2 channel blockers, as supported by the experimental confirmation of the irreversible binding of a pyrrolidine analogue from electrophysiological current assays. Finally, the results reveal that the thermodynamics and kinetics of Amt (un)binding is very sensitive to the V27A mutation, providing a quantitative rationale to the drastic decrease in inhibitory potency against the V27A variant. Overall, these findings pave the way to explore the inhibitory activity of Amt-related analogues in mutated M2 channel variants, providing guidelines for the design of novel inhibitors against resistant virus strains.

  7. Desensitization and internalization of the m2 muscarinic acetylcholine receptor are directed by independent mechanisms.

    PubMed

    Pals-Rylaarsdam, R; Xu, Y; Witt-Enderby, P; Benovic, J L; Hosey, M M

    1995-12-01

    The phenomenon of acute desensitization of G-protein-coupled receptors has been associated with several events, including receptor phosphorylation, loss of high affinity agonist binding, receptor:G-protein uncoupling, and receptor internalization. However, the biochemical events underlying these processes are not fully understood, and their contributions to the loss of signaling remain correlative. In addition, the nature of the kinases and the receptor domains which are involved in modulation of activity have only begun to be investigated. In order to directly measure the role of G-protein-coupled receptor kinases (GRKs) in the desensitization of the m2 muscarinic acetylcholine receptor (m2 mAChR), a dominant-negative allele of GRK2 was used to inhibit receptor phosphorylation by endogenous GRK activity in a human embryonic kidney cell line. The dominant-negative GRK2K220R reduced agonist-dependent phosphorylation of the m2 mAChR by approximately 50% and prevented acute desensitization of the receptor as measured by the ability of the m2 mAChR to attenuate adenylyl cyclase activity. In contrast, the agonist-induced internalization of the m2 mAChR was unaffected by the GRK2K220R construct. Further evidence linking receptor phosphorylation to acute receptor desensitization was obtained when two deletions of the third intracellular loop were made which created m2 mAChRs that did not become phosphorylated in an agonist-dependent manner and did not desensitize. However, the mutant mAChRs retained the ability to internalize. These data provide the first direct evidence that GRK-mediated receptor phosphorylation is necessary for m2 mAChR desensitization; the likely sites of in vivo phosphorylation are in the central portion of the third intracellular loop (amino acids 282-323). These results also indicate that internalization of the m2 receptor is not a key event in desensitization and is mediated by mechanisms distinct from GRK phosphorylation of the receptor.

  8. Spontaneous mobility of GABAA receptor M2 extracellular half relative to noncompetitive antagonist action.

    PubMed

    Chen, Ligong; Durkin, Kathleen A; Casida, John E

    2006-12-15

    The gamma-aminobutyric acid type A receptor beta(3) homopentamer is spontaneously open and highly sensitive to many noncompetitive antagonists(NCAs) and Zn(2+). Our earlier study of the M2 cytoplasmic half (-1' to 10') established a model in which NCAs bind at pore-lining residues Ala(2)', Thr(6)', and Leu(9)'. To further define transmembrane 2 (M2) structure relative to NCA action, we extended the Cys scanning to the extra cellular half of the beta(3) homopentamer (11' to 20'). Spontaneous disulfides formed with T13'C, L18'C, and E20'C from M2/M2 cross-linking and with I14'C (weak), H17'C, and R19'Con bridging M2/M3 intersubunits, based on single (M2 Cys only) and dual (M2 Cys plus M3 C289S) mutations. Induced disulfides also formed with T16'C, but there were few or none with M11'C, T12'C, and N15'C. These findings show conformational flexibility/mobility in the M2 extracellular half 17' to 20' region interpreted as a deformed beta-like conformation in the open channel. The NCA radioligands used were [(3)H]1-(4-ethynylphenyl)-4-n-propyl-2,6,7-trioxabicyclo[2.2.2]octane ([(3)H]EBOB) and [(3)H]3,3-bis-trifluoromethylbicyclo[2.2.1]heptane-2,2-dicarbonitrile with essentially the same results. NCA binding was disrupted by individual Cys substitutions at 13',14',16',17', and 19'. The inactivity of T13'C/T13'S may have been due to disturbance of the channel gate; I14'S and T16'S showed much better binding activity than their Cys counterparts, and the low activities of H17'C and R19'C were reversed by dithiothreitol. Zn(2+) potency for inhibition of [(3)H]EBOB binding was lowered 346-fold by the mutation H17'A. We propose that NCAs enter their binding site both directly, through the channel pore, and indirectly, through the water cavity of adjacent subunits.

  9. Spontaneous thermal motion of the GABA(A) receptor M2 channel-lining segments.

    PubMed

    Bera, Amal K; Akabas, Myles H

    2005-10-21

    The gamma-aminobutyric acid type A (GABA(A)) receptor channel opening involves translational and rotational motions of the five channel-lining, M2 transmembrane segments. The M2 segment's extracellular half is loosely packed and undergoes significant thermal motion. To characterize the extent of the M2 segment's motion, we used disulfide trapping experiments between pairs of engineered cysteines. In alpha1beta1 gamma2S receptors the single gamma subunit is flanked by an alpha and beta subunit. The gamma2 M2-14' position is located in the alpha-gamma subunit interface. Gamma2 13' faces the channel lumen. We expressed either the gamma2 14' or the gamma2 13' cysteine substitution mutants with alpha1 cysteine substitution mutants between 12' and 16' and wild-type beta1. Disulfide bonds formed spontaneously between gamma2 14'C and both alpha1 15'C and alpha1 16'C and also between gamma2 13'C and alpha1 13'C. Oxidation by copper phenanthroline induced disulfide bond formation between gamma2 14'C and alpha1 13'C. Disulfide bond formation rates with gamma2 14'C were similar in the presence and absence of GABA, although the rate with alpha1 13'C was slower than with the other two positions. In a homology model based on the acetylcholine receptor structure, alphaM2 would need to rotate in opposite directions by approximately 80 degrees to bring alpha1 13' and alpha1 15' into close proximity with gamma2 14'. Alternatively, translational motion of alphaM2 would reduce the extent of rotational motion necessary to bring these two alpha subunit residues into close proximity with the gamma2 14' position. These experiments demonstrate that in the closed state the M2 segments undergo continuous spontaneous motion in the region near the extracellular end of the channel gate. Opening the gate may involve similar but concerted motions of the M2 segments.

  10. Open M2-branes with flux and the modified Basu-Harvey equation

    NASA Astrophysics Data System (ADS)

    Chu, Chong-Sun; Sehmbi, Gurdeep S.

    2011-04-01

    The supersymmetric actions of closed multiple M2 branes with flux for the Bagger-Lambert (BL) and ABJM theories have been constructed recently by Lambert and Richmond (2009 J. High Energy Phys. JHEP10(2009)084). In this paper, we extend the construction to the case of open M2-branes with flux and derive the boundary conditions. This allows us to derive the modified Basu-Harvey equation in the presence of flux. As an example, we consider the Lorentzian BL model. A new feature of the fuzzy funnel solution describing a D2-D4 intersection is obtained as a result of the flux.

  11. Pharmacokinetics of PEGylated recombinant human endostatin (M2ES) in rats

    PubMed Central

    Li, Zuo-gang; Jia, Lin; Guo, Li-fang; Yu, Min; Sun, Xu; Nie, Wen; Fu, Yan; Rao, Chun-ming; Wang, Jun-zhi; Luo, Yong-zhang

    2015-01-01

    Aim: M2ES is PEGylated recombinant human endostatin. In this study we investigated the pharmacokinetics, tissue distribution, and excretion of M2ES in rats. Methods: 125I-radiolabeled M2ES was administered to rats by intravenous bolus injection at 3 mg/kg. The pharmacokinetics, tissue distribution and excretion of M2ES were investigated using the trichloroacetic acid (TCA) precipitation method. Results: The serum M2ES concentration-time curve after a single intravenous dose of 3 mg/kg in rats was fitted with a non-compartment model. The pharmacokinetic parameters were evaluated as follows: Cmax=28.3 μg·equ/mL, t1/2=71.5 h, AUC(0–∞)=174.6 μg·equ·h/mL, Cl=17.2 mL·h−1·kg−1, MRT=57.6 h, and Vss=989.8 mL/kg for the total radioactivity; Cmax=30.3 μg·equ/mL, t1/2=60.1 h, AUC(0–∞)=146.2 μg·equ·h/mL, Cl=20.6 mL·h−1·kg−1, MRT=47.4 h, and Vss=974.6 mL/kg for the TCA precipitate radioactivity. M2ES was rapidly and widely distributed in various tissues and showed substantial deposition in kidney, adrenal gland, lung, spleen, bladder and liver. The radioactivity recovered in the urine and feces by 432 h post-dose was 71.3% and 8.3%, respectively. Only 0.98% of radioactivity was excreted in the bile by 24 h post-dose. Conclusion: PEG modification substantially prolongs the circulation time of recombinant human endostatin and effectively improves its pharmacokinetic behavior. M2ES is extensively distributed in most tissues of rats, including kidney, adrenal gland, lung, spleen, bladder and liver. Urinary excretion was the major elimination route for M2ES. PMID:26027657

  12. Modelling the enigmatic Late Pliocene Glacial Event - Marine Isotope Stage M2

    USGS Publications Warehouse

    Dolan, Aisling M.; Haywood, Alan M.; Hunter, Stephen J.; Tindall, Julia C.; Dowsett, Harry J.; Hill, Daniel J.; Pickering, Steven J.

    2015-01-01

    The Pliocene Epoch (5.2 to 2.58 Ma) has often been targeted to investigate the nature of warm climates. However, climate records for the Pliocene exhibit significant variability and show intervals that apparently experienced a cooler than modern climate. Marine Isotope Stage (MIS) M2 (~ 3.3 Ma) is a globally recognisable cooling event that disturbs an otherwise relatively (compared to present-day) warm background climate state. It remains unclear whether this event corresponds to significant ice sheet build-up in the Northern and Southern Hemisphere. Estimates of sea level for this interval vary, and range from modern values to estimates of 65 m sea level fall with respect to present day. Here we implement plausible M2 ice sheet configurations into a coupled atmosphere–ocean climate model to test the hypothesis that larger-than-modern ice sheet configurations may have existed at M2. Climate model results are compared with proxy climate data available for M2 to assess the plausibility of each ice sheet configuration. Whilst the outcomes of our data/model comparisons are not in all cases straight forward to interpret, there is little indication that results from model simulations in which significant ice masses have been prescribed in the Northern Hemisphere are incompatible with proxy data from the North Atlantic, Northeast Arctic Russia, North Africa and the Southern Ocean. Therefore, our model results do not preclude the possibility of the existence of larger ice masses during M2 in the Northern or Southern Hemisphere. Specifically they are not able to discount the possibility of significant ice masses in the Northern Hemisphere during the M2 event, consistent with a global sea-level fall of between 40 m and 60 m. This study highlights the general need for more focused and coordinated data generation in the future to improve the coverage and consistency in proxy records for M2, which will allow these and future M2 sensitivity tests to be interrogated

  13. Lama glama αS1-casein: Identification of new polymorphisms in the CSN1S1 gene.

    PubMed

    Pauciullo, A; Gauly, M; Cosenza, G; Wagner, H; Erhardt, G

    2017-02-01

    South American camelids have been poorly genetically investigated and little information is available in llamas (Lama glama) regarding the diversity of the caseins at the protein and gene level. Exon skipping and duplication events previously reported in the αS1-casein gene (CSN1S1) led us to investigate the genetic variability at this locus. Seventy-two positive clones for the αS1-casein transcripts were analyzed and randomly sequenced. The comparative analysis of the sequences revealed 2 transitions, c.366A>G and c.690T>C, at the 10th nucleotide of exon 12 and 94 bp of exon 19, respectively. These SNP are responsible for 2 amino acid changes, Ile→Val in position 86 and Tyr→His in position 194 of the mature protein. Both polymorphisms clarify the genetic events behind the protein variants A and B. This result was confirmed by isoelectric focusing analysis of llama milk samples. Quick methods based on PCR-RFLP and allele-specific PCR were set up for allelic discrimination in a population of 128 animals. Based on genotyping results, 4 haplotypes were observed and the estimated frequencies indicated B as the most common haplotype (0.629) in the investigated population. These data add knowledge to the genetic variability of a species little investigated, and open opportunity for new investigation in the field of milk protein for South American camelids, including the possibility, in the future, to select alleles with favorable characteristics.

  14. Highly selective and potent agonists of sphingosine-1-phosphate 1 (S1P1) receptor.

    PubMed

    Vachal, Petr; Toth, Leslie M; Hale, Jeffrey J; Yan, Lin; Mills, Sander G; Chrebet, Gary L; Koehane, Carol A; Hajdu, Richard; Milligan, James A; Rosenbach, Mark J; Mandala, Suzanne

    2006-07-15

    Novel series of sphingosine-1-phosphate (S1P) receptor agonists were developed through a systematic SAR aimed to achieve high selectivity for a single member of the S1P family of receptors, S1P1. The optimized structure represents a highly S1P1-selective and efficacious agonist: S1P1/S1P2, S1P1/S1P3, S1P1/S1P4>10,000-fold, S1P1/S1P5>600-fold, while EC50 (S1P1) <0.2 nM. In vivo experiments are consistent with S1P1 receptor agonism alone being sufficient for achieving desired lymphocyte-lowering effect.

  15. M2-F1 in flight over lakebed on tow line

    NASA Technical Reports Server (NTRS)

    1963-01-01

    Following the first M2-F1 airtow flight on 16 August 1963, the Flight Research Center used the vehicle for both research flights and to check out new lifting-body pilots. These included Bruce Peterson, Don Mallick, Fred Haise, and Bill Dana from NASA. Air Force pilots who flew the M2-F1 included Chuck Yeager, Jerry Gentry, Joe Engle, Jim Wood, and Don Sorlie, although Wood, Haise, and Engle only flew on car tows. In the three years between the first and last flights of the M2-F1, it made about 400 car tows and 77 air tows. The wingless, lifting body aircraft design was initially concieved as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop near Long Beach for modification. With a special gearbox and

  16. M2-F1 lifting body aircraft on a flatbed truck

    NASA Technical Reports Server (NTRS)

    1997-01-01

    After the grounding of the M2-F1 in 1966, it was kept in outside storage on the Dryden complex. After several years, its fabric and plywood structure was damaged by the sun and weather. Restoration of the vehicle began in February 1994 under the leadership of NASA retiree Dick Fischer, with other retirees who had originally worked on the M2-F1's construction and flight research three decades before also participating. The photo shows the now-restored M2-F1 returning to the site of its flight research, now called the Dryden Flight Research Center, on 22 August 1997. The wingless, lifting body aircraft design was initially conceived as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, NASA Flight Research Center (later Dryden Flight Research Center, Edwards, CA) management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available

  17. Effect of plastoquinone derivative 10-(6'-plastoquinonyl) decyltriphenylphosphonium (SkQ1) on estrous cycle and 17β-estradiol level in rats.

    PubMed

    Chistyakov, V A; Dem'yanenko, S V; Alexandrova, A A; Gutnikova, L V; Prokof'ev, V N; Kosheleva, O N

    2012-12-01

    Administration of the plastoquinone derivative 10-(6'-plastoquinonyl)decyltriphenylphosphonium (SkQ1) to female Wistar rats with regular estrous cycle once a day for two weeks at doses of 25 nmol/kg (but not 250 nmol/kg) leads to increase in proestrus duration by reducing the phase of diestrus and metestrus. Neither dose caused significant changes in serum 17β-estradiol level for any stage of the cycle. However, relative elongation of the proestrus stage leads to an increase in average per cycle estradiol levels by 20%.

  18. Investigation on the Ability of Antireflection Coating to Withstand the Destructive Effects of Laser Radiation in IR Range (10.6 Micrometers),

    DTIC Science & Technology

    2014-09-26

    at the mid-IR, KCl and NaCl are commonly selected as substrates. But for the CO2 laser , a Ge substrate coated with a *i ZnS AR coating, is still widely...FOREIGN TECHNOLOGY DIVISION INVESTIGATION ON THE ABILITY OF ANTIREFLECTION COATING TO WITHSTAND THE DESTRUCTIVE EFFECTS OF LASER RADIATION IN IR RANGE...INVESTIGATION ON THE ABILITY OF ANTIREFLECTION COATING TO WITHSTAND THE DESTRUCTIVE EFFECTS OF LASER RADIATION IN IR RANGE (10.6 pm) By: Wang Jingrui, Liu Jien

  19. Marine microbial biodiversity, bioinformatics and biotechnology (M2B3) data reporting and service standards

    PubMed Central

    2015-01-01

    Contextual data collected concurrently with molecular samples are critical to the use of metagenomics in the fields of marine biodiversity, bioinformatics and biotechnology. We present here Marine Microbial Biodiversity, Bioinformatics and Biotechnology (M2B3) standards for “Reporting” and “Serving” data. The M2B3 Reporting Standard (1) describes minimal mandatory and recommended contextual information for a marine microbial sample obtained in the epipelagic zone, (2) includes meaningful information for researchers in the oceanographic, biodiversity and molecular disciplines, and (3) can easily be adopted by any marine laboratory with minimum sampling resources. The M2B3 Service Standard defines a software interface through which these data can be discovered and explored in data repositories. The M2B3 Standards were developed by the European project Micro B3, funded under 7th Framework Programme “Ocean of Tomorrow”, and were first used with the Ocean Sampling Day initiative. We believe that these standards have value in broader marine science. PMID:26203332

  20. M2-F1 lifting body and Paresev 1B on ramp

    NASA Technical Reports Server (NTRS)

    1963-01-01

    In this photo of the M2-F1 lifting body and the Paresev 1B on the ramp, the viewer sees two vehicles representing different approaches to building a research craft to simulate a spacecraft able to land on the ground instead of splashing down in the ocean as the Mercury capsules did. The M2-F1 was a lifting body, a shape able to re-enter from orbit and land. The Paresev (Paraglider Research Vehicle) used a Rogallo wing that could be (but never was) used to replace a conventional parachute for landing a capsule-type spacecraft, allowing it to make a controlled landing on the ground. The wingless, lifting body aircraft design was initially conceived as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop

  1. Chronic hepatitis C infection–induced liver fibrogenesis is associated with M2 macrophage activation

    PubMed Central

    Bility, Moses T.; Nio, Kouki; Li, Feng; McGivern, David R.; Lemon, Stanley M.; Feeney, Eoin R.; Chung, Raymond T.; Su, Lishan

    2016-01-01

    The immuno-pathogenic mechanisms of chronic hepatitis C virus (HCV) infection remain to be elucidated and pose a major hurdle in treating or preventing chronic HCV-induced advanced liver diseases such as cirrhosis. Macrophages are a major component of the inflammatory milieu in chronic HCV–induced liver disease, and are generally derived from circulating inflammatory monocytes; however very little is known about their role in liver diseases. To investigate the activation and role of macrophages in chronic HCV–induced liver fibrosis, we utilized a recently developed humanized mouse model with autologous human immune and liver cells, human liver and blood samples and cell culture models of monocyte/macrophage and/or hepatic stellate cell activation. We showed that M2 macrophage activation was associated with liver fibrosis during chronic HCV infection in the livers of both humanized mice and patients, and direct-acting antiviral therapy attenuated M2 macrophage activation and associated liver fibrosis. We demonstrated that supernatant from HCV-infected liver cells activated human monocytes/macrophages with M2-like phenotypes. Importantly, HCV-activated monocytes/macrophages promoted hepatic stellate cell activation. These results suggest a critical role for M2 macrophage induction in chronic HCV-associated immune dysregulation and liver fibrosis. PMID:28000758

  2. Adenosine augments IL-10-induced STAT3 signaling in M2c macrophages.

    PubMed

    Koscsó, Balázs; Csóka, Balázs; Kókai, Endre; Németh, Zoltán H; Pacher, Pál; Virág, László; Leibovich, S Joseph; Haskó, György

    2013-12-01

    The alternatively activated macrophage phenotype induced by IL-10 is called M2c. Adenosine is an endogenous purine nucleoside that accumulates in the extracellular space in response to metabolic disturbances, hypoxia, inflammation, physical damage, or apoptosis. As adenosine is known to regulate classically activated M1 and IL4- and IL-13-activated M2a macrophages, the goal of the present study was to explore its effects on M2c macrophages. We found that adenosine augmented the IL-10-induced expression of TIMP-1 and arginase-1 by the mouse macrophage cell line RAW 264.7 and by mouse BMDMs. The effects of AR stimulation on IL-10-induced TIMP-1 or arginase-1 expression were lacking in A2BAR KO macrophages. The role of A2BAR on TIMP-1 production of RAW 264.7 cells was confirmed with specific agonist BAY606583 and antagonist PSB0788. AR stimulation augmented IL-10-induced STAT3 phosphorylation in macrophages, and pharmacological inhibition or silencing of STAT3 using siRNA reduced the stimulatory effect of AR stimulation on TIMP-1 production. In contrast to its stimulatory effect on IL-10-induced STAT3 activation, adenosine inhibited IL-6-induced STAT3 phosphorylation and SAA3 expression. In conclusion, adenosine enhances IL-10-induced STAT3 signaling and M2c macrophage activation.

  3. M2C precipitates in isothermal tempering of high Co-Ni secondary hardening steel

    NASA Astrophysics Data System (ADS)

    Yoo, Choong Hwa; Lee, Hyuck Mo; Chan, Jin W.; Morris, John W.

    1996-11-01

    The effects of isothermal tempering on the coarsening behavior of hexagonal M2C precipitates and the secondary hardening reaction in ultrahigh-strength AerMet 100 steel were investigated. The tempering temperatures were 468 °C, 482 °C, and 510 °C, and the tempering time spanned the range from 1 to 400 hours. Experimental studies of the coarsening behavior of the carbides were made by utilizing transmission electron microscopy (TEM), scanning electron microscopy (SEM), and X-ray diffractometry (XRD). The hardness at the secondary hardening peak was about HRc 55. The average length and diameter of M2C carbides were 4 to 8 nm and 1.5 to 2.5 nm, respectively, at all three tempering temperatures; hence, the aspect ratio was almost 3, an equilibrium value in this case. The size of the M2C carbides increased monotonically with time, but the growth kinetics did not exactly follow the classical coarsening behavior. The amount of precipitated austenite increased with tempering time and temperature. M2C precipitates were still relatively fine even after 200 hours of tempering. This feature seemed to be closely related to the high hardness maintained after prolonged tempering.

  4. Abundance, distribution, mobility and oligomeric state of M2 muscarinic acetylcholine receptors in live cardiac muscle

    PubMed Central

    Nenasheva, Tatiana A.; Neary, Marianne; Mashanov, Gregory I.; Birdsall, Nigel J.M.; Breckenridge, Ross A.; Molloy, Justin E.

    2013-01-01

    M2 muscarinic acetylcholine receptors modulate cardiac rhythm via regulation of the inward potassium current. To increase our understanding of M2 receptor physiology we used Total Internal Reflection Fluorescence Microscopy to visualize individual receptors at the plasma membrane of transformed CHOM2 cells, a cardiac cell line (HL-1), primary cardiomyocytes and tissue slices from pre- and post-natal mice. Receptor expression levels between individual cells in dissociated cardiomyocytes and heart slices were highly variable and only 10% of murine cardiomyocytes expressed muscarinic receptors. M2 receptors were evenly distributed across individual cells and their density in freshly isolated embryonic cardiomyocytes was ~ 1 μm− 2, increasing at birth (to ~ 3 μm− 2) and decreasing back to ~ 1 μm− 2 after birth. M2 receptors were primarily monomeric but formed reversible dimers. They diffused freely at the plasma membrane, moving approximately 4-times faster in heart slices than in cultured cardiomyocytes. Knowledge of receptor density and mobility has allowed receptor collision rate to be modeled by Monte Carlo simulations. Our estimated encounter rate of 5–10 collisions per second, may explain the latency between acetylcholine application and GIRK channel opening. PMID:23357106

  5. M2-F1 mounted in NASA Ames Research Center 40x80 foot wind tunnel

    NASA Technical Reports Server (NTRS)

    1962-01-01

    After the first attempted ground-tow tests of the M2-F1 in March 1963, the vehicle was taken to the Ames Research Center, Mountain View, CA, for wind-tunnel testing. During these tests, Milt Thompson and others were in the M2-F1 to position the control surfaces for each test. The wingless, lifting body aircraft design was initially conceived as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop near Long Beach for modification. With a special gearbox and racing slicks, the Pontiac could tow the 1,000-pound M2-F1 110 miles per hour in 30 seconds. It proved adequate for the roughly 400 car tows that got the M2-F1 airborne to prove it could fly safely and to train pilots before they were towed behind a C

  6. Wooden shell of M2-F1 being assembled at El Mirage

    NASA Technical Reports Server (NTRS)

    1962-01-01

    Wooden shell of the M2-F1 being assembled at El Mirage, CA. While Flight Research Center technicians built the internal steel structure of the M2-F1, sailplane builder Gus Briegleb built the vehicle's outer wooden shell. Its skin was 3/32-inch mahogany plywood, with 1/8-inch mahogany rib sections reinforced with spruce. The wingless, lifting body aircraft design was initially conceived as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop near Long Beach for modification. With a special gearbox and racing slicks, the Pontiac could tow the 1,000-pound M2-F1 110 miles per hour in 30 seconds. It proved adequate for the roughly 400 car tows that got the M2-F1 airborne to prove it could fly safely and to

  7. Proposed Ames M2-F1, M1-L half-cone, and Langley lenticular bodies.

    NASA Technical Reports Server (NTRS)

    1962-01-01

    Dale Reed, who inaugurated the lifting-body flight research at NASA's Flight Research Center (later, Dryden Flight Research Center, Edwards, CA), originally proposed that three wooden outer shells be built. These would then be attached to the single internal steel structure. The three shapes were (viewer's left to right) the M2-F1, the M1-L, and a lenticular shape. Milt Thompson, who supported Reed's advocacy for a lifting-body research project, recommended that only the M2-F1 shell be built, believing that the M1-L shape was 'too radical,' while the lenticular one was 'too exotic.' Although the lenticular shape was often likened to that of a flying saucer, Reed's wife Donna called it the 'powder puff.' The wingless, lifting body aircraft design was initially conceived as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey

  8. M2-F1 in flight over lakebed on tow line

    NASA Technical Reports Server (NTRS)

    1963-01-01

    After initial ground-tow flights of the M2-F1 using the Pontiac as a tow vehicle, the way was clear to make air tows behind a C-47. The first air tow took place on 16 August 1963. Pilot Milt Thompson found that the M2-F1 flew well, with good control. This first flight lasted less than two minutes from tow-line release to touchdown. The descent rate was 4,000 feet per minute. The wingless, lifting body aircraft design was initially concieved as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop near Long Beach for modification. With a special gearbox and racing slicks, the Pontiac could tow the 1,000-pound M2-F1 110 miles per hour in 30 seconds. It proved adequate for the roughly 400 car tows that got

  9. Structure of the human M2 muscarinic acetylcholine receptor bound to an antagonist.

    PubMed

    Haga, Kazuko; Kruse, Andrew C; Asada, Hidetsugu; Yurugi-Kobayashi, Takami; Shiroishi, Mitsunori; Zhang, Cheng; Weis, William I; Okada, Tetsuji; Kobilka, Brian K; Haga, Tatsuya; Kobayashi, Takuya

    2012-01-25

    The parasympathetic branch of the autonomic nervous system regulates the activity of multiple organ systems. Muscarinic receptors are G-protein-coupled receptors that mediate the response to acetylcholine released from parasympathetic nerves. Their role in the unconscious regulation of organ and central nervous system function makes them potential therapeutic targets for a broad spectrum of diseases. The M2 muscarinic acetylcholine receptor (M2 receptor) is essential for the physiological control of cardiovascular function through activation of G-protein-coupled inwardly rectifying potassium channels, and is of particular interest because of its extensive pharmacological characterization with both orthosteric and allosteric ligands. Here we report the structure of the antagonist-bound human M2 receptor, the first human acetylcholine receptor to be characterized structurally, to our knowledge. The antagonist 3-quinuclidinyl-benzilate binds in the middle of a long aqueous channel extending approximately two-thirds through the membrane. The orthosteric binding pocket is formed by amino acids that are identical in all five muscarinic receptor subtypes, and shares structural homology with other functionally unrelated acetylcholine binding proteins from different species. A layer of tyrosine residues forms an aromatic cap restricting dissociation of the bound ligand. A binding site for allosteric ligands has been mapped to residues at the entrance to the binding pocket near this aromatic cap. The structure of the M2 receptor provides insights into the challenges of developing subtype-selective ligands for muscarinic receptors and their propensity for allosteric regulation.

  10. M2-polarized macrophages contribute to neovasculogenesis, leading to relapse of oral cancer following radiation

    PubMed Central

    Okubo, Makiko; Kioi, Mitomu; Nakashima, Hideyuki; Sugiura, Kei; Mitsudo, Kenji; Aoki, Ichiro; Taniguchi, Hideki; Tohnai, Iwai

    2016-01-01

    Despite the fact that radiation is one of the standard therapies in the treatment of patients with oral cancer, tumours can recur even in the early stages of the disease, negatively impacting prognosis and quality of life. We previously found that CD11b+ bone marrow-derived cells (BMDCs) were recruited into human glioblastoma multiforme (GBM), leading to re-organization of the vasculature and tumour regrowth. However, it is not yet known how these cells contribute to tumour vascularization. In the present study, we investigated the role of infiltrating CD11b+ myeloid cells in the vascularization and recurrence of oral squamous cell carcinoma (OSCC). In a xenograft mouse model, local irradiation caused vascular damage and hypoxia in the tumour and increased infiltration of CD11b+ myeloid cells. These infiltrating cells showed characteristics of M2 macrophages (M2Mφs) and are associated with the promotion of vascularization. M2Mφs promoted tumour progression in recurrence after irradiation compared to non-irradiated tumours. In addition, we found that CD11b+ myeloid cells, as well as CD206+ M2Mφs, are increased during recurrence after radiotherapy in human OSCC specimens. Our findings may lead to the development of potential clinical biomarkers or treatment targets in irradiated OSCC patients. PMID:27271009

  11. Nonylphenol biodegradation characterizations and bacterial composition analysis of an effective consortium NP-M2.

    PubMed

    Bai, Naling; Abuduaini, Rexiding; Wang, Sheng; Zhang, Meinan; Zhu, Xufen; Zhao, Yuhua

    2017-01-01

    Nonylphenol (NP), ubiquitously detected as the degradation product of nonionic surfactants nonylphenol polyethoxylates, has been reported as an endocrine disrupter. However, most pure microorganisms can degrade only limited species of NP with low degradation efficiencies. To establish a microbial consortium that can effectively degrade different forms of NP, in this study, we isolated a facultative microbial consortium NP-M2 and characterized the biodegradation of NP by it. NP-M2 could degrade 75.61% and 89.75% of 1000 mg/L NP within 48 h and 8 days, respectively; an efficiency higher than that of any other consortium or pure microorganism reported so far. The addition of yeast extract promoted the biodegradation more significantly than that of glucose. Moreover, surface-active compounds secreted into the extracellular environment were hypothesized to promote high-efficiency metabolism of NP. The detoxification of NP by this consortium was determined. The degradation pathway was hypothesized to be initiated by oxidization of the benzene ring, followed by step-wise side-chain biodegradation. The bacterial composition of NP-M2 was determined using 16S rDNA library, and the consortium was found to mainly comprise members of the Sphingomonas, Pseudomonas, Alicycliphilus, and Acidovorax genera, with the former two accounting for 86.86% of the consortium. The high degradation efficiency of NP-M2 indicated that it could be a promising candidate for NP bioremediation in situ.

  12. Universal M2 ectodomain-based influenza A vaccines: preclinical and clinical developments

    PubMed Central

    Schotsaert, Michael; De Filette, Marina; Fiers, Walter; Saelens, Xavier

    2009-01-01

    Influenza vaccines used today are strain specific and need to be adapted every year to try and match the antigenicity of the virus strains that are predicted to cause the next epidemic. The strain specificity of the next pandemic is unpredictable. An attractive alternative approach would be to use a vaccine that matches multiple influenza virus strains, including multiple subtypes. In this review, we focus on the development and clinical potential of a vaccine that is based on the conserved ectodomain of matrix protein 2 (M2) of influenza A virus. Since 1999, a number of studies have demonstrated protection against influenza A virus challenge in animal models using chemical or genetic M2 external domain (M2e) fusion constructs. More recently, Phase I clinical studies have been conducted with M2e vaccine candidates, demonstrating their safety and immunogenicity in humans. Ultimately, and possibly in the near future, efficacy studies in humans should provide proof that this novel vaccine concept can mitigate epidemic and even pandemic influenza A virus infections. PMID:19348565

  13. Embryonic stem cell-derived M2-like macrophages delay cutaneous wound healing.

    PubMed

    Dreymueller, Daniela; Denecke, Bernd; Ludwig, Andreas; Jahnen-Dechent, Willi

    2013-01-01

    In adults, repair of deeply injured skin wounds results in the formation of scar tissue, whereas in embryos wounds heal almost scar-free. Macrophages are important mediators of wound healing and secrete cytokines and tissue remodeling enzymes. In contrast to host defense mediated by inflammatory M1 macrophages, wound healing and tissue repair involve regulatory M2/M2-like macrophages. Embryonic/fetal macrophages are M2-like, and this may promote scar-free wound healing. In the present study, we asked whether atopical application of ex vivo generated, embryonic stem cell-derived macrophages (ESDM) improve wound healing in mice. ESDM were tested side by side with bone marrow-derived macrophages (BMDM). Compared to BMDM, ESDM resembled a less inflammatory and more M2-like macrophage subtype as indicated by their reduced responsiveness to lipopolysaccharide, reduced expression of Toll-like receptors, and reduced bacterial phagocytosis. Despite this anti-inflammatory phenotype in cell culture, ESDM prolonged the healing of deep skin wounds even more than BMDM. Healed wounds had more scar formation compared to wounds receiving BMDM or cell-free treatment. Our data indicate that atopical application of ex vivo generated macrophages is not a suitable cell therapy of dermal wounds.

  14. Structure of the human M2 muscarinic acetylcholine receptor bound to an antagonist

    SciTech Connect

    Haga, Kazuko; Kruse, Andrew C.; Asada, Hidetsugu; Yurugi-Kobayashi, Takami; Shiroishi, Mitsunori; Zhang, Cheng; Weis, William I.; Okada, Tetsuji; Kobilka, Brian K.; Haga, Tatsuya; Kobayashi, Takuya

    2012-03-15

    The parasympathetic branch of the autonomic nervous system regulates the activity of multiple organ systems. Muscarinic receptors are G-protein-coupled receptors that mediate the response to acetylcholine released from parasympathetic nerves. Their role in the unconscious regulation of organ and central nervous system function makes them potential therapeutic targets for a broad spectrum of diseases. The M2 muscarinic acetylcholine receptor (M2 receptor) is essential for the physiological control of cardiovascular function through activation of G-protein-coupled inwardly rectifying potassium channels, and is of particular interest because of its extensive pharmacological characterization with both orthosteric and allosteric ligands. Here we report the structure of the antagonist-bound human M2 receptor, the first human acetylcholine receptor to be characterized structurally, to our knowledge. The antagonist 3-quinuclidinyl-benzilate binds in the middle of a long aqueous channel extending approximately two-thirds through the membrane. The orthosteric binding pocket is formed by amino acids that are identical in all five muscarinic receptor subtypes, and shares structural homology with other functionally unrelated acetylcholine binding proteins from different species. A layer of tyrosine residues forms an aromatic cap restricting dissociation of the bound ligand. A binding site for allosteric ligands has been mapped to residues at the entrance to the binding pocket near this aromatic cap. The structure of the M2 receptor provides insights into the challenges of developing subtype-selective ligands for muscarinic receptors and their propensity for allosteric regulation.

  15. A Survey on M2M Systems for mHealth: A Wireless Communications Perspective

    PubMed Central

    Kartsakli, Elli; Lalos, Aris S.; Antonopoulos, Angelos; Tennina, Stefano; Di Renzo, Marco; Alonso, Luis; Verikoukis, Christos

    2014-01-01

    In the new era of connectivity, marked by the explosive number of wireless electronic devices and the need for smart and pervasive applications, Machine-to-Machine (M2M) communications are an emerging technology that enables the seamless device interconnection without the need of human interaction. The use of M2M technology can bring to life a wide range of mHealth applications, with considerable benefits for both patients and healthcare providers. Many technological challenges have to be met, however, to ensure the widespread adoption of mHealth solutions in the future. In this context, we aim to provide a comprehensive survey on M2M systems for mHealth applications from a wireless communication perspective. An end-to-end holistic approach is adopted, focusing on different communication aspects of the M2M architecture. Hence, we first provide a systematic review of Wireless Body Area Networks (WBANs), which constitute the enabling technology at the patient's side, and then discuss end-to-end solutions that involve the design and implementation of practical mHealth applications. We close the survey by identifying challenges and open research issues, thus paving the way for future research opportunities. PMID:25264958

  16. A survey on M2M systems for mHealth: a wireless communications perspective.

    PubMed

    Kartsakli, Elli; Lalos, Aris S; Antonopoulos, Angelos; Tennina, Stefano; Renzo, Marco Di; Alonso, Luis; Verikoukis, Christos

    2014-09-26

    In the new era of connectivity, marked by the explosive number of wireless electronic devices and the need for smart and pervasive applications, Machine-to-Machine (M2M) communications are an emerging technology that enables the seamless device interconnection without the need of human interaction. The use of M2M technology can bring to life a wide range of mHealth applications, with considerable benefits for both patients and healthcare providers. Many technological challenges have to be met, however, to ensure the widespread adoption of mHealth solutions in the future. In this context, we aim to provide a comprehensive survey on M2M systems for mHealth applications from a wireless communication perspective. An end-to-end holistic approach is adopted, focusing on different communication aspects of the M2M architecture. Hence, we first provide a systematic review ofWireless Body Area Networks (WBANs), which constitute the enabling technology at the patient's side, and then discuss end-to-end solutions that involve the design and implementation of practical mHealth applications. We close the survey by identifying challenges and open research issues, thus paving the way for future research opportunities.

  17. LTE-advanced random access mechanism for M2M communication: A review

    NASA Astrophysics Data System (ADS)

    Mustafa, Rashid; Sarowa, Sandeep; Jaglan, Reena Rathee; Khan, Mohammad Junaid; Agrawal, Sunil

    2016-03-01

    Machine Type Communications (MTC) enables one or more self-sufficient machines to communicate directly with one another without human interference. MTC applications include smart grid, security, e-Health and intelligent automation system. To support huge numbers of MTC devices, one of the challenging issues is to provide a competent way for numerous access in the network and to minimize network overload. In this article, the different control mechanisms for overload random access are reviewed to avoid congestion caused by random access channel (RACH) of MTC devices. However, past and present wireless technologies have been engineered for Human-to-Human (H2H) communications, in particular, for transmission of voice. Consequently the Long Term Evolution (LTE) -Advanced is expected to play a central role in communicating Machine to Machine (M2M) and are very optimistic about H2H communications. Distinct and unique characteristics of M2M communications create new challenges from those in H2H communications. In this article, we investigate the impact of massive M2M terminals attempting random access to LTE-Advanced all at once. We discuss and review the solutions to alleviate the overload problem by Third Generation Partnership Project (3GPP). As a result, we evaluate and compare these solutions that can effectively eliminate the congestion on the random access channel for M2M communications without affecting H2H communications.

  18. Chronic hepatitis C infection-induced liver fibrogenesis is associated with M2 macrophage activation.

    PubMed

    Bility, Moses T; Nio, Kouki; Li, Feng; McGivern, David R; Lemon, Stanley M; Feeney, Eoin R; Chung, Raymond T; Su, Lishan

    2016-12-21

    The immuno-pathogenic mechanisms of chronic hepatitis C virus (HCV) infection remain to be elucidated and pose a major hurdle in treating or preventing chronic HCV-induced advanced liver diseases such as cirrhosis. Macrophages are a major component of the inflammatory milieu in chronic HCV-induced liver disease, and are generally derived from circulating inflammatory monocytes; however very little is known about their role in liver diseases. To investigate the activation and role of macrophages in chronic HCV-induced liver fibrosis, we utilized a recently developed humanized mouse model with autologous human immune and liver cells, human liver and blood samples and cell culture models of monocyte/macrophage and/or hepatic stellate cell activation. We showed that M2 macrophage activation was associated with liver fibrosis during chronic HCV infection in the livers of both humanized mice and patients, and direct-acting antiviral therapy attenuated M2 macrophage activation and associated liver fibrosis. We demonstrated that supernatant from HCV-infected liver cells activated human monocytes/macrophages with M2-like phenotypes. Importantly, HCV-activated monocytes/macrophages promoted hepatic stellate cell activation. These results suggest a critical role for M2 macrophage induction in chronic HCV-associated immune dysregulation and liver fibrosis.

  19. Polarization of M2 macrophages requires Lamtor1 that integrates cytokine and amino-acid signals

    PubMed Central

    Kimura, Tetsuya; Nada, Shigeyuki; Takegahara, Noriko; Okuno, Tatsusada; Nojima, Satoshi; Kang, Sujin; Ito, Daisuke; Morimoto, Keiko; Hosokawa, Takashi; Hayama, Yoshitomo; Mitsui, Yuichi; Sakurai, Natsuki; Sarashina-Kida, Hana; Nishide, Masayuki; Maeda, Yohei; Takamatsu, Hyota; Okuzaki, Daisuke; Yamada, Masaki; Okada, Masato; Kumanogoh, Atsushi

    2016-01-01

    Macrophages play crucial roles in host defence and tissue homoeostasis, processes in which both environmental stimuli and intracellularly generated metabolites influence activation of macrophages. Activated macrophages are classified into M1 and M2 macrophages. It remains unclear how intracellular nutrition sufficiency, especially for amino acid, influences on macrophage activation. Here we show that a lysosomal adaptor protein Lamtor1, which forms an amino-acid sensing complex with lysosomal vacuolar-type H+-ATPase (v-ATPase), and is the scaffold for amino acid-activated mTORC1 (mechanistic target of rapamycin complex 1), is critically required for M2 polarization. Lamtor1 deficiency, amino-acid starvation, or inhibition of v-ATPase and mTOR result in defective M2 polarization and enhanced M1 polarization. Furthermore, we identified liver X receptor (LXR) as the downstream target of Lamtor1 and mTORC1. Production of 25-hydroxycholesterol is dependent on Lamtor1 and mTORC1. Our findings demonstrate that Lamtor1 plays an essential role in M2 polarization, coupling immunity and metabolism. PMID:27731330

  20. Chlorogenic acid inhibits glioblastoma growth through repolarizating macrophage from M2 to M1 phenotype

    PubMed Central

    Xue, Nina; Zhou, Qin; Ji, Ming; Jin, Jing; Lai, Fangfang; Chen, Ju; Zhang, Mengtian; Jia, Jing; Yang, Huarong; Zhang, Jie; Li, Wenbin; Jiang, Jiandong; Chen, Xiaoguang

    2017-01-01

    Glioblastoma is an aggressive tumor that is associated with distinctive infiltrating microglia/macrophages populations. Previous studies demonstrated that chlorogenic acid (5-caffeoylquinic acid, CHA), a phenolic compound with low molecular weight, has an anti-tumor effect in multiple malignant tumors. In the present study, we focused on the macrophage polarization to investigate the molecular mechanisms behind the anti-glioma response of CHA in vitro and in vivo. We found that CHA treatment increased the expression of M1 markers induced by LPS/IFNγ, including iNOS, MHC II (I-A/I-E subregions) and CD11c, and reduced the expression of M2 markers Arg and CD206 induced by IL-4, resulting in promoting the production of apoptotic-like cancer cells and inhibiting the growth of tumor cells by co-culture experiments. The activations of STAT1 and STAT6, which are two crucial signaling events in M1 and M2-polarization, were significantly promoted and suppressed by CHA in macrophages, respectively. Furthermore, In G422 xenograft mice, CHA increased the proportion of CD11c-positive M1 macrophages and decreased the distribution of CD206-positive M2 macrophages in tumor tissue, consistent with the reduction of tumor weight observed in CHA-treated mice. Overall these findings indicated CHA as a potential therapeutic approach to reduce glioma growth through promoting M1-polarized macrophage and inhibiting M2 phenotypic macrophage. PMID:28045028

  1. M2-F1 on lakebed with Pontiac convertible tow vehicle

    NASA Technical Reports Server (NTRS)

    1963-01-01

    The M2-F1 lifting body, dubbed the 'flying bathtub' by the media, was the precursor of a remarkable series of wingless flying vehicles that contributed data used in the space shuttle and the X-38 Technology Demonstrator for crew return from the International Space Station. The early tow tests were done using the 1963 Pontiac Catalina convertible modified for the purpose. The first flight attempt occurred on 1 March 1963 but was unsuccessful due to control-system problems. It was not until 5 April 1963, after tests in the Ames Research Center wind tunnel, that Milt Thompson made the first M2-F1 tow flight. Based on the ideas and basic design of Alfred J. Eggers and others at the Ames Aeronautical Laboratory (now the Ames Research Center), Mountain View, Calif., in the mid-1950s, the M2-F1 came to be built over a four-month period in 1962-63 for a cost of only about $30,000 plus perhaps an additional $8,000-$10,000 for an ejection seat and $10,000 for solid-propellant rockets to add time to the landing flare. Engineers and technicians at the NASA Flight Research Center (now NASA Dryden) kept costs low by designing and fabricating it partly in-house, with the plywood shell constructed by a local sailplane builder. Someone at the time estimated that it would have cost a major aircraft company $150,000 to build the same vehicle. Unlike the later lifting bodies, the M2-F1 was unpowered and was initially towed until it was airborne by a souped-up Pontiac convertible. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina

  2. Complete genome sequence of Rhodospirillum rubrum type strain (S1).

    PubMed

    Munk, A Christine; Copeland, Alex; Lucas, Susan; Lapidus, Alla; Del Rio, Tijana Glavina; Barry, Kerrie; Detter, John C; Hammon, Nancy; Israni, Sanjay; Pitluck, Sam; Brettin, Thomas; Bruce, David; Han, Cliff; Tapia, Roxanne; Gilna, Paul; Schmutz, Jeremy; Larimer, Frank; Land, Miriam; Kyrpides, Nikos C; Mavromatis, Konstantinos; Richardson, Paul; Rohde, Manfred; Göker, Markus; Klenk, Hans-Peter; Zhang, Yaoping; Roberts, Gary P; Reslewic, Susan; Schwartz, David C

    2011-07-01

    Rhodospirillum rubrum (Esmarch 1887) Molisch 1907 is the type species of the genus Rhodospirillum, which is the type genus of the family Rhodospirillaceae in the class Alphaproteobacteria. The species is of special interest because it is an anoxygenic phototroph that produces extracellular elemental sulfur (instead of oxygen) while harvesting light. It contains one of the most simple photosynthetic systems currently known, lacking light harvesting complex 2. Strain S1(T) can grow on carbon monoxide as sole energy source. With currently over 1,750 PubMed entries, R. rubrum is one of the most intensively studied microbial species, in particular for physiological and genetic studies. Next to R. centenum strain SW, the genome sequence of strain S1(T) is only the second genome of a member of the genus Rhodospirillum to be published, but the first type strain genome from the genus. The 4,352,825 bp long chromosome and 53,732 bp plasmid with a total of 3,850 protein-coding and 83 RNA genes were sequenced as part of the DOE Joint Genome Institute Program DOEM 2002.

  3. Generation and characterization of a Tet-On (rtTA-M2) transgenic rat

    PubMed Central

    2010-01-01

    Background The tetracycline-inducible gene regulation system is a powerful tool that allows temporal and dose-dependent regulation of target transgene expression in vitro and in vivo. Several tetracycline-inducible transgenic mouse models have been described with ubiquitous or tissue-specific expression of tetracycline-transactivator (tTA), reverse tetracycline-transactivator (rtTA) or Tet repressor (TetR). Here we describe a Tet-On transgenic rat that ubiquitously expresses rtTA-M2 driven by the murine ROSA 26 promoter. Results The homozygous rat line (ROSA-rtTA-M2) generated by lentiviral vector injection, has a single integration site and was derived from the offspring of a genetic mosaic founder with multiple transgene integrations. The rtTA-M2 transgene integrated into an intron of a putative gene on chromosome 2 and does not appear to affect the tissue-specificity or expression of that gene. Fibroblasts from the ROSA-rtTA-M2 rats were transduced with a TetO7/CMV-EGFP lentivirus and exhibited doxycycline dose-dependent expression of the EGFP reporter transgene, in vitro. In addition, doxycycline-inducible EGFP expression was observed, in vivo, when the TetO7/CMV-EGFP lentivirus was injected into testis, kidney and muscle tissues of ROSA-rtTA-M2 rats. Conclusions This conditional expression rat model may have application for transgenic overexpression or knockdown studies of gene function in development, disease and gene therapy. PMID:20158911

  4. Unprimed, M1 and M2 Macrophages Differentially Interact with Porphyromonas gingivalis

    PubMed Central

    Lenzo, Jason C.; Fong, Shao B.; Reynolds, Eric C.

    2016-01-01

    Porphyromonas gingivalis is a keystone pathogen in the development of chronic periodontitis. Tissue macrophages are amongst the first immune cells to respond to bacteria and depending on the cytokine profile at the infection site, macrophages are primed to react to infection in different ways. Priming of naive macrophages with IFN-γ produces a classical pro-inflammatory, antibacterial M1 macrophage after TLR ligation, whereas priming with IL-4 induces an anti-inflammatory tissue-repair M2 phenotype. Previous work has shown that M1 are preferentially generated in gingival tissue following infection with P. gingivalis. However, few studies have investigated the interactions of macrophage subsets with P. gingivalis cells. The aim of this study was to determine the ability of naive, M1 and M2 macrophages to phagocytose P. gingivalis and investigate how this interaction affects both the bacterial cell and the macrophage. M1 and M2 macrophages were both found to have enhanced phagocytic capacity compared with that of naive macrophages, however only the naive and M1 macrophages were able to produce a respiratory burst in order to clear the bacteria from the phagosome. P. gingivalis was found to persist in naive and M2, but not M1 macrophages for 24 hours. Phagocytosis of P. gingivalis also induced high levels of TNF-α, IL-12 and iNOS in M1 macrophages, but not in naive or M2 macrophages. Furthermore, infection of macrophages with P. gingivalis at high bacteria to macrophage ratios, while inducing an inflammatory response, was also found to be deleterious to macrophage longevity, with high levels of apoptotic cell death found in macrophages after infection. The activation of M1 macrophages observed in this study may contribute to the initiation and maintenance of a pro-inflammatory state during chronic periodontitis. PMID:27383471

  5. Viral M2 ion channel protein: a promising target for anti-influenza drug discovery.

    PubMed

    Moorthy, N S Hari Narayana; Poongavanam, Vasanthanathan; Pratheepa, V

    2014-01-01

    Influenza virus is an important RNA virus causing pandemics (Spanish Flu (1918), Asian Flu (1957), Hong Kong Flu (1968) and Swine Flu (2009)) over the last decades. Due to the spontaneous mutations of these viral proteins, currently available antiviral and anti-influenza drugs quickly develop resistance. To account this, only limited antiinfluenza drugs have been approved for the therapeutic use. These include amantadine and rimantadine (M2 proton channel blockers), zanamivir, oseltamivir and peramivir (neuraminidase inhibitors), favipravir (polymerase inhibitor) and laninamivir. This review provides an outline on the strategies to develop novel, potent chemotherapeutic agents against M2 proton channel. Primarily, the M2 proton channel blockers elicit pharmacological activity through destabilizing the helices by blocking the proton transport across the transmembrane. The biologically important compounds discovered using the scaffolds such as bisnoradmantane, noradamantane, triazine, spiroadamantane, isoxazole, amino alcohol, azaspiro, spirene, pinanamine, etc are reported to exhibit anti-influenza activity against wild or mutant type (S31N and V27A) of M2 proton channel protein. The reported studies explained that the adamantane based compounds (amantadine and rimantadine) strongly interact with His37 (through hydrogen bonding) and Ala30, Ile33 and Gly34 residues (hydrophobic interactions). The adamantane and the non-adamantane scaffolds fit perfectly in the active site pocket present in the wild type and the charged amino groups (ammonium) create positive electrostatic potential, which blocks the transport of protons across the pore. In the mutated proteins, larger or smaller binding pocket are created by small or large mutant residues, which do not allow the molecules fit in the active site. This causes the channel to be unblocked and the protons are allowed to transfer inside the pore. The structural analysis of the M2 proton channel blockers illustrated that

  6. Neisseria gonorrhoeae Modulates Immunity by Polarizing Human Macrophages to a M2 Profile

    PubMed Central

    Ortiz, María Carolina; Lefimil, Claudia; Rodas, Paula I.; Vernal, Rolando; Lopez, Mercedes; Acuña-Castillo, Claudio; Imarai, Mónica; Escobar, Alejandro

    2015-01-01

    Current data suggest that Neisseria gonorrhoeae is able to suppress the protective immune response at different levels, such as B and T lymphocytes and antigen-presenting cells. The present report is focused on gonococcus evasion mechanism on macrophages (MФ) and its impact in the subsequent immune response. In response to various signals MФ may undergo classical-M1 (M1-MФ) or alternative-M2 (M2-MФ) activation. Until now there are no reports of the gonococcus effects on human MФ polarization. We assessed the phagocytic ability of monocyte-derived MФ (MDM) upon gonococcal infection by immunofluorescence and gentamicin protection experiments. Then, we evaluated cytokine profile and M1/M2 specific-surface markers on MФ challenged with N. gonorrhoeae and their proliferative effect on T cells. Our findings lead us to suggest N. gonorrhoeae stimulates a M2-MФ phenotype in which some of the M2b and none of the M1-MФ-associated markers are induced. Interestingly, N. gonorrhoeae exposure leads to upregulation of a Programmed Death Ligand 1 (PD-L1), widely known as an immunosuppressive molecule. Moreover, functional results showed that N. gonorrhoeae-treated MФ are unable to induce proliferation of human T-cells, suggesting a more likely regulatory phenotype. Taken together, our data show that N. gonorroheae interferes with MФ polarization. This study has important implications for understanding the mechanisms of clearance versus long-term persistence of N. gonorroheae infection and might be applicable for the development of new therapeutic strategies. PMID:26125939

  7. Dietary oleic acid increases m2 macrophages in the mesenteric adipose tissue.

    PubMed

    Camell, Christina; Smith, C Wayne

    2013-01-01

    Several studies have implicated fatty-acids as inflammatory regulators, suggesting that there may be a direct role for common dietary fatty-acids in regulating innate immune cells. In humans, a single high-fat meal increases systemic cytokines and leukocytes. In mice, short term high-fat feeding increases adipose tissue (AT) leukocytes and alters the inflammatory profile of AT macrophages. We have seen that short term high fat feeding to C57BL/6J male mice increases palmitic and oleic acid within AT depots, but oleic acid increase is highest in the mesenteric AT (MAT). In vitro, oleic acid increases M2 macrophage markers (CD206, MGL1, and ARG1) in a murine macrophage cell line, while addition of palmitic acid is able to inhibit that increase. Three day supplementation of a chow diet, with oleic acid, induced an increase in M2 macrophage markers in the MAT, but not in the epididymal AT. We tested whether increases in M2 macrophages occur during short term ad lib feeding of a high fat diet, containing oleic acid. Experiments revealed two distinct populations of macrophages were altered by a three day high milk-fat diet. One population, phenotypically intermediate for F4/80, showed diet-induced increases in CD206, an anti-inflammatory marker characteristic of M2 macrophages intrinsic to the AT. Evidence for a second population, phenotypically F4/80(HI)CD11b(HI) macrophages, showed increased association with the MAT following short term feeding that is dependent on the adhesion molecule, ICAM-1. Collectively, we have shown that short term feeding of a high-fat diet changes two population of macrophages, and that dietary oleic acid is responsible for increases in M2 macrophage polarization.

  8. Bilateral key comparison CCM.P-K3.1 for absolute pressure measurements from 3 × 10-6 Pa to 9 × 10-4 Pa

    NASA Astrophysics Data System (ADS)

    Fedchak, J. A.; Bock, Th; Jousten, K.

    2014-01-01

    This report describes the bilateral key comparison CCM.P-K3.1 between the National Institute of Standards and Technology (NIST) and Physikalisch-Technische Bundesanstalt (PTB) for absolute pressure in the range from 3 × 10-6 Pa to 9 × 10-4 Pa. This comparison was a follow-up to the comparison CCM.P-K3. Two ionization gauges and two spinning rotor gauges (SRGs) were used as the transfer standards for the comparison. The SRGs were used to compare the standards at a pressure of 9 × 10-4 Pa and to normalize the ionization gauge readings. The two ionization gauges were used to compare the standards in the pressure range of from 3 × 10-6 Pa to 3 × 10-4 Pa. Both laboratories used dynamic expansion chambers as standards in the comparison. The two labs showed excellent agreement with each other and with the CCM.P-K3 key comparison reference value (KCRV) over the entire range. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  9. M2-F1 in flight during low-speed car tow

    NASA Technical Reports Server (NTRS)

    1963-01-01

    The M2-F1 shown in flight during a low-speed car tow runs across the lakebed. Such tests allowed about two minutes to test the vehicle's handling in flight. NASA Flight Research Center (later redesignated the Dryden Flight Research Center) personnel conducted as many as 8 to 14 ground-tow flights in a single day either to test the vehicle in preparation for air tows or to train pilots to fly the vehicle before they undertook air tows. The wingless, lifting body aircraft design was initially concieved as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop near Long Beach for modification. With a special gearbox and racing slicks, the Pontiac could tow the 1,000-pound M2-F1 110 miles per hour in 30

  10. M2-F1 fabrication by Grierson Hamilton, Bob Green, and Ed Browne

    NASA Technical Reports Server (NTRS)

    1962-01-01

    Flight Research Center discretionary funds paid for the M2-F-1's construction. NASA mechanics, sheet-metal smiths, and technicians did much of the work in a curtained-off area of a hangar called the 'Wright Bicycle Shop.' The wingless, lifting body aircraft design was initially conceived as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop near Long Beach for modification. With a special gearbox and racing slicks, the Pontiac could tow the 1,000-pound M2-F1 110 miles per hour in 30 seconds. It proved adequate for the roughly 400 car tows that got the M2-F1 airborne to prove it could fly safely and to train pilots before they were towed behind a C-47 aircraft and released. These initial car-tow tests

  11. A phase I study of S-1 with concurrent thoracic radiotherapy in elderly patients with localized advanced non-small cell lung cancer.

    PubMed

    Takigawa, Nagio; Kiura, Katsuyuki; Hotta, Katsuyuki; Hosokawa, Shinobu; Nogami, Naoyuki; Aoe, Keisuke; Gemba, Kenichi; Fujiwara, Keiichi; Harita, Shingo; Takemoto, Mitsuhiro; Himei, Kengo; Shinkai, Tetsu; Fujiwara, Yoshirou; Takata, Saburo; Tabata, Masahiro; Kanazawa, Susumu; Tanimoto, Mitsune

    2011-01-01

    S-1, an oral 5-fluorouracil derivative, is effective against advanced non-small cell lung cancer (NSCLC) with mild toxicity and synergistic effects with radiation in preclinical trials. In this phase I study, we evaluated the dose-limiting toxicity and recommended dose of S-1 for a future phase II study when administered concurrently with thoracic radiation (total dose of 60 Gy at 2 Gy per daily fraction) in elderly patients (>75 years old) with localized advanced NSCLC. S-1 was administered on days 1-14 and 29-42 at the following dosages: 60, 70, and 80 mg/m(2)/day. Twenty-two previously untreated patients were enrolled in this study. Dose-limiting toxicity included febrile neutropenia, thrombocytopenia, stomatitis, and pneumonitis. One patient had grade 5 radiation pneumonitis. No other patient experienced radiation pneumonitis or esophagitis exceeding grade 2. The recommended dose for S-1 was determined to be 80 mg/m(2)/day, which produced an overall response rate of 75% (n=12). The median progression-free survival time was 11.5 months (95% confidence interval: 7.1-15.8 months) with a median follow-up time of 27.9 months. These results indicate that concurrent treatment with S-1 and thoracic radiation is a feasible option for NSCLC in the elderly. A phase II study is currently under way.

  12. Sphingosine 1-phosphate (S1P)/S1P receptor 1 signaling regulates receptor activator of NF-{kappa}B ligand (RANKL) expression in rheumatoid arthritis

    SciTech Connect

    Takeshita, Harunori; Kitano, Masayasu; Iwasaki, Tsuyoshi; Kitano, Sachie; Tsunemi, Sachi; Sato, Chieri; Sekiguchi, Masahiro; Azuma, Naoto; Miyazawa, Keiji; Hla, Timothy; Sano, Hajime

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer MH7A cells and CD4{sup +} T cells expressed S1P1 and RANKL. Black-Right-Pointing-Pointer S1P increased RANKL expression in MH7A cells and CD4{sup +} T cells. Black-Right-Pointing-Pointer The effect of S1P in MH7A cells was inhibited by specific Gi/Go inhibitors. -- Abstract: Sphingosine 1-phosphate (S1P)/S1P receptor 1 (S1P1) signaling plays an important role in synovial cell proliferation and inflammatory gene expression by rheumatoid arthritis (RA) synoviocytes. The purpose of this study is to clarify the role of S1P/S1P1 signaling in the expression of receptor activator of NF-{kappa}B ligand (RANKL) in RA synoviocytes and CD4{sup +} T cells. We demonstrated MH7A cells, a human RA synovial cell line, and CD4{sup +} T cells expressed S1P1 and RANKL. Surprisingly, S1P increased RANKL expression in MH7A cells and CD4{sup +} T cells in a dose-dependent manner. Moreover, S1P enhanced RANKL expression induced by stimulation with TNF-{alpha} in MH7A cells and CD4{sup +} T cells. These effects of S1P in MH7A cells were inhibited by pretreatment with PTX, a specific Gi/Go inhibitor. These findings suggest that S1P/S1P1 signaling may play an important role in RANKL expression by MH7A cells and CD4{sup +} T cells. S1P/S1P1 signaling of RA synoviocytes is closely connected with synovial hyperplasia, inflammation, and RANKL-induced osteoclastogenesis in RA. Thus, regulation of S1P/S1P1 signaling may become a novel therapeutic target for RA.

  13. Safety and efficacy of stereotactic body radiation therapy combined with S-1 simultaneously followed by sequential S-1 as an initial treatment for locally advanced pancreatic cancer (SILAPANC) trial: study design and rationale of a phase II clinical trial

    PubMed Central

    Zhu, Xiaofei; Ju, Xiaoping; Cao, Fei; Fang, Fang; Qing, Shuiwang; Shen, Yuxin; Jia, Zhen; Cao, Yangsen; Zhang, Huojun

    2016-01-01

    Introduction Upfront surgeries are not beneficial to most patients with pancreatic cancer. Therefore, more emphasis has been placed chemoradiotherapy in locally advanced pancreatic cancer recently. Gemcitabine-based regimens or FOLFIRINOX (a chemotherapy regimen including leucovorin, 5-FU, irinotecan, oxaliplatin) has been proven as a standard chemotherapy in pancreatic cancer. However, severe toxicities may prevent the completion of chemotherapy. S-1 has showed better objective response rates, similar overall survival rates and progression-free survival rates compared with gemcitabine, revealing that S-1 may be a potential candidate in treating pancreatic cancer, especially for patients refractory to gemcitabine. Additionally, stereotactic body radiation therapy with Cyberknife could provide better efficacy than conventional radiotherapy in pancreatic cancer. Therefore, Cyberknife with S-1 simultaneously followed by sequential S-1 as an initial treatment may bring about favourable outcomes but needs further studies. Methods and analysis The S-1 as an initial treatment for locally advanced pancreatic cancer (SILAPANC) trial is a prospective, single-centre, one armed ongoing study. 190 eligible patients are required to initially receive Cyberknife with 1 cycle of S-1 simultaneously. After the concurrent chemoradiotherapy, 2 or 3 cycles of S-1 are sequentially given. Doses and fractions depend on the locations and volumes of tumours and the adjacent organs at risk. S-1 is taken orally, 2 times a day, at a dose of 80 mg/m2 for 28 days, followed by a 14-day interval. The primary objectives are overall survival and 1-year, 2-year, 3-year, 4-year and 5-year overall survival rates. The secondary objectives are cancer-specific survival, progression-free survival, time to progression, local control rates, clinical benefit rates, radiation-induced acute and late toxicities, adverse effects of chemotherapy and quality of life of patients. Besides, variables most

  14. Motion-to-Energy (M2Eâ„¢) Power Generation Technology

    ScienceCinema

    Idaho National Laboratory

    2016-07-12

    INL researchers developed M2E, a new technology that converts motion to energy. M2E uses an innovative, optimized microgenerator with power management circuitry that kinetically charges mobile batteries from natural motion such as walking. To learn more,

  15. The modulatory role of M2 muscarinic receptor on apomorphine-induced yawning and genital grooming.

    PubMed

    Gamberini, Maria Thereza; Bolognesi, Maria Laura; Nasello, Antonia Gladys

    2012-12-07

    The interaction between dopaminergic and cholinergic pathways in the induction of behavioral responses has been previously established. In the brain, M2 receptors are found predominantly in presynaptic cholinergic neurons as autoreceptors, and in dopaminergic neurons as heteroceptors, suggesting a control role of acetylcholine and dopamine release, respectively. Our aim was to investigate the role of M2 receptors on the yawning and genital grooming of rats induced by apomorphine, a dopaminergic receptor agonist, focusing on the interaction between cholinergic and dopaminergic pathways. Initially, the effect of atropine, a non-selective muscarinic antagonist, on yawning and genital grooming induced by apomorphine (100 μg/kg s.c.) was analyzed. Atropine doses of 0.5, 1 and 2 mg/kg i.p. were administered to Wistar rats 30 min before induction of the behavioral responses by apomorphine. Number of yawns and time spent genital grooming were quantified over a 60 min period. Apomorphine-induced yawning was increased by low dose (0.5 mg/kg i.p.) but not by high doses (1 and 2 mg/kg, i.p.) of atropine. Genital grooming was antagonized by 2 mg/kg i.p. of atropine and showed no changes at the other doses tested. Tripitramine, a selective M2 cholinergic antagonist, was used as a tool for distinguishing between M2 and all other muscarinic receptor subtypes in yawning and genital grooming. Tripitramine doses of 0.01, 0.02 and 0.04 μmol/kg i.p. were administered to Wistar rats 30 min before apomorphine (100 μg/kg s.c.). Number of yawns and time spent genital grooming were also quantified over a 60 min period. Tripitramine 0.01 μmol/kg increased all parameters. Higher doses, which possibly block all subtypes of muscarinic receptor, did not modify the response of apomorphine, suggesting a non-selective effect of tripitramine at these doses. Given that low doses of tripitramine increased the behavioral responses induced by apomorphine and that the main distribution of the M2

  16. A phase I study of combination S-1 plus cisplatin chemotherapy with concurrent thoracic radiation for locally advanced non-small cell lung cancer.

    PubMed

    Chikamori, Kenichi; Kishino, Daizo; Takigawa, Nagio; Hotta, Katsuyuki; Nogami, Naoyuki; Kamei, Haruhito; Kuyama, Shoichi; Gemba, Kenichi; Takemoto, Mitsuhiro; Kanazawa, Susumu; Ueoka, Hiroshi; Segawa, Yoshihiko; Takata, Saburo; Tabata, Masahiro; Kiura, Katsuyuki; Tanimoto, Mitsune

    2009-07-01

    A combination of S-1, a newly developed oral 5-fluorouracil derivative, and cisplatin is reported to show anti-tumour activity against advanced non-small cell lung cancer (NSCLC). Because S-1 shows synergistic effects with radiation, we conducted a phase I study to evaluate the maximum tolerated doses (MTDs), recommended doses (RDs), and dose-limiting toxicities (DLTs) of cisplatin and S-1 when combined with concurrent thoracic radiation (total dose of 60 Gy with 2 Gy per daily fraction) in patients with locally advanced NSCLC. Chemotherapy consisted of two 4-week cycles of cisplatin administered on days 1 and 8, and S-1 administered on days 1-14. S-1/cisplatin dosages (mg/m(2)/day) were escalated as follows: 60/30, 60/40, 70/40, 80/40 and 80/50. Twenty-two previously untreated patients were enrolled. The MTDs and RDs for S-1/cisplatin were 80/50 and 80/40, respectively. DLTs included febrile neutropaenia, thrombocytopaenia, bacterial pneumonia and delayed second cycle of chemotherapy. No patient experienced radiation pneumonitis>grade 2 and only one patient experienced grade 3 radiation oesophagitis. The overall response rate was 86.4% with a median survival time of 24.4 months. These results indicate that combination cisplatin-S-1 chemotherapy with concurrent thoracic radiation would be a feasible treatment option and a phase II study is currently under way.

  17. Effect of anisotropy in the S=1 underscreened Kondo lattice

    NASA Astrophysics Data System (ADS)

    Thomas, Christopher; da Rosa Simões, Acirete S.; Lacroix, Claudine; Iglesias, José Roberto; Coqblin, Bernard

    2014-12-01

    We study the effect of crystal field anisotropy in the underscreened S=1 Kondo lattice model. Starting from the two orbital Anderson lattice model and including a local anisotropy term, we show, through Schrieffer-Wolff transformation, that local anisotropy is equivalent to an anisotropic Kondo interaction (J∥≠J⊥). The competition and coexistence between ferromagnetism and Kondo effect in this effective model is studied within a generalized mean-field approximation. Several regimes are obtained, depending on the parameters, exhibiting or not coexistence of magnetic order and Kondo effect. Particularly, we show that a re-entrant Kondo phase at low temperature can be obtained. We are also able to describe phases where the Kondo temperature is smaller than the Curie temperature (TK

  18. Confinement and power balance in the S-1 spheromak

    SciTech Connect

    Levinton, F.M.; Meyerhofer, D.D.; Mayo, R.M.; Janos, A.C.; Ono, Y.; Ueda, Y.; Yamada, M.

    1989-07-01

    The confinement and scaling features of the S-1 spheromak have been investigated using magnetic, spectroscopic, and Thomson scattering data in conjunction with numerical modeling. Results from the multipoint Thomson scattering diagnostic shows that the central beta remains constant (/beta//sub to/ /approximately/ 5%) as the plasma current density increases from 0.68--2.1 MA/m/sup 2/. The density is observed to increase slowly over this range, while the central electron temperature increases much more rapidly. Analysis of the global plasma parameters shows a decrease in the volume average beta and energy confinement as the total current is increased. The power balance has been modeled numerically with a 0-D non-equilibrium time-dependent coronal model and is consistent with the experimental observations. 20 refs., 12 figs., 2 tabs.

  19. Transitive Lie groups on S^1\\times S^{2m}

    NASA Astrophysics Data System (ADS)

    Gorbatsevich, Vladimir V.

    2007-10-01

    The structure of Lie groups acting transitively on the direct product of a circle and an even-dimensional sphere is described. For products of two spheres of dimension >1 a similar problem has already been solved by other authors. The minimal transitive Lie groups on S^1 and S^{2m} are also indicated. As an application of these results, the structure of the automorphism group of one class of geometric structures, generalized quadrangles (a special case of Tits buildings) is considered. A conjecture put forward by Kramer is proved: the automorphism group of a connected generalized quadrangle of type (1,2m) always contains a transitive subgroup that is the direct product of a compact simple Lie group and a one-dimensional Lie group. Bibliography: 16 titles.

  20. Magnetoelectric Behavior from S =1 /2 Asymmetric Square Cupolas

    NASA Astrophysics Data System (ADS)

    Kato, Yasuyuki; Kimura, Kenta; Miyake, Atsushi; Tokunaga, Masashi; Matsuo, Akira; Kindo, Koichi; Akaki, Mitsuru; Hagiwara, Masayuki; Sera, Masakazu; Kimura, Tsuyoshi; Motome, Yukitoshi

    2017-03-01

    Magnetoelectric properties are studied by a combined experimental and theoretical study of a quasi-two-dimensional material composed of square cupolas, Ba(TiO )Cu4(PO4 ) 4 . The magnetization is measured up to the field above the saturation, and several anomalies are observed depending on the field directions. We propose a S =1 /2 spin model with Dzyaloshinskii-Moriya interactions, which reproduces the full magnetization curves well. Elaborating the phase diagram of the model, we show that the anomalies are explained by magnetoelectric phase transitions. Our theory also accounts for the scaling of the dielectric anomaly observed in the experiments. The results elucidate the crucial role of the in-plane component of Dzyaloshinskii-Moriya interactions, which is induced by the noncoplanar buckling of a square cupola. We also predict a "hidden" phase and another magnetoelectric response, both of which appear in a nonzero magnetic field.

  1. Sphingosine 1-phosphate (S1P) induces COX-2 expression and PGE2 formation via S1P receptor 2 in renal mesangial cells.

    PubMed

    Völzke, Anja; Koch, Alexander; Meyer Zu Heringdorf, Dagmar; Huwiler, Andrea; Pfeilschifter, Josef

    2014-01-01

    Understanding the mechanisms of sphingosine 1-phosphate (S1P)-induced cyclooxygenase (COX)-2 expression and prostaglandin E2 (PGE2) formation in renal mesangial cells may provide potential therapeutic targets to treat inflammatory glomerular diseases. Thus, we evaluated the S1P-dependent signaling mechanisms which are responsible for enhanced COX-2 expression and PGE2 formation in rat mesangial cells under basal conditions. Furthermore, we investigated whether these mechanisms are operative in the presence of angiotensin II (Ang II) and of the pro-inflammatory cytokine interleukin-1β (IL-1β). Treatment of rat and human mesangial cells with S1P led to concentration-dependent enhanced expression of COX-2. Pharmacological and molecular biology approaches revealed that the S1P-dependent increase of COX-2 mRNA and protein expression was mediated via activation of S1P receptor 2 (S1P2). Further, inhibition of Gi and p42/p44 MAPK signaling, both downstream of S1P2, abolished the S1P-induced COX-2 expression. In addition, S1P/S1P2-dependent upregulation of COX-2 led to significantly elevated PGE2 levels, which were further potentiated in the presence of Ang II and IL-1β. A functional consequence downstream of S1P/S1P2 signaling is mesangial cell migration that is stimulated by S1P. Interestingly, inhibition of COX-2 by celecoxib and SC-236 completely abolished the migratory response. Overall, our results demonstrate that extracellular S1P induces COX-2 expression via activation of S1P2 and subsequent Gi and p42/p44 MAPK-dependent signaling in renal mesangial cells leading to enhanced PGE2 formation and cell migration that essentially requires COX-2. Thus, targeting S1P/S1P2 signaling pathways might be a novel strategy to treat renal inflammatory diseases.

  2. Selective coupling of the S1P3 receptor subtype to S1P-mediated RhoA activation and cardioprotection.

    PubMed

    Yung, Bryan S; Brand, Cameron S; Xiang, Sunny Y; Gray, Charles B B; Means, Christopher K; Rosen, Hugh; Chun, Jerold; Purcell, Nicole H; Brown, Joan Heller; Miyamoto, Shigeki

    2017-02-01

    Sphingosine-1-phosphate (S1P), a bioactive lysophospholipid, is generated and released at sites of tissue injury in the heart and can act on S1P1, S1P2, and S1P3 receptor subtypes to affect cardiovascular responses. We established that S1P causes little phosphoinositide hydrolysis and does not induce hypertrophy indicating that it does not cause receptor coupling to Gq. We previously demonstrated that S1P confers cardioprotection against ischemia/reperfusion by activating RhoA and its downstream effector PKD. The S1P receptor subtypes and G proteins that regulate RhoA activation and downstream responses in the heart have not been determined. Using siRNA or pertussis toxin to inhibit different G proteins in NRVMs we established that S1P regulates RhoA activation through Gα13 but not Gα12, Gαq, or Gαi. Knockdown of the three major S1P receptors using siRNA demonstrated a requirement for S1P3 in RhoA activation and subsequent phosphorylation of PKD, and this was confirmed in studies using isolated hearts from S1P3 knockout (KO) mice. S1P treatment reduced infarct size induced by ischemia/reperfusion in Langendorff perfused wild-type (WT) hearts and this protection was abolished in the S1P3 KO mouse heart. CYM-51736, an S1P3-specific agonist, also decreased infarct size after ischemia/reperfusion to a degree similar to that achieved by S1P. The finding that S1P3 receptor- and Gα13-mediated RhoA activation is responsible for protection against ischemia/reperfusion suggests that selective targeting of S1P3 receptors could provide therapeutic benefits in ischemic heart disease.

  3. Regulation of human cerebro-microvascular endothelial baso-lateral adhesion and barrier function by S1P through dual involvement of S1P1 and S1P2 receptors.

    PubMed

    Wiltshire, Rachael; Nelson, Vicky; Kho, Dan Ting; Angel, Catherine E; O'Carroll, Simon J; Graham, E Scott

    2016-01-27

    Herein we show that S1P rapidly and acutely reduces the focal adhesion strength and barrier tightness of brain endothelial cells. xCELLigence biosensor technology was used to measure focal adhesion, which was reduced by S1P acutely and this response was mediated through both S1P1 and S1P2 receptors. S1P increased secretion of several pro-inflammatory mediators from brain endothelial cells. However, the magnitude of this response was small in comparison to that mediated by TNFα or IL-1β. Furthermore, S1P did not significantly increase cell-surface expression of any key cell adhesion molecules involved in leukocyte recruitment, included ICAM-1 and VCAM-1. Finally, we reveal that S1P acutely and dynamically regulates microvascular endothelial barrier tightness in a manner consistent with regulated rapid opening followed by closing and strengthening of the barrier. We hypothesise that the role of the S1P receptors in this process is not to cause barrier dysfunction, but is related to controlled opening of the endothelial junctions. This was revealed using real-time measurement of barrier integrity using ECIS ZΘ TEER technology and endothelial viability using xCELLigence technology. Finally, we show that these responses do not occur simply though the pharmacology of a single S1P receptor but involves coordinated action of S1P1 and S1P2 receptors.

  4. Regulation of human cerebro-microvascular endothelial baso-lateral adhesion and barrier function by S1P through dual involvement of S1P1 and S1P2 receptors

    PubMed Central

    Wiltshire, Rachael; Nelson, Vicky; Kho, Dan Ting; Angel, Catherine E.; O’Carroll, Simon J.; Graham, E. Scott

    2016-01-01

    Herein we show that S1P rapidly and acutely reduces the focal adhesion strength and barrier tightness of brain endothelial cells. xCELLigence biosensor technology was used to measure focal adhesion, which was reduced by S1P acutely and this response was mediated through both S1P1 and S1P2 receptors. S1P increased secretion of several pro-inflammatory mediators from brain endothelial cells. However, the magnitude of this response was small in comparison to that mediated by TNFα or IL-1β. Furthermore, S1P did not significantly increase cell-surface expression of any key cell adhesion molecules involved in leukocyte recruitment, included ICAM-1 and VCAM-1. Finally, we reveal that S1P acutely and dynamically regulates microvascular endothelial barrier tightness in a manner consistent with regulated rapid opening followed by closing and strengthening of the barrier. We hypothesise that the role of the S1P receptors in this process is not to cause barrier dysfunction, but is related to controlled opening of the endothelial junctions. This was revealed using real-time measurement of barrier integrity using ECIS ZΘ TEER technology and endothelial viability using xCELLigence technology. Finally, we show that these responses do not occur simply though the pharmacology of a single S1P receptor but involves coordinated action of S1P1 and S1P2 receptors. PMID:26813587

  5. 75 FR 74740 - Measure M2 Natural Community Conservation Plan/Habitat Conservation Plan/Master Streambed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-01

    ... Fish and Wildlife Service Measure M2 Natural Community Conservation Plan/Habitat Conservation Plan... Environmental Impact Report (EIR)/EIS for the Measure M2 (M2) Natural Community Conservation Plan/Habitat Conservation Plan/Master Streambed Alteration Agreement (NCCP/HCP/ MSAA). We are furnishing this notice...

  6. Deletion of the M2-2 gene from avian metapneumovirus subgroup C impairs virus replication and immunogenicity in turkeys

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The second matrix (M2) gene of avian metapneumovirus subgroup C (aMPV-C) virus contains two overlapping open reading frames (ORFs), encoding two putative proteins, M2-1 and M2-2. Both proteins are believed to be involved in the RNA transcription or replication process. To further characterize the fu...

  7. M2 protein from influenza A: from multiple structures to biophysical and functional insights.

    PubMed

    Cross, Timothy A; Dong, Hao; Sharma, Mukesh; Busath, David D; Zhou, Huan-Xiang

    2012-04-01

    The M2 protein from influenza A is a proton channel as a tetramer, with a single transmembrane helix from each monomer lining the pore. Val27 and Trp41 form gates at either end of the pore and His37 mediates the shuttling of protons across a central barrier between the N-terminal and C-terminal aqueous pore regions. Numerous structures of this transmembrane domain and of a longer construct that includes an amphipathic helix are now in the Protein Data Bank. Many structural differences are apparent from samples obtained in a variety of membrane mimetic environments. High-resolution structural results in lipid bilayers have provided novel insights into the functional mechanism of the unique HxxxW cluster in the M2 proton channel.

  8. Characterization of M2X formed during 5 MeV Fe2+ irradiation

    NASA Astrophysics Data System (ADS)

    Getto, E.; Sun, K.; Was, G. S.

    2017-03-01

    The growth of M2X phase in HT9 irradiated to high dpa was explored using self-ion irradiation. HT9 was pre-implanted with 10 appm He and irradiated with a raster-scanned Fe2+ beam with a damage rate of ∼1 × 10-3 dpa/s at 460 °C. The precipitation of M2X was observed and a combination of high resolution transmission electron microscopy (HRTEM), energy filtered transmission electron microscopy (EFTEM) and diffraction analysis was used to characterize the Cr-rich carbide observed at 250 dpa and above. Cr2C was determined to be semi-coherent with the matrix such that [ 100 ] Cr2 C / /[100]α and [ 001 ] Cr2 C / /[ 10 1 bar ] α .with a = 2.71 Å and c = 2.82 Å.

  9. Foton-M2 Russian/US Biology Experiments - Development, Implementation, and Operations

    NASA Technical Reports Server (NTRS)

    Ilyin, Eugene A.; Tairbekov, Murad G.; Vasques, Marilyn F.; Skidmore, Michael G.

    2006-01-01

    The Russian Foton-M2 unmanned research satellite launched from Baikonur, Kazakhstan on May 31, 2005. The satellite was recovered 16 days later in northern Kazakhstan near Kustanay. Prior to this mission, the long history of joint NASA/IMBP research using Russian unmanned spacecraft was in danger of withering due to inactivity. This cooperative history included 9 Bion Russian spaceflights in the period from 1975 to 1997 where NASA had participated first as a guest and finally as a contractual partner. In an effort to reinvigorate this long-standing collaboration, the Institute for Biomedical Problems (IMBP) invited NASA participation in Russian experiments that had been manifested to fly on the Foton-M2 mission.

  10. Proton conductance of influenza virus M2 protein in planar lipid bilayers.

    PubMed

    Vijayvergiya, Viksita; Wilson, Ryan; Chorak, Adam; Gao, Philip Fei; Cross, Timothy A; Busath, David D

    2004-09-01

    Purified M2 protein from the Udorn strain of influenza virus was reconstituted into planar lipid bilayers from liposomes. In 1 mM HCl, the single-channel conductance was measured as 6 pS with open probability of < or =0.03. The current voltage curve is linear over the achievable voltage range. The current amplitude is amantadine sensitive. In HCl solutions, the single-channel current was essentially invariant with changes in [Cl(-)], [Na(+)], and [tetraethylammonium] ([TEA(+)]), but dependent on [H(+)]. The reversal potential, determined with asymmetrical hydrogen chloride solution, is very close to the equilibrium potential of hydrogen. This appears to be the first report of single-channel proton currents with the full-length M2 protein.

  11. The new VLT-DSM M2 unit: construction and electromechanical testing

    NASA Astrophysics Data System (ADS)

    Gallieni, Daniele; Biasi, Roberto

    2013-12-01

    We present the design, construction and validation of the new M2 unit of the VLT Deformable Secondary Mirror. In the framework of the Adaptive Optics Facility program, ADS and Microgate designed a new secondary unit which replaces the current Dornier one. The M2 is composed by the mechanical structure, a new hexapod positioner and the Deformable Secondary Mirror unit.The DSM is based on the well proven contactless, voice coil motor technology that has been already successfully implemented in the MMT, LBT and Magellan adaptive secondaries, and is considered a promising technical choice for the E-ELT M4 and the GMT ASM. The VLT adaptive unit has been fully integrated and, before starting the optical calibration, has completed the electromechanical characterization, focused on the dynamic performance. With respect to the previous units we introduced several improvements, both in hardware and control architecture that allowed achieving a significant enhancement of the system dynamics and reduction of power consumption.

  12. M2 to D2 and vice versa by 3-Lie and Lie bialgebra

    NASA Astrophysics Data System (ADS)

    Aali-Javanangrouh, M.; Rezaei-Aghdam, A.

    2016-11-01

    Using the concept of a 3-Lie bialgebra, which has recently been defined in arXiv:1604.04475, we construct a Bagger-Lambert-Gustavson (BLG) model for the M2-brane on a Manin triple of a special 3-Lie bialgebra. Then by using the correspondence and the relation between those 3-Lie bialgebra with Lie bialgebra, we reduce this model to an N=(4,4) WZW model (D2-brane), such that its algebraic structure is a Lie bialgebra with one 2-cocycle. In this manner by using the correspondence of the 3-Lie bialgebra and Lie bialgebra (for this special 3-Lie algebra) one can construct the M2-brane from a D2-brane and vice versa.

  13. M2-like macrophage polarization in high lactic acid-producing head and neck cancer.

    PubMed

    Ohashi, Toshimitsu; Aoki, Mitsuhiro; Tomita, Hiroyuki; Akazawa, Takashi; Sato, Katsuya; Kuze, Bunya; Mizuta, Keisuke; Hara, Akira; Nagaoka, Hitoshi; Inoue, Norimitsu; Ito, Yatsuji

    2017-04-01

    Reprogramming of glucose metabolism in tumor cells is referred to as the Warburg effect and results in increased lactic acid secretion into the tumor microenvironment. We have previously shown that lactic acid has important roles as a proinflammatory and immunosuppressive mediator and promotes tumor progression. In this study, we examined the relationship between the lactic acid concentration and expression of lactate dehydrogenase-A (LDHA) and glucose transporter-1 (GLUT1), which are related to the Warburg effect, in human head and neck squamous cell carcinoma (HNSCC). Tumors expressing lower levels of LDHA and GLUT1 had a higher concentration of lactic acid than those with higher LDHA and GLUT1 expression. Lactic acid also suppressed the expression of LDHA and GLUT1 in vitro. We previously reported that lactic acid enhances expression of a M2 macrophage marker, arginase I (ARG1), in murine macrophages. Therefore, we investigated the relationship between the lactic acid concentration and polarization of M2 macrophages in HNSCC by measuring the expression of M2 macrophage markers, colony stimulating factor 1 receptor (CSF1R) and CD163, normalized using a pan-macrophage marker, CD68. Tumors with lower levels of CD68 showed a higher concentration of lactic acid, while those with higher levels of CSF1R showed a significantly higher concentration of lactic acid. A similar tendency was observed for CD163. These results suggest that tumor-secreted lactic acid is linked to the reduction of macrophages in tumors and promotes induction of M2-like macrophage polarization in human HNSCC. This article is protected by copyright. All rights reserved.

  14. Industry 4.0, M2m, Iot&S - All Equal?

    NASA Astrophysics Data System (ADS)

    Dobrin, Carmen

    2014-11-01

    Similarity between Industry 4.0, M2M, IOT&S. Advantages and disadvantages obtained using this three important methods. Decreasing costs while components are getting smaller and smaller in a world with better networking. Influence of business management applications integrated in smart factory logistic. The most important impacts in merging virtual and real production world, with the improvement of best processes having the same goal: creating value by open innovation

  15. Agonists with supraphysiological efficacy at the muscarinic M2 ACh receptor

    PubMed Central

    Schrage, R; Seemann, WK; Klöckner, J; Dallanoce, C; Racké, K; Kostenis, E; De Amici, M; Holzgrabe, U; Mohr, K

    2013-01-01

    Background and Purpose Artificial agonists may have higher efficacy for receptor activation than the physiological agonist. Until now, such ‘superagonism’ has rarely been reported for GPCRs. Iperoxo is an extremely potent muscarinic receptor agonist. We hypothesized that iperoxo is a ‘superagonist’. Experimental Approach Signalling of iperoxo and newly synthesized structural analogues was compared with that of ACh at label-free M2 muscarinic receptors applying whole cell dynamic mass redistribution, measurement of G-protein activation, evaluation of cell surface agonist binding and computation of operational efficacies. Key Results In CHO-hM2 cells, iperoxo significantly exceeds ACh in Gi/Gs signalling competence. In the orthosteric loss-of-function mutant M2-Y1043.33A, the maximum effect of iperoxo is hardly compromised in contrast to ACh. ‘Superagonism’ is preserved in the physiological cellular context of MRC-5 human lung fibroblasts. Structure–signalling relationships including iperoxo derivatives with either modified positively charged head group or altered tail suggest that ‘superagonism’ of iperoxo is mechanistically based on parallel activation of the receptor protein via two orthosteric interaction points. Conclusion and Implications Supraphysiological agonist efficacy at muscarinic M2 ACh receptors is demonstrated for the first time. In addition, a possible underlying molecular mechanism of GPCR ‘superagonism’ is provided. We suggest that iperoxo-like orthosteric GPCR activation is a new avenue towards a novel class of receptor activators. Linked Article This article is commented on by Langmead and Christopoulos, pp. 353–356 of this issue. To view this commentary visit http://dx.doi.org/10.1111/bph.12142 PMID:23062057

  16. Regional outbreak of CTX-M-2 β-lactamase-producing Proteus mirabilis in Japan.

    PubMed

    Nakano, Ryuichi; Nakano, Akiyo; Abe, Michiko; Inoue, Matsuhisa; Okamoto, Ryoichi

    2012-12-01

    Proteus mirabilis is a common cause of urinary tract infection. Wild-type P. mirabilis strains are usually susceptible to penicillins and cephalosporins, but occurrences of P. mirabilis producing extended-spectrum β-lactamases (ESBLs) have been recently reported. Here, we surveyed the prevalence of cefotaxime resistance among P. mirabilis strains at seven different hospitals in Kanagawa Prefecture, Japan, and investigated their molecular epidemiology to explain the mechanism of their spread. The prevalence of cefotaxime resistance among P. mirabilis increased annually, from 10.1 % in 1998 to 23.1 % in 2003, and increased drastically in 2004, exceeding 40 %. We collected 105 consecutive and non-duplicate cefotaxime-resistant P. mirabilis isolates (MIC 16 to >256 µg ml(-1)) from these hospitals from June 2004 to May 2005 and characterized their profile. PCR and sequence analysis revealed that all resistant strains produced exclusively CTX-M-2 β-lactamase. PFGE analysis identified 47 banding patterns with 83 % or greater similarity. These results indicated that a regional outbreak of P. mirabilis producing CTX-M-2 β-lactamase has occurred in Japan and suggest that the epidemic spread occurred within and across hospitals and communities by extended clonal strains. Plasmid analysis revealed that 44.8 % of plasmids harboured by bla(CTX-M-2) isolates had common profiles, encoding ISEcp1, IS26 and Int1, and belonged to incompatibility group T. Spread of the resistant isolates in Japan resulted from dissemination of narrow-host-range plasmids of the IncT group encoding bla(CTX-M-2). These findings indicate the rapidly developing problem of treating the species to prevent dissemination of ESBL producers.

  17. M2 Internal Tide Propagation Through a Geostrophic Front Near the Critical Latitude

    NASA Astrophysics Data System (ADS)

    Chavanne, C. P.; Massad, A.; Heywood, K. J.

    2012-12-01

    A year-long (February 2009 - February 2010) record of ocean currents from instruments (RDI ADCP and Nortek Aquadopp) moored across the continental shelf and slope in the south-east Weddell Sea (~18 W, ~72.5 S) is analysed to investigate the propagation of M2 internal tides through a geostrophic front, the Antarctic Slope Front, near the M2 critical latitude (74.5 S). The record is long enough to separate M2 tides from local inertial currents, as confirmed by the downward phase propagation of M2 currents, indicative of upward energy propagation consistent with topographically-generated internal tides. Vertically-localized peaks of kinetic energy, indicative of internal tide beams, are found just above the bottom at the shelf break, and between 100 and 200 m depths at four of the five moorings. Ray tracing in the absence of background currents predicts internal ray paths inconsistent with the observed kinetic energy peak locations. The effects of the Antarctic Slope Front on internal tide propagation are investigated in two steps. Firstly, the background shears are neglected in the dispersion relation (except for their effect on the local buoyancy frequency), but allowed to refract the internal tides. Predicted internal ray paths are substantially modified from those in an ocean at rest, but they are still inconsistent with observations. Secondly, the background shears are allowed to modify the dispersion relation, dramatically modifying the predicted ray paths and vertical wavenumbers. These results demonstrate that geostrophic shears strongly affect internal tides propagation near their critical latitude, with implications on localization and parametrisation of internal-tide induced diapycnal mixing.

  18. Spreading depression requires microglia and is decreased by their M2a polarization from environmental enrichment.

    PubMed

    Pusic, Kae M; Pusic, Aya D; Kemme, Jordan; Kraig, Richard P

    2014-07-01

    Microglia play an important role in fine-tuning neuronal activity. In part, this involves their production of tumor necrosis factor-alpha (TNFα), which increases neuronal excitability. Excessive synaptic activity is necessary to initiate spreading depression (SD). Increased microglial production of proinflammatory cytokines promotes initiation of SD, which, when recurrent, may play a role in conversion of episodic to high frequency and chronic migraine. Previous work shows that this potentiation of SD occurs through increased microglial production of TNFα and reactive oxygen species, both of which are associated with an M1-skewed microglial population. Hence, we explored the role of microglia and their M1 polarization in SD initiation. Selective ablation of microglia from rat hippocampal slice cultures confirmed that microglia are essential for initiation of SD. Application of minocycline to dampen M1 signaling led to increased SD threshold. In addition, we found that SD threshold was increased in rats exposed to environmental enrichment. These rats had increased neocortical levels of interleukin-11 (IL-11), which decreases TNFα signaling and polarized microglia to an M2a-dominant phenotype. M2a microglia reduce proinflammatory signaling and increase production of anti-inflammatory cytokines, and therefore may protect against SD. Nasal administration of IL-11 to mimic effects of environmental enrichment likewise increased M2a polarization and increased SD threshold, an effect also seen in vitro. Similarly, application of conditioned medium from M2a polarized primary microglia to slice cultures also increased SD threshold. Thus, microglia and their polarization state play an essential role in SD initiation, and perhaps by extension migraine with aura and migraine.

  19. A picrotoxin-specific conformational change in the glycine receptor M2-M3 loop.

    PubMed

    Hawthorne, Rebecca; Lynch, Joseph W

    2005-10-28

    The external loop linking the M2 and M3 transmembrane domains is crucial for coupling agonist binding to channel gating in the glycine receptor chloride channel (GlyR). A substituted cysteine accessibility scan previously showed that glycine activation increased the surface accessibility of 6 contiguous residues (Arg271-Lys276) toward the N-terminal end of the homomeric alpha1 GlyR M2-M3 loop. In the present study we used a similar approach to determine whether the allosteric antagonist, picrotoxin, could impose conformational changes to this domain that cannot be induced by varying agonist concentrations alone. Picrotoxin slowed the reaction rate of a sulfhydryl-containing compound (MTSET) with A272C, S273C, and L274C. Before interpreting this as a picrotoxin-specific conformational change, it was necessary to eliminate the possibility of steric competition between picrotoxin and MTSET. Accordingly, we showed that picrotoxin and the structurally unrelated blocker, bilobalide, were both trapped in the R271C GlyR in the closed state and that a point mutation to the pore-lining Thr6' residue abolished inhibition by both compounds. We also demonstrated that the picrotoxin dissociation rate was linearly related to the channel open probability. These observations constitute a strong case for picrotoxin binding in the pore. We thus conclude that the picrotoxin-specific effects on the M2-M3 loop are mediated allosterically. This suggests that the M2-M3 loop responds differently to the occupation of different binding sites.

  20. Seasonal variability of the M2 tide in the seas adjacent to Korea

    NASA Astrophysics Data System (ADS)

    Kang, Sok Kuh; Chung, Jong-yul; Lee, Sang-Ryong; Yum, Ki-Dat

    1995-08-01

    Seasonal variability of the M2 tidal harmonic constants is revealed through analyses of monthly tidal data at 12 representative tidal stations in the seas adjacent to the Korean peninsula. The variability remain systematic over the 9 years (1965-1973) of data analysis with a range comparable to that of the 18.6 year nodal modulation. Spatial inhomogeneity of the seasonal variability in the observed harmonic constants is found to exist. The largest seasonal variability in M2 appears in the stations located along the Korea Strait. This variability is not explained by the equilibrium theory of tides, and such a variability or irregularities in the harmonic constants are considered as either a noise as done by Cartwright and Amin (1986), Deutsch Hydrography Zeitschrift, 39, 235-253, or a manifestation of frictional interaction as done by Godin and Gutierrez (1986) Continental Shelf Research, 5, 379-402 for the Bay of Fundy. Considering the opposite relation between monthly mean sea level differences in Izuhara-Pusan section and tidal characteristics in the Korea Strait, it is hypothesized that the interaction between the predominant tidal currents and oceanic currents varying with the seasons might be the main cause of the observed temporal variability in the M2 tide. The nonlinear effect of the Kuroshio is investigated along the shelf break region through scale analyses, which show that the presence of a mean current increases the non-linear terms in the momentum balance by about one order of magnitude. The seasonally different damping effect of the Tsushima Current to the M2 tide is also discussed to explain the process of dominant seasonal variability along the Korea Strait based on the actual current data, but further thorough investigation, considering the advection effect of the mean current, is required to investigate the associated dynamics more completely.

  1. Epitope Mapping of Avian Influenza M2e Protein: Different Species Recognise Various Epitopes

    PubMed Central

    Hasan, Noor Haliza; Ignjatovic, Jagoda; Tarigan, Simson; Peaston, Anne; Hemmatzadeh, Farhid

    2016-01-01

    A common approach for developing diagnostic tests for influenza virus detection is the use of mouse or rabbit monoclonal and/or polyclonal antibodies against a target antigen of the virus. However, comparative mapping of the target antigen using antibodies from different animal sources has not been evaluated before. This is important because identification of antigenic determinants of the target antigen in different species plays a central role to ensure the efficiency of a diagnostic test, such as competitive ELISA or immunohistochemistry-based tests. Interest in the matrix 2 ectodomain (M2e) protein of avian influenza virus (AIV) as a candidate for a universal vaccine and also as a marker for detection of virus infection in vaccinated animals (DIVA) is the rationale for the selection of this protein for comparative mapping evaluation. This study aimed to map the epitopes of the M2e protein of avian influenza virus H5N1 using chicken, mouse and rabbit monoclonal or monospecific antibodies. Our findings revealed that rabbit antibodies (rAbs) recognized epitope 6EVETPTRN13 of the M2e, located at the N-terminal of the protein, while mouse (mAb) and chicken antibodies (cAbs) recognized epitope 10PTRNEWECK18, located at the centre region of the protein. The findings highlighted the difference between the M2e antigenic determinants recognized by different species that emphasized the importance of comparative mapping of antibody reactivity from different animals to the same antigen, especially in the case of multi-host infectious agents such as influenza. The findings are of importance for antigenic mapping, as well as diagnostic test and vaccine development. PMID:27362795

  2. M2 Proton Channel: Toward a Model of a Primitive Proton Pump

    NASA Astrophysics Data System (ADS)

    Wei, Chenyu; Pohorille, Andrew

    2015-06-01

    Transmembrane proton transfer was essential to early cellular systems in order to transduce energy for metabolic functions. The reliable, efficient and controlled generation of proton gradients became possible only with the emergence of active proton pumps. On the basis of features shared by most modern proton pumps we identify the essential mechanistic steps in active proton transport. Further, we discuss the mechanism of action of a small, transmembrane M2 proton channel from influenza A virus as a model for proton transport in protocells. The M2 channel is a 94-residue long, α-helical tetramer that is activated at low pH and exhibits high selectivity and directionality. A shorter construct, built of transmembrane fragments that are only 24 amino acids in length, exhibits very similar proton transport properties. Molecular dynamics simulations on the microsecond time-scale carried out for the M2 channel provided atomic level details on the activation of the channel in response to protonation of the histidine residue, His37. The pathway of proton conduction is mediated by His37, which accepts and donates protons at different interconverting conformation states when pH is lower than 6.5. The Val27 and Trp41 gates and the salt bridge between Asp44 and Arg45 further enhance the directionality of proton transport. It is argued that the architecture and the mechanism of action similar to that found in the M2 channel might have been the perfect starting point for evolution towards the earliest proton pumps, indicating that active proton transport could have readily emerged from simple, passive proton channels.

  3. M2 proton channel: toward a model of a primitive proton pump.

    PubMed

    Wei, Chenyu; Pohorille, Andrew

    2015-06-01

    Transmembrane proton transfer was essential to early cellular systems in order to transduce energy for metabolic functions. The reliable, efficient and controlled generation of proton gradients became possible only with the emergence of active proton pumps. On the basis of features shared by most modern proton pumps we identify the essential mechanistic steps in active proton transport. Further, we discuss the mechanism of action of a small, transmembrane M2 proton channel from influenza A virus as a model for proton transport in protocells. The M2 channel is a 94-residue long, α-helical tetramer that is activated at low pH and exhibits high selectivity and directionality. A shorter construct, built of transmembrane fragments that are only 24 amino acids in length, exhibits very similar proton transport properties. Molecular dynamics simulations on the microsecond time-scale carried out for the M2 channel provided atomic level details on the activation of the channel in response to protonation of the histidine residue, His37. The pathway of proton conduction is mediated by His37, which accepts and donates protons at different interconverting conformation states when pH is lower than 6.5. The Val27 and Trp41 gates and the salt bridge between Asp44 and Arg45 further enhance the directionality of proton transport. It is argued that the architecture and the mechanism of action similar to that found in the M2 channel might have been the perfect starting point for evolution towards the earliest proton pumps, indicating that active proton transport could have readily emerged from simple, passive proton channels.

  4. Interaction of Tacrine at M1 and M2 Cholinoceptors in Guinea Pig Brain

    DTIC Science & Technology

    1993-01-01

    Alzheimer’s disease used for the preparation of cerebral cortex and cerebel- [1]. While oral doses alleviated some symp- lure for M, and M2 binding...determined by the Hartree Alzheimer’s disease progressed. Therefore, modification of the Lowry protein assay [10]. THA’s efficacy is yet to be...implications in the a radioligand binding technique. The equilibrium dis- sociation constant (KD) and apparent maximum num-treatment of Alzheimer’s disease 131

  5. Structure of the atypical bacteriocin pectocin M2 implies a novel mechanism of protein uptake

    PubMed Central

    Grinter, Rhys; Josts, Inokentijs; Zeth, Kornelius; Roszak, Aleksander W; McCaughey, Laura C; Cogdell, Richard J; Milner, Joel J; Kelly, Sharon M; Byron, Olwyn; Walker, Daniel

    2014-01-01

    The colicin-like bacteriocins are potent protein antibiotics that have evolved to efficiently cross the outer membrane of Gram-negative bacteria by parasitizing nutrient uptake systems. We have structurally characterized the colicin M-like bacteriocin, pectocin M2, which is active against strains of Pectobacterium spp. This unusual bacteriocin lacks the intrinsically unstructured translocation domain that usually mediates translocation of these bacteriocins across the outer membrane, containing only a single globular ferredoxin domain connected to its cytotoxic domain by a flexible α-helix, which allows it to adopt two distinct conformations in solution. The ferredoxin domain of pectocin M2 is homologous to plant ferredoxins and allows pectocin M2 to parasitize a system utilized by Pectobacterium to obtain iron during infection of plants. Furthermore, we identify a novel ferredoxin-containing bacteriocin pectocin P, which possesses a cytotoxic domain homologous to lysozyme, illustrating that the ferredoxin domain acts as a generic delivery module for cytotoxic domains in Pectobacterium. PMID:24865810

  6. M1 and M2 Macrophages: The Chicken and the Egg of Immunity

    PubMed Central

    Mills, Charles D.; Ley, Klaus

    2015-01-01

    The purpose of this perspective is to describe a critical advance in understanding how immune responses work. Macrophages are required for all animal life: ‘Inhibit’ type macrophages in all animals (called M1) can rapidly kill pathogens, and are thus the primary host defense, and ‘Heal’ type macrophages (M2) routinely repair and maintain tissue integrity. Macrophages perform these activities in all animals without T cells, and also in T cell-deficient vertebrates. Although adaptive immunity can amplify macrophage polarization, the long-held notion that macrophages need to be ‘activated’ or ‘alternatively activated’ by T cells is incorrect; indeed, immunology has had it backward. M1/M2-type macrophages necessarily direct T cells toward Th1- or Th2-like activities, respectively. That such macrophage-innate activities are the central directing element in immune responses is a dramatic change in understanding how immune systems operate. Most important, this revelation is opening up whole new approaches to immunotherapy. For example, many modern diseases, such as cancer and atherosclerosis, may not display ‘foreign’ antigens. However, there are clear imbalances in M1/M2-type responses. Correcting such innate imbalances can result in better health. Macrophages are the chicken and the egg of immunity. PMID:25138714

  7. M1 and M2 macrophages: the chicken and the egg of immunity.

    PubMed

    Mills, Charles D; Ley, Klaus

    2014-01-01

    The purpose of this perspective is to describe a critical advance in understanding how immune responses work. Macrophages are required for all animal life: 'Inhibit' type macrophages in all animals (called M1) can rapidly kill pathogens, and are thus the primary host defense, and 'Heal' type macrophages (M2) routinely repair and maintain tissue integrity. Macrophages perform these activities in all animals without T cells, and also in T cell-deficient vertebrates. Although adaptive immunity can amplify macrophage polarization, the long-held notion that macrophages need to be 'activated' or 'alternatively activated' by T cells is incorrect; indeed, immunology has had it backward. M1/M2-type macrophages necessarily direct T cells toward Th1- or Th2-like activities, respectively. That such macrophage-innate activities are the central directing element in immune responses is a dramatic change in understanding how immune systems operate. Most important, this revelation is opening up whole new approaches to immunotherapy. For example, many modern diseases, such as cancer and atherosclerosis, may not display 'foreign' antigens. However, there are clear imbalances in M1/M2-type responses. Correcting such innate imbalances can result in better health. Macrophages are the chicken and the egg of immunity.

  8. M2-F3 and project personnel after the 100th flight

    NASA Technical Reports Server (NTRS)

    1972-01-01

    The 100th flight of the heavy-weight lifting bodies was completed on October 5, 1972, with pilot Bill Dana soaring to an altitude of 66,300 feet and a Mach number of 1.370 (about 904 miles per hour) in the M2-F3. This was call for a celebration as the crew responsible for maintaining and operating the vehicle, the engineers who requested the flight, the pilots who flew the M2, and the Director of the NASA Flight Research Center gather in front of the M2-F3 lifting body for a photograph. Kneeling left to right are Bill Dana, (unknown person),* Jay King, and Herb Anderson. In the cockpit is Bill Szuwalski. Standing left to right are: Dale Reed, Robert Kempel, Milt Thompson, Bill Clifton, an Air Force fire fighter, Jerry Brandt, Johnny Armstrong, an Air Force fire fighter, Gary Layton, Jack Kolf, Ming Tang, (unknown person),* Byron Gibbs, Joe Huxman, (unknown person)*, Bill Mersereau, Bill Arnold, John Manke, Dr. Bill Winters, (unknown person)*, Bill LePage, Glenn Ford, Lee Scherer, Director of Center, (two unknown people),* Stan Butchart, and Berwin Kock. *=Identification incomplete at this time.)

  9. Dynamic RACH Partition for Massive Access of Differentiated M2M Services

    PubMed Central

    Du, Qinghe; Li, Wanyu; Liu, Lingjia; Ren, Pinyi; Wang, Yichen; Sun, Li

    2016-01-01

    In machine-to-machine (M2M) networks, a key challenge is to overcome the overload problem caused by random access requests from massive machine-type communication (MTC) devices. When differentiated services coexist, such as delay-sensitive and delay-tolerant services, the problem becomes more complicated and challenging. This is because delay-sensitive services often use more aggressive policies, and thus, delay-tolerant services get much fewer chances to access the network. To conquer the problem, we propose an efficient mechanism for massive access control over differentiated M2M services, including delay-sensitive and delay-tolerant services. Specifically, based on the traffic loads of the two types of services, the proposed scheme dynamically partitions and allocates the random access channel (RACH) resource to each type of services. The RACH partition strategy is thoroughly optimized to increase the access performances of M2M networks. Analyses and simulation demonstrate the effectiveness of our design. The proposed scheme can outperform the baseline access class barring (ACB) scheme, which ignores service types in access control, in terms of access success probability and the average access delay. PMID:27043568

  10. Characterization of the hrpZ gene from Pseudomonas syringae pv. maculicolaM2

    PubMed Central

    Álvarez-Mejía, César; Rodríguez-Ríos, Dalia; Hernández-Guzmán, Gustavo; López-Ramírez, Varinia; Valenzuela-Soto, Humberto; Marsch, Rodolfo

    2015-01-01

    Pseudomonas syringae pv. maculicola is a natural pathogen of members of the Brassicaceae plant family. Using a transposon-based mutagenesis strategy in Pseudomonas syringaepv. maculicola M2 (PsmM2), we conducted a genetic screen to identify mutants that were capable of growing in M9 medium supplemented with a crude extract from the leaves of Arabidopsis thaliana. A mutant containing a transposon insertion in the hrpZ gene (PsmMut8) was unable to infect adult plants from Arabidopsis thaliana or Brassica oleracea, suggesting a loss of pathogenicity. The promotorless cat reporter present in the gene trap was expressed if PsmMut8 was grown in minimal medium (M9) supplemented with the leaf extract but not if grown in normal rich medium (KB). We conducted phylogenetic analysis using hrpAZB genes, showing the classical 5-clade distribution, and nucleotide diversity analysis, showing the putative position for selective pressure in this operon. Our results indicate that the hrpAZB operon from Pseudomonas syringaepv. maculicola M2 is necessary for its pathogenicity and that its diversity would be under host-mediated diversifying selection. PMID:26413080

  11. Characterization of the hrpZ gene from Pseudomonas syringae pv. maculicola M2.

    PubMed

    Álvarez-Mejía, César; Rodríguez-Ríos, Dalia; Hernández-Guzmán, Gustavo; López-Ramírez, Varinia; Valenzuela-Soto, Humberto; Marsch, Rodolfo

    2015-01-01

    Pseudomonas syringae pv. maculicola is a natural pathogen of members of the Brassicaceae plant family. Using a transposon-based mutagenesis strategy in Pseudomonas syringaepv. maculicola M2 (PsmM2), we conducted a genetic screen to identify mutants that were capable of growing in M9 medium supplemented with a crude extract from the leaves of Arabidopsis thaliana. A mutant containing a transposon insertion in the hrpZ gene (PsmMut8) was unable to infect adult plants from Arabidopsis thaliana or Brassica oleracea, suggesting a loss of pathogenicity. The promotorless cat reporter present in the gene trap was expressed if PsmMut8 was grown in minimal medium (M9) supplemented with the leaf extract but not if grown in normal rich medium (KB). We conducted phylogenetic analysis using hrpAZB genes, showing the classical 5-clade distribution, and nucleotide diversity analysis, showing the putative position for selective pressure in this operon. Our results indicate that the hrpAZB operon from Pseudomonas syringaepv. maculicola M2 is necessary for its pathogenicity and that its diversity would be under host-mediated diversifying selection.

  12. TPL-2 Regulates Macrophage Lipid Metabolism and M2 Differentiation to Control TH2-Mediated Immunopathology

    PubMed Central

    Entwistle, Lewis J.; Khoury, Hania; Papoutsopoulou, Stamatia; Mahmood, Radma; Mansour, Nuha R.; Ching-Cheng Huang, Stanley; Pearce, Edward J.; Pedro S. de Carvalho, Luiz; Ley, Steven C.

    2016-01-01

    Persistent TH2 cytokine responses following chronic helminth infections can often lead to the development of tissue pathology and fibrotic scarring. Despite a good understanding of the cellular mechanisms involved in fibrogenesis, there are very few therapeutic options available, highlighting a significant medical need and gap in our understanding of the molecular mechanisms of TH2-mediated immunopathology. In this study, we found that the Map3 kinase, TPL-2 (Map3k8; Cot) regulated TH2-mediated intestinal, hepatic and pulmonary immunopathology following Schistosoma mansoni infection or S. mansoni egg injection. Elevated inflammation, TH2 cell responses and exacerbated fibrosis in Map3k8–/–mice was observed in mice with myeloid cell-specific (LysM) deletion of Map3k8, but not CD4 cell-specific deletion of Map3k8, indicating that TPL-2 regulated myeloid cell function to limit TH2-mediated immunopathology. Transcriptional and metabolic assays of Map3k8–/–M2 macrophages identified that TPL-2 was required for lipolysis, M2 macrophage activation and the expression of a variety of genes involved in immuno-regulatory and pro-fibrotic pathways. Taken together this study identified that TPL-2 regulated TH2-mediated inflammation by supporting lipolysis and M2 macrophage activation, preventing TH2 cell expansion and downstream immunopathology and fibrosis. PMID:27487182

  13. The outer envelopes of globular clusters - I. NGC 7089 (M2)

    NASA Astrophysics Data System (ADS)

    Kuzma, P. B.; Da Costa, G. S.; Mackey, A. D.; Roderick, T. A.

    2016-10-01

    We present the results of a wide-field imaging survey of the periphery of the Milky Way globular cluster NGC 7089 (M2). Data were obtained with MegaCam on the Magellan Clay Telescope and the Dark Energy Camera on the Blanco Telescope. We find that M2 is embedded in a diffuse stellar envelope extending to a radial distance of at least ˜60 arcmin (˜210 pc) - five times the nominal tidal radius of the cluster. The envelope appears nearly circular in shape, has a radial density decline well described by a power law of index γ = -2.2 ± 0.2, and contains approximately 1.6 per cent of the luminosity of the entire system. While the origin of the envelope cannot be robustly identified using the presently available data, the fact that M2 also hosts stellar populations exhibiting a broad dispersion in the abundances of both iron and a variety of neutron capture elements suggests that this object might plausibly constitute the stripped nucleus of a dwarf galaxy that was long ago accreted and destroyed by the Milky Way.

  14. RESTful M2M Gateway for Remote Wireless Monitoring for District Central Heating Networks

    PubMed Central

    Cheng, Bo; Wei, Zesan

    2014-01-01

    In recent years, the increased interest in energy conservation and environmental protection, combined with the development of modern communication and computer technology, has resulted in the replacement of distributed heating by central heating in urban areas. This paper proposes a Representational State Transfer (REST) Machine-to-Machine (M2M) gateway for wireless remote monitoring for a district central heating network. In particular, we focus on the resource-oriented RESTful M2M gateway architecture, and present an uniform devices abstraction approach based on Open Service Gateway Initiative (OSGi) technology, and implement the resource mapping mechanism between resource address mapping mechanism between RESTful resources and the physical sensor devices, and present the buffer queue combined with polling method to implement the data scheduling and Quality of Service (QoS) guarantee, and also give the RESTful M2M gateway open service Application Programming Interface (API) set. The performance has been measured and analyzed. Finally, the conclusions and future work are presented. PMID:25436650

  15. Dynamic RACH Partition for Massive Access of Differentiated M2M Services.

    PubMed

    Du, Qinghe; Li, Wanyu; Liu, Lingjia; Ren, Pinyi; Wang, Yichen; Sun, Li

    2016-03-30

    In machine-to-machine (M2M) networks, a key challenge is to overcome the overload problem caused by random access requests from massive machine-type communication (MTC) devices. When differentiated services coexist, such as delay-sensitive and delay-tolerant services, the problem becomes more complicated and challenging. This is because delay-sensitive services often use more aggressive policies, and thus, delay-tolerant services get much fewer chances to access the network. To conquer the problem, we propose an efficient mechanism for massive access control over differentiated M2M services, including delay-sensitive and delay-tolerant services. Specifically, based on the traffic loads of the two types of services, the proposed scheme dynamically partitions and allocates the random access channel (RACH) resource to each type of services. The RACH partition strategy is thoroughly optimized to increase the access performances of M2M networks. Analyses and simulation demonstrate the effectiveness of our design. The proposed scheme can outperform the baseline access class barring (ACB) scheme, which ignores service types in access control, in terms of access success probability and the average access delay.

  16. The catalytic role of the M2 metal ion in PP2Cα.

    PubMed

    Pan, Chang; Tang, Jun-yi; Xu, Yun-fei; Xiao, Peng; Liu, Hong-da; Wang, Hao-an; Wang, Wen-bo; Meng, Fan-guo; Yu, Xiao; Sun, Jin-peng

    2015-02-24

    PP2C family phosphatases (the type 2C family of protein phosphatases; or metal-dependent phosphatase, PPM) constitute an important class of signaling enzymes that regulate many fundamental life activities. All PP2C family members have a conserved binuclear metal ion active center that is essential for their catalysis. However, the catalytic role of each metal ion during catalysis remains elusive. In this study, we discovered that mutations in the structurally buried D38 residue of PP2Cα (PPM1A) redefined the water-mediated hydrogen network in the active site and selectively disrupted M2 metal ion binding. Using the D38A and D38K mutations of PP2Cα as specific tools in combination with enzymology analysis, our results demonstrated that the M2 metal ion determines the rate-limiting step of substrate hydrolysis, participates in dianion substrate binding and stabilizes the leaving group after P-O bond cleavage. The newly characterized catalytic role of the M2 metal ion in this family not only provides insight into how the binuclear metal centers of the PP2C phosphatases are organized for efficient catalysis but also helps increase our understanding of the function and substrate specificity of PP2C family members.

  17. Human mesenchymal stromal cell-secreted lactate induces M2-macrophage differentiation by metabolic reprogramming

    PubMed Central

    Civini, Sara; Pacelli, Consiglia; Dieng, Mame Massar; Lemieux, William; Jin, Ping; Bazin, Renée; Patey, Natacha; Marincola, Francesco M.; Moldovan, Florina; Zaouter, Charlotte; Trudeau, Louis-Eric; Benabdhalla, Basma; Louis, Isabelle; Beauséjour, Christian; Stroncek, David; Le Deist, Françoise; Haddad, Elie

    2016-01-01

    Human mesenchymal stromal cells (MSC) have been shown to dampen immune response and promote tissue repair, but the underlying mechanisms are still under investigation. Herein, we demonstrate that umbilical cord-derived MSC (UC-MSC) alter the phenotype and function of monocyte-derived dendritic cells (DC) through lactate-mediated metabolic reprogramming. UC-MSC can secrete large quantities of lactate and, when present during monocyte-to-DC differentiation, induce instead the acquisition of M2-macrophage features in terms of morphology, surface markers, migratory properties and antigen presentation capacity. Microarray expression profiling indicates that UC-MSC modify the expression of metabolic-related genes and induce a M2-macrophage expression signature. Importantly, monocyte-derived DC obtained in presence of UC-MSC, polarize naïve allogeneic CD4+ T-cells into Th2 cells. Treatment of UC-MSC with an inhibitor of lactate dehydrogenase strongly decreases lactate concentration in culture supernatant and abrogates the effect on monocyte-to-DC differentiation. Metabolic analysis further revealed that UC-MSC decrease oxidative phosphorylation in differentiating monocytes while strongly increasing the spare respiratory capacity proportional to the amount of secreted lactate. Because both MSC and monocytes are recruited in vivo at the site of tissue damage and inflammation, we propose the local increase of lactate concentration induced by UC-MSC and the consequent enrichment in M2-macrophage generation as a mechanism to achieve immunomodulation. PMID:27070086

  18. Channel opening by anesthetics and GABA induces similar changes in the GABAA receptor M2 segment.

    PubMed

    Rosen, Ayelet; Bali, Moez; Horenstein, Jeffrey; Akabas, Myles H

    2007-05-01

    For many general anesthetics, their molecular basis of action involves interactions with GABA(A) receptors. Anesthetics produce concentration-dependent effects on GABA(A) receptors. Low concentrations potentiate submaximal GABA-induced currents. Higher concentrations directly activate the receptors. Functional effects of anesthetics have been characterized, but little is known about the conformational changes they induce. We probed anesthetic-induced conformational changes in the M2 membrane-spanning, channel-lining segment using disulfide trapping between engineered cysteines. Previously, we showed that oxidation by copper phenanthroline in the presence of GABA of the M2 6' cysteine mutants, alpha(1)T261Cbeta(1)T256C and alpha(1)beta(1)T256C resulted in formation of an intersubunit disulfide bond between the adjacent beta-subunits that significantly increased the channels' spontaneous open probability. Oxidation in GABA's absence had no effect. We examined the effect on alpha(1)T261Cbeta(1)T256C and on alpha(1)beta(1)T256C of oxidation by copper phenanthroline in the presence of potentiating and directly activating concentrations of the general anesthetics propofol, pentobarbital, and isoflurane. Oxidation in the presence of potentiating concentration of anesthetics had little effect. Oxidation in the presence of directly activating anesthetic concentrations significantly increased the channels' spontaneous open probability. We infer that activation by anesthetics and GABA induces a similar conformational change at the M2 segment 6' position that is related to channel opening.

  19. Conformational variability of the glycine receptor M2 domain in response to activation by different agonists.

    PubMed

    Pless, Stephan A; Dibas, Mohammed I; Lester, Henry A; Lynch, Joseph W

    2007-12-07

    Models describing the structural changes mediating Cys loop receptor activation generally give little attention to the possibility that different agonists may promote activation via distinct M2 pore-lining domain structural rearrangements. We investigated this question by comparing the effects of different ligands on the conformation of the external portion of the homomeric alpha1 glycine receptor M2 domain. Conformational flexibility was assessed by tethering a rhodamine fluorophore to cysteines introduced at the 19' or 22' positions and monitoring fluorescence and current changes during channel activation. During glycine activation, fluorescence of the label attached to R19'C increased by approximately 20%, and the emission peak shifted to lower wavelengths, consistent with a more hydrophobic fluorophore environment. In contrast, ivermectin activated the receptors without producing a fluorescence change. Although taurine and beta-alanine were weak partial agonists at the alpha1R19'C glycine receptor, they induced large fluorescence changes. Propofol, which drastically enhanced these currents, did not induce a glycine-like blue shift in the spectral emission peak. The inhibitors strychnine and picrotoxin elicited fluorescence and current changes as expected for a competitive antagonist and an open channel blocker, respectively. Glycine and taurine (or beta-alanine) also produced an increase and a decrease, respectively, in the fluorescence of a label attached to the nearby L22'C residue. Thus, results from two separate labeled residues support the conclusion that the glycine receptor M2 domain responds with distinct conformational changes to activation by different agonists.

  20. Fasciola hepatica tegumental antigens indirectly induce an M2 macrophage-like phenotype in vivo.

    PubMed

    Adams, P N; Aldridge, A; Vukman, K V; Donnelly, S; O'Neill, S M

    2014-10-01

    The M2 subset of macrophages has a critical role to play in host tissue repair, tissue fibrosis and modulation of adaptive immunity during helminth infection. Infection with the helminth, Fasciola hepatica, is associated with M2 macrophages in its mammalian host, and this response is mimicked by its excretory-secretory products (FhES). The tegumental coat of F. hepatica (FhTeg) is another major source of immune-modulatory molecules; we have previously shown that FhTeg can modulate the activity of both dendritic cells and mast cells inhibiting their ability to prime a Th1 immune response. Here, we report that FhTeg does not induce Th2 immune responses but can induce M2-like phenotype in vivo that modulates cytokine production from CD4(+) cells in response to anti-CD3 stimulation. FhTeg induces a RELMα expressing macrophage population in vitro, while in vivo, the expression of Arg1 and Ym-1/2 but not RELMα in FhTeg-stimulated macrophages was STAT6 dependent. To support this finding, FhTeg induces RELMα expression in vivo prior to the induction of IL-13. FhTeg can induce IL-13-producing peritoneal macrophages following intraperitoneal injection This study highlights the important role of FhTeg as an immune-modulatory source during F. hepatica infection and sheds further light on helminth-macrophage interactions.

  1. The catalytic role of the M2 metal ion in PP2Cα

    NASA Astrophysics Data System (ADS)

    Pan, Chang; Tang, Jun-Yi; Xu, Yun-Fei; Xiao, Peng; Liu, Hong-Da; Wang, Hao-An; Wang, Wen-Bo; Meng, Fan-Guo; Yu, Xiao; Sun, Jin-Peng

    2015-02-01

    PP2C family phosphatases (the type 2C family of protein phosphatases; or metal-dependent phosphatase, PPM) constitute an important class of signaling enzymes that regulate many fundamental life activities. All PP2C family members have a conserved binuclear metal ion active center that is essential for their catalysis. However, the catalytic role of each metal ion during catalysis remains elusive. In this study, we discovered that mutations in the structurally buried D38 residue of PP2Cα (PPM1A) redefined the water-mediated hydrogen network in the active site and selectively disrupted M2 metal ion binding. Using the D38A and D38K mutations of PP2Cα as specific tools in combination with enzymology analysis, our results demonstrated that the M2 metal ion determines the rate-limiting step of substrate hydrolysis, participates in dianion substrate binding and stabilizes the leaving group after P-O bond cleavage. The newly characterized catalytic role of the M2 metal ion in this family not only provides insight into how the binuclear metal centers of the PP2C phosphatases are organized for efficient catalysis but also helps increase our understanding of the function and substrate specificity of PP2C family members.

  2. Measurement of M2-Curve for Asymmetric Beams by Self-Referencing Interferometer Wavefront Sensor

    PubMed Central

    Du, Yongzhao

    2016-01-01

    For asymmetric laser beams, the values of beam quality factor Mx2 and My2 are inconsistent if one selects a different coordinate system or measures beam quality with different experimental conditionals, even when analyzing the same beam. To overcome this non-uniqueness, a new beam quality characterization method named as M2-curve is developed. The M2-curve not only contains the beam quality factor Mx2 and My2 in the x-direction and y-direction, respectively; but also introduces a curve of Mxα2 versus rotation angle α of coordinate axis. Moreover, we also present a real-time measurement method to demonstrate beam propagation factor M2-curve with a modified self-referencing Mach-Zehnder interferometer based-wavefront sensor (henceforth SRI-WFS). The feasibility of the proposed method is demonstrated with the theoretical analysis and experiment in multimode beams. The experimental results showed that the proposed measurement method is simple, fast, and a single-shot measurement procedure without movable parts. PMID:27916845

  3. RESTful M2M gateway for remote wireless monitoring for district central heating networks.

    PubMed

    Cheng, Bo; Wei, Zesan

    2014-11-27

    In recent years, the increased interest in energy conservation and environmental protection, combined with the development of modern communication and computer technology, has resulted in the replacement of distributed heating by central heating in urban areas. This paper proposes a Representational State Transfer (REST) Machine-to-Machine (M2M) gateway for wireless remote monitoring for a district central heating network. In particular, we focus on the resource-oriented RESTful M2M gateway architecture, and present an uniform devices abstraction approach based on Open Service Gateway Initiative (OSGi) technology, and implement the resource mapping mechanism between resource address mapping mechanism between RESTful resources and the physical sensor devices, and present the buffer queue combined with polling method to implement the data scheduling and Quality of Service (QoS) guarantee, and also give the RESTful M2M gateway open service Application Programming Interface (API) set. The performance has been measured and analyzed. Finally, the conclusions and future work are presented.

  4. M2 baroclinic tide variability modulated by the ocean circulation south of Japan

    NASA Astrophysics Data System (ADS)

    Varlamov, Sergey M.; Guo, Xinyu; Miyama, Toru; Ichikawa, Kaoru; Waseda, Takuji; Miyazawa, Yasumasa

    2015-05-01

    We analyze a concurrent simulation result of the ocean circulation and tidal currents using a data-assimilative ocean general circulation model covering the Western North Pacific with horizontal resolution of 1/36° to investigate possible interactions between them. Four sites of active M2 internal tide variability in open ocean (hot spots), such as Tokara Strait, Izu Ridge, Luzon Strait, and Ogasawara Ridge, are detected from both the satellite observation and the simulation. Energy cycle analysis of the simulated M2 baroclinic tide indicates two types of the hot spots: dissipation (Tokara Strait and Izu Ridge) and radiation (Luzon Strait and Ogasawara Ridge) dominant sites. Energy conversion from barotropic to baroclinic M2 tides at the hot spots is modulated considerably by the lower-frequency changes in the density field. Modulation at the two spots (Tokara Strait and Izu Ridge) is affected by the Kuroshio path variation together with the seasonal variation of the shallow thermocline. At the other two sites, influence from changes in the relatively deep stratification through the Kuroshio intrusion into South China Sea (Luzon Strat) and mesoscale eddy activity (Ogasawara Ridge) is dominant in the modulation.

  5. Non-Neuronal Functions of the M2 Muscarinic Acetylcholine Receptor

    PubMed Central

    Ockenga, Wymke; Kühne, Sina; Bocksberger, Simone; Banning, Antje; Tikkanen, Ritva

    2013-01-01

    Acetylcholine is an important neurotransmitter whose effects are mediated by two classes of receptors. The nicotinic acetylcholine receptors are ion channels, whereas the muscarinic receptors belong to the large family of G protein coupled seven transmembrane helix receptors. Beyond its function in neuronal systems, it has become evident that acetylcholine also plays an important role in non-neuronal cells such as epithelial and immune cells. Furthermore, many cell types in the periphery are capable of synthesizing acetylcholine and express at least some of the receptors. In this review, we summarize the non-neuronal functions of the muscarinic acetylcholine receptors, especially those of the M2 muscarinic receptor in epithelial cells. We will review the mechanisms of signaling by the M2 receptor but also the cellular trafficking and ARF6 mediated endocytosis of this receptor, which play an important role in the regulation of signaling events. In addition, we provide an overview of the M2 receptor in human pathological conditions such as autoimmune diseases and cancer. PMID:24705159

  6. Parthenolide Relieves Pain and Promotes M2 Microglia/Macrophage Polarization in Rat Model of Neuropathy.

    PubMed

    Popiolek-Barczyk, Katarzyna; Kolosowska, Natalia; Piotrowska, Anna; Makuch, Wioletta; Rojewska, Ewelina; Jurga, Agnieszka M; Pilat, Dominika; Mika, Joanna

    2015-01-01

    Neuropathic pain treatment remains a challenge because pathomechanism is not fully understood. It is believed that glial activation and increased spinal nociceptive factors are crucial for neuropathy. We investigated the effect of parthenolide (PTL) on the chronic constriction injury to the sciatic nerve (CCI)-induced neuropathy in rat. We analyzed spinal changes in glial markers and M1 and M2 polarization factors, as well as intracellular signaling pathways. PTL (5 µg; i.t.) was preemptively and then daily administered for 7 days after CCI. PTL attenuated the allodynia and hyperalgesia and increased the protein level of IBA1 (a microglial/macrophage marker) but did not change GFAP (an astrocyte marker) on day 7 after CCI. PTL reduced the protein level of M1 (IL-1β, IL-18, and iNOS) and enhanced M2 (IL-10, TIMP1) factors. In addition, it downregulated the phosphorylated form of NF-κB, p38MAPK, and ERK1/2 protein level and upregulated STAT3. In primary microglial cell culture we have shown that IL-1β, IL-18, iNOS, IL-6, IL-10, and TIMP1 are of microglial origin. Summing up, PTL directly or indirectly attenuates neuropathy symptoms and promotes M2 microglia/macrophages polarization. We suggest that neuropathic pain therapies should be shifted from blanketed microglia/macrophage suppression toward maintenance of the balance between neuroprotective and neurotoxic microglia/macrophage phenotypes.

  7. Parthenolide Relieves Pain and Promotes M2 Microglia/Macrophage Polarization in Rat Model of Neuropathy

    PubMed Central

    Popiolek-Barczyk, Katarzyna; Kolosowska, Natalia; Makuch, Wioletta; Rojewska, Ewelina; Jurga, Agnieszka M.; Pilat, Dominika

    2015-01-01

    Neuropathic pain treatment remains a challenge because pathomechanism is not fully understood. It is believed that glial activation and increased spinal nociceptive factors are crucial for neuropathy. We investigated the effect of parthenolide (PTL) on the chronic constriction injury to the sciatic nerve (CCI)-induced neuropathy in rat. We analyzed spinal changes in glial markers and M1 and M2 polarization factors, as well as intracellular signaling pathways. PTL (5 µg; i.t.) was preemptively and then daily administered for 7 days after CCI. PTL attenuated the allodynia and hyperalgesia and increased the protein level of IBA1 (a microglial/macrophage marker) but did not change GFAP (an astrocyte marker) on day 7 after CCI. PTL reduced the protein level of M1 (IL-1β, IL-18, and iNOS) and enhanced M2 (IL-10, TIMP1) factors. In addition, it downregulated the phosphorylated form of NF-κB, p38MAPK, and ERK1/2 protein level and upregulated STAT3. In primary microglial cell culture we have shown that IL-1β, IL-18, iNOS, IL-6, IL-10, and TIMP1 are of microglial origin. Summing up, PTL directly or indirectly attenuates neuropathy symptoms and promotes M2 microglia/macrophages polarization. We suggest that neuropathic pain therapies should be shifted from blanketed microglia/macrophage suppression toward maintenance of the balance between neuroprotective and neurotoxic microglia/macrophage phenotypes. PMID:26090236

  8. Aerodynamic characteristics of an all-body hypersonic aircraft configuration at Mach numbers from 0.65 to 10.6

    NASA Technical Reports Server (NTRS)

    Nelms, W. P., Jr.; Thomas, C. L.

    1971-01-01

    Aerodynamic characteristics of a model designed to represent an all body, hypersonic cruise aircraft are presented for Mach numbers from 0.65 to 10.6. The configuration had a delta planform with an elliptic cone forebody and an afterbody of elliptic cross section. Detailed effects of varying angle of attack (-2 to +15 deg), angle of sideslip (-2 to +8 deg), Mach number, and configuration buildup were considered. In addition, the effectiveness of horizontal tail, vertical tail, and canard stabilizing and control surfaces was investigated. The results indicate that all configurations were longitudinally stable near maximum lift drag ratio. The configurations with vertical tails were directionally stable at all angles of attack. Trim penalties were small at hypersonic speeds for a center of gravity location representative of the airplane, but because of the large rearward travel of the aerodynamic center, trim penalties were severe at transonic Mach numbers.

  9. 1.95  μm-pumped OP-GaAs optical parametric oscillator with 10.6  μm idler wavelength.

    PubMed

    Wueppen, Jochen; Nyga, Sebastian; Jungbluth, Bernd; Hoffmann, Dieter

    2016-09-15

    We report on an optical parametric oscillator that generates output idler wavelengths around 10.6 μm. On the basis of orientation-patterned gallium arsenide (OP-GaAs) as a nonlinear medium and a 1.95 μm ns-pulsed pump laser, a signal-resonant bow-tie resonator was designed in order to maximize the output power at moderate intensities well below the damage threshold of the optical components. With this setup, the average idler output power at 50 kHz and 100 ns idler pulse length was more than 800 mW, which corresponds to a pulse energy of 16 μJ. The maximum quantum conversion efficiency of 36.8% is the highest value measured so far for comparable setups to the best of our knowledge.

  10. Evidence of WW and WZ production with lepton + jets final states in pp collisions at square root s=1.96 TeV.

    PubMed

    Abazov, V M; Abbott, B; Abolins, M; Acharya, B S; Adams, M; Adams, T; Aguilo, E; Ahsan, M; Alexeev, G D; Alkhazov, G; Alton, A; Alverson, G; Alves, G A; Anastasoaie, M; Ancu, L S; Andeen, T; Andrieu, B; Anzelc, M S; Aoki, M; Arnoud, Y; Arov, M; Arthaud, M; Askew, A; Asman, B; Jesus, A C S Assis; Atramentov, O; Avila, C; Badaud, F; Bagby, L; Baldin, B; Bandurin, D V; Banerjee, P; Banerjee, S; Barberis, E; Barfuss, A-F; Bargassa, P; Baringer, P; Barreto, J; Bartlett, J F; Bassler, U; Bauer, D; Beale, S; Bean, A; Begalli, M; Begel, M; Belanger-Champagne, C; Bellantoni, L; Bellavance, A; Benitez, J A; Beri, S B; Bernardi, G; Bernhard, R; Bertram, I; Besançon, M; Beuselinck, R; Bezzubov, V A; Bhat, P C; Bhatnagar, V; Blazey, G; Blekman, F; Blessing, S; Bloom, K; Boehnlein, A; Boline, D; Bolton, T A; Boos, E E; Borissov, G; Bose, T; Brandt, A; Brock, R; Brooijmans, G; Bross, A; Brown, D; Bu, X B; Buchanan, N J; Buchholz, D; Buehler, M; Buescher, V; Bunichev, V; Burdin, S; Burnett, T H; Buszello, C P; Calfayan, P; Calvet, S; Cammin, J; Carrasco-Lizarraga, M A; Carrera, E; Carvalho, W; Casey, B C K; Castilla-Valdez, H; Chakrabarti, S; Chakraborty, D; Chan, K M; Chandra, A; Cheu, E; Cho, D K; Choi, S; Choudhary, B; Christofek, L; Christoudias, T; Cihangir, S; Claes, D; Clutter, J; Cooke, M; Cooper, W E; Corcoran, M; Couderc, F; Cousinou, M-C; Crépé-Renaudin, S; Cuplov, V; Cutts, D; Cwiok, M; da Motta, H; Das, A; Davies, G; De, K; de Jong, S J; De La Cruz-Burelo, E; De Oliveira Martins, C; Devaughan, K; Déliot, F; Demarteau, M; Demina, R; Denisov, D; Denisov, S P; Desai, S; Diehl, H T; Diesburg, M; Dominguez, A; Dorland, T; Dubey, A; Dudko, L V; Duflot, L; Dugad, S R; Duggan, D; Duperrin, A; Dutt, S; Dyer, J; Dyshkant, A; Eads, M; Edmunds, D; Ellison, J; Elvira, V D; Enari, Y; Eno, S; Ermolov, P; Evans, H; Evdokimov, A; Evdokimov, V N; Ferapontov, A V; Ferbel, T; Fiedler, F; Filthaut, F; Fisher, W; Fisk, H E; Fortner, M; Fox, H; Fu, S; Fuess, S; Gadfort, T; Galea, C F; Garcia, C; Garcia-Bellido, A; Gavrilov, V; Gay, P; Geist, W; Geng, W; Gerber, C E; Gershtein, Y; Gillberg, D; Ginther, G; Gómez, B; Goussiou, A; Grannis, P D; Greenlee, H; Greenwood, Z D; Gregores, E M; Grenier, G; Gris, Ph; Grivaz, J-F; Grohsjean, A; Grünendahl, S; Grünewald, M W; Guo, F; Guo, J; Gutierrez, G; Gutierrez, P; Haas, A; Hadley, N J; Haefner, P; Hagopian, S; Haley, J; Hall, I; Hall, R E; Han, L; Harder, K; Harel, A; Hauptman, J M; Hays, J; Hebbeker, T; Hedin, D; Hegeman, J G; Heinson, A P; Heintz, U; Hensel, C; Herner, K; Hesketh, G; Hildreth, M D; Hirosky, R; Hoang, T; Hobbs, J D; Hoeneisen, B; Hohlfeld, M; Hossain, S; Houben, P; Hu, Y; Hubacek, Z; Hynek, V; Iashvili, I; Illingworth, R; Ito, A S; Jabeen, S; Jaffré, M; Jain, S; Jakobs, K; Jarvis, C; Jesik, R; Johns, K; Johnson, C; Johnson, M; Johnston, D; Jonckheere, A; Jonsson, P; Juste, A; Kajfasz, E; Karmanov, D; Kasper, P A; Katsanos, I; Kaushik, V; Kehoe, R; Kermiche, S; Khalatyan, N; Khanov, A; Kharchilava, A; Kharzheev, Y N; Khatidze, D; Kim, T J; Kirby, M H; Kirsch, M; Klima, B; Kohli, J M; Konrath, J-P; Kozelov, A V; Kraus, J; Kuhl, T; Kumar, A; Kupco, A; Kurca, T; Kuzmin, V A; Kvita, J; Lacroix, F; Lam, D; Lammers, S; Landsberg, G; Lebrun, P; Lee, W M; Leflat, A; Lellouch, J; Li, J; Li, L; Li, Q Z; Lietti, S M; Lim, J K; Lima, J G R; Lincoln, D; Linnemann, J; Lipaev, V V; Lipton, R; Liu, Y; Liu, Z; Lobodenko, A; Lokajicek, M; Love, P; Lubatti, H J; Luna-Garcia, R; Lyon, A L; Maciel, A K A; Mackin, D; Madaras, R J; Mättig, P; Magerkurth, A; Mal, P K; Malbouisson, H B; Malik, S; Malyshev, V L; Maravin, Y; Martin, B; McCarthy, R; Meijer, M M; Melnitchouk, A; Mendoza, L; Mercadante, P G; Merkin, M; Merritt, K W; Meyer, A; Meyer, J; Mitrevski, J; Mommsen, R K; Mondal, N K; Moore, R W; Moulik, T; Muanza, G S; Mulhearn, M; Mundal, O; Mundim, L; Nagy, E; Naimuddin, M; Narain, M; Neal, H A; Negret, J P; Neustroev, P; Nilsen, H; Nogima, H; Novaes, S F; Nunnemann, T; O'Neil, D C; Obrant, G; Ochando, C; Onoprienko, D; Oshima, N; Osman, N; Osta, J; Otec, R; Otero Y Garzón, G J; Owen, M; Padley, P; Pangilinan, M; Parashar, N; Park, S-J; Park, S K; Parsons, J; Partridge, R; Parua, N; Patwa, A; Pawloski, G; Penning, B; Perfilov, M; Peters, K; Peters, Y; Pétroff, P; Petteni, M; Piegaia, R; Piper, J; Pleier, M-A; Podesta-Lerma, P L M; Podstavkov, V M; Pogorelov, Y; Pol, M-E; Polozov, P; Pope, B G; Popov, A V; Potter, C; Prado da Silva, W L; Prosper, H B; Protopopescu, S; Qian, J; Quadt, A; Quinn, B; Rakitine, A; Rangel, M S; Ranjan, K; Ratoff, P N; Renkel, P; Rich, P; Rijssenbeek, M; Ripp-Baudot, I; Rizatdinova, F; Robinson, S; Rodrigues, R F; Rominsky, M; Royon, C; Rubinov, P; Ruchti, R; Safronov, G; Sajot, G; Sánchez-Hernández, A; Sanders, M P; Sanghi, B; Savage, G; Sawyer, L; Scanlon, T; Schaile, D; Schamberger, R D; Scheglov, Y; Schellman, H; Schliephake, T; Schlobohm, S; Schwanenberger, C; Schwartzman, A; Schwienhorst, R; Sekaric, J; Severini, H; Shabalina, E; Shamim, M; Shary, V; Shchukin, A A; Shivpuri, R K; Siccardi, V; Simak, V; Sirotenko, V; Skubic, P; Slattery, P; Smirnov, D; Snow, G R; Snow, J; Snyder, S; Söldner-Rembold, S; Sonnenschein, L; Sopczak, A; Sosebee, M; Soustruznik, K; Spurlock, B; Stark, J; Stolin, V; Stoyanova, D A; Strandberg, J; Strandberg, S; Strang, M A; Strauss, E; Strauss, M; Ströhmer, R; Strom, D; Stutte, L; Sumowidagdo, S; Svoisky, P; Sznajder, A; Tanasijczuk, A; Taylor, W; Tiller, B; Tissandier, F; Titov, M; Tokmenin, V V; Torchiani, I; Tsybychev, D; Tuchming, B; Tully, C; Tuts, P M; Unalan, R; Uvarov, L; Uvarov, S; Uzunyan, S; Vachon, B; van den Berg, P J; Van Kooten, R; van Leeuwen, W M; Varelas, N; Varnes, E W; Vasilyev, I A; Verdier, P; Vertogradov, L S; Verzocchi, M; Vilanova, D; Villeneuve-Seguier, F; Vint, P; Vokac, P; Voutilainen, M; Wagner, R; Wahl, H D; Wang, M H L S; Warchol, J; Watts, G; Wayne, M; Weber, G; Weber, M; Welty-Rieger, L; Wenger, A; Wermes, N; Wetstein, M; White, A; Wicke, D; Williams, M R J; Wilson, G W; Wimpenny, S J; Wobisch, M; Wood, D R; Wyatt, T R; Xie, Y; Xu, C; Yacoob, S; Yamada, R; Yang, W-C; Yasuda, T; Yatsunenko, Y A; Yin, H; Yip, K; Yoo, H D; Youn, S W; Yu, J; Zeitnitz, C; Zelitch, S; Zhao, T; Zhou, B; Zhu, J; Zielinski, M; Zieminska, D; Zieminski, A; Zivkovic, L; Zutshi, V; Zverev, E G

    2009-04-24

    We present first evidence for WW+WZ production in lepton + jets final states at a hadron collider. The data correspond to 1.07 fb-1 of integrated luminosity collected with the D0 detector at the Fermilab Tevatron in pp collisions at square root s=1.96 TeV. The observed cross section for WW+WZ production is 20.2+/-4.5 pb, consistent with the standard model and more precise than previous measurements in fully leptonic final states. The probability that background fluctuations alone produce this excess is <5.4 x 10-6, which corresponds to a significance of 4.4 standard deviations.

  11. S1P lyase in thymic perivascular spaces promotes egress of mature thymocytes via up-regulation of S1P receptor 1.

    PubMed

    Maeda, Yasuhiro; Yagi, Hideki; Takemoto, Kana; Utsumi, Hiroyuki; Fukunari, Atsushi; Sugahara, Kunio; Masuko, Takashi; Chiba, Kenji

    2014-05-01

    Sphingosine 1-phosphate (S1P) and S1P receptor 1 (S1P1) play an important role in the egress of mature CD4 or CD8 single-positive (SP) thymocytes from the thymus. Fingolimod hydrochloride (FTY720), an S1P1 functional antagonist, induced significant accumulation of CD62L(high)CD69(low) mature SP thymocytes in the thymic medulla. Immunohistochemical staining using anti-S1P1 antibody revealed that S1P1 is predominantly expressed on thymocytes in the thymic medulla and is strongly down-regulated even at 3h after FTY720 administration. 2-Acetyl-4-tetrahydroxybutylimidazole (THI), an S1P lyase inhibitor, also induced accumulation of mature SP thymocytes in the thymic medulla with an enlargement of the perivascular spaces (PVS). At 6h after THI administration, S1P1-expressing thymocytes reduced partially as if to form clusters and hardly existed in the proximity of CD31-expressing blood vessels in the thymic medulla, suggesting S1P lyase expression in the cells constructing thymic medullary PVS. To determine the cells expressing S1P lyase in the thymus, we newly established a mAb (YK19-2) specific for mouse S1P lyase. Immunohistochemical staining with YK19-2 revealed that S1P lyase is predominantly expressed in non-lymphoid thymic stromal cells in the thymic medulla. In the thymic medullary PVS, S1P lyase was expressed in ER-TR7-positive cells (reticular fibroblasts and pericytes) and CD31-positive vascular endothelial cells. Our findings suggest that S1P lyase expressed in the thymic medullary PVS keeps the tissue S1P concentration low around the vessels and promotes thymic egress via up-regulation of S1P1.

  12. Phase II multi-institutional prospective randomised trial comparing S-1+paclitaxel with S-1+cisplatin in patients with unresectable and/or recurrent advanced gastric cancer

    PubMed Central

    Mochiki, E; Ogata, K; Ohno, T; Toyomasu, Y; Haga, N; Fukai, Y; Aihara, R; Ando, H; Uchida, N; Asao, T; Kuwano, H

    2012-01-01

    Background: A combination of S-1 and cisplatin has been shown to be effective with acceptable safety for the first-line treatment of far-advanced gastric cancer in Japan. This is the first randomised phase II trial to compare S-1+paclitaxel with S-1+cisplatin in this setting. Methods: Patients with unresectable and/or recurrent advanced gastric cancer were randomly assigned to receive one of the two regimens: S-1 (40 mg m−2 twice daily) on days 1–14 plus paclitaxel (60 mg m−2) on days 1, 8, and 15 of a 4-week cycle (S-1+paclitaxel) or S-1 (40 mg m−2 twice daily) on days 1–21 plus cisplatin (60 mg m−2) on day 8 of a 5-week cycle (S-1+cisplatin). The primary end point was the response rate (RR). Secondary end points included progression-free survival (PFS), overall survival (OS), and safety. Results: A total of 83 patients were eligible for safety and efficacy analyses. In the S-1+paclitaxel and S-1+cisplatin groups, RRs (52.3% vs 48.7% P=0.74) and median PFS (9 vs 6 months; P=0.50) were similar. The median OS was similar in the S-1+paclitaxel and S-1+cisplatin groups (16 vs 17 months; P=0.84). The incidence of grade 3 or higher haematological toxicity was 19.0% with S-1+paclitaxel and 19.5% with S-1+cisplatin. The incidence of grade 3 or higher non-haematological toxicity was 14.2% with S-1+paclitaxel and 17.1% with S-1+cisplatin. Conclusion: S-1+paclitaxel was suggested to be a feasible and effective non-platinum-based regimen for chemotherapy in patients with advanced gastric cancer. Our results should be confirmed in multicenter, phase III-controlled clinical trials. PMID:22617130

  13. Synthesis and Immunogenicity Assessment of Elastin-Like Polypeptide-M2e Construct as an Influenza Antigen

    PubMed Central

    Ingrole, Rohan S.; Tao, Wenqian; Tripathy, Jatindra N.; Gill, Harvinder S.

    2014-01-01

    The 23 amino acid-long extracellular domain of the influenza virus transmembrane protein M2 (M2e) has remained highly conserved since the 1918 pandemic, and is thus considered a good candidate for development of a universal influenza A vaccine. However, M2e is poorly immunogenic. In this study we assessed the potential of increasing immunogenicity of M2e by constructing a nanoscale-designed protein polymer containing the M2e sequence and an elastin-like polypeptide (ELP) nanodomain consisting of alanine and tyrosine guest residues (ELP(A2YA2)24). The ELP nanodomain was included to increase antigen size, and to exploit the inherent thermal inverse phase transition behavior of ELPs to purify the protein polymer. The ELP(A2YA2)24 + M2e nanodomained molecule was recombinantly synthesized. Characterization of its inverse phase transition behavior demonstrated that attachment of M2e to ELP(A2YA2)24 increased its transition temperature compared to ELP(A2YA2)24. Using a dot blot test we determined that M2e conjugated to ELP is recognizable by M2e–specific antibodies, suggesting that the conjugation process does not adversely affect the immunogenic property of M2e. Further, upon vaccinating mice with ELP(A2YA2)24 + M2e it was found that indeed the nanodomained protein enhanced M2e–specific antibodies in mouse serum compared to free M2e peptide and ELP(A2YA2)24. The immune serum could also recognize M2 expressed on influenza virions. Overall, this data suggests the potential of using molecules containing M2e–ELP nano-domains to develop a universal influenza vaccine. PMID:25825595

  14. SULFUR- AND SILICON-BEARING MOLECULES IN PLANETARY NEBULAE: THE CASE OF M2-48

    SciTech Connect

    Edwards, J. L.; Ziurys, L. M.

    2014-10-20

    Molecular-line observations of the bipolar planetary nebula (PN) M2-48 have been conducted using the Sub-Millimeter Telescope and the 12 m antenna of the Arizona Radio Observatory at 1, 2, and 3 mm. M2-48 is estimated to be ∼4800 yr old, midway through the PN evolutionary track. SiO and SO{sub 2} were detected in this source—the first identification of either molecule in a PN. CN, HCN, HNC, CS, SO, HCO{sup +}, N{sub 2}H{sup +}, and several {sup 13}C isotopologues such as {sup 13}CN, H{sup 13}CN, and H{sup 13}CO{sup +} were also observed toward this object. A radiative transfer analysis of multiple SiO transitions indicates a gas kinetic temperature of T {sub K} ∼ 55 K and a density of n(H{sub 2}) ∼ 9 × 10{sup 5} cm{sup –3} in M2-48, in agreement with previous CS and CO modeling. After CO, CN, and SO were found to be the most prevalent molecules in this nebula, with fractional abundances, relative to H{sub 2}, of f ∼ 3.8 × 10{sup –7} and 2.4 × 10{sup –7}, respectively. SO{sub 2} and HCN are also abundant, with f ∼ 1.2 × 10{sup –7}, indicating an [SO]/[SO{sub 2}] ratio of ∼2. Relatively high ion abundances were measured in M2-48 as well, with f ∼ 10{sup –7} for both HCO{sup +} and N{sub 2}H{sup +}. An [HCN]/[HNC] ratio of ∼2 was determined, as typically observed in other PNe, independent of age. The high abundances of SO and SO{sub 2}, along with the presence of SiO with f ∼ 2.9 × 10{sup –8}, suggest O/C > 1 in this source; furthermore, the prevalence of CN and N{sub 2}H{sup +} indicates nitrogen enrichment. The {sup 12}C/{sup 13}C ratio of ∼3 in the nebula was also established. These factors indicate hot-bottom burning occurred in the progenitor star of M2-48, suggesting an initial mass > 4 M {sub ☉}.

  15. Alternatively Activated (M2) Macrophage Phenotype Is Inducible by Endothelin-1 in Cultured Human Macrophages

    PubMed Central

    Soldano, Stefano; Pizzorni, Carmen; Paolino, Sabrina; Trombetta, Amelia Chiara; Montagna, Paola; Brizzolara, Renata; Ruaro, Barbara; Sulli, Alberto; Cutolo, Maurizio

    2016-01-01

    Background Alternatively activated (M2) macrophages are phenotypically characterized by the expression of specific markers, mainly macrophage scavenger receptors (CD204 and CD163) and mannose receptor-1 (CD206), and participate in the fibrotic process by over-producing pro-fibrotic molecules, such as transforming growth factor-beta1 (TGFbeta1) and metalloproteinase (MMP)-9. Endothelin-1 (ET-1) is implicated in the fibrotic process, exerting its pro-fibrotic effects through the interaction with its receptors (ETA and ETB). The study investigated the possible role of ET-1 in inducing the transition from cultured human macrophages into M2 cells. Methods Cultured human monocytes (THP-1 cell line) were activated into macrophages (M0 macrophages) with phorbol myristate acetate and subsequently maintained in growth medium (M0-controls) or treated with either ET-1 (100nM) or interleukin-4 (IL-4, 10ng/mL, M2 inducer) for 72 hours. Similarly, primary cultures of human peripheral blood monocyte (PBM)-derived macrophages obtained from healthy subjects, were maintained in growth medium (untreated cells) or treated with ET-1 or IL-4 for 6 days. Both M0 and PBM-derived macrophages were pre-treated with ET receptor antagonist (ETA/BRA, bosentan 10-5M) for 1 hour before ET-1 stimulation. Protein and gene expression of CD204, CD206, CD163, TGFbeta1 were analysed by immunocytochemistry, Western blotting and quantitative real time polymerase chain reaction (qRT-PCR). Gene expression of interleukin(IL)-10 and macrophage derived chemokine (CCL-22) was evaluated by qRT-PCR. MMP-9 production was investigated by gel zymography. Results ET-1 significantly increased the expression of M2 phenotype markers CD204, CD206, CD163, IL-10 and CCL-22, and the production of MMP-9 in both cultures of M0 and PBM-derived macrophages compared to M0-controls and untreated cells. In cultured PBM-derived macrophages, ET-1 increased TGFbeta1 protein and gene expression compared to untreated cells. The ET-1

  16. Thermal testing results of an electroformed nickel secondary (M2) mirror

    NASA Astrophysics Data System (ADS)

    Smith, David R.; Gale, David M.; Cabrera Cuevas, Lizeth; Lucero Álvarez, Maribel; Castro Santos, David; Olmos Tapia, Arak

    2016-07-01

    To support higher-frequency operation, the Large Millimeter Telescope/Gran Telescopio Milimetrico (or LMT/GTM) is replacing its existing monolithic aluminum secondary mirror (M2). The new mirror is a segmented design based on the same electroformed nickel reflector panel technology that is already in use for the primary reflector segments. While the new M2 is lighter and has better surface accuracy than the original mirror, the electroformed panels are more sensitive to high temperatures. During the design phase, concerns were raised over the level of temperature increase that could occur at M2 during daytime observations. Although the panel surface is designed to scatter visible light, the LMT primary mirror is large enough to cause substantial solar heating, even at significant angular separation from the Sun. To address these concerns, the project conducted a series of field tests, within the constraint of having minimum impact on night time observations. The supplier sent two coupon samples of a reflector panel prepared identically to their proposed M2 surface. Temperature sensors were mounted on the samples and they were temporarily secured to the existing M2 mirror at different distances from the center. The goal was to obtain direct monitoring of the surface temperature under site thermal conditions and the concentration effects from the primary reflector. With the sensors installed, the telescope was then commanded to track the Sun with an elevation offset. Initially, elevation offsets from as far as 40 degrees to as close as 6 degrees were tested. The 6 degree separation test quickly passed the target maximum temperature and the telescope was returned to a safer separation. Based on these initial results, a second set of tests was performed using elevation separations from 30 degrees to 8 degrees. To account for the variability of site conditions, the temperature data were analyzed using multiple metrics. These metrics included maximum temperature, final

  17. Sphingosine 1-phosphate receptor 1 (S1P(1)) upregulation and amelioration of experimental autoimmune encephalomyelitis by an S1P(1) antagonist.

    PubMed

    Cahalan, Stuart M; Gonzalez-Cabrera, Pedro J; Nguyen, Nhan; Guerrero, Miguel; Cisar, Elizabeth A George; Leaf, Nora B; Brown, Steven J; Roberts, Edward; Rosen, Hugh

    2013-02-01

    Sphingosine 1-phosphate receptor 1 (S1P(1)) is a G protein-coupled receptor that is critical for proper lymphocyte development and recirculation. Agonists to S1P(1) are currently in use clinically for the treatment of multiple sclerosis, and these drugs may act on both S1P(1) expressed on lymphocytes and S1P(1) expressed within the central nervous system. Agonists to S1P(1) and deficiency in S1P(1) both cause lymphocyte sequestration in the lymph nodes. In the present study, we show that S1P(1) antagonism induces lymphocyte sequestration in the lymph nodes similar to that observed with S1P(1) agonists while upregulating S1P(1) on lymphocytes and endothelial cells. Additionally, we show that S1P(1) antagonism reverses experimental autoimmune encephalomyelitis in mice without acting on S1P(1) expressed within the central nervous system, demonstrating that lymphocyte sequestration via S1P(1) antagonism is sufficient to alleviate autoimmune pathology.

  18. First Global Climate Model Simulations of the M2 Pliocene Glacial

    NASA Astrophysics Data System (ADS)

    Dolan, A.; Haywood, A.; Hunter, S. J.; Tindall, J.; Valdes, P. J.

    2013-12-01

    The Pliocene Epoch (5.2 to 2.6 Ma) and specifically the PRISM interval (3.0 to 3.3 Ma) have frequently been targeted to investigate warm intervals in Earth history (e.g. Haywood et al., 2013). However, climate variability within the Pliocene is often overlooked. Although not as dramatic as the glacial and interglacial cycles that typified the Pleistocene, the Pliocene also exhibited climate variability and periods which were apparently cooler than modern (Lisiecki and Raymo, 2005). Of particular interest is the major cooling event that occurred around 3.3 Ma during Marine Isotope Stage (MIS) M2. This 'Pliocene glacial' punctuates an otherwise relatively warm background climate and has been referred to as a failed attempt of the climate to reach a full glacial state (De Schepper et al., 2009; Haug and Tiedemann, 1998). The onset of full Northern Hemisphere (NH) glaciation finally occurred at the end of the Pliocene (~ 2.75 Ma). Although numerous temperature reconstructions from around the world's oceans tend to capture the MIS M2 cooling event, the exact nature of M2 remains enigmatic. Sea level records vary but suggest a maximum sea level drop of ~65 m compared to modern, which in itself is significant enough to necessitate the growth of a NH ice sheet (Dwyer and Chandler, 2009). Previous ice sheet modelling suggests that ~8 m sea level equivalent (SLE) ice could be stored on Antarctica (Pollard and DeConto, 2009) and this larger ice sheet (compared to modern) is potentially supported by the increase in ice-rafted debris (IRD) found offshore of East Antarctica during this time (Passchier, 2011). IRD in the North Atlantic would suggest the presence of an ice sheet on Greenland (e.g. Kleiven et al., 2002), but the locations of other ice caps in the NH are not determined due to the destructive nature of subsequent Pleistocene ice sheet advances. Moreover, recent evidence questions whether the climate in the NH was favourable at all for the initiation of ice sheets

  19. Hyperoxia-induced p47phox activation and ROS generation is mediated through S1P transporter Spns2, and S1P/S1P1&2 signaling axis in lung endothelium.

    PubMed

    Harijith, Anantha; Pendyala, Srikanth; Ebenezer, David L; Ha, Alison W; Fu, Panfeng; Wang, Yue-Ting; Ma, Ke; Toth, Peter T; Berdyshev, Evgeny V; Kanteti, Prasad; Natarajan, Viswanathan

    2016-08-01

    Hyperoxia-induced lung injury adversely affects ICU patients and neonates on ventilator assisted breathing. The underlying culprit appears to be reactive oxygen species (ROS)-induced lung damage. The major contributor of hyperoxia-induced ROS is activation of the multiprotein enzyme complex NADPH oxidase. Sphingosine-1-phosphate (S1P) signaling is known to be involved in hyperoxia-mediated ROS generation; however, the mechanism(s) of S1P-induced NADPH oxidase activation is unclear. Here, we investigated various steps in the S1P signaling pathway mediating ROS production in response to hyperoxia in lung endothelium. Of the two closely related sphingosine kinases (SphKs)1 and 2, which synthesize S1P from sphingosine, only Sphk1(-/-) mice conferred protection against hyperoxia-induced lung injury. S1P is metabolized predominantly by S1P lyase and partial deletion of Sgpl1 (Sgpl1(+/-)) in mice accentuated lung injury. Hyperoxia stimulated S1P accumulation in human lung microvascular endothelial cells (HLMVECs), and downregulation of S1P transporter spinster homolog 2 (Spns2) or S1P receptors S1P1&2, but not S1P3, using specific siRNA attenuated hyperoxia-induced p47(phox) translocation to cell periphery and ROS generation in HLMVECs. These results suggest a role for Spns2 and S1P1&2 in hyperoxia-mediated ROS generation. In addition, p47(phox) (phox:phagocyte oxidase) activation and ROS generation was also reduced by PF543, a specific SphK1 inhibitor in HLMVECs. Our data indicate a novel role for Spns2 and S1P1&2 in the activation of p47(phox) and production of ROS involved in hyperoxia-mediated lung injury in neonatal and adult mice.

  20. Possible Dust Models for C/2012 S1

    NASA Astrophysics Data System (ADS)

    Yanamandra-Fisher, P. A.

    2014-12-01

    Comet C/2012 S1 (ISON) provided a great opportunity to study a dynamically new Oort-cloud comet on its initial and only passage through the inner solar system. Contrary to expectations, the comet's activity fluctuated from high through a quiescent phase, and a major outburst days before its perihelion passage, ending in a dramatic race to complete disintegration on perihelion day, 28 November 2013. Amateur observations to professional ground-based, sub-orbital telescopes indicate the various changes of visible factors such as Afrho, a proxy for dust activity, and the measured production rates for water, consistent with the disintegration of the nucleus. Hines et al. (2013; ApJ Lett. 780) detected positive polarization in the inner coma and negative polarization in the outer coma, indicative of a jet, independently confirmed by Li et al. (2013, ApJ Lett., 779). Thermal emission observations of the comet pre-perihelion from NAOJ/Subaru/COMICS, a mid-infrared spectrometer, indicated a body with an equivalent brightness temperature of 265K (Ootsubo et al., 2013, ACM, Helsinki,FI); thermal observations acquired at the NASA/Infrared Telescope Facility (IRTF) with The Aerospace Corporation spectrometer (BASS, PI. R. Russell), before and after the November 12, 2013 outburst observed by the CIOC_ISON amateur network, indicates a brightness temperature of 330K and the presence, albeit weak, of the 11.3-micron crystalline silicate feature (Sitko et al., 2014, LPI abstract 1537). A Monte Carlo comet dust tail model, applied to extract the dust environment parameters of comet C/2012 S1 (ISON) from both Earth-based and Solar and Heliospheric Observatory (SOHO) calibrated observations, performed from about 6 AU (inbound), to right after perihelion passage, when just a small portion of the original comet nucleus survived in the form of a cloud of tiny particles, indicates that particles underwent disintegration and fragmentation (Moreno et al., 2014, ApJ Lett., 791). Ongoing work

  1. Dale Reed with model in front of M2-F1

    NASA Technical Reports Server (NTRS)

    1967-01-01

    Dale Reed with a model of the M2-F1 in front of the actual lifting body. Reed used the model to show the potential of the lifting bodies. He first flew it into tall grass to test stability and trim, then hand-launched it from buildings for longer flights. Finally, he towed the lifting-body model aloft using a powered model airplane known as the 'Mothership.' A timer released the model and it glided to a landing. Dale's wife Donna used a 9 mm. camera to film the flights of the model. Its stability as it glided--despite its lack of wings--convinced Milt Thompson and some Flight Research Center engineers including the center director, Paul Bikle, that a piloted lifting body was possible. The lifting body concept evolved in the mid-1950s as researchers considered alternatives to ballistic reentries of piloted space capsules. The designs for hypersonic, wingless vehicles were on the boards at NASA Ames and NASA Langley facilities, while the US Air Force was gearing up for its Dyna-Soar program, which defined the need for a spacecraft that would land like an airplane. Despite favorable research on lifting bodies, there was little support for a flight program. Dryden engineer R. Dale Reed was intrigued with the lifting body concept, and reasoned that some sort of flight demonstration was needed before wingless aircraft could be taken seriously. In February 1962, he built a model lifting body based upon the Ames M2 design, and air-launched it from a radio controlled 'mothership.' Home movies of these flights, plus the support of research pilot Milt Thompson, helped pursuade the facilities director, Paul Bikle, to give the go-ahead for the construction of a full-scale version, to be used as a wind-tunnel model and possibly flown as a glider. Comparing lifting bodies to space capsules, an unofficial motto of the project was, 'Don't be Rescued from Outer Space--Fly Back in Style.' The construction of the M2-F1 was a joint effort by Dryden and a local glider manufacturer, the

  2. Carboxyl- and amino-functionalized polystyrene nanoparticles differentially affect the polarization profile of M1 and M2 macrophage subsets.

    PubMed

    Fuchs, Ann-Kathrin; Syrovets, Tatiana; Haas, Karina A; Loos, Cornelia; Musyanovych, Anna; Mailänder, Volker; Landfester, Katharina; Simmet, Thomas

    2016-04-01

    Macrophages are key regulators of innate and adaptive immune responses. Exposure to microenvironmental stimuli determines their polarization into proinflammatory M1 and anti-inflammatory M2 macrophages. M1 exhibit high expression of proinflammatory TNF-α and IL-1β, and M2 promote tissue repair, but likewise support tumor growth and cause immune suppression by expressing IL-10. Thus, the M1/M2 balance critically determines tissue homeostasis. By using carboxyl- (PS-COOH) and amino-functionalized (PS-NH2) polystyrene nanoparticles, the effects of surface decoration on the polarization of human macrophages were investigated. The nanoparticles did not compromise macrophage viability nor did they affect the expression of the M1 markers CD86, NOS2, TNF-α, and IL-1β. By contrast, in M2, both nanoparticles impaired expression of scavenger receptor CD163 and CD200R, and the release of IL-10. PS-NH2 also inhibited phagocytosis of Escherichia coli by both, M1 and M2. PS-COOH did not impair phagocytosis by M2, but increased protein mass in M1 and M2, TGF-β1 release by M1, and ATP levels in M2. Thus, nanoparticles skew the M2 macrophage polarization without affecting M1 markers. Given the critical role of the M1 and M2 polarization for the immunological balance in patients with cancer or chronic inflammation, functionalized nanoparticles might serve as tools for reprogramming the M1/M2 polarization.

  3. Sphingosine kinase-1, S1P transporter spinster homolog 2 and S1P2 mRNA expressions are increased in liver with advanced fibrosis in human.

    PubMed

    Sato, Masaya; Ikeda, Hitoshi; Uranbileg, Baasanjav; Kurano, Makoto; Saigusa, Daisuke; Aoki, Junken; Maki, Harufumi; Kudo, Hiroki; Hasegawa, Kiyoshi; Kokudo, Norihiro; Yatomi, Yutaka

    2016-08-26

    The role of sphingosine 1-phosphate (S1P) in liver fibrosis or inflammation was not fully examined in human. Controversy exists which S1P receptors, S1P1 and S1P3 vs S1P2, would be importantly involved in its mechanism. To clarify these matters, 80 patients who received liver resection for hepatocellular carcinoma and 9 patients for metastatic liver tumor were enrolled. S1P metabolism was analyzed in background, non-tumorous liver tissue. mRNA levels of sphingosine kinase 1 (SK1) but not SK2 were increased in livers with fibrosis stages 3-4 compared to those with 0-2 and to normal liver. However, S1P was not increased in advanced fibrotic liver, where mRNA levels of S1P transporter spinster homolog 2 (SPNS2) but not S1P-degrading enzymes were enhanced. Furthermore, mRNA levels of S1P2 but not S1P1 or S1P3 were increased in advanced fibrotic liver. These increased mRNA levels of SK1, SPNS2 and S1P2 in fibrotic liver were correlated with α-smooth muscle actin mRNA levels in liver, and with serum ALT levels. In conclusion, S1P may be actively generated, transported to outside the cells, and bind to its specific receptor in human liver to play a role in fibrosis or inflammation. Altered S1P metabolism in fibrotic liver may be their therapeutic target.

  4. Outgassing and chemical evolution of C/2012 S1 (ISON)

    NASA Astrophysics Data System (ADS)

    Dello Russo, Neil; Vervack, Ronald J.; Kawakita, Hideyo; Cochran, Anita; McKay, Adam J.; Harris, Walter M.; Weaver, Harold A.; Lisse, Carey M.; DiSanti, Michael A.; Kobayashi, Hitomi; Biver, Nicolas; Bockelée-Morvan, Dominique; Crovisier, Jacques; Opitom, Cyrielle; Jehin, Emmanuel

    2015-11-01

    Volatile production rates, relative abundances, rotational temperatures, and spatial distributions in the coma were measured in C/2012 S1 (ISON) using long-slit high-dispersion (λ/Δλ ~ 25,000) infrared spectroscopy as part of a worldwide observing campaign. Spectra were obtained on UT 2013 October 26 and 28 with NIRSPEC at the W. M. Keck Observatory, and UT 2013 November 19 and 20 with CSHELL at the NASA IRTF. H2O was detected on all dates, with production rates increasing by about a factor of 40 between October 26 (Rh = 1.12 AU) and November 20 (Rh = 0.43 AU). Short-term variability of H2O was also seen as the production rate increased by nearly a factor of two during observations obtained over a period of about six hours on November 19. C2H6, CH3OH and CH4 abundances were slightly depleted relative to H2O in ISON compared to mean values for comets measured at infrared wavelengths. On the November dates, C2H2, HCN and OCS abundances relative to H2O appear to be close to the range of mean values, whereas H2CO and NH3 were significantly enhanced. We will compare derived chemical abundances in ISON to other comets measured with infrared spectroscopy.

  5. Synthesis and characterization of trans-M2(T(i)PB)2(O2C-CH=CH-2-C4H3S)2 (M = Mo or W) and comments on the metal-to-ligand charge transfer bands in MM quadruply bonded complexes of the type trans-M2(T(i)PB)2L2, where T(i)PB = 2,4,6-triisopropylbenzoate and L = π-accepting carboxylate ligand.

    PubMed

    Alberding, Brian G; Chisholm, Malcolm H; Lear, Benjamin J; Naseri, Vesal; Reed, Carly R

    2011-10-28

    The preparation and characterization of the compounds trans-M(2)(T(i)PB)(2)(O(2)C-CH=CH-2-C(4)H(3)S)(2) where M = Mo or W and T(i)PB = 2,4,6-triisopropylbenzoate are reported. The optical spectra of the new compounds are compared with those of related trans-M(2)(T(i)PB)(2)L(2) compounds where L = O(2)C-C(6)H(4)-4-CN, O(2)C-α,α'-terthienyl (TTh), and O(2)C-4-C(6)H(4)N-B(C(6)F(5))(3), that show strong metal-to-ligand charge transfer bands because of M(2)δ to Lπ conjugation, and are notably temperature dependant due to the various conformations of the two trans-L groups. Upon cooling the spectral features sharpen as the planar geometry that optimizes M(2)δ-Lπ conjugation is favored. As the electronic coupling of the two trans-Lπ systems increases the (0,0) electronic transition gains intensity indicating a greater nesting of the ground state (S(0)) and excited state (S(1)) potential energy surfaces. These features are discussed in terms of the related electronic coupling of [M(2)]-[M(2)] complexes.

  6. Downregulation of sphingosine 1-phosphate (S1P) receptor 1 by dexamethasone inhibits S1P-induced mesangial cell migration.

    PubMed

    Koch, Alexander; Jäger, Manuel; Völzke, Anja; Grammatikos, Georgios; Zu Heringdorf, Dagmar Meyer; Huwiler, Andrea; Pfeilschifter, Josef

    2015-06-01

    Sphingosine 1-phosphate (S1P) is generated by sphingosine kinase (SK)-1 and -2 and acts mainly as an extracellular ligand at five specific receptors, denoted S1P1-5. After activation, S1P receptors regulate important processes in the progression of renal diseases, such as mesangial cell migration and survival. Previously, we showed that dexamethasone enhances SK-1 activity and S1P formation, which protected mesangial cells from stress-induced apoptosis. Here we demonstrate that dexamethasone treatment lowered S1P1 mRNA and protein expression levels in rat mesangial cells. This effect was abolished in the presence of the glucocorticoid receptor antagonist RU-486. In addition, in vivo studies showed that dexamethasone downregulated S1P1 expression in glomeruli isolated from mice treated with dexamethasone (10 mg/kg body weight). Functionally, we identified S1P1 as a key player mediating S1P-induced mesangial cell migration. We show that dexamethasone treatment significantly lowered S1P-induced migration of mesangial cells, which was again reversed in the presence of RU-486. In summary, we suggest that dexamethasone inhibits S1P-induced mesangial cell migration via downregulation of S1P1. Overall, these results demonstrate that dexamethasone has functional important effects on sphingolipid metabolism and action in renal mesangial cells.

  7. Towards efficient mobile M2M communications: survey and open challenges.

    PubMed

    Pereira, Carlos; Aguiar, Ana

    2014-10-20

    Machine-to-Machine (M2M) communications enable networked devices and services to exchange information and perform actions seamlessly without the need for human intervention. They are viewed as a key enabler of the Internet of Things (IoT) and ubiquitous applications, like mobile healthcare, telemetry, or intelligent transport systems. We survey existing work on mobile M2M communications, we identify open challenges that have a direct impact on performance and resource usage efficiency, especially the impact on energy efficiency, and we review techniques to improve communications. We review the ETSI standard and application protocols, and draw considerations on the impact of their use in constrained mobile devices. Nowadays, smartphones are equipped with a wide range of embedded sensors, with varied local and wide area connectivity capabilities, and thus they offer a unique opportunity to serve as mobile gateways for other more constrained devices with local connectivity. At the same time, they can gather context data about users and environment from the embedded sensors. These capabilities may be crucial for mobile M2M applications. Finally, in this paper, we consider a scenario where smartphones are used as gateways that collect and aggregate data from sensors in a cellular network. We conclude that, in order for their use to the feasible in terms of a normal depletion time of a smartphone's battery, it is a good advice to maximize the collection of data necessary to be transmitted from nearby sensors, and maximize the intervals between transmissions. More research is required to devise energy efficient transmission methods that enable the use of smartphones as mobile gateways.

  8. Towards Efficient Mobile M2M Communications: Survey and Open Challenges

    PubMed Central

    Pereira, Carlos; Aguiar, Ana

    2014-01-01

    Machine-to-Machine (M2M) communications enable networked devices and services to exchange information and perform actions seamlessly without the need for human intervention. They are viewed as a key enabler of the Internet of Things (IoT) and ubiquitous applications, like mobile healthcare, telemetry, or intelligent transport systems. We survey existing work on mobile M2M communications, we identify open challenges that have a direct impact on performance and resource usage efficiency, especially the impact on energy efficiency, and we review techniques to improve communications. We review the ETSI standard and application protocols, and draw considerations on the impact of their use in constrained mobile devices. Nowadays, smartphones are equipped with a wide range of embedded sensors, with varied local and wide area connectivity capabilities, and thus they offer a unique opportunity to serve as mobile gateways for other more constrained devices with local connectivity. At the same time, they can gather context data about users and environment from the embedded sensors. These capabilities may be crucial for mobile M2M applications. Finally, in this paper, we consider a scenario where smartphones are used as gateways that collect and aggregate data from sensors in a cellular network. We conclude that, in order for their use to the feasible in terms of a normal depletion time of a smartphone's battery, it is a good advice to maximize the collection of data necessary to be transmitted from nearby sensors, and maximize the intervals between transmissions. More research is required to devise energy efficient transmission methods that enable the use of smartphones as mobile gateways. PMID:25333291

  9. Role for Microglia in Sex Differences after ischemic stroke: Importance of M2

    PubMed Central

    Bodhankar, Sheetal; Lapato, Andrew; Chen, Yingxin; Vandenbark, Arthur A.; Saugstad, Julie A.; Offner, Halina

    2015-01-01

    Inflammation plays a critical role in the pathogenesis of ischemic stroke. This process depends, in part, upon proinflammatory factors released by activated resident central nervous system (CNS) microglia (MG). Previous studies demonstrated that transfer of IL-10+ B-cells reduced infarct volumes in male C57BL/6J recipient mice when given 24 h prior to or therapeutically at 4 h or 24 h after experimental stroke induced by 60 min middle cerebral artery occlusion (MCAO). The present study assesses possible sex differences in immunoregulation by IL-10+ B-cells on primary male vs. female MG cultured from naïve and ischemic stroke-induced mice. Thus, MG cultures were treated with recombinant (r)IL-10, rIL-4 or IL-10+ B-cells after lipopolysaccharide (LPS) activation and evaluated by flow cytometry for production of proinflammatory and anti-inflammatory factors. We found that IL-10+ B-cells significantly reduced MG production of TNF-α, IL-1β and CCL3 post-MCAO and increased their expression of the anti-inflammatory M2 marker, CD206, by cell-cell interactions. Moreover, MG from female vs. male mice had higher expression of IL-4 and IL-10 receptors and increased production of IL-4, especially after treatment with IL-10+ B-cells. These findings indicate that IL-10-producing B-cells play a crucial role in regulating MG activation, proinflammatory cytokine release and M2 phenotype induction, post-MCAO, with heightened sensitivity of female MG to IL-4 and IL-10. This study, coupled with our previous demonstration of increased numbers of transferred IL-10+ B-cells in the ischemic hemisphere, provide a mechanistic basis for local regulation by secreted IL-10 and IL-4 as well as direct B-cell/MG interactions that promote M2+-MG. PMID:26246072

  10. Optical trapping with superfocused high-M2 laser diode beam

    NASA Astrophysics Data System (ADS)

    Sokolovskii, G. S.; Dudelev, V. V.; Melissinaki, V.; Losev, S. N.; Soboleva, K. K.; Deryagin, A. G.; Kuchinskii, V. I.; Farsari, M.; Sibbett, W.; Rafailov, E. U.

    2015-03-01

    Many applications of high-power laser diodes demand tight focusing. This is often not possible due to the multimode nature of semiconductor laser radiation possessing beam propagation parameter M2 values in double-digits. We propose a method of `interference' superfocusing of high-M2 diode laser beams with a technique developed for the generation of Bessel beams based on the employment of an axicon fabricated on the tip of a 100 μm diameter optical fiber with high-precision direct laser writing. Using axicons with apex angle 1400 and rounded tip area as small as ~10 μm diameter, we demonstrate 2-4 μm diameter focused laser `needle' beams with approximately 20 μm propagation length generated from multimode diode laser with beam propagation parameter M2=18 and emission wavelength of 960 nm. This is a few-fold reduction compared to the minimal focal spot size of ~11 μm that could be achieved if focused by an `ideal' lens of unity numerical aperture. The same technique using a 1600 axicon allowed us to demonstrate few-μm-wide laser `needle' beams with nearly 100 μm propagation length with which to demonstrate optical trapping of 5-6 μm rat blood red cells in a water-heparin solution. Our results indicate the good potential of superfocused diode laser beams for applications relating to optical trapping and manipulation of microscopic objects including living biological objects with aspirations towards subsequent novel lab-on-chip configurations.

  11. Epigenetic regulation of pro-inflammatory cytokine secretion by sphingosine 1-phosphate (S1P) in acute lung injury: Role of S1P lyase.

    PubMed

    Ebenezer, David L; Fu, Panfeng; Suryadevara, Vidyani; Zhao, Yutong; Natarajan, Viswanathan

    2017-01-01

    Cellular level of sphingosine-1-phosphate (S1P), the simplest bioactive sphingolipid, is tightly regulated by its synthesis catalyzed by sphingosine kinases (SphKs) 1 & 2 and degradation mediated by S1P phosphatases, lipid phosphate phosphatases, and S1P lyase. The pleotropic actions of S1P are attributed to its unique inside-out (extracellular) signaling via G-protein-coupled S1P1-5 receptors, and intracellular receptor independent signaling. Additionally, S1P generated in the nucleus by nuclear SphK2 modulates HDAC1/2 activity, regulates histone acetylation, and transcription of pro-inflammatory genes. Here, we present data on the role of S1P lyase mediated S1P signaling in regulating LPS-induced inflammation in lung endothelium. Blocking S1P lyase expression or activity attenuated LPS-induced histone acetylation and secretion of pro-inflammatory cytokines. Degradation of S1P by S1P lyase generates Δ2-hexadecenal and ethanolamine phosphate and the long-chain fatty aldehyde produced in the cytoplasmic compartment of the endothelial cell seems to modulate histone acetylation pattern, which is different from the nuclear SphK2/S1P signaling and inhibition of HDAC1/2. These in vitro studies suggest that S1P derived long-chain fatty aldehyde may be an epigenetic regulator of pro-inflammatory genes in sepsis-induced lung inflammation. Trapping fatty aldehydes and other short chain aldehydes such as 4-hydroxynonenal derived from S1P degradation and lipid peroxidation, respectively by cell permeable agents such as phloretin or other aldehyde trapping agents may be useful in treating sepsis-induced lung inflammation via modulation of histone acetylation. .

  12. ApoA-I/SR-BI modulates S1P/S1PR2-mediated inflammation through the PI3K/Akt signaling pathway in HUVECs.

    PubMed

    Ren, Kun; Lu, Yan-Ju; Mo, Zhong-Cheng; -Liu, Xing; Tang, Zhen-Li; Jiang, Yue; Peng, Xiao-Shan; Li, Li; Zhang, Qing-Hai; Yi, Guang-Hui

    2017-02-08

    Endothelial dysfunction plays a vital role during the initial stage of atherosclerosis. Oxidized low-density lipoprotein (ox-LDL) induces vascular endothelial injury and vessel wall inflammation. Sphingosine-1-phosphate (S1P) exerts numerous vasoprotective effects by binding to diverse S1P receptors (S1PRs; S1PR1-5). A number of studies have shown that in endothelial cells (ECs), S1PR2 acts as a pro-atherosclerotic mediator by stimulating vessel wall inflammation through the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Scavenger receptor class B member I (SR-BI), a high-affinity receptor for apolipoprotein A-I (apoA-I)/high-density lipoprotein (HDL), inhibits nuclear factor-κB (NF-κB) translocation and decreases the plasma levels of inflammatory mediators via the PI3K/Akt pathway. We hypothesized that the inflammatory effects of S1P/S1PR2 on ECs may be regulated by apoA-I/SR-BI. The results showed that ox-LDL, a pro-inflammatory factor, augmented the S1PR2 level in human umbilical vein endothelial cells (HUVECs) in a dose- and time-dependent manner. In addition, S1P/S1PR2 signaling influenced the levels of inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-10, aggravating inflammation in HUVECs. Moreover, the pro-inflammatory effects induced by S1P/S1PR2 were attenuated by SR-BI overexpression and enhanced by an SR-BI inhibitor, BLT-1. Further experiments showed that the PI3K/Akt signaling pathway was involved in this process. Taken together, these results demonstrate that apoA-I/SR-BI negatively regulates S1P/S1PR2-mediated inflammation in HUVECs by activating the PI3K/Akt signaling pathway.

  13. Sphingosine 1-phosphate (S1P) receptor agonists mediate pro-fibrotic responses in normal human lung fibroblasts via S1P2 and S1P3 receptors and Smad-independent signaling.

    PubMed

    Sobel, Katrin; Menyhart, Katalin; Killer, Nina; Renault, Bérengère; Bauer, Yasmina; Studer, Rolf; Steiner, Beat; Bolli, Martin H; Nayler, Oliver; Gatfield, John

    2013-05-24

    Synthetic sphingosine 1-phosphate receptor 1 modulators constitute a new class of drugs for the treatment of autoimmune diseases. Sphingosine 1-phosphate (S1P) signaling, however, is also involved in the development of fibrosis. Using normal human lung fibroblasts, we investigated the induction of fibrotic responses by the S1P receptor (S1PR) agonists S1P, FTY720-P, ponesimod, and SEW2871 and compared them with the responses induced by the known fibrotic mediator TGF-β1. In contrast to TGF-β1, S1PR agonists did not induce expression of the myofibroblast marker α-smooth muscle actin. However, TGF-β1, S1P, and FTY720-P caused robust stimulation of extracellular matrix (ECM) synthesis and increased pro-fibrotic marker gene expression including connective tissue growth factor. Ponesimod showed limited and SEW2871 showed no pro-fibrotic potential in these readouts. Analysis of pro-fibrotic signaling pathways showed that in contrast to TGF-β1, S1PR agonists did not activate Smad2/3 signaling but rather activated PI3K/Akt and ERK1/2 signaling to induce ECM synthesis. The strong induction of ECM synthesis by the nonselective agonists S1P and FTY720-P was due to the stimulation of S1P2 and S1P3 receptors, whereas the weaker induction of ECM synthesis at high concentrations of ponesimod was due to a low potency activation of S1P3 receptors. Finally, in normal human lung fibroblast-derived myofibroblasts that were generated by TGF-β1 pretreatment, S1P and FTY720-P were effective stimulators of ECM synthesis, whereas ponesimod was inactive, because of the down-regulation of S1P3R expression in myofibroblasts. These data demonstrate that S1PR agonists are pro-fibrotic via S1P2R and S1P3R stimulation using Smad-independent pathways.

  14. Distinct interneuron types express m2 muscarinic receptor immunoreactivity on their dendrites or axon terminals in the hippocampus.

    PubMed

    Hájos, N; Papp, E C; Acsády, L; Levey, A I; Freund, T F

    1998-01-01

    In previous studies m2 muscarinic acetylcholine receptor-immunoreactive interneurons and various types of m2-positive axon terminals have been described in the hippocampal formation. The aim of the present study was to identify the types of interneurons expressing m2 receptor and to examine whether the somadendritic and axonal m2 immunostaining labels the same or distinct cell populations. In the CA1 subfield, neurons immunoreactive for m2 have horizontal dendrites, they are located at the stratum oriens/alveus border and have an axon that project to the dendritic region of pyramidal cells. In the CA3 subfield and the hilus, m2-positive neurons are multipolar and are scattered in all layers except stratum lacunosum-moleculare. In stratum pyramidale of the CA1 and CA3 regions, striking axon terminal staining for m2 was observed, surrounding the somata and axon initial segments of pyramidal cells in a basket-like manner. The co-localization of m2 with neurochemical markers and GABA was studied using the "mirror" technique and fluorescent double-immunostaining at the light microscopic level and with double-labelling using colloidal gold-conjugated antisera and immunoperoxidase reaction (diaminobenzidine) at the electron microscopic level. GABA was shown to be present in the somata of most m2-immunoreactive interneurons, as well as in the majority of m2-positive terminals in all layers. The calcium-binding protein parvalbumin was absent from practically all m2-immunoreactive cell bodies and dendrites. In contrast, many of the terminals synapsing on pyramidal cell somata and axon initial segments co-localized parvalbumin and m2, suggesting a differential distribution of m2 receptor immunoreactivity on the axonal and somadendritic membrane of parvalbumin-containing basket and axo-axonic cells. The co-existence of m2 receptors with the calcium-binding protein calbindin and the neuropeptides cholecystokinin and vasoactive intestinal polypeptide was rare throughout the

  15. Putative M2 muscarinic receptors of rat heart have high affinity for organophosphorus anticholinesterases

    SciTech Connect

    Silveira, C.L.; Eldefrawi, A.T.; Eldefrawi, M.E. )

    1990-05-01

    The M2 subtype of muscarinic receptor is predominant in heart, and such receptors were reported to be located in muscles as well as in presynaptic cholinergic and adrenergic nerve terminals. Muscarinic receptors of rat heart were identified by the high affinity binding of the agonist (+)-(3H)cis-methyldioxolane ((3H)CD), which has been used to label a high affinity population of M2 receptors. A single population of sites was detected and (3H)CD binding was sensitive to the M2 antagonist himbacine but much less so to pirenzepine, the M1 antagonist. These cardiac receptors had different sensitivities to NiCl2 and N-ethylmaleimide from brain muscarinic receptors, that were also labeled with (3H)CD and considered to be of the M2 subtype. Up to 70% of the (3H)CD-labeled cardiac receptors had high affinities for several organophosphate (OP) anticholinesterases. (3H)CD binding was inhibited by the nerve agents soman, VX, sarin, and tabun, with K0.5 values of 0.8, 2, 20, and 50 nM, respectively. It was also inhibited by echothiophate and paraoxon with K0.5 values of 100 and 300 nM, respectively. The apparent competitive nature of inhibition of (3H)CD binding by both sarin and paraoxon suggests that the OPs bind to the acetylcholine binding site of the muscarinic receptor. Other OP insecticides had lower potencies, inhibiting less than 50% of 5 nM (3H)CD binding by 1 microM of EPN, coumaphos, dioxathion, dichlorvos, or chlorpyriphos. There was poor correlation between the potencies of the OPs in reversibly inhibiting (3H)CD binding, and their anticholinesterase activities and toxicities. Acetylcholinesterases are the primary targets for these OP compounds because of the irreversible nature of their inhibition, which results in building of acetylcholine concentrations that activate muscarinic and nicotinic receptors and desensitize them, thereby inhibiting respiration.

  16. Atmospheric Turbulence Measurements With the Automatic Mini UAV 'M2AV Carolo'

    NASA Astrophysics Data System (ADS)

    Bange, J.; van den Kroonenberg, A. C.; Spieß, T.; Buschmann, M.; Krüger, L.; Heindorf, A.; Vörsmann, P.

    2007-05-01

    The limitations of manned airborne meteorological measurements led to the development of an autonomously operating mini aircraft, the Meteorological Mini-UAV (M2AV), at the Institute of Aerospace Systems, Technical University of Braunschweig, Germany. The task was to develop, test and verify a meteorological sensor package as payload for an already available automatic carrier aircraft, the UAV 'Carolo T200', which operates autonomously i.e. without remote control. The M2AV is a self constructed model aircraft with two electrically powered engines and a wingspan of two meters. The maximum take-off weight is 4.5~kg (the M2AV is therefore classified as an model plane which simplifies authority issues), including 1.5~kg of payload. It is hand-launched which makes operation of the aircraft easy. With an endurance of approximately 50 minutes, the range accounts for 60 km at a cruising speed of 20~m/s. The M2AV is capable of performing turbulence measurements (wind vector, temperature and humidity) within the troposphere and offers an economic component during meteorological campaigns. The meteorological sensors are mounted on a noseboom to minimise the aircraft's influence on the measurements and to position the sensors closely to each other. Wind is measured via a small five-hole probe, an inertia measurement unit and GPS. The flight mission (waypoints, altitudes, airspeed) is planned and assigned to the aircraft before the semi- automatic launch. The flight is only controlled by the on-board autopilot system which only communicates with a ground station (laptop PC) for the exchange of measured data and command updates like new waypoints etc. The talk gives details on the technical items, calibration and first missions. Results from first field experiments like the LAUNCH-2005 campaign near Berlin are used for data quality assessment by comparison with simultaneous lidar and sodar measurements. An in situ comparison with the highly accurate helicopter-borne turbulence

  17. Autoresonances of m=2 diocotron oscillations in non-neutral electron plasmas.

    PubMed

    Gomberoff, K; Higaki, H; Kaga, C; Ito, K; Okamoto, H

    2016-10-01

    The existence of autoresonances for m=2 diocotron oscillations of non-neutral electron plasmas in a uniform magnetic field was predicted by particle-in-cell simulations and it was confirmed in experiments. The obtained results show clear deviations from the standard threshold amplitude dependence on the sweep rate. The threshold amplitude approaches a constant at a lower sweep rate when there is a damping force. It was also found that the aspect ratio for the oval cross section of the confined plasma can be controlled by the frequency of the externally applied driving force.

  18. Autoresonances of m =2 diocotron oscillations in non-neutral electron plasmas

    NASA Astrophysics Data System (ADS)

    Gomberoff, K.; Higaki, H.; Kaga, C.; Ito, K.; Okamoto, H.

    2016-10-01

    The existence of autoresonances for m =2 diocotron oscillations of non-neutral electron plasmas in a uniform magnetic field was predicted by particle-in-cell simulations and it was confirmed in experiments. The obtained results show clear deviations from the standard threshold amplitude dependence on the sweep rate. The threshold amplitude approaches a constant at a lower sweep rate when there is a damping force. It was also found that the aspect ratio for the oval cross section of the confined plasma can be controlled by the frequency of the externally applied driving force.

  19. IRF5 regulates lung macrophages M2 polarization during severe acute pancreatitis in vitro

    PubMed Central

    Sun, Kang; He, Song-Bing; Qu, Jian-Guo; Dang, Sheng-Chun; Chen, Ji-Xiang; Gong, Ai-Hua; Xie, Rong; Zhang, Jian-Xin

    2016-01-01

    AIM To investigate the role of interferon regulatory factor 5 (IRF5) in reversing polarization of lung macrophages during severe acute pancreatitis (SAP) in vitro. METHODS A mouse SAP model was established by intraperitoneal (ip) injections of 20 μg/kg body weight caerulein. Pathological changes in the lung were observed by hematoxylin and eosin staining. Lung macrophages were isolated from bronchoalveolar lavage fluid. The quantity and purity of lung macrophages were detected by fluorescence-activated cell sorting and evaluated by real-time polymerase chain reaction (RT-PCR). They were treated with IL-4/IRF5 specific siRNA (IRF5 siRNA) to reverse their polarization and were evaluated by detecting markers expression of M1/M2 using RT-PCR. RESULTS SAP associated acute lung injury (ALI) was induced successfully by ip injections of caerulein, which was confirmed by histopathology. Lung macrophages expressed high levels of IRF5 as M1 phenotype during the early acute pancreatitis stages. Reduction of IRF5 expression by IRF5 siRNA reversed the action of macrophages from M1 to M2 phenotype in vitro. The expressions of M1 markers, including IRF5 (S + IRF5 siRNA vs S + PBS, 0.013 ± 0.01 vs 0.054 ± 0.047, P < 0.01), TNF-α (S + IRF5 siRNA vs S + PBS, 0.0003 ± 0.0002 vs 0.019 ± 0.018, P < 0.001), iNOS (S + IRF5 siRNA vs S + PBS, 0.0003 ± 0.0002 vs 0.026 ± 0.018, P < 0.001) and IL-12 (S + IRF5 siRNA vs S + PBS, 0.000005 ± 0.00004 vs 0.024 ± 0.016, P < 0.001), were decreased. In contrast, the expressions of M2 markers, including IL-10 (S + IRF5 siRNA vs S + PBS, 0.060 ± 0.055 vs 0.0230 ± 0.018, P < 0.01) and Arg-1 (S + IRF5 siRNA vs S + PBS, 0.910 ± 0.788 vs 0.0036 ± 0.0025, P < 0.001), were increased. IRF5 siRNA could reverse the lung macrophage polarization more effectively than IL-4. CONCLUSION Treatment with IRF5 siRNA can reverse the pancreatitis-induced activation of lung macrophages from M1 phenotype to M2 phenotype in SAP associated with ALI. PMID:27895424

  20. Seasonal modulation of M2 tide in the Northern Bay of Bengal

    NASA Astrophysics Data System (ADS)

    Tazkia, A. R.; Krien, Y.; Durand, F.; Testut, L.; Islam, AKM S.; Papa, F.; Bertin, X.

    2017-04-01

    The Northern Bay of Bengal (BoB) with its adjoining Ganges-Brahmaputra-Meghna delta (GBM) forms the largest deltaic region in the world. It is surrounded by a wide area of low-lying land (less than a few meters above mean sea level), very densely populated. It is home to a strong variability of sea level, across all timescales, with ample tides and frequent storm surges. It is also subject to extended river flooding during the monsoon season, with frequent overflows of two of the world's largest rivers (Brahmaputra and Ganges). There is thus a need to understand and predict the various mechanisms responsible for coastal and estuarine water level variability in this area. In this study, we address one of the least understood facets of this variability: the low-frequency modulation of tides. We focus on the seasonal changes of amplitude of the semi-diurnal lunar tide, M2. It is found that M2 amplitude shows marked changes between winter and summer seasons (of order 10 cm), incommensurate with most of the world's coastal ocean. We observe contrasted patterns from the open areas of the coastal ocean to the inner part of the GBM estuary. In the coastal ocean and over most of the GBM delta, M2 amplitude is stronger during summer and decreases until winter. Conversely, in the far northern part of GBM estuary, M2 amplitude is stronger during winter and weaker during summer. We make use of a hydrodynamic barotropic tidal model to decipher the processes responsible for this evolution. It is found that throughout the coastal ocean and over most of the GBM delta, this evolution is driven by frictional effects, with a seasonal modulation of bottom dissipation of tidal energy. Our simple barotropic model, however, does not capture the observed range of seasonal modulation of tides in the GBM estuary and at its mouth. Our study advocates for a careful consideration of these processes for a proper representation of the tidal dynamics as well as of the flooding hazard in the Bengal

  1. Resonant Photoemission and M_{2,3}-Absorption Spectra in Nickel Dichloride

    NASA Astrophysics Data System (ADS)

    Igarashi, J.

    Ni 3p-resonant photoemission and Ni M_{2,3}-absorption spectra are calculated in detail on a cluster of (NiCl_6)^{4-} with the use of the transition matrix elements evaluated on the Herman-Skillman potential in Ni atom. Overall spectral shape agrees well with experiment, allowing a determination of the parameters which characterize Ni 3d and Cl 3p states. Resonance behavior is discussed near the Ni 3p-core level photothreshold. The resonant enhancement is found to be larger for the peak with higher binding energy in the d^7-multiplets.

  2. The r-step Fibonacci-Hurwitz sequences in the binary polyhedral group <2, m, 2>

    NASA Astrophysics Data System (ADS)

    Deveci, Ömür; Ćiçekci, Deniz

    2016-04-01

    In [1], Deveci et al. defined the r-step Fibonacci-Hurwitz sequences from the Hurwitz matrices obtained from the characteristic polynomial of the k-step Fibonacci sequence. Also, they extended the r-step Fibonacci-Hurwitz sequences to groups. In this work, we obtain the periods of the r-step Fibonacci-Hurwitz sequences in the binary polyhedral group <2, m, 2> for generating triple {x, y, z} and generating pair {y, z} by the aid of the periods of the r-step Fibonacci-Hurwitz sequences according to modulo m.

  3. Vitamin K(3) and K(5) are inhibitors of tumor pyruvate kinase M2.

    PubMed

    Chen, Jing; Jiang, Zheng; Wang, Beibei; Wang, Yanguang; Hu, Xun

    2012-03-28

    Pyruvate kinase M2 (PKM2) is a rate-limiting enzyme of aerobic glycolysis in cancer cells and plays important roles in cancer metabolism and growth. Here we show that vitamin K(3) and K(5) (VK(3) and VK(5)) are relatively specific PKM2 inhibitors. VK(3) and VK(5) showed a significantly stronger potency to inhibit PKM2 than to inhibit PKM1 and PKL, 2 other isoforms of PK dominantly expressed in most adult tissues and liver. This study combined with previous reports supports that VK(3) and VK(5) have potential as adjuvant for cancer chemotherapy.

  4. The turbomachine blading design using S2-S1 approach

    NASA Technical Reports Server (NTRS)

    Luu, T. S.; Bencherif, L.; Viney, B.; Duc, J. M. Nguyen

    1991-01-01

    The boundary conditions corresponding to the design problem when the blades being simulated by the bound vorticity distribution are presented. The 3D flow is analyzed by the two steps S2 - S1 approach. In the first step, the number of blades is supposed to be infinite, the vortex distribution is transformed into an axisymmetric one, so that the flow field can be analyzed in a meridional plane. The thickness distribution of the blade producing the flow channel striction is taken into account by the modification of metric tensor in the continuity equation. Using the meridional stream function to define the flow field, the mass conservation is satisfied automatically. The governing equation is deduced from the relation between the azimuthal component of the vorticity and the meridional velocity. The value of the azimuthal component of the vorticity is provided by the hub to shroud equilibrium condition. This step leads to the determination of the axisymmetric stream sheets as well as the approximate camber surface of the blade. In the second step, the finite number of blades is taken into account, the inverse problem corresponding to the blade to blade flow confined in each stream sheet is analyzed. The momentum equation implies that the free vortex of the absolute velocity must be tangential to the stream sheet. The governing equation for the blade to blade flow stream function is deduced from this condition. At the beginning, the upper and the lower surfaces of the blades are created from the camber surface obtained from the first step with the assigned thickness distribution. The bound vorticity distribution and the penetrating flux conservation applied on the presumed blade surface constitute the boundary conditions of the inverse problem. The detection of this flux leads to the rectification of the geometry of the blades.

  5. Search for ammonia in comet C/2012 S1 (ISON)

    NASA Astrophysics Data System (ADS)

    Faggi, S.; Codella, C.; Tozzi, G.; Comoretto, G.; Crovisier, J.; Nesti, R.; Panella, D.; Boissier, J.; Bolli, P.; Brucato, J.; Massi, F.; Tofani, G.

    2014-07-01

    Comets are pristine bodies of the Solar System and their studies can give precious hints on the formation of the Solar System itself. New comets, coming form the Oort Colud at their first passage close to the Sun, are particularly important, because they are not differentiated by the Solar radiation and they are supposed to have a large quantity of organic matter close to the surface. Here we report the results of a search for NH_3(1,1) emission at 23.7 GHz in comet C/2012 S1 ISON using a new dual-feed K-band receiver mounted on the Medicina 32-m antenna. We observed the comet once close to its perihelion, from 2013 Nov. 25 to Nov. 28, when its heliocentric distance changed from 0.25 au to 0.03 au. We integrated about 6 hrs per day, obtaining high-spectral-resolution (1 km/s) spectra with a typical rms noise of 10 mK. Such sensitivity allowed us to derive an upper limit of Q(NH_3) of about 2.5 ×10^{29} mol/s on November 26. This upper limit would correspond to a Q(H_2O) of about 2.5 ×10^{31} mol/s, assuming the typical Q(H_2O)/Q(NH_3) ratio of 100. These findings confirm that no significant Q(H_2O) enhancement happened near the perihelion, consistent with a definitive decrease of molecules production rate.

  6. WILL COMET ISON (C/2012 S1) SURVIVE PERIHELION?

    SciTech Connect

    Knight, Matthew M.; Walsh, Kevin J.

    2013-10-10

    On 2013 November 28 Comet ISON (C/2012 S1) will pass by the Sun with a perihelion distance of 2.7 solar radii. Understanding the possible outcomes for the comet's response to such a close passage by the Sun is important for planning observational campaigns and for inferring ISON's physical properties. We present new numerical simulations and interpret them in context with the historical track record of comet disruptions and of sungrazing comet behavior. Historical data suggest that sizes below ∼200 m are susceptible to destruction by sublimation driven mass loss, while we find that for ISON's perihelion distance, densities lower than 0.1 g cm{sup –3} are required to tidally disrupt a retrograde or non-spinning body. Such low densities are substantially below the range of the best-determined comet nucleus densities, though dynamically new comets such as ISON have few measurements of physical properties. Disruption may occur for prograde rotation at densities up to 0.7 g cm{sup –3}, with the chances of disruption increasing for lower density, faster prograde rotation, and increasing elongation of the nucleus. Given current constraints on ISON's nucleus properties and the typically determined values for these properties among all comets, we find tidal disruption to be unlikely unless other factors (e.g., spin-up via torquing) affect ISON substantially. Whether or not disruption occurs, the largest remnant must be big enough to survive subsequent mass loss due to sublimation in order for ISON to remain a viable comet well after perihelion.

  7. M2 macrophages or IL-33 treatment attenuate ongoing Mycobacterium tuberculosis infection

    PubMed Central

    Piñeros, A. R.; Campos, L. W.; Fonseca, D. M.; Bertolini, T. B.; Gembre, A. F.; Prado, R. Q.; Alves-Filho, J. C.; Ramos, S. G.; Russo, M.; Bonato, V. L. D.

    2017-01-01

    The protective effects of mycobacterial infections on lung allergy are well documented. However, the inverse relationship between tuberculosis and type 2 immunity is still elusive. Although type 1 immunity is essential to protection against Mycobacterium tuberculosis it might be also detrimental to the host due to the induction of extensive tissue damage. Here, we determined whether lung type 2 immunity induced by allergen sensitization and challenge could affect the outcome of M. tuberculosis infection. We used two different protocols in which sensitization and allergen challenge were performed before or after M. tuberculosis infection. We found an increased resistance to M. tuberculosis only when allergen exposure was given after, but not before infection. Infected mice exposed to allergen exhibited lower bacterial load and cellular infiltrates in the lungs. Enhanced resistance to infection after allergen challenge was associated with increased gene expression of alternatively activated macrophages (M2 macrophages) and IL-33 levels. Accordingly, either adoptive transfer of M2 macrophages or systemic IL-33 treatment was effective in attenuating M. tuberculosis infection. Notably, the enhanced resistance induced by allergen exposure was dependent on IL-33 receptor ST2. Our work indicates that IL-33 might be an alternative therapeutic treatment for severe tuberculosis. PMID:28128217

  8. Feedback mechanisms between M2 macrophages and Th17 cells in colorectal cancer patients.

    PubMed

    Mao, Hui; Pan, Fei; Guo, Hongxia; Bu, Fangfang; Xin, Tong; Chen, Shukun; Guo, Yajun

    2016-09-01

    IL-17 and IL-22 are linked to the development of intestinal inflammation and colorectal cancer (CRC). However, the maintenance of IL-17 and IL-22 production, as well as the cell type (Th17) that mediates these cytokines in CRC patients, remains unknown. To examine this, untreated CRC patients and healthy controls were recruited in this study. We first observed that CRC patients contained significantly elevated levels of IL-17- and IL-22-producing CD4(+) T cells. The vast majority of IL-22-expressing CD4(+) T cells also expressed IL-17. We then found that the production of both IL-17 and IL-22 required support from autologous monocytes, since the depletion of monocytes significantly downregulated IL-17 and IL-22 secretion. Naive T cells from CRC patients did not secrete IL-17 or IL-22 initially, but long-term coculture with autologous monocytes significantly upregulated IL-17 and IL-22 production in an IL-6-dependent manner. Blockade of IL-6 significantly reduced the levels of both IL-17 and IL-22. We then observed that CD163(+) M2 macrophages were the main contributor of IL-6. Interestingly, incubation of monocytes with CCR4(+)CCR6(+) Th17 cells resulted in significantly higher levels of CD163(+) macrophages as well as higher IL-6 secretion, than incubation with non-Th17 CD4(+) T cells. Together, our study discovered a positive feedback mechanism between Th17 and M2 macrophages in CRC patients.

  9. M2-like macrophages are responsible for collagen degradation through a mannose receptor–mediated pathway

    PubMed Central

    Madsen, Daniel H.; Leonard, Daniel; Masedunskas, Andrius; Moyer, Amanda; Jürgensen, Henrik Jessen; Peters, Diane E.; Amornphimoltham, Panomwat; Selvaraj, Arul; Yamada, Susan S.; Brenner, David A.; Burgdorf, Sven; Engelholm, Lars H.; Behrendt, Niels; Holmbeck, Kenn; Weigert, Roberto

    2013-01-01

    Tissue remodeling processes critically depend on the timely removal and remodeling of preexisting collagen scaffolds. Nevertheless, many aspects related to the turnover of this abundant extracellular matrix component in vivo are still incompletely understood. We therefore took advantage of recent advances in optical imaging to develop an assay to visualize collagen turnover in situ and identify cell types and molecules involved in this process. Collagen introduced into the dermis of mice underwent cellular endocytosis in a partially matrix metalloproteinase–dependent manner and was subsequently routed to lysosomes for complete degradation. Collagen uptake was predominantly executed by a quantitatively minor population of M2-like macrophages, whereas more abundant Col1a1-expressing fibroblasts and Cx3cr1-expressing macrophages internalized collagen at lower levels. Genetic ablation of the collagen receptors mannose receptor (Mrc1) and urokinase plasminogen activator receptor–associated protein (Endo180 and Mrc2) impaired this intracellular collagen degradation pathway. This study demonstrates the importance of receptor-mediated cellular uptake to collagen turnover in vivo and identifies a key role of M2-like macrophages in this process. PMID:24019537

  10. M2-like macrophages are responsible for collagen degradation through a mannose receptor-mediated pathway.

    PubMed

    Madsen, Daniel H; Leonard, Daniel; Masedunskas, Andrius; Moyer, Amanda; Jürgensen, Henrik Jessen; Peters, Diane E; Amornphimoltham, Panomwat; Selvaraj, Arul; Yamada, Susan S; Brenner, David A; Burgdorf, Sven; Engelholm, Lars H; Behrendt, Niels; Holmbeck, Kenn; Weigert, Roberto; Bugge, Thomas H

    2013-09-16

    Tissue remodeling processes critically depend on the timely removal and remodeling of preexisting collagen scaffolds. Nevertheless, many aspects related to the turnover of this abundant extracellular matrix component in vivo are still incompletely understood. We therefore took advantage of recent advances in optical imaging to develop an assay to visualize collagen turnover in situ and identify cell types and molecules involved in this process. Collagen introduced into the dermis of mice underwent cellular endocytosis in a partially matrix metalloproteinase-dependent manner and was subsequently routed to lysosomes for complete degradation. Collagen uptake was predominantly executed by a quantitatively minor population of M2-like macrophages, whereas more abundant Col1a1-expressing fibroblasts and Cx3cr1-expressing macrophages internalized collagen at lower levels. Genetic ablation of the collagen receptors mannose receptor (Mrc1) and urokinase plasminogen activator receptor-associated protein (Endo180 and Mrc2) impaired this intracellular collagen degradation pathway. This study demonstrates the importance of receptor-mediated cellular uptake to collagen turnover in vivo and identifies a key role of M2-like macrophages in this process.

  11. From Monocytes to M1/M2 Macrophages: Phenotypical vs. Functional Differentiation

    PubMed Central

    Italiani, Paola; Boraschi, Diana

    2014-01-01

    Studies on monocyte and macrophage biology and differentiation have revealed the pleiotropic activities of these cells. Macrophages are tissue sentinels that maintain tissue integrity by eliminating/repairing damaged cells and matrices. In this M2-like mode, they can also promote tumor growth. Conversely, M1-like macrophages are key effector cells for the elimination of pathogens, virally infected, and cancer cells. Macrophage differentiation from monocytes occurs in the tissue in concomitance with the acquisition of a functional phenotype that depends on microenvironmental signals, thereby accounting for the many and apparently opposed macrophage functions. Many questions arise. When monocytes differentiate into macrophages in a tissue (concomitantly adopting a specific functional program, M1 or M2), do they all die during the inflammatory reaction, or do some of them survive? Do those that survive become quiescent tissue macrophages, able to react as naïve cells to a new challenge? Or, do monocyte-derived tissue macrophages conserve a “memory” of their past inflammatory activation? This review will address some of these important questions under the general framework of the role of monocytes and macrophages in the initiation, development, resolution, and chronicization of inflammation. PMID:25368618

  12. Status of the secondary mirrors (M2) for the Gemini 8-m telescopes

    NASA Astrophysics Data System (ADS)

    Knohl, Ernst-Dieter; Schoeppach, Armin; Pickering, Michael A.

    1998-08-01

    The 1-m diameter lightweight secondary mirrors (M2) for the Gemini 8-m telescopes will be the largest CVD-SiC mirrors ever produced. The design and manufacture of these mirrors is a very challenging task. In this paper we will discuss the mirror design, structural and mechanical analysis, and the CVD manufacturing process used to produce the mirror blanks. The lightweight design consist of a thin faceplate (4-mm) and triangular backstructure cells with ribs of varying heights. The main drivers in the design were weight (40 kg) and manufacturing limitations imposed on the backstructure cells and mirror mounts. Finite element modeling predicts that the mirror design will meet all of the Gemini M2 requirements for weight, mechanical integrity, resonances, and optical performance. Special design considerations were necessary to avoid stress concentration in the mounting areas and to meet the requirement that the mirror survive an 8-g earthquake. The highest risk step in the mirror blank manufacturing process is the near-net-shape CVD deposition of the thin, curved faceplate. Special tooling and procedures had to be developed to produce faceplates free of fractures, cracks, and stress during the cool-down from deposition temperature (1350 C) to room temperature. Due to time delay with the CVD manufacturing process in the meantime a backup solution from Zerodur has been started. This mirror is now in the advanced polishing process. Because the design of both mirrors is very similar an excellent comparison of both solutions is possible.

  13. Myeloid PTEN deficiency protects livers from ischemia reperfusion injury by facilitating M2 macrophage differentiation.

    PubMed

    Yue, Shi; Rao, Jianhua; Zhu, Jianjun; Busuttil, Ronald W; Kupiec-Weglinski, Jerzy W; Lu, Ling; Wang, Xuehao; Zhai, Yuan

    2014-06-01

    Although the role of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in regulating cell proliferation is well established, its function in immune responses remains to be fully appreciated. In the current study, we analyzed myeloid-specific PTEN function in regulating tissue inflammatory immune response in a murine liver partial warm ischemia model. Myeloid-specific PTEN knockout (KO) resulted in liver protection from ischemia reperfusion injury (IRI) by deviating the local innate immune response against ischemia reperfusion toward the regulatory type: expression of proinflammatory genes was selectively decreased and anti-inflammatory IL-10 was simultaneously increased in ischemia reperfusion livers of PTEN KO mice compared with those of wild-type (WT) mice. PI3K inhibitor and IL-10-neutralizing Abs, but not exogenous LPS, recreated liver IRI in these KO mice. At the cellular level, Kupffer cells and peritoneal macrophages isolated from KO mice expressed higher levels of M2 markers and produced lower TNF-α and higher IL-10 in response to TLR ligands than did their WT counterparts. They had enhanced Stat3- and Stat6-signaling pathway activation, but diminished Stat1-signaling pathway activation, in response to TLR4 stimulation. Inactivation of Kupffer cells by gadolinium chloride enhanced proinflammatory immune activation and increased IRI in livers of myeloid PTEN KO mice. Thus, myeloid PTEN deficiency protects livers from IRI by facilitating M2 macrophage differentiation.

  14. Characterizing detergent mediated reconstitution of viral protein M2 in large unilamellar vesicles

    NASA Astrophysics Data System (ADS)

    Freyre, Mariel; Grossman, Carl; Crouch, Catherine; Howard, Kathleen

    2015-03-01

    Influenza M2 is a model membrane protein whose function is to induce curvature and vesicle formation in the process of viral infection. To study embedded M2 in synthetic phospholipid vesicles (large unilamellar vesicles or LUVs), a concentration of detergent and buffer is optimized to balance protein solubility, proteolipid concentration, and LUV stability. Adding detergent also causes the LUVs to partially disassemble and form micelles, which warrants detergent removal to restore LUV integrity. We explore methods of measuring the coexistence of detergent micelles and LUVs to track the different phases of the system as detergent is removed. A combination of Fluorescence Correlation Spectroscopy, Dynamic Light Scattering, and chemical analysis are used to measure the properties of this system. With detergent/LUV number densities as high as 5 we find coexistence of micelles and LUVs at 50% to 60%. As the detergent is removed, the micelle concentration drops to lower than 30% while detergent levels drop to nearly zero. These results may indicate a polydispersed LUV size distribution after detergent mediated reconstitution. Supported by HHMI and Swarthmore College.

  15. Machine to machine (M2M) technology in demand responsive commercial buildings

    SciTech Connect

    Watson, David S.; Piette, Mary Ann; Sezgen, Osman; Motegi, Naoya; ten Hope, Laurie

    2004-08-01

    Machine to Machine (M2M) is a term used to describe the technologies that enable computers, embedded processors, smart sensors, actuators and mobile devices to communicate with one another, take measurements and make decisions--often without human intervention. M2M technology was applied to five commercial buildings in a test. The goal was to reduce electric demand when a remote price signal rose above a predetermine price. In this system, a variable price signal was generated from a single source on the Internet and distributed using the meta-language, XML (Extensible Markup Language). Each of five commercial building sites monitored the common price signal and automatically shed site-specific electric loads when the price increased above predetermined thresholds. Other than price signal scheduling, which was set up in advance by the project researchers, the system was designed to operate without human intervention during the two-week test period. Although the buildings responded to the same price signal, the communication infrastructures used at each building were substantially different. This study provides an overview of the technologies used at each building site, the price generator/server, and each link in between. Network architecture, security, data visualization and site-specific system features are characterized. The results of the test are discussed, including: functionality at each site, measurement and verification techniques, and feedback from energy managers and building operators. Lessons learned from the test and potential implications for widespread rollout are provided.

  16. Decisive disappearance search at high Δ m2 with monoenergetic muon neutrinos

    NASA Astrophysics Data System (ADS)

    Axani, S.; Collin, G.; Conrad, J. M.; Shaevitz, M. H.; Spitz, J.; Wongjirad, T.

    2015-11-01

    "KPipe" is a proposed experiment which will study muon neutrino disappearance for a sensitive test of the Δ m2˜1 eV2 anomalies, possibly indicative of one or more sterile neutrinos. The experiment is to be located at the J-PARC Materials and Life Science Experimental Facility's spallation neutron source, which represents the world's most intense source of charged kaon decay-at-rest monoenergetic (236 MeV) muon neutrinos. The detector vessel, designed to measure the charged-current interactions of these neutrinos, will be 3 m in diameter and 120 m long, extending radially at a distance of 32 to 152 m from the source. This design allows a sensitive search for νμ disappearance associated with currently favored light sterile neutrino models and features the ability to reconstruct the neutrino oscillation wave within a single, extended detector. The required detector design, technology, and costs are modest. The KPipe measurements will be robust since they depend on a known energy neutrino source with low expected backgrounds. Further, since the measurements rely only on the measured rate of detected events as a function of distance, with no required knowledge of the initial flux and neutrino interaction cross section, the results will be largely free of systematic errors. The experimental sensitivity to oscillations, based on a shape-only analysis of the L /E distribution, will extend an order of magnitude beyond present experimental limits in the relevant high-Δ m2 parameter space.

  17. A role of the sphingosine-1-phosphate (S1P)-S1P receptor 2 pathway in epithelial defense against cancer (EDAC).

    PubMed

    Yamamoto, Sayaka; Yako, Yuta; Fujioka, Yoichiro; Kajita, Mihoko; Kameyama, Takeshi; Kon, Shunsuke; Ishikawa, Susumu; Ohba, Yusuke; Ohno, Yusuke; Kihara, Akio; Fujita, Yasuyuki

    2016-02-01

    At the initial step of carcinogenesis, transformation occurs in single cells within epithelia, where the newly emerging transformed cells are surrounded by normal epithelial cells. A recent study revealed that normal epithelial cells have an ability to sense and actively eliminate the neighboring transformed cells, a process named epithelial defense against cancer (EDAC). However, the molecular mechanism of this tumor-suppressive activity is largely unknown. In this study, we investigated a role for the sphingosine-1-phosphate (S1P)-S1P receptor 2 (S1PR2) pathway in EDAC. First, we show that addition of the S1PR2 inhibitor significantly suppresses apical extrusion of RasV12-transformed cells that are surrounded by normal cells. In addition, knockdown of S1PR2 in normal cells induces the same effect, indicating that S1PR2 in the surrounding normal cells plays a positive role in the apical elimination of the transformed cells. Of importance, not endogenous S1P but exogenous S1P is involved in this process. By using FRET analyses, we demonstrate that S1PR2 mediates Rho activation in normal cells neighboring RasV12-transformed cells, thereby promoting accumulation of filamin, a crucial regulator of EDAC. Collectively these data indicate that S1P is a key extrinsic factor that affects the outcome of cell competition between normal and transformed epithelial cells.

  18. Sphingosine-1-phosphate promotes extravillous trophoblast cell invasion by activating MEK/ERK/MMP-2 signaling pathways via S1P/S1PR1 axis activation.

    PubMed

    Yang, Weiwei; Li, Qinghua; Pan, Zhifang

    2014-01-01

    Successful placentation depends on the proper invasion of extravillous trophoblast (EVT) cells into maternal tissues. Previous reports demonstrated that S1P receptors are expressed in the EVT cells and S1P could regulate migration and function of trophoblast cells via S1P receptors. However, little is known about roles of S1P in the invasion of EVT cells. Our study was performed to investigate S1P effect on the invasion of EVT cells. We used the extravillous trophoblast cell line HTR8/SVneo cells to evaluate the effect. In vitro invasion assay was employed to determine the invasion of HTR8/SVneo cells induced by S1P. MMP-2 enzyme activity and relative level in the supernatants of HTR8/SVneo was assessed by gelatin zymography and western blot. Based on the above, siRNA and specific inhibitors were used for the intervention and study of potential signal pathways, and Real-time qPCR and western blot were used to test the mRNA and protein level of potential signal targets. We found that S1P could promote HTR8/SVneo cell invasion and upregulates activity and level of MMP-2. The promotion requires activation of MEK-ERK and is dependent on the axis of S1P/S1PR1. Our investigation of S1P may provide new insights into the molecular mechanisms of EVT invasion.

  19. Patterned FeNi soft magnetic strips film with tunable resonance frequency from 1 to 10.6 GHz

    PubMed Central

    Ren, Yong; Li, Xinxi; Wang, Yan; Ren, Jiankun; Zhang, Yan; Dai, Bo; Yan, Haiyang; Sun, Guangai; Peng, Shuming

    2016-01-01

    Soft magnetic films with a wide-range tunable ferromagnetic resonance frequency are suitable for miniaturization and multifunctionalization of microwave integrated circuits. Fabrication of these films for high-frequency applications is usually complicated and difficult. We demonstrate a simple method to fabricate patterned FeNi soft magnetic strip films by magnetron sputtering and photolithography. Films prepared by this method exhibits a tunable in-plane uniaxial magnetic anisotropy (IPUMA) for different strip widths and gaps. As the strip widths changing from 500 to 2 μm, the IPUMA field increases monotonically from 2.2 to 576 Oe and resonance frequency from 1 to 10.6 GHz(which covers four microwave bands, including the L,S,C and X bands) respectively. This ultra-wide-range adjustability of resonance frequency can be attributed to shape anisotropy of strips. Considering that FeNi alloy has relatively low magnetocrystalline anisotropy, so a wider adjustable range of resonance frequency could be obtained using materials with stronger magnetocrystalline anisotropy. PMID:27561328

  20. HYDROGEN CHLORIDE IN DIFFUSE INTERSTELLAR CLOUDS ALONG THE LINE OF SIGHT TO W31C (G10.6-0.4)

    SciTech Connect

    Monje, R. R.; Lis, D. C.; Phillips, T. G.; Roueff, E.; Gerin, M.; De Luca, M.; Neufeld, D. A.; Godard, B.

    2013-04-10

    We report the detection of hydrogen chloride, HCl, in diffuse molecular clouds on the line of sight toward the star-forming region W31C (G10.6-0.4). The J = 1-0 lines of the two stable HCl isotopologues, H{sup 35}Cl and H{sup 37}Cl, are observed using the 1b receiver of the Heterodyne Instrument for the Far-Infrared (HIFI) on board the Herschel Space Observatory. The HCl line is detected in absorption, over a wide range of velocities associated with diffuse clouds along the line of sight to W31C. The analysis of the absorption strength yields a total HCl column density of a few 10{sup 13} cm{sup -2}, implying that HCl accounts for {approx}0.6% of the total gas-phase chlorine, which exceeds the theoretical model predictions by a factor of {approx}6. This result is comparable to those obtained from the chemically related species H{sub 2}Cl{sup +} and HCl{sup +}, for which large column densities have also been reported on the same line of sight. The source of discrepancy between models and observations is still unknown; however, the detection of these Cl-bearing molecules provides key constraints for the chlorine chemistry in the diffuse gas.

  1. Aerosol backscatter measurements at 10.6 microns with airborne and ground-based CO2 Doppler lidars over the Colorado High Plains. I - Lidar intercomparison

    NASA Technical Reports Server (NTRS)

    Bowdle, David A.; Rothermel, Jeffry; Vaughan, J. Michael; Brown, Derek W.; Post, Madison J.

    1991-01-01

    An airborne continuous-wave (CW) focused CO2 Doppler lidar and a ground-based pulsed CO2 Doppler lidar were to obtain seven pairs of comparative measurements of tropospheric aerosol backscatter profiles at 10.6-micron wavelength, near Denver, Colorado, during a 20-day period in July 1982. In regions of uniform backscatter, the two lidars show good agreement, with differences usually less than about 50 percent near 8-km altitude and less than a factor of 2 or 3 elsewhere but with the pulsed lidar often lower than the CW lidar. Near sharp backscatter gradients, the two lidars show poorer agreement, with the pulsed lidar usually higher than the CW lidar. Most discrepancies arise from a combination of atmospheric factors and instrument factors, particularly small-scale areal and temporal backscatter heterogeneity above the planetary boundary layer, unusual large-scale vertical backscatter structure in the upper troposphere and lower stratosphere, and differences in the spatial resolution, detection threshold, and noise estimation for the two lidars.

  2. Influence of CO2 (10.6 μm) and Nd:YAG laser irradiation on the prevention of enamel caries around orthodontic brackets.

    PubMed

    Seino, Priscila Yumi; Freitas, Patrícia Moreira; Marques, Márcia Martins; de Souza Almeida, Fernanda Campos; Botta, Sérgio Brossi; Moreira, Maria Stella Nunes Araújo

    2015-02-01

    One possible undesirable consequence of orthodontic therapy is the development of incipient caries lesions of enamel around brackets. The aim of this study was to compare the effects of CO2 (λ = 10.6 μm) and Nd:YAG (λ = 1,064 nm) lasers associated or not with topical fluoride application on the prevention of caries lesions around brackets. Brackets were bonded to the enamel of 65 premolars. The experimental groups (n = 13) were: G1--application of 1.23% acidulated fluoride phosphate gel (AFP, control); G2--Nd:YAG laser irradiation (0.6 W, 84.9 J/cm(2), 10 Hz, 110 μs, contact mode); G3--Nd:YAG laser irradiation associated with AFP; G4--CO2 laser irradiation (0.5 W, 28.6 J/cm(2), 50 Hz, 5 μs, and 10 mm focal distance); and G5--CO2 laser irradiation associated with AFP. Quantitative light-induced fluorescence was used to assess enamel demineralization. The data were statistically compared (α = 5%). The highest demineralization occurred in the Nd:YAG laser group (G2, 26.15% ± 1.94). The demineralization of all other groups was similar to that of the control group. In conclusion, CO2 laser alone was able to control enamel demineralization around brackets at the same level as that obtained with topical fluoride application.

  3. Phase II study of S-1, a novel oral fluorouracil, in advanced non-small-cell lung cancer

    PubMed Central

    Kawahara, M; Furuse, K; Segawa, Y; Yoshimori, K; Matsui, K; Kudoh, S; Hasegawa, K; Niitani, H

    2001-01-01

    The purpose of this study was to evaluate the efficacy and safety of a novel oral anticancer fluoropyrimidine derivative, S-1, in patients receiving initial chemotherapy for unresectable, advanced non-small-cell lung cancer (NSCLC). Between June 1996 and July 1998, 62 patients with NSCLC who had not received previous chemotherapy for advanced disease were enrolled in this study. 59 patients (22 stage IIIB and 37 stage IV) were eligible for the evaluation of efficacy and safety. S-1 was administered orally, twice daily, after meals. 3 dosages of S-1 were prescribed according to body surface area (BSA) so that they would be approximately equivalent to 80 mg m−2day−1: BSA < 1.25 m2, 40 mg b.i.d.; BSA≥1.25 but <1.5 m2; 50 mg b.i.d., and BSA≥1.5 m2: 60 mg b.i.d. One cycle consisted of consecutive administration of S-1 for 28 days followed by a 2-week rest period, and cycles were repeated up to 4 times. The partial response (PR) rate of the eligible patients was 22.0% (13/59); (95% confidence interval: 12.3–34.7%). A PR was observed in 22.7% (5/22) of the stage IIIB patients and 21.6% (8/37) of the stage IV patients. The median response duration was 3.4 months (1.1–13.7 months or longer). Grade 4 neutropenia was observed in one of the 59 patients (1.7%). The grade 3 or 4 toxicities consisted of decreased haemoglobin level in 1.7% of patients (1/59), neutropenia in 6.8% (4/59), thrombocytopenia in 1.7% (1/59), anorexia in 10.2% (6/59), diarrhoea in 8.5% (5/59), stomatitis in 1.7% (1/59), and malaise in 6.8% (4/59), and their incidences were relatively low. There were no irreversible, severe or unexpected toxicities. The median survival time (MST) of all patients was 10.2 months (95% confidence interval: 7.7–14.5 months), and the one-year survival rate was 41.1%. The MST of the stage IIIB patients was 7.9 months, and that of the stage IV patients was 11.1 months. The one-year survival rates of the stage IIIB and IV patients were 30.7% and 47

  4. Novel selective allosteric and bitopic ligands for the S1P(3) receptor.

    PubMed

    Jo, Euijung; Bhhatarai, Barun; Repetto, Emanuela; Guerrero, Miguel; Riley, Sean; Brown, Steven J; Kohno, Yasushi; Roberts, Edward; Schürer, Stephan C; Rosen, Hugh

    2012-12-21

    Sphingosine 1-phosphate (S1P) is a lysophospholipid signaling molecule that regulates important biological functions, including lymphocyte trafficking and vascular development, by activating G protein-coupled receptors for S1P, namely, S1P(1) through S1P(5). Here, we map the S1P(3) binding pocket with a novel allosteric agonist (CYM-5541), an orthosteric agonist (S1P), and a novel bitopic antagonist (SPM-242). With a combination of site-directed mutagenesis, ligand competition assay, and molecular modeling, we concluded that S1P and CYM-5541 occupy different chemical spaces in the ligand binding pocket of S1P(3). CYM-5541 allowed us to identify an allosteric site where Phe263 is a key gate-keeper residue for its affinity and efficacy. This ligand lacks a polar moiety, and the novel allosteric hydrophobic pocket permits S1P(3) selectivity of CYM-5541 within the highly similar S1P receptor family. However, a novel S1P(3)-selective antagonist, SPM-242, in the S1P(3) pocket occupies the ligand binding spaces of both S1P and CYM-5541, showing its bitopic mode of binding. Therefore, our coordinated approach with biochemical data and molecular modeling, based on our recently published S1P(1) crystal structure data in a highly conserved set of related receptors with a shared ligand, provides a strong basis for the successful optimization of orthosteric, allosteric, and bitopic modulators of S1P(3).

  5. Subcellular redistribution of m2 muscarinic acetylcholine receptors in striatal interneurons in vivo after acute cholinergic stimulation.

    PubMed

    Bernard, V; Laribi, O; Levey, A I; Bloch, B

    1998-12-01

    The purpose of our work was to investigate how the cholinergic environment influences the targeting and the intracellular trafficking of the muscarinic receptor m2 (m2R) in vivo. To address this question, we have used immunohistochemical approaches at light and electron microscopic levels to detect the m2R in control rats and rats treated with muscarinic receptor agonists. In control animals, m2Rs were located mostly at postsynaptic sites at the plasma membrane of perikarya and dendrites of cholinergic and NPY-somatostatin interneurons as autoreceptors and heteroreceptors, respectively. Presynaptic receptors were also detected in boutons. The m2Rs were usually detected at extrasynaptic sites, but they could be found rarely in association with symmetrical synapses, suggesting that the cholinergic transmission mediated by m2R occurs via synaptic and nonsynaptic mechanisms. The stimulation of muscarinic receptors with oxotremorine provoked a dramatic alteration of m2R compartmentalization, including endocytosis with a decrease of the density of m2R at the membrane (-63%) and an increase of those associated with endosomes (+86%) in perikarya. The very strong increase of m2R associated with multivesicular bodies (+732%) suggests that oxotremorine activated degradation. The slight increase in the Golgi apparatus (+26%) suggests that the m2R stimulation had an effect on the maturation of m2R. The substance P receptor located at the membrane of the same neurons was unaffected by oxotremorine. Our data demonstrate that cholinergic stimulation dramatically influences the subcellular distribution of m2R in striatal interneurons in vivo. These events may have key roles in controlling abundance and availability of muscarinic receptors via regulation of receptor endocytosis, degradation, and/or neosynthesis. Further, the control of muscarinic receptor trafficking may influence the activity of striatal interneurons, including neurotransmitter release and/or electric activity.

  6. Speciation of [Cp*(2)M(2)O(5)] in polar and donor solvents.

    PubMed

    Sözen-Aktaş, Pelin; Del Rosal, Iker; Manoury, Eric; Demirhan, Funda; Lledós, Agustí; Poli, Rinaldo

    2013-03-18

    The speciation of compounds [Cp*2 M2 O5 ] (M=Mo, W; Cp*=pentamethylcyclopentadienyl) in different protic and aprotic polar solvents (methanol, dimethyl sulfoxide, acetone, acetonitrile), in the presence of variable amounts of water or acid/base, has been investigated by (1) H NMR spectrometry and electrical conductivity. Specific hypotheses suggested by the experimental results have been further probed by DFT calculations. The solvent (S)-assisted ionic dissociation to generate [Cp*MO2 (S)](+) and [Cp*MO3 ](-) takes place extensively for both metals only in water/methanol mixtures. Equilibrium amounts of the neutral hydroxido species [Cp*MO2 (OH)] are generated in the presence of water, with the relative amount increasing in the order MeCN≈acetoneM2 O5 ] into [Et3 NH](+) [Cp*MO3 ](-) , for which the presence of a NH⋅⋅⋅OM interaction is revealed by (1) H NMR spectroscopy in comparison with the sodium salts, Na(+) [Cp*MO3 ](-) . These are fully dissociated in DMSO and MeOH, but display a slow equilibrium between free ions and the ion pair in MeCN and acetone. Only one resonance is observed for mixtures of [Cp*MO3 ](-) and [Cp*MO2 (OH)] because of a rapid self-exchange. In the presence of extensive ionic dissociation, only one resonance is observed for mixtures of the cationic [Cp*MO2 (S)](+) product and the residual undissociated [Cp*2 M2 O5 ] because of a rapid associative exchange via the trinuclear [Cp*3 M3 O7 ](+) intermediate. In neat methanol, complex [Cp*2 W2 O5 ] reacts to yield extensive amounts of a new species, formulated as the mononuclear methoxido complex [Cp*WO2 (OMe)] on the basis of the DFT study. An equivalent product is not observed for the Mo system. The addition of increasing amounts of water results in the rapid decrease of this product in favor of [Cp*2 W2 O5 ] and [Cp*WO2 (OH)].

  7. Smad3 deficiency leads to mandibular condyle degradation via the sphingosine 1-phosphate (S1P)/S1P3 signaling axis.

    PubMed

    Mori, Hiroki; Izawa, Takashi; Tanaka, Eiji

    2015-10-01

    Temporomandibular joint osteoarthritis is a degenerative disease that is characterized by permanent cartilage destruction. Transforming growth factor (TGF)-β is one of the most abundant cytokines in the bone matrix and is shown to regulate the migration of osteoprogenitor cells. It is hypothesized that TGF-β/Smad3 signaling affects cartilage homeostasis by influencing sphingosine 1-phosphate (S1P)/S1P receptor signaling and chondrocyte migration. We therefore investigated the molecular mechanisms by which crosstalk may occur between TGF-β/Smad3 and S1P/S1P receptor signaling to maintain condylar cartilage and to prevent temporomandibular joint osteoarthritis. Abnormalities in the condylar subchondral bone, including dynamic changes in bone mineral density and microstructure, were observed in Smad3(-/-) mice by microcomputed tomography. Cell-free regions and proteoglycan loss characterized the cartilage degradation present, and increased numbers of apoptotic chondrocytes and matrix metalloproteinase 13(+) chondrocytes were also detected. Furthermore, expression of S1P receptor 3 (S1P3), but not S1P1 or S1P2, was significantly down-regulated in the condylar cartilage of Smad3(-/-) mice. By using RNA interference technology and pharmacologic tools, S1P was found to transactivate Smad3 in an S1P3/TGF-β type II receptor-dependent manner, and S1P3 was found to be required for TGF-β-induced migration of chondrocyte cells and downstream signal transduction via Rac1, RhoA, and Cdc42. Taken together, these results indicate that the Smad3/S1P3 signaling pathway plays an important role in the pathogenesis of temporomandibular joint osteoarthritis.

  8. The SphKs/S1P/S1PR1 axis in immunity and cancer: more ore to be mined.

    PubMed

    Jin, Lei; Liu, Wei-Ren; Tian, Meng-Xin; Fan, Jia; Shi, Ying-Hong

    2016-04-29

    Over the past two decades, huge amounts of research were launched to understand the functions of sphingosine. Many pathways were uncovered that convey the relative functions of biomacromolecules. In this review, we discuss the recent advances of the role of the SphKs/S1P/S1PR1 axis in immunity and cancer. Finally, we investigate the therapeutic potential of new drugs that target S1P signaling in cancer therapy.

  9. Oncogenic S1P signalling in EBV-associated nasopharyngeal carcinoma activates AKT and promotes cell migration through S1P receptor 3.

    PubMed

    Lee, Hui Min; Lo, Kwok-Wai; Wei, Wenbin; Tsao, Sai Wah; Chung, Grace Tin Yun; Ibrahim, Maha Hafez; Dawson, Christopher W; Murray, Paul G; Paterson, Ian C; Yap, Lee Fah

    2017-02-27

    Undifferentiated nasopharyngeal carcinoma (NPC) is a cancer with high metastatic potential that is consistently associated with Epstein-Barr virus (EBV) infection. In this study, we have investigated the functional contribution of sphingosine-1-phosphate (S1P) signalling to the pathogenesis of NPC. We show that EBV infection or ectopic expression of the EBV-encoded latent genes (EBNA1, LMP1 and LMP2A) can up-regulate sphingosine kinase 1 (SPHK1), the key enzyme that produces S1P, in NPC cell lines. Exogenous addition of S1P promotes the migration of NPC cells through the activation of AKT; shRNA knockdown of SPHK1 resulted in a reduction in the levels of activated AKT and inhibition of cell migration. We also show that S1P receptor 3 (S1PR3) mRNA is over-expressed in EBV-positive NPC patient-derived xenografts and a subset of primary NPC tissues, and that knockdown of S1PR3 suppressed the activation of AKT and the S1P-induced migration of NPC cells. Taken together, our data point to a central role for EBV in mediating the oncogenic effects of S1P in NPC and identify S1P signalling as a potential therapeutic target in this disease.

  10. Aberrant expression of the S1P regulating enzymes, SPHK1 and SGPL1, contributes to a migratory phenotype in OSCC mediated through S1PR2.

    PubMed

    Patmanathan, Sathya Narayanan; Johnson, Steven P; Lai, Sook Ling; Panja Bernam, Suthashini; Lopes, Victor; Wei, Wenbin; Ibrahim, Maha Hafez; Torta, Federico; Narayanaswamy, Pradeep; Wenk, Markus R; Herr, Deron R; Murray, Paul G; Yap, Lee Fah; Paterson, Ian C

    2016-05-10

    Oral squamous cell carcinoma (OSCC) is a lethal disease with a 5-year mortality rate of around 50%. Molecular targeted therapies are not in routine use and novel therapeutic targets are required. Our previous microarray data indicated sphingosine 1-phosphate (S1P) metabolism and signalling was deregulated in OSCC. In this study, we have investigated the contribution of S1P signalling to the pathogenesis of OSCC. We show that the expression of the two major enzymes that regulate S1P levels were altered in OSCC: SPHK1 was significantly upregulated in OSCC tissues compared to normal oral mucosa and low levels of SGPL1 mRNA correlated with a worse overall survival. In in vitro studies, S1P enhanced the migration/invasion of OSCC cells and attenuated cisplatin-induced death. We also demonstrate that S1P receptor expression is deregulated in primary OSCCs and that S1PR2 is over-expressed in a subset of tumours, which in part mediates S1P-induced migration of OSCC cells. Lastly, we demonstrate that FTY720 induced significantly more apoptosis in OSCC cells compared to non-malignant cells and that FTY720 acted synergistically with cisplatin to induce cell death. Taken together, our data show that S1P signalling promotes tumour aggressiveness in OSCC and identify S1P signalling as a potential therapeutic target.

  11. Full pharmacological efficacy of a novel S1P1 agonist that does not require S1P-like head-group interactions

    PubMed Central

    Gonzalez-Cabrera, Pedro J.; Jo, Euijung; Sanna, M. Germana; Brown, Steven; Leaf, Nora; Marsolais, David; Schaeffer, Marie-Therese; Chapman, Jacqueline; Cameron, Michael; Guerrero, Miguel; Roberts, Edward; Rosen, Hugh

    2008-01-01

    Strong evidence exists for interactions of zwitterionic phosphate and amine groups in Sphingosine-1 phosphate (S1P) to conserved R and E residues present at the extracellular face of transmembrane-3 (TM3) of S1P receptors. The contribution of R120 and E121 for high affinity ligand-receptor interactions is essential, as single-point R120A or E121A S1P1 mutants neither bind S1P nor transduce S1P function. Because S1P receptors are therapeutically interesting, identifying potent selective agonists with different binding modes and in vivo efficacy is of pharmacological importance. Here we describe a modestly water-soluble highly-selective S1P1 agonist (CYM-5442) that does not require R120 or E121 residues for activating S1P1-dependent p42/p44 MAPK phosphorylation, which defines a new hydrophobic pocket in S1P1. CYM-5442 is a full agonist in vitro for S1P1 internalization, phosphorylation and ubiquitination. Importantly, CYM-5442 was a full agonist for induction and maintenance of S1P1-dependent lymphopenia, decreasing B-lymphocytes by 65% and T-lymphocytes by 85% of vehicle. Induction of CYM-5442 lymphopenia was dose and time-dependent, requiring serum concentrations in the 50 nM range. In vitro measures of S1P1 activation by CYM-5442 were non-competitively inhibited by a specific S1P1 antagonist (W146), competitive for S1P, FTY720-P and SEW2871. In addition, lymphopenia by CYM-5442 was reversed by W146 administration or upon pharmacokinetic agonist clearance. Pharmacokinetics in mice also indicated that CYM-5442 partitions significantly in central nervous tissue. These data show that CYM-5442 activates S1P1-dependent pathways in vitro and to levels of full efficacy in vivo through a hydrophobic pocket, separable from the orthosteric site of S1P binding that is headgroup dependent. PMID:18708635

  12. Hypothalamic S1P/S1PR1 axis controls energy homeostasis in Middle-Aged Rodents: the reversal effects of physical exercise

    PubMed Central

    Silva, Vagner Ramon Rodrigues; Katashima, Carlos Kiyoshi; Bueno Silva, Carla G.; Lenhare, Luciene; Micheletti, Thayana Oliveira; Camargo, Rafael Ludemann; Ghezzi, Ana Carolina; Camargo, Juliana Alves; Assis, Alexandre Moura; Tobar, Natalia; Morari, Joseane; Razolli, Daniela S.; Moura, Leandro Pereira; Pauli, José Rodrigo; Cintra, Dennys Esper; Velloso, Lício Augusto; Saad, Mario J.A; Ropelle, Eduardo Rochete

    2017-01-01

    Recently, we demonstrated that the hypothalamic S1PR1/STAT3 axis plays a critical role in the control of food consumption and energy expenditure in rodents. Here, we found that reduction of hypothalamic S1PR1 expression occurs in an age-dependent manner, and was associated with defective thermogenic signaling and weight gain. To address the physiological relevance of these findings, we investigated the effects of chronic and acute exercise on the hypothalamic S1PR1/STAT3 axis. Chronic exercise increased S1PR1 expression and STAT3 phosphorylation in the hypothalamus, restoring the anorexigenic and thermogenic signals in middle-aged mice. Acutely, exercise increased sphingosine-1-phosphate (S1P) levels in the cerebrospinal fluid (CSF) of young rats, whereas the administration of CSF from exercised young rats into the hypothalamus of middle-aged rats at rest was sufficient to reduce the food intake. Finally, the intracerebroventricular (ICV) administration of S1PR1 activators, including the bioactive lipid molecule S1P, and pharmacological S1PR1 activator, SEW2871, induced a potent STAT3 phosphorylation and anorexigenic response in middle-aged rats. Overall, these results suggest that hypothalamic S1PR1 is important for the maintenance of energy balance and provide new insights into the mechanism by which exercise controls the anorexigenic and thermogenic signals in the central nervous system during the aging process. PMID:28039439

  13. Ligand-binding pocket shape differences between S1P1 and S1P3 determine efficiency of chemical probe identification by uHTS

    PubMed Central

    Schürer, Stephan C.; Brown, Steven J.; Cabrera, Pedro Gonzales; Schaeffer, Marie-Therese; Chapman, Jacqueline; Jo, Euijung; Chase, Peter; Spicer, Tim; Hodder, Peter; Rosen, Hugh

    2008-01-01

    We have studied the Sphingosine 1-phosphate (S1P) receptor system to better understand why certain molecular targets within a closely related family are much more tractable when identifying compelling chemical leads. Five medically important G protein-coupled receptors for S1P regulate heart rate, coronary artery caliber, endothelial barrier integrity, and lymphocyte trafficking. Selective S1P receptor agonist probes would be of great utility to study receptor subtype-specific function. Through systematic screening of the same libraries, we identified novel selective agonists chemotypes for each of the S1P1 and S1P3 receptors. uHTS for S1P1 was more effective than for S1P3, with many selective, low nanomolar hits of proven mechanism emerging for. Receptor structure modeling and ligand docking reveal differences between the receptor binding pockets, which are the basis for sub-type selectivity. Novel selective agonists interact primarily in the hydrophobic pocket of the receptor in the absence of head-group interactions. Chemistry-space and shape-based analysis of the screening libraries in combination with the binding models explain the observed differential hit rates and enhanced efficiency for lead discovery for S1P1 vs. S1P3 in this closely related receptor family. PMID:18590333

  14. The toluene-Ar complex: S0 and S1 van der Waals modes, changes to methyl rotation, and torsion-van der Waals vibration coupling.

    PubMed

    Gascooke, Jason R; Lawrance, Warren D

    2013-02-28

    The methyl rotor and van der Waals vibrational levels in the S1 and S0 states of toluene-Ar have been investigated by the technique of two-dimensional laser induced fluorescence (2D-LIF). The S0 van der Waals and methyl rotor levels are reported for the first time, while improved S1 values are presented. The correlations seen in the 2D-LIF images between the S0 and S1 states lead to a reassignment of key features in the S1 ← S0 excitation spectrum. This reassignment reveals that there are significant changes in the methyl rotor levels in the complex compared with those in bare toluene, particularly at low m. The observed rotor energies are explained by the introduction of a three-fold, V3, term in the torsion potential (this term is zero in toluene) and a reduction in the height of the six-fold, V6, barriers in S0 and S1 from their values in bare toluene. The V3 term is larger in magnitude than the V6 term in both S0 and S1. The constants determined are ∣V3(S1)∣ = 33.4 ± 1.0 cm(-1), ∣V3(S0)∣ = 20.0 ± 1.0 cm(-1), V6(S1) = -10.7 ± 1.0 cm(-1), and V6(S0) = -1.7 ± 1.0 cm(-1). The methyl rotor is also found to couple with van der Waals vibration; specifically, the m(") = 2 rotor state couples with the combination level involving one quantum of the long axis bend and m(") = 1. The coupling constant is determined to be 1.9 cm(-1), which is small compared with the values typically reported for torsion-vibration coupling involving ring modes.

  15. Aft Body Closure: Predicted Strut Effects at M=2.4

    NASA Technical Reports Server (NTRS)

    Lamar, John E.; Garritz, Javier A.

    1999-01-01

    This paper reports the predicted M = 2.4 strut-interference effects on a closed aftbody with empennage for the TCA baseline model. The strut mounting technique was needed in order to assess the impact of aft-end shaping, i.e. open for a sting or closed to better represent a flight vehicle. However,this technique can potentially lead to unanticipated effects that are measured on the aft body. Therefore, a set of computations were performed in order to examine the closed aft body with and without strut present, at both zero and non-zero angles of sideslip (AOS). The work was divided into a computational task performed by Javier A. Garriz, using an inviscid (Euler) solver, and a monitoring/reporting task done by John E. Lamar. All this work was performed during FY98 at the NASA Langley Research Center.

  16. Magnetic anisotropy of S m2F e17 single crystals

    NASA Astrophysics Data System (ADS)

    Diop, L. V. B.; Kuz'min, M. D.; Skokov, K. P.; Karpenkov, D. Yu.; Gutfleisch, O.

    2016-10-01

    The previously accepted notion that the spontaneous magnetization of S m2F e17 lies in the basal plane of the crystal is true only approximately, and then only around room temperature. At low temperatures the magnetization, whose orientation is not fixed by the symmetry, is found to deviate from the basal plane by as much as 10∘. The threefold symmetry axis is a hard direction; to magnetize the crystal in this direction, a magnetic field of about 9 T is required. The hard-axis magnetization arrives at saturation discontinuously, by way of a first-order phase transition. The behavior is a general one for trigonal ferromagnets where K1<0 and the leading trigonal anisotropy constant is nonzero, K2'≠0 . Although of universal occurrence, the first-order transition is only visible at low temperatures, where it is accompanied by a magnetization anomaly of sufficient size.

  17. Development of the multi-mode external lighting system for aircraft (M2ESA)

    NASA Astrophysics Data System (ADS)

    Martin, John J.

    2005-08-01

    This paper documents the development of the Multi-Mode External Lighting System for Aircraft (M2ESA), a solid-state near-IR and visible light emitting diode-based programmable system designed to replace existing incandescent navigation lights on the exterior of military aircraft, and tailored for use with night vision goggles. Integrated systems of optics, electronics and mechanical structures were designed that were compatible with legacy aircraft systems, and which thus conformed to rigid configuration requirements and severe volume constraints. The genesis of the concept, evolution and general architecture of the system, top-level performance and environmental requirements, integration on the designated aircraft platform (the F-15), and general results of flight demonstration assessments are described.

  18. Primary structure of the human M2 mitochondrial autoantigen of primary biliary cirrhosis: Dihydrolipoamide acetyltransferase

    SciTech Connect

    Coppel, R.L.; McNeilage, L.J.; Surh, C.D.; Van De Water, J.; Spithill, T.W.; Whittingham, S.; Gershwin, M.E. )

    1988-10-01

    Primary biliary cirrhosis is a chronic, destructive autoimmune liver disease of humans. Patient sera are characterized by a high frequency of autoantibodies to a M{sub r} 70,000 mitochondrial antigen a component of the M2 antigen complex. The authors have identified a human cDNA clone encoding the complete amino acid sequence of this autoantigen. The predicted structure has significant similarity with the dihydrolipoamide acetyltransferase of the Escherichia coli pyruvate dehydrogenase multienzyme complex. The human sequence preserves the Glu-Thr-Asp-Lys-Ala motif of the lipoyl-binding site and has two potential binding sites. Expressed fragments of the cDNA react strongly with sera from patients with primary biliary cirrhosis but not with sera from patients with autoimmune chronic active hepatitis or sera from healthy subjects.

  19. M1/M2 Macrophage Polarity in Normal and Complicated Pregnancy

    PubMed Central

    Brown, Mary B.; von Chamier, Maria; Allam, Ayman B.; Reyes, Leticia

    2014-01-01

    Tissue macrophages play an important role in all stages of pregnancy, including uterine stromal remodeling (decidualization) before embryo implantation, parturition, and post-partum uterine involution. The activation state and function of utero-placental macrophages are largely dependent on the local tissue microenvironment. Thus, macrophages are involved in a variety of activities such as regulation of immune cell activities, placental cell invasion, angiogenesis, and tissue remodeling. Disruption of the uterine microenvironment, particularly during the early stages of pregnancy (decidualization, implantation, and placentation) can have profound effects on macrophage activity and subsequently impact pregnancy outcome. In this review, we will provide an overview of the temporal and spatial regulation of utero-placental macrophage activation during normal pregnancy in human beings and rodents with a focus on more recent findings. We will also discuss the role of M1/M2 dysregulation within the intrauterine environment during adverse pregnancy outcomes. PMID:25505471

  20. Gamma rays emitted in the decay of 31-year 178m2Hf

    SciTech Connect

    MB, S; PW, W; GC, B; JJ, C; PE, G; G, H; R, P; F, S; HC, S

    2003-10-15

    The spontaneous decay of the K{sup {pi}} = 16{sup +}, 31-year {sup 178m2}Hf isomer has been investigated with a 15 kBq source placed at the center of a 20-element {gamma}-ray spectrometer. High-multipolarity M4 and E5 transitions, which represent the first definitive observation of direct {gamma}-ray emission from the isomer, have been identified, together with other low-intensity transitions. Branching ratios for these other transitions have elucidated the spin dependence of the mixing between the two known K{sup {pi}} = 8{sup -} bands. The M4 and E5 {gamma}-ray decays are the first strongly K-forbidden transitions to be identified with such high multipolarities, and demonstrate a consistent extension of K-hindrance systematics, with an inhibition factor of approximately 100 per degree of K forbiddenness. Some unplaced transitions are also reported.

  1. M2-F1 lifting body and Paresev 1B on ramp

    NASA Technical Reports Server (NTRS)

    1963-01-01

    In this photo of the M2-F1 lifting body and the Paresev 1B on the ramp, the viewer sees two vehicles representing different approaches to building a research craft to simulate a spacecraft able to land on the ground instead of splashing down in the ocean as the Mercury capsules did. The M2-F1 was a lifting body, a shape able to re-enter from orbit and land. The Paresev (Paraglider Research Vehicle) used a Rogallo wing that could be (but never was) used to replace a conventional parachute for landing a capsule-type spacecraft, allowing it to make a controlled landing on the ground. The wingless, lifting body aircraft design was initially conceived as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop

  2. M2, S2, K1 models of the global ocean tide

    NASA Technical Reports Server (NTRS)

    Parke, M. E.; Hendershott, M. C.

    1979-01-01

    Ocean tidal signals appear in many geophysical measurements. Geophysicists need realistic tidal models to aid in interpretation of their data. Because of the closeness to resonance of dissipationless ocean tides, it is difficult for numerical models to correctly represent the actual open ocean tide. As an approximate solution to this problem, test functions derived by solving Laplace's Tidal Equations with ocean loading and self gravitation are used as a basis for least squares dynamic interpolation of coastal and island tidal data for the constituents M2, S2, and Kl. The resulting representations of the global tide are stable over at least a ?5% variation in the mean depth of the model basin, and they conserve mass. Maps of the geocentric tide, the induced free space potential, the induced vertical component of the solid earth tide, and the induced vertical component of the gravitational field for each contituent are presented.

  3. Spaceflight Effects on Hemopoiesis of Lower Vertebrates Flown on Foton-M2

    NASA Technical Reports Server (NTRS)

    Domaratskaya, E. I.; Payushina, O. V.; Butorina, M. N.; Nikonova, T. M.; Grigorian, E. N.; Mitashov, V. I.; Tairbekov, M. G.; Almeida, E.; Khrushchov, N. G.

    2006-01-01

    Intact and operated newts Pleumdeles waltl flown on Foton-M2 for 16 days were used to study the effects of spaceflight as well as tail amputation and lensectomy on their hemopoiesis. The flight did not produce noticeable changes in the peripheral blood of nonoperated newts. However, in operated animals, the number of lymphocytes increased whereas that of neutrophils decreased. There were no morphological differences in hemopoietic organs (liver and spleen) between flown non-operated and operated animals or their controls. However, in both non-operated and operated newts the liver weight and the number of hemopoietic cells in it increased. In contrast to nonoperated newts, space-flown mammals typically showed significant changes in blood cell counts. Experiments with BrdU incorporation revealed labeled cells in the hemopoietic area of the liver as well as in blood and spleen. This observation gives evidence that the BrdU label can be used to study proliferation of hemopoietic cells.

  4. The Warburg Effect Mediator Pyruvate Kinase M2 Expression and Regulation in the Retina

    PubMed Central

    Rajala, Raju V. S.; Rajala, Ammaji; Kooker, Christopher; Wang, Yuhong; Anderson, Robert E.

    2016-01-01

    The tumor form of pyruvate kinase M2 (PKM2) undergoes tyrosine phosphorylation and gives rise to the Warburg effect. The Warburg effect defines a pro-oncogenic metabolism switch such that cancer cells take up more glucose than normal tissue and favor incomplete oxidation of glucose, even in the presence of oxygen. Retinal photoreceptors are highly metabolic and their energy consumption is equivalent to that of a multiplying tumor cell. In the present study, we found that PKM2 is the predominant isoform in both rod- and cone-dominant retina, and that it undergoes a light-dependent tyrosine phosphorylation. We also discovered that PKM2 phosphorylation is signaled through photobleaching of rhodopsin. Our findings suggest that phosphoinositide 3-kinase activation promotes PKM2 phosphorylation. Light and tyrosine phosphorylation appear to regulate PKM2 to provide a metabolic advantage to photoreceptor cells, thereby promoting cell survival. PMID:27883057

  5. Structure of the transmembrane region of the M2 protein H+ channel

    PubMed Central

    Wang, Junfeng; Kim, Sanguk; Kovacs, Frank; Cross, Timothy A.

    2001-01-01

    The transmembrane domain of the M2 protein from influenza A virus forms a nearly uniform and ideal helix in a liquid crystalline bilayer environment. The exposure of the hydrophilic backbone structure is minimized through uniform hydrogen bond geometry imposed by the low dielectric lipid environment. A high-resolution structure of the monomer backbone and a detailed description of its orientation with respect to the bilayer were achieved using orientational restraints from solid-state NMR. With this unique information, the tetrameric structure of this H+ channel is constrained substantially. Features of numerous published models are discussed in light of the experimental structure of the monomer and derived features of the tetrameric bundle. PMID:11604531

  6. Sphingosine 1-phosphate (S1P) carrier-dependent regulation of endothelial barrier: high density lipoprotein (HDL)-S1P prolongs endothelial barrier enhancement as compared with albumin-S1P via effects on levels, trafficking, and signaling of S1P1.

    PubMed

    Wilkerson, Brent A; Grass, G Daniel; Wing, Shane B; Argraves, W Scott; Argraves, Kelley M

    2012-12-28

    Sphingosine 1-phosphate (S1P) is a blood-borne lysosphingolipid that acts to promote endothelial cell (EC) barrier function. In plasma, S1P is associated with both high density lipoproteins (HDL) and albumin, but it is not known whether the carriers impart different effects on S1P signaling. Here we establish that HDL-S1P sustains EC barrier longer than albumin-S1P. We showed that the sustained barrier effects of HDL-S1P are dependent on signaling by the S1P receptor, S1P1, and involve persistent activation of Akt and endothelial NOS (eNOS), as well as activity of the downstream NO target, soluble guanylate cyclase (sGC). Total S1P1 protein levels were found to be higher in response to HDL-S1P treatment as compared with albumin-S1P, and this effect was not associated with increased S1P1 mRNA or dependent on de novo protein synthesis. Several pieces of evidence indicate that long term EC barrier enhancement activity of HDL-S1P is due to specific effects on S1P1 trafficking. First, the rate of S1P1 degradation, which is proteasome-mediated, was slower in HDL-S1P-treated cells as compared with cells treated with albumin-S1P. Second, the long term barrier-promoting effects of HDL-S1P were abrogated by treatment with the recycling blocker, monensin. Finally, cell surface levels of S1P1 and levels of S1P1 in caveolin-enriched microdomains were higher after treatment with HDL-S1P as compared with albumin-S1P. Together, the findings reveal S1P carrier-specific effects on S1P1 and point to HDL as the physiological mediator of sustained S1P1-PI3K-Akt-eNOS-sGC-dependent EC barrier function.

  7. M2Di: Concise and efficient MATLAB 2-D Stokes solvers using the Finite Difference Method

    NASA Astrophysics Data System (ADS)

    Räss, Ludovic; Duretz, Thibault; Podladchikov, Yury Y.; Schmalholz, Stefan M.

    2017-02-01

    Recent development of many multiphysics modeling tools reflects the currently growing interest for studying coupled processes in Earth Sciences. The core of such tools should rely on fast and robust mechanical solvers. Here we provide M2Di, a set of routines for 2-D linear and power law incompressible viscous flow based on Finite Difference discretizations. The 2-D codes are written in a concise vectorized MATLAB fashion and can achieve a time to solution of 22 s for linear viscous flow on 10002 grid points using a standard personal computer. We provide application examples spanning from finely resolved crystal-melt dynamics, deformation of heterogeneous power law viscous fluids to instantaneous models of mantle flow in cylindrical coordinates. The routines are validated against analytical solution for linear viscous flow with highly variable viscosity and compared against analytical and numerical solutions of power law viscous folding and necking. In the power law case, both Picard and Newton iterations schemes are implemented. For linear Stokes flow and Picard linearization, the discretization results in symmetric positive-definite matrix operators on Cartesian grids with either regular or variable grid spacing allowing for an optimized solving procedure. For Newton linearization, the matrix operator is no longer symmetric and an adequate solving procedure is provided. The reported performance of linear and power law Stokes flow is finally analyzed in terms of wall time. All MATLAB codes are provided and can readily be used for educational as well as research purposes. The M2Di routines are available from Bitbucket and the University of Lausanne Scientific Computing Group website, and are also supplementary material to this article.

  8. A disc inside the bipolar planetary nebula M2-9

    NASA Astrophysics Data System (ADS)

    Lykou, F.; Chesneau, O.; Zijlstra, A. A.; Castro-Carrizo, A.; Lagadec, E.; Balick, B.; Smith, N.

    2011-03-01

    Aims: Bipolarity in proto-planetary and planetary nebulae is associated with events occurring in or around their cores. Past infrared observations have revealed the presence of dusty structures around the cores, many in the form of discs. Characterising those dusty discs provides invaluable constraints on the physical processes that govern the final mass expulsion of intermediate mass stars. We focus this study on the famous M2-9 bipolar nebula, where the moving lighthouse beam pattern indicates the presence of a wide binary. The compact and dense dusty core in the centre of the nebula can be studied by means of optical interferometry. Methods: M2-9 was observed with VLTI/MIDI at 39-47 m baselines with the UT2-UT3 and UT3-UT4 baseline configurations. These observations are interpreted using a dust radiative transfer Monte Carlo code. Results: A disc-like structure is detected perpendicular to the lobes, and a good fit is found with a stratified disc model composed of amorphous silicates. The disc is compact, 25 × 35 mas at 8 μm and 37 × 46 mas at 13 μm. For the adopted distance of 1.2 kpc, the inner rim of the disc is ~15 AU. The mass represents a few percent of the mass found in the lobes. The compactness of the disc puts strong constraints on the binary content of the system, given an estimated orbital period 90-120 yr. We derive masses of the binary components between 0.6-1.0 M⊙ for a white dwarf and 0.6-1.4 M⊙ for an evolved star. We present different scenarios on the geometric structure of the disc accounting for the interactions of the binary system, which includes an accretion disc as well. Based on observations collected at the European Organisation for Astronomical Research in the Southern Hemisphere, Chile, ESO N: 079.D-146.

  9. Microwave & Magnetic (M2) Proteomics of a Mouse Model of Mild Traumatic Brain Injury

    PubMed Central

    Evans, Teresa M.; Van Remmen, Holly; Purkar, Anjali; Mahesula, Swetha; Gelfond, J AL; Sabia, Marian; Qi, Wenbo; Lin, Ai-Ling; Jaramillo, Carlos A.; Haskins, William E.

    2014-01-01

    Short-term increases in oxidative stress and decreases in motor function, including debilitating effects on balance and motor control, can occur following primary mild traumatic brain injuries (mTBI). However, the long-term effects on motor unit impairment and integrity as well as the molecular mechanisms underlying secondary injuries are poorly understood. We hypothesized that changes in central nervous system-specific protein (CSP) expression might correlate to these long-term effects. To test our hypothesis, we longitudinally assessed a closed-skull mTBI mouse model, vs. sham control, at 1, 7, 30, and 120 days post-injury. Motor impairment was determined by rotarod and grip strength performance measures, while motor unit integrity was determined using electromyography. Relative protein expression was determined by microwave & magnetic (M2) proteomics of ipsilateral brain tissue, as previously described. Isoprostane measurements were performed to confirm a primary oxidative stress response. Decoding the relative expression of 476 ± 56 top-ranked proteins for each specimen revealed statistically significant changes in the expression of two well-known CSPs at 1, 7 and 30 days post-injury: P < 0.001 for myelin basic protein (MBP) and P < 0.05 for myelin associated glycoprotein (MAG). This was confirmed by Western blot. Moreover, MAG, αII-spectrin (SPNA2) and neurofilament light (NEFL) expression at 30 days post-injury were directly related to grip strength (P < 0.05). While higher-powered studies of larger cohorts merit further investigation, this study supports the proof-of-concept that M2 proteomics is a rapid method to quantify putative protein biomarkers and therapeutic targets of mTBI and suggests the feasibility of CSP expression correlations to long-term effects on motor impairment. PMID:26157646

  10. Schistosomal-derived lysophosphatidylcholine triggers M2 polarization of macrophages through PPARγ dependent mechanisms.

    PubMed

    Assunção, Leonardo Santos; Magalhães, Kelly G; Carneiro, Alan Brito; Molinaro, Raphael; Almeida, Patrícia E; Atella, Georgia C; Castro-Faria-Neto, Hugo C; Bozza, Patrícia T

    2017-02-01

    Mansonic schistosomiasis is a disease caused by the trematode Schistosoma mansoni, endemic to tropical countries. S. mansoni infection induces the formation of granulomas and potent polarization of Th2-type immune response. There is great interest in understanding the mechanisms used by this parasite that causes a modulation of the immune system. Recent studies from our group demonstrated that lipids of S. mansoni, including lysophosphatidylcholine (LPC) have immunomodulatory activity. In the present study, our aim was to investigate the role of lipids derived from S. mansoni in the activation and polarization of macrophages and to characterize the mechanisms involved in this process. Peritoneal macrophages obtained from wild type C57BL/6mice or bone marrow derived macrophages were stimulated in vitro with lipids extracted from adult worms of S. mansoni. We demonstrated that total schistosomal-derived lipids as well as purified LPC induced alternatively activated macrophages/M2 profile observed by increased expression of arginase-1, mannose receptor, Chi3l3, TGFβ and production of IL-10 and PGE2 24h after stimulation. The involvement of the nuclear receptor PPARγ in macrophage response against LPC was investigated. Through Western blot and immunofluorescence confocal microscopy we demonstrated that schistosomal-derived LPC induces increased expression of PPARγ in macrophages. The LPC-induced increased expression of arginase-1 were significantly inhibited by the PPAR-γ antagonist GW9662. Together, these results demonstrate an immunomodulatory role of schistosomal-derived LPC in activating macrophages to a profile of the type M2 through PPARγ-dependent mechanisms, indicating a novel pathway for macrophage polarization triggered by parasite-derived LPC with potential implications to disease pathogenesis.

  11. Mass-Analyzed Threshold Ionization of M_2O_2 ( M = ce and Pr)

    NASA Astrophysics Data System (ADS)

    Wu, Lu; Dangi, Beni; Rounjane, Mourad; Yang, Dong-Sheng

    2012-06-01

    M_2O_2 ( M = Ce and Pr) is produced in a pulsed laser-vaporization metal-cluster source and studied by mass-analyzed threshold ionization (MATI) spectroscopy. From the MATI spectra, the adiabatic ionization energy is determined to be 37300(5) cm-1 for Ce2O2, and 37885 (5) cm-1 for Pr2O2. Like group 3 transition metal M2O2 (M=Sc, Y, and La) clusters we reported previously, these lanthanide clusters have a D2h planer structure and the vibrational modes observed are from the in-plane motions. However, the ground and other low-energy electronic states of the lanthanide oxides have a much higher electron spin multiplicity due to the existence of 4f electrons in the Ce and Pr atoms. The 4f electron of Ce atom has significantly lower energies than the 5d or 6s electrons and remain uncoupled in Ce2O2. On the other hand, the energy differences between the 4f and 5d/6s electrons of Pr atom are relatively small, and a 4f → 5d electron promotion is required in the formation of Pr2O2. The electronic transitions responsible for the observed MATI spectra are tentatively determined to be ^4B1u ← ^5Ag for Ce2O2 and ^6B1u ← ^7B2g and ^6B1u ← ^5B1u for Pr2O2.

  12. Influenza virus M2 targets cystic fibrosis transmembrane conductance regulator for lysosomal degradation during viral infection

    PubMed Central

    Londino, James David; Lazrak, Ahmed; Noah, James W.; Aggarwal, Saurabh; Bali, Vedrana; Woodworth, Bradford A.; Bebok, Zsuzsanna; Matalon, Sadis

    2015-01-01

    We sought to determine the mechanisms by which influenza infection of human epithelial cells decreases cystic fibrosis transmembrane conductance regulator (CFTR) expression and function. We infected human bronchial epithelial (NHBE) cells and murine nasal epithelial (MNE) cells with various strains of influenza A virus. Influenza infection significantly reduced CFTR short circuit currents (Isc) and protein levels at 8 hours postinfection. We then infected CFTR expressing human embryonic kidney (HEK)-293 cells (HEK-293 CFTRwt) with influenza virus encoding a green fluorescent protein (GFP) tag and performed whole-cell and cell-attached patch clamp recordings. Forskolin-stimulated, GlyH-101-sensitive CFTR conductances, and CFTR open probabilities were reduced by 80% in GFP-positive cells; Western blots also showed significant reduction in total and plasma membrane CFTR levels. Knockdown of the influenza matrix protein 2 (M2) with siRNA, or inhibition of its activity by amantadine, prevented the decrease in CFTR expression and function. Lysosome inhibition (bafilomycin-A1), but not proteasome inhibition (lactacystin), prevented the reduction in CFTR levels. Western blots of immunoprecipitated CFTR from influenza-infected cells, treated with BafA1, and probed with antibodies against lysine 63-linked (K-63) or lysine 48-linked (K-48) polyubiquitin chains supported lysosomal targeting. These results highlight CFTR damage, leading to early degradation as an important contributing factor to influenza infection-associated ion transport defects.—Londino, J. D., Lazrak, A., Noah, J. W., Aggarwal, S., Bali, V., Woodworth, B. A., Bebok, Z., Matalon, S. Influenza virus M2 targets cystic fibrosis transmembrane conductance regulator for lysosomal degradation during viral infection. PMID:25795456

  13. nuMoM2b Sleep Disordered Breathing Study: Objectives and Methods

    PubMed Central

    Facco, Francesca L.; Parker, Corette B.; Reddy, Uma M.; Silver, Robert M.; Louis, Judette M.; Basner, Robert C.; Chung, Judith H.; Schubert, Frank P.; Pien, Grace W.; Redline, Susan; Mobley, Daniel; Koch, Matthew A.; Simhan, Hyagriv N.; Chia-Ling, Nhan-Chang; Parry, Samuel; Grobman, William A.; Haas, David M.; Wing, Deborah A.; Mercer, Brian M.; Saade, George R.; Zee, Phyllis C.

    2015-01-01

    Objective The objective of the Sleep Disordered Breathing substudy of the Nulliparous Pregnancy Outcomes Study Monitoring Mothers-to-be (nuMoM2b) is to determine whether sleep disordered breathing during pregnancy is a risk factor for adverse pregnancy outcomes. Methods nuMoM2b is a prospective cohort study of 10,037 nulliparous women with singleton gestations, conducted across 8 sites, with a central Data Coordinating and Analysis Center. The Sleep Disordered Breathing substudy recruited 3702 women from the cohort to undergo objective, overnight in-home assessments of sleep disordered breathing. A standardized Level 3 home sleep test was performed between 60–150 weeks of pregnancy (Visit 1) and again between 220–310 weeks of pregnancy (Visit 3). Scorings of tests were conducted by a central Sleep Reading Center. Participants and their health care providers were notified if test results met “urgent referral” criteria based on threshold levels of apnea hypopnea indices, oxygen saturation levels or ECG abnormalities, but otherwise were not notified of test results. The primary pregnancy outcomes to be analyzed in relation to maternal sleep disordered breathing are preeclampsia, gestational hypertension, gestational diabetes, fetal growth restriction, and preterm birth. Results Objective data were obtained at Visit 1 on 3261 women, 88.1% of studies attempted; and at Visit 3 on 2511 women, 87.6% of studies attempted. Basic characteristics of the substudy cohort are reported in this methods paper. Conclusion The substudy is designed to address important questions regarding the relationship of sleep disordered breathing on the risk of preeclampsia and other outcomes of relevance to maternal and child health. PMID:25746730

  14. Plasma control of shock wave configuration in off-design mode of M = 2 inlet

    NASA Astrophysics Data System (ADS)

    Falempin, Francois; Firsov, Alexander A.; Yarantsev, Dmitry A.; Goldfeld, Marat A.; Timofeev, Konstantin; Leonov, Sergey B.

    2015-03-01

    The objective of this work was to study the steering effect of a weakly ionized plasma on a supersonic flow structure in a two-dimensional aerodynamic configuration with a three-shock compression ramp in an off-design operational mode. Experiments were performed in wind tunnel T-313 of ITAM SB RAS, with the model air inlet designed for operation at a flow of Mach number M = 2. The inlet was tested at M = 2, 2.5, and 3 and with Re = (25-36) × 106/m and an angle of attack AoA = 0°, 5°, and 8°. For the regulation of the inlet characteristics, a plasma generator with electrical power W pl = 2-10 kW was flush-mounted upstream of the compression ramp. A significant plasma effect on the shock configuration at the inlet and on the flow parameters after air compression is considered. It is shown that the main shock wave angle is controllable by means of the plasma power magnitude and, therefore, can be accurately adjusted to the cowl lip of an inlet with a fixed geometry. An additional plasma effect has been demonstrated through a notable increase in the pressure recovery coefficient in a flowpass extension behind the inlet because of an nearly isentropic pattern of flow compression with the plasma turned on. Numerical simulation brings out the details of 3D distribution of the flow structure and parameters throughout the model at thermal energy deposition in inlet near the compression surfaces. We conclude that the plasma-based technique may be a feasible method for expanding supersonic inlet operational limits.

  15. Cardiac M2 muscarinic cholinoceptor activation by human chagasic autoantibodies: association with bradycardia

    PubMed Central

    Goin, J; Borda, E; Auger, S; Storino, R; Sterin-Borda, L

    1999-01-01

    OBJECTIVE—To assess whether exposure of cardiac muscarinic acetylcholine receptors (mAChR) to activating chagasic antimyocardial immunoglobulins results in bradycardia and other dysautonomic symptoms associated with the regulation of heart rate.
METHODS—Trypanosoma cruzi infected patients with bradycardia and other abnormalities in tests of the autonomic nervous system were studied and compared with normal subjects. Antipeptide antibodies in serum were demonstrated by an enzyme linked immunosorbent assay using a synthetic 24-mer-peptide corresponding antigenically to the second extracellular loop of the human heart M2 mAChR. The functional effect of affinity purified antipeptide IgG from chagasic patients on spontaneous beating frequency and cAMP production of isolated normal rat atria was studied.
RESULTS—There was a strong association between the finding of antipeptide antibodies in chagasic patients and the presence of basal bradycardia and an altered Valsalva manoeuvre (basal bradycardia: χ2 = 37.5, p < 0.00001; Valsalva manoeuvre: χ2 = 70.0, p < 0.00001). The antipeptide autoantibodies also showed agonist activity, decreasing the rate of contraction and cAMP production. The effects on rat atria resembled the effects of the authentic agonist and those of the total polyclonal chagasic IgG, being selectively blunted by atropine and AF-DX 116, and neutralised by the synthetic peptide corresponding in amino acid sequence to the second extracellular loop of the human M2 mAChR.
CONCLUSIONS—There is an association between circulating antipeptide autoantibodies in chagasic patients and the presence of bradycardia and other dysautonomic symptoms. Thus these autoantibodies are a marker of autoimmune cardiac autonomic dysfunction. The results support the hypothesis that autoimmune mechanisms play a role in the pathogenesis of chagasic cardioneuromyopathy.


Keywords: heart rate; bradycardia; autoantibodies; chagasic cardiomyopathy PMID

  16. Coupling of G Proteins to Reconstituted Monomers and Tetramers of the M2 Muscarinic Receptor*

    PubMed Central

    Redka, Dar'ya S.; Morizumi, Takefumi; Elmslie, Gwendolynne; Paranthaman, Pranavan; Shivnaraine, Rabindra V.; Ellis, John; Ernst, Oliver P.; Wells, James W.

    2014-01-01

    G protein-coupled receptors can be reconstituted as monomers in nanodiscs and as tetramers in liposomes. When reconstituted with G proteins, both forms enable an allosteric interaction between agonists and guanylyl nucleotides. Both forms, therefore, are candidates for the complex that controls signaling at the level of the receptor. To identify the biologically relevant form, reconstituted monomers and tetramers of the purified M2 muscarinic receptor were compared with muscarinic receptors in sarcolemmal membranes for the effect of guanosine 5′-[β,γ-imido]triphosphate (GMP-PNP) on the inhibition of N-[3H]methylscopolamine by the agonist oxotremorine-M. With monomers, a stepwise increase in the concentration of GMP-PNP effected a lateral, rightward shift in the semilogarithmic binding profile (i.e. a progressive decrease in the apparent affinity of oxotremorine-M). With tetramers and receptors in sarcolemmal membranes, GMP-PNP effected a vertical, upward shift (i.e. an apparent redistribution of sites from a state of high affinity to one of low affinity with no change in affinity per se). The data were analyzed in terms of a mechanistic scheme based on a ligand-regulated equilibrium between uncoupled and G protein-coupled receptors (the “ternary complex model”). The model predicts a rightward shift in the presence of GMP-PNP and could not account for the effects at tetramers in vesicles or receptors in sarcolemmal membranes. Monomers present a special case of the model in which agonists and guanylyl nucleotides interact within a complex that is both constitutive and stable. The results favor oligomers of the M2 receptor over monomers as the biologically relevant state for coupling to G proteins. PMID:25023280

  17. Antibodies against MAEBL Ligand Domains M1 and M2 Inhibit Sporozoite Development In Vitro

    PubMed Central

    Preiser, Peter; Rénia, Laurent; Singh, Naresh; Balu, Bharath; Jarra, William; Voza, Tatiana; Kaneko, Osamu; Blair, Peter; Torii, Motomi; Landau, Irène; Adams, John H.

    2004-01-01

    MAEBL is a type 1 membrane protein that is implicated in the merozoite invasion of erythrocytes and sporozoite invasion of mosquito salivary glands. This apical organelle protein is structurally similar to the ebl erythrocyte binding proteins, such as EBA-175, except that the tandem ligand domains of MAEBL are similar to part of the extracellular domain of apical membrane antigen 1 and not the Duffy binding-like domain. Although midgut and salivary gland sporozoites are morphologically similar, salivary gland sporozoites undergo a period of new gene expression after infecting the salivary glands, display distinct phenotypic differences, and are more infectious for the mammalian host. The objectives of this project were to determine the molecular form of MAEBL in the infectious salivary gland sporozoites and whether the ligand has a role in the sporozoite development to exoerythrocytic stages in hepatocytes. We determined that MAEBL is newly expressed in salivary gland sporozoites and in a form distinct from what is present in the midgut sporozoites or present in erythrocytic stages. Both ligand domains (M1 and M2) were expressed as part of a full-length membrane form of MAEBL in the salivary gland sporozoites in contrast to the other stages that retain only the M2 ligand domain as part of the membrane form of the protein. Antisera developed against the cysteine-rich regions of the extracellular portion of MAEBL inhibited sporozoite development to exoerythrocytic forms in vitro. Together these data indicate that MAEBL has a role in this third developmental stage in the life cycle of the malaria parasite. Thus, MAEBL is another target for pre-erythrocytic-stage vaccine development against malaria parasites. PMID:15155670

  18. Sequestration of muscarinic acetylcholine receptor m2 subtypes. Facilitation by G protein-coupled receptor kinase (GRK2) and attenuation by a dominant-negative mutant of GRK2.

    PubMed

    Tsuga, H; Kameyama, K; Haga, T; Kurose, H; Nagao, T

    1994-12-23

    Sequestration of m2 receptors (muscarinic acetylcholine receptor m2 subtypes), which was assessed as loss of N-[3H]methyls