Science.gov

Sample records for 10-8 mol m-2

  1. 32 CFR 10.8 - Amendment.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false Amendment. 10.8 Section 10.8 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE MILITARY COMMISSIONS MILITARY COMMISSION INSTRUCTIONS § 10.8 Amendment. The General Counsel may issue, supplement, amend, or revoke any...

  2. 15 CFR 10.8 - Standing Committee.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... PRODUCT STANDARDS § 10.8 Standing Committee. (a) The Department shall establish and appoint the members of..., distributors, and users or consumers of the product covered by the standard, and representatives of appropriate...) The product or products covered by the standard; (2) The standard itself; and (3) Industry and...

  3. 24 CFR 10.8 - Notice of proposed rulemaking.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Notice of proposed rulemaking. 10.8 Section 10.8 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development RULEMAKING: POLICY AND PROCEDURES Procedures § 10.8 Notice of proposed rulemaking. Each notice...

  4. MolView users guide

    SciTech Connect

    Walenz, B.P.

    1996-06-01

    A system for viewing molecular data in a CAVE virtual reality environment is presented. The system, called MolView, consists of a frontend driver program that prepares the data and a backend CAVE program that displays the data. Both are written so that modifications and extensions are relatively easy to accomplish.

  5. 28 CFR 10.8 - Information to be kept current.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 1 2013-07-01 2013-07-01 false Information to be kept current. 10.8... kept current. A supplemental statement must be filed with the Attorney General within thirty days after... information and documents previously filed accurate and current with respect to the preceding six...

  6. 28 CFR 10.8 - Information to be kept current.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Information to be kept current. 10.8... kept current. A supplemental statement must be filed with the Attorney General within thirty days after... information and documents previously filed accurate and current with respect to the preceding six...

  7. 28 CFR 10.8 - Information to be kept current.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 1 2011-07-01 2011-07-01 false Information to be kept current. 10.8... kept current. A supplemental statement must be filed with the Attorney General within thirty days after... information and documents previously filed accurate and current with respect to the preceding six...

  8. 28 CFR 10.8 - Information to be kept current.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 1 2012-07-01 2012-07-01 false Information to be kept current. 10.8... kept current. A supplemental statement must be filed with the Attorney General within thirty days after... information and documents previously filed accurate and current with respect to the preceding six...

  9. 28 CFR 10.8 - Information to be kept current.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 1 2014-07-01 2014-07-01 false Information to be kept current. 10.8... kept current. A supplemental statement must be filed with the Attorney General within thirty days after... information and documents previously filed accurate and current with respect to the preceding six...

  10. 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

  11. 19 CFR 10.8a - Imported articles exported and reimported.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Imported articles exported and reimported. 10.8a...; DEPARTMENT OF THE TREASURY ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. General Provisions Articles Exported and Returned § 10.8a Imported articles exported and reimported. (a) In addition...

  12. 19 CFR 10.8a - Imported articles exported and reimported.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 1 2012-04-01 2012-04-01 false Imported articles exported and reimported. 10.8a...; DEPARTMENT OF THE TREASURY ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. General Provisions Articles Exported and Returned § 10.8a Imported articles exported and reimported. (a) In addition...

  13. 19 CFR 10.8a - Imported articles exported and reimported.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 1 2011-04-01 2011-04-01 false Imported articles exported and reimported. 10.8a...; DEPARTMENT OF THE TREASURY ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. General Provisions Articles Exported and Returned § 10.8a Imported articles exported and reimported. (a) In addition...

  14. 19 CFR 10.8a - Imported articles exported and reimported.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 1 2014-04-01 2014-04-01 false Imported articles exported and reimported. 10.8a...; DEPARTMENT OF THE TREASURY ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. General Provisions Articles Exported and Returned § 10.8a Imported articles exported and reimported. (a) In addition...

  15. 44 CFR 10.8 - Determination of requirement for environmental review.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Determination of requirement for environmental review. 10.8 Section 10.8 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY GENERAL ENVIRONMENTAL CONSIDERATIONS Agency...

  16. 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.

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

    PubMed

    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

  18. 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

  19. International key comparison CCQM-K94: 10 μmol/mol dimethyl sulfide in nitrogen

    NASA Astrophysics Data System (ADS)

    Lee, S.; Heo, G. S.; Kim, Y.; Oh, S.; Han, Q.; Wu, H.; Konopelko, L. A.; Kustikov, Y. A.; Kolobova, A. V.; Efremova, O. V.; Pankratov, V. V.; Pavlov, M. V.; Culleton, L. P.; Brown, A. S.; Brookes, C.; Li, J.; Ziel, P. R.; van der Veen, A. M. H.

    2016-01-01

    Dimethyl sulfide (DMS) is an important compound in monitoring climate change and is monitored by the World Meteorological Organization Global Atmospheric Watch Volatile Organic Compounds (WMO-GAW VOC) program at several monitoring sites. It is essential that measurement results are accurate and consistent among the assigned values for primary gas mixtures to meet the WMO requirement. The purpose of this comparison is to compare the measurement capability of DMS at approximately 10 μ­mol/mol and expectation to contribute the establishment of traceability to single measurement scale for DMS between NMIs. 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 CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  20. Anti-influenza M2e antibody

    DOEpatents

    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.

  1. Anti-influenza M2e antibody

    DOEpatents

    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.

  2. 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

  3. 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.

  4. COSTAR GHRS m2 Mirror Arm Deployment

    NASA Astrophysics Data System (ADS)

    Troeltzsch, John

    1994-01-01

    The following activities will take place during this proposal. 1. Deploy the GHRS M2 Mirror Arm. This test requires a mix of real-time activities performed by the STOCC and stored command activities performed by the STSCI via SMS commanding. The activities in this proposal involve many COSTAR CARD items. This proposal requires careful attention during proposal implementation and execution to ensure the CARD is correctly implemented.

  5. Superconformal indices and M2-branes

    NASA Astrophysics Data System (ADS)

    Eager, Richard; Schmude, Johannes

    2015-12-01

    We derive the superconformal index of the world-volume theory on M2-branes probing the cone over an arbitrary Sasaki-Einstein seven-manifold. The index is expressed in terms of the cohomology groups of the cone. We match our supergravity results with known results from gauge theory. Along the way we derive the spectrum of short Kaluza-Klein multiplets on generic Sasaki-Einstein seven-manifolds.

  6. 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

  7. Free-energy profiles for ions in the influenza M2-TMD channel.

    PubMed

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

    2009-09-01

    M(2) transmembrane domain channel (M(2)-TMD) permeation properties are studied using molecular dynamics simulations of M(2)-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 M(2)-TMD tetramer are modeled for which the four His(37) residues, forming the selectivity filter, are net uncharged, +2 charged, or +3 charged. M(2)-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 occasionally occupy the positively-charged selectivity filter region, and from umbrella sampling simulations, Cl(-) has a lower free-energy barrier in the selectivity-filter region than either Na(+) or NH(4) (+), and NH(4) (+) 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 Trp(41) that could fully occlude the channel.

  8. 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.

  9. Exoplanets in the M2K Survey

    NASA Astrophysics Data System (ADS)

    Boyajian, Tabetha; Fischer, Debra; Gaidos, Eric; Giguere, Matt

    2013-07-01

    Late type stars are ideal targets for the detection of low-mass planets residing in habitable zones. In such systems, not only is the stellar noise a minimum, but the lower stellar mass affords larger reflex velocities and the lower stellar luminosity moves the habitable zone inward. The M2K program is a high precision Doppler survey monitoring a couple hundred late-type stars over the past few years in search for such important exoplanetary systems. We present updated orbits of known exoplanet systems and newly detected exoplanet systems that have resulted from this program. We also advertise the Planethunters.org "Guest Scientist" program as well as our survey to measure stellar diameters and temperatures with long baseline optical interferometry.

  10. The (178m2)Hf Controversy

    SciTech Connect

    Becker, J A; Gemmell, D S; Schiffer, J P; Wilhelmy, J B

    2003-07-24

    Since its discovery in the 1960's the {sup 178m2}Hf isomer has garnered high attention from both the basic and applied communities in nuclear science. It's combination of high spin (16+), long half life (31 yrs), and high excitation energy (2.446 MeV) offer unique possibilities as an energy storage medium. Interest in the isomer was rekindled beginning in 1999 when a series of publications began to appear from a group (referred to here as the ''Texas collaboration'') primarily based at the University of Texas, Dallas [1]. They reported observations that some of the stored energy could be released (''triggered'') when the isomer was exposed to a fluence of photons in the energy range {approx}10 to {approx}60 keV. The implications of this observation are profound. Even though the claimed cross section for the process was {approx}7 orders of magnitude greater than would be predicted from the known systematics of photon absorption by nuclei in this mass range [2], such a highly efficient method for triggering the isomeric deexcitation immediately suggested applications utilizing the explosive or the controlled gradual energy release from a very compact source. The prospect of such applications has focused considerable interest on realizing the promise that is implicit in the reported observations. However, two experiments performed by a group from ANL/LANL/LLNL at the Advanced Photon Source at Argonne (the ''APS collaboration'') reported negative results for the observation of any photon-triggered deexcitation of the {sup 178m2}Hf isomer [3]. This has led to a continued controversy, where both sides have adamantly defended their observations. At this point an outsider has difficulty determining whether there is indeed a triggering effect that should be pursued energetically with substantial resources, or whether the phenomenon consists of overly optimistic interpretation of data.

  11. A new potassium ion current induced by stimulation of M2 cholinoreceptors in fish atrial myocytes.

    PubMed

    Abramochkin, Denis V; Tapilina, Svetlana V; Vornanen, Matti

    2014-05-15

    A novel potassium ion current induced by muscarinic stimulation (IKACh2) is characterized in atrial cardiomyocytes of teleost fishes (crucian carp, Carassius carassius; rainbow trout, Oncorhynchus mykiss) by means of the whole-cell patch-clamp technique. The current is elicited in atrial, but not ventricular, cells by application of carbamylcholine (CCh) in moderate to high concentrations (10(-7)-10(-4) mol l(-1)). It can be distinguished from the classic IKACh, activated by the βγ-subunit of the Gi-protein, because of its low sensitivity to Ba(2+) ions and distinct current-voltage relationship with a very small inward current component. Ni(2+) ions (5 mmol l(-1)) and KB-R7943 (10(-5) mol l(-1)), non-selective blockers of the sodium-calcium exchange current (INCX), strongly reduced and completely abolished, respectively, the IKACh2. Therefore, IKACh2 was initially regarded as a CCh-induced outward component of the INCX. However, the current is not affected by either exclusion of intracellular Na(+) or extracellular Ca(2+), but is completely abolished by intracellular perfusion with K(+)-free solution. Atropine (10(-6) mol l(-1)), a non-selective muscarinic blocker, completely eliminated the IKACh2. A selective antagonist of M2 cholinoreceptors, AF-DX 116 (2×10(-7) mol l(-1)) and an M3 antagonist, 4-DAMP (10(-9) mol l(-1)), decreased IKACh2 by 84.4% and 16.6%, respectively. Pertussis toxin, which irreversibly inhibits Gi-protein coupled to M2 receptors, reduced the current by 95%, when applied into the pipette solution. It is concluded that IKACh2, induced by stimulation of M2 cholinoceptors and subsequent Gi-protein activation, represents a new molecular target for the cardiac parasympathetic innervation. PMID:24526726

  12. MolProbity for the masses—of data

    PubMed Central

    Chen, Vincent B.; Wedell, Jonathan R.; Wenger, R. Kent; Ulrich, Eldon L.

    2015-01-01

    MolProbity is a powerful software program for validating structures of proteins and nucleic acids. Although MolProbity includes scripts for batch analysis of structures, because these scripts analyze structures one at a time, they are not well suited for the validation of a large dataset of structures. We have created a version of MolProbity (MolProbity-HTC) that circumvents these limitations and takes advantage of a high-throughput computing cluster by using the HTCondor software. MolProbity-HTC enables the longitudinal analysis of large sets of structures, such as those deposited in the PDB or generated through theoretical computation—tasks that would have been extremely time-consuming using previous versions of MolProbity. We have used MolProbity-HTC to validate the entire PDB, and have developed a new visual chart for the BioMagResBank (BMRB) website that enables users to easily ascertain the quality of each model in an NMR ensemble and to compare the quality of those models to the rest of the PDB. PMID:26195077

  13. Muscovy duck reovirus p10.8 protein localizes to the nucleus via a nonconventional nuclear localization signal

    PubMed Central

    2014-01-01

    Background It was previously report that the first open reading frame of Muscovy duck reocvirus S4 gene encodes a 95-amino-acid protein, designed p10.8, which has no sequence similarity to other known proteins. Its amino acid sequence offers no clues about its function. Results Subcellular localization and nuclear import signal of p10.8 were characterized. We found that p10.8 protein localizes to the nucleus of infected and transfected cells, suggesting that p10.8 nuclear localization is not facilitated by viral infection or any other viral protein. A functional non-canonical nuclear localization signal (NLS) for p10.8 was identified and mapped to N-terminus residues 1–40. The NLS has the ability to retarget a large cytoplasmic protein to the nucleus. Conclusions p10.8 imported into the nucleus might via a nonconventional signal nuclear signal. PMID:24564937

  14. Throughput vs. the M2 quality factor

    NASA Astrophysics Data System (ADS)

    Alda, Javier; Alonso, Jose; Bernabeu, Eusebio

    1998-10-01

    The quality parameter M2 has been accepted as an useful averaged magnitude for comparing and classify laser beams with respect to their behavior in their propagation. Its definition is based on the product of two magnitudes: (the spatial size of the laser beam) X (the angular size of the laser beam). This product resembles very much a characteristic magnitude used in radiometry: the throughput, or etendue. In this work we will relate both concepts in order to identify one to the other. From a radiometry point of view the laser beam propagation can be seen as the transportation of light flux from a given source plane to a receiving plane. In most of the cases the practical situation involving laser beam propagation requires this kind of radiometric calculation for safety and energy delivery purposes. On the other hand the radiance of a laser source has been formally related with the Wigner distribution what show up some close relations between moment parametrization of laser beams and radiometric magnitudes. The description of the laser beam in terms of the moments of its amplitude distribution works very well in the formalism but it finds some difficulties to be reached in an experimental setup. Otherwise, the measurement of the energy of the beam can be easily obtained by several methods, such as the knife edge technique and some other related procedures. Our goal is find out the intrinsic relations between the easy to measure radiometric quantities and the easy to calculate generalized parameters. We will focus our attention in the relation between quality factor and throughput.

  15. MOL1 is required for cambium homeostasis in Arabidopsis.

    PubMed

    Gursanscky, Nial Rau; Jouannet, Virginie; Grünwald, Karin; Sanchez, Pablo; Laaber-Schwarz, Martina; Greb, Thomas

    2016-05-01

    Plants maintain pools of pluripotent stem cells which allow them to constantly produce new tissues and organs. Stem cell homeostasis in shoot and root tips depends on negative regulation by ligand-receptor pairs of the CLE peptide and leucine-rich repeat receptor-like kinase (LRR-RLK) families. However, regulation of the cambium, the stem cell niche required for lateral growth of shoots and roots, is poorly characterized. Here we show that the LRR-RLK MOL1 is necessary for cambium homeostasis in Arabidopsis thaliana. By employing promoter reporter lines, we reveal that MOL1 is active in a domain that is distinct from the domain of the positively acting CLE41/PXY signaling module. In particular, we show that MOL1 acts in an opposing manner to the CLE41/PXY module and that changing the domain or level of MOL1 expression both result in disturbed cambium organization. Underlining discrete roles of MOL1 and PXY, both LRR-RLKs are not able to replace each other when their expression domains are interchanged. Furthermore, MOL1 but not PXY is able to rescue CLV1 deficiency in the shoot apical meristem. By identifying genes mis-expressed in mol1 mutants, we demonstrate that MOL1 represses genes associated with stress-related ethylene and jasmonic acid hormone signaling pathways which have known roles in coordinating lateral growth of the Arabidopsis stem. Our findings provide evidence that common regulatory mechanisms in different plant stem cell niches are adapted to specific niche anatomies and emphasize the importance of a complex spatial organization of intercellular signaling cascades for a strictly bidirectional tissue production. PMID:26991973

  16. Comparison of primary standard gas mixtures: gravimetric production of carbon monoxide in nitrogen (3 μmol/mol)

    NASA Astrophysics Data System (ADS)

    Konopelko, L. A.; Kustikov, Y. A.; Kolobova, A. V.; Pankratov, V. V.; Pankov, A. A.; Efremova, O. V.; Augusto, Cristiane R.; Fioravante, Andreia L.; Ribeiro, Claudia C.; Teixeira, Denise C. G. S.; Elias, Elizandra C. S.; Oudwater, Rutger J.; Fagundes, Fátima A.; Silva, Marceli C.

    2016-01-01

    COOMET.QM-S3 is a supplementary comparison of primary standard gas mixtures—'Carbon monoxide in Nitrogen (3 μmol/mol)'. This is a bilateral comparison between VNIIM and INMETRO and it was conducted in 2013. Carbon monoxide is a toxic gas and in concentrations higher than 3-5 μmol/mol it is hazardous to human health. Therefore, it is important for NMIs to have the capability of an accurate carbon monoxide measurements. This comparison has shown that primary standard gas mixtures of carbon monoxide in nitrogen on the level of 3 μmol/mol, prepared in VNIIM and Inmetro, do not agree—the pair-wise degree of equivalence D (0.77%) is higher than the appropriate expanded uncertainty U(D) (0.29%). 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 CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  17. 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.

  18. 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.

  19. 26 CFR 1.401(m)-2 - ACP test.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... determined under § 1.401(m)-2(b)(2)(iv) (as it appeared in the April 1, 2007, edition of 26 CFR part 1). (E... determined under § 1.401(m)-2(b)(2)(vi) (as it appeared in the April 1, 2007, edition of 26 CFR Part 1). If... 26 Internal Revenue 5 2010-04-01 2010-04-01 false ACP test. 1.401(m)-2 Section 1.401(m)-2...

  20. Crystal and mol­ecular structure of aflatrem

    PubMed Central

    Lenta, Bruno N.; Ngatchou, Jules; Kenfack, Patrice T.; Neumann, Beate; Stammler, Hans-Georg; Sewald, Norbert

    2015-01-01

    The crystal structure of the title compound, C32H39NO4, confirms the absolute configuration of the seven chiral centres in the mol­ecule. The molecule has a 1,1-dimethylprop-2-enyl substituent on the indole nucleus and this nucleus shares one edge with the five-membered ring which is, in turn, connected to a sequence of three edge-shared fused rings. The skeleton is completed by the 7,7-trimethyl-6,8-dioxabi­cyclo­[3.2.1]oct-3-en-2-one group connected to the terminal cyclohexene ring. The two cyclohexane rings adopt chair and half-chair conformations, while in the dioxabi­cyclo­[3.2.1]oct-3-en-2-one unit, the six-membered ring has a half-chair conformation. The indole system of the mol­ecule exhibits a tilt of 2.02 (1)° between its two rings. In the crystal, O—H⋯O hydrogen bonds connect mol­ecules into chains along [010]. Weak N—H⋯π inter­actions connect these chains, forming sheets parallel to (10-1). PMID:26594569

  1. Absorptions moléculaires à grand redshift.

    NASA Astrophysics Data System (ADS)

    Combes, F.; Wiklind, T.

    L'observation de molécules en absorption est une technique pleine de promesses pour sonder le gaz froid à grand redshift. Les futurs instruments millimétriques bénéficieront de plus grandes surfaces collectrices, et un nombre bien supérieur de sources continuum deviendront accessibles, car le nombre de sources croit extre^mement rapidement à flux décroissant. D'autre part, à cause du biais de magnification gravitationnelle, on s'attend à trouver un excès de galaxies sur la ligne de visée des quasars brillants très lointains.

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

    PubMed

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

    2012-12-01

    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

  3. Calixarene-based mol-ecular capsule from olefin metathesis.

    PubMed

    Hailu, Shimelis T; Butcher, Ray J; Hudrlik, Paul F; Hudrlik, Anne M

    2013-01-01

    The reaction of tetra-kis-(all-yloxy)calix[4]arene with the first-generation Grubbs catalyst, followed by catalytic hydrogenation, gave the novel bis-calixarene 15,20,46,51,64,69,74,79-octa-oxatridecacyclo[32.28.8.8(3,28).1(13,53).1(22,44).0(9,14).0(21,26).0(38,70).0(40,45).0(52,57).0(59,63).0(7,80).0(32,73)]octa-conta-1(63),3,5,7(80),9(14),10,12,21,23,25,28(73),29,31,34,36,38(70),40,42,44,52,54,56,59,61-tetra-cosa-ene benzene monosolvate, C72H72O8·C6H6. The structure consists of two calix[4]arene units connected by four-carbon chains at each of the four O atoms on their narrow rims, to form a cage. Each of the calix[4]arene units has a flattened cone conformation in which two of the opposite aryl groups are closer together and nearly parallel [dihedral angle between planes = 7.35 (16)°], and the other two aryl groups are splayed outward [dihedral angle between planes = 72.20 (8)°]. While the cavity contains no solvent or other guest mol-ecule, there is benzene solvent mol-ecule in the lattice. Two of the alkyl linking arms were disordered over two conformations with occupancies of 0.582 (3)/0.418 (3) and 0.33 (4)/0.467 (4). They were constrained to have similar metrical and thermal parameters. PMID:24046590

  4. 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.

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

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... be distributed under the plan. Second, the plan must apportion the total amount of excess aggregate... determined under § 1.401(m)-2(b)(2)(iv) (as it appeared in the April 1, 2007, edition of 26 CFR part 1). (E... determined under § 1.401(m)-2(b)(2)(vi) (as it appeared in the April 1, 2007, edition of 26 CFR Part 1)....

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

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... employee contributions under Plan S and Plan T, two calendar-year profit-sharing plans of Employer H. Plan... determined under § 1.401(m)-2(b)(2)(iv) (as it appeared in the April 1, 2007, edition of 26 CFR part 1). (E... determined under § 1.401(m)-2(b)(2)(vi) (as it appeared in the April 1, 2007, edition of 26 CFR Part 1)....

  7. 26 CFR 1.401(m)-2 - ACP test.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... employee contributions under Plan S and Plan T, two calendar-year profit-sharing plans of Employer H. Plan... determined under § 1.401(m)-2(b)(2)(iv) (as it appeared in the April 1, 2007, edition of 26 CFR part 1). (E... determined under § 1.401(m)-2(b)(2)(vi) (as it appeared in the April 1, 2007, edition of 26 CFR Part 1)....

  8. Test of Equivalence Principle at 10(-8) Level by a Dual-Species Double-Diffraction Raman Atom Interferometer.

    PubMed

    Zhou, Lin; Long, Shitong; Tang, Biao; Chen, Xi; Gao, Fen; Peng, Wencui; Duan, Weitao; Zhong, Jiaqi; Xiong, Zongyuan; Wang, Jin; Zhang, Yuanzhong; Zhan, Mingsheng

    2015-07-01

    We report an improved test of the weak equivalence principle by using a simultaneous 85Rb-87Rb dual-species atom interferometer. We propose and implement a four-wave double-diffraction Raman transition scheme for the interferometer, and demonstrate its ability in suppressing common-mode phase noise of Raman lasers after their frequencies and intensity ratios are optimized. The statistical uncertainty of the experimental data for Eötvös parameter η is 0.8×10(-8) at 3200 s. With various systematic errors corrected, the final value is η=(2.8±3.0)×10(-8). The major uncertainty is attributed to the Coriolis effect. PMID:26182096

  9. Test of Equivalence Principle at 10(-8) Level by a Dual-Species Double-Diffraction Raman Atom Interferometer.

    PubMed

    Zhou, Lin; Long, Shitong; Tang, Biao; Chen, Xi; Gao, Fen; Peng, Wencui; Duan, Weitao; Zhong, Jiaqi; Xiong, Zongyuan; Wang, Jin; Zhang, Yuanzhong; Zhan, Mingsheng

    2015-07-01

    We report an improved test of the weak equivalence principle by using a simultaneous 85Rb-87Rb dual-species atom interferometer. We propose and implement a four-wave double-diffraction Raman transition scheme for the interferometer, and demonstrate its ability in suppressing common-mode phase noise of Raman lasers after their frequencies and intensity ratios are optimized. The statistical uncertainty of the experimental data for Eötvös parameter η is 0.8×10(-8) at 3200 s. With various systematic errors corrected, the final value is η=(2.8±3.0)×10(-8). The major uncertainty is attributed to the Coriolis effect.

  10. Diode laser spectra of CCl2F2 near 10.8 muon M: Air-broadening effects

    NASA Technical Reports Server (NTRS)

    Jennings, D. E.

    1977-01-01

    Laboratory spectra of CCL2F2 in the 10.8 micron region was recorded, using a tuneable diode laser spectrometer. Effects of air-broadening at pressures up to 48 Torr show that spectral structure should be exhibited under high resolution at altitudes as low as 19 Km. The single line, pressure-broadening coefficient for CCL2F2 was estimated to be 8 MHz/Torr FWHM.

  11. M2 polarization enhances silica nanoparticle uptake by macrophages

    PubMed Central

    Hoppstädter, Jessica; Seif, Michelle; Dembek, Anna; Cavelius, Christian; Huwer, Hanno; Kraegeloh, Annette; Kiemer, Alexandra K.

    2015-01-01

    While silica nanoparticles have enabled numerous industrial and medical applications, their toxicological safety requires further evaluation. Macrophages are the major cell population responsible for nanoparticle clearance in vivo. The prevailing macrophage phenotype largely depends on the local immune status of the host. Whereas M1-polarized macrophages are considered as pro-inflammatory macrophages involved in host defense, M2 macrophages exhibit anti-inflammatory and wound-healing properties, but also promote tumor growth. We employed different models of M1 and M2 polarization: granulocyte-macrophage colony-stimulating factor/lipopolysaccharide (LPS)/interferon (IFN)-γ was used to generate primary human M1 cells and macrophage colony-stimulating factor (M-CSF)/interleukin (IL)-10 to differentiate M2 monocyte-derived macrophages (MDM). PMA-differentiated THP-1 cells were polarized towards an M1 type by LPS/IFN-γ and towards M2 by IL-10. Uptake of fluorescent silica nanoparticles (Ø26 and 41 nm) and microparticles (Ø1.75 μm) was quantified. At the concentration used (50 μg/ml), silica nanoparticles did not influence cell viability as assessed by MTT assay. Nanoparticle uptake was enhanced in M2-polarized primary human MDM compared with M1 cells, as shown by flow cytometric and microscopic approaches. In contrast, the uptake of microparticles did not differ between M1 and M2 phenotypes. M2 polarization was also associated with increased nanoparticle uptake in the macrophage-like THP-1 cell line. In accordance, in vivo polarized M2-like primary human tumor-associated macrophages obtained from lung tumors took up more nanoparticles than M1-like alveolar macrophages isolated from the surrounding lung tissue. In summary, our data indicate that the M2 polarization of macrophages promotes nanoparticle internalization. Therefore, the phenotypical differences between macrophage subsets should be taken into consideration in future investigations on nanosafety, but

  12. 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.

  13. 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

  14. Polarized M2 macrophages in dogs with visceral leishmaniasis.

    PubMed

    Moreira, Pamela Rodrigues Reina; Fernando, Filipe Santos; Montassier, Hélio José; André, Marcos Rogério; de Oliveira Vasconcelos, Rosemeri

    2016-08-15

    The objective of the present study was to analyze the skin (nasal surface and ear regions), lymph nodes (popliteal and pre-scapular), spleen and liver of dogs with visceral leishmaniasis (VL), in order to investigate the relationship between the parasite load measured as DNA copy number of Alpha gene of DNA polymerase of Leishmania infantum by quantitative PCR and the number of M2 macrophages by immunohistochemistry. A set of 29 naturally infected dogs from an endemic area for VL were sampled and another set of six dogs negative for VL and from a non-endemic area were analyzed as the control group (C). The spleen presented the highest number of Leishmania DNA copies, with significant differences between the groups G1 and G2 (with and without skin lesions, respectively). The M2 phenotype immunostaining predominated among the macrophages in granulomas and inflammatory infiltrates of samples from the skin, lymph nodes and spleens examined. The presence of M2 macrophages in dogs from infected group differed significantly from the control group, in all organs analyzed, excepted liver. The highest proportion of M2 macrophages coincided with the highest parasitism loads found in more susceptible organs of VL dogs, even in the skin, considered a more resistant organ, while the liver showed low parasitism load and low immunostaining for M2 macrophages with no significant differences between infected and negative groups. It was concluded that the predominance of M2 phenotype in VL dogs favored the multiplication of Leishmania infantum in organs of dogs that are more susceptible to Leishmania infection, as skin, lymph nodes and spleen. PMID:27514887

  15. 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

  16. M2-branes and the (2, 0) superalgebra

    NASA Astrophysics Data System (ADS)

    Lambert, N.; Sacco, D.

    2016-09-01

    We present a generalization of the six-dimensional (2, 0) system of arXiv:1007.2982 to include a constant abelian 3-form. For vanishing 3-form this system is known to provide a variety descriptions of parallel M5-branes. For a particular choice of 3-form the system is shown to reduce to that of two M2-branes. Thus this generalised (2, 0) system provides a unified description of two parallel M2-branes or M5-branes.

  17. COSTAR FOC M1/M2 Mirror Arm Deployment

    NASA Astrophysics Data System (ADS)

    Bacinski, John

    1997-07-01

    The COSTAR's FOC M1/M2 arms will be returned to their pre-servicing mission positions. WFPC-2's shutter is required to remain closed during and for 30 minutes after the deployment of the FOC COSTAR arms. The FOC arm deployment activities will be executed with a combinations of R/T and SPC commanding. FOC M1/M2 arm deployments will not be executed until FOC baseline observations have been performed. The activities in this proposal involve many COSTAR CARD items. This proposal requires careful attention during proposal implementation and execution to ensure the CARD is correctly implemented.

  18. Mercury thiogallate nanosecond optical parametric oscillator continuously tunable from 4.2 to 10.8 μm

    NASA Astrophysics Data System (ADS)

    Kostyukova, N. Yu; Kolker, D. B.; Zenov, K. G.; Boyko, A. A.; Starikova, M. K.; Sherstov, I. V.; Karapuzikov, A. A.

    2015-09-01

    We demonstrate an optical parametric oscillator based on two HgGa2S4 crystals with an extremely wide tuning range from 4.2 to 10.8 μm. The HgGa2S4 optical parametric oscillator was pumped by a Q-switched nanosecond Nd : YLF laser at 1.053 μm. The absorption spectrum of ammonia was presented to demonstrate the feasibility of the developed optical parametric oscillator system for spectroscopic measurements and gas detection.

  19. 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

  20. 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.

  1. 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

  2. M2-branes, Einstein Manifolds and Triple Systems

    SciTech Connect

    Figueroa-O'Farrill, Jose Miguel

    2009-12-15

    This is the written version of a talk given on 1 July 2009 at the XXV Max Born Symposium: the Planck Scale, held in Wroclaw, Poland. I review the possible transverse geometries to supersymmetric M2-brane configurations and discuss the representation-theoretic description of their conjectured dual superconformal Chern-Simons theories.

  3. 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

  4. Perivascular M2 Macrophages Stimulate Tumor Relapse after Chemotherapy

    PubMed Central

    Hughes, Russell; Qian, Bin-Zhi; Rowan, Charlotte; Muthana, Munitta; Keklikoglou, Ioanna; Olson, Oakley C.; Tazzyman, Simon; Danson, Sarah; Addison, Christina; Clemons, Mark; Gonzalez-Angulo, Ana Maria; Joyce, Johanna A.; De Palma, Michele; Pollard, Jeffrey W.; Lewis, Claire E.

    2016-01-01

    Tumor relapse after chemotherapy-induced regression is a major clinical problem, because it often involves inoperable metastatic disease. Tumor-associated macrophages (TAM) are known to limit the cytotoxic effects of chemotherapy in preclinical models of cancer. Here, we report that an alternatively activated (M2) subpopulation of TAMs (MRC1+TIE2HiCXCR4Hi) accumulate around blood vessels in tumors after chemotherapy, where they promote tumor revascularization and relapse, in part, via VEGF-A release. A similar perivascular, M2-related TAM subset was present in human breast carcinomas and bone metastases after chemotherapy. Although a small proportion of M2 TAMs were also present in hypoxic tumor areas, when we genetically ablated their ability to respond to hypoxia via hypoxia-inducible factors 1 and 2, tumor relapse was unaffected. TAMs were the predominant cells expressing immunoreactive CXCR4 in chemotherapy-treated mouse tumors, with the highest levels expressed by MRC1+ TAMs clustering around the tumor vasculature. Furthermore, the primary CXCR4 ligand, CXCL12, was upregulated in these perivascular sites after chemotherapy, where it was selectively chemotactic for MRC1+ TAMs. Interestingly, HMOX-1, a marker of oxidative stress, was also upregulated in perivascular areas after chemotherapy. This enzyme generates carbon monoxide from the breakdown of heme, a gas known to upregulate CXCL12. Finally, pharmacologic blockade of CXCR4 selectively reduced M2-related TAMs after chemotherapy, especially those in direct contact with blood vessels, thereby reducing tumor revascularization and regrowth. Our studies rationalize a strategy to leverage chemotherapeutic efficacy by selectively targeting this perivascular, relapse-promoting M2-related TAM cell population. PMID:26269531

  5. 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

  6. 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

  7. Plasmids pMOL28 and pMOL30 of Cupriavidus metallidurans Are Specialized in the Maximal Viable Response to Heavy Metals▿ †

    PubMed Central

    Monchy, Sébastien; Benotmane, Mohammed A.; Janssen, Paul; Vallaeys, Tatiana; Taghavi, Safiyh; van der Lelie, Daniel; Mergeay, Max

    2007-01-01

    We fully annotated two large plasmids, pMOL28 (164 open reading frames [ORFs]; 171,459 bp) and pMOL30 (247 ORFs; 233,720 bp), in the genome of Cupriavidus metallidurans CH34. pMOL28 contains a backbone of maintenance and transfer genes resembling those found in plasmid pSym of C. taiwanensis and plasmid pHG1 of C. eutrophus, suggesting that they belong to a new class of plasmids. Genes involved in resistance to the heavy metals Co(II), Cr(VI), Hg(II), and Ni(II) are concentrated in a 34-kb region on pMOL28, and genes involved in resistance to Ag(I), Cd(II), Co(II), Cu(II), Hg(II), Pb(II), and Zn(II) occur in a 132-kb region on pMOL30. We identified three putative genomic islands containing metal resistance operons flanked by mobile genetic elements, one on pMOL28 and two on pMOL30. Transcriptomic analysis using quantitative PCR and microarrays revealed metal-mediated up-regulation of 83 genes on pMOL28 and 143 genes on pMOL30 that coded for all known heavy metal resistance proteins, some new heavy metal resistance proteins (czcJ, mmrQ, and pbrU), membrane proteins, truncated transposases, conjugative transfer proteins, and many unknown proteins. Five genes on each plasmid were down-regulated; for one of them, chrI localized on pMOL28, the down-regulation occurred in the presence of five cations. We observed multiple cross-responses (induction of specific metal resistance by other metals), suggesting that the cellular defense of C. metallidurans against heavy metal stress involves various regulons and probably has multiple stages, including a more general response and a more metal-specific response. PMID:17675385

  8. Tyrosine 129 of the Murine Gammaherpesvirus M2 Protein Is Critical for M2 Function In Vivo

    PubMed Central

    Rangaswamy, Udaya S.; O’Flaherty, Brigid M.; Speck, Samuel H.

    2014-01-01

    A common strategy shared by all known gammaherpesviruses is their ability to establish a latent infection in lymphocytes – predominantly in B cells. In immunocompromised patients, such as transplant recipients or AIDS patients, gammaherpesvirus infections can lead to the development of lymphoproliferative disease and lymphoid malignancies. The human gamma-herpesviruses, EBV and KSHV, encode proteins that are capable of modulating the host immune signaling machinery, thereby subverting host immune responses. Murine gamma-herpesvirus 68 (MHV68) infection of laboratory strains of mice has proven to be useful small-animal model that shares important pathogenic strategies with the human gamma-herpesviruses. The MHV68 M2 protein is known to manipulate B cell signaling and, dependent on route and dose of virus inoculation, plays a role in both the establishment of latency and virus reactivation. M2 contains two tyrosines that are targets for phosphorylation, and have been shown to interact with the B cell signaling machinery. Here we describe in vitro and in vivo studies of M2 mutants which reveals that while both tyrosines Y120 and Y129 are required for M2 induction of IL-10 expression from primary murine B cells in vitro, only Y129 is critical for reactivation from latency and plasma cell differentiation in vivo. PMID:25122496

  9. Tyrosine 129 of the murine gammaherpesvirus M2 protein is critical for M2 function in vivo.

    PubMed

    Rangaswamy, Udaya S; O'Flaherty, Brigid M; Speck, Samuel H

    2014-01-01

    A common strategy shared by all known gammaherpesviruses is their ability to establish a latent infection in lymphocytes--predominantly in B cells. In immunocompromised patients, such as transplant recipients or AIDS patients, gammaherpesvirus infections can lead to the development of lymphoproliferative disease and lymphoid malignancies. The human gamma-herpesviruses, EBV and KSHV, encode proteins that are capable of modulating the host immune signaling machinery, thereby subverting host immune responses. Murine gamma-herpesvirus 68 (MHV68) infection of laboratory strains of mice has proven to be useful small-animal model that shares important pathogenic strategies with the human gamma-herpesviruses. The MHV68 M2 protein is known to manipulate B cell signaling and, dependent on route and dose of virus inoculation, plays a role in both the establishment of latency and virus reactivation. M2 contains two tyrosines that are targets for phosphorylation, and have been shown to interact with the B cell signaling machinery. Here we describe in vitro and in vivo studies of M2 mutants which reveals that while both tyrosines Y120 and Y129 are required for M2 induction of IL-10 expression from primary murine B cells in vitro, only Y129 is critical for reactivation from latency and plasma cell differentiation in vivo.

  10. 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.

  11. On relating multiple M2 and D2-branes

    NASA Astrophysics Data System (ADS)

    Gran, U.; Nilsson, B. E. W.; Petersson, C.

    2008-10-01

    Due to the difficulties of finding superconformal Lagrangian theories for multiple M2-branes, we will in this paper instead focus on the field equations. By relaxing the requirement of a Lagrangian formulation we can explore the possibility of having structure constants fABCD satisfying the fundamental identity but which are not totally antisymmetric. We exemplify this discussion by making use of an explicit choice of a non-antisymmetric fABCD constructed from the Lie algebra structure constants fabc of an arbitrary gauge group. Although this choice of fABCD does not admit an obvious Lagrangian description, it does reproduce the correct SYM theory for a stack of N D2-branes to leading order in gYM-1 upon reduction and, moreover, it sheds new light on the centre of mass coordinates for multiple M2-branes.

  12. 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.

  13. COSTAR FOC M1/M2 Mirror Arm Deployment

    NASA Astrophysics Data System (ADS)

    Troeltzsch, John

    1994-01-01

    The following activities will take place during this proposal. 1. Deploy the FOC M2 Mirror Arm. 2. Deploy the FOC M1 Mirror Arm. This test requires a mix of real-time activities performed by the STOCC and stored command activities performed by the STSCI via SMS commanding. The activities in this proposal involve many COSTAR CARD items. This proposal requires careful attention during proposal implementation and execution to ensure the CARD is correctly implemented.

  14. Kinetics of bainite transformation in carburized 4317 M2

    NASA Astrophysics Data System (ADS)

    Chupatanakul, Smati

    The bainite transformation in steels has become increasingly important for industry in recent years. Nevertheless certain aspects the bainite transformation are still not fully understood. Understanding the bainite transformation in 4317 M2 type steels requires a thorough knowledge of the bainite transformation kinetics, the effect of carbon concentration to the kinetics and the understanding of carbon partitioning during the bainite transformation. Austempering experiments were performed in order to study the bainite transformation kinetics in three steels based on 4317 M2 with different carbon contents. The dilatometry technique was used to obtain the dilation as a function of transformation time and temperature. The fraction transformed ( f) was determined as a function of transformation time to generate a TTT diagram. The relationship of Ms temperature as a function of carbon content was determined. For the first time carbon partitioning during the bainite transformation was deduced from the change in Ms as a function of austempering holding time and temperature. The maximum values of carbon content achieved in the residual austenite were determined and compared to the T0 carbon composition calculated from Thermocalc(TM) for each austempering temperature. Excellent agreement was found and the experimental results therefore support the bainite transformation model of shear displacement followed by carbon partitioning. X-ray diffraction, microstructure examination and hardness analysis were used in order to understand the transformation kinetics and optimize processing for case carburized 4317 M2. All the results were compared and analyzed in terms of the carbon concentration gradient in case carburized 4317 M2 steel.

  15. COSTAR Dob/fos m2 Mirror Arm Deployment

    NASA Astrophysics Data System (ADS)

    Troeltzsch, John

    1994-01-01

    This proposal describes the activities needed to deploy the Deployable Optical Bench (DOB) from its stowed position to its operational position and verify that the deployment will not cause damage to the other instruments. The deployment of the DOB is done in two stages in order to prevent contact between the FOS M2 mirror arm and the other structures within the Hub region. If the DOB was deployed directly to the operational position, the FOS M2 mirror could not be deployed safely. An intermediate position is used to allow the arm to clear both the COSTAR enclosure and the other structures within the Hub region. As it is critical that the arm be completely deployed before moving the DOB to the operational position, a set of check images are taken with the FOS just before and after the arm deployment. If the deployment was successful, the FOS will show no signal in the after image. This proposal requires a mix of real-time activities performed by the STOCC and stored command activities performed by the STScI SMS. The implementation of this proposal requires careful attention to the implementation details as deployment of the FOS M2 mirror could result in physical damage to the HST instruments as defined in the CARD.

  16. Photoinducing the hidden M2 phase in VO2

    NASA Astrophysics Data System (ADS)

    Walko, D. A.; Smith, R. K.; Wen, Haidan; Dichiara, A. D.; Jeong, Jaewoo; Samant, Mahensh G.; Parkin, Stuart S. P.

    We used time-resolved x-ray diffraction to study photoinduced structural phase transitions in a 170-nm-thick VO2 film grown on sapphire (1,0,-1,0). Heating the unstrained film from room temperature induces the well-known phase transition from the monoclinic (M1) phase directly to the high-temperature tetragonal rutile (R) phase. In contrast, upon ultrafast optical excitation, the phase transition depends strongly on the laser intensity. At low fluences, the film is partially transformed into the monoclinic M2 phase, a phase which generally is observed only in doped or strained materials. Above a threshold at higher fluences, a small portion of the film is transformed into the M2 phase, decaying on a time scale of a few nanoseconds, while the majority of the film is transformed into the R phase which can persist for tens of nanoseconds. We further discuss the effects of laser wavelength on the efficiency of producing the M2 phase. Work at the Advanced Photon Source supported by DOE Contract No. DE-AC02-06CH11357.

  17. 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.

  18. 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

  19. Deep Sub-micro mol{\\cdot }mol^{-1} Water-Vapor Measurement by Dual-Ball SAW Sensors for Temperature Compensation

    NASA Astrophysics Data System (ADS)

    Takeda, N.; Oizumi, T.; Tsuji, T.; Akao, S.; Takayanagi, K.; Nakaso, N.; Yamanaka, K.

    2015-12-01

    A collimated surface acoustic wave (SAW) circles around the equator of a sphere hundreds of times. Because of the long distance travel of the collimated SAW, a small change in the SAW propagation caused by the environment of the sphere can be accumulated as a measurable range in amplitude and/or in delay time. So, a spherical SAW device enables highly sensitive water-vapor measurements. In this paper, deep sub \\upmu mol{\\cdot }mol^{-1} water-vapor detection by 1 mm diameter quartz crystal ball SAW sensors is described. To measure such a low water-vapor concentration in real time, it is necessary to compensate the temperature dependence of the ball SAW sensor, which is about 20 ppm{\\cdot }°C^{-1} in delay time change. A dual-frequency burst analog detector was developed for the temperature compensation in real time. By using a harmonic SAW sensor, which was excited by 80 MHz and 240 MHz at the same time, it was confirmed that the delay time drift for a temperature range of 21.0°C ± 1.0°C became less than 0.05 ppm in delay time change. By using dual-ball SAW sensors (which included a 150 MHz sensor with a water-vapor sensitive layer and a 240 MHz sensor as a reference), water-vapor concentrations from 0.1 \\upmu mol{\\cdot }mol^{-1} to 5 \\upmu mol{\\cdot }mol^{-1} were successfully measured. It appears that the delay time change is proportional to the square root of the water-vapor concentration. The detection limit determined by the electrical noise of the system was estimated at 0.01 \\upmu mol{\\cdot }mol^{-1}.

  20. Microglial M1/M2 polarization and metabolic states.

    PubMed

    Orihuela, Ruben; McPherson, Christopher A; Harry, Gaylia Jean

    2016-02-01

    Microglia are critical nervous system-specific immune cells serving as tissue-resident macrophages influencing brain development, maintenance of the neural environment, response to injury and repair. As influenced by their environment, microglia assume a diversity of phenotypes and retain the capability to shift functions to maintain tissue homeostasis. In comparison with peripheral macrophages, microglia demonstrate similar and unique features with regards to phenotype polarization, allowing for innate immunological functions. Microglia can be stimulated by LPS or IFN-γ to an M1 phenotype for expression of pro-inflammatory cytokines or by IL-4/IL-13 to an M2 phenotype for resolution of inflammation and tissue repair. Increasing evidence suggests a role of metabolic reprogramming in the regulation of the innate inflammatory response. Studies using peripheral immune cells demonstrate that polarization to an M1 phenotype is often accompanied by a shift in cells from oxidative phosphorylation to aerobic glycolysis for energy production. More recently, the link between polarization and mitochondrial energy metabolism has been considered in microglia. Under these conditions, energy demands would be associated with functional activities and cell survival and thus, may serve to influence the contribution of microglia activation to various neurodegenerative conditions. This review examines the polarization states of microglia and their relationship to mitochondrial metabolism. Additional supporting experimental data are provided to demonstrate mitochondrial metabolic shifts in primary microglia and the BV-2 microglia cell line induced under LPS (M1) and IL-4/IL-13 (M2) polarization.

  1. KIT oncogene inhibition drives intratumoral macrophage M2 polarization

    PubMed Central

    Cavnar, Michael J.; Zeng, Shan; Kim, Teresa S.; Sorenson, Eric C.; Ocuin, Lee M.; Balachandran, Vinod P.; Seifert, Adrian M.; Greer, Jonathan B.; Popow, Rachel; Crawley, Megan H.; Cohen, Noah A.; Green, Benjamin L.; Rossi, Ferdinand; Besmer, Peter; Antonescu, Cristina R.

    2013-01-01

    Tumor-associated macrophages (TAMs) are a major component of the cancer microenvironment. Modulation of TAMs is under intense investigation because they are thought to be nearly always of the M2 subtype, which supports tumor growth. Gastrointestinal stromal tumor (GIST) is the most common human sarcoma and typically results from an activating mutation in the KIT oncogene. Using a spontaneous mouse model of GIST and 57 freshly procured human GISTs, we discovered that TAMs displayed an M1-like phenotype and function at baseline. In both mice and humans, the KIT oncoprotein inhibitor imatinib polarized TAMs to become M2-like, a process which involved TAM interaction with apoptotic tumor cells leading to the induction of CCAAT/enhancer binding protein (C/EBP) transcription factors. In human GISTs that eventually developed resistance to imatinib, TAMs reverted to an M1-like phenotype and had a similar gene expression profile as TAMs from untreated human GISTs. Therefore, TAM polarization depends on tumor cell oncogene activity and has important implications for immunotherapeutic strategies in human cancers. PMID:24323358

  2. 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.

  3. Behavior of welds in liquid lead containing 10-6 wt% and 10-8 wt% oxygen

    NASA Astrophysics Data System (ADS)

    Heinzel, A.; Müller, G.; Weisenburger, A.

    2013-06-01

    Specimens with welded joints of P91 TIG (tungsten inert gas welding), P91 EB (electron beam welding) and frictions stir welding, with P92 (EB), PM2000 (EB) and combination of P91-PM2000 EB were tested 2000 h in stagnant liquid Pb at 550 °C with an oxygen concentration of 10-6 wt% and 10-8 wt%. After exposure at 10-6 wt% all specimens showed an oxide layer on the surface. If the grain size of the welds varies strongly from that of the bulk material like in the friction stir welds, a change in oxide thickness could be observed. Also precipitations which pin the oxide formers or reduce the diffusion rate can lead to thicker oxide layers or a stronger dissolution attack like it was observed on the dissimilar weld P91/PM2000 EB. The specimens have similar microstructures in all regions (weld, heat affected zone and bulk material) and due to a post-weld heat treatment show everywhere the same behavior.

  4. Calculation of anharmonic effects in the unimolecular dissociation of M2+(H2O)2 (M = Be, Mg, and Ca)

    NASA Astrophysics Data System (ADS)

    Li, Qian; Yao, Li; Xia, Wenwen; Lin, S. H.

    2015-11-01

    The anharmonic and harmonic rate constants of the unimolecular dissociation of M2+(H2O)2 (M = Be, Mg, and Ca) were calculated using the Rice-Ramsperger-Kassel-Marcus theory. The anharmonic effects of the reactions were investigated. The results show that the energy barrier of the dissociation of Be2+(H2O)2 is 68.47 kcal/mol, and the anharmonic (T4000K = 4.28×108 s-1) and harmonic (T4000K = 4.22×108 s-1) rate constants were close in value in both the canonical and microcanonical systems. The energy barriers of the two steps for the dissociation, Mg2+(H2O)2 → MgOH++H3O+, were 37.41 and 11.39 kcal/mol, and those for the dissociation, Ca2+(H2O)2 → CaOH++H3O+, were 21.15 and 26.42 kcal/mol. The anharmonic effect of the two reactions is significant and cannot be neglected in both the canonical and microcanonical systems. The comparison also shows that the rate constants of the dissociation of Ca2+(H2O)2 have the maximum values, while those of Be2+(H2O)2 have the minimum values in the three reactions; however, the anharmonic effect also shows the similar trend in the comparison.

  5. Vortex loop operators, M2-branes and holography

    NASA Astrophysics Data System (ADS)

    Drukker, Nadav; Gomis, Jaume; Young, Donovan

    2009-03-01

    We construct vortex loop operators in the three-dimensional Script N = 6 supersymmetric Chern-Simons theory recently constructed by Aharony, Bergman, Jafferis and Maldacena. These disorder loop operators are specified by a vortex-like singularity for the scalar and gauge fields along a one dimensional curve in spacetime. We identify the 1/2, 1/3 and 1/6 BPS loop operators in the Chern-Simons theory with excitations of M-theory corresponding to M2-branes ending along a curve on the boundary of AdS4 × S7/Bbb Zk. The vortex loop operators can also be given a purely geometric description in terms of regular ``bubbling'' solutions of eleven dimensional supergravity which are asymptotically AdS4 × S7/Bbb Zk.

  6. Astrometry and photometry in the globular cluster M2

    NASA Astrophysics Data System (ADS)

    Cudworth, Kyle M.; Rauscher, Bernard J.

    1987-04-01

    Proper motions and photometry have been obtained for 301 stars down to V = about 16 in the region of the globular cluster M2. Membership probabilities derived from the proper motions show that over 200 of these stars are highly probable cluster members, including a number of UV-bright stars. A few stars suspected of being field stars in a recent dynamical study of the cluster of Pryor et al. (1986) are confirmed to be nonmembers. The internal proper-motion dispersion has been detected and is clearly isotropic out to about 3 arcmin from the cluster center. The proper-motion and radial-velocity dispersions have been equated to yield a distance of 11.0 + or - 1.7 kpc independent of any standard-candle assumptions. An accurate position of the cluster center has been measured that differs markedly from that found by Shawl and White (1986). A large space velocity has been derived for the cluster.

  7. 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.

  8. 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

  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. An Introduction to Using the Method of Levels (MOL) Therapy to Work with People Experiencing Psychosis.

    PubMed

    Tai, Sara J

    2016-01-01

    This paper provides a basic introduction to using method of levels (MOL) therapy with people experiencing psychosis. As MOL is a direct application of perceptual control theory (PCT), a brief overview of the three main theoretical principles of this theory--control, conflict, and reorganization will be outlined in relation to understanding psychosis. In particular, how these principles form the basis of problem conceptualisation and determine what an MOL therapist is required to do during therapy will be illustrated. A practical description of MOL will be given, using case examples and short excerpts of therapeutic interactions. Some direct contrasts will also be made with cognitive behaviour therapy for psychosis (CBTp) and psychodynamic approaches (PA) in order to help illustrate the theory and practice of MOL. PMID:27052610

  11. HackaMol: An Object-Oriented Modern Perl Library for Molecular Hacking on Multiple Scales.

    PubMed

    Riccardi, Demian; Parks, Jerry M; Johs, Alexander; Smith, Jeremy C

    2015-04-27

    HackaMol is an open source, object-oriented toolkit written in Modern Perl that organizes atoms within molecules and provides chemically intuitive attributes and methods. The library consists of two components: HackaMol, the core that contains classes for storing and manipulating molecular information, and HackaMol::X, the extensions that use the core. The core is well-tested, well-documented, and easy to install across computational platforms. The goal of the extensions is to provide a more flexible space for researchers to develop and share new methods. In this application note, we provide a description of the core classes and two extensions: HackaMol::X::Calculator, an abstract calculator that uses code references to generalize interfaces with external programs, and HackaMol::X::Vina, a structured class that provides an interface with the AutoDock Vina docking program. PMID:25793330

  12. HackaMol: An Object-Oriented Modern Perl Library for Molecular Hacking on Multiple Scales.

    PubMed

    Riccardi, Demian; Parks, Jerry M; Johs, Alexander; Smith, Jeremy C

    2015-04-27

    HackaMol is an open source, object-oriented toolkit written in Modern Perl that organizes atoms within molecules and provides chemically intuitive attributes and methods. The library consists of two components: HackaMol, the core that contains classes for storing and manipulating molecular information, and HackaMol::X, the extensions that use the core. The core is well-tested, well-documented, and easy to install across computational platforms. The goal of the extensions is to provide a more flexible space for researchers to develop and share new methods. In this application note, we provide a description of the core classes and two extensions: HackaMol::X::Calculator, an abstract calculator that uses code references to generalize interfaces with external programs, and HackaMol::X::Vina, a structured class that provides an interface with the AutoDock Vina docking program.

  13. 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.

  14. Sum rules for M2 and other cases

    SciTech Connect

    Kurath, D.

    1995-08-01

    Sum rules were derived for parity-changing operators consisting of an odd-l spherical harmonic coupled to the spin operator sigma. The conditions are that the valence nucleons are in the oscillator shell with Q quanta and the shell with Q-1 quanta is full and the shell with Q+1 quanta is empty. Thus this applies to the 1p, 2sd and 3pf as valence shells, where the sum rules would be useful for inelastic electron scattering and other reactions. In particular a complete M2 sum rule was derived including the weak contribution from the orbital operator. The contribution from the spurious center-of-mass motion was also derived. The expression was tested by comparing to summations of transition strengths given by shell-model calculations. For nuclei with mass greater than {approximately}A = 70 one would need to include the effect of the intruding level with Q+1 quanta and J = Q+3/2. This problem will be considered in the coming year.

  15. Elastic and electronic properties of select M2AX phases

    NASA Astrophysics Data System (ADS)

    Lofland, S. E.; Hettinger, J. D.; Harrell, K.; Finkel, P.; Gupta, S.; Barsoum, M. W.; Hug, G.

    2004-01-01

    In this letter we report on the low-temperature specific heat of several M2AX phases: Ti2AlC, V2AlC, V2AsC, Nb2SnC, Ti2AlN, Hf2InC, Nb2AlC, and Cr2AlC. The Debye temperatures are quite high. The density of states at the Fermi level, N(EF) varies from ≈1.4 (eV formula unit)-1 to 6 (eV formula unit)-1. Ab initio calculations show that N(EF) is dictated by the transition metal d-d bands; the A-group element has little effect. We also measured the velocity of sound in V2AlC, V2AsC, Ti2AlC, and Ti2AlN. The average bulk modulus of these materials is over 100 GPa, with a high of ≈140 GPa for Ti2AlN. Our theoretical calculations correctly predict the trend in both the density of states and the bulk modulus, although there is some disagreement in the actual values.

  16. Human pyruvate kinase M2: a multifunctional protein.

    PubMed

    Gupta, Vibhor; Bamezai, Rameshwar N K

    2010-11-01

    Glycolysis, a central metabolic pathway, harbors evolutionary conserved enzymes that modulate and potentially shift the cellular metabolism on requirement. Pyruvate kinase, which catalyzes the last but rate-limiting step of glycolysis, is expressed in four isozymic forms, depending on the tissue requirement. M2 isoform (PKM2) is exclusively expressed in embryonic and adult dividing/tumor cells. This tetrameric allosterically regulated isoform is intrinsically designed to downregulate its activity by subunit dissociation (into dimer), which results in partial inhibition of glycolysis at the last step. This accumulates all upstream glycolytic intermediates as an anabolic feed for synthesis of lipids and nucleic acids, whereas reassociation of PKM2 into active tetramer replenishes the normal catabolism as a feedback after cell division. In addition, involvement of this enzyme in a variety of pathways, protein-protein interactions, and nuclear transport suggests its potential to perform multiple nonglycolytic functions with diverse implications, although multidimensional role of this protein is as yet not fully explored. This review aims to provide an overview of the involvement of PKM2 in various physiological pathways with possible functional implications. PMID:20857498

  17. Theoretical exploration of the nanoscale host-guest interactions between [n]cycloparaphenylenes (n = 10, 8 and 9) and fullerene C₆₀: from single- to three-potential well.

    PubMed

    Yuan, Kun; Zhou, Cai-Hua; Zhu, Yuan-Cheng; Zhao, Xiang

    2015-07-28

    The nanoscale host-guest interactions between [n]cycloparaphenylene ([n]CPP; n = 10, 8 and 9) nano-ring and fullerene C60 were explored theoretically. It is found that relatively small variations in the sizes of the [n]CPP host lead to very significant changes in encapsulation property toward the fullerene C60 guest. Expectedly, one stable inclusion-configuration of [10]CPP⊃C60 and one floating-configuration of [8]CPP⊃C60 are located on the potential surfaces of the two complexes, respectively. Unexpectedly, besides a floating-configuration (F-[9]CPP⊃C60), another stable inclusion-configuration (I-[9]CPP⊃C60) is also located on the potential surface of [9]CPP⊃C60 host-guest complex. Interaction energies and natural steric analysis show that these complexes are stabilized by balancing concave-convex π-π attractive and steric repulsive host-guest interactions. In contrast, the steric repulsive energy (Es) between host and guest of I-[9]CPP⊃C60 is as high as 233.12 kJ mol(-1), which is much larger than those in other complexes. The movements of C60 guest through the cavities of [n]CPP host (n = 10, 8 and 9) are simulated by calculating the energy profile, and the results interestingly reveal that the encapsulation of C60 by [10]CPP is in the manner of a single-potential well, by [8]CPP in the manner of a double-potential well, and by [9]CPP in the special manner of a three-potential well. We predict that the movement of C60 guest through the cavity of [9]CPP host should be experimentally observable owing to the relatively low energy barrier (<50 kJ mol(-1), M06-2X/6-31G(d)). Charge population analysis shows that an obvious charge transfer between host and guest takes place during the formation of I-[9]CPP⊃C60, which is different from those during the formation of [8]CPP⊃C60, [10]CPP⊃C60 and F-[9]CPP⊃C60. Additionally, the host-guest interaction regions were detected and visualized in real space based on the electron density and reduced density

  18. Alchemical Free Energy Calculations and Isothermal Titration Calorimetry Measurements of Aminoadamantanes Bound to the Closed State of Influenza A/M2TM.

    PubMed

    Ioannidis, Harris; Drakopoulos, Antonios; Tzitzoglaki, Christina; Homeyer, Nadine; Kolarov, Felix; Gkeka, Paraskevi; Freudenberger, Kathrin; Liolios, Christos; Gauglitz, Günter; Cournia, Zoe; Gohlke, Holger; Kolocouris, Antonios

    2016-05-23

    Adamantane derivatives, such as amantadine and rimantadine, have been reported to block the transmembrane domain (TM) of the M2 protein of influenza A virus (A/M2) but their clinical use has been discontinued due to evolved resistance in humans. Although experiments and simulations have provided adequate information about the binding interaction of amantadine or rimantadine to the M2 protein, methods for predicting binding affinities of whole series of M2 inhibitors have so far been scarcely applied. Such methods could assist in the development of novel potent inhibitors that overcome A/M2 resistance. Here we show that alchemical free energy calculations of ligand binding using the Bennett acceptance ratio (BAR) method are valuable for determining the relative binding potency of A/M2 inhibitors of the aminoadamantane type covering a binding affinity range of only ∼2 kcal mol(-1). Their binding affinities measured by isothermal titration calorimetry (ITC) against the A/M2TM tetramer from the Udorn strain in its closed form at pH 8 were used as experimental probes. The binding constants of rimantadine enantiomers against M2TMUdorn were measured for the first time and found to be equal. Two series of alchemical free energy calculations were performed using 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) lipids to mimic the membrane environment. A fair correlation was found for DPPC that was significantly improved using DMPC, which resembles more closely the DPC lipids used in the ITC experiments. This demonstrates that binding free energy calculations by the BAR approach can be used to predict relative binding affinities of aminoadamantane derivatives toward M2TM with good accuracy. PMID:27105206

  19. Fotoexcitación de Moléculas Pequeñas

    NASA Astrophysics Data System (ADS)

    González Díaz, P. F.

    El modelo estocástico no puede justificar la excitación multi-fotónica de moléculas pequeñas o muy simétricas. Basándonos en un escenario de interacción radiación-molécula cooperativo para la absorción de N-1 fotones IR por un sistema de N niveles, se especula que un posible mecanismo para la excitación no estocástica de moléculas pudiera ser la generación de procesos caóticos intra-moleculares.

  20. 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 SYSTEM TRUTH IN LENDING (REGULATION Z) Pt. 226, App. M2 Appendix M2 to Part 226—Actual...

  1. MolLoc: a web tool for the local structural alignment of molecular surfaces.

    PubMed

    Angaran, Stefano; Bock, Mary Ellen; Garutti, Claudio; Guerra, Concettina

    2009-07-01

    MolLoc stands for Molecular Local surface comparison, and is a web server for the structural comparison of molecular surfaces. Given two structures in PDB format, the user can compare their binding sites, cavities or any arbitrary residue selection. Moreover, the web server allows the comparison of a query structure with a list of structures. Each comparison produces a structural alignment that maximizes the extension of the superimposition of the surfaces, and returns the pairs of atoms with similar physicochemical properties that are close in space after the superimposition. Based on this subset of atoms sharing similar physicochemical properties a new rototranslation is derived that best superimposes them. MolLoc approach is both local and surface-oriented, and therefore it can be particularly useful when testing if molecules with different sequences and folds share any local surface similarity. The MolLoc web server is available at http://bcb.dei.unipd.it/MolLoc.

  2. 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

  3. MOLS 2.0: software package for peptide modeling and protein-ligand docking.

    PubMed

    Paul, D Sam; Gautham, N

    2016-10-01

    We previously developed an algorithm to perform conformational searches of proteins and peptides, and to perform the docking of ligands to protein receptors. In order to identify optimal conformations and docked poses, this algorithm uses mutually orthogonal Latin squares (MOLS) to rationally sample the vast conformational (or docking) space, and then analyzes this relatively small sample using a variant of mean field theory. The conformational search part of the algorithm was denoted MOLS 1.0. The docking portion of the algorithm, which allows only "flexible ligand/rigid receptor" docking, was denoted MOLSDOCK. Both are FORTRAN-based command-line-only molecular docking computer programs, though a GUI was developed later for MOLS 1.0. Both the conformational search and the rigid receptor docking parts of the algorithm have been extensively validated. We have now further enhanced the capabilities of the program by incorporating "induced fit" side-chain receptor flexibility for docking peptide ligands. Benchmarking and extensive testing is now being carried out for the flexible receptor portion of the docking. Additionally, to make both the peptide conformational search and docking algorithms (the latter including both flexible ligand/rigid receptor and flexible ligand/flexible receptor techniques) more accessible to the research community, we have developed MOLS 2.0, which incorporates a new Java-based graphical user interface (GUI). Here, we give a detailed description of MOLS 2.0. The source code and binary for MOLS 2.0 are distributed free (under a GNU Lesser General Public License) to the scientific community. They are freely available for download at https://sourceforge.net/projects/mols2-0/files/ . PMID:27638416

  4. MOLS 2.0: software package for peptide modeling and protein-ligand docking.

    PubMed

    Paul, D Sam; Gautham, N

    2016-10-01

    We previously developed an algorithm to perform conformational searches of proteins and peptides, and to perform the docking of ligands to protein receptors. In order to identify optimal conformations and docked poses, this algorithm uses mutually orthogonal Latin squares (MOLS) to rationally sample the vast conformational (or docking) space, and then analyzes this relatively small sample using a variant of mean field theory. The conformational search part of the algorithm was denoted MOLS 1.0. The docking portion of the algorithm, which allows only "flexible ligand/rigid receptor" docking, was denoted MOLSDOCK. Both are FORTRAN-based command-line-only molecular docking computer programs, though a GUI was developed later for MOLS 1.0. Both the conformational search and the rigid receptor docking parts of the algorithm have been extensively validated. We have now further enhanced the capabilities of the program by incorporating "induced fit" side-chain receptor flexibility for docking peptide ligands. Benchmarking and extensive testing is now being carried out for the flexible receptor portion of the docking. Additionally, to make both the peptide conformational search and docking algorithms (the latter including both flexible ligand/rigid receptor and flexible ligand/flexible receptor techniques) more accessible to the research community, we have developed MOLS 2.0, which incorporates a new Java-based graphical user interface (GUI). Here, we give a detailed description of MOLS 2.0. The source code and binary for MOLS 2.0 are distributed free (under a GNU Lesser General Public License) to the scientific community. They are freely available for download at https://sourceforge.net/projects/mols2-0/files/ .

  5. SCWRL and MolIDE: computer programs for side-chain conformation prediction and homology modeling.

    PubMed

    Wang, Qiang; Canutescu, Adrian A; Dunbrack, Roland L

    2008-01-01

    SCWRL and MolIDE are software applications for prediction of protein structures. SCWRL is designed specifically for the task of prediction of side-chain conformations given a fixed backbone usually obtained from an experimental structure determined by X-ray crystallography or NMR. SCWRL is a command-line program that typically runs in a few seconds. MolIDE provides a graphical interface for basic comparative (homology) modeling using SCWRL and other programs. MolIDE takes an input target sequence and uses PSI-BLAST to identify and align templates for comparative modeling of the target. The sequence alignment to any template can be manually modified within a graphical window of the target-template alignment and visualization of the alignment on the template structure. MolIDE builds the model of the target structure on the basis of the template backbone, predicted side-chain conformations with SCWRL and a loop-modeling program for insertion-deletion regions with user-selected sequence segments. SCWRL and MolIDE can be obtained at (http://dunbrack.fccc.edu/Software.php).

  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. Microwave sintering of ZrO{sub 2}-12 mol% CeO{sub 2}

    SciTech Connect

    Janney, M.A.; Jackson, M.L.; Kimrey, H.D.

    1993-12-31

    Sintering of ZrO{sub 2}-12 mol% CeO{sub 2} was accelerated by microwave processing at 2.45 GHz as compared with conventional firing. However, the size of the ``microwave effect`` was significantly smaller than that which was previously observed for microwave sintering of ZrO{sub 2}-8 mol% Y{sub 2}O{sub 3}. The difference in the effect that the microwave field had on the two zirconia systems is interpreted in terms of their ionic conductivities.

  8. COOMET.QM-K93 (COOMET 615/RU/13): key comparison in the field of measuring of the ethanol amount fraction in nitrogen (120 μmol/mol)

    NASA Astrophysics Data System (ADS)

    Konopelko, L. A.; Efremova, O. V.; Fatina, O. V.; Orshanskaia, A. A.; Rozhnov, M. S.; Melnyk, D. M.; Petryshyn, P. V.

    2016-01-01

    The relevance of the COOMET.QM-K93 comparison is founded on paying particular attention to reliability of measurements which are performed during the medical examination of drivers of vehicles in order to assess the degree of alcoholic intoxication. Standard gas mixtures of ethanol in nitrogen in cylinders under pressure play a key role in providing metrological assurance of breath-alcohol analyzers. Participating laboratories: VNIIM and Ukrmetrteststandart. This comparison was carried out in 2014-2015. This supplementary comparison supports CMC claims for: ethanol in the range 50-500 μmol/mol in a matrix of either nitrogen or synthetic air. Results: The results are consistent with the reference values. 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 CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  9. Simplifying and enhancing the use of PyMOL with horizontal scripts.

    PubMed

    Mooers, Blaine H M

    2016-10-01

    Scripts are used in PyMOL to exert precise control over the appearance of the output and to ease remaking similar images at a later time. We developed horizontal scripts to ease script development. A horizontal script makes a complete scene in PyMOL like a traditional vertical script. The commands in a horizontal script are separated by semicolons. These scripts are edited interactively on the command line with no need for an external text editor. This simpler workflow accelerates script development. In using PyMOL, the illustration of a molecular scene requires an 18-element matrix of view port settings. The default format spans several lines and is laborious to manually reformat for one line. This default format prevents the fast assembly of horizontal scripts that can reproduce a molecular scene. We solved this problem by writing a function that displays the settings on one line in a compact format suitable for horizontal scripts. We also demonstrate the mapping of aliases to horizontal scripts. Many aliases can be defined in a single script file, which can be useful for applying costume molecular representations to any structure. We also redefined horizontal scripts as Python functions to enable the use of the help function to print documentation about an alias to the command history window. We discuss how these methods of using horizontal scripts both simplify and enhance the use of PyMOL in research and education.

  10. Automated protein motif generation in the structure-based protein function prediction tool ProMOL.

    PubMed

    Osipovitch, Mikhail; Lambrecht, Mitchell; Baker, Cameron; Madha, Shariq; Mills, Jeffrey L; Craig, Paul A; Bernstein, Herbert J

    2015-12-01

    ProMOL, a plugin for the PyMOL molecular graphics system, is a structure-based protein function prediction tool. ProMOL includes a set of routines for building motif templates that are used for screening query structures for enzyme active sites. Previously, each motif template was generated manually and required supervision in the optimization of parameters for sensitivity and selectivity. We developed an algorithm and workflow for the automation of motif building and testing routines in ProMOL. The algorithm uses a set of empirically derived parameters for optimization and requires little user intervention. The automated motif generation algorithm was first tested in a performance comparison with a set of manually generated motifs based on identical active sites from the same 112 PDB entries. The two sets of motifs were equally effective in identifying alignments with homologs and in rejecting alignments with unrelated structures. A second set of 296 active site motifs were generated automatically, based on Catalytic Site Atlas entries with literature citations, as an expansion of the library of existing manually generated motif templates. The new motif templates exhibited comparable performance to the existing ones in terms of hit rates against native structures, homologs with the same EC and Pfam designations, and randomly selected unrelated structures with a different EC designation at the first EC digit, as well as in terms of RMSD values obtained from local structural alignments of motifs and query structures. This research is supported by NIH grant GM078077. PMID:26573864

  11. Mol-ecular and crystal structure of gossypol tetra-methyl ether with an unknown solvate.

    PubMed

    Honkeldieva, Muhabbat; Talipov, Samat; Mardanov, Rustam; Ibragimov, Bakhtiyar

    2015-02-01

    The title compound, C34H38O8 (systematic name: 5,5'-diisopropyl-2,2',3,3'-tetra-meth-oxy-7,7'-dimethyl-2H,2'H-8,8'-bi-[naphtho-[1,8-bc]furan]-4,4'-diol), has been obtained from a gossypol solution in a mixture of dimethyl sulfate and methanol. The mol-ecule is situated on a twofold rotation axis, so the asymmetric unit contains one half-mol-ecule. In the mol-ecule, the hy-droxy groups are involved in intra-molecular O-H⋯O hydrogen bonds, and the two naphthyl fragments are inclined each to other by 83.8 (1)°. In the crystal, weak C-H⋯O and C-H⋯π inter-actions consolidate the packing, which exhibits channels with an approximate diameter of 6 Å extending along the c-axis direction. These channels are filled with highly disordered solvent mol-ecules, so their estimated scattering contribution was subtracted from the observed diffraction data using the SQUEEZE option in PLATON [Spek, A. L. (2015). Acta Cryst. C71, 9-18]. PMID:25878814

  12. Simplifying and enhancing the use of PyMOL with horizontal scripts.

    PubMed

    Mooers, Blaine H M

    2016-10-01

    Scripts are used in PyMOL to exert precise control over the appearance of the output and to ease remaking similar images at a later time. We developed horizontal scripts to ease script development. A horizontal script makes a complete scene in PyMOL like a traditional vertical script. The commands in a horizontal script are separated by semicolons. These scripts are edited interactively on the command line with no need for an external text editor. This simpler workflow accelerates script development. In using PyMOL, the illustration of a molecular scene requires an 18-element matrix of view port settings. The default format spans several lines and is laborious to manually reformat for one line. This default format prevents the fast assembly of horizontal scripts that can reproduce a molecular scene. We solved this problem by writing a function that displays the settings on one line in a compact format suitable for horizontal scripts. We also demonstrate the mapping of aliases to horizontal scripts. Many aliases can be defined in a single script file, which can be useful for applying costume molecular representations to any structure. We also redefined horizontal scripts as Python functions to enable the use of the help function to print documentation about an alias to the command history window. We discuss how these methods of using horizontal scripts both simplify and enhance the use of PyMOL in research and education. PMID:27488983

  13. Final report on international comparison CCQM-K74: Nitrogen dioxide, 10 µmol/mol

    NASA Astrophysics Data System (ADS)

    Flores, Edgar; Idrees, Faraz; Moussay, Philippe; Viallon, Joële; Wielgosz, Robert; Fernández, Teresa; Ramírez, Sergio; Rojo, Andrés; Shinji, Uehara; Waldén, Jari; Sega, Michela; Sang-Hyub, Oh; Macé, Tatiana; Couret, Cedric; Qiao, Han; Smeulders, Damian; Guenther, Franklin R.; Thorn, William J., III; Tshilongo, James; Godwill Ntsasa, Napo; Štovcík, Viliam; Valková, Miroslava; Konopelko, Leonid; Gromova, Elena; Nieuwenkamp, Gerard; Wessel, Rob M.; Milton, Martin; Harling, Alice; Vargha, Gergely; Tuma, Dirk; Kohl, Anka; Schulz, Gert

    2012-01-01

    There is a high international priority attached to activities which reduce NOx in the atmosphere. The current level of permitted emissions is typically between 50 µmol/mol and 100 µmol/mol, but lower values are expected in the future. Currently, ambient air quality monitoring regulations also require the measurement of NOx mole fractions as low as 0.2 µmol/mol. The production of accurate standards at these levels of mole fractions requires either dilution of a stable higher concentration gas standard or production by a dynamic technique, for example one based on permeation tubes. The CCQM-K74 key comparison was designed to evaluate the level of comparability of National Metrology Institutes' measurement capabilities and standards for nitrogen dioxide (NO2) at a nominal mole fraction of 10 µmol/mol. The measurements of this key comparison took place from June 2009 to May 2010. Seventeen laboratories took part in this comparison coordinated by the BIPM and VSL. The key comparison reference value was based on BIPM measurement results, and the standard measurement uncertainty of the reference value was 0.042 µmol/mol. This key comparison demonstrated that the results of the majority of the participants agreed within limits of ±3% relative to the reference value. The results of only one laboratory lay significantly outside these limits. Likewise this comparison made clear that a full interpretation of the results of the comparison needed to take into account the presence of nitric acid (in the range 100 nmol/mol to 350 nmol/mol) in the cylinders circulated as part of the comparison, as well as the possible presence of nitric acid in the primary standards used by participating laboratories. 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 CCQM, according to the

  14. Influenza M2 Transmembrane Domain Senses Membrane Heterogeneity and Enhances Membrane Curvature.

    PubMed

    Ho, Chian Sing; Khadka, Nawal K; She, Fengyu; Cai, Jianfeng; Pan, Jianjun

    2016-07-01

    Targeting host cell membranes by M2 of influenza A virus is important for virus invasion and replication. We study the transmembrane domain of M2 (M2TM) interacting with mica-supported planar bilayers and free-standing giant unilamellar vesicles (GUVs). Using solution atomic force microscopy (AFM), we show that the size of M2TM oligomers is dependent on lipid composition. The addition of M2TM to lipid bilayers containing liquid-ordered (Lo) and liquid-disordered (Ld) phases reveals that M2TM preferentially partitions into the Ld phase; phase-dependent partitioning results in a larger rigidity of the Ld phase. We next use fluorescence microscopy to study the effects of M2TM on phase-coexisting GUVs. In particular, M2TM is found to increase GUVs' miscibility transition temperature Tmix. The augmented thermodynamic stability can be accounted for by considering an enhanced energy barrier of lipid mixing between coexisting phases. Our GUV study also shows that M2TM can elicit an array of vesicle shapes mimicking virus budding. M2TM enhanced membrane curvature is consistent with our AFM data, which show altered membrane rigidity and consequently line tension at domain edges. Together, our results highlight that in addition to conducting protons, M2TM can actively regulate membrane heterogeneity and augment membrane curvature. PMID:27285399

  15. 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

  16. Identification of a new gene, molR, essential for utilization of molybdate by Escherichia coli.

    PubMed Central

    Lee, J H; Wendt, J C; Shanmugam, K T

    1990-01-01

    A mutation in a new gene, molR, prevented the synthesis in Escherichia coli of molybdoenzymes, including the two formate dehydrogenase isoenzymes, nitrate reductase and trimethylamine-N-oxide reductase. This phenotype was suppressed by supplementing the media with molybdate. Thus, the molR mutant was phenotypically similar to previously described chlD mutants, thought to be defective in molybdate transport. The molR gene is located at 65.3 min in the E. coli chromosome, in contrast to the chlD gene, which maps at 17 min and thus can be readily distinguished. The molR gene is also cotransducible with a hitherto unidentified gene essential for the production of 2-oxoglutarate from isocitrate, designated icdB (located at 66 min). The molR mutant strain SE1100 also failed to produce the hydrogenase component of formate hydrogenlyase (HYD3) in molybdate-unsupplemented media. The amount of molybdate required by strain SE1100 for the production of parental levels of formate hydrogenlyase activity was dependent on the growth medium. In Luria-Bertani medium, this value was about 100 microM, and in glucose-minimal medium, 1.0 microM was sufficient. In low-sulfur medium, this value decreased to about 50 nM. The addition of sulfate or selenite increased the amount of molybdate needed for the production of formate hydrogenlyase activity. These data suggest that in the absence of the high-affinity molybdate transport system, E. coli utilizes sulfate and selenite transport systems for transporting molybdate, preferring sulfate transport over the selenite transport system. PMID:2156810

  17. Effects of bimetallic doping on small cyclic and tubular boron clusters: B7M2 and B14M2 structures with M = Fe, Co.

    PubMed

    Pham, Hung Tan; Nguyen, Minh Tho

    2015-07-14

    Using density functional theory with the TPSSh functional and the 6-311+G(d) basis set, we extensively searched for the global minima of two metallic atoms doped boron clusters B6M2, B7M2, B12M2 and B14M2 with transition metal element M being Co and Fe. Structural identifications reveal that B7Co2, B7Fe2 and B7CoFe clusters have global minima in a B-cyclic motif, in which a perfectly planar B7 is coordinated with two metallic atoms placed along the C7 axis. The B6 cluster is too small to form a cycle with the presence of two metals. Similarly, the B12 cluster is not large enough to stabilize the metallic dimer within a double ring 2 × B6 tube. The doped B14M2 clusters including B14Co2, B14Fe2 and B14CoFe have a double ring 2 × B7 tubular shape in which one metal atom is encapsulated by the B14 tube and the other is located at an exposed position. Dissociation energies demonstrate that while bimetallic cyclic cluster B7M2 prefers a fragmentation channel that generates the B7 global minimum plus metallic dimer, the tubular structure B14M2 tends to dissociate giving a bimetallic cyclic structure B7M2 and a B@B6 cluster. The enhanced stability of the bimetallic doped boron clusters considered can be understood from the stabilizing interactions between the anti-bonding MOs of metal-metal dimers and the levels of a disk aromatic configuration (for bimetallic cyclic structures), or the eigenstates of the B14 tubular form (in case of bimetallic tubular structure).

  18. 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

  19. β-Adrenergic-stimulated macrophages: Comprehensive localization in the M1-M2 spectrum.

    PubMed

    Lamkin, Donald M; Ho, Hsin-Yun; Ong, Tiffany H; Kawanishi, Carly K; Stoffers, Victoria L; Ahlawat, Nivedita; Ma, Jeffrey C Y; Arevalo, Jesusa M G; Cole, Steve W; Sloan, Erica K

    2016-10-01

    β-Adrenergic signaling can regulate macrophage involvement in several diseases and often produces anti-inflammatory properties in macrophages, which are similar to M2 properties in a dichotomous M1 vs. M2 macrophage taxonomy. However, it is not clear that β-adrenergic-stimulated macrophages may be classified strictly as M2. In this in vitro study, we utilized recently published criteria and transcriptome-wide bioinformatics methods to map the relative polarity of murine β-adrenergic-stimulated macrophages within a wider M1-M2 spectrum. Results show that β-adrenergic-stimulated macrophages did not fit entirely into any one pre-defined category of the M1-M2 spectrum but did express genes that are representative of some M2 side categories. Moreover, transcript origin analysis of genome-wide transcriptional profiles located β-adrenergic-stimulated macrophages firmly on the M2 side of the M1-M2 spectrum and found active suppression of M1 side gene transcripts. The signal transduction pathways involved were mapped through blocking experiments and bioinformatics analysis of transcription factor binding motifs. M2-promoting effects were mediated specifically through β2-adrenergic receptors and were associated with CREB, C/EBPβ, and ATF transcription factor pathways but not with established M1-M2 STAT pathways. Thus, β-adrenergic-signaling induces a macrophage transcriptome that locates on the M2 side of the M1-M2 spectrum but likely accomplishes this effect through a signaling pathway that is atypical for M2-spectrum macrophages. PMID:27485040

  20. The ExoMol database: Molecular line lists for exoplanet and other hot atmospheres

    NASA Astrophysics Data System (ADS)

    Tennyson, Jonathan; Yurchenko, Sergei N.; Al-Refaie, Ahmed F.; Barton, Emma J.; Chubb, Katy L.; Coles, Phillip A.; Diamantopoulou, S.; Gorman, Maire N.; Hill, Christian; Lam, Aden Z.; Lodi, Lorenzo; McKemmish, Laura K.; Na, Yueqi; Owens, Alec; Polyansky, Oleg L.; Rivlin, Tom; Sousa-Silva, Clara; Underwood, Daniel S.; Yachmenev, Andrey; Zak, Emil

    2016-09-01

    The ExoMol database (www.exomol.com) provides extensive line lists of molecular transitions which are valid over extended temperatures ranges. The status of the current release of the database is reviewed and a new data structure is specified. This structure augments the provision of energy levels (and hence transition frequencies) and Einstein $A$ coefficients with other key properties, including lifetimes of individual states, temperature-dependent cooling functions, Land\\'e $g$-factors, partition functions, cross sections, $k$-coefficients and transition dipoles with phase relations. Particular attention is paid to the treatment of pressure broadening parameters. The new data structure includes a definition file which provides the necessary information for utilities accessing ExoMol through its application programming interface (API). Prospects for the inclusion of new species into the database are discussed.

  1. Ligand-based virtual screening interface between PyMOL and LiSiCA.

    PubMed

    Dilip, Athira; Lešnik, Samo; Štular, Tanja; Janežič, Dušanka; Konc, Janez

    2016-01-01

    Ligand-based virtual screening of large small-molecule databases is an important step in the early stages of drug development. It is based on the similarity principle and is used to reduce the chemical space of large databases to a manageable size where chosen ligands can be experimentally tested. Ligand-based virtual screening can also be used to identify bioactive molecules with different basic scaffolds compared to already known bioactive molecules, thus having the potential to increase the structural variability of compounds. Here, we present an interface between the popular molecular graphics system PyMOL and the ligand-based virtual screening software LiSiCA available at http://insilab.org/lisica-plugin and demonstrate how this interface can be used in the early stages of drug discovery process.Graphical AbstractLigand-based virtual screening interface between PyMOL and LiSiCA. PMID:27606012

  2. A systematic framework for evaluating standard cell middle-of-line (MOL) robustness for multiple patterning

    NASA Astrophysics Data System (ADS)

    Xu, Xiaoqing; Cline, Brian; Yeric, Greg; Yu, Bei; Pan, David Z.

    2015-03-01

    Multiple patterning (triple and quadruple patterning) is being considered for use on the Middle-Of-Line (MOL) layers at the 10nm technology node and beyond.1 For robust standard cell design, designers need to improve the inter-cell compatibility for all combinations of cells and cell placements. Multiple patterning colorability checks break the locality of traditional rule checking and N-wise checks are strongly needed to verify the multiple patterning colorability for layout interaction across cell boundaries. In this work, a systematic framework is proposed to evaluate the library-level robustness over multiple patterning from two perpectives, including illegal cell combinations and full chip interactions. With efficient N-wise checks, the vertical and horizontal boundary checks are explored to predict illegal cell combinations. For full chip interactions, random benchmarks are generated by cell shifting and tested to evaluate the placement-level efforts needed to reduce the quadruple patterning to triple patterning for the MOL layer.

  3. Towards J/mol Accuracy for the Cohesive Energy of Solid Argon.

    PubMed

    Schwerdtfeger, Peter; Tonner, Ralf; Moyano, Gloria E; Pahl, Elke

    2016-09-26

    The cohesive energies of argon in its cubic and hexagonal closed packed structures are computed with an unprecedented accuracy of about 5 J mol(-1) (corresponding to 0.05 % of the total cohesive energy). The same relative accuracy with respect to experimental data is also found for the face-centered cubic lattice constant deviating by ca. 0.003 Å. This level of accuracy was enabled by using high-level theoretical, wave-function-based methods within a many-body decomposition of the interaction energy. Static contributions of two-, three-, and four-body fragments of the crystal are all individually converged to sub-J mol(-1) accuracy and complemented by harmonic and anharmonic vibrational corrections. Computational chemistry is thus achieving or even surpassing experimental accuracy for the solid-state rare gases. PMID:27593519

  4. Repeated high-dose (5 × 10(8) TCID50) toxicity study of a third generation smallpox vaccine (IMVAMUNE) in New Zealand white rabbits.

    PubMed

    Tree, Julia A; Hall, Graham; Rees, Peter; Vipond, Julia; Funnell, Simon G P; Roberts, Allen D

    2016-07-01

    Concern over the release of variola virus as an agent of bioterrorism remains high and a rapid vaccination regimen is desirable for use in the event of a confirmed release of virus. A single, high-dose (5×10(8) TCID50) of Bavarian Nordic's IMVAMUNE was tested in a Phase-II clinical trial, in humans, as a substitute for the standard (1×10(8) TCID50), using a 2-dose, 28-days apart regimen. Prior to this clinical trial taking place a Good Laboratory Practice, repeated high-dose, toxicology study was performed using IMVAMUNE, in New Zealand white rabbits and the results are reported here. Male and female rabbits were dosed twice, subcutaneously, with 5×10(8) TCID50 of IMVAMUNE (test) or saline (control), 7-days apart. The clinical condition, body-weight, food consumption, haematology, blood chemistry, immunogenicity, organ-weight, and macroscopic and microscopic pathology were investigated. Haematological investigations indicated changes within the white blood cell profile that were attributed to treatment with IMVAMUNE; these comprised slight increases in neutrophil and monocyte numbers, on study days 1-3 and a marginal increase in lymphocyte numbers on day 10. Macroscopic pathology revealed reddening at the sites of administration and thickened skin in IMVAMUNE, treated animals. After the second dose of IMVAMUNE 9/10 rabbits seroconverted, as detected by antibody ELISA on day 10, by day 21, 10/10 rabbits seroconverted. Treatment-related changes were not detected in other parameters. In conclusion, the subcutaneous injection of 2 high-doses of IMVAMUNE, to rabbits, was well tolerated producing only minor changes at the site of administration. Vaccinia-specific antibodies were raised in IMVAMUNE-vaccinated rabbits only.

  5. Repeated high-dose (5 × 10(8) TCID50) toxicity study of a third generation smallpox vaccine (IMVAMUNE) in New Zealand white rabbits.

    PubMed

    Tree, Julia A; Hall, Graham; Rees, Peter; Vipond, Julia; Funnell, Simon G P; Roberts, Allen D

    2016-07-01

    Concern over the release of variola virus as an agent of bioterrorism remains high and a rapid vaccination regimen is desirable for use in the event of a confirmed release of virus. A single, high-dose (5×10(8) TCID50) of Bavarian Nordic's IMVAMUNE was tested in a Phase-II clinical trial, in humans, as a substitute for the standard (1×10(8) TCID50), using a 2-dose, 28-days apart regimen. Prior to this clinical trial taking place a Good Laboratory Practice, repeated high-dose, toxicology study was performed using IMVAMUNE, in New Zealand white rabbits and the results are reported here. Male and female rabbits were dosed twice, subcutaneously, with 5×10(8) TCID50 of IMVAMUNE (test) or saline (control), 7-days apart. The clinical condition, body-weight, food consumption, haematology, blood chemistry, immunogenicity, organ-weight, and macroscopic and microscopic pathology were investigated. Haematological investigations indicated changes within the white blood cell profile that were attributed to treatment with IMVAMUNE; these comprised slight increases in neutrophil and monocyte numbers, on study days 1-3 and a marginal increase in lymphocyte numbers on day 10. Macroscopic pathology revealed reddening at the sites of administration and thickened skin in IMVAMUNE, treated animals. After the second dose of IMVAMUNE 9/10 rabbits seroconverted, as detected by antibody ELISA on day 10, by day 21, 10/10 rabbits seroconverted. Treatment-related changes were not detected in other parameters. In conclusion, the subcutaneous injection of 2 high-doses of IMVAMUNE, to rabbits, was well tolerated producing only minor changes at the site of administration. Vaccinia-specific antibodies were raised in IMVAMUNE-vaccinated rabbits only. PMID:26836234

  6. MolProbity: all-atom structure validation for macromolecular crystallography

    SciTech Connect

    Chen, Vincent B.; Arendall, W. Bryan III; Headd, Jeffrey J.; Keedy, Daniel A.; Immormino, Robert M.; Kapral, Gary J.; Murray, Laura W.; Richardson, Jane S.; Richardson, David C.

    2010-01-01

    MolProbity structure validation will diagnose most local errors in macromolecular crystal structures and help to guide their correction. MolProbity is a structure-validation web service that provides broad-spectrum solidly based evaluation of model quality at both the global and local levels for both proteins and nucleic acids. It relies heavily on the power and sensitivity provided by optimized hydrogen placement and all-atom contact analysis, complemented by updated versions of covalent-geometry and torsion-angle criteria. Some of the local corrections can be performed automatically in MolProbity and all of the diagnostics are presented in chart and graphical forms that help guide manual rebuilding. X-ray crystallography provides a wealth of biologically important molecular data in the form of atomic three-dimensional structures of proteins, nucleic acids and increasingly large complexes in multiple forms and states. Advances in automation, in everything from crystallization to data collection to phasing to model building to refinement, have made solving a structure using crystallography easier than ever. However, despite these improvements, local errors that can affect biological interpretation are widespread at low resolution and even high-resolution structures nearly all contain at least a few local errors such as Ramachandran outliers, flipped branched protein side chains and incorrect sugar puckers. It is critical both for the crystallographer and for the end user that there are easy and reliable methods to diagnose and correct these sorts of errors in structures. MolProbity is the authors’ contribution to helping solve this problem and this article reviews its general capabilities, reports on recent enhancements and usage, and presents evidence that the resulting improvements are now beneficially affecting the global database.

  7. Dimetallaborane analogues of the octaboranes of the type Cp2M2B6H10: structural variations with changes in the skeletal electron count.

    PubMed

    Brânzanic, Adrian M V; Lupan, Alexandru; King, R Bruce

    2016-05-31

    The structures and energetics of the complete series of hydrogen-rich dimetallaboranes Cp2M2B6H10 and Cp*2M2B6H10 (Cp = η(5)-C5H5; Cp* = η(5)-Me5C5; M = Pd, Pt; Rh, Ir; Ru, Os; Re; Mo, W; Ta), including the experimentally known Cp*2Rh2B6H10 and Cp*2W2B6H10 (Cp* = η(5)-Me5C5), have been investigated by density functional theory. The lowest energy structures of the hyperelectronic Cp2M2B6H10 (M = Pd, Pt; Rh, Ir) systems have central M2B6 frameworks with a hexagonal open face similar to the B8 networks in arachno-B8H14 and nido-B8H12. The two lowest energy structures for Cp2Rh2B6H10 and Cp*2Rh2B6H10, lying within 1 kcal mol(-1) of energy, differ only in the locations of the bridging hydrogen atoms around the hexagonal hole consistent with the experimentally observed fluxionality of the hydrogen atoms in Cp*2Rh2B6H10. Most of the lowest energy Cp2M2B6H10 (M = Ru, Os) structures also have a central M2B6 framework similar to B8H12, typically with such additional features as an additional metal-metal bond or a formal metal-metal double bond. A common motif for the low-energy structures of the hypoelectronic Cp2M2B6H10 (M = Re; Mo, W; Ta) systems, including the experimentally known Cp*2W2B6H10, is a central M2B4 octahedron with its two M2B faces capped by the remaining boron atoms and with four M-B edges bridged by hydrogen atoms. Such structures can also be considered as oblatonido structures derived from the experimentally known 9-vertex oblatocloso Cp*2Re2B7H7 structure by removal of the unique degree 4 vertex atom. PMID:27186632

  8. Azahar: a PyMOL plugin for construction, visualization and analysis of glycan molecules.

    PubMed

    Arroyuelo, Agustina; Vila, Jorge A; Martin, Osvaldo A

    2016-08-01

    Glycans are key molecules in many physiological and pathological processes. As with other molecules, like proteins, visualization of the 3D structures of glycans adds valuable information for understanding their biological function. Hence, here we introduce Azahar, a computing environment for the creation, visualization and analysis of glycan molecules. Azahar is implemented in Python and works as a plugin for the well known PyMOL package (Schrodinger in The PyMOL molecular graphics system, version 1.3r1, 2010). Besides the already available visualization and analysis options provided by PyMOL, Azahar includes 3 cartoon-like representations and tools for 3D structure caracterization such as a comformational search using a Monte Carlo with minimization routine and also tools to analyse single glycans or trajectories/ensembles including the calculation of radius of gyration, Ramachandran plots and hydrogen bonds. Azahar is freely available to download from http://www.pymolwiki.org/index.php/Azahar and the source code is available at https://github.com/agustinaarroyuelo/Azahar . PMID:27549814

  9. SigMol: repertoire of quorum sensing signaling molecules in prokaryotes.

    PubMed

    Rajput, Akanksha; Kaur, Karambir; Kumar, Manoj

    2016-01-01

    Quorum sensing is a widespread phenomenon in prokaryotes that helps them to communicate among themselves and with eukaryotes. It is driven through quorum sensing signaling molecules (QSSMs) in a density dependent manner that assists in numerous biological functions like biofilm formation, virulence factors secretion, swarming motility, bioluminescence, etc. Despite immense implications, dedicated resources of QSSMs are lacking. Therefore, we have developed SigMol (http://bioinfo.imtech.res.in/manojk/sigmol), a specialized repository of these molecules in prokaryotes. SigMol harbors information on QSSMs pertaining to different quorum sensing signaling systems namely acylated homoserine lactones (AHLs), diketopiperazines (DKPs), 4-hydroxy-2-alkylquinolines (HAQs), diffusible signal factors (DSFs), autoinducer-2 (AI-2) and others. Database contains 1382: entries of 182: unique signaling molecules from 215: organisms. It encompasses biological as well as chemical aspects of signaling molecules. Biological information includes genes, preliminary bioassays, identification assays and applications, while chemical detail comprises of IUPAC name, SMILES and structure. We have provided user-friendly browsing and searching facilities for easy data retrieval and comparison. We have gleaned information of diverse QSSMs reported in literature at a single platform 'SigMol'. This comprehensive resource will assist the scientific community in understanding intraspecies, interspecies or interkingdom networking and further help to unfold different facets of quorum sensing and related therapeutics. PMID:26490957

  10. SigMol: repertoire of quorum sensing signaling molecules in prokaryotes.

    PubMed

    Rajput, Akanksha; Kaur, Karambir; Kumar, Manoj

    2016-01-01

    Quorum sensing is a widespread phenomenon in prokaryotes that helps them to communicate among themselves and with eukaryotes. It is driven through quorum sensing signaling molecules (QSSMs) in a density dependent manner that assists in numerous biological functions like biofilm formation, virulence factors secretion, swarming motility, bioluminescence, etc. Despite immense implications, dedicated resources of QSSMs are lacking. Therefore, we have developed SigMol (http://bioinfo.imtech.res.in/manojk/sigmol), a specialized repository of these molecules in prokaryotes. SigMol harbors information on QSSMs pertaining to different quorum sensing signaling systems namely acylated homoserine lactones (AHLs), diketopiperazines (DKPs), 4-hydroxy-2-alkylquinolines (HAQs), diffusible signal factors (DSFs), autoinducer-2 (AI-2) and others. Database contains 1382: entries of 182: unique signaling molecules from 215: organisms. It encompasses biological as well as chemical aspects of signaling molecules. Biological information includes genes, preliminary bioassays, identification assays and applications, while chemical detail comprises of IUPAC name, SMILES and structure. We have provided user-friendly browsing and searching facilities for easy data retrieval and comparison. We have gleaned information of diverse QSSMs reported in literature at a single platform 'SigMol'. This comprehensive resource will assist the scientific community in understanding intraspecies, interspecies or interkingdom networking and further help to unfold different facets of quorum sensing and related therapeutics.

  11. Trends in M2M Application Services Based on a Smart Phone

    NASA Astrophysics Data System (ADS)

    Ahn, Jae Young; Song, Jae-Gu; Hwang, Dae-Joon; Kim, Seoksoo

    M2M, which stands for communications between machines, offers various services today thanks to advanced communication networks and sensor systems. Also, a powerful terminal such as a smart phone provides sufficient physical environments, not requiring a special device for the services. However, the smart phone M2M environment involves various complex technologies, and there have been no clear policies or standards for the technology. This study, therefore, analyzes the current status of M2M service introduction and the trends in M2M application services using a smart phone.

  12. MicroRNA-720 suppresses M2 macrophage polarization by targeting GATA3.

    PubMed

    Zhong, Yan; Yi, Chun

    2016-08-01

    Macrophages are highly plastic cells with the ability to differentiate into both M1- and M2-polarized phenotypes. As a distinct M2-polarized population, tumour-associated macrophages (TAMs) promote tumorigenesis owing to their pro-angiogenic and immune-suppressive functions in tumour microenvironment. In the present study, we found that the microRNA-720 (miR-720) was down-regulated in TAMs isolated from breast carcinomas and M2-polarization macrophages. Overexpression of miR-720 attenuated M2 phenotype expression and thus inhibited M2 polarization. We further identified GATA binding protein 3 (GATA3), a transcriptional factor that plays an important role in M2 macrophage polarization, was the downstream target of miR-720 Ectopic expression of GATA3 restored the M2 phenotype in miR-720 overexpressed macrophages. Importantly, overexpression of miR-720 inhibited pro-migration behaviour and phagocytic ability of M2-polarized macrophages. Thus, our data suggest that miR-720 plays an important role in regulating M2 macrophage polarization and function.

  13. MicroRNA-720 suppresses M2 macrophage polarization by targeting GATA3

    PubMed Central

    Zhong, Yan; Yi, Chun

    2016-01-01

    Macrophages are highly plastic cells with the ability to differentiate into both M1- and M2-polarized phenotypes. As a distinct M2-polarized population, tumour-associated macrophages (TAMs) promote tumorigenesis owing to their pro-angiogenic and immune-suppressive functions in tumour microenvironment. In the present study, we found that the microRNA-720 (miR-720) was down-regulated in TAMs isolated from breast carcinomas and M2-polarization macrophages. Overexpression of miR-720 attenuated M2 phenotype expression and thus inhibited M2 polarization. We further identified GATA binding protein 3 (GATA3), a transcriptional factor that plays an important role in M2 macrophage polarization, was the downstream target of miR-720. Ectopic expression of GATA3 restored the M2 phenotype in miR-720 overexpressed macrophages. Importantly, overexpression of miR-720 inhibited pro-migration behaviour and phagocytic ability of M2-polarized macrophages. Thus, our data suggest that miR-720 plays an important role in regulating M2 macrophage polarization and function. PMID:27354564

  14. Protection against Influenza A Virus Challenge with M2e-Displaying Filamentous Escherichia coli Phages

    PubMed Central

    Deng, Lei; Ibañez, Lorena Itatí; Van den Bossche, Veronique; Roose, Kenny; Youssef, Sameh A.; de Bruin, Alain; Fiers, Walter; Saelens, Xavier

    2015-01-01

    Human influenza viruses are responsible for annual epidemics and occasional pandemics that cause severe illness and mortality in all age groups worldwide. Matrix protein 2 (M2) of influenza A virus is a tetrameric type III membrane protein that functions as a proton-selective channel. The extracellular domain of M2 (M2e) is conserved in human and avian influenza A viruses and is being pursued as a component for a universal influenza A vaccine. To develop a M2e vaccine that is economical and easy to purify, we genetically fused M2e amino acids 2–16 to the N-terminus of pVIII, the major coat protein of filamentous bacteriophage f88. We show that the resulting recombinant f88−M2e2-16 phages are replication competent and display the introduced part of M2e on the phage surface. Immunization of mice with purified f88−M2e2-16 phages in the presence of incomplete Freund’s adjuvant, induced robust M2e-specific serum IgG and protected BALB/c mice against challenge with human and avian influenza A viruses. Thus, replication competent filamentous bacteriophages can be used as efficient and economical carriers to display conserved B cell epitopes of influenza A. PMID:25973787

  15. 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.

  16. Doxycycline inhibits polarization of macrophages to the proangiogenic M2-type and subsequent neovascularization.

    PubMed

    He, Lizhi; Marneros, Alexander G

    2014-03-21

    Macrophages occur along a continuum of functional states between M1-type polarized macrophages with antiangiogenic and antitumor activity and M2-type polarized macrophages, which have been implicated to promote angiogenesis and tumor growth. Proangiogenic M2-type macrophages promote various pathologic conditions, including choroidal neovascularization in models of neovascular age-related macular degeneration, or certain cancers, such as glioblastoma multiforme. Thus, a potential novel therapeutic approach to target pathological angiogenesis in these conditions would be to inhibit the polarization of macrophages toward the proangiogenic M2-type. However, no pharmacological inhibitors of M2-type macrophage polarization have been identified yet. Here we performed an unbiased pharmacological and small chemical screen to identify drugs that inhibit proangiogenic M2-type macrophage polarization and block pathologic macrophage-driven neovascularization. We identified the well tolerated and commonly used antibiotic doxycycline as a potent inhibitor of M2-type polarization of macrophages. Doxycycline inhibited, in a dose-dependent manner, M2-type polarization of human and bone marrow-derived mouse macrophages without affecting cell viability. Furthermore, doxycycline inhibited M2-type macrophage polarization and subsequent neovascularization in vivo in a laser injury model of choroidal neovascularization. Thus, doxycycline could be used to enhance current antiangiogenic treatment approaches in various conditions that are promoted by proangiogenic M2-type macrophages, including neovascular age-related macular degeneration and certain cancers.

  17. 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

  18. Optimized anisotropic magnetoelectric response of Fe61.6Co16.4Si10.8B11.2/PVDF/Fe61.6Co16.4Si10.8B11.2 laminates for AC/DC magnetic field sensing

    NASA Astrophysics Data System (ADS)

    Reis, S.; Silva, M. P.; Castro, N.; Correia, V.; Gutierrez, J.; Lasheras, A.; Lanceros-Mendez, S.; Martins, P.

    2016-05-01

    The anisotropic magnetoelectric (ME) effect on a Fe61.6Co16.4Si10.8B11.2/PVDF Fe61.6Co16.4Si10.8B11.2 laminate composite has been used for the development of a magnetic field sensor able to detect both the magnitude and direction of AC and DC magnetic fields. The accuracy (99% for both AC and DC sensors), linearity (92% for the DC sensor and 99% for the AC sensor) and reproducibility (99% for both sensors) indicate the suitability of the sensor for applications. Furthermore, the sensitivity of the Fe61.6Co16.4Si10.8B11.2/PVDF/Fe61.6Co16.4Si10.8B11.2 anisotropic magnetic sensor—15 and 1400 mV Oe-1 for the DC and AC fields, respectively—are the highest reported in the literature for polymer-based ME materials. Such features, combined with its flexibility, versatility, light weight, low cost and low-temperature fabrication, lead to the suitability of the developed sensor for use in magnetic sensor applications.

  19. Phase Equilibrium Study of ZnO-"FeO"-SiO2 System at Fixed Po2 10-8 atm

    NASA Astrophysics Data System (ADS)

    Liu, Hongquan; Cui, Zhixiang; Chen, Mao; Zhao, Baojun

    2016-02-01

    Experimental studies of phase equilibria and liquidus temperatures have been carried out in the systems "FeO"-SiO2 and ZnO-"FeO"-SiO2 at Po2 10-8 atm. Research techniques have been developed to enable the ZnO-containing system to be investigated under reducing conditions controlled by CO-CO2 gas mixture. The experimental approach includes master slag preparation, high-temperature equilibration, quench, and electron probe X-ray microanalysis (EPMA). Phase compositions in the quenched samples were measured by EPMA and used for construction of phase diagram. It was found that the isotherms of the system ZnO-"FeO"-SiO2 at Po2 10-8 atm are significantly different from those in equilibrium with metallic iron and those predicted by FactSage. The presence of ZnO in copper smelting slag significantly increases the liquidus temperature in spinel primary phase field. Partitioning of ZnO in liquid and spinel is also discussed in this paper.

  20. 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…

  1. A Study on M2M-based System for Hygienic Meteorology Service

    NASA Astrophysics Data System (ADS)

    Song, Jae-Gu; Ahn, Jae Young; Kim, Seoksoo

    M2M proposes a standardized communications technology between network and devices. This study has designed an M2M-based system to smoothly deliver information between devices which were required to provide hygienic meteorology services. Especially, an efficient plan for service provision has been studied, by classifying the types of information at each stage of user, EM, SM, HSM and SPM.

  2. Identity Crisis: CD301b(+) Mononuclear Phagocytes Blur the M1-M2 Macrophage Line.

    PubMed

    Knudsen, Nelson H; Lee, Chih-Hao

    2016-09-20

    Obesity shifts the immune phenotype from M2 macrophage polarization to M1, which causes metabolic dysfunction. In this issue of Immunity, Kumamoto et al. (2016) identify a tissue-resident mononuclear phagocyte population that promotes weight gain and glucose intolerance but are defined by the M2 marker CD301b. PMID:27653596

  3. Cyclooxygenase-2 inhibition attenuates hypoxic cancer cells induced m2-polarization of macrophages.

    PubMed

    Dubey, P; Shrivastava, R; Tripathi, C; Jain, N K; Tewari, B N; Lone, M-U-D; Baghel, K S; Kumar, V; Misra, S; Bhadauria, S; Bhatt, M L B

    2014-09-12

    Tumor-associated macrophages (TAMs), represent a major subpopulation of tumor infiltrating immune cells. These alternatively activated M2-polarized macrophages are well known for their pro-tumor functions. Owing to their established role in potentiating tumor-neovasculogenesis and metastasis, TAMs have emerged as promising target for anti-cancer immunotherapy. One of the key TAMs related phenomenon that is amenable to therapeutic intervention is their phenotype switching into alternatively activated M2-polarized macrophages. Hindering macrophage polarization towards a pro-tumor M2 phenotype, or better still reprogramming the M2 like TAMs towards M1 subtype is being considered a beneficial anti-cancer strategy. Hypoxic tumor milieu has been proposed as one of the most plausible factor governing M2-polarization of macrophages. We recently demonstrated that hypoxic tumor cells imparted a pro—angiogenic M2 skewed phenotype to macrophages. Furthermore, sizeable body of data indicates for participation of cyclooxygenase-2 (COX-2) in macrophage polarization. Concordantly, inhibition of COX-2 is associated with impaired macrophage polarization. Prompted by this in the current study we decided to explore if inhibition of COX-2 activity via chemical inhibitors may prevent hypoxic cancer cell induced M2-polarization of macrophages. We observed that treatment with Flunixin meglumine, an established preferential inhibitor of COX-2 activity markedly inhibited hypoxic cancer cell induced of M2-polarization of macrophages thereby indicating for usage of COX-2 inhibition as possible anti-cancer treatment modality.

  4. Identity Crisis: CD301b(+) Mononuclear Phagocytes Blur the M1-M2 Macrophage Line.

    PubMed

    Knudsen, Nelson H; Lee, Chih-Hao

    2016-09-20

    Obesity shifts the immune phenotype from M2 macrophage polarization to M1, which causes metabolic dysfunction. In this issue of Immunity, Kumamoto et al. (2016) identify a tissue-resident mononuclear phagocyte population that promotes weight gain and glucose intolerance but are defined by the M2 marker CD301b.

  5. Inhibition of Influenza M2-Induced Cell Death Alleviates Its Negative Contribution to Vaccination Efficiency

    PubMed Central

    Ilyinskii, Petr O.; Gambaryan, Alexandra S.; Meriin, Anatoli B.; Gabai, Vladimir; Kartashov, Alex; Thoidis, Galini; Shneider, Alexander M.

    2008-01-01

    The effectiveness of recombinant vaccines encoding full-length M2 protein of influenza virus or its ectodomain (M2e) have previously been tested in a number of models with varying degrees of success. Recently, we reported a strong cytotoxic effect exhibited by M2 on mammalian cells in vitro. Here we demonstrated a decrease in protection when M2 was added to a DNA vaccination regimen that included influenza NP. Furthermore, we have constructed several fusion proteins of conserved genes of influenza virus and tested their expression in vitro and protective potential in vivo. The four-partite NP-M1-M2-NS1 fusion antigen that has M2 sequence engineered in the middle part of the composite protein was shown to not be cytotoxic in vitro. A three-partite fusion protein (consisting of NP, M1 and NS1) was expressed much more efficiently than the four-partite protein. Both of these constructs provided statistically significant protection upon DNA vaccination, with construct NP-M1-M2-NS1 being the most effective. We conclude that incorporation of M2 into a vaccination regimen may be beneficial only when its apparent cytotoxicity-linked negative effects are neutralized. The possible significance of this data for influenza vaccination regimens and preparations is discussed. PMID:18197240

  6. 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…

  7. Notch signaling regulates M2 type macrophage polarization during the development of proliferative vitreoretinopathy.

    PubMed

    Zhang, Jingjing; Zhou, Qingjun; Yuan, Gongqiang; Dong, Muchen; Shi, Weiyun

    2015-01-01

    Macrophages play an important role in the pathogenesis of proliferative vitreoretinopathy (PVR). M2 macrophages can promote tissue remodeling and repair. In this study, CD206 positive M2 type macrophages were found in preretinal fibrous membranes of the mouse model of PVR induced by the intravitreal injection of retinal pigment epithelial (RPE) cells. Notch signaling determines M2 macrophage polarization. The specific inhibition of Notch signaling pathway by the intravitreal injection of γ-secretase inhibitor DAPT attenuated RPE cells-induced PVR formation as demonstrated by the decreased expression of α-SMA, and inhibited M2 type macrophage infiltation as demonstrated by the decreased expression of Arg-1. Notch signaling may modulate PVR formation by regulating M2 type macrophage polarization. PMID:26410397

  8. Bilayer Incorporated Influenza A M2 Single Molecule Time-Dependent AFM Studies

    NASA Astrophysics Data System (ADS)

    Hughes, Travis; Bradley, Strongin; Davis, Robert; Vijayvergiya, Viksita; Busath, David

    2004-03-01

    We report the observation of Influenza A M2 incorporated in a DPPC supported planar bilayer (SPB) on mica, formed by use of a modified vesicle fusion method from proteoliposomes using contact mode Atomic Force Microscopy (AFM). Incubation of proteoliposomes in a hypertonic solution and increased DPPC:M2 weight ratios improved SPB formation by M2/DPPC proteoliposomes. M2's extra-bilayer domains were observed as particles estimated to protrude 1-1.5 nm above the bilayer surface and < 4nm in diameter. Movement of M2 independent of the probe tip was observed with a calculated lateral diffusion coefficient of ˜5 × 10-14cm2/s and a mobile fraction of ˜80%. Protein- protein interaction was also observed.

  9. ExoMol: Molecular Line List for Exoplanets and Other Atmospheres

    NASA Astrophysics Data System (ADS)

    Tennyson, Jonathan; Yurchenko, Sergei N.; Polyansky, Oleg

    2016-06-01

    The discovery of extrasolar planets is one of the major scientific advances of the last two decades. Thousands of planets have now been detected and astronomers are beginning to characterize their composition and physical characteristics. To do this requires a huge quantity of spectroscopic data most of which are not available from laboratory studies. The ExoMol project [1] is generating a comprehensive solution to this problem by providing spectroscopic data on all the molecular transitions of importance in the atmospheres of exoplanets. These data are widely applicable to other problems such studies on cool stars, brown dwarfs and circumstellar environments as well as industrial and technological problems on earth. ExoMol employs a mixture of first principles and empirically tuned quantum mechanical methods to compute comprehensive and very large rotation-vibration and rovibronic line lists. Results span a variety of closed (NaH, SiO, PN, NaCl, KCl, CS) and open (BeH, MgH, CaH, AlO, VO) shell diatomics to triatomics (HCN/HNC, SO_2, H_2S, H_3^+), tetratomics (H_2CO, PH_3, SO_3, H_2O_2), plus methane [2] and nitric acid [3]. This has led directly to the detection of new species in the atmospheres of exoplanets [4]. A new comprehensive data release has just been completed [5]. Progress on and future prospects of the project will be summarised. J. Tennyson, S. N. Yurchenko, Mon. Not. R. astr. Soc., 425, 21, 2012. S. N. Yurchenko, J. Tennyson, J. Bailey, M. D. J. Hollis, G Tinetti, Proc. Nat. Acad. Sci., 111, 9379, 2014. A. I. Pavlyuchko, S. N. Yurchenko, J. Tennyson, Mon. Not. R. astr. Soc., 452, 1702, 2015. A. Tsiaras et al, Astrophys. J., in press. J. Tennyson et al, J. Mol. Spectrosc., in press.

  10. VizieR Online Data Catalog: ExoMol line list for KCl (Barton+, 2014)

    NASA Astrophysics Data System (ADS)

    Barton, E. J.; Chui, C.; Golpayegani, S.; Yurchenko, S. N.; Tennyson, J.; Frohman, D. J.; Bernath, P. F.

    2014-03-01

    The files comprising this line list are in the standard ExoMol format, and are named sXXkYYcl.dat and tXXkYYcl.dat, where XX and YY are the mass numbers of the potassium and chlorine isotopes, respectively. The isotopologues covered are: (39K)(35Cl), (39K)(37Cl), (41K)(35Cl) and (41K)(37Cl). The partition functions from 1-3000K in 1K intervals for these isotopologues of KCl are also provided in files named pXXkYYcl.dat and consist of two columns (T/K followed by Q). (12 data files).

  11. Classification moléculaire du cancer du sein au Maroc

    PubMed Central

    Fouad, Abbass; Yousra, Akasbi; Kaoutar, Znati; Omar, El Mesbahi; Afaf, Amarti; Sanae, Bennis

    2012-01-01

    Introduction La classification moléculaire des cancers du sein basée sur l'expression génique puis sur le profil protéique a permis de distinguer cinq groupes moléculaires: luminal A, luminal B, Her2/neu, basal-like et non-classées. L'objectif de cette étude réalisée au CHU Hassan II de Fès est de classer 335 cancers du sein infiltrant en groupes moléculaires, puis de les corréler avec les caractéristiques clinicopathologiques. Méthodes Etude rétrospective étalée sur 45 mois, comportant 335 patientes colligées au CHU pour le diagnostic et le suivi. Les tumeurs sont analysées histologiquement et classées après une étude immunohistochimique en groupes: luminal A, luminal B, Her2+, basal-like et non-classées. Résultats 54.3% des tumeurs sont du groupe luminal A, 16% luminal B, 11.3% Her2+, 11.3% basal-like et 7% non-classées. Le groupe luminal A renferme le plus faible taux de grade III, d'emboles vasculaires ainsi que de métastases; alors que le groupe des non-classées et basal-like représentent un taux élevé de grade III, une faible proportion d'emboles vasculaires et d'envahissement ganglionnaire. Ces facteurs sont significativement élevés dans les groupes luminal B et Her2+ avec un taux de survie globale de 78% et 76% respectivement. Dans le groupe luminal A, la survie globale des patientes est élevée (87%) alors qu'elle n'est que de 49% dans le groupe des triples négatifs (basal-like et non-classés). Conclusion Le groupe luminal B est différent du luminal A et il est de pronostic péjoratif vis à vis du groupe Her2+. Les caractéristiques clinicopathologiques concordent avec le profil moléculaire donc devraient être pris en considération comme facteurs pronostiques. PMID:23396646

  12. Moléculas orgánicas obtenidas en simulaciones experimentales del medio interestelar.

    NASA Astrophysics Data System (ADS)

    Muñoz-Caro, Guillermo Manuel

    Las nubes moleculares son regiones de formación de estrellas, con temperaturas cinéticas entre 10-50 K y densidades de 103-106 átomos cm-3. Su materia está formada por gas y polvo interestelar. Estas partículas de polvo están cubiertas por una fina capa de hielo, de unos 0.01 μm, que contiene H2O y a menudo CO, CO2, CH3OH y NH3. El hielo es presumiblemente irradiado por fotones ultravioleta y rayos cósmicos en las zonas poco profundas de las nubes moleculares y las regiones circunestelares. En un sistema de vacío, P ˜ 10-7 mbar, simulamos la deposición de hielo a partir de 10 K y la irradiación ultravioleta por medio de una lámpara de descarga de hidrógeno activada con microondas. La evolución del hielo se observa por medio de un espectrómetro infrarrojo. De este modo es posible determinar la composición del hielo observado en el medio interestelar y predecir la presencia de moléculas aún no detectadas en el espacio, que han sido producto del procesamiento del hielo en nuestros experimentos. También es posible calentar el sistema hasta temperatura ambiente para sublimar el hielo depositado. Cuando el hielo ha sido previamente irradiado, se observa un residuo compuesto por moléculas orgánicas complejas, algunas prebióticas, como varios ácidos carboxílicos, aminas, amidas, ésteres y en menor proporción moléculas heterocíclicas y aminoácidos. Algunas de estas moléculas podrían detectarse en estado gaseoso por medio de observaciones milimétricas y de radio. También podrían estar presentes en el polvo cometario, cuyo análisis químico está planeado por las misiones Stardust y Rosetta. Mientras tanto, nuestro grupo está llevando a cabo el análisis de partículas de polvo interplanetario (IDPs), algunas de las cuales pueden ser de origen cometario. Al igual que ocurre con los productos obtenidos por irradiación del hielo en nuestros experimentos, algunas IDPs son ricas en material orgánico que contiene oxígeno.

  13. [Characterization of M2 gene of H3N2 subtype swine influenza virus].

    PubMed

    Wang, Xiaodu; Chen, Peijun; Shen, Yang; Qiu, Yafeng; Deng, Xufang; Shi, Zixue; Peng, Lina; Luo, Jinyan; Liu, Chao; Ma, Zhiyong

    2010-01-01

    M2 protein of influenza A virus is encoded by a spliced mRNA derived from RNA segment 7 and plays an important role in influenza virus replication. It is also a target molecule of anti-virus drugs. We extracted the viral genome RNAs from MDCK cells infected with swine influenza A virus (SIV) H3N2 subtype and amplified the SIV M2 gene by reverse transcriptase-polymerase chain reaction using the isloated viral genome RNAs as template. The amplified cDNA was cloned into a prokaryotic expression vector pET-28a(+) (designated pET-28a(+)-M2) and a eukaryotic expression vector p3xFLAG-CMV-7.1 (designated p3xFLAG-CMV-7.1-M2), respectively. The resulted constructs were confirmed by restriction enzyme digestion and DNA sequencing analysis. We then transformed the plasmid pET-28a(+)-M2 into Escherichia coli BL21 (DE3) strain and expressed it by adding 1 mmol/L of IPTG (isopropyl-beta-D-thiogalactopyranoside). The recombinant M2 protein was purified from the induced bacterial cells using Ni(2+) affinity chromatography. Wistar rats were immunized with the purified M2 protein for producing polyclonal antibodies specific for it. Western blotting analysis and immunofluorescence analysis showed that the produced antibodies were capable of reacting with M2 protein expressed in p3xFLAG-CMV-7.1-M2-transfected cells as well as that synthesized in SIV-infected cells. We also transfected plasmid p3xFLAG-CMV-7.1-M2 into Vero cells and analyzed its subcellular localization by immunofluorescence. The M2 protein expressed in the Vero cells was 20 kDa in size and dominantly localized in the cytoplasm, showing a similar distribution to that in SIV-infected cells. Western blotting analysis of SIV-infected cells suggested that M2 was a late phase protein, which was detectable 12 h post-infection, later than NS1, NP and M1 proteins. It would be a potential molecular indicator of late phases replication of virus. Our results would be useful for studying the biological function of M2 protein in SIV

  14. Ionization of Au{sup 78+} and electron capture by Au{sup 79+} at 10.8 GeV/nucleon

    SciTech Connect

    Claytor, N.; Belkacem, A.; Dinneen, T.; Feinberg, B.; Gould, H.

    1997-02-01

    We have measured the cross sections for ionizating one-electron Au{sup 78+} and the total cross sections for electron capture by bare Au{sup 79+} at 10.8 GeV/nucleon in C, Al, Cu, Ag, and Au targets. We made the measurement by magnetically separating the charge states and measuring the fraction of Au{sup 78+} as a function of target thickness for each element. In contrast to the results reported by Westphal and He [Phys. Rev. Lett. {bold 71}, 1160 (1993)], our ionization measurements agree with the calculation of Anholt and Becker [Phys. Rev. A {bold 36}, 4628 (1987)]. Our capture cross-section measurements are in agreement with theory for those targets where radiative electron capture is the dominant capture process. {copyright} {ital 1997} {ital The American Physical Society}

  15. 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

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

    PubMed

    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

  17. A unique role for p53 in the regulation of M2 macrophage polarization.

    PubMed

    Li, L; Ng, D S W; Mah, W-C; Almeida, F F; Rahmat, S A; Rao, V K; Leow, S C; Laudisi, F; Peh, M T; Goh, A M; Lim, J S Y; Wright, G D; Mortellaro, A; Taneja, R; Ginhoux, F; Lee, C G; Moore, P K; Lane, D P

    2015-07-01

    P53 is critically important in preventing oncogenesis but its role in inflammation in general and in the function of inflammatory macrophages in particular is not clear. Here, we show that bone marrow-derived macrophages exhibit endogenous p53 activity, which is increased when macrophages are polarized to the M2 (alternatively activated macrophage) subtype. This leads to reduced expression of M2 genes. Nutlin-3a, which destabilizes the p53/MDM2 (mouse double minute 2 homolog) complex, promotes p53 activation and further downregulates M2 gene expression. In contrast, increased expression of M2 genes was apparent in M2-polarized macrophages from p53-deficient and p53 mutant mice. Furthermore, we show, in mice, that p53 also regulates M2 polarization in peritoneal macrophages from interleukin-4-challenged animals and that nutlin-3a retards the development of tolerance to Escherichia coli lipopolysaccharide. P53 acts via transcriptional repression of expression of c-Myc (v-myc avian myelocytomatosis viral oncogene homolog) gene by directly associating with its promoter. These data establish a role for the p53/MDM2/c-MYC axis as a physiological 'brake' to the M2 polarization process. This work reveals a hitherto unknown role for p53 in macrophages, provides further insight into the complexities of macrophage plasticity and raises the possibility that p53-activating drugs, many of which are currently being trialled clinically, may have unforeseen effects on macrophage function. PMID:25526089

  18. 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.

  19. A unique role for p53 in the regulation of M2 macrophage polarization.

    PubMed

    Li, L; Ng, D S W; Mah, W-C; Almeida, F F; Rahmat, S A; Rao, V K; Leow, S C; Laudisi, F; Peh, M T; Goh, A M; Lim, J S Y; Wright, G D; Mortellaro, A; Taneja, R; Ginhoux, F; Lee, C G; Moore, P K; Lane, D P

    2015-07-01

    P53 is critically important in preventing oncogenesis but its role in inflammation in general and in the function of inflammatory macrophages in particular is not clear. Here, we show that bone marrow-derived macrophages exhibit endogenous p53 activity, which is increased when macrophages are polarized to the M2 (alternatively activated macrophage) subtype. This leads to reduced expression of M2 genes. Nutlin-3a, which destabilizes the p53/MDM2 (mouse double minute 2 homolog) complex, promotes p53 activation and further downregulates M2 gene expression. In contrast, increased expression of M2 genes was apparent in M2-polarized macrophages from p53-deficient and p53 mutant mice. Furthermore, we show, in mice, that p53 also regulates M2 polarization in peritoneal macrophages from interleukin-4-challenged animals and that nutlin-3a retards the development of tolerance to Escherichia coli lipopolysaccharide. P53 acts via transcriptional repression of expression of c-Myc (v-myc avian myelocytomatosis viral oncogene homolog) gene by directly associating with its promoter. These data establish a role for the p53/MDM2/c-MYC axis as a physiological 'brake' to the M2 polarization process. This work reveals a hitherto unknown role for p53 in macrophages, provides further insight into the complexities of macrophage plasticity and raises the possibility that p53-activating drugs, many of which are currently being trialled clinically, may have unforeseen effects on macrophage function.

  20. Data structures for ExoMol: Molecular line lists for exoplanet and other atmospheres

    NASA Astrophysics Data System (ADS)

    Tennyson, Jonathan; Hill, Christian; Yurchenko, Sergei N.

    2013-07-01

    At elevated temperatures the spectra of polyatomic molecules become extremely complicated with millions, or even billions, of transitions potentially playing an important role. The atmospheres of cool stars and "hot Jupiter" extrasolar planets are rich with molecules in the temperature range 1000 to 3000 K and their properties are strongly influenced by the infrared and visible spectra of these molecules. Access to extensive lists of transitions is essential for interpreting even the rather simple spectra that can be obtained from exoplanets. So far there are extensive, reliable lists of spectral lines for a number species including some stable diatomics, water and ammonia. Data are almost completely lacking for many key species such as methane. The ExoMol project aims to construct line lists of molecular transitions suitable for spectroscopic and atmospheric modelling of cool stars and exoplanets. At high temperatures it is necessary to consider huge numbers of lines even for a single species. Examples of line lists are given; data protocols defined and data handling issues which arise from trying to distribute these huge datasets discussed. In particular, a uniform but flexible format is given for the representation of line lists and cross sections resulting from the ExoMol project.

  1. MolProbity’s Ultimate Rotamer-Library Distributions for Model Validation

    PubMed Central

    Hintze, Bradley J.; Lewis, Steven M.; Richardson, Jane S.; Richardson, David C.

    2016-01-01

    Here we describe the updated MolProbity rotamer-library distributions derived from an order-of-magnitude larger and more stringently quality-filtered dataset of about 8000 (vs. 500) protein chains, and we explain the resulting changes and improvements to model validation as seen by users. To include only sidechains with satisfactory justification for their given conformation, we added residue-specific filters for electron-density value and model-to-density fit. The combined new protocol retains a million residues of data, while cleaning up false-positive noise in the multi-χ datapoint distributions. It enables unambiguous characterization of conformational clusters nearly 1000-fold less frequent than the most common ones. We describe examples of local interactions that favor these rare conformations, including the role of authentic covalent bond-angle deviations in enabling presumably strained sidechain conformations. Further, along with favored and outlier, an allowed category (0.3% to 2.0% occurrence in reference data) has been added, analogous to Ramachandran validation categories. The new rotamer distributions are used for current rotamer validation in Mol-Probity and PHENIX, and for rotamer choice in PHENIX model-building and refinement. The multi-dimensional χ distributions and Top8000 reference dataset are freely available on GitHub. These rotamers are termed “ultimate” because data sampling and quality are now fully adequate for this task, and also because we believe the future of conformational validation should integrate sidechain with backbone criteria. PMID:27018641

  2. SigMol: repertoire of quorum sensing signaling molecules in prokaryotes

    PubMed Central

    Rajput, Akanksha; Kaur, Karambir; Kumar, Manoj

    2016-01-01

    Quorum sensing is a widespread phenomenon in prokaryotes that helps them to communicate among themselves and with eukaryotes. It is driven through quorum sensing signaling molecules (QSSMs) in a density dependent manner that assists in numerous biological functions like biofilm formation, virulence factors secretion, swarming motility, bioluminescence, etc. Despite immense implications, dedicated resources of QSSMs are lacking. Therefore, we have developed SigMol (http://bioinfo.imtech.res.in/manojk/sigmol), a specialized repository of these molecules in prokaryotes. SigMol harbors information on QSSMs pertaining to different quorum sensing signaling systems namely acylated homoserine lactones (AHLs), diketopiperazines (DKPs), 4-hydroxy-2-alkylquinolines (HAQs), diffusible signal factors (DSFs), autoinducer-2 (AI-2) and others. Database contains 1382 entries of 182 unique signaling molecules from 215 organisms. It encompasses biological as well as chemical aspects of signaling molecules. Biological information includes genes, preliminary bioassays, identification assays and applications, while chemical detail comprises of IUPAC name, SMILES and structure. We have provided user-friendly browsing and searching facilities for easy data retrieval and comparison. We have gleaned information of diverse QSSMs reported in literature at a single platform ‘SigMol’. This comprehensive resource will assist the scientific community in understanding intraspecies, interspecies or interkingdom networking and further help to unfold different facets of quorum sensing and related therapeutics. PMID:26490957

  3. 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.

  4. 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.

  5. Investigation of M2 factor influence for paraxial computer generated hologram reconstruction using a statistical method

    NASA Astrophysics Data System (ADS)

    Flury, M.; Gérard, P.; Takakura, Y.; Twardworski, P.; Fontaine, J.

    2005-04-01

    In this paper, we study the influence of the M2 quality factor of an incident beam on the reconstruction performance of a computer generated hologram (CGH). We use a statistical method to analyze the evolution of different quality criteria such as diffraction efficiency, root mean square error, illumination uniformity or correlation coefficient calculated in the numerical reconstruction versus the increasing M2 quality factor. The simulation results show us that this factor must always be taken into account in the CGH design when the M2 value is bigger than 2.

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

    PubMed

    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. PMID:9636297

  7. From a 32 m2 system with 90 CPV modules to a 105 m2 system with 12 CPV modules - Soitec's new CPV system CX-S530

    NASA Astrophysics Data System (ADS)

    Gombert, Andreas; Wanka, Sven; Gerster, Eckart; van Riesen, Sascha; Neubauer, Martin; Lange, Gerrit; Hamidi, Amir; Burke, Thomas; Stör, Jakob; Aipperspach, Wolfgang; Taliercio, Cecile; Mader, Lucas; Valli, Alessandro; Ziegler, Martin; Hepp, Stefan; Heile, Inka; Gerstmaier, Tobias; Haarburger, Karl-Friedrich

    2012-10-01

    In 2008, Soitec started to launch a 32m2 CPV system which included 90 modules per tracker. In order to realize the fast installation of multi-MW power plants the CPV module CX-M500 with an aperture area of 7,84 m2 was developed together with the new tracker CX-T030 which is optimized for carrying 12 of the new modules. This paper gives an overview over the evolution of this CPV system. The module is based on components of the field proven earlier Concentrix module generations. The tracker is a classical pylon type with two AC motor powered slewing ring drives. A new control device was developed which uses the power-optimized sun tracking algorithm. The major development steps and their results are presented.

  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. 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.

  10. 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

  11. 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.

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

    PubMed

    Ten Hoopen, Petra; Pesant, Stéphane; Kottmann, Renzo; Kopf, Anna; Bicak, Mesude; Claus, Simon; Deneudt, Klaas; Borremans, Catherine; Thijsse, Peter; Dekeyzer, Stefanie; Schaap, Dick Ma; Bowler, Chris; Glöckner, Frank Oliver; Cochrane, Guy

    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 7(th) 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.

  13. Trypsin, Tryptase, and Thrombin Polarize Macrophages towards a Pro-Fibrotic M2a Phenotype

    PubMed Central

    White, Michael J. V.; Gomer, Richard H.

    2015-01-01

    For both wound healing and the formation of a fibrotic lesion, circulating monocytes enter the tissue and differentiate into fibroblast-like cells called fibrocytes and pro-fibrotic M2a macrophages, which together with fibroblasts form scar tissue. Monocytes can also differentiate into classically activated M1 macrophages and alternatively activated M2 macrophages. The proteases thrombin, which is activated during blood clotting, and tryptase, which is released by activated mast cells, potentiate fibroblast proliferation and fibrocyte differentiation, but their effect on macrophages is unknown. Here we report that thrombin, tryptase, and the protease trypsin bias human macrophage differentiation towards a pro-fibrotic M2a phenotype expressing high levels of galectin-3 from unpolarized monocytes, or from M1 and M2 macrophages, and that these effects appear to operate through protease-activated receptors. These results suggest that proteases can initiate scar tissue formation by affecting fibroblasts, fibrocytes, and macrophages. PMID:26407067

  14. M2 Polarization of Human Macrophages Favors Survival of the Intracellular Pathogen Chlamydia pneumoniae.

    PubMed

    Buchacher, Tanja; Ohradanova-Repic, Anna; Stockinger, Hannes; Fischer, Michael B; Weber, Viktoria

    2015-01-01

    Intracellular pathogens have developed various strategies to escape immunity to enable their survival in host cells, and many bacterial pathogens preferentially reside inside macrophages, using diverse mechanisms to penetrate their defenses and to exploit their high degree of metabolic diversity and plasticity. Here, we characterized the interactions of the intracellular pathogen Chlamydia pneumoniae with polarized human macrophages. Primary human monocytes were pre-differentiated with granulocyte macrophage colony-stimulating factor or macrophage colony-stimulating factor for 7 days to yield M1-like and M2-like macrophages, which were further treated with interferon-γ and lipopolysaccharide or with interleukin-4 for 48 h to obtain fully polarized M1 and M2 macrophages. M1 and M2 cells exhibited distinct morphology with round or spindle-shaped appearance for M1 and M2, respectively, distinct surface marker profiles, as well as different cytokine and chemokine secretion. Macrophage polarization did not influence uptake of C. pneumoniae, since comparable copy numbers of chlamydial DNA were detected in M1 and M2 at 6 h post infection, but an increase in chlamydial DNA over time indicating proliferation was only observed in M2. Accordingly, 72±5% of M2 vs. 48±7% of M1 stained positive for chlamydial lipopolysaccharide, with large perinuclear inclusions in M2 and less clearly bordered inclusions for M1. Viable C. pneumoniae was present in lysates from M2, but not from M1 macrophages. The ability of M1 to restrict chlamydial replication was not observed in M1-like macrophages, since chlamydial load showed an equal increase over time for M1-like and M2-like macrophages. Our findings support the importance of macrophage polarization for the control of intracellular infection, and show that M2 are the preferred survival niche for C. pneumoniae. M1 did not allow for chlamydial proliferation, but failed to completely eliminate chlamydial infection, giving further evidence

  15. Development of live attenuated Bordetella pertussis strains expressing the universal influenza vaccine candidate M2e.

    PubMed

    Li, Rui; Lim, Annabelle; Ow, Stephanie T L; Phoon, Meng Chee; Locht, Camille; Chow, Vincent T; Alonso, Sylvie

    2011-07-26

    The attenuated Bordetella pertussis BPZE1 vaccine strain represents an attractive platform for the delivery of heterologous vaccine candidates via the nasal route. The filamentous hemagglutinin (FHA) has been used to secrete or expose the foreign antigens at the bacterial surface. In this study, one, two and three copies of the Cys-containing ectodomain of matrix protein 2 (M2e) from influenza A virus were genetically fused to full length FHA and expressed in BPZE1. The secretion efficacy of the FHA-(M2e)(1,2,3) chimera in the extracellular milieu and the ability of the recombinant bacteria to colonize the mouse lungs inversely correlated with the number of M2e copies fused to FHA. Nevertheless FHA-(M2e)(3)-producing bacteria (BPLR3) triggered the highest systemic anti-M2e antibody response upon nasal administration to BALB/c mice. Nasal immunization with BPLR3 bacteria resulted in a significant reduction in the viral loads upon challenge with H1N1/PR8 influenza A virus, but did not improve the survival rate compared to BPZE1-immunized mice. Furthermore, since previous work reported that disulfide bond formation in Cys-containing passenger antigens affects the secretion efficacy of the FHA chimera, the dsbA gene encoding a periplasmic disulfide isomerase was deleted in the FHA-(M2e)(3)-producing strain. Despite improving significantly the secretion efficacy of the FHA-(M2e)(3) chimera, the dsbA deletion did not result in higher anti-M2e antibody titers in mice, due to impaired bacterial fitness and colonization ability.

  16. Fourier transform infrared double-flash experiments resolve bacteriorhodopsin's M1 to M2 transition.

    PubMed Central

    Hessling, B; Herbst, J; Rammelsberg, R; Gerwert, K

    1997-01-01

    The orientation of the central proton-binding site, the protonated Schiff base, away from the proton release side to the proton uptake side is crucial for the directionality of the proton pump bacteriorhodopsin. It has been proposed that this movement, called the reprotonation switch, takes place in the M1 to M2 transition. To resolve the molecular events in this M1 to M2 transition, we performed double-flash experiments. In these experiments a first pulse initiates the photocycle and a second pulse selectively drives bR molecules in the M intermediate back into the BR ground state. For short delay times between initiating and resetting pulses, most of the M molecules being reset are in the M1 intermediate, and for longer delay times most of the reset M molecules are in the M2 intermediate. The BR-M1 and BR-M2 difference spectra are monitored with nanosecond step-scan Fourier transform infrared spectroscopy. Because the Schiff base reprotonation rate is kM1 = 0.8 x 10(7) s(-1) in the light-induced M1 back-reaction and kM2 = 0.36 x 10(7) s(-1) in the M2 back-reaction, the two different M intermediates represent two different proton accessibility configurations of the Schiff base. The results show only a minute movement of one or two peptide bonds in the M1 to M2 transition that changes the interaction of the Schiff base with Y185. This backbone movement is distinct from the larger one in the subsequent M to N transition. No evidence of a chromophore isomerization is seen in the M1 to M2 transition. Furthermore, the results show time-resolved reprotonation of the Schiff base from D85 in the M photo-back-reaction, instead of from D96, as in the conventional cycle. Images Scheme 2 PMID:9336202

  17. 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

  18. Immunization with the MAEBL M2 Domain Protects against Lethal Plasmodium yoelii Infection.

    PubMed

    Leite, Juliana A; Bargieri, Daniel Y; Carvalho, Bruna O; Albrecht, Letusa; Lopes, Stefanie C P; Kayano, Ana Carolina A V; Farias, Alessandro S; Chia, Wan Ni; Claser, Carla; Malleret, Benoit; Russell, Bruce; Castiñeiras, Catarina; Santos, Leonilda M B; Brocchi, Marcelo; Wunderlich, Gerhard; Soares, Irene S; Rodrigues, Mauricio M; Rénia, Laurent; Costa, Fabio T M

    2015-10-01

    Malaria remains a world-threatening disease largely because of the lack of a long-lasting and fully effective vaccine. MAEBL is a type 1 transmembrane molecule with a chimeric cysteine-rich ectodomain homologous to regions of the Duffy binding-like erythrocyte binding protein and apical membrane antigen 1 (AMA1) antigens. Although MAEBL does not appear to be essential for the survival of blood-stage forms, ectodomains M1 and M2, homologous to AMA1, seem to be involved in parasite attachment to erythrocytes, especially M2. MAEBL is necessary for sporozoite infection of mosquito salivary glands and is expressed in liver stages. Here, the Plasmodium yoelii MAEBL-M2 domain was expressed in a prokaryotic vector. C57BL/6J mice were immunized with doses of P. yoelii recombinant protein rPyM2-MAEBL. High levels of antibodies, with balanced IgG1 and IgG2c subclasses, were achieved. rPyM2-MAEBL antisera were capable of recognizing the native antigen. Anti-MAEBL antibodies recognized different MAEBL fragments expressed in CHO cells, showing stronger IgM and IgG responses to the M2 domain and repeat region, respectively. After a challenge with P. yoelii YM (lethal strain)-infected erythrocytes (IE), up to 90% of the immunized animals survived and a reduction of parasitemia was observed. Moreover, splenocytes harvested from immunized animals proliferated in a dose-dependent manner in the presence of rPyM2-MAEBL. Protection was highly dependent on CD4(+), but not CD8(+), T cells toward Th1. rPyM2-MAEBL antisera were also able to significantly inhibit parasite development, as observed in ex vivo P. yoelii erythrocyte invasion assays. Collectively, these findings support the use of MAEBL as a vaccine candidate and open perspectives to understand the mechanisms involved in protection. PMID:26169268

  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. Immunization with the MAEBL M2 Domain Protects against Lethal Plasmodium yoelii Infection

    PubMed Central

    Leite, Juliana A.; Bargieri, Daniel Y.; Carvalho, Bruna O.; Albrecht, Letusa; Lopes, Stefanie C. P.; Kayano, Ana Carolina A. V.; Farias, Alessandro S.; Chia, Wan Ni; Claser, Carla; Malleret, Benoit; Russell, Bruce; Castiñeiras, Catarina; Santos, Leonilda M. B.; Brocchi, Marcelo; Wunderlich, Gerhard; Soares, Irene S.; Rodrigues, Mauricio M.; Rénia, Laurent

    2015-01-01

    Malaria remains a world-threatening disease largely because of the lack of a long-lasting and fully effective vaccine. MAEBL is a type 1 transmembrane molecule with a chimeric cysteine-rich ectodomain homologous to regions of the Duffy binding-like erythrocyte binding protein and apical membrane antigen 1 (AMA1) antigens. Although MAEBL does not appear to be essential for the survival of blood-stage forms, ectodomains M1 and M2, homologous to AMA1, seem to be involved in parasite attachment to erythrocytes, especially M2. MAEBL is necessary for sporozoite infection of mosquito salivary glands and is expressed in liver stages. Here, the Plasmodium yoelii MAEBL-M2 domain was expressed in a prokaryotic vector. C57BL/6J mice were immunized with doses of P. yoelii recombinant protein rPyM2-MAEBL. High levels of antibodies, with balanced IgG1 and IgG2c subclasses, were achieved. rPyM2-MAEBL antisera were capable of recognizing the native antigen. Anti-MAEBL antibodies recognized different MAEBL fragments expressed in CHO cells, showing stronger IgM and IgG responses to the M2 domain and repeat region, respectively. After a challenge with P. yoelii YM (lethal strain)-infected erythrocytes (IE), up to 90% of the immunized animals survived and a reduction of parasitemia was observed. Moreover, splenocytes harvested from immunized animals proliferated in a dose-dependent manner in the presence of rPyM2-MAEBL. Protection was highly dependent on CD4+, but not CD8+, T cells toward Th1. rPyM2-MAEBL antisera were also able to significantly inhibit parasite development, as observed in ex vivo P. yoelii erythrocyte invasion assays. Collectively, these findings support the use of MAEBL as a vaccine candidate and open perspectives to understand the mechanisms involved in protection. PMID:26169268

  1. Organophosphorus Pesticides Decrease M2 Muscarinic Receptor Function in Guinea Pig Airway Nerves via Indirect Mechanisms

    PubMed Central

    Proskocil, Becky J.; Bruun, Donald A.; Thompson, Charles M.; Fryer, Allison D.; Lein, Pamela J.

    2010-01-01

    Background Epidemiological studies link organophosphorus pesticide (OP) exposures to asthma, and we have shown that the OPs chlorpyrifos, diazinon and parathion cause airway hyperreactivity in guinea pigs 24 hr after a single subcutaneous injection. OP-induced airway hyperreactivity involves M2 muscarinic receptor dysfunction on airway nerves independent of acetylcholinesterase (AChE) inhibition, but how OPs inhibit neuronal M2 receptors in airways is not known. In the central nervous system, OPs interact directly with neurons to alter muscarinic receptor function or expression; therefore, in this study we tested whether the OP parathion or its oxon metabolite, paraoxon, might decrease M2 receptor function on peripheral neurons via similar direct mechanisms. Methodology/Principal Findings Intravenous administration of paraoxon, but not parathion, caused acute frequency-dependent potentiation of vagally-induced bronchoconstriction and increased electrical field stimulation (EFS)-induced contractions in isolated trachea independent of AChE inhibition. However, paraoxon had no effect on vagally-induced bradycardia in intact guinea pigs or EFS-induced contractions in isolated ileum, suggesting mechanisms other than pharmacologic antagonism of M2 receptors. Paraoxon did not alter M2 receptor expression in cultured cells at the mRNA or protein level as determined by quantitative RT-PCR and radio-ligand binding assays, respectively. Additionally, a biotin-labeled fluorophosphonate, which was used as a probe to identify molecular targets phosphorylated by OPs, did not phosphorylate proteins in guinea pig cardiac membranes that were recognized by M2 receptor antibodies. Conclusions/Significance These data indicate that neither direct pharmacologic antagonism nor downregulated expression of M2 receptors contributes to OP inhibition of M2 function in airway nerves, adding to the growing evidence of non-cholinergic mechanisms of OP neurotoxicity. PMID:20479945

  2. The M2 phase of vanadium dioxide: a view from infrared and optical spectroscopy

    NASA Astrophysics Data System (ADS)

    Huffman, T. J.; Xu, Peng; Qazilbash, M. M.; Yoon, Joonseok; Ju, Honglyoul; Smith, R.; Carr, G. L.

    2014-03-01

    Bulk single crystalline vanadium dioxide (VO2) undergoes a metal-insulator transition (MIT) at 340K. This thermally-driven MIT is accompanied by a structural phase transition that results in pairing of all vanadium ions in the insulating, monoclinic M1 phase. However, there also exists an insulating monoclinic M2 phase, usually only accessible via external strain or chemical doping, in which only half of the vanadium chains exhibit pairing. The M2 phase of VO2 is vital for understanding the roles of electronic correlations and vanadium pairing to the MIT. Recent x-ray diffraction studies show that small pure VO2 crystals can exhibit an M2 phase below 318K, likely due to internal strain.[1] These crystals undergo phase transitions from M2 to M1 and from M1 to rutile metal upon heating. We have performed reflectance micro-spectroscopy with polarized light and generalized spectroscopic micro-ellipsometry between 12 meV and 5.5 eV on these VO2 crystals as a function of temperature, uncomplicated by external strain or chemical doping. We report infrared and optical data on the M1, M2 and rutile phases and compare electronic and phonon properties of M1 and M2 phases.

  3. The common Cryptococcus neoformans glucuronoxylomannan M2 motif elicits non-protective antibodies

    PubMed Central

    Nakouzi, Antonio; Zhang, Tong; Oscarson, Stefan; Casadevall, Arturo

    2009-01-01

    The Cryptococcus neoformans capsular glucuronoxylomannan (GXM) is a potential vaccine antigen that can elicit protective and non-protective antibodies. In an attempt to focus the immune response on a single antigenic component, a heptasaccharide oligosaccharide representing the major structural motif (M2) of the most common clinical isolate was synthesized and conjugated to Human serum albumin (HSA). Monoclonal antibodies (mAbs) generated from mice immunized with M2-HSA produced the characteristic punctuate immunofluorescence associated with non-protective mAbs. None of the mAbs elicited by M2 immunization were opsonic. Passive administration of mAbs elicited by M2-HSA was not protective and there was no difference in the survival of mice immunized with M2-HSA and HSA. Hence, we conclude that the M2 motif represents an antigenic determinant in C. neoformans GXM that elicits non-protective responses and is not a suitable vaccine candidate. Furthermore, the results illustrate the first molecular assignment of a C. neoformans polysaccharide epitope and suggest a general strategy for the identification of GXM epitopes. PMID:19464529

  4. Tumor M2 pyruvate kinase: a tumor marker and its clinical application in gastrointestinal malignancy.

    PubMed

    Hardt, Philip D; Ewald, Nils

    2008-09-01

    Proliferating cells, in particular tumor cells, express a dimeric isoenzyme of pyruvate kinase, termed Tumor M2 pyruvate kinase. In the last few years, much attention has been paid to this novel tumor marker that can be determined in EDTA-plasma and in the feces. It has been used in diagnosis and surveillance of a variety of malignant diseases. As compared with the established tumor markers, Tumor M2-PK in EDTA-plasma proves to have at least equal sensitivity in pancreatic, gastric, esophageal, colorectal and cholangiocellular cancer. In combination with established tumor markers, EDTA-plasma M2-PK is a useful tool in diagnosis and surveillance of gastrointestinal tumors. In colorectal cancer, M2-PK in EDTA-plasma even proves superiority as compared with CEA. Fecal Tumor M2-PK testing resembles a good noninvasive screening parameter for colorectal cancer with a reported sensitivity of 68.8-91.0% and a specificity of 71.9-100%. It is superior to fecal occult blood testing in colorectal cancer screening. Since it is effective, easy to handle and bears rather low costs, fecal Tumor M2-PK testing is recommended for large-scale CRC screening.

  5. Quantification and localization of M2 macrophages in human kidneys with acute tubular injury

    PubMed Central

    Palmer, Matthew B; Vichot, Alfred A; Cantley, Lloyd G; Moeckel, Gilbert W

    2014-01-01

    This study addresses for the first time the question whether there is significant macrophage population in human kidney sections from patients with acute tubular injury (ATI). We examined therefore the interstitial macrophage population in human kidney tissue with biopsy-proven diagnosis of ATI, minimal change disease (MCD), and MCD with ATI. Kidney biopsies from patients with the above diagnoses were stained with antibodies directed against CD68 (general macrophage marker), CD163 (M2 marker), and HLA-DR (M1 marker) and their respective electron microscopy samples were evaluated for the presence of interstitial macrophages. Our study shows that patients with ATI have significantly increased numbers of interstitial CD68+ macrophages, with an increase in both HLA-DR+ M1 macrophages and CD163+ M2 macrophages as compared to patients with MCD alone. Approximately 75% of macrophages were M2 (CD163+) whereas only 25% were M1 (HLA-DR+). M2 macrophages, which are believed to be critical for wound healing, were found to localize close to the tubular basement membrane of injured proximal tubule cells. Ultra structural examination showed close adherence of macrophages to the basement membrane of injured tubular epithelial cells. We conclude that macrophages accumulate around injured tubules following ATI and exhibit predominantly an M2 phenotype. We further speculate that macrophage-mediated repair may involve physical contact between the M2 macrophage and the injured tubular epithelial cell. PMID:25404860

  6. 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

  7. M2-polarized macrophages in keratocystic odontogenic tumor: relation to tumor angiogenesis

    PubMed Central

    Zhong, Wen-Qun; Chen, Gang; Zhang, Wei; Xiong, Xue-Peng; Zhao, Yi; Liu, Bing; Zhao, Yi-Fang

    2015-01-01

    The purpose of this study was to evaluate the presence of M2-polarized macrophages and their relationships to angiogenesis in keratocystic odontogenic tumor (KCOT). M2-polarized macrophages were detected in KCOT samples by immunohistochemistry and immunofluorescence. Meanwhile, microvessel density measured with antibody against CD31 was closely correlated with the presence of M2-polarized macrophages. In addition, macrophage colony-stimulating factor (M-CSF) significantly contributed to the activation of M2-polarized macrophages. Moreover, the results of in vitro wound healing, cell migration and tube formation assays further revealed the pro-angiogenic function of M2-polarized macrophage-like cells. This function might be associated with secretion of angiogenic cytokines, such as vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β) and matrix metalloprotein-9 (MMP-9). This study demonstrates for the first time that M2-polarized macrophages are prevalent in KCOT, and their presence is dependent on M-CSF expression. More importantly, these tumor-supportive cells can also promote tumor angiogenesis by secreting angiogenic cytokines. PMID:26508096

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

    PubMed Central

    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

    2015-01-01

    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. PMID:26399191

  9. 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

  10. Kilogramm und Mol: SI-Basiseinheiten für Masse und Stoffmenge

    NASA Astrophysics Data System (ADS)

    Becker, Peter; Gläser, Michael

    2001-11-01

    Das Kilogramm ist eine SI-Basiseinheit, die bislang nicht hinreichend genau auf Naturkonstanten zurückgeführt werden kann. Gegenwärtig gibt es verschiedene Vorschläge, dieses Problem zu lösen. Ein Vorschlag ist die Neudefinition des Kilogramm auf Basis atomarer Massen. An der Physikalisch-Technischen Bundesanstalt (PTB) wird dazu an zwei verschiedenen Verfahren geforscht. Beim ersten Verfahren werden Goldionen zu einer Referenzmasse akkumuliert, beim zweiten die Avogadro-Konstante an einem Silizium-Einkristall bestimmt. Beide Verfahren könnten eine genau bestimmbare Zahl von Atomen liefern, mit der das Kilogramm neu definiert werden könnte. Dies könnte eine Zahl von 197 Au, von 28 Si oder auch von 12 C-Atomen sein, auf der bereits die SI-Einheit der Stoffmenge des Mol basiert.

  11. VizieR Online Data Catalog: ExoMol line lists for CS isotopologues (Paulose+, 2015)

    NASA Astrophysics Data System (ADS)

    Paulose, G.; Barton, E. J.; Yurchenko, S. N.; Tennyson, J.

    2015-07-01

    The files comprising this line list are in the standard ExoMol format, and are named XXcYYsst.dat, XXcYYstr.dat, where XX and YY are the mass numbers of the Carbon and Sulphur isotopes, respectively. The isotopologues covered including their nuclear spin degeneracy factors g_ns are: (12C)(32S) g_ns = 1 (12C)(33S) g_ns = 4 (12C)(34S) g_ns = 1 (12C)(36S) g_ns = 1 (13C)(32S) g_ns = 2 (13C)(33S) g_ns = 8 (13C)(34S) g_ns = 2 (13C)(36S) g_ns = 2 The partition functions from 1-3000K in 1K intervals for these isotopologues of CS are also provided in files named XXcYYspf.dat. (24 data files).

  12. Moléculas orgánicas no-rígidas

    NASA Astrophysics Data System (ADS)

    Senent Díez, M. L.

    Se destaca la importancia del estudio espectroscópico ab initio de una serie de moléculas no-rígidas detectadas en el medio interestelar (acetona, dimetil-eter, etanol, metanol, metilamina, ldots), así como los últimos avances del desarrollo de la metodología para el tratamiento teórico de estas especies. Se describe, a modo de ejemplo, el análisis del espectro roto-torsional de la molécula de glicoaldehido que ha sido recientemente detectada en el centro Galáctico Sagitario B2 (N) [1]. Esta especie presenta dos movimientos de gran amplitud que interaccionan, descansan en el Infrarrojo Lejano y le confiere propiedades no-rígidas. La molécula puede existir en posiciones cis y trans y presenta cinco confórmeros estables, tres de simetría Cs (I, II y IV) y un doble mínimo trans de simetría C1 (III) . La conformación favorita, I, presenta simetría Cs y se estabiliza por la formación de un puente de hidrógeno entre los grupos OH y C=O. Los mínimos secundarios II, III, y IV se han determinado a 1278.2 cm-1 (trans, Cs), 1298.8 cm-1 (trans, C1) y 1865.2 cm-1 (cis, Cs) con cálculos MP4/cc-pVQZ que incluyen sustituciones triples. Para determinar que vibraciones interaccionan con las torsiones, se ha realizado un análisis armónico en los mínimos. Las frecuencias fundamentales armónicas correspondientes al mínimo I se han calculado en 213.4 cm-1 (torsión C-C) y 425.7 cm-1 (torsión OH). Es de esperar que tan sólo dos vibraciones, la flexión del grupo C-C-O y el aleteo del hidrógeno del grupo aldehídico puedan desplazar el espectro torsional de la molécula aislada. Para determinar el espectro torsional, se ha determinado la superficie de potencial en dos dimensiones mediante el cálculo ab initio de las geometrías y energías de 74 conformaciones seleccionadas. Estas últimas se han ajustado a un doble serie de Fourier. A partir de la PES y de los parámetros cinéticos del Hamiltoniano vibracional se han obtenido frecuencias e intensidades

  13. W4 theory for computational thermochemistry : in pursuit of confident sub-kJ/mol predictions.

    SciTech Connect

    Karton, A.; Rabinovich, E.; Martin, J. M. L.; Ruscic, B.; Chemistry; Weizmann Institute of Science

    2006-01-01

    In an attempt to improve on our earlier W3 theory [A. D. Boese et al., J. Chem. Phys. 120, 4129 (2004)] we consider such refinements as more accurate estimates for the contribution of connected quadruple excitations ({cflx T}{sub 4}), inclusion of connected quintuple excitations ({cflx T}{sub 5}), diagonal Born-Oppenheimer corrections (DBOC), and improved basis set extrapolation procedures. Revised experimental data for validation purposes were obtained from the latest version of the Active Thermochemical Tables thermochemical network. The recent CCSDT(Q) method offers a cost-effective way of estimating {cflx T}{sub 4} but is insufficient by itself if the molecule exhibits some nondynamical correlation. The latter considerably slows down basis set convergence for {cflx T}{sub 4}, and anomalous basis set convergence in highly polar systems makes two-point extrapolation procedures unusable. However, we found that the CCSDTQ-CCSDT(Q) difference converges quite rapidly with the basis set, and that the formula 1.10[CCSDT(Q)/cc-pVTZ+CCSDTQ/cc-pVDZ-CCSDT(Q)/cc-pVDZ] offers a very reliable as well as fairly cost-effective estimate of the basis set limit {cflx T}{sub 4} contribution. The {cflx T}{sub 5} contribution converges very rapidly with the basis set, and even a simple double-zeta basis set appears to be adequate. The largest {cflx T}{sub 5} contribution found in the present work is on the order of 0.5 kcal/mol (for ozone). DBOCs are significant at the 0.1 kcal/mol level in hydride systems. Post-CCSD(T) contributions to the core-valence correlation energy are only significant at that level in systems with severe nondynamical correlation effects. Based on the accumulated experience, a new computational thermochemistry protocol for first- and second-row main-group systems, to be known as W4 theory, is proposed. Its computational cost is not insurmountably higher than that of the earlier W3 theory, while performance is markedly superior. Our W4 atomization energies for

  14. GTKDynamo: a PyMOL plug-in for QC/MM hybrid potential simulations.

    PubMed

    Bachega, José Fernando R; Timmers, Luís Fernando S M; Assirati, Lucas; Bachega, Leonardo R; Field, Martin J; Wymore, Troy

    2013-09-30

    Hybrid quantum chemical/molecular mechanical (QCMM) potentials are very powerful tools for molecular simulation. They are especially useful for studying processes in condensed phase systems, such as chemical reactions that involve a relatively localized change in electronic structure and where the surrounding environment contributes to these changes but can be represented with more computationally efficient functional forms. Despite their utility, however, these potentials are not always straightforward to apply since the extent of significant electronic structure changes occurring in the condensed phase process may not be intuitively obvious. To facilitate their use, we have developed an open-source graphical plug-in, GTKDynamo that links the PyMOL visualization program and the pDynamo QC/MM simulation library. This article describes the implementation of GTKDynamo and its capabilities and illustrates its application to QC/MM simulations.

  15. Rotation moléculaire en temps réel dans l'eau liquide

    NASA Astrophysics Data System (ADS)

    Amir, W.; Lascoux, N.; Gallot, G.; Gale, G.; Pommeret, S.; Leicknam, J.-Ci.; Bratos, S.

    2002-06-01

    La connaissance déjà acquise sur la dynamique de la liaison hydrogène dans l'eau liquide grâce au développement de laser délivrant des impulsions ultra-courtes dans l'infrarouge moyen nous permet de filmer la rotation de molécules HDO dans une solution D2O. L'expérience réalisée au laboratoire est basée sur la technique de spectroscopie pompe sonde résolue en polarisation. L'anisotropie mesurée permet de détecter en temps réel l'angle de déflexion du moment dipolaire de transition dont le point de départ est la direction du faisceau laser de pompe.

  16. Calixarene-based mol­ecular capsule from olefin metathesis

    PubMed Central

    Hailu, Shimelis T.; Butcher, Ray J.; Hudrlik, Paul F.; Hudrlik, Anne M.

    2013-01-01

    The reaction of tetra­kis­(all­yloxy)calix[4]arene with the first-generation Grubbs catalyst, followed by catalytic hydrogenation, gave the novel bis-calixarene 15,20,46,51,64,69,74,79-octa­oxatridecacyclo[32.28.8.83,28.113,53.122,44.09,14.021,26.038,70.040,45.052,57.059,63.07,80.032,73]octa­conta-1(63),3,5,7(80),9(14),10,12,21,23,25,28(73),29,31,34,36,38(70),40,42,44,52,54,56,59,61-tetra­cosa­ene benzene monosolvate, C72H72O8·C6H6. The structure consists of two calix[4]arene units connected by four-carbon chains at each of the four O atoms on their narrow rims, to form a cage. Each of the calix[4]arene units has a flattened cone conformation in which two of the opposite aryl groups are closer together and nearly parallel [dihedral angle between planes = 7.35 (16)°], and the other two aryl groups are splayed outward [dihedral angle between planes = 72.20 (8)°]. While the cavity contains no solvent or other guest mol­ecule, there is benzene solvent mol­ecule in the lattice. Two of the alkyl linking arms were disordered over two conformations with occupancies of 0.582 (3)/0.418 (3) and 0.33 (4)/0.467 (4). They were constrained to have similar metrical and thermal parameters. PMID:24046590

  17. The MHV68 M2 protein drives IL-10 dependent B cell proliferation and differentiation.

    PubMed

    Siegel, Andrea M; Herskowitz, Jeremy H; Speck, Samuel H

    2008-04-01

    Murine gammaherpesvirus 68 (MHV68) establishes long-term latency in memory B cells similar to the human gammaherpesvirus Epstein Barr Virus (EBV). EBV encodes an interleukin-10 (IL-10) homolog and modulates cellular IL-10 expression; however, the role of IL-10 in the establishment and/or maintenance of chronic EBV infection remains unclear. Notably, MHV68 does not encode an IL-10 homolog, but virus infection has been shown to result in elevated serum IL-10 levels in wild-type mice, and IL-10 deficiency results in decreased establishment of virus latency. Here we show that a unique MHV68 latency-associated gene product, the M2 protein, is required for the elevated serum IL-10 levels observed at 2 weeks post-infection. Furthermore, M2 protein expression in primary murine B cells drives high level IL-10 expression along with increased secretion of IL-2, IL-6, and MIP-1alpha. M2 expression was also shown to significantly augment LPS driven survival and proliferation of primary murine B cells. The latter was dependent on IL-10 expression as demonstrated by the failure of IL10-/- B cells to proliferate in response to M2 protein expression and rescue of M2-associated proliferation by addition of recombinant murine IL-10. M2 protein expression in primary B cells also led to upregulated surface expression of the high affinity IL-2 receptor (CD25) and the activation marker GL7, along with down-regulated surface expression of B220, MHC II, and sIgD. The cells retained CD19 and sIgG expression, suggesting differentiation to a pre-plasma memory B cell phenotype. These observations are consistent with previous analyses of M2-null MHV68 mutants that have suggested a role for the M2 protein in expansion and differentiation of MHV68 latently infected B cells-perhaps facilitating the establishment of virus latency in memory B cells. Thus, while the M2 protein is unique to MHV68, analysis of M2 function has revealed an important role for IL-10 in MHV68 pathogenesis-identifying a

  18. Perovskite CH3NH3PbI3(Cl) Single Crystals: Rapid Solution Growth, Unparalleled Crystalline Quality, and Low Trap Density toward 10(8) cm(-3).

    PubMed

    Lian, Zhipeng; Yan, Qingfeng; Gao, Taotao; Ding, Jie; Lv, Qianrui; Ning, Chuangang; Li, Qiang; Sun, Jia-Lin

    2016-08-01

    Single crystal reflects the intrinsic physical properties of a material, and single crystals with high-crystalline quality are highly desired for the acquisition of high-performance devices. We found that large single crystals of perovskite CH3NH3PbI3(Cl) could be grown rapidly from chlorine-containing solutions. Within 5 days, CH3NH3PbI3(Cl) single crystal as large as 20 mm × 18 mm × 6 mm was harvested. As a most important index to evaluate the crystalline quality, the full width at half-maximum (fwhm) in the high-resolution X-ray rocking curve (HR-XRC) of as-grown CH3NH3PbI3(Cl) single crystal was measured as 20 arcsec, which is far superior to so far reported CH3NH3PbI3 single crystals (∼1338 arcsec). The unparalleled crystalline quality delivered a low trap-state density of down to 7.6 × 10(8) cm(-3), high carrier mobility of 167 ± 35 cm(2) V(-1) s(-1), and long transient photovoltaic carrier lifetime of 449 ± 76 μs. The improvement in the crystalline quality, together with the rapid growth rate and excellent carrier transport property, provides state-of-the-art single crystalline hybrid perovskite materials for high-performance optoelectronic devices. PMID:27458057

  19. CO2 laser photoacoustic measurements of ethanol absorption coefficients within infrared region of 9.2-10.8 μm

    NASA Astrophysics Data System (ADS)

    Ivascu, I. R.; Matei, C. E.; Patachia, M.; Bratu, A. M.; Dumitras, D. C.

    2016-06-01

    Absorption coefficients of the ethanol vapors at atmospheric pressure and room temperature were measured by photoacoustic technique using a cw, line-tunable, frequency-stabilized CO2 laser as radiation source. The spectrum of the employed CO2 laser includes 54 lines with wavelengths in the infrared region of 9.2-10.8 μm and power levels up to 4.7 W. Measurements revealed a predominant absorption for ethanol within 9.4 μm band of the CO2 laser spectrum, where the highest values of the absorption coefficients were recorded: 3.68 cm- 1 atm- 1 at 9R(20) line and 3.65 cm- 1 atm- 1 at 9R(22) line. The estimated detection range covers six orders of magnitude, from a minimum of 30 ppbV to a maximum of 4% concentration of ethanol in nitrogen, which proves the suitability of the photoacoustic technique for accurate measurements of the ethanol concentration in various applications.

  20. CO2 laser photoacoustic measurements of ethanol absorption coefficients within infrared region of 9.2-10.8 μm.

    PubMed

    Ivascu, I R; Matei, C E; Patachia, M; Bratu, A M; Dumitras, D C

    2016-06-15

    Absorption coefficients of the ethanol vapors at atmospheric pressure and room temperature were measured by photoacoustic technique using a cw, line-tunable, frequency-stabilized CO2 laser as radiation source. The spectrum of the employed CO2 laser includes 54 lines with wavelengths in the infrared region of 9.2-10.8μm and power levels up to 4.7W. Measurements revealed a predominant absorption for ethanol within 9.4μm band of the CO2 laser spectrum, where the highest values of the absorption coefficients were recorded: 3.68cm(-1)atm(-1) at 9R(20) line and 3.65cm(-1)atm(-1) at 9R(22) line. The estimated detection range covers six orders of magnitude, from a minimum of 30ppbV to a maximum of 4% concentration of ethanol in nitrogen, which proves the suitability of the photoacoustic technique for accurate measurements of the ethanol concentration in various applications.

  1. CO2 laser photoacoustic measurements of ethanol absorption coefficients within infrared region of 9.2-10.8 μm.

    PubMed

    Ivascu, I R; Matei, C E; Patachia, M; Bratu, A M; Dumitras, D C

    2016-06-15

    Absorption coefficients of the ethanol vapors at atmospheric pressure and room temperature were measured by photoacoustic technique using a cw, line-tunable, frequency-stabilized CO2 laser as radiation source. The spectrum of the employed CO2 laser includes 54 lines with wavelengths in the infrared region of 9.2-10.8μm and power levels up to 4.7W. Measurements revealed a predominant absorption for ethanol within 9.4μm band of the CO2 laser spectrum, where the highest values of the absorption coefficients were recorded: 3.68cm(-1)atm(-1) at 9R(20) line and 3.65cm(-1)atm(-1) at 9R(22) line. The estimated detection range covers six orders of magnitude, from a minimum of 30ppbV to a maximum of 4% concentration of ethanol in nitrogen, which proves the suitability of the photoacoustic technique for accurate measurements of the ethanol concentration in various applications. PMID:27045783

  2. M2 macrophage polarization modulates epithelial-mesenchymal transition in cisplatin-induced tubulointerstitial fibrosis.

    PubMed

    Yu, Chia-Cherng; Chien, Chiang-Ting; Chang, Tzu-Ching

    2016-03-01

    Cisplatin-induced nephrotoxicity leaded to apoptosis of tubular epithelial cells (ECs) and tubulointerstitial fibrosis through ROS stress and inflammatory cytokines. Tubulointerstitial fibrosis caused by cisplatin might be via activation of resident fibroblasts and epithelial-mesenchymal transition (EMT) of tubular ECs. Inflammatory niche was crucial for progression of fibroblast activation or EMT. It had been reported that M1/M2 macrophage polarization regulated pro-inflammation or pro-resolving phase in damage repairing. However, the role of macrophage polarization on cisplatin-induced EMT of tubular ECs had not been well elucidated. In this study, we used co-cultured cell model and condition medium to examine the interaction between tubular ECs, fibroblasts and M1/M2 macrophages. Our data showed that cisplatin alone induced incomplete EMT of tubular ECs, whereas fibroblasts co-cultured with cisplatin-treated ECs could lead to fibroblast activation by detection of α-SMA and collagen-1. Moreover, decrease of iNOS and increase of argenase-1 and CD206 expression indicated that macrophages co-cultured with cisplatin-treated ECs would turn to M2 phenotype. Finally, we found that condition medium of M2 macrophages could promote complete EMT of cisplatin-treated ECs. Taken together, cisplatin created an inflammatory niche via tubular ECs to activate fibroblasts and stimulated M2 macrophage polarization. M2 macrophages could turn back to promote EMT of cisplatin-treated ECs. These results revealed the cooperative roles of tubular ECs, fibroblast and M2 macrophages to facilitate the progression of renal fibroblasis.

  3. 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.

  4. A novel M2e-multiple antigenic peptide providing heterologous protection in mice.

    PubMed

    Wen, Feng; Ma, Ji-Hong; Yu, Hai; Yang, Fu-Ru; Huang, Meng; Zhou, Yan-Jun; Li, Ze-Jun; Wang, Xiu-Hui; Li, Guo-Xin; Jiang, Yi-Feng; Tong, Wu; Tong, Guang-Zhi

    2016-03-01

    Swine influenza viruses (SwIVs) cause considerable morbidity and mortality in domestic pigs, resulting in a significant economic burden. Moreover, pigs have been considered to be a possible mixing vessel in which novel strains loom. Here, we developed and evaluated a novel M2e-multiple antigenic peptide (M2e-MAP) as a supplemental antigen for inactivated H3N2 vaccine to provide cross-protection against two main subtypes of SwIVs, H1N1 and H3N2. The novel tetra-branched MAP was constructed by fusing four copies of M2e to one copy of foreign T helper cell epitopes. A high-yield reassortant H3N2 virus was generated by plasmid based reverse genetics. The efficacy of the novel H3N2 inactivated vaccines with or without M2e-MAP supplementation was evaluated in a mouse model. M2e-MAP conjugated vaccine induced strong antibody responses in mice. Complete protection against the heterologous swine H1N1 virus was observed in mice vaccinated with M2e-MAP combined vaccine. Moreover, this novel peptide confers protection against lethal challenge of A/Puerto Rico/8/34 (H1N1). Taken together, our results suggest the combined immunization of reassortant inactivated H3N2 vaccine and the novel M2e-MAP provided cross-protection against swine and human viruses and may serve as a promising approach for influenza vaccine development. PMID:27051342

  5. A novel M2e-multiple antigenic peptide providing heterologous protection in mice

    PubMed Central

    Wen, Feng; Ma, Ji-Hong; Yang, Fu-Ru; Huang, Meng; Zhou, Yan-Jun; Li, Ze-Jun; Wang, Xiu-Hui; Li, Guo-Xin; Jiang, Yi-Feng; Tong, Wu

    2016-01-01

    Swine influenza viruses (SwIVs) cause considerable morbidity and mortality in domestic pigs, resulting in a significant economic burden. Moreover, pigs have been considered to be a possible mixing vessel in which novel strains loom. Here, we developed and evaluated a novel M2e-multiple antigenic peptide (M2e-MAP) as a supplemental antigen for inactivated H3N2 vaccine to provide cross-protection against two main subtypes of SwIVs, H1N1 and H3N2. The novel tetra-branched MAP was constructed by fusing four copies of M2e to one copy of foreign T helper cell epitopes. A high-yield reassortant H3N2 virus was generated by plasmid based reverse genetics. The efficacy of the novel H3N2 inactivated vaccines with or without M2e-MAP supplementation was evaluated in a mouse model. M2e-MAP conjugated vaccine induced strong antibody responses in mice. Complete protection against the heterologous swine H1N1 virus was observed in mice vaccinated with M2e-MAP combined vaccine. Moreover, this novel peptide confers protection against lethal challenge of A/Puerto Rico/8/34 (H1N1). Taken together, our results suggest the combined immunization of reassortant inactivated H3N2 vaccine and the novel M2e-MAP provided cross-protection against swine and human viruses and may serve as a promising approach for influenza vaccine development. PMID:27051342

  6. Rac2 Controls Tumor Growth, Metastasis and M1-M2 Macrophage Differentiation In Vivo

    PubMed Central

    Joshi, Shweta; Singh, Alok R.; Zulcic, Muamera; Bao, Lei; Messer, Karen; Ideker, Trey; Dutkowski, Janusz; Durden, Donald L.

    2014-01-01

    Although it is well-established that the macrophage M1 to M2 transition plays a role in tumor progression, the molecular basis for this process remains incompletely understood. Herein, we demonstrate that the small GTPase, Rac2 controls macrophage M1 to M2 differentiation and the metastatic phenotype in vivo. Using a genetic approach, combined with syngeneic and orthotopic tumor models we demonstrate that Rac2-/- mice display a marked defect in tumor growth, angiogenesis and metastasis. Microarray, RT-PCR and metabolomic analysis on bone marrow derived macrophages isolated from the Rac2-/- mice identify an important role for Rac2 in M2 macrophage differentiation. Furthermore, we define a novel molecular mechanism by which signals transmitted from the extracellular matrix via the α4β1 integrin and MCSF receptor lead to the activation of Rac2 and potentially regulate macrophage M2 differentiation. Collectively, our findings demonstrate a macrophage autonomous process by which the Rac2 GTPase is activated downstream of the α4β1 integrin and the MCSF receptor to control tumor growth, metastasis and macrophage differentiation into the M2 phenotype. Finally, using gene expression and metabolomic data from our Rac2-/- model, and information related to M1-M2 macrophage differentiation curated from the literature we executed a systems biologic analysis of hierarchical protein-protein interaction networks in an effort to develop an iterative interactome map which will predict additional mechanisms by which Rac2 may coordinately control macrophage M1 to M2 differentiation and metastasis. PMID:24770346

  7. The m2 form of the Helicobacter pylori cytotoxin has cell type-specific vacuolating activity

    PubMed Central

    Pagliaccia, Cristina; de Bernard, Marina; Lupetti, Pietro; Ji, Xuhuai; Burroni, Daniela; Cover, Timothy L.; Papini, Emanuele; Rappuoli, Rino; Telford, John L.; Reyrat, Jean-Marc

    1998-01-01

    The Helicobacter pylori toxin VacA causes vacuolar degeneration in mammalian cell lines in vitro and plays a key role in peptic ulcer disease. Two alleles, m1 and m2, of the mid-region of the vacA gene have been described, and the m2 cytotoxin always has been described as inactive in the in vitro HeLa cell assay. However, the m2 allele is associated with peptic ulcer and is prevalent in populations in which peptic ulcer and gastric cancer have high incidence. In this paper, we show that, despite the absence of toxicity on HeLa cells, the m2 cytotoxin is able to induce vacuolization in primary gastric cells and in other cell lines such as RK-13. The absence of Hela cell activity is due to an inability to interact with the cell surface, suggesting a receptor-mediated interaction. This result is consistent with the observation that the m2 allele is found in a population that has a high prevalence of peptic ulcer disease and gastric cancer. VacA is the first bacterial toxin described for which the same active subunit can be delivered by different receptor binding domains. PMID:9707626

  8. Quantitative changes in tumor-associated M2 macrophages characterize cholangiocarcinoma and their association with metastasis.

    PubMed

    Thanee, Malinee; Loilome, Watcharin; Techasen, Anchalee; Namwat, Nisana; Boonmars, Thidarut; Pairojkul, Chawalit; Yongvanit, Puangrat

    2015-01-01

    The tumor microenvironment (TME) includes numerous non-neoplastic cells such as leukocytes and fibroblasts that surround the neoplasm and influence its growth. Tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) are documented as key players in facilitating cancer appearance and progression. Alteration of the macrophage (CD68, CD163) and fibroblast (α-SMA, FSP-1) cells in Opisthorchis viverrini (Ov)-induced cholangiocarcinoma (CCA) was here assessed using liver tissues from an established hamster model and from 43 human cases using immunohistochemistry. We further investigated whether M2-activated TAMs influence CCA cell migration ability by wound healing assay and Western blot analysis. Macrophages and fibroblasts change their phenotypes to M2-TAMs (CD68+, CD163+) and CAFs (α-SMA+, FSP-1+), respectively in the early stages of carcinogenesis. Interestingly, a high density of the M2-TAMs CCA in patients is significantly associated with the presence of extrahepatic metastases (p=0.021). Similarly, CD163+ CCA cells are correlated with metastases (p=0.002), and they may be representative of an epithelial-to-mesenchymal transition (EMT) with increased metastatic activity. We further showed that M2-TAM conditioned medium can induce CCA cell migration as well as increase N-cadherin expression (mesenchymal marker). The present work revealed that significant TME changes occur at an early stage of Ov-induced carcinogenesis and that M2-TAMs are key factors contributing to CCA metastasis, possibly via EMT processes. PMID:25854403

  9. Xuebijing Injection Promotes M2 Polarization of Macrophages and Improves Survival Rate in Septic Mice

    PubMed Central

    Liu, Yan-Cun; Yao, Feng-Hua; Chai, Yan-Fen; Dong, Ning; Sheng, Zhi-Yong; Yao, Yong-Ming

    2015-01-01

    Xuebijing (XBJ) injection, a concoction of several Chinese herbs, has been widely used as an immunomodulator for the treatment of severe sepsis in China. However, the precise mechanisms responsible for its efficacy have not been fully elucidated. In our study, we determined the flow cytometry markers (F4/80, CD11c, and CD206), the levels of secreted cytokines (TNF-α, IL-6, and IL-10), and the expression of specific proteins of M2 (Ym1, Fizz1, and Arg1) to assess macrophage polarization. Treatment with XBJ lowered M1 associated cytokine levels and increased the level of M2 associated cytokine level. The percentage of M2 phenotype cells of XBJ group was much higher than that of the control group. Expressions of phosphorylated Janus kinase 1 (JAK1) and signal transducer and activator of transcription 6 (STAT6) were markedly enhanced after the administration of XBJ; on the other hand, the M2 associated cytokines and proteins were decreased following treatment with JAK1 or STAT6 inhibitor. In addition, the treatment of XBJ significantly improved the survival rate of septic mice. These studies demonstrate that XBJ can markedly promote M2 polarization and improve the survival rate of septic mice, thereby contributing to therapeutic effect in the treatment of septic complications. PMID:26064161

  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. Wireless Access Control with Smart Antenna for M2M Communications

    NASA Astrophysics Data System (ADS)

    Sakamoto, Hiroshi; Bandai, Masaki; Watanabe, Takashi

    Machine to machine (M2M) is a promising technology to achieve an ubiquitous environment by uniting machines and machines over the Internet. The network used for M2M consists of core network and access network. This paper discusses effective controls of the wireless access network for M2M. Among typical examples of the wireless access network for M2M is a wireless sensor network (WSN). WSN for M2M may require energy efficiency, high reliability and throughput. For these requirements, in this paper, we propose a scheme to build a hierarchical sensor network using smart antenna. The proposed scheme uses omni-directional antennas together with smart antennas. Since smart antennas can extend communications distance, the proposed scheme enables reduction of number of hops to reduce the traffic load on relay nodes. As a result, the energy consumption, data collection ratio and throughput can be improved. We implement the proposed scheme on a real testbed. The testbed uses UNAGI as smart antenna nodes and Mica Mote as sensor nodes. In addition to the fundamental evaluation on the testbed, we simulate large-scale sensor networks. The results show the effectiveness of the proposed hierarchical sensor network with smart antennas.

  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. 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.

  14. 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. PMID:26538329

  15. MMP28 promotes macrophage polarization toward M2 cells and augments pulmonary fibrosis.

    PubMed

    Gharib, Sina A; Johnston, Laura K; Huizar, Isham; Birkland, Timothy P; Hanson, Josiah; Wang, Ying; Parks, William C; Manicone, Anne M

    2014-01-01

    Members of the MMP family function in various processes of innate immunity, particularly in controlling important steps in leukocyte trafficking and activation. MMP28 (epilysin) is a member of this family of proteinases, and we have found that MMP28 is expressed by macrophages and regulates their recruitment to the lung. We hypothesized that MMP28 regulates other key macrophage responses, such as macrophage polarization. Furthermore, we hypothesized that these MMP28-dependent changes in macrophage polarization would alter fibrotic responses in the lung. We examined the gene expression changes in WT and Mmp28-/- BMDMs, stimulated with LPS or IL-4/IL-13 to promote M1 and M2 cells, respectively. We also collected macrophages from the lungs of Pseudomonas aeruginosa-exposed WT and Mmp28-/- mice to evaluate changes in macrophage polarization. Lastly, we evaluated the macrophage polarization phenotypes during bleomycin-induced pulmonary fibrosis in WT and Mmp28-/- mice and assessed mice for differences in weight loss and total collagen levels. We found that MMP28 dampens proinflammatory macrophage function and promots M2 programming. In both in vivo models, we found deficits in M2 polarization in Mmp28-/- mice. In bleomycin-induced lung injury, these changes were associated with reduced fibrosis. MMP28 is an important regulator of macrophage polarization, promoting M2 function. Loss of MMP28 results in reduced M2 polarization and protection from bleomycin-induced fibrosis. These findings highlight a novel role for MMP28 in macrophage biology and pulmonary disease.

  16. M2 muscarinic receptor activation regulates Schwann cell differentiation and myelin organization.

    PubMed

    Uggenti, Carolina; De Stefano, M Egle; Costantino, Michele; Loreti, Simona; Pisano, Annalinda; Avallone, Bice; Talora, Claudio; Magnaghi, Valerio; Tata, Ada Maria

    2014-07-01

    Glial cells express acetylcholine receptors. In particular, rat Schwann cells express different muscarinic receptor subtypes, the most abundant of which is the M2 subtype. M2 receptor activation causes a reversible arrest of the cell cycle. This negative effect on Schwann cell proliferation suggests that these cells may possibly progress into a differentiating program. In this study we analyzed the in vitro modulation, by the M2 agonist arecaidine, of transcription factors and specific signaling pathways involved in Schwann cell differentiation. The arecaidine-induced M2 receptor activation significantly upregulates transcription factors involved in the promyelinating phase (e.g., Sox10 and Krox20) and downregulates proteins involved in the maintenance of the undifferentiated state (e.g., c-jun, Notch-1, and Jagged-1). Furthermore, arecaidine stimulation significantly increases the expression of myelin proteins, which is accompanied by evident changes in cell morphology, as indicated by electron microscopy analysis, and by substantial cellular re-distribution of actin and cell adhesion molecules. Moreover, ultrastructural and morphometric analyses on sciatic nerves of M2/M4 knockout mice show numerous degenerating axons and clear alterations in myelin organization compared with wild-type mice. Therefore, our data demonstrate that acetylcholine mediates axon-glia cross talk, favoring Schwann cell progression into a differentiated myelinating phenotype and contributing to compact myelin organization.

  17. M2 receptor activation inhibits cell cycle progression and survival in human glioblastoma cells.

    PubMed

    Ferretti, Michela; Fabbiano, Cinzia; Di Bari, Maria; Conte, Claudia; Castigli, Emilia; Sciaccaluga, Miriam; Ponti, Donatella; Ruggieri, Paola; Raco, Antonino; Ricordy, Ruggero; Calogero, Antonella; Tata, Ada Maria

    2013-04-01

    Muscarinic receptors, expressed in several primary and metastatic tumours, appear to be implicated in their growth and propagation. In this work we have demonstrated that M2 muscarinic receptors are expressed in glioblastoma human specimens and in glioblastoma cell lines. Moreover, we have characterized the effects of the M2 agonist arecaidine on cell growth and survival both in two different glioblastoma cell lines (U251MG and U87MG) and in primary cultures obtained from different human biopsies. Cell growth analysis has demonstrated that the M2 agonist arecaidine strongly decreased cell proliferation in both glioma cell lines and primary cultures. This effect was dose and time dependent. FACS analysis has confirmed cell cycle arrest at G1/S and at G2/M phase in U87 cells and U251 respectively. Cell viability analysis has also shown that arecaidine induced severe apoptosis, especially in U251 cells. Chemosensitivity assays have, moreover, shown arecaidine and temozolomide similar effects on glioma cell lines, although IC50 value for arecaidine was significantly lower than temozolomide. In conclusion, we report for the first time that M2 receptor activation has a relevant role in the inhibition of glioma cell growth and survival, suggesting that M2 may be a new interesting therapeutic target to investigate for glioblastoma therapy.

  18. Dynamic Changes of Microglia/Macrophage M1 and M2 Polarization in Theiler's Murine Encephalomyelitis.

    PubMed

    Herder, Vanessa; Iskandar, Cut Dahlia; Kegler, Kristel; Hansmann, Florian; Elmarabet, Suliman Ahmed; Khan, Muhammad Akram; Kalkuhl, Arno; Deschl, Ulrich; Baumgärtner, Wolfgang; Ulrich, Reiner; Beineke, Andreas

    2015-11-01

    Microglia and macrophages play a central role for demyelination in Theiler's murine encephalomyelitis (TME) virus infection, a commonly used infectious model for chronic-progressive multiple sclerosis. In order to determine the dynamic changes of microglia/macrophage polarization in TME, the spinal cord of Swiss Jim Lambert (SJL) mice was investigated by gene expression profiling and immunofluorescence. Virus persistence and demyelinating leukomyelitis were confirmed by immunohistochemistry and histology. Electron microscopy revealed continuous myelin loss together with abortive myelin repair during the late chronic infection phase indicative of incomplete remyelination. A total of 59 genes out of 151 M1- and M2-related genes were differentially expressed in TME virus-infected mice over the study period. The onset of virus-induced demyelination was associated with a dominating M1 polarization, while mounting M2 polarization of macrophages/microglia together with sustained prominent M1-related gene expression was present during the chronic-progressive phase. Molecular results were confirmed by immunofluorescence, showing an increased spinal cord accumulation of CD16/32(+) M1-, arginase-1(+) M2- and Ym1(+) M2-type cells associated with progressive demyelination. The present study provides a comprehensive database of M1-/M2-related gene expression involved in the initiation and progression of demyelination supporting the hypothesis that perpetuating interaction between virus and macrophages/microglia induces a vicious circle with persistent inflammation and impaired myelin repair in TME.

  19. Identification of Aquifex aeolicus tRNA (m2(2G26) methyltransferase gene.

    PubMed

    Takeda, Hiroshi; Hori, Hiroyuki; Endo, Yaeta

    2002-01-01

    The modifications of N2,N2-dimethylguanine (m2(2)G) are found in tRNAs and rRNAs from eukarya and archaea. In tRNAs, modification at position G26 is generated by tRNA (m2(2)G26) methyltransferase, which is encoded by the corresponding gene, trm1. This enzyme catalyzes the methyl-transfer from S-adenosyl-L-methionine to the semi-conserved residue, G26, via the intermediate modified base, m2G26. Recent genome sequencing project has been reported that the putative trm1 is encoded in the genome of Aquifex aeolicus, a hyper-thermophilic eubacterium as only one exception among eubacteria. In order to confirm whether this bacterial trm1 gene product is a real tRNA (m2(2)G26) methyltransferase or not, we expressed this protein by wheat germ in vitro cell-free translation system. Our biochemical analysis clearly showed that this gene product possessed tRNA (m2(2)G26) methyltransferase activity.

  20. M2 tidal parameter modulation revealed by superconducting gravimeter time series

    NASA Astrophysics Data System (ADS)

    Meurers, Bruno; Van Camp, Michel; Francis, Olivier; Pálinkáš, Vojtech

    2016-04-01

    Analyzing consecutive and independent 1-yr data sets of 10 European superconducting gravimeters (SG) reveals statistically significant temporal variations of M2 tidal parameters. Both common short-term (< 2 yr) and long-term (> 2 yr) features are identified in all SG time series but one. The averaged variations of the amplitude factor are about 0.2 per mille. The path of load vector variations equivalent to the temporal changes of tidal parameters suggests the presence of an 8.85 yr modulation (lunar perigee). The tidal waves having the potential to modulate M2 with this period belong to the 3rd degree constituents. Their amplitude factors turn out to be much closer to body tide model predictions than that of the main 2nd degree M2, which indicates ocean loading for 3rd degree waves to be less prominent than for 2nd degree waves within the M2 group. These two different responses to the loading suggest that the observed long-term modulation is more due to insufficient frequency resolution of limited time series rather than to time variable loading. Presently, SG gravity time series are still too short to prove if time variable loading processes are involved too as in case of the annual M2 modulation known to appear for analysis intervals of less than 1 yr. The observed variations provide an upper accuracy limit for Earth model validation and permit estimating the temporal stability of SG scale factors and assessing the quality of gravity time series.

  1. Tensionless supersymmetric M2 branes in AdS4 × S7 and giant diabolo

    NASA Astrophysics Data System (ADS)

    López Carballo, Jaume; Lugo, Adrián R.; Russo, Jorge G.

    2009-11-01

    We find various supersymmetric configurations of toroidal M2 brane solutions in AdS4 × S7 or, more generally, in AdS4 × S7/Bbb Zk. In this class we identify solutions preserving 1/4 and 1/8 supersymmetries of the background. The supersymmetric M2 branes have angular momenta and winding on S7, and null world-volumes. In certain cases they collapse to string-like configurations. These configurations can be viewed as a higher-dimensional (membrane) analog of BMN states. We compute the energy and angular momenta, showing that all supersymmetric configurations obey the BPS relation E = J/R, J≡∑i = 14|Ji| with E,J → ∞. Finally, we also study another class of supersymmetric M2-branes, including uncompact rotating membranes of ``diabolo'' shape.

  2. 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.

  3. Purinergic signaling during macrophage differentiation results in M2 alternative activated macrophages.

    PubMed

    Barberà-Cremades, Maria; Baroja-Mazo, Alberto; Pelegrín, Pablo

    2016-02-01

    Macrophages represent a highly heterogenic cell population of the innate immune system, with important roles in the initiation and resolution of the inflammatory response. Purinergic signaling regulates both M1 and M2 macrophage function at different levels by controlling the secretion of cytokines, phagocytosis, and the production of reactive oxygen species. We found that extracellular nucleotides arrest macrophage differentiation from bone marrow precursors via adenosine and P2 receptors. This results in a mature macrophage with increased expression of M2, but not M1, genes. Similar to adenosine and ATP, macrophage growth arrested with LPS treatment resulted in an increase of the M2-related marker Ym1. Recombinant Ym1 was able to affect macrophage proliferation and could, potentially, be involved in the arrest of macrophage growth during hematopoiesis.

  4. Test Pilot John A. Manke and M2-F3 Lifting Body

    NASA Technical Reports Server (NTRS)

    1972-01-01

    NASA research pilot John A. Manke is seen here in front of the M2-F3 lifting body. Manke was hired by NASA on May 25, 1962, as a flight research engineer. He was later assigned to the pilot's office and flew various support aircraft including the F-104, F-5D, F-111 and C-47. The M2-F3 reached a top speed of l,064 mph (Mach 1.6). Highest altitude reached by the vehicle was 7l,500 feet on December 21, 1972, the date of its last flight with NASA pilot John Manke at the controls. The information the lifting body program generated contributed to the data base that led to development of today's Space Shuttle program. NASA donated The M2-F3 vehicle to the Smithsonian Institution in December 1973.

  5. Structure of the atypical bacteriocin pectocin M2 implies a novel mechanism of protein uptake.

    PubMed

    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

    2014-07-01

    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.

  6. Differential Binding of Rimantadine Enantiomers to Influenza A M2 Proton Channel.

    PubMed

    Wright, Anna K; Batsomboon, Paratchata; Dai, Jian; Hung, Ivan; Zhou, Huan-Xiang; Dudley, Gregory B; Cross, Timothy A

    2016-02-10

    Rimantadine hydrochloride (α-methyl-1-adamantane-methalamine hydrochloride) is a chiral compound which exerts antiviral activity against the influenza A virus by inhibiting proton conductance of the M2 ion channel. In complex with M2, rimantadine has always been characterized as a racemic mixture. Here, we report the novel enantioselective synthesis of deuterium-labeled (R)- and (S)-rimantadine and the characterization of their protein-ligand interactions using solid-state NMR. Isotropic chemical shift changes strongly support differential binding of the enantiomers to the proton channel. Position restrained simulations satisfying distance restraints from (13)C-(2)H rotational-echo double-resonance NMR show marked differences in the hydrogen-bonding pattern of the two enantiomers at the binding site. Together these results suggest a complex set of interactions between (R)-rimantadine and the M2 proton channel, leading to a higher stability for this enantiomer of the drug in the channel pore. PMID:26804976

  7. Critical illness induces alternative activation of M2 macrophages in adipose tissue

    PubMed Central

    2011-01-01

    Introduction We recently reported macrophage accumulation in adipose tissue of critically ill patients. Classically activated macrophage accumulation in adipose tissue is a known feature of obesity, where it is linked with increasing insulin resistance. However, the characteristics of adipose tissue macrophage accumulation in critical illness remain unknown. Methods We studied macrophage markers with immunostaining and gene expression in visceral and subcutaneous adipose tissue from healthy control subjects (n = 20) and non-surviving prolonged critically ill patients (n = 61). For comparison, also subcutaneous in vivo adipose tissue biopsies were studied from 15 prolonged critically ill patients. Results Subcutaneous and visceral adipose tissue biopsies from non-surviving prolonged critically ill patients displayed a large increase in macrophage staining. This staining corresponded with elevated gene expression of "alternatively activated" M2 macrophage markers arginase-1, IL-10 and CD163 and low levels of the "classically activated" M1 macrophage markers tumor necrosis factor (TNF)-α and inducible nitric-oxide synthase (iNOS). Immunostaining for CD163 confirmed positive M2 macrophage staining in both visceral and subcutaneous adipose tissue biopsies from critically ill patients. Surprisingly, circulating levels and tissue gene expression of the alternative M2 activators IL-4 and IL-13 were low and not different from controls. In contrast, adipose tissue protein levels of peroxisome proliferator-activated receptor-γ (PPARγ), a nuclear receptor required for M2 differentiation and acting downstream of IL-4, was markedly elevated in illness. In subcutaneous abdominal adipose tissue biopsies from surviving critically ill patients, we could confirm positive macrophage staining with CD68 and CD163. We also could confirm elevated arginase-1 gene expression and elevated PPARγ protein levels. Conclusions Unlike obesity, critical illness evokes adipose tissue

  8. Proton and cation transport activity of the M2 proton channel from influenza A virus.

    PubMed

    Leiding, Thom; Wang, Jun; Martinsson, Jonas; DeGrado, William F; Arsköld, Sindra Peterson

    2010-08-31

    The M2 protein is a small, single-span transmembrane (TM) protein from the influenza A virus. This virus enters cells via endosomes; as the endosomes mature and become more acidic M2 facilitates proton transport into the viral interior, thereby disrupting matrix protein/RNA interactions required for infectivity. A mystery has been how protons can accumulate in the viral interior without developing a large electrical potential that impedes further inward proton translocation. Progress in addressing this question has been limited by the availability of robust methods of unidirectional insertion of the protein into virus-like vesicles. Using an optimized procedure for reconstitution, we show that M2 has antiporter-like activity, facilitating K(+) or Na(+) efflux when protons flow down a concentration gradient into the vesicles. Cation efflux is very small except under conditions mimicking those encountered by the endosomally entrapped virus, in which protons are flowing through the channel. This proton/cation exchange function is consistent with the known high proton selectivity of the channel. Thus, M2 acts as a proton uniporter that occasionally allows K(+) to flow to maintain electrical neutrality. Remarkably, as the pH inside M2-containing vesicles (pH(in)) decreases, the proton channel activity of M2 is inhibited, but its cation transport activity is activated. This reciprocal inhibition of proton flux and activation of cation flux with decreasing pH(in) first allows accumulation of protons in the early stages of acidification, then trapping of protons within the virus when low pH(in) is achieved.

  9. Sphingosine 1-phosphate induced anti-atherogenic and atheroprotective M2 macrophage polarization through IL-4.

    PubMed

    Park, Soo-Jin; Lee, Kyoung-Pil; Kang, Saeromi; Lee, Jaewon; Sato, Koichi; Chung, Hae Young; Okajima, Fumikazu; Im, Dong-Soon

    2014-10-01

    Sphingosine 1-phosphate (S1P) has been implicated in anti-atherogenic properties of high-density lipoproteins. However, the roles and signaling of S1P in macrophages, the main contributor to atherosclerosis, have not been well studied. Furthermore, pro-inflammatory M1 and anti-inflammatory M2 macrophage phenotypes may influence the development of atherosclerosis. Therefore, we investigated the effects of S1P on macrophage phenotypes, especially on M2 polarization and its signaling in relation to the anti-atherogenic properties of S1P. It was found that S1P induced anti-inflammatory M2 polarization via IL-4 secretion and its signaling, and induced IL-4Rα and IL-2Rγ. In addition, down-stream signalings, such as, stat-6 phosphorylation, SOCS1 induction, and SOCS3 suppression were also observed in macrophages in response to S1P. Furthermore, S1P-induced ERK activation, and the inhibitions of p38 MAPK and JNK were found to be key signals for IL-4 induction. Moreover, the anti-atherogenic effect of S1P in HDL was confirmed by the observation that oxidized LDL-induced lipid accumulation was attenuated in S1P-treated M2 macrophages. Furthermore, the atheroprotective effect of S1P was demonstrated by its anti-apoptotic effect on S1P-treated macrophages. The present study shows that S1P-induced M2 polarization of macrophages could be mediated via IL-4 signaling, and suggests that M2 polarization by S1P is responsible for the anti-atherogenic and atheroprotective properties of high-density lipoproteins in vivo.

  10. Ovarian cancer stem-like cells elicit the polarization of M2 macrophages.

    PubMed

    Zhang, Qing; Cai, Da-Jun; Li, Bin

    2015-06-01

    Ovarian cancer is a life‑threatening disease in females worldwide. The polarization of macrophages is crucial in oncogenesis and the development of ovarian cancer. Increasing evidence has supported the correlation between ovarian cancer stem‑like cells (OCSCs) and macrophages, however, whether OCSCs can affect the polarization of macrophages and the underlying mechanisms involved remain to be elucidated. To examine the interplay between OCSCs and macrophages, a co‑culture system was used to detect the effect of OCSCs on macrophage polarization. The expression of cluster of differentiation 206+ and the secretion of interleukin‑10 were significantly increased and the production of tumor necrosis factor‑α was suppressed, confirming macrophage polarization to M2 macrophages. Further investigation of the macrophages in a Transwell culture system with OCSCs revealed polarization to the M2 macrophages to a similar extent, indicating that the cytokines of the OCSCs, rather than direct cell‑cell contact, are important for the polarization of M2 macrophages. Furthermore, the expression levels of chemokine (C‑C motif) ligand (CCL)2, cyclooxygenase (COX)‑2 and prostaglandin E2 (PGE2) were increased in the Transwell system and the inhibition of COX‑2, but not CCL2, significantly decreased the polarization of the M2 macrophages. In addition, mechanistic analysis revealed the importance of the COX‑2/PGE2 pathway in OCSCs to activate Janus kinase (JAK) signaling in macrophages to elicit M2 polarization. These findings provided the first evidence, to the best of our knowledge, that OCSCs are capable of altering macrophages into the M2 phenotype via the overexpression of COX‑2 and the increased production of PGE2 cytokines and that the JAK signaling pathway in macrophages is important for this alteration. The present study provided evidence supporting possible molecular targets for cancer treatment.

  11. Micropropagation of Prosopis chilensis (Mol.) Stuntz from young and mature plants.

    PubMed

    Caro, L A; Polci, P A; Lindström, L I; Echenique, C V; Hernández, L F

    2002-04-01

    Prosopis chilensis (Mol.) Stuntz (Algarrobo de Chile) is an important native tree species that can be grown in arid and semiarid regions for wood and forage production and environmental protection. Developing a simple and reliable in vitro protocol for cloning it would enable to improve it genetically. Explants of P. chilensis were taken from 4 months-old plants grown in the greenhouse or from adult trees grown in a natural environment. Nodal segments 1-2 cm long containing an axillary bud were selected from elongating shoots. These cuttings were aseptically cultured on two agar-solid basal media, MS or BTMm, and treated with 0.05 mg L-1 BA and 3 mg L-1 of either IAA, IBA or NAA. Sucrose (3% w/v) was used as carbon source. The percentage of sprouted cuttings and whole plant regeneration as well as its shoot and root length were recorded. Number, length and dry weight of shoots and roots were also measured. Rooting was successful with cuttings taken from young or adult plants, but explants from young plants showed a better response. Culturing in BTMm resulted in significantly greater shoot and root biomass than culturing in MS. Moreover, this response was higher in young explants when IBA was used as growth regulator. This paper reports a simple and effective method to micropropagate P. chilensis from young and adult plants. PMID:12058379

  12. [Use of mesquite cotyledon (Prosopis chilensis (Mol) Shuntz) in the manufacturing of cereal bars].

    PubMed

    Estévez, A M; Escobar, B; Ugarte, V

    2000-06-01

    Cereal bars with peanut and walnut has shown to be snack foods of good organoleptic characteristics and high caloric value, due to their content of protein, lipids and carbohydrates. Cotyledons of mezquite seeds have a high protein content which biological quality improves with thermal processing like toasting, microwave or moist heat under pressure. The purposes of this research were to study the use of mezquite cotyledon (Prosopis chilensis (Mol) Stuntz) in cereal bars with two different levels of peanut or walnut; and to determine the effect of two thermal treatment applied on the cotyledon upon the bar characteristics. Twelve different kind of bars were developed through the combination of two levels of peanut or walnut (15% and 18%); the use of mezquite cotyledon (0% and 6%); and the application of two thermal processing to the cotyledon (microwave and toasting). Cereal bars were analysed for chemical, physical and sensory characteristics: moisture, water activity, proximate chemical composition, sensory quality and acceptability. Moisture content of bars with peanut ranged between 10.4% and 10.9%; and for those with walnut, between 10.5% and 12.3%. Protein content was higher in the bars with mezquite cotiledon, being higher those with peanut. Thermal processing did not have any effect on the chemical composition. Bars with mezquite cotyledon treated by microwave showed a higher acceptability. PMID:11048586

  13. [Use of mesquite cotyledon (Prosopis chilensis (Mol) Shuntz) in the manufacturing of cereal bars].

    PubMed

    Estévez, A M; Escobar, B; Ugarte, V

    2000-06-01

    Cereal bars with peanut and walnut has shown to be snack foods of good organoleptic characteristics and high caloric value, due to their content of protein, lipids and carbohydrates. Cotyledons of mezquite seeds have a high protein content which biological quality improves with thermal processing like toasting, microwave or moist heat under pressure. The purposes of this research were to study the use of mezquite cotyledon (Prosopis chilensis (Mol) Stuntz) in cereal bars with two different levels of peanut or walnut; and to determine the effect of two thermal treatment applied on the cotyledon upon the bar characteristics. Twelve different kind of bars were developed through the combination of two levels of peanut or walnut (15% and 18%); the use of mezquite cotyledon (0% and 6%); and the application of two thermal processing to the cotyledon (microwave and toasting). Cereal bars were analysed for chemical, physical and sensory characteristics: moisture, water activity, proximate chemical composition, sensory quality and acceptability. Moisture content of bars with peanut ranged between 10.4% and 10.9%; and for those with walnut, between 10.5% and 12.3%. Protein content was higher in the bars with mezquite cotiledon, being higher those with peanut. Thermal processing did not have any effect on the chemical composition. Bars with mezquite cotyledon treated by microwave showed a higher acceptability.

  14. molSimplify: A toolkit for automating discovery in inorganic chemistry.

    PubMed

    Ioannidis, Efthymios I; Gani, Terry Z H; Kulik, Heather J

    2016-08-15

    We present an automated, open source toolkit for the first-principles screening and discovery of new inorganic molecules and intermolecular complexes. Challenges remain in the automatic generation of candidate inorganic molecule structures due to the high variability in coordination and bonding, which we overcome through a divide-and-conquer tactic that flexibly combines force-field preoptimization of organic fragments with alignment to first-principles-trained metal-ligand distances. Exploration of chemical space is enabled through random generation of ligands and intermolecular complexes from large chemical databases. We validate the generated structures with the root mean squared (RMS) gradients evaluated from density functional theory (DFT), which are around 0.02 Ha/au across a large 150 molecule test set. Comparison of molSimplify results to full optimization with the universal force field reveals that RMS DFT gradients are improved by 40%. Seamless generation of input files, preparation and execution of electronic structure calculations, and post-processing for each generated structure aids interpretation of underlying chemical and energetic trends. © 2016 Wiley Periodicals, Inc. PMID:27364957

  15. Ixmyelocel-T, an expanded multicellular therapy, contains a unique population of M2-like macrophages

    PubMed Central

    2013-01-01

    Introduction M2 macrophages promote tissue repair and regeneration through various mechanisms including immunomodulation and scavenging of tissue debris. Delivering increased numbers of these cells to ischemic tissues may limit tissue injury and promote repair. Ixmyelocel-T is an expanded, autologous multicellular therapy cultured from bone-marrow mononuclear cells (BMMNCs). The purpose of this study was to characterize further a unique expanded population of M2-like macrophages, generated in ixmyelocel-T therapy. Methods Approximately 50 ml of whole bone marrow was obtained from healthy donors and shipped overnight. BMMNCs were produced by using density-gradient separation and cultured for approximately 12 days to generate ixmyelocel-T. CD14+ cells were isolated from ixmyelocel-T with positive selection for analysis. Cell-surface phenotype was examined with flow cytometry and immunofluorescence, and expression of cytokines and chemokines was analyzed with enzyme-linked immunosorbent assay (ELISA). Quantitative real-time PCR was used to analyze expression of genes in BMMNCs, ixmyelocel-T, the CD14+ population from ixmyelocel-T, and M1 and M2 macrophages. Ixmyelocel-T was cultured with apoptotic BMMNCs, and then visualized under fluorescence microscopy to assess efferocytosis. Results Macrophages in ixmyelocel-T therapy expressed surface markers of M2 macrophages, CD206, and CD163. These cells were also found to express several M2 markers, and few to no M1 markers. After stimulation with lipopolysaccharide (LPS), they showed minimal secretion of the proinflammatory cytokines interleukin-12 (IL-12) and tumor necrosis factor alpha (TNF-α) compared with M1 and M2 macrophages. Ixmyelocel-T macrophages efficiently ingested apoptotic BMMNCs. Conclusions Ixmyelocel-T therapy contains a unique population of M2-like macrophages that are characterized by expression of M2 markers, decreased secretion of proinflammatory cytokines after inflammatory stimuli, and efficient

  16. Search for variability in the kinematics of the ionised circumstellar region of M2-9

    NASA Astrophysics Data System (ADS)

    Torres-Peimbert, S.; Arrieta, A.; Georgiev, L.

    In our previous study of M2-9 we found that the radial velocities of the forbidden lines of the ionized species in the nuclear spectra show a negative gradient which correlates with density, electron temperature and electron pressure. The size of the ionized region is relatively small and the travel time with the observed velocities is of order of decades. In an attempt to reveal the nature of the unusual velocity gradient, we present second epoch observational spectral data of the nucleus of M2-9.

  17. 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

  18. 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

  19. 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

  20. 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

  1. Transport of coenzyme M (2-mercaptoethanesulfonic acid) and methylcoenzyme M [(2-methylthio)ethanesulfonic acid] in Methanococcus voltae: identification of specific and general uptake systems.

    PubMed Central

    Dybas, M; Konisky, J

    1989-01-01

    A transport system for coenzyme M (2-mercaptoethanesulfonic acid [HS-CoM]) and methylcoenzyme M [(2-(methylthio)ethanesulfonic acid (CH3-S-CoM)] in Methanococcus voltae required energy, showed saturation kinetics, and concentrated both forms of coenzyme M against a concentration gradient. Transport required hydrogen and carbon dioxide for maximal uptake. CH3-S-CoM uptake was inhibited by N-ethylmaleimide and monensin. Both HS-CoM and CH3-S-CoM uptake showed sodium dependence. In wild-type M. voltae, HS-CoM uptake was concentration dependent, with a Vmax of 960 pmol/min per mg of protein and an apparent Km of 61 microM. Uptake of CH3-S-CoM showed a Vmax of 88 pmol/min per mg of protein and a Km of 53 microM. A mutant of M. voltae resistant to the coenzyme M analog 2-bromoethanesulfonic acid (BES) showed no uptake of CH3-S-CoM but accumulated HS-CoM at the wild-type rate. While the higher-affinity uptake system was specific for HS-CoM, the lower-affinity system mediated uptake of HS-CoM, CH3-S-CoM, and BES. Analysis of the intracellular coenzyme M pools in metabolizing cells showed an intracellular HS-CoM concentration of 14.8 mM and CH3-S-CoM concentration of 0.21 mM. PMID:2509421

  2. Bone morphogenetic protein 7 polarizes THP-1 cells into M2 macrophages.

    PubMed

    Rocher, Crystal; Singla, Reetu; Singal, Pawan K; Parthasarathy, Sampath; Singla, Dinender K

    2012-07-01

    It was hypothesized that monocyte treatment with bone morphogenetic protein 7 (BMP7) would significantly enhance monocyte polarization into M2 macrophages as well as increasing the levels of anti-inflammatory cytokines. In a cell culture system using monocytes (human acute monocytic leukemia cell line THP-1), we studied the effects of BMP7 on monocytes polarizing into M2 macrophages. The data demonstrate that THP-1 cells contain a BMP type II receptor (BMPR2), and that its activation is significantly (p < 0.05) increased following treatment with BMP7. Furthermore, there was an increase of M2 macrophages, BMPR2, and anti-inflammatory cytokines interleukin (IL)-10 and IL-1ra compared with the respective controls. Moreover, treatment with BMP7 caused a significant (p < 0.05) decrease in the levels of pro-inflammatory cytokines IL-6, tumour necrosis factor (TNF-α), and monocyte chemotactic protein-1 (MCP-1), compared with the controls. In conclusion, we suggest for the first time that BMP7 has a unique potential to polarize monocytes into M2 macrophages, required for tissue repair, which will have significant applications for the treatment of atherosclerosis. PMID:22720873

  3. On bistochastic Kadison-Schwarz operators on M2(Bbb C)

    NASA Astrophysics Data System (ADS)

    Mukhamedov, Farrukh; Abduganiev, Abduaziz

    2013-04-01

    In this paper we describe bistochastic Kadison-Schawrz operators acting on M2(Bbb C). Such a description allows us to find positive, but not Kadison-Schwarz operators. Moreover, by means of that characterization we are able to construct Kadison-Schawrz operators, which are not completely positive.

  4. The fuzzy S2 structure of M2-M5 systems in ABJM membrane theories

    NASA Astrophysics Data System (ADS)

    Nastase, Horatiu; Papageorgakis, Constantinos; Ramgoolam, Sanjaye

    2009-05-01

    We analyse the fluctuations of the ground-state/funnel solutions proposed to describe M2-M5 systems in the level-k mass-deformed/pure Chern-Simons-matter ABJM theory of multiple membranes. We show that in the large N limit the fluctuations approach the space of functions on the 2-sphere rather than the naively expected 3-sphere. This is a novel realisation of the fuzzy 2-sphere in the context of Matrix Theories, which uses bifundamental instead of adjoint scalars. Starting from the multiple M2-brane action, a U(1) Yang-Mills theory on Bbb R2,1 × S2 is recovered at large N, which is consistent with a single D4-brane interpretation in Type IIA string theory. This is as expected at large k, where the semiclassical analysis is valid. Several aspects of the fluctuation analysis, the ground-state/funnel solutions and the mass-deformed/pure ABJM equations can be understood in terms of a discrete noncommutative realisation of the Hopf fibration. We discuss the implications for the possibility of finding an M2-brane worldvolume derivation of the classical S3 geometry of the M2-M5 system. Using a rewriting of the equations of the SO(4)-covariant fuzzy 3-sphere construction, we also directly compare this fuzzy 3-sphere against the ABJM ground-state/funnel solutions and show them to be different.

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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

  17. Molecular Mechanisms That Influence the Macrophage M1–M2 Polarization Balance

    PubMed Central

    Wang, Nan; Liang, Hongwei; Zen, Ke

    2014-01-01

    As an essential component of innate immunity, macrophages have multiple functions in both inhibiting or promoting cell proliferation and tissue repair. Diversity and plasticity are hallmarks of macrophages. Classical M1 and alternative M2 activation of macrophages, mirroring the Th1–Th2 polarization of T cells, represent two extremes of a dynamic changing state of macrophage activation. M1-type macrophages release cytokines that inhibit the proliferation of surrounding cells and damage contiguous tissue, and M2-type macrophages release cytokines that promote the proliferation of contiguous cells and tissue repair. M1–M2 polarization of macrophage is a tightly controlled process entailing a set of signaling pathways, transcriptional and posttranscriptional regulatory networks. An imbalance of macrophage M1–M2 polarization is often associated with various diseases or inflammatory conditions. Therefore, identification of the molecules associated with the dynamic changes of macrophage polarization and understanding their interactions is crucial for elucidating the molecular basis of disease progression and designing novel macrophage-mediated therapeutic strategies. PMID:25506346

  18. 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.

  19. ExoMol molecular line lists - XIII. The spectrum of CaO

    NASA Astrophysics Data System (ADS)

    Yurchenko, Sergei N.; Blissett, Audra; Asari, Usama; Vasilios, Marcus; Hill, Christian; Tennyson, Jonathan

    2016-03-01

    An accurate line list for calcium oxide is presented covering transitions between all bound ro-vibronic levels from the five lowest electronic states X 1Σ+, A' 1Π, A 1Σ+, a 3Π, and b 3Σ+. The ro-vibronic energies and corresponding wavefunctions were obtained by solving the fully coupled Schrödinger equation. Ab initio potential energy, spin-orbit, and electronic angular momentum curves were refined by fitting to the experimental frequencies and experimentally derived energies available in the literature. Using our refined model we could (1) reassign the vibronic states for a large portion of the experimentally derived energies (van Groenendael A., Tudorie M., Focsa C., Pinchemel B., Bernath P. F., 2005, J. Mol. Spectrosc., 234, 255), (2) extended this list of energies to J = 61-118 and (3) suggest a new description of the resonances from the A 1Σ+-X 1Σ+ system. We used high level ab initio electric dipole moments reported previously (Khalil H., Brites V., Le Quere F., Leonard C., 2011, Chem. Phys., 386, 50) to compute the Einstein A coefficients. Our work is the first fully coupled description of this system. Our line list is the most complete catalogue of spectroscopic transitions available for 40Ca16O and is applicable for temperatures up to at least 5000 K. CaO has yet to be observed astronomically but its transitions are characterized by being particularly strong which should facilitate its detection. The CaO line list is made available in an electronic form as supplementary data to this article and at www.exomol.com.

  20. Dietary fibre concentrate from Chilean algarrobo (Prosopis chilensis (Mol.) Stuntz) pods: purification and characterization.

    PubMed

    Estévez, Ana María; Figuerola, Fernando; Bernuy, Enrique; Sáenz, Carmen

    2014-12-01

    Prosopis species are generally fast-growing, drought-resistant, nitrogen-fixing trees or shrubs. Fruits of Prosopis spp are indehiscent pods, where pericarp is formed by the epicarp, light brown in colour, and fibrous nature; the mesocarp known as pulp, which is rich in sugars; and the endocarp. The aim of this work was to obtain a fibre concentrate from the pods of Prosopis chilensis Mol. (Stuntz) and to determine the chemical, physical, and technological properties of the pod flour (PF) and of a fibre concentrate or pod purified flour (PPF). Acetone, ethanol, and water at different conditions of time and temperature were used in the purification process. PF showed 53.7 g/100 g of total sugar content, 4.2 g/100 g of reducing sugar content, 41.8 g/100 g of total dietary fibre, 35.8 g/100 g of insoluble fibre, and 6.0 g/100 g of soluble fibre content. The PPF has a total sugar content of 3.8 g/100 g, reducing sugar content of 2.2 g/100 g, total dietary fibre content of 80.8 g/100 g, insoluble fibre content of 75.1 g/100 g, and soluble fibre content of 5.7 g/100 g. The scanning electron microscopy analysis showed the existence of voids in the structure of PPF flour, which reveals the efficiency of the purification process with a high decrease in the total sugar content.

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

    PubMed

    Lam, Roselind S; O'Brien-Simpson, Neil M; Holden, James A; 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

  3. 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

  4. Structure and Mechanism of the M2 Proton Channel of Influenza A Virus

    PubMed Central

    Schnell, Jason R.; Chou, James J.

    2011-01-01

    The integral membrane protein, M2, of influenza virus forms pH-gated proton channels in the viral lipid envelope1. The low pH of an endosome activates the M2 channel prior to hemagglutinin-mediated fusion. Conductance of protons acidifies the viral interior and thereby facilitates dissociation of the matrix protein from the viral nucleoproteins – a required process for unpacking of the viral genome2. In addition to its role in release of viral nucleoproteins, M2 in the trans-Golgi network (TGN) membrane prevents premature conformational rearrangement of newly synthesized hemagglutinin during transport to the cell surface by equilibrating the pH of the TGN with that of the host cell cytoplasm3. Inhibitng the proton conductance of M2 with the anti-viral drug amantadine or rimantadine inhibits viral replication4–7. We have determined by NMR the structure of the tetrameric M2 channel in complex with rimantadine. In the closed state, four tightly packed transmembrane (TM) helices define a narrow channel, in which a “tryptophan gate” is locked by inter-molecular interactions with aspartic acid. A C-terminal, amphipathic (AP) helix oriented nearly perpendicular to the TM helix, forms an inward facing base. Lowering the pH destabilizes the TM helical packing and unlocks the gate, admitting water to conduct protons, while the C-terminal base remains intact, preventing dissociation of the tetramer. Rimantadine binds at four equivalent sites near the gate on the lipid facing side of the channel and stabilizes the closed conformation of the pore. Drug-resistance mutations are predicted to counter the effect of drug binding by either increasing the hydrophilicity of the pore or weakening helix-helix packing, thus facilitating channel opening. PMID:18235503

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

    PubMed

    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

  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. 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

  8. 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

  9. An accurate and efficient computational protocol for obtaining the complete basis set limits of the binding energies of water clusters at the MP2 and CCSD(T) levels of theory: Application to (H2O)m, m = 2-6, 8, 11, 16, and 17.

    PubMed

    Miliordos, Evangelos; Xantheas, Sotiris S

    2015-06-21

    We report MP2 and Coupled Cluster Singles, Doubles, and perturbative Triples [CCSD(T)] binding energies with basis sets up to pentuple zeta quality for the (H2O)m=2-6,8 water clusters. Our best CCSD(T)/Complete Basis Set (CBS) estimates are -4.99 ± 0.04 kcal/mol (dimer), -15.8 ± 0.1 kcal/mol (trimer), -27.4 ± 0.1 kcal/mol (tetramer), -35.9 ± 0.3 kcal/mol (pentamer), -46.2 ± 0.3 kcal/mol (prism hexamer), -45.9 ± 0.3 kcal/mol (cage hexamer), -45.4 ± 0.3 kcal/mol (book hexamer), -44.3 ± 0.3 kcal/mol (ring hexamer), -73.0 ± 0.5 kcal/mol (D2d octamer), and -72.9 ± 0.5 kcal/mol (S4 octamer). We have found that the percentage of both the uncorrected (De) and basis set superposition error-corrected (De (CP)) binding energies recovered with respect to the CBS limit falls into a narrow range on either sides of the CBS limit for each basis set for all clusters. In addition, this range decreases upon increasing the basis set. Relatively accurate estimates (within <0.5%) of the CBS limits can be obtained when using the "23, 13" (for the AVDZ set) or the "12, 12" (for the AVTZ, AVQZ, and AV5Z sets) mixing ratio between De and De (CP). These mixing rations are determined via a least-mean-squares approach from a dataset that encompasses clusters of various sizes. Based on those findings, we propose an accurate and efficient computational protocol that can be presently used to estimate accurate binding energies of water clusters containing up to 30 molecules (for CCSD(T)) and up to 100 molecules (for MP2).

  10. 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,

  11. Thermodynamics of antagonist binding to rat muscarinic M2 receptors: antimuscarinics of the pridinol, sila-pridinol, diphenidol and sila-diphenidol type.

    PubMed Central

    Waelbroeck, M.; Camus, J.; Tastenoy, M.; Lambrecht, G.; Mutschler, E.; Kropfgans, M.; Sperlich, J.; Wiesenberger, F.; Tacke, R.; Christophe, J.

    1993-01-01

    1. We studied the effect of temperature on the binding to rat heart M2 muscarinic receptors of antagonists related to the carbon/silicon pairs pridinol/sila-pridinol and diphenidol/sila-diphenidol (including three germanium compounds) and six structurally related pairs of enantiomers [(R)- and (S)-procyclidine, (R)- and (S)-trihexyphenidyl, (R)- and (S)-tricyclamol, (R)- and (S)-trihexyphenidyl methiodide, (R)- and (S)-hexahydro-diphenidol and (R)- and (S)-hexbutinol]. Binding affinities were determined in competition experiments using [3H]-N-methyl-scopolamine chloride as radioligand. The reference drugs were scopolamine and N-methyl-scopolamine bromide. 2. The affinity of the antagonists either increased or decreased with temperature. van't Hoff plots were linear in the 278-310 degrees K temperature range. Binding of all antagonists was entropy driven. Enthalpy changes varied from large negative values (down to -29 kJ mol-1) to large positive values (up to +30 kJ mol-1). 3. (R)-configurated drugs had a 10 to 100 fold greater affinity for M2 receptors than the corresponding (S)-enantiomers. Enthalpy and entropy changes of the respective enantiomers were different but no consistent pattern was observed. 4. When silanols (R3SiOH) were compared to carbinols (R3COH), the affinity increase caused by C/Si exchange varied between 3 and 10 fold for achiral drugs but was negligible in the case of chiral drugs. Silanols induced more favourable enthalpy and less favourable entropy changes than the corresponding carbinols when binding. Organogermanium compounds (R4Ge) when compared to their silicon counterparts (R4Si) showed no significant difference in affinity as well as in enthalpy and entropy changes. 5. Exchange of a cyclohexyl by a phenyl moiety was associated with an increase or a decrease in drug affinity (depending on the absolute configuration in the case of chiral drugs) and generally also with a more favourable enthalpy change and a less favourable entropy change

  12. Phase transformation and wear studies of plasma sprayed yttria stabilized zirconia coatings containing various mol% of yttria

    SciTech Connect

    Aruna, S.T. Balaji, N.; Rajam, K.S.

    2011-07-15

    Plasma sprayable grade zirconia powders doped with various mol% of yttria (0, 2, 3, 4, 6, 8 and 12 mol%) were synthesized by a chemical co-precipitation route. The coprecipitation conditions were adjusted such that the powders possessed good flowability in the as calcined condition and thus avoiding the agglomeration step like spray drying. Identical plasma spray parameters were used for plasma spraying all the powders on stainless steel plates. The powders and plasma sprayed coatings were characterized by X-ray diffractometry, Scanning Electron Microscopy and Raman spectroscopy. Zirconia powders are susceptible to phase transformations when subjected to very high temperatures during plasma spraying and XRD is insensitive to the presence of some non crystalline phases and hence Raman spectroscopy was used as an important tool. The microstructure of the plasma sprayed coatings showed a bimodal distribution containing fully melted and unmelted zones. The microhardness and wear resistance of the plasma sprayed coatings were determined. Among the plasma sprayed coatings, 3 mol% yttria stabilized zirconia coating containing pure tetragonal zirconia showed the highest wear resistance. - Research Highlights: {yields} Preparation plasma sprayable YSZ powders without any agglomeration process and plasma spraying {yields} Phase transformation studies of plasma sprayed YSZ coatings by XRD and Raman spectroscopy {yields} Microstructure of the plasma sprayed coatings exhibited bimodal distribution {yields} Plasma sprayed 3 mol% YSZ coating exhibited the highest wear resistance {yields} Higher wear resistance is due to the higher fracture toughness of tetragonal 3 mol% YSZ phase.

  13. Macrophage Polarisation: an Immunohistochemical Approach for Identifying M1 and M2 Macrophages

    PubMed Central

    Barros, Mário Henrique M.; Hauck, Franziska; Dreyer, Johannes H.; Kempkes, Bettina; Niedobitek, Gerald

    2013-01-01

    Macrophage polarization is increasingly recognised as an important pathogenetic factor in inflammatory and neoplastic diseases. Proinflammatory M1 macrophages promote T helper (Th) 1 responses and show tumoricidal activity. M2 macrophages contribute to tissue repair and promote Th2 responses. CD68 and CD163 are used to identify macrophages in tissue sections. However, characterisation of polarised macrophages in situ has remained difficult. Macrophage polarisation is regulated by transcription factors, pSTAT1 and RBP-J for M1, and CMAF for M2. We reasoned that double-labelling immunohistochemistry for the detection of macrophage markers together with transcription factors may be suitable to characterise macrophage polarisation in situ. To test this hypothesis, we have studied conditions associated with Th1- and Th2-predominant immune responses: infectious mononucleosis and Crohn’s disease for Th1 and allergic nasal polyps, oxyuriasis, wound healing and foreign body granulomas for predominant Th2 response. In all situations, CD163+ cells usually outnumbered CD68+ cells. Moreover, CD163+ cells, usually considered as M2 macrophages, co-expressing pSTAT1 and RBP-J were found in all conditions examined. The numbers of putative M1 macrophages were higher in Th1- than in Th2-associated diseases, while more M2 macrophages were seen in Th2- than in Th1 related disorders. In most Th1-related diseases, the balance of M1 over M2 cells was shifted towards M1 cells, while the reverse was observed for Th2-related conditions. Hierarchical cluster analysis revealed two distinct clusters: cluster I included Th1 diseases together with cases with high numbers of CD163+pSTAT1+, CD68+pSTAT1+, CD163+RBP-J+ and CD68+RBP-J+ macrophages; cluster II comprised Th2 conditions together with cases displaying high numbers of CD163+CMAF+ and CD68+CMAF+ macrophages. These results suggest that the detection of pSTAT1, RBP-J, and CMAF in the context of CD68 or CD163 expression is a suitable tool

  14. Evidence for a 3 X 10^8 M_⊙ Black Hole in NGC 7052 from Hubble Space Telescope Observations of the Nuclear Gas Disk

    NASA Astrophysics Data System (ADS)

    van der Marel, Roeland P.; van den Bosch, Frank C.

    1998-11-01

    We present a Hubble Space Telescope (HST) study of the nuclear region of the E4 radio galaxy NGC 7052, which has a nuclear disk of dust and gas. The Second Wide Field and Planetary Camera (WFPC2) was used to obtain B, V, and I broadband images and an Hα + [N II] narrowband image. The images yield the stellar surface brightness profile, the optical depth of the dust, and the flux distribution of the ionized gas. The Faint Object Spectrograph was used to obtain Hα + [N II] spectra at six different positions along the major axis, using a 0.26" diameter circular aperture. The emission lines yield the rotation curve of the ionized gas and the radial profile of its velocity dispersion. The observed rotation velocity at r = 0.2" from the nucleus is V = 155 +/- 17 km s^-1. The Gaussian dispersion of the emission lines increases from sigma ~ 70 km s^-1 at r = 1" to sigma ~ 400 km s^-1 on the nucleus. To interpret the gas kinematics, we construct axisymmetric models in which the gas and dust reside in a disk in the equatorial plane of the stellar body and are viewed at an inclination of 70 deg. It is assumed that the gas moves on circular orbits, with an intrinsic velocity dispersion due to turbulence (or otherwise nongravitational motion). The latter is required to fit the observed increase in the line widths toward the nucleus and must reach a value in excess of 500 km s^-1 in the central 0.1". The circular velocity is calculated from the combined gravitational potential of the stars and a possible nuclear black hole. Models without a black hole predict a rotation curve that is shallower than observed (V_pred = 92 km s^-1 at r = 0.2") and are ruled out at greater than 99% confidence. Models with a black hole of mass M_a=3.3^+2.3_-1.3x10^8 M_⊙ provide an acceptable fit. The best-fitting model with a black hole adequately reproduces the observed emission-line shapes on the nucleus, which have a narrower peak and broader wings than a Gaussian. NGC 7052 can be added to the

  15. 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.

  16. The Construction of M2M System with Sensor Networks Using Digital Plethysmograph Sensor

    NASA Astrophysics Data System (ADS)

    Segawa, Norihisa; Asakawa, Kazuhisa; Takahashi, Yoshitsugu; Yamada, Tomoko; Togashi, Atsushi; Sawamoto, Jun

    In recent years, the research of sensor networks advances and it is expected to be used in a wide variety of fields such as traceability system of products, environmental monitoring, health care, etc. We develop a M2M system with the sensor network technology for collection and analysis of the state of health and feedback of advices for better physical activity without human intervention. The system detects abnormality from pulse wave data from pulse wave sensor attached to the user. In this paper, we construct M2M sensor network system with continuous monitoring of arterial pulse wave and an advice generation function based on pr-installed rules, then we evaluate the usefulness of the system through experiment.

  17. M2-brane surface operators and gauge theory dualities in Toda

    NASA Astrophysics Data System (ADS)

    Gomis, Jaume; Le Floch, Bruno

    2016-04-01

    We give a microscopic two dimensional {N} = (2, 2) gauge theory description of arbitrary M2-branes ending on N f M5-branes wrapping a punctured Riemann surface. These realize surface operators in four dimensional {N} = 2 field theories. We show that the expectation value of these surface operators on the sphere is captured by a Toda CFT correlation function in the presence of an additional degenerate vertex operator labelled by a representation {R} of SU( N f ), which also labels M2-branes ending on M5-branes. We prove that symmetries of Toda CFT correlators provide a geometric realization of dualities between two dimensional gauge theories, including {N} = (2, 2) analogues of Seiberg and Kutasov-Schwimmer dualities. As a bonus, we find new explicit conformal blocks, braiding matrices, and fusion rules in Toda CFT.

  18. Stability of the M2 phase of vanadium dioxide induced by coherent epitaxial strain

    NASA Astrophysics Data System (ADS)

    Quackenbush, N. F.; Paik, H.; Wahila, M. J.; Sallis, S.; Holtz, M. E.; Huang, X.; Ganose, A.; Morgan, B. J.; Scanlon, D. O.; Gu, Y.; Xue, F.; Chen, L.-Q.; Sterbinsky, G. E.; Schlueter, C.; Lee, T.-L.; Woicik, J. C.; Guo, J.-H.; Brock, J. D.; Muller, D. A.; Arena, D. A.; Schlom, D. G.; Piper, L. F. J.

    2016-08-01

    Tensile strain along the cR axis in epitaxial VO2 films raises the temperature of the metal insulator transition and is expected to stabilize the intermediate monoclinic M2 phase. We employ surface-sensitive x-ray spectroscopy to distinguish from the TiO2 substrate and identify the phases of VO2 as a function of temperature in epitaxial VO2/TiO2 thin films with well-defined biaxial strain. Although qualitatively similar to our Landau-Ginzburg theory predicted phase diagrams, the M2 phase is stabilized by nearly an order of magnitude more strain than expected for the measured temperature window. Our results reveal that the elongation of the cR axis is insufficient for describing the transition pathway of VO2 epitaxial films and that a strain induced increase of electron correlation effects must be considered.

  19. High temperature embrittlement caused by traces of calcium or strontium in an Al-5.5 mol% Mg alloy

    SciTech Connect

    Horikawa, Keitaro; Kuramoto, Shigeru; Kanno, Motohiro

    1998-09-04

    Al-5--10mol%Mg alloys are now being developed for automotive parts since they have good formability. However, an alloy containing magnesium of more than 5mol% has poor hot rolling characteristics. It has been reported that an Al-5.5mol%Mg alloy shows high temperature embrittlement (HTE) based on intergranular fracture at around 300 C depending on strain rate. This embrittlement is considered to be closely related to the unfavorable hot rolling characteristics of the Al-Mg alloy. One of the present authors reported recently that this embrittlement is caused by a trace amount of sodium of only of only 0.6mass ppm (0.7mol ppm) in a coarse-grained Al-5.5mol%Mg alloy produced using high purity ingots. Although numerous studies have been made on the effect of sodium, little is known about the effect of alkali and alkaline-earth elements other than sodium. However, unusual impurities may inevitably creep in the recycling process in future. For example, it is reported that the Al-Mg alloy is contaminated by calcium through the ceramic tube filter using during melting and casting, and strontium is used commercially as an additional element in Al-Si alloys. Hence, aluminum alloys made using recycled stock may be contaminated at least by calcium and strontium. The purpose of this study is to determine the effect of traces of calcium or strontium on hot ductility of an Al-5.5mol%Mg alloy.

  20. 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.

  1. 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.

  2. Spreading Depression Requires Microglia and is Decreased by their M2a Polarization from Environmental Enrichment

    PubMed Central

    Pusic, Kae M.; Pusic, Aya D.; Kemme, Jordan; Kraig, Richard P.

    2014-01-01

    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 pro-inflammatory 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 pro-inflammatory 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. PMID:24723305

  3. 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

  4. 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

  5. Flowing to higher dimensions: a new strongly-coupled phase on M2 branes

    NASA Astrophysics Data System (ADS)

    Pilch, Krzysztof; Tyukov, Alexander; Warner, Nicholas P.

    2015-11-01

    We describe a one-parameter family of new holographic RG flows that start from AdS 4 × S 7 and go to widehat{Ad{S}_5}× {B}6 , where {B}6 is conformal to a Kähler manifold and widehat{Ad{S}_5} is Poincaré AdS 5 with one spatial direction compactified and fibered over {B}6 . The new solutions "flow up dimensions," going from the (2 + 1)-dimensional conformal field theory on M2 branes in the UV to a (3 + 1)-dimensional field theory on intersecting M5 branes in the infra-red. The M2 branes completely polarize into M5 branes along the flow and the Poincaré sections of the widehat{Ad{S}_5} are the (3 + 1)-dimensional common intersection of the M5 branes. The emergence of the extra dimension in the infra-red suggests a new strongly-coupled phase of the M2 brane and ABJM theories in which charged solitons are becoming massless. The flow solution is first analyzed by finding a four-dimensional {N}=2 supersymmetric flow in {N}=8 gauged supergravity. This is then generalized to a one parameter family of non-supersymmetric flows. The infra-red limit of the solutions appears to be quite singular in four dimensions but the uplift to eleven-dimensional supergravity is remarkable and regular (up to orbifolding). Our construction is a non-trivial application of the recently derived uplift formulae for fluxes, going well beyond the earlier constructions of stationary points solutions. The eleven-dimensional supersymmetry is also analyzed and shows how, for the supersymmetric flow, the M2-brane supersymmetry in the UV is polarized entirely into M5-brane supersymmetry in the infra-red.

  6. Chemerin aggravates DSS-induced colitis by suppressing M2 macrophage polarization.

    PubMed

    Lin, Yuli; Yang, Xuguang; Yue, Wenjie; Xu, Xiaofei; Li, Bingji; Zou, Linlin; He, Rui

    2014-07-01

    Chemerin is present in various inflammatory sites and is closely involved in tissue inflammation. Recent studies have demonstrated that chemerin treatment can cause either anti-inflammatory or pro-inflammatory effects according to the disease model being investigated. Elevated circulating chemerin was recently found in patients with inflammatory bowel disease (IBD); however, the role of chemerin in intestinal inflammation remains unknown. In this study, we demonstrated that the administration of exogenous chemerin (aa17-156) aggravated the severity of dextran sulfate sodium (DSS)-induced colitis, which was characterized by higher clinical scores, extensive mucosal damage and significantly increased local and systemic production of pro-inflammatory cytokines, including IL-6, TNF-α and interferon (IFN-γ). Interestingly, chemerin did not appear to influence the magnitudes of inflammatory infiltrates in the colons, but did result in significantly decreased colonic expression of M2 macrophage-associated genes, including Arginase 1 (Arg-1), Ym1, FIZZ1 and IL-10, following DSS exposure, suggesting an impaired M2 macrophage skewing in vivo. Furthermore, an in vitro experiment showed that the addition of chemerin directly suppressed M2 macrophage-associated gene expression and STAT6 phosphorylation in IL-4-stimulated macrophages. Significantly elevated chemerin levels were found in colons from DSS-exposed mice and from ulcerative colitis (UC) patients and appeared to positively correlate with disease severity. Moreover, the in vivo administration of neutralizing anti-chemerin antibody significantly improved intestinal inflammation following DSS exposure. Taken together, our findings reveal a pro-inflammatory role for chemerin in DSS-induced colitis and the ability of chemerin to suppress the anti-inflammatory M2 macrophage response. Our study also suggests that upregulated chemerin in inflamed colons may contribute to the pathogenesis of IBD.

  7. 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

  8. Immunization with M2e-Displaying T7 Bacteriophage Nanoparticles Protects against Influenza A Virus Challenge

    PubMed Central

    Hashemi, Hamidreza; Pouyanfard, Somayeh; Bandehpour, Mojgan; Noroozbabaei, Zahra; Kazemi, Bahram; Saelens, Xavier; Mokhtari-Azad, Talat

    2012-01-01

    Considering the emergence of highly pathogenic influenza viruses and threat of worldwide pandemics, there is an urgent need to develop broadly-protective influenza vaccines. In this study, we demonstrate the potential of T7 bacteriophage-based nanoparticles with genetically fused ectodomain of influenza A virus M2 protein (T7-M2e) as a candidate universal flu vaccine. Immunization of mice with non-adjuvanted T7-M2e elicited M2e-specific serum antibody responses that were similar in magnitude to those elicited by M2e peptide administered in Freund’s adjuvant. Comparable IgG responses directed against T7 phage capsomers were induced following vaccination with wild type T7 or T7-M2e. T7-M2e immunization induced balanced amounts of IgG1 and IgG2a antibodies and these antibodies specifically recognized native M2 on the surface of influenza A virus-infected mammalian cells. The frequency of IFN-γ-secreting T cells induced by T7-M2e nanoparticles was comparable to those elicited by M2e peptide emulsified in Freund’s adjuvant. Emulsification of T7-M2e nanoparticles in Freund’s adjuvant, however, induced a significantly stronger T cell response. Furthermore, T7-M2e-immunized mice were protected against lethal challenge with an H1N1 or an H3N2 virus, implying the induction of hetero-subtypic immunity in our mouse model. T7-M2e-immunized mice displayed considerable weight loss and had significantly reduced viral load in their lungs compared to controls. We conclude that display of M2e on the surface of T7 phage nanoparticles offers an efficient and economical opportunity to induce cross-protective M2e-based immunity against influenza A. PMID:23029232

  9. 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

    2015-01-01

    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. PMID:25708299

  10. 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.

  11. 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

  12. 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

  13. Dynamic RACH Partition for Massive Access of Differentiated M2M Services.

    PubMed

    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

  14. RESTful M2M gateway for remote wireless monitoring for district central heating networks.

    PubMed

    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. 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

  17. 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

  18. 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.

  19. M2 Macrophage Polarization Mediates Anti-inflammatory Effects of Endothelial Nitric Oxide Signaling

    PubMed Central

    Lee, Woo Je; Tateya, Sanshiro; Cheng, Andrew M.; Rizzo-DeLeon, Norma; Wang, Nicholas F.; Handa, Priya; Wilson, Carole L.; Clowes, Alexander W.; Sweet, Ian R.; Bomsztyk, Karol; Schwartz, Michael W.

    2015-01-01

    Endothelial nitric oxide (NO) signaling plays a physiological role in limiting obesity-associated insulin resistance and inflammation. This study was undertaken to investigate whether this NO effect involves polarization of macrophages toward an anti-inflammatory M2 phenotype. Mice with transgenic endothelial NO synthase overexpression were protected against high-fat diet (HFD)-induced hepatic inflammation and insulin resistance, and this effect was associated with reduced proinflammatory M1 and increased anti-inflammatory M2 activation of Kupffer cells. In cell culture studies, exposure of macrophages to endothelial NO similarly reduced inflammatory (M1) and increased anti-inflammatory (M2) gene expression. Similar effects were induced by macrophage overexpression of vasodilator-stimulated phosphoprotein (VASP), a key downstream mediator of intracellular NO signaling. Conversely, VASP deficiency induced proinflammatory M1 macrophage activation, and the transplantation of bone marrow from VASP-deficient donor mice into normal recipients caused hepatic inflammation and insulin resistance resembling that induced in normal mice by consumption of an HFD. These data suggest that proinflammatory macrophage M1 activation and macrophage-mediated inflammation are tonically inhibited by NO → VASP signal transduction, and that reduced NO → VASP signaling is involved in the effect of HFD feeding to induce M1 activation of Kupffer cells and associated hepatic inflammation. Our data implicate endothelial NO → VASP signaling as a physiological determinant of macrophage polarization and show that signaling via this pathway is required to prevent hepatic inflammation and insulin resistance. PMID:25845662

  20. Determination of Foton M-2 satellite attitude motion by the data of microacceleration measurements

    NASA Astrophysics Data System (ADS)

    Beuselinck, T.; van Bavinchove, C.; Sazonov, V. V.; Chebukov, S. Yu.

    2009-12-01

    The results of reconstruction of uncontrolled attitude motion of the Foton M-2 satellite using measurements with the accelerometer TAS-3 are presented. The attitude motion of this satellite has been previously determined by the measurement data of the Earth’s magnetic field and the angular velocity. The TAS-3 data for this purpose are used for the first time. These data contain a well-pronounced additional component which made impossible their direct employment for the reconstruction of the attitude motion and whose origin was unknown several years ago. Later it has become known that the additional component is caused by the influence of the Earth’s magnetic field. The disclosure of this fact allowed us to take into account a necessary correction in processing of TAS-3 data and to use them for the reconstruction of the attitude motion of Foton M-2. Here, a modified method of processing TAS-3 data is described, as well as results of its testing and employing. The testing consisted in the direct comparison of the motion reconstructed by the new method with the motion constructed by the magnetic measurements. The new method allowed us to find the actual motion of Foton M-2 in the period June 9, 2005-June 14, 2005, when no magnetic measurements were carried out.

  1. 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

    2007-12-01

    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. PMID:17911099

  2. 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

  3. 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.

  4. 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

  5. Comparing the computational complexity of the PNN, the PDM, and the MMNN (M2N2)

    NASA Astrophysics Data System (ADS)

    Chettri, Samir R.; Murakami, Yoshimichi; Nagano, Isamu; Garegnani, Jerry

    1998-03-01

    In classification, the goal is to assign an input vector to a discrete number of output classes. Classifier design has a long history and they have been put to a large number of uses. In this paper we continue the task of categorizing classifiers by their computational complexity as begun. In particular, we derive analytical formulas for the number of arithmetic operations in the probabilistic neural network (PNN) and its polynomial expansion, also known as the polynomial discriminant method (PDM) and the mixture model neural network (M2N2). In addition we perform tests of the classification accuracy of the PDM with respect to the PNN and the M2N2 find that all three are close in accuracy. Based on this research we now have the ability to choose one or the other based on the computational complexity, the memory requirements and the size of the training set. This is a great advantage in an operational environment. We also discus the extension of such methods to hyperspectral data and find that only the M2N2 is suitable for application to such data.

  6. 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.

  7. TPL-2 Regulates Macrophage Lipid Metabolism and M2 Differentiation to Control TH2-Mediated Immunopathology.

    PubMed

    Kannan, Yashaswini; Perez-Lloret, Jimena; Li, Yanda; 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; Wilson, Mark S

    2016-08-01

    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

  8. 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

  9. 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.)

  10. 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. PMID:26413080

  11. 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 ☉}.

  12. Cross Protection against Influenza A Virus by Yeast-Expressed Heterologous Tandem Repeat M2 Extracellular Proteins.

    PubMed

    Lee, Yu-Na; Kim, Min-Chul; Lee, Young-Tae; Hwang, Hye Suk; Lee, Jongsang; Kim, Cheol; Kang, Sang-Moo

    2015-01-01

    The influenza M2 ectodomain (M2e) is well conserved across human influenza A subtypes, but there are few residue changes among avian and swine origin influenza A viruses. We expressed a tandem repeat construct of heterologous M2e sequences (M2e5x) derived from human, swine, and avian origin influenza A viruses using the yeast expression system. Intramuscular immunization of mice with AS04-adjuvanted M2e5x protein vaccines was effective in inducing M2e-specific antibodies reactive to M2e peptide and native M2 proteins on the infected cells with human, swine, or avian influenza virus, mucosal and systemic memory cellular immune responses, and cross-protection against H3N2 virus. Importantly, M2e5x immune sera were found to confer protection against different subtypes of H1N1 and H5N1 influenza A viruses in naïve mice. Also, M2e5x-immune complexes of virus-infected cells stimulated macrophages to secrete cytokines via Fc receptors, indicating a possible mechanism of protection. The present study provides evidence that M2e5x proteins produced in yeast cells could be developed as a potential universal influenza vaccine. PMID:26366729

  13. 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

  14. Asymmetric domino synthesis of indanes bearing four contiguous stereocentres catalyzed by sub-mol% loadings of a squaramide in minutes.

    PubMed

    Loh, Charles C J; Hack, Daniel; Enders, Dieter

    2013-11-11

    An efficient diastereo- and enantioselective synthesis of polyfunctionalized indanes bearing four contiguous stereogenic centres in generally very short reaction times and sub-mol% squaramide catalyst loadings has been developed. The novel methodology creates a maximum of two stereocentres per bond formation via an organocatalytic Michael-Henry domino reaction.

  15. New efficient ligand for sub-mol % copper-catalyzed C-N cross-coupling reactions running under air.

    PubMed

    Larsson, Per-Fredrik; Astvik, Peter; Norrby, Per-Ola

    2012-01-01

    A new efficient ligand, N,N''-dimethyldiethylene triamine (DMDETA), has been synthesized and evaluated for sub-mol % copper-catalyzed C-N cross-coupling reactions. The efficiency of the ligand was determined by kinetic methods. DMDETA proved to display efficiency similar to DMEDA and, in addition, the resulting catalyst was tolerant to air. PMID:23209530

  16. New efficient ligand for sub-mol % copper-catalyzed C–N cross-coupling reactions running under air

    PubMed Central

    Larsson, Per-Fredrik; Astvik, Peter

    2012-01-01

    Summary A new efficient ligand, N,N’’-dimethyldiethylene triamine (DMDETA), has been synthesized and evaluated for sub-mol % copper-catalyzed C–N cross-coupling reactions. The efficiency of the ligand was determined by kinetic methods. DMDETA proved to display efficiency similar to DMEDA and, in addition, the resulting catalyst was tolerant to air. PMID:23209530

  17. 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

  18. Baicalin ameliorates experimental inflammatory bowel disease through polarization of macrophages to an M2 phenotype.

    PubMed

    Zhu, Wei; Jin, Zaishun; Yu, Jianbo; Liang, Jun; Yang, Qingdong; Li, Fujuan; Shi, Xuekui; Zhu, Xiaodong; Zhang, Xiaoli

    2016-06-01

    Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders of the intestinal tract. Baicalin, originally isolated from the root of the Chinese herb Huangqin (Scutellaria baicalensis Georgi) and its main active ingredient, has a protective effect against inflammatory responses in several diseases. The present study investigated the effects of baicalin on macrophage polarization and its therapeutic role in IBD. Murine peritoneal macrophages and mice with colitis were treated with baicalin. Macrophage subset distribution, M1 and M2 macrophage-associated mRNA expression, and interferon regulatory factor 4 and 5 (IRF4 and IRF5) expression were analyzed. siRNA transfection into mouse peritoneal macrophages was utilized to suppress IRF4. Fluorescence-activated cell sorting, western blot, and real-time PCR analyses were performed. Baicalin (50μM) limited lipopolysaccharide (LPS)-induced M1 macrophage polarization; decreased LPS-induced tumor necrosis factor α, interleukin (IL)-23, and IRF5 expression; and increased IL-10, arginase-1 (Arg-1), and IRF4 expression. siRNA-mediated IRF4 silencing significantly impaired baicalin activity. Furthermore, pretreatment with baicalin (100mg/kg) in mice with dextran sodium sulfate (DSS)-induced colitis ameliorated the severity of colitis and significantly decreased the disease activity index (baicalin group, 3.33±0.52 vs. DSS group, 5.67±1.03). Baicalin (100mg/kg) also repressed IRF5 protein expression and promoted IRF4 protein expression in the lamina propria mononuclear cells, and induced macrophage polarization to the M2 phenotype. In summary, our results showed that baicalin upregulates IRF4 protein expression and reverses LPS-induced macrophage subset redistribution. Thus, baicalin alleviates DSS-induced colitis by modulating macrophage polarization to the M2 phenotype.

  19. 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

  20. 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.

  1. Extended culture of macrophages from different sources and maturation results in a common M2 phenotype.

    PubMed

    Chamberlain, Lisa M; Holt-Casper, Dolly; Gonzalez-Juarrero, Mercedes; Grainger, David W

    2015-09-01

    Inflammatory responses to biomaterials heavily influence the environment surrounding implanted devices, often producing foreign-body reactions. The macrophage is a key immunomodulatory cell type consistently associated with implanted biomaterials and routinely used in short-term in vitro cell studies of biomaterials aiming to reproduce host responses. Inconsistencies within these studies, including differently sourced cells, different durations of culture, and assessment of different activation markers, lead to many conflicting results in vitro that confound consistency and conclusions. We hypothesize that different experimentally popular monocyte-macrophage cell types have intrinsic in vitro culture-specific differences that yield conflicting results. Recent studies demonstrate changes in cultured macrophage cytokine expression over time, leading to the hypothesis that changes in macrophage phenotype also occur in response to extended culture. Here, macrophage cells of different transformed and primary-derived origins were cultured for 21 days on model polymer biomaterials. Cell type-based differences in morphology and cytokine/chemokine expression as well as changes in cell surface biomarkers associated with differentiation stage, activation state, and adhesion were compared. Results reflect consistent macrophage development toward an M2 phenotype via up-regulation of the macrophage mannose receptor for all cell types following 21-day extended culture. Significantly, implanted biomaterials experiencing the foreign-body response and encapsulation in vivo often elicit a shift toward an analogous M2 macrophage phenotype. In vitro "default" of macrophage cultures, regardless of lineage, to this M2 state in the presence of biomaterials at long culture periods is not recognized, but has important implications to in vitro modeling of in vivo host response.

  2. EXTENDED CULTURE OF MACROPHAGES FROM DIFFERENT SOURCES AND MATURATION RESULTS IN A COMMON M2 PHENOTYPE

    PubMed Central

    Chamberlain, Lisa M.; Holt-Casper, Dolly; Gonzalez-Juarrero, Mercedes; Grainger, David W.

    2015-01-01

    Inflammatory responses to biomaterials heavily influence the environment surrounding implanted devices, often producing foreign body reactions. The macrophage is a key immunomodulatory cell type consistently associated with implanted biomaterials and routinely employed in short term in vitro cell studies of biomaterials aiming to reproduce host responses. Inconsistencies within these studies, including differently sourced cells, different durations of culture, and assessment of different activation markers, lead to many conflicting results in vitro that confound consistency and conclusions. We hypothesize that different experimentally popular monocyte-macrophage cell types have intrinsic in vitro culture-specific differences that yield conflicting results. Recent studies demonstrate changes in cultured macrophage cytokine expression over time, leading to the hypothesis that changes in macrophage phenotype also occur in response to extended culture. Here, macrophage cells of different transformed and primary-derived origins were cultured for 21 days on model polymer biomaterials. Cell type-based differences in morphology and cytokine/chemokine expression as well as changes in cell surface biomarkers associated with differentiation stage, activation state, and adhesion were compared. Results reflect consistent macrophage development towards an M2 phenotype via up-regulation of the macrophage mannose receptor for all cell types following 21-day extended culture. Significantly, implanted biomaterials experiencing the foreign body response and encapsulation in vivo often elicit a shift towards an analogous M2 macrophage phenotype. In vitro “default” of macrophage cultures, regardless of lineage, to this M2 state in the presence of biomaterials at long culture periods is not recognized but has important implications to in vitro modeling of in vivo host response. PMID:25684281

  3. 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.

  4. 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

  5. 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.

  6. Coprecipitation and hydrothermal synthesis of ultrafine 5.5 mol% CeO{sub 2}-2 mol% YO{sub 1.5}-ZrO{sub 2} powders

    SciTech Connect

    Lin, J.D.; Duh, J.G.

    1997-01-01

    Ultrafine 5.5 mol% CeO{sub 2}-2 mol% YO{sub 1.5}-ZrO{sub 2} powders with controllable crystallite size were synthesized by two kinds of coprecipitation methods and subsequent crystallization treatment. The amorphous gel produced by ammonia coprecipitation and hydrothermal treatment at 200 C for 3.5 h results in an ultrafine powder with a surface area of 206 m{sup 2}/g and a crystallite size of 4.8 nm. The powder produced by urea hydrolysis and calcination exhibits a purely tetragonal phase. In addition, the powders crystallized by hydrothermal treatment exhibit high packing density and can be sintered at lower temperature (<1,400 C) with nearly 100% tetragonal phase achieved.

  7. 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. PMID:24771857

  8. 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.

  9. IEEE802.15.6 NB portable BAN clinic and M2M international standardization.

    PubMed

    Kuroda, Masahiro; Nohara, Yasunobu

    2013-01-01

    The increase of non communicable diseases (NCDs) will change the direction of health services to emphasize the role of preventive medicine in healthcare services. The first short-range medical body are network (BAN) standard IEEE802.15.6 is expected to be used for secure and user-friendly sensor devices for portable medical equipment. A BAN is an enabler for uploading medical data to a backend system for remote diagnoses and treatment. Machine-to-Machine (M2M) infrastructure is also a key technology for providing flexible and affordable services extending electronic health record (EHR) systems. This paper proposes a BAN-based portable clinic that collects health-check data from user-friendly medical devices and sensors and sends the data to a local backend server, and it evaluates the clinic in fields of actual usage. We discuss issues experienced from actual deployment of the system and focus on integrating it into upcoming healthcare M2M infrastructure to achieve affordable and dependable clinic services. We explain the components and workflow of the clinic and the system model. The system is set up at a temporary health center and has a network link to a remote medical help center. The paper concludes with our plan to introduce our system to contribute to internationally standardized preventive medicine. PMID:24110023

  10. 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.

  11. IEEE802.15.6 NB portable BAN clinic and M2M international standardization.

    PubMed

    Kuroda, Masahiro; Nohara, Yasunobu

    2013-01-01

    The increase of non communicable diseases (NCDs) will change the direction of health services to emphasize the role of preventive medicine in healthcare services. The first short-range medical body are network (BAN) standard IEEE802.15.6 is expected to be used for secure and user-friendly sensor devices for portable medical equipment. A BAN is an enabler for uploading medical data to a backend system for remote diagnoses and treatment. Machine-to-Machine (M2M) infrastructure is also a key technology for providing flexible and affordable services extending electronic health record (EHR) systems. This paper proposes a BAN-based portable clinic that collects health-check data from user-friendly medical devices and sensors and sends the data to a local backend server, and it evaluates the clinic in fields of actual usage. We discuss issues experienced from actual deployment of the system and focus on integrating it into upcoming healthcare M2M infrastructure to achieve affordable and dependable clinic services. We explain the components and workflow of the clinic and the system model. The system is set up at a temporary health center and has a network link to a remote medical help center. The paper concludes with our plan to introduce our system to contribute to internationally standardized preventive medicine.

  12. 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.

  13. Straining to observe the M2 phase in epitaxial VO2 films

    NASA Astrophysics Data System (ADS)

    Quackenbush, Nicholas; Wahila, Matthew; Piper, Louis; Paik, Hanjong; Holtz, Megan; Huang, Xin; Brock, Joel; Muller, David; Schlom, Darrell; Woicik, Joseph; Arena, Dario

    It has been more than a decade since it was shown that the transition temperature TMIT of VO2 in epitaxial thin films can be tuned by compressive and tensile strain along the rutile c-axis. Since this discovery, uniaxial strain studies of VO2 nanobeams have demonstrated that compressive strain indeed lowers TMIT, thus stabilizing the metallic rutile phase. However, even minor tensile strain induces an intermediate insulating monoclinic M2 phase. Whether this phase can be stabilized in thin films remains contentious owing to the constraints of sample and/or interface quality. Here, we present hard x-ray photoelectron spectroscopy and temperature-dependent soft x-ray absorption spectroscopy of high quality ultrathin epitaxial VO2 films on TiO2 (001) and (100) substrates. The VO2/TiO2(001) are absent of intermediate phases and maintain a MIT similar to unstrained VO2, while the VO2/TiO2(100) films display a stable M2 phase between the M1 and rutile endpoint phases. We discuss our findings in terms of differences between uniaxial and biaxial strain. This research is supported by the National Science Foundation under DMR-1409912.

  14. Oxysterol mixture and, in particular, 27-hydroxycholesterol drive M2 polarization of human macrophages.

    PubMed

    Marengo, Barbara; Bellora, Francesca; Ricciarelli, Roberta; De Ciucis, Chiara; Furfaro, AnnaLisa; Leardi, Riccardo; Colla, Renata; Pacini, Davide; Traverso, Nicola; Moretta, Alessandro; Pronzato, Maria Adelaide; Bottino, Cristina; Domenicotti, Cinzia

    2016-01-01

    Macrophages play a crucial role in atherosclerosis progression. Classically activated M1 macrophages have been found in rupture-prone atherosclerotic plaques whereas alternatively activated macrophages, M2, localize in stable plaque. Macrophage accumulation of cholesterol and of its oxidized derivatives (oxysterols) leads to the formation of foam cells, a hallmark of atherosclerotic lesions. In this study, the effects of oxysterols in determining the functional polarization of human macrophages were investigated. Monocytes, purified from peripheral blood mononuclear cells of healthy donors, were differentiated into macrophages (M0) and treated with an oxysterol mixture, cholesterol, or ethanol, every 4 H for a total of 4, 8, and 12 H. The administration of the compounds was repeated in order to maintain the levels of oxysterols constant throughout the treatment. Compared with ethanol treatment, the oxysterol mixture decreased the surface expression of CD36 and CD204 scavenger receptors and reduced the amount of reactive oxygen species whereas it did not affect either cell viability or matrix metalloprotease-9 activity. Moreover, the oxysterol mixture increased the expression of both liver X receptor α and ATP-binding cassette transporter 1. An enhanced secretion of the immunoregulatory cytokine IL-10 accompanied these events. The results supported the hypothesis that the constant levels of oxysterols and, in particular, of 27-hydroxycholesterol stimulate macrophage polarization toward the M2 immunomodulatory functional phenotype, contributing to the stabilization of atherosclerotic plaques.

  15. M2SG: mapping human disease-related genetic variants to protein sequences and genomic loci

    PubMed Central

    Ji, Renkai; Cong, Qian; Li, Wenlin; Grishin, Nick V.

    2013-01-01

    Summary: Online Mendelian Inheritance in Man (OMIM) is a manually curated compendium of human genetic variants and the corresponding phenotypes, mostly human diseases. Instead of directly documenting the native sequences for gene entries, OMIM links its entries to protein and DNA sequences in other databases. However, because of the existence of gene isoforms and errors in OMIM records, mapping a specific OMIM mutation to its corresponding protein sequence is not trivial. Combining computer programs and extensive manual curation of OMIM full-text descriptions and original literature, we mapped 98% of OMIM amino acid substitutions (AASs) and all SwissProt Variant (SwissVar) disease-related AASs to reference sequences and confidently mapped 99.96% of all AASs to the genomic loci. Based on the results, we developed an online database and interactive web server (M2SG) to (i) retrieve the mapped OMIM and SwissVar variants for a given protein sequence; and (ii) obtain related proteins and mutations for an input disease phenotype. This database will be useful for analyzing sequences, understanding the effect of mutations, identifying important genetic variations and designing experiments on a protein of interest. Availability and implementation: The database and web server are freely available at http://prodata.swmed.edu/M2S/mut2seq.cgi. Contact: grishin@chop.swmed.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:24002112

  16. Metal hydride preheater for the M2 diesel burner. Final report, September 1992--October 1997

    SciTech Connect

    Gerstmann, J.; Golben, M.

    1999-03-01

    This report describes the results of a Phase 1 Small Business Innovative Research (SBIR) project to demonstrate the feasibility of preheating the catalytic generator of the M2 diesel burner using a metal hydride preheater. Preliminary testing of an electrically heated generator showed that the originally proposed concept of preheating the catalytic generator of the burner would have resulted in excessive weight for the hydride system. An alternate approach of preheating only the 'superheater,' and using it to vaporize the fuel at start-up, was implemented instead. This resulted in an extremely compact and lightweight burner system that ignited cleanly an rapidly. The Phase 1 results indicate that the 'hydride superheater' is an effective means of obtaining clean ignition of a diesel cook stove burner. Furthermore, the resulting burner is considerably smaller and lighter than the M2 burner. Additional work is required to optimize the designs of the preheater and the superheater, to scale-up the capacity of the burner and to develop practical burner controls.

  17. IL-33 Contributes to Schistosoma japonicum-induced Hepatic Pathology through Induction of M2 Macrophages

    PubMed Central

    Peng, Hui; Zhang, Qixian; Li, Xiaojuan; Liu, Zhen; Shen, Jia; Sun, Rui; Wei, Jie; Zhao, Jia; Wu, Xiaoying; Feng, Feng; Zhong, Shuping; Sun, Xi; Wu, Zhongdao

    2016-01-01

    Interleukin (IL)-33 is involved in T helper (Th)2-biased immune responses in mice infected with Schistosoma, but the precise mechanism remains to be elucidated. Herein, we investigated the role of IL-33 and its receptor ST2L in hepatic granuloma pathology induced by Schistosoma japonicum infection. We found that IL-33 induced the increased production of IL-5 and IL-13 from splenocytes and liver mononuclear cells (MNCs) of infected mice. The infected mice developed significantly higher number of ST2L-expressing cells in spleen and liver. Most of the ST2L-expressing cells in liver were F4/80+ macrophages, indicating the key role of macrophages in the response to IL-33. However, the liver MNCs in male-only worm infection had a poor response to IL-33, though elevated serum IL-33 was observed. ST2L+F4/80+ cells were lower in male-only worm infection than that of mixed infection. IL-33 and soluble egg antigen (SEA) upregulated ST2L expression on macrophages in vitro and ST2L-expressing macrophage displayed MHCII-CD11b+M2 phenotype. Macrophage deletion significantly attenuated IL-33-induced type 2 immunity and egg granuloma formation during S. japonicum infection. These data demonstrate that IL-33 contributes to hepatic granuloma pathology through induction of M2 macrophages during S. japonicum infection. PMID:27445267

  18. Myeloid Angiogenic Cells Act as Alternative M2 Macrophages and Modulate Angiogenesis through Interleukin-8

    PubMed Central

    Medina, Reinhold J; O’Neill, Christina L; O’Doherty, T Michelle; Knott, Henry; Guduric-Fuchs, Jasenka; Gardiner, Tom A; Stitt, Alan W

    2011-01-01

    Endothelial progenitor cells (EPCs) promote angiogenesis, and clinical trials have shown such cell therapy to be feasible for treating ischemic disease. However, clinical outcomes have been contradictory owing to the diverse range of EPC types used. We recently characterized two EPC subtypes, and identified outgrowth endothelial cells as the only EPC type with true progenitor and endothelial characteristics. By contrast, myeloid angiogenic cells (MACs) were shown to be monocytic cells without endothelial characteristics despite being widely described as “EPCs.” In the current study we demonstrated that although MACs do not become endothelial cells or directly incorporate into a microvascular network, they can significantly induce endothelial tube formation in vitro and vascular repair in vivo. MAC-derived interleukin-8 (IL-8) was identified as a key paracrine factor, and blockade of IL-8 but not vascular endothelial growth factor (VEGF) prevented MAC-induced angiogenesis. Extracellular IL-8 transactivates VEGFR2 and induces phosphorylation of extracellular signal-regulated kinases. Further transcriptomic and immunophenotypic analysis indicates that MACs represent alternative activated M2 macrophages. Our findings demonstrate an unequivocal role for MACs in angiogenesis, which is linked to paracrine release of cytokines such as IL-8. We also show, for the first time, the true identity of these cells as alternative M2 macrophages with proangiogenic, antiinflammatory and pro–tissue-repair properties. PMID:21670847

  19. Inducible and constitutive expression of pMOL28-encoded nickel resistance in Alcaligenes eutrophus N9A.

    PubMed Central

    Siddiqui, R A; Schlegel, H G; Meyer, M

    1988-01-01

    The nickel and cobalt resistance plasmid pMOL28 was transferred by conjugation from its natural host Alcaligenes eutrophus CH34 to the susceptible A. eutrophus N9A. Strain N9A and its pMOL28-containing transconjugant M220 were studied in detail. At a concentration of 3.0 mM NiCl2, the wild-type N9A did not grow, while M220 started to grow at its maximum exponential growth rate after a lag of 12 to 24 h. When grown in the presence of subinhibitory concentrations (0.5 mM) of nickel salt, M220 grew actively at 3 mM NiCl2 without a lag, indicating that nickel resistance is an inducible property. Expression of nickel resistance required active growth in the presence of nickel salts at a concentration higher than 0.05 mM. Two mutants of M220 were isolated which expressed nickel resistance constitutively. When the plasmids, pMOL28.1 and pMOL28.2, carried by the mutants were transferred to strains H16 and CH34, the transconjugants expressed constitutive nickel resistance. This indicates that the mutation is plasmid located. Both mutants expressed constitutive resistance to nickel and cobalt. Physiological studies revealed the following differences between strain N9A and its pMOL28.1-harboring mutant derivatives. (i) The uptake of 63NiCl2 occurred more rapidly in the susceptible strain and reached a 30- to 60-fold-higher amount that in the pMOL28.1-harboring mutant; (ii) in intact cells of the susceptible strain N9A, the cytoplasmic hydrogenase was inhibited by 1 to 5 nM NiCl2, whereas 10 mM Ni2+ was needed to inhibit the hydrogenase of mutant cells; (iii) the minimal concentration of nickel chloride for the derepressed synthesis of cytoplasmic hydrogenase was lower in strain N9A (1 to 3 microM) than in the constitutive mutant (8 to 10 microM). PMID:3410828

  20. Gold nanoparticle–M2e conjugate coformulated with CpG induces protective immunity against influenza A virus

    PubMed Central

    Tao, Wenqian; Ziemer, Katherine S; Gill, Harvinder S

    2014-01-01

    Aim: This study aimed to develop a novel influenza A vaccine by conjugating the highly conserved extracellular region of the matrix 2 protein (M2e) of influenza A virus to gold nanoparticles (AuNPs) and to test the vaccine in a mouse influenza challenge model. Materials & methods: Citrate-reduced AuNPs (diameter: 12 nm) were synthesized, and characterized by transmission electron microscopy and dynamic light scattering. M2e was conjugated to AuNPs through thiol–gold interactions to form M2e–AuNP conjugates. Particle stability was confirmed by UV–visible spectra, and M2e conjugation was further characterized by x-ray photoelectron spectroscopy. Mice were immunized with M2e–AuNPs with or without CpG (cytosine-guanine rich oligonucleotide) as an adjuvant with appropriate control groups. Sera was collected and M2e-specific immunoglobulin (IgG) was measured, and immunized mice were challenged with PR8-H1N1 influenza virus. Results: M2e-capped AuNPs could be lyophilized and stably resuspended in water. Intranasal vaccination of mice with M2e–AuNP conjugates induced M2e-specific IgG serum antibodies, which significantly increased upon addition of soluble CpG as adjuvant. Upon challenge with lethal PR8, mice vaccinated with M2e-AuNP conjugates were only partially protected, while mice that received soluble CpG as adjuvant in addition to M2e–AuNP were fully protected. Conclusion: Overall, this study demonstrates the potential of using the M2e–AuNP conjugates with CpG as an adjuvant as a platform for developing an influenza A vaccine. PMID:23829488

  1. mol2chemfig, a tool for rendering chemical structures from molfile or SMILES format to LATE X code

    PubMed Central

    2012-01-01

    Displaying chemical structures in LATE X documents currently requires either hand-coding of the structures using one of several LATE X packages, or the inclusion of finished graphics files produced with an external drawing program. There is currently no software tool available to render the large number of structures available in molfile or SMILES format to LATE X source code. We here present mol2chemfig, a Python program that provides this capability. Its output is written in the syntax defined by the chemfig TE X package, which allows for the flexible and concise description of chemical structures and reaction mechanisms. The program is freely available both through a web interface and for local installation on the user’s computer. The code and accompanying documentation can be found at http://chimpsky.uwaterloo.ca/mol2chemfig. PMID:23031664

  2. 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)].

  3. Preparation of TiO2 Nanocrystallite Powders Coated with 9 mol% ZnO for Cosmetic Applications in Sunscreens

    PubMed Central

    Ko, Horng-Huey; Chen, Hui-Ting; Yen, Feng-Ling; Lu, Wan-Chen; Kuo, Chih-Wei; Wang, Moo-Chin

    2012-01-01

    The preparation of TiO2 nanocrystallite powders coated with and without 9 mol% ZnO has been studied for cosmetic applications in sunscreens by a co-precipitation process using TiCl4 and Zn(NO3)2·6H2O as starting materials. XRD results show that the phases of anatase TiO2 and rutile TiO2 coexist for precursor powders without added ZnO (T-0Z) and calcined at 523 to 973 K for 2 h. When the T-0Z precursor powders are calcined at 1273 K for 2 h, only the rutile TiO2 appears. In addition, when the TiO2 precursor powders contain 9 mol% ZnO (T-9Z) are calcined at 873 to 973 K for 2 h, the crystallized samples are composed of the major phase of rutile TiO2 and the minor phases of anatase TiO2 and Zn2Ti3O8. The analyses of UV/VIS/NIR spectra reveal that the absorption of the T-9Z precursor powders after being calcined has a red-shift effect in the UV range with increasing calcination temperature. Therefore, the TiO2 nanocrystallite powders coated with 9 mol% ZnO can be used as the attenuate agent in the UV-A region for cosmetic applications in sunscreens. PMID:22408415

  4. Observational data and orbits of the asteroids discovered at the Molėtai Observatory in 2005-2007

    NASA Astrophysics Data System (ADS)

    Černis, K.; Wlodarczyk, I.; Zdanavičius, J.

    The paper presents statistics of the asteroids observed and discovered at the Molėtai Observatory, Lithuania, in 2005-2007 within the project for astrometric observations of the near-Earth objects (NEOs), the main belt asteroids and comets. CCD observations of asteroids were obtained with the 35/51 cm Maksutov-type meniscus telescope and the 1.65 m Ritchey-Chretien reflector. In the Minor Planet Circulars and the Minor Planet Electronic Circulars (2005-2007) we published 17 003 astrometric positions of 2980 asteroids. Among them 112 were new normal asteroids and one NEO (2006 SF77) discovered at Molėtai; a few NEOs were found by our team independently. For the asteroids discovered at Molėtai their precise orbits were calculated. Because of short observational arc, a few asteroids have low-precision orbits and some asteroids have been lost. For three of them with low-precision orbital elements (NEO 2006 SF77 and two Mars crossers - 2006 SN368 and 2007 VM315), we present their ephemerides for 2016-2018.

  5. PyMod: sequence similarity searches, multiple sequence-structure alignments, and homology modeling within PyMOL

    PubMed Central

    2012-01-01

    Background In recent years, an exponential growing number of tools for protein sequence analysis, editing and modeling tasks have been put at the disposal of the scientific community. Despite the vast majority of these tools have been released as open source software, their deep learning curves often discourages even the most experienced users. Results A simple and intuitive interface, PyMod, between the popular molecular graphics system PyMOL and several other tools (i.e., [PSI-]BLAST, ClustalW, MUSCLE, CEalign and MODELLER) has been developed, to show how the integration of the individual steps required for homology modeling and sequence/structure analysis within the PyMOL framework can hugely simplify these tasks. Sequence similarity searches, multiple sequence and structural alignments generation and editing, and even the possibility to merge sequence and structure alignments have been implemented in PyMod, with the aim of creating a simple, yet powerful tool for sequence and structure analysis and building of homology models. Conclusions PyMod represents a new tool for the analysis and the manipulation of protein sequences and structures. The ease of use, integration with many sequence retrieving and alignment tools and PyMOL, one of the most used molecular visualization system, are the key features of this tool. Source code, installation instructions, video tutorials and a user's guide are freely available at the URL http://schubert.bio.uniroma1.it/pymod/index.html PMID:22536966

  6. Using a PyMOL Activity to Reinforce the Connection between Genotype and Phenotype in an Undergraduate Genetics Laboratory

    PubMed Central

    Simmons, Alexandra D.; Nguyen, Thao K. T.; Follis, Jack L.; Ribes-Zamora, Albert

    2014-01-01

    With the purpose of developing an activity that would help clarify genetic concepts related to the connection between genotype and phenotype and the nature of mutations, we designed a three hour teaching module using the PyMol software. The activity starts with two pre-laboratory assignments, one to learn how to use PyMol and the other to read about a specific protein or protein family. During the laboratory students are given instructions where and how to find additional information on a specific disease and its causal mutations in order to prepare a 10-minute, in-class presentation. Using a post activity, anonymous quiz, we found a statistically significant different grade distribution in students that participated in the PyMol activity relative to a control group. We also found a significant improvement in the student’s comprehension when answering questions regarding the nature of mutations and protein structure. This demonstrates the utility of this simulation activity as a vehicle to improve student’s understanding of specific key genetic concepts. PMID:25461967

  7. Efectos de la irradiación iónica en hielos de moléculas carbonadas

    NASA Astrophysics Data System (ADS)

    Satorre, M. A.

    En Astrofísica podemos encontrar numerosos contextos en los cuales se observan moléculas en estado sólido que, en condiciones estándar de presión y temperatura, se encontrarían como gases o líquidos. Dichas moléculas se denominan hielos y han sido observadas en nubes densas del medio interestelar, en envolturas circumestelares, en satélites del Sistema Solar, en cometas, etc. Los hielos pueden ser alterados en su composición química debido a diversos factores como por ejemplo variaciones de temperatura o aportes energéticos por parte de la irradiación, ya sea tanto de fotones ultravioleta como de iones. Dependiendo del escenario astrofísico que analicemos, unos factores cobran más importancia que otros. Los experimentos de laboratorio muestran el efecto que produce sobre la composición de los hielos la irradiación iónica, en particular sobre los que contenían alguna molécula con átomos de carbono. Dicha composición se analiza con espectroscopía IR en el rango de 2 a ˜ 25μ m. La aplicabilidad de los resultados de los experimentos es distinta dependiendo de la composición química inicial de los hielos, del tipo de ion utilizado y de la dosis total de irradiación. Existen efectos generales de la irradiación sobre la materia en los experimentos de relevancia astrofísica como son: - la formación de nuevas moléculas, que pueden incluir o no el ion incidente; - la progresiva pérdida de hidrógeno (carbonización) cuando irradiamos muestras que originalmente contienen una determinada relación carbono/hidrógeno; - la variación de la temperatura de sublimación que presentan algunos hielos. Esto puede suceder tanto en hielos que estaban presentes antes de la irradiación como en hielos formados por ésta. Se presentará el papel del ion en la formación de nuevas moléculas a partir de las que originalmente se encontraban en el hielo. Al penetrar en él, el ion provoca distintos procesos como rotura de enlaces y excitaciones electr

  8. Characterization of the N-glycans of recombinant bee venom hyaluronidase (Api m 2) expressed in insect cells.

    PubMed

    Soldatova, Lyudmila N; Tsai, Chaoming; Dobrovolskaia, Ekaterina; Marković-Housley, Zora; Slater, Jay E

    2007-01-01

    Honeybee venom hyaluronidase (Api m 2) is a major glycoprotein allergen. Previous studies have indicated that recombinant Api m 2 expressed in insect cells has enzyme activity and IgE binding comparable with that of native Api m 2. In contrast, Api m 2 expressed in Escherichia coli does not. In this study, we characterized the carbohydrate side chains of Api m 2 expressed in insect cells, and compared our data with the established carbohydrate structure of native Api m 2. We assessed both the monosaccharide and the oligosaccharide content of recombinant Api m 2 using fluorophore-assisted carbohydrate electrophoresis and HPLC. To identify the amino acid residues at which glycosylation occurs, we digested recombinant Api m 2 with endoproteinase Glu-C and identified the fragments that contained carbohydrate by specific staining. Recombinant Api m 2 expressed in insect cells contains N-acetylglucosamine, mannose, and fucose, as well as trace amounts of glucose and galactose, and the oligosaccharide analysis is consistent with heterogeneous oligosaccharide chains consisting of two to seven monosaccharides. No sialic acid or N-acetylgalactosamine were detected. These results are similar to published data for native Api m 2, although some monosaccharide components appear to be absent in the recombinant protein. Analysis of proteolytic digests indicates that of the four candidate N-glycosylation sites, carbohydrate chains are attached at asparagines 115 and 263. Recombinant Api m 2 expressed in insect cells has enzymic activity and IgE binding comparable with the native protein, and its carbohydrate composition is very similar. PMID:17479607

  9. 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.

  10. PET imaging of tumor glycolysis downstream of hexokinase through noninvasive measurement of pyruvate kinase M2.

    PubMed

    Witney, Timothy H; James, Michelle L; Shen, Bin; Chang, Edwin; Pohling, Christoph; Arksey, Natasha; Hoehne, Aileen; Shuhendler, Adam; Park, Jun-Hyung; Bodapati, Deepika; Weber, Judith; Gowrishankar, Gayatri; Rao, Jianghong; Chin, Frederick T; Gambhir, Sanjiv Sam

    2015-10-21

    Cancer cells reprogram their metabolism to meet increased biosynthetic demands, commensurate with elevated rates of replication. Pyruvate kinase M2 (PKM2) catalyzes the final and rate-limiting step in tumor glycolysis, controlling the balance between energy production and the synthesis of metabolic precursors. We report here the synthesis and evaluation of a positron emission tomography (PET) radiotracer, [(11)C]DASA-23, that provides a direct noninvasive measure of PKM2 expression in preclinical models of glioblastoma multiforme (GBM). In vivo, orthotopic U87 and GBM39 patient-derived tumors were clearly delineated from the surrounding normal brain tissue by PET imaging, corresponding to exclusive tumor-associated PKM2 expression. In addition, systemic treatment of mice with the PKM2 activator TEPP-46 resulted in complete abrogation of the PET signal in intracranial GBM39 tumors. Together, these data provide the basis for the clinical evaluation of imaging agents that target this important gatekeeper of tumor glycolysis. PMID:26491079

  11. The evolution of M 2-9 from 2000 to 2010

    NASA Astrophysics Data System (ADS)

    Corradi, R. L. M.; Balick, B.; Santander-García, M.

    2011-05-01

    Context. Understanding the formation of collimated outflows is one of the most debated and controversial topics in the study of the late stages of stellar evolution. Aims: M 2-9 is an outstanding representative of extreme aspherical flows. It presents unique features such as a pair of high-velocity dusty polar blobs and a mirror-symmetric rotating pattern in the inner lobes. Their study provides important information on the nature of the poorly understood central source of M 2-9 and its nebula. Methods: Imaging monitoring at sub-arcsec resolution of the evolution of the nebula in the past decade is presented. Spectroscopic data provide complementary information. Results: We determine the proper motions of the dusty blobs, which infer a new distance estimate of 1.3 ± 0.2 kpc, a total nebular size of 0.8 pc, a speed of 147 km s-1, and a kinematical age of 2500 yr. The corkscrew geometry of the inner rotating pattern is confirmed and quantified. Different recombination timescales for different ions explain the observed surface brightness distribution. According to the images taken after 1999, the pattern rotates with a period of 92 ± 4 years. On the other hand, the analysis of images taken between 1952 and 1977 measures a faster angular velocity. If the phenomenon were related to orbital motion, this would correspond to a modest orbital eccentricity (e = 0.10 ± 0.05), and a slightly shorter period (86 ± 5 years). New features have appeared after 2005 on the west side of the lobes and at the base of the pattern. Conclusions: The geometry and travelling times of the rotating pattern support our previous proposal that the phenomenon is produced by a collimated spray of high velocity particles (jet) from the central source, which excites the walls of the inner cavity of M 2-9, rather than by a ionizing photon beam. The speed of such a jet would be remarkable: between 11 000 and 16 000 km s-1. The rotating-jet scenario may explain the formation and excitation of most

  12. 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.

  13. A polarizing question: do M1 and M2 microglia exist?

    PubMed

    Ransohoff, Richard M

    2016-07-26

    Microglial research has entered a fertile, dynamic phase characterized by novel technologies including two-photon imaging, whole-genome transcriptomic and epigenomic analysis with complementary bioinformatics, unbiased proteomics, cytometry by time of flight (CyTOF; Fluidigm) cytometry, and complex high-content experimental models including slice culture and zebrafish. Against this vivid background of newly emerging data, investigators will encounter in the microglial research literature a body of published work using the terminology of macrophage polarization, most commonly into the M1 and M2 phenotypes. It is the assertion of this opinion piece that microglial polarization has not been established by research findings. Rather, the adoption of this schema was undertaken in an attempt to simplify data interpretation at a time when the ontogeny and functional significance of microglia had not yet been characterized. Now, terminology suggesting established meaningful pathways of microglial polarization hinders rather than aids research progress and should be discarded. PMID:27459405

  14. 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

  15. Integrated memristor-MOS (M2) sensor for basic pattern matching applications.

    PubMed

    Kavehei, Omid; Cho, Kyoung-Rok; Lee, Sang-Jin; Al-Sarawi, Said; Eshraghian, Kamran; Abbott, Derek

    2013-05-01

    This paper introduces an integrated sensor circuit based on an analog Memristor-MOS (M2) pattern matching building block that calculates the similarity/dissimilarity between two analog values. A new approach for a pulse-width modulation pixel image sensor compatible with the memristive-MOS matching structure is introduced allowing direct comparison between incoming and stored images. The pulsed-width encoded information from the pixels is forwarded to a matching circuitry that provides an anti-Gaussian-like comparison between the states of memristors. The non-volatile and multi-state memory characteristics of memristor, together with the related ability to be programmed at any one of the intermediate states between logic '1' and logic '0' brings us closer to the implementation of bio-machines that can eventually emulate human-like sensory functions. PMID:23858918

  16. 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.

  17. FAST TRACK COMMUNICATION: Multiple M2-branes and the embedding tensor

    NASA Astrophysics Data System (ADS)

    Bergshoeff, Eric A.; de Roo, Mees; Hohm, Olaf

    2008-07-01

    We show that the Bagger Lambert theory of multiple M2-branes fits into the general construction of maximally supersymmetric gauge theories using the embedding tensor technique. We apply the embedding tensor technique in order to systematically obtain the consistent gaugings of {\\cal N}=8 superconformal theories in 2 + 1 dimensions. This leads to the Bagger Lambert theory, with the embedding tensor playing the role of the four-index antisymmetric tensor defining a '3-algebra'. We present an alternative formulation of the theory in which the embedding tensor is replaced by a set of unrestricted scalar fields. By taking these scalar fields to be parity-odd, the Chern Simons term can be made parity-invariant.

  18. Integrated memristor-MOS (M2) sensor for basic pattern matching applications.

    PubMed

    Kavehei, Omid; Cho, Kyoung-Rok; Lee, Sang-Jin; Al-Sarawi, Said; Eshraghian, Kamran; Abbott, Derek

    2013-05-01

    This paper introduces an integrated sensor circuit based on an analog Memristor-MOS (M2) pattern matching building block that calculates the similarity/dissimilarity between two analog values. A new approach for a pulse-width modulation pixel image sensor compatible with the memristive-MOS matching structure is introduced allowing direct comparison between incoming and stored images. The pulsed-width encoded information from the pixels is forwarded to a matching circuitry that provides an anti-Gaussian-like comparison between the states of memristors. The non-volatile and multi-state memory characteristics of memristor, together with the related ability to be programmed at any one of the intermediate states between logic '1' and logic '0' brings us closer to the implementation of bio-machines that can eventually emulate human-like sensory functions.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. Exact relations between M2-brane theories with and without orientifolds

    NASA Astrophysics Data System (ADS)

    Honda, Masazumi

    2016-06-01

    We study partition functions of low-energy effective theories of M2-branes, whose type IIB brane constructions include orientifolds. We mainly focus on circular quiver superconformal Chern-Simons theory on S 3, whose gauge group is O(2 N + 1) × USp(2 N ) × ···× O(2 N +1)×USp(2 N). This theory is the natural generalization of the mathcal{N} = 5 ABJM theory with the gauge group O(2 N + 1)2 k × USp(2 N )- k . We find that the partition function of this type of theory has a simple relation to the one of the M2-brane theory without the orientifolds, whose gauge group is U( N ) × · · · × U( N ). By using this relation, we determine an exact form of the grand partition function of the O(2 N +1)2 ×USp(2 N )-1 ABJM theory, where its supersymmetry is expected to be enhanced to mathcal{N} = 6. As another interesting application, we discuss that our result gives a natural physical interpretation of a relation between the grand partition functions of the U( N + 1)4 × U( N )-4 ABJ theory and U( N )2 × U( N )-2 ABJM theory, recently conjectured by Grassi-Hatsuda-Mariño. We also argue that partition functions of  3 quiver theories have representations in terms of an ideal Fermi gas systems associated with widehat{D} -type quiver theories and this leads an interesting relation between certain U( N ) and USp(2 N ) supersymmetric gauge theories.

  5. 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.

  6. Sequence Analysis of the Matrix (M2) Protein Gene of Avian Pneumovirus Recovered from Turkey Flocks in the United States

    PubMed Central

    Dar, Arshud M.; Munir, Shirin; Goyal, Sagar M.; Kapur, Vivek

    2003-01-01

    We here report the comparative sequence and phylogenetic analysis of the avian pneumovirus subgroup C (APV C) matrix (M2) gene of cell culture-adapted isolates and clinical samples. Limited heterogeneity was observed among the M2 sequences, suggesting that diagnostic tests and vaccines against APV C are likely to exhibit broad cross-reactivity. PMID:12791921

  7. Human eosinophil major basic protein is an endogenous allosteric antagonist at the inhibitory muscarinic M2 receptor.

    PubMed Central

    Jacoby, D B; Gleich, G J; Fryer, A D

    1993-01-01

    The effect of human eosinophil major basic protein (MBP) as well as other eosinophil proteins, on binding of [3H]N-methyl-scopolamine ([3H]NMS: 1 x 10(-10) M) to muscarinic M2 receptors in heart membranes and M3 receptors in submandibular gland membranes was studied. MBP inhibited specific binding of [3H]NMS to M2 receptors but not to M3 receptors. MBP also inhibited atropine-induced dissociation of [3H]NMS-receptor complexes in a dose-dependent fashion, demonstrating that the interaction of MBP with the M2 muscarinic receptor is allosteric. This effect of MBP suggests that it may function as an endogenous allosteric inhibitor of agonist binding to the M2 muscarinic receptor. Inhibition of [3H]NMS binding by MBP was reversible by treatment with heparin, which binds and neutralizes MBP. Eosinophil peroxidase (EPO) also inhibited specific binding of [3H]NMS to M2 receptors but not to M3 receptors and inhibited atropine-induced dissociation of [3H]NMS-receptor complexes. On a molar basis, EPO is less potent than MBP. Neither eosinophil cationic protein nor eosinophil-derived neurotoxin affected binding of [3H]NMS to M2 receptors. Thus both MBP and EPO are selective allosteric antagonists at M2 receptors. The effects of these proteins may be important causes of M2 receptor dysfunction and enhanced vagally mediated bronchoconstriction in asthma. Images PMID:8473484

  8. Modular unfolding and dissociation of the human respiratory syncytial virus phosphoprotein p and its interaction with the m(2-1) antiterminator: a singular tetramer-tetramer interface arrangement.

    PubMed

    Esperante, Sebastián A; Paris, Gastón; de Prat-Gay, Gonzalo

    2012-10-16

    Paramyxoviruses share the essential RNA polymerase complex components, namely, the polymerase (L), phosphoprotein (P), and nucleoprotein (N). Human respiratory syncytial virus (RSV) P is the smallest polypeptide among the family, sharing a coiled coil tetramerization domain, which disruption renders the virus inactive. We show that unfolding of P displays a first transition with low cooperativity but substantial loss of α-helix content and accessibility to hydrophobic sites, indicative of loose chain packing and fluctuating tertiary structure, typical of molten globules. The lack of unfolding baseline indicates a native state in conformational exchange and metastable at 20 °C. The second transition starts from a true intermediate state, with only the tetramerization domain remaining folded. The tetramerization domain undergoes a two-state dissociation/unfolding reaction (37.3 kcal mol(-1)). The M(2-1) transcription antiterminator, unique to RSV and Metapneumovirus, forms a nonglobular P:M(2-1) complex with a 1:1 stoichiometry and a K(D) of 8.1 nM determined by fluorescence anisotropy, far from the strikingly coincident dissociation range of P and M(2-1) tetramers (10(-28) M(3)). The M(2-1) binding region has been previously mapped to the N-terminal module of P, strongly suggesting the latter as the metastable molten globule domain. Folding, oligomerization, and assembly events between proteins and with RNA are coupled in the RNA polymerase complex. Quantitative assessment of the hierarchy of these interactions and their mechanisms contribute to the general understanding of RNA replication and transcription in Paramyxoviruses. In particular, the unique P-M(2-1) interface present in RSV provides a valuable antiviral target for this worldwide spread human pathogen. PMID:22978633

  9. An efficient blocking M2L translation for low-frequency fast multipole method in three dimensions

    NASA Astrophysics Data System (ADS)

    Takahashi, Toru; Shimba, Yuta; Isakari, Hiroshi; Matsumoto, Toshiro

    2016-05-01

    We propose an efficient scheme to perform the multipole-to-local (M2L) translation in the three-dimensional low-frequency fast multipole method (LFFMM). Our strategy is to combine a group of matrix-vector products associated with M2L translation into a matrix-matrix product in order to diminish the memory traffic. For this purpose, we first developed a grouping method (termed as internal blocking) based on the congruent transformations (rotational and reflectional symmetries) of M2L-translators for each target box in the FMM hierarchy (adaptive octree). Next, we considered another method of grouping (termed as external blocking) that was able to handle M2L translations for multiple target boxes collectively by using the translational invariance of the M2L translation. By combining these internal and external blockings, the M2L translation can be performed efficiently whilst preservingthe numerical accuracy exactly. We assessed the proposed blocking scheme numerically and applied it to the boundary integral equation method to solve electromagnetic scattering problems for perfectly electrical conductor. From the numerical results, it was found that the proposed M2L scheme achieved a few times speedup compared to the non-blocking scheme.

  10. Pyruvate Kinase M2 Regulates Gene Transcription by Acting as A Protein Kinase

    PubMed Central

    Gao, Xueliang; Wang, Haizhen; Jenny, J. Yang; Liu, Xiaowei; Liu, Zhi-Ren

    2012-01-01

    Summary Pyruvate kinase isoform M2 (PKM2) is a glycolysis enzyme catalyzing conversion of phosphoenolpyruvate (PEP) to pyruvate with transferring a phosphate from PEP to ADP. We report here that PKM2 localizes to the cell nucleus. The levels of nuclear PKM2 correlate with cell proliferation. PKM2 activates transcription of MEK5 by phosphorylating stat3 at Y705. In vitro phosphorylation assays show that PKM2 is a protein kinase using PEP as phosphate donor. ADP competes with the protein substrate binding, indicating that the substrate may bind to the ADP site of PKM2. Our experiments suggest that PKM2 dimer is an active protein kinase, while the tetramer is an active pyruvate kinase. Expression a PKM2 mutant that exists as a dimer promotes cell proliferation, indicating that protein kinase activity of PKM2 plays a role in promoting cell proliferation. Our study reveals an important link between metabolism alteration and gene expression during tumor transformation and progression. PMID:22306293

  11. Rates of E1, E2, M1, and M2 transitions in Ni II

    NASA Astrophysics Data System (ADS)

    Cassidy, C. M.; Hibbert, A.; Ramsbottom, C. A.

    2016-03-01

    Aims: We present rates for all E1, E2, M1, and M2 transitions among the 295 fine-structure levels of the configurations 3d9, 3d84s, 3d74s2, 3d84p, and 3d74s4p, determined through an extensive configuration interaction calculation. Methods: The CIV3 code developed by Hibbert and coworkers is used to determine for these levels configuration interaction wave functions with relativistic effects introduced through the Breit-Pauli approximation. Results: Two different sets of calculations have been undertaken with different 3d and 4d functions to ascertain the effect of such variation. The main body of the text includes a representative selection of data, chosen so that key points can be discussed. Some analysis to assess the accuracy of the present data has been undertaken, including comparison with earlier calculations and the more limited range of experimental determinations. The full set of transition data is given in the supplementary material as it is very extensive. Conclusions: We believe that the present transition data are the best currently available. Full Table 4 and Tables 5-8 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/587/A107

  12. Activation and proton transport mechanism in influenza A M2 channel.

    PubMed

    Wei, Chenyu; Pohorille, Andrew

    2013-11-01

    Molecular dynamics trajectories 2 μs in length have been generated for the pH-activated, tetrameric M2 proton channel of the influenza A virus in all protonation states of the pH sensor located at the His(37) tetrad. All simulated structures are in very good agreement with high-resolution structures. Changes in the channel caused by progressive protonation of His(37) provide insight into the mechanism of proton transport. The channel is closed at both His(37) and Trp(41) sites in the singly and doubly protonated states, but it opens at Trp(41) upon further protonation. Anions access the charged His(37) and by doing so stabilize the protonated states of the channel. The narrow opening at the His(37) site, further blocked by anions, is inconsistent with the water-wire mechanism of proton transport. Instead, conformational interconversions of His(37) correlated with hydrogen bonding to water molecules indicate that these residues shuttle protons in high-protonation states. Hydrogen bonds between charged and uncharged histidines are rare. The valve at Val(27) remains on average quite narrow in all protonation states but fluctuates sufficiently to support water and proton transport. A proton transport mechanism in which the channel, depending on pH, opens at either the histidine or valine gate is only partially supported by the simulations. PMID:24209848

  13. Switching of pyruvate kinase isoform L to M2 promotes metabolic reprogramming in hepatocarcinogenesis.

    PubMed

    Wong, Carmen Chak-Lui; Au, Sandy Leung-Kuen; Tse, Aki Pui-Wah; Xu, Iris Ming-Jing; Lai, Robin Kit-Ho; Chiu, David Kung-Chun; Wei, Larry Lai; Fan, Dorothy Ngo-Yin; Tsang, Felice Ho-Ching; Lo, Regina Cheuk-Lam; Wong, Chun-Ming; Ng, Irene Oi-Lin

    2014-01-01

    Hepatocellular carcinoma (HCC) is an aggressive tumor, with a high mortality rate due to late symptom presentation and frequent tumor recurrences and metastasis. It is also a rapidly growing tumor supported by different metabolic mechanisms; nevertheless, the biological and molecular mechanisms involved in the metabolic reprogramming in HCC are unclear. In this study, we found that pyruvate kinase M2 (PKM2) was frequently over-expressed in human HCCs and its over-expression was associated with aggressive clinicopathological features and poor prognosis of HCC patients. Furthermore, knockdown of PKM2 suppressed aerobic glycolysis and cell proliferation in HCC cell lines in vitro. Importantly, knockdown of PKM2 hampered HCC growth in both subcutaneous injection and orthotopic liver implantation models, and reduced lung metastasis in vivo. Of significance, PKM2 over-expression in human HCCs was associated with a down-regulation of a liver-specific microRNA, miR-122. We further showed that miR-122 interacted with the 3UTR of the PKM2 gene. Re-expression of miR-122 in HCC cell lines reduced PKM2 expression, decreased glucose uptake in vitro, and suppressed HCC tumor growth in vivo. Our clinical data and functional studies have revealed a novel biological mechanism involved in HCC metabolic reprogramming. PMID:25541689

  14. A new 2D monolayer BiXene, M2C (M = Mo, Tc, Os).

    PubMed

    Sun, Weiwei; Li, Yunguo; Wang, Baotian; Jiang, Xue; Katsnelson, Mikhail I; Korzhavyi, Pavel; Eriksson, Olle; Di Marco, Igor

    2016-08-25

    The existence of BiXenes, a new family of 2D monolayers, is hereby predicted. Theoretically, BiXenes have 1H symmetry (P6[combining macron]m2) and can be formed from the 4d/5d binary carbides. As the name suggests, they are close relatives of MXenes, which instead have 1T symmetry (P3[combining macron]m1). The newly found BiXenes, as well as some new MXenes, are shown to have formation energies close to that of germanene, which suggests that these materials should be possible to be synthesised. Among them, we illustrate that 1H-Tc2C and 1T-Mo2C are dynamically stable at 0 K, while 1H-Mo2C, 1T-Tc2C, 1H-Os2C, and 1T-Rh2C are likely to be stabilised via strain or temperature. In addition, the nature of the chemical bonding is analysed, emphasizing that the covalency between the transition metal ions and carbon is much stronger in BiXenes than in MXenes. The emergence of BiXenes can not only open up a new era of conducting 2D monolayers, but also provide good candidates for carrier materials aimed at energy storage and spintronic devices that have already been unveiled in MXenes. PMID:27528499

  15. The Lichens experiment at Foton M-2 mission: Survival capacity in space

    NASA Astrophysics Data System (ADS)

    de La Torre, R.; Horneck, G.; Garcia-Sancho, L.

    Lichens are one of the most resistant organisms at Earth They live at very extreme environments in deserts Atacama desert high mountains Himalaya Antarctica Dry Valleys etc This is possible due to the symbiotic relationship between both constituents the algae and the fungui and to their poikilohidric nature characteristic that allows them to survive latent when environmental conditions are very extreme i e when UV radiation is very high temperatures are extreme and dryness exists If humidity returns and temperature tendencies turn near the optimum around 10 C dormant lichens starts to photosynthetice We have selected two epilithic lichen species for the LICHENS experiment which was included at the ESA Biopan-facility located at the outer shell of the satellite Foton M-2 launched into low Earth orbit the 31th of Mai 2005 from Baikonur Russia On of this species was Rhizocarpon geographicum a bipolar epilithic lichen which grows at high mountain regions e g Sierra de Gredos Central Spain with continental climate has been systematically studied in the natural environment Plataforma de Gredos at 2000 m altitude as well as under simulated space conditions at the space simulation facilities of the DLR The sensitivity of the photosynthetic system PSII to the different environmental conditions dryness including vacuum treatment high temperature fluctuations high UV intensity was fluorometrically measured with a MINI PAM Walz Germany The lichen Rhizocarpon geographicum was

  16. NREL National Wind Technology Center (NWTC): M2 Tower; Boulder, Colorado (Data)

    DOE Data Explorer

    Jager, D.; Andreas, A.

    1996-09-24

    The National Wind Technology Center (NWTC), located at the foot of the Rocky Mountains near Boulder, Colorado, is a world-class research facility managed by NREL for the U.S. Department of Energy. NWTC researchers work with members of the wind energy industry to advance wind power technologies that lower the cost of wind energy through research and development of state-of-the-art wind turbine designs. NREL's Measurement and Instrument Data Center provides data from NWTC's M2 tower which are derived from instruments mounted on or near an 82 meter (270 foot) meteorological tower located at the western edge of the NWTC site and about 11 km (7 miles) west of Broomfield, and approximately 8 km (5 miles) south of Boulder, Colorado. The data represent the mean value of readings taken every two seconds and averaged over one minute. The wind speed and direction are measured at six heights on the tower and air temperature is measured at three heights. The dew point temperature, relative humidity, barometric pressure, totalized liquid precipitation, and global solar radiation are also available.

  17. Experiment "Regeneration" Performed Aboard the Russian Spacecraft Foton-M2 in 2005

    NASA Technical Reports Server (NTRS)

    Grigoryan, Elonora; Almeida, Eduardo; Domaratskaya, Elena; Poplinskaya, Valentina; Aleinikova, Karina; Tairbekov, Murad; Mitashov, Victor

    2006-01-01

    The experiments on the newts performed earlier aboard Russian biosate llites showed that the rate of lens and tail regeneration in space wa s greater than on the ground. In parallel it was found that the numbe r of cells in S-phase was greater in space-flown animals than in the ground controls. However, it was unclear whether cell proliferation stimulation was induced by micro-g per se. Molecular mechanisms under lying the change also remained obscure. These issues were addressed b y the joint Russian-American experiment "Regeneration" flown on Foton -M2 in 2005. The method for in-flight delivering DNA precursor BrdU was developed. The experiment showed that during the flight the numbe r of S-phase cells in the regenerating eyes and tails increased. Thes e data together with those obtained earlier suggest that cell prolife ration increases in response to the effects of both micro-g and 1-g a fter return to Earth. The expression of bFGF in regenerating tissues of "flown" newts and ground controls was examined using immuno-histo chemistry. Obtained results suggest that this growth factor is a part icipant of the promotional effect of space flight upon cell prolifera tion in lens and tail regenerates.

  18. The transglutaminase type 2 and pyruvate kinase isoenzyme M2 interplay in autophagy regulation

    PubMed Central

    Altuntas, Sara; Rossin, Federica; Marsella, Claudia; D'Eletto, Manuela; Hidalgo, Laura Diaz; Farrace, Maria Grazia; Campanella, Michelangelo; Antonioli, Manuela; Fimia, Gian Maria; Piacentini, Mauro

    2015-01-01

    Autophagy is a self-degradative physiological process by which the cell removes worn-out or damaged components. Constant at basal level it may become highly active in response to cellular stress. The type 2 transglutaminase (TG2), which accumulates under stressful cell conditions, plays an important role in the regulation of autophagy and cells lacking this enzyme display impaired autophagy/mitophagy and a consequent shift their metabolism to glycolysis. To further define the molecular partners of TG2 involved in these cellular processes, we analysed the TG2 interactome under normal and starved conditions discovering that TG2 interacts with various proteins belonging to different functional categories. Herein we show that TG2 interacts with pyruvate kinase M2 (PKM2), a rate limiting enzyme of glycolysis which is responsible for maintaining a glycolytic phenotype in malignant cells and displays non metabolic functions, including transcriptional co-activation and protein kinase activity. Interestingly, the ablation of PKM2 led to the decrease of intracellular TG2's transamidating activity paralleled by an increase of its tyrosine phosphorylation. Along with this, a significant decrease of ULK1 and Beclin1 was also recorded, thus suggesting a block in the upstream regulation of autophagosome formation. These data suggest that the PKM2/TG2 interplay plays an important role in the regulation of autophagy in particular under cellular stressful conditions such as those displayed by cancer cells. PMID:26702927

  19. A PRIMAL view of the Milky Way, made possible by Gaia and M2M modelling

    NASA Astrophysics Data System (ADS)

    Hunt, J. A. S.; Kawata, D.

    2014-07-01

    We have developed our original made-to-measure (M2M) algorithm, primal, with the aim of modelling the Galactic disc from upcoming Gaia data. From a Milky Way like N-body disc galaxy simulation, we have created mock Gaia data using M0III stars as tracers, taking into account extinction and the expected Gaia errors. In primal, observables calculated from the N-body model are compared with the target stars, at the position of the target stars. Using primal, the masses of the N-body model particles are changed to reproduce the target mock data, and the gravitational potential is automatically adjusted by the changing mass of the model particles. We have also adopted a new resampling scheme for the model particles to keep the mass resolution of the N-body model relatively constant. We have applied primalto this mock Gaia data and we show that primalcan recover the structure and kinematics of a Milky Way like barred spiral disc, along with the apparent bar structure and pattern speed of the bar despite the galactic extinction and the observational errors.

  20. Distributed net-centric architecture of m2m acquisition units with optical GVA

    NASA Astrophysics Data System (ADS)

    Guha, Dipnarayan; Choi, Jun; Hassan, Mashfique

    2005-05-01

    This paper describes the architecture of a low-latency symmetric multiprocessing optical soft memory system to cluster computing inside the core of an adaptive optical signal processor with the aid of soft decision algebraic polynomial algorithms. The optical system hardware is shown to evolve along with the iterator instantiations of the soft algorithm that forms the core of the memory map. The system enables efficient cache coherence protocols used in unit multiprocessors to be run across a homogeneous cluster in optical soft memory systems. We define a structure called the Optical Generalized Viterbi Algorithm Data Structure (Optical GVA DS) that makes up the system map for adaptive optical signal processing. The system executes transforms where algorithms for handling the entire data vector is processed, shortening the computational complexity effectively. Thus the optical soft memory system as described by the evolving Optical GVA DS iterator instantiates enables the design of parallel processors to handle modulated data in the optical domain. This is of importance in the realization of distributed netcentric architectures and forms the basis of large-scale real-time data processing and acquisition in m2m units.

  1. M2M modelling of the Galactic disc via PRIMAL: fitting to Gaia error added data

    NASA Astrophysics Data System (ADS)

    Hunt, Jason A. S.; Kawata, Daisuke

    2014-09-01

    We have adapted our made-to-measure (M2M) algorithm PRIMAL to use mock Milky Way like data constructed from an N-body barred galaxy with a boxy bulge in a known dark matter potential. We use M0 giant stars as tracers, with the expected error of the ESA (European Space Agency) space astrometry mission Gaia. We demonstrate the process of constructing mock Gaia data from an N-body model, including the conversion of a galactocentric Cartesian coordinate N-body model into equatorial coordinates and how to add error to it for a single stellar type. We then describe the modifications made to PRIMAL to work with observational error. This paper demonstrates that PRIMAL can recover the radial profiles of the surface density, radial velocity dispersion, vertical velocity dispersion and mean rotational velocity of the target disc, along with the pattern speed of the bar, to a reasonable degree of accuracy despite the lack of accurate target data. We also construct mock data which take into account dust extinction and show that PRIMAL recovers the structure and kinematics of the disc reasonably well. In other words, the expected accuracy of the Gaia data is good enough for PRIMAL to recover these global properties of the disc, at least in a simplified condition, as used in this paper.

  2. 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.

  3. M2L4 coordination capsules with tunable anticancer activity upon guest encapsulation.

    PubMed

    Ahmedova, Anife; Mihaylova, Rositsa; Momekova, Denitsa; Shestakova, Pavletta; Stoykova, Silviya; Zaharieva, Joana; Yamashina, Masahiro; Momekov, Georgi; Akita, Munetaka; Yoshizawa, Michito

    2016-08-16

    Metallosupramolecular cages and capsules have gained increasing popularity as both molecular containers and anticancer agents. For successful combination of these properties a thorough analysis of the effect of guest encapsulation on the host's cytotoxic properties is highly required. Here we report on the cytotoxicity modulation of Pt(ii) and Pd(ii)-linked M2L4 coordination capsules upon encapsulation of guest molecules such as pyrene and caffeine. The anticancer activity of the capsules against various human cancer cells (HT-29, T-24, HL-60 and its resistant counterparts HL-60/Dox and HL-60/CDDP) significantly altered upon the guest encapsulation. The encapsulation of pyrene molecules causes a decrease in the cytotoxicity of the Pt(ii) capsule, which is stronger than that of the Pd(ii) capsule. The cytotoxicities of the caffeine containing capsules are lower than that of the empty capsules (except for HL-60), but still superior to cisplatin under the same conditions. The observed trends in the anticancer activity of the capsules and their host-guest complexes correlate with their different stabilities toward glutathione, estimated by NMR-based kinetic experiments. Mechanistic insights into the observed cytotoxicities are obtained by fluorescence microscopy imaging of tumor cells treated with the capsules and their pyrene complexes. The data suggest the glutathione-triggered disassembly of the capsular structures as a potential activation pathway for their cytotoxicities. PMID:27488015

  4. Reduction of the linear reflex gain explained from the M1-M2 refractory period.

    PubMed

    Klomp, Asbjorn; de Vlugt, Erwin; Meskers, Carel G M; de Groot, Jurriaan H; Arendzen, J Hans; van der Helm, Frans C T

    2013-06-01

    Linear system identification methods combined with neuromechanical modeling enable the quantification of reflex gains from recorded joint angular perturbation, torque, and/or electromyography (EMG). However, the stretch reflex response as recorded by EMG consists of multiple consecutive activation volleys (M1 and M2 responses) separated by a period of reduced activity and is nonlinearly related to joint perturbation. The goal of this study is to assess to what extent linear assumptions hold when quantifying these reflexive responses. Series of ramp-and-hold angular perturbations with fixed velocity but different ramp durations (and, therefore, different amplitudes) were applied to the wrist joint of seven healthy volunteers. Evoked EMG responses were compared to the reflex response estimated from a common linear reflex model relating EMG to perturbation velocity. Model fits described the measured EMG responses best when the perturbation and M1 response durations were equivalent. With increasing perturbation duration, i.e., amplitude, EMG response increased but reflex gain decreased due to the inert period after M1, which is believed to be related to alignment of the refractory period of the motoneurons. For angular joint perturbations exceeding the M1 duration (coinciding with 2 (°) of wrist joint rotation in this study), reflex gain variation may be largely explained from a shortcoming of the linear model in describing the nonlinear reflex response, and in particular the period of low reflexive activity after M1.

  5. Fast, Low-ionization Emission Regions of the Planetary Nebula M2-42

    NASA Astrophysics Data System (ADS)

    Danehkar, A.; Parker, Q. A.; Steffen, W.

    2016-02-01

    Spatially resolved observations of the planetary nebula M2-42 (PN G008.2-04.8) obtained with the Wide Field Spectrograph on the Australian National University 2.3 m telescope have revealed the remarkable features of bipolar collimated jets emerging from its main structure. Velocity-resolved channel maps derived from the [N ii] λ6584 emission line disentangle different morphological components of the nebula. This information is used to develop a three-dimensional morpho-kinematic model, which consists of an equatorial dense torus and a pair of asymmetric bipolar outflows. The expansion velocity of about 20 km s-1 is measured from the spectrum integrated over the main shell. However, the deprojected velocities of the jets are found to be in the range of 80-160 km s-1 with respect to the nebular center. It is found that the mean density of the collimated outflows, 595 ± 125 cm-3, is five times lower than that of the main shell, 3150 cm-3, whereas their singly ionized nitrogen and sulfur abundances are about three times higher than those determined from the dense shell. The results indicate that the features of the collimated jets are typical of fast, low-ionization emission regions.

  6. SH2 domain-containing phosphatase 1 regulates pyruvate kinase M2 in hepatocellular carcinoma

    PubMed Central

    Tai, Wei-Tien; Hung, Man-Hsin; Chu, Pei-Yi; Chen, Yao-Li; Chen, Li-Ju; Tsai, Ming-Hsien; Chen, Min-Husan; Shiau, Chung-Wai; Boo, Yin-Pin; Chen, Kuen-Feng

    2016-01-01

    Pyruvate kinase M2 (PKM2) is known to promote tumourigenesis through dimer formation of p-PKM2Y105. Here, we investigated whether SH2-containing protein tyrosine phosphatase 1 (SHP-1) decreases p-PKM2Y105 expression and, thus, determines the sensitivity of sorafenib through inhibiting the nuclear-related function of PKM2. Immunoprecipitation and immunoblot confirmed the effect of SHP-1 on PKM2Y105 dephosphorylation. Lactate production was assayed in cells and tumor samples to determine whether sorafenib reversed the Warburg effect. Clinical hepatocellular carcinoma (HCC) tumor samples were assessed for PKM2 expression. SHP-1 directly dephosphorylated PKM2 at Y105 and further decreased the proliferative activity of PKM2; similar effects were found in sorafenib-treated HCC cells. PKM2 was also found to determine the sensitivity of targeted drugs, such as sorafenib, brivanib, and sunitinib, by SHP-1 activation. Significant sphere-forming activity was found in HCC cells stably expressing PKM2. Clinical findings suggest that PKM2 acts as a predicting factor of early recurrence in patients with HCC, particularly those without known risk factors (63.6%). SHP-1 dephosphorylates PKM2 at Y105 to inhibit nuclear function of PKM2 and determines the efficacy of targeted drugs. Targeting PKM2 by SHP-1 might provide new therapeutic insights for patients with HCC. PMID:26959741

  7. Microstructural changes in as-cast M2 grade high speed steel during hot forging

    SciTech Connect

    Ghomashchi, M.R. . Metallurgy Dept.); Sellars, C.M. . Dept. of Engineering Materials)

    1993-10-01

    High speed steels have a complex carbide pattern in the as-cast state which has to be modified to achieve the desired properties of adequate toughness, hot hardness, and wear resistance. The High speed steels have a complex carbide pattern in the as-cast state which has to be modified to achieve the desired properties of adequate toughness, hot hardness, and wear resistance. The effects of hot forging and postdeformation annealing on carbide distribution and morphology in M2 grade high speed steel were studied, and it was shown that hot forging accelerates the spheroidization rate of M[sub 6]C carbide with little effect on coarsening. The mechanism responsible for such acceleration is dominated by mechanical disintegration of M[sub 6]C carbide plates, while diffusion-controlled spheroidization was not significant. For MC carbide particles, coarsening was the dominant mechanism, but it was not possible to ascertain whether diffusion had been unaffected by deformation or even increased by a factor that could be as high as 10,000 times. Annealing after deformation accelerated spheroidization which was attributed to the damaging of carbide plates during forging rather than an increase in diffusion rate, since the matrix was almost substructure-free in the annealed condition, i.e., lack of short-circuiting paths for diffusion.

  8. Pyruvate Kinase M2: A Novel Biomarker for the Early Detection of Acute Kidney Injury

    PubMed Central

    Cheon, Ji Hyun; Kim, Sun Young; Son, Ji Yeon; Kang, Ye Rim; An, Ji Hye; Kwon, Ji Hoon; Song, Ho Sub; Moon, Aree; Lee, Byung Mu; Kim, Hyung Sik

    2016-01-01

    The identification of biomarkers for the early detection of acute kidney injury (AKI) is clinically important. Acute kidney injury (AKI) in critically ill patients is closely associated with increased morbidity and mortality. Conventional biomarkers, such as serum creatinine (SCr) and blood urea nitrogen (BUN), are frequently used to diagnose AKI. However, these biomarkers increase only after significant structural damage has occurred. Recent efforts have focused on identification and validation of new noninvasive biomarkers for the early detection of AKI, prior to extensive structural damage. Furthermore, AKI biomarkers can provide valuable insight into the molecular mechanisms of this complex and heterogeneous disease. Our previous study suggested that pyruvate kinase M2 (PKM2), which is excreted in the urine, is a sensitive biomarker for nephrotoxicity. To appropriately and optimally utilize PKM2 as a biomarker for AKI requires its complete characterization. This review highlights the major studies that have addressed the diagnostic and prognostic predictive power of biomarkers for AKI and assesses the potential usage of PKM2 as an early biomarker for AKI. We summarize the current state of knowledge regarding the role of biomarkers and the molecular and cellular mechanisms of AKI. This review will elucidate the biological basis of specific biomarkers that will contribute to improving the early detection and diagnosis of AKI. PMID:26977258

  9. Pentraxin-3 Attenuates Renal Damage in Diabetic Nephropathy by Promoting M2 Macrophage Differentiation.

    PubMed

    Sun, Huaibin; Tian, Jun; Xian, Wanhua; Xie, Tingting; Yang, Xiangdong

    2015-10-01

    As one of the most important long-term complications of diabetes, diabetic nephropathy (DN) is the major cause of end-stage renal disease and high mortality in diabetic patients. The long pentraxin 3 (Ptx3) is a member of a superfamily of conserved proteins characterized by a cyclic multimeric structure and a conserved C-terminal domain. Several clinical investigations have demonstrated that elevated plasma Ptx3 levels are associated with cardiovascular and chronic kidney diseases (CKD). However, the therapeutic effect of Ptx3 on DN has never been investigated. In our current study, we showed a crucial role for Ptx3 in attenuating renal damage in DN. In our mouse hyperglycemia-induced nephropathy model, Ptx3 treatment showed significantly increased expression of nephrin, acetylated nephrin, and Wilm's tumor-1 protein (WT-1) when compared with control. The number of CD4(+) T cells, CD8(+) T cells, Ly6G(+) neutrophils, and CD11b(+) macrophages were all significantly lower in the Ptx3-treated group than that in the control group in DN. The IL-4 and IL-13 levels in the Ptx3-treated group were markedly higher than that in the control group in DN. Correspondingly, the Ptx3-treated group showed increased numbers of Arg1- or CD206-expressing macrophages compared with the control group. Furthermore, inhibition of Ptx3-treated macrophages abrogated the alleviated renal damage induced by Ptx3 treatment. In conclusion, Ptx3 attenuates renal damage in DN by promoting M2 macrophage differentiation.

  10. Nitroxyl (HNO) reduces endothelial and monocyte activation and promotes M2 macrophage polarization.

    PubMed

    Andrews, Karen L; Sampson, Amanda K; Irvine, Jennifer C; Shihata, Waled A; Michell, Danielle L; Lumsden, Natalie G; Lim, Chloe; Huet, Olivier; Drummond, Grant R; Kemp-Harper, Barbara K; Chin-Dusting, Jaye P F

    2016-09-01

    Nitroxyl anion (HNO) donors are currently being assessed for their therapeutic utility in several cardiovascular disorders including heart failure. Here, we examine their effect on factors that precede atherosclerosis including endothelial cell and monocyte activation, leucocyte adhesion to the endothelium and macrophage polarization. Similar to the NO donor glyceryl trinitrate (GTN), the HNO donors Angeli's salt (AS) and isopropylamine NONOate (IPA/NO) decreased leucocyte adhesion to activated human umbilical vein endothelial cells (HUVECs) and mouse isolated aorta. This reduction in adhesion was accompanied by a reduction in intercellular adhesion molecule-1 (ICAM-1) and the cytokines monocyte chemoattractant protein 1 (MCP-1) and interleukin 6 (IL-6) which was inhibitor of nuclear factor κB (NFκB) α (IκBα)- and subsequently NFκB-dependent. Intriguingly, the effects of AS on leucocyte adhesion, like those on vasodilation, were found to not be susceptible to pharmacological tolerance, unlike those observed with GTN. As well, HNO reduces monocyte activation and promotes polarization of M2 macrophages. Taken together, our data demonstrate that HNO donors can reduce factors that are associated with and which precede atherosclerosis and may thus be useful therapeutically. Furthermore, since the effects of the HNO donors were not subject to tolerance, this confers an additional advantage over NO donors. PMID:27231254

  11. Allosteric interactions of three muscarine antagonists at bovine tracheal smooth muscle and cardiac M2 receptors.

    PubMed

    Roffel, A F; Elzinga, C R; Meurs, H; Zaagsma, J

    1989-03-01

    The kinetics of [3H]dexetimide dissociation from muscarine receptors in bovine cardiac left ventricular and tracheal smooth muscle membranes were studied in the absence and presence of three muscarine antagonists. It was found that [3H]dexetimide dissociation from cardiac muscarine receptors was monophasic and very fast (half life less than 1 min) and was slowed by the cardioselective muscarine antagonists, gallamine, methoctramine and AF-DX 116, concentration dependently. [3H]Dexetimide dissociation from tracheal muscarine receptors was biphasic, with a fast phase (half-life less than 1 min) followed after 4-5 min by a slow phase (half-life = 38.5 min). The fast component, but not the slow component, was slowed by the muscarine antagonists with concentration dependencies very similar to those found in the heart. We conclude from these data that the major population of tracheal smooth muscle muscarine receptors resembles the cardiac M2 type not only with respect to equilibrium binding affinities but also with respect to the secondary, allosteric binding site on the muscarine receptor. The results also imply that the cardiac receptor subtype is much more sensitive to allosteric modulation than the glandular/smooth muscle receptor subtype. PMID:2714370

  12. Nuclear pyruvate kinase M2 complex serves as a transcriptional coactivator of arylhydrocarbon receptor.

    PubMed

    Matsuda, Shun; Adachi, Jun; Ihara, Masaru; Tanuma, Nobuhiro; Shima, Hiroshi; Kakizuka, Akira; Ikura, Masae; Ikura, Tsuyoshi; Matsuda, Tomonari

    2016-01-29

    Pyruvate kinase M2 (PKM2) and pyruvate dehydrogenase complex (PDC) regulate production of acetyl-CoA, which functions as an acetyl donor in diverse enzymatic reactions, including histone acetylation. However, the mechanism by which the acetyl-CoA required for histone acetylation is ensured in a gene context-dependent manner is not clear. Here we show that PKM2, the E2 subunit of PDC and histone acetyltransferase p300 constitute a complex on chromatin with arylhydrocarbon receptor (AhR), a transcription factor associated with xenobiotic metabolism. All of these factors are recruited to the enhancer of AhR-target genes, in an AhR-dependent manner. PKM2 contributes to enhancement of transcription of cytochrome P450 1A1 (CYP1A1), an AhR-target gene, acetylation at lysine 9 of histone H3 at the CYP1A1 enhancer. Site-directed mutagenesis of PKM2 indicates that this enhancement of histone acetylation requires the pyruvate kinase activity of the enzyme. Furthermore, we reveal that PDC activity is present in nuclei. Based on these findings, we propose a local acetyl-CoA production system in which PKM2 and PDC locally supply acetyl-CoA to p300 from abundant PEP for histone acetylation at the gene enhancer, and our data suggest that PKM2 sensitizes AhR-mediated detoxification in actively proliferating cells such as cancer and fetal cells.

  13. Cross section for inelastic neutron ''acceleration'' by {sup 178}Hf{sup m2}

    SciTech Connect

    Karamian, S. A.; Carroll, J. J.

    2011-02-15

    The scattering of thermal neutrons from isomeric nuclei may include events in which the outgoing neutrons have increased kinetic energy. This process has been called inelastic neutron acceleration, or INNA, and occurs when the final nucleus, after emission of the neutron, is left in a state with lower energy than that of the isomer. The result, therefore, is an induced depletion of the isomer to the ground state. A cascade of several {gamma}'s must accompany the neutron emission to release the high angular momentum of the initial isomeric state. INNA was previously observed in a few cases, and the measured cross sections were only in modest agreement with theoretical estimates. The most recent measurement of an INNA cross section was {sigma}{sub INNA}=258{+-}58 b for neutron scattering by {sup 177}Lu{sup m}. In the present work, an INNA cross section of {sigma}{sub INNA}=168 {+-} 33 b was deduced from measurements of the total burnup of the high-spin, four-quasiparticle isomer {sup 178}Hf{sup m2} during irradiation by thermal neutrons. Statistical estimates for the probability of different reaction channels past neutron absorption were used in the analysis, and the deduced {sigma}{sub INNA} was compared to the theoretically predicted cross section.

  14. Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis

    SciTech Connect

    Anastasiou, Dimitrios; Yu, Yimin; Israelsen, William J.; Jiang, Jian-Kang; Boxer, Matthew B.; Hong, Bum Soo; Tempel, Wolfram; Dimov, Svetoslav; Shen, Min; Jha, Abhishek; Yang, Hua; Mattaini, Katherine R.; Metallo, Christian M.; Fiske, Brian P.; Courtney, Kevin D.; Malstrom, Scott; Khan, Tahsin M.; Kung, Charles; Skoumbourdis, Amanda P.; Veith, Henrike; Southall, Noel; Walsh, Martin J.; Brimacombe, Kyle R.; Leister, William; Lunt, Sophia Y.; Johnson, Zachary R.; Yen, Katharine E.; Kunii, Kaiko; Davidson, Shawn M.; Christofk, Heather R.; Austin, Christopher P.; Inglese, James; Harris, Marian H.; Asara, John M.; Stephanopoulos, Gregory; Salituro, Francesco G.; Jin, Shengfang; Dang, Lenny; Auld, Douglas S.; Park, Hee-Won; Cantley, Lewis C.; Thomas, Craig J.; Vander Heiden, Matthew G.

    2012-08-26

    Cancer cells engage in a metabolic program to enhance biosynthesis and support cell proliferation. The regulatory properties of pyruvate kinase M2 (PKM2) influence altered glucose metabolism in cancer. The interaction of PKM2 with phosphotyrosine-containing proteins inhibits enzyme activity and increases the availability of glycolytic metabolites to support cell proliferation. This suggests that high pyruvate kinase activity may suppress tumor growth. We show that expression of PKM1, the pyruvate kinase isoform with high constitutive activity, or exposure to published small-molecule PKM2 activators inhibits the growth of xenograft tumors. Structural studies reveal that small-molecule activators bind PKM2 at the subunit interaction interface, a site that is distinct from that of the endogenous activator fructose-1,6-bisphosphate (FBP). However, unlike FBP, binding of activators to PKM2 promotes a constitutively active enzyme state that is resistant to inhibition by tyrosine-phosphorylated proteins. This data supports the notion that small-molecule activation of PKM2 can interfere with anabolic metabolism.

  15. Two-dimensional topological insulators in group-11 chalcogenide compounds: M2Te (M =Cu ,Ag )

    NASA Astrophysics Data System (ADS)

    Ma, Yandong; Kou, Liangzhi; Dai, Ying; Heine, Thomas

    2016-06-01

    Two-dimensional (2D) topological insulators (TIs) are recently recognized states of quantum matter that are highly interesting for lower-power-consuming electronic devices owing to their nondissipative transport properties protected from backscattering. So far, only few 2D TIs, suffering from small bulk band gap (<10 meV ), have been experimentally confirmed. Here, through first-principles calculations, we propose a family of 2D TIs in group-11 chalcogenide 2D crystals, M2Te (M =Cu ,Ag ) . The nontrivial topological states in C u2Te and A g2Te 2D crystals, identified by topological invariant and edge state calculations, exhibit sizeable bulk gaps of 78 and 150 meV, respectively, suggesting that they are candidates for room-temperature applications. Moreover, strain engineering leads to effective control of the nontrivial gaps of C u2Te and A g2Te , and a topological phase transition can be realized in C u2Te , while the nontrivial phase in A g2Te is stable against strain. Their dynamic and thermal stabilities are further confirmed by employing phonon calculations and ab initio molecular dynamic simulations.

  16. Efficient Plasma Production in Low Background Neutral Pressures with the M2P2 Prototype

    NASA Technical Reports Server (NTRS)

    Ziemba, T.; Euripides, P.; Winglee, R.; Slough, J.; Giersch, L.

    2003-01-01

    Mini-Magnetospheric Plasma Propulsion (M2P2) seeks the creation of a large-scale (10 km radius) magnetic wall or bubble (i.e. a magnetosphere) by the electromagnetic inflation of a small-scale (20 cm radius) dipole magnet. The inflated magnetosphere will intercept the solar wind and thereby provide high-speed propulsion with modest power and fuel requirements due to the gain provided by the ambient medium. Magnetic field inflation is produced by the injection of plasma onto the dipole magnetic field eliminating the need for large mechanical structures and added material weight at launch. For successful inflation of the magnetic bubble a beta near unity must be achieved along the imposed dipole field. This is dependent on the plasma parameters that can be achieved with a plasma source that provide continuous operation at the desired power levels of 1 to 2 kilowatts. Over the last two years we have been developing a laboratory prototype to demonstrate the inflation of the magnetic field under space-like conditions. In this paper we will present some of the latest results from the prototype development at the University of Washington and show that the prototype can produce high ionization efficiencies while operating in near space like neutral background pressures producing electron temperatures of a few tens of electron volts. This allows for operation with propellant expenditures lower than originally estimated.

  17. Nuclear pyruvate kinase M2 complex serves as a transcriptional coactivator of arylhydrocarbon receptor

    PubMed Central

    Matsuda, Shun; Adachi, Jun; Ihara, Masaru; Tanuma, Nobuhiro; Shima, Hiroshi; Kakizuka, Akira; Ikura, Masae; Ikura, Tsuyoshi; Matsuda, Tomonari

    2016-01-01

    Pyruvate kinase M2 (PKM2) and pyruvate dehydrogenase complex (PDC) regulate production of acetyl-CoA, which functions as an acetyl donor in diverse enzymatic reactions, including histone acetylation. However, the mechanism by which the acetyl-CoA required for histone acetylation is ensured in a gene context-dependent manner is not clear. Here we show that PKM2, the E2 subunit of PDC and histone acetyltransferase p300 constitute a complex on chromatin with arylhydrocarbon receptor (AhR), a transcription factor associated with xenobiotic metabolism. All of these factors are recruited to the enhancer of AhR-target genes, in an AhR-dependent manner. PKM2 contributes to enhancement of transcription of cytochrome P450 1A1 (CYP1A1), an AhR-target gene, acetylation at lysine 9 of histone H3 at the CYP1A1 enhancer. Site-directed mutagenesis of PKM2 indicates that this enhancement of histone acetylation requires the pyruvate kinase activity of the enzyme. Furthermore, we reveal that PDC activity is present in nuclei. Based on these findings, we propose a local acetyl-CoA production system in which PKM2 and PDC locally supply acetyl-CoA to p300 from abundant PEP for histone acetylation at the gene enhancer, and our data suggest that PKM2 sensitizes AhR-mediated detoxification in actively proliferating cells such as cancer and fetal cells. PMID:26405201

  18. Analysis of Cell Proliferation in Newt (Pleurodeles waltl) Tissue Regeneration during Spaceflight in Foton M-2

    NASA Technical Reports Server (NTRS)

    Almeida, E. A. C.; Roden, C.; Phillips, J. A.; Yusuf, R.; Globus, R. K.; Searby, N.; Vercoutere, W.; Morey-Holton, E.; Tairbekov, M.; Grigoryan, N.; Domaratskaya, E.; Poplinskaya, V.; Mitashov, V.

    2006-01-01

    Terrestrial organisms exposed to microgravity during spaceflight expe rience musculoskeletal degeneration. It is still not understood if lo nger-term exposures to microgravity induce degeneration in other tiss ues, and if these effects are also observed in neutrally buoyant aqu atic organisms that may be pre-adapted to mechanical unloading. The " Regeneration" experiment conducted collaboratively between Russian an d US scientists for 16 days in the Russian Foton M-2 spaceflight soug ht to test the hypothesis that microgravity alters the proliferation of cells in regenerating tail tissue of the newt Pleurodeles waltl. Our initial results indicate that we successfUlly delivered the proli feration marker 5-bromo-2'-deoxy Uridine (BrdU) during spaceflight, and that it was incorporated in the nuclei of cells in regenerating tis sues. Cells in spaceflight tail regenerates proliferated at a slight ly slower rate and were more undifferentiated than those in ground sy nchronous controls. In addition, the size of regenerating tails from spaceflight was smaller than synchronous controls. However, onboard temperature recordings show that the temperature in spaceflight was a bout 2 C lower than ground synchronous controls, possibly explaining the observed differences. Additional post-facto ground controls at ma tched temperatures will correctly determine the effects of spaceflig ht on regenerative cell proliferation in the newt.

  19. First passage times in M2[X ]|G |1 |R queue with hysteretic overload control policy

    NASA Astrophysics Data System (ADS)

    Pechinkin, Alexander V.; Razumchik, Rostislav R.; Zaryadov, Ivan S.

    2016-06-01

    One of the reported approaches towards the solution of overload problem in networks of SIP servers is the implementation of multi-level hysteretic control of arrivals in SIP servers. Each level, being the parameter of the policy, specifies operation mode of SIP server i.e. it implicitly indicates what SIP server must do with the arriving packets. The choice of parameters' values is not guided by standards and is usually left for the network owner. In general, all operation modes of the considered policy can be grouped into two groups: normal mode (when all arriving packets are accepted) and congested mode (when part or all arriving packets are being dropped). Such grouping may serve as the criteria for choosing parameters' values of the policy: pick those values which minimize SIP server sojourn time in congested mode. In this short note we propose some analytical results which facilitate the solution of stated minimization problem. The considered mathematical model of SIP server is the queueing system M2[X ]|G |1 |R with batch arrivals and bi-level hysteretic control policy, which specifies three operation modes: normal (customers both flows are accepted), overload (only customers from one flow are accepted), discard (customers from both flows are blocked/lost)). The switching between modes can occur only on service completions. Analytical method allowing computation of stationary sojourn times in different operation modes (as well as first passage times between modes) is presented in brief. Numerical example is given.

  20. The transglutaminase type 2 and pyruvate kinase isoenzyme M2 interplay in autophagy regulation.

    PubMed

    Altuntas, Sara; Rossin, Federica; Marsella, Claudia; D'Eletto, Manuela; Diaz-Hidalgo, Laura; Farrace, Maria Grazia; Campanella, Michelangelo; Antonioli, Manuela; Fimia, Gian Maria; Piacentini, Mauro

    2015-12-29

    Autophagy is a self-degradative physiological process by which the cell removes worn-out or damaged components. Constant at basal level it may become highly active in response to cellular stress. The type 2 transglutaminase (TG2), which accumulates under stressful cell conditions, plays an important role in the regulation of autophagy and cells lacking this enzyme display impaired autophagy/mitophagy and a consequent shift their metabolism to glycolysis. To further define the molecular partners of TG2 involved in these cellular processes, we analysed the TG2 interactome under normal and starved conditions discovering that TG2 interacts with various proteins belonging to different functional categories. Herein we show that TG2 interacts with pyruvate kinase M2 (PKM2), a rate limiting enzyme of glycolysis which is responsible for maintaining a glycolytic phenotype in malignant cells and displays non metabolic functions, including transcriptional co-activation and protein kinase activity. Interestingly, the ablation of PKM2 led to the decrease of intracellular TG2's transamidating activity paralleled by an increase of its tyrosine phosphorylation. Along with this, a significant decrease of ULK1 and Beclin1 was also recorded, thus suggesting a block in the upstream regulation of autophagosome formation. These data suggest that the PKM2/TG2 interplay plays an important role in the regulation of autophagy in particular under cellular stressful conditions such as those displayed by cancer cells. PMID:26702927

  1. Holographic, Script N = 1 supersymmetric RG flows on M2 branes

    NASA Astrophysics Data System (ADS)

    Bobev, Nikolay; Halmagyi, Nick; Pilch, Krzysztof; Warner, Nicholas P.

    2009-09-01

    We find a family of holographic Script N = 1 supersymmetric RG flows on M2 branes. These flows are driven by two mass parameters from the maximally (Script N = 8) supersymmetric theory and the infra-red theory is controlled by two fixed points, one with G2 symmetry and the other with SU(3) × U(1) symmetry and Script N = 2 supersymmetry. The generic flow, with unequal mass parameters, is Script N = 1 supersymmetric but goes to the SU(3) × U(1) symmetric, Script N = 2 supersymmetric fixed point, where the masses are equal. The only flow that goes to the G2 symmetric point occurs when one of the mass parameters is set to zero. There is an Script N = 1 supersymmetric flow from the G2 symmetric point to the SU(3) × U(1) symmetric point and supergravity gives a prediction of ±1/61/2 for the anomalous dimensions of the operators that drive this flow. We examine these flows from the field theory perspective but find that one is limited to qualitative results since Script N = 1 supersymmetry in three dimensions is insufficient to protect the form and dimensions of the operators involved in the flow.

  2. Subcellular Distribution of M2-muscarinic Receptors in Relation to Dopaminergic Neurons of the Rat Ventral Tegmental Area

    PubMed Central

    Garzón, Miguel; Pickel, Virginia M.

    2008-01-01

    Acetylcholine can affect cognitive functions and reward, in part, through activation of muscarinic receptors in the ventral tegmental area (VTA) to evoke changes in mesocorticolimbic dopaminergic transmission. Of the known muscarinic receptor subtypes present in the VTA, the M2 receptor (M2R) is most implicated in autoregulation, and also may play a heteroreceptor role in regulation of the output of the dopaminergic neurons. We sought to determine the functionally relevant sites for M2R activation in relation to VTA dopaminergic neurons by examining the electron microscopic immunolabeling of M2R and the dopamine transporter (DAT) in the VTA of rat brain. The M2R was localized to endomembranes in DAT-containing somatodendritic profiles, but showed a more prominent, size-dependent plasmalemmal location in non-dopaminergic dendrites. M2R also was located on the plasma membrane of morphologically heterogenous axon terminals contacting unlabeled as well as M2R or DAT-labeled dendrites. Some of these terminals formed asymmetric synapses resembling those of cholinergic terminals in the VTA. The majority, however, formed symmetric, inhibitory-type synapses, or were apposed without recognized junctions. Our results provide the first ultrastructural evidence that the M2R is expressed, but largely not available for local activation, on the plasma membrane of VTA dopaminergic neurons. Instead, the M2R in this region has a distribution suggesting more indirect regulation of mesocorticolimbic transmission through autoregulation of acetylcholine release and changes in the physiological activity or release of other, largely inhibitory transmitters. These findings could have implications for understanding the muscarinic control of cognitive and goal-directed behaviors within the VTA. PMID:16927256

  3. miR-181a Induces Macrophage Polarized to M2 Phenotype and Promotes M2 Macrophage-mediated Tumor Cell Metastasis by Targeting KLF6 and C/EBPα.

    PubMed

    Bi, Jia; Zeng, Xianxin; Zhao, Lin; Wei, Qian; Yu, Lifeng; Wang, Xinnan; Yu, Zhaojin; Cao, Yaming; Shan, Fengping; Wei, Minjie

    2016-01-01

    Macrophages can acquire a variety of polarization status and functions: classically activated macrophages (M1 macrophages); alternatively activated macrophages (M2 macrophages). However, the molecular basis of the process is still unclear. Here, this study addresses that microRNA-181a (miR-181a) is a key molecule controlling macrophage polarization. We found that miR-181a is overexpressed in M2 macrophages than in M1 macrophages. miR-181a expression was decreased when M2 phenotype converted to M1, whereas it increased when M1 phenotype converted to M2. Overexpression of miR-181a in M1 macrophages diminished M1 phenotype expression while promoting polarization to the M2 phenotype. In contrast, knockdown of miR-181a in M2 macrophages promoted M1 polarization and diminished M2 phenotype expression. Mechanistically, Bioinformatic analysis revealed that Kruppel-like factor 6 (KLF6) and CCAAT/enhancer binding protein-α (C/EBPα) is a potential target of miR-181a and luciferase assay confirmed that KLF6 and C/EBPα translation is suppressed by miR-181a through interaction with the 3'UTR of KLF6 and C/EBPα mRNA. Further analysis showed that induction of miR-181a suppressed KLF6 and C/EBPα protein expression. Importantly, miR-181a also diminishes M2 macrophages-mediated migration and invasion capacity of tumor cells. Collectively, our results suggest that miR-181a plays a significant role in regulating macrophage polarization through directly target KLF6 and C/EBPα. PMID:27673564

  4. miR-181a Induces Macrophage Polarized to M2 Phenotype and Promotes M2 Macrophage-mediated Tumor Cell Metastasis by Targeting KLF6 and C/EBPα

    PubMed Central

    Bi, Jia; Zeng, Xianxin; Zhao, Lin; Wei, Qian; Yu, Lifeng; Wang, Xinnan; Yu, Zhaojin; Cao, Yaming; Shan, Fengping; Wei, Minjie

    2016-01-01

    Macrophages can acquire a variety of polarization status and functions: classically activated macrophages (M1 macrophages); alternatively activated macrophages (M2 macrophages). However, the molecular basis of the process is still unclear. Here, this study addresses that microRNA-181a (miR-181a) is a key molecule controlling macrophage polarization. We found that miR-181a is overexpressed in M2 macrophages than in M1 macrophages. miR-181a expression was decreased when M2 phenotype converted to M1, whereas it increased when M1 phenotype converted to M2. Overexpression of miR-181a in M1 macrophages diminished M1 phenotype expression while promoting polarization to the M2 phenotype. In contrast, knockdown of miR-181a in M2 macrophages promoted M1 polarization and diminished M2 phenotype expression. Mechanistically, Bioinformatic analysis revealed that Kruppel-like factor 6 (KLF6) and CCAAT/enhancer binding protein-α (C/EBPα) is a potential target of miR-181a and luciferase assay confirmed that KLF6 and C/EBPα translation is suppressed by miR-181a through interaction with the 3′UTR of KLF6 and C/EBPα mRNA. Further analysis showed that induction of miR-181a suppressed KLF6 and C/EBPα protein expression. Importantly, miR-181a also diminishes M2 macrophages-mediated migration and invasion capacity of tumor cells. Collectively, our results suggest that miR-181a plays a significant role in regulating macrophage polarization through directly target KLF6 and C/EBPα. PMID:27673564

  5. A randomized comparison of daunorubicin 90 mg/m2 vs 60 mg/m2 in AML induction: results from the UK NCRI AML17 trial in 1206 patients

    PubMed Central

    Russell, Nigel H.; Hills, Robert K.; Kell, Jonathan; Cavenagh, Jamie; Kjeldsen, Lars; McMullin, Mary-Frances; Cahalin, Paul; Dennis, Mike; Friis, Lone; Thomas, Ian F.; Milligan, Don; Clark, Richard E.

    2015-01-01

    Modifying induction therapy in acute myeloid leukemia (AML) may improve the remission rate and reduce the risk of relapse, thereby improving survival. Escalation of the daunorubicin dose to 90 mg/m2 has shown benefit for some patient subgroups when compared with a dose of 45 mg/m2, and has been recommended as a standard of care. However, 60 mg/m2 is widely used and has never been directly compared with 90 mg/m2. As part of the UK National Cancer Research Institute (NCRI) AML17 trial, 1206 adults with untreated AML or high-risk myelodysplastic syndrome, mostly younger than 60 years of age, were randomized to a first-induction course of chemotherapy, which delivered either 90 mg/m2 or 60 mg/m2 on days 1, 3, and 5 combined with cytosine arabinoside. All patients then received a second course that included daunorubicin 50 mg/m2 on days 1, 3, and 5. There was no overall difference in complete remission rate (73% vs 75%; odds ratio, 1.07 [0.83-1.39]; P = .6) or in any recognized subgroup. The 60-day mortality was increased in the 90 mg/m2 arm (10% vs 5% (hazard ratio [HR] 1.98 [1.30-3.02]; P = .001), which resulted in no difference in overall 2-year survival (59% vs 60%; HR, 1.16 [0.95-1.43]; P = .15). In an exploratory subgroup analysis, there was no subgroup that showed significant benefit, although there was a significant interaction by FLT3 ITD mutation. This trial is registered at http://www.isrctn.com as #ISRCTN55675535. PMID:25833957

  6. 43 CFR 10.8 - Summaries.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... REGULATIONS Human Remains, Funerary Objects, Sacred Objects, or Objects of Cultural Patrimony in Museums and... may contain unassociated funerary objects, sacred objects, or objects of cultural patrimony must... repatriation of such objects. The summary serves in lieu of an object-by-object inventory of these...

  7. 43 CFR 10.8 - Summaries.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...: 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 in Museums and... may contain unassociated funerary objects, sacred objects, or objects of cultural patrimony...

  8. 43 CFR 10.8 - Summaries.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...: 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 in Museums and... may contain unassociated funerary objects, sacred objects, or objects of cultural patrimony...

  9. 43 CFR 10.8 - Summaries.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... of a deceased Native American individual with whom unassociated funerary objects and sacred objects...: 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 in Museums...

  10. 43 CFR 10.8 - Summaries.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... of a deceased Native American individual with whom unassociated funerary objects and sacred objects...: 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 in Museums...

  11. 15 CFR 10.8 - Standing Committee.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... practices relating to the standard. (e) The committee shall: (1) Keep itself informed of any advancing technology that might affect the standard; (2) Provide the Department with interpretations of provisions...

  12. 15 CFR 10.8 - Standing Committee.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... practices relating to the standard. (e) The committee shall: (1) Keep itself informed of any advancing technology that might affect the standard; (2) Provide the Department with interpretations of provisions...

  13. 15 CFR 10.8 - Standing Committee.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... practices relating to the standard. (e) The committee shall: (1) Keep itself informed of any advancing technology that might affect the standard; (2) Provide the Department with interpretations of provisions...

  14. 15 CFR 10.8 - Standing Committee.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... practices relating to the standard. (e) The committee shall: (1) Keep itself informed of any advancing technology that might affect the standard; (2) Provide the Department with interpretations of provisions...

  15. The M2 Proton Channel of Influenza Virus: How Does It Work?

    NASA Technical Reports Server (NTRS)

    Pohorille, Andrew; Wilson, Michael; Schweighofer, Karl; Fonda, Mark (Technical Monitor)

    2002-01-01

    The transport of protons across membranes is an essential process for both bioenergetics of modem cells and the origins of cellular life. All living systems make use of proton gradients across cell walls to convert environmental energy into a high-energy chemical compound, adenosine triphosphate (ATR), synthesized from adenosine diphosphate. ATR, in turn, is used as a source of energy to drive many cellular reactions. The ubiquity of this process in biology suggests that even the earliest cellular systems were relying on proton gradient for harvesting environmental energy needed to support their survival and growth. In contemporary cells, proton transfer is assisted by large, complex proteins embedded in membranes. The issue addressed in this study was: how the same process can be accomplished with the aid of similar, but much simpler molecules that could have existed in the protobiological milieu? The model system used in the study contained a bilayer membrane made of phospholipid, dimyristoylphosphatidylcholine (DMPC), which is a good model of the biological membranes focusing cellular boundaries. Both sides of the bilayer were surrounded by water which simulated the environment inside and outside the cell. Embedded in the membrane was a fragment of the Influenza-A M2 protein and enough sodium counterions to maintain system neutrality. This protein has been shown to exhibit remarkably high rates of proton transport and, therefore, is an excellent model to study the formation of proton gradients across membranes. The Influenza M2 protein is 97 amino acids in length, but a fragment 25 amino acids long, which contains a transmembrane domain of 19 amino acids flanked by 3 amino acids on each side, is sufficient to transport protons. Four identical protein fragments, each folded into a helix, aggregate to form small channels spanning the membrane. Protons are conducted through a narrow pore in the middle of the channel in response to applied voltage. This channel is

  16. Facilitation of memory storage by the acetylcholine M2 muscarinic receptor antagonist AF-DX 116.

    PubMed

    Baratti, C M; Opezzo, J W; Kopf, S R

    1993-07-01

    Post-training administration of the acetylcholine muscarinic M2 presynaptic receptor antagonist AF-DX 116 (0.1-10.0 mg/kg, ip), facilitated 48 h retention, in male Swiss mice, of a one-trial step-through inhibitory avoidance task. The dose-response curve was an inverted U. AF-DX 116 did not increase the retention latencies of mice that had not received a footshock during training. The influence of AF-DX 116 (1 mg/kg, ip) on retention was time-dependent, which suggests that the drug facilitated memory storage. The memory facilitation induced by AF-DX 116 (1 mg/kg, ip) was prevented by atropine (0.5 mg/kg, ip) administered after training, but 10 min prior to AF-DX 116 treatment. In contrast, neither methylatropine (0.5 mg/kg, ip), a peripherally acting muscarinic receptor blocker, nor mecamylamine (5 mg/kg, ip) or hexamethonium (5 mg/kg, ip), two cholinergic nicotinic receptor antagonists, prevented the effects of post-training AF-DX 116 on retention. Low subeffective doses of the central acting anticholinesterase physostigmine (35 micrograms/kg, ip), administered immediately after training, and AF-DX 116 (0.1 mg/kg, ip), given 10 min after training, acted synergistically to improve retention. The effects of AF-DX 116 (0.1 mg/kg, ip) were not influenced by the peripherally acting anticholinesterase neostigmine (35 micrograms/kg, ip). Considered together, these findings suggest that the activation of a muscarinic cholinergic presynaptic inhibitory mechanism, probably by increasing brain acetylcholine release, may modulate the activity of post-training processes involved in memory storage. PMID:8216161

  17. Some properties of YBamCu1+mOy(m = 2, 3, 4, 5) superconductors

    NASA Astrophysics Data System (ADS)

    Chainok, Piyamas; Khuntak, Thanarat; Sujinnapram, Supphadate; Tiyasri, Somporn; Wongphakdee, Wirat; Kruaehong, Thitipong; Nilkamjon, Tunyanop; Ratreng, Sermsuk; Udomsamuthirun, Pongkaew

    2015-02-01

    We synthesized the YBamCu1+mOy superconductors; m = 2, 3, 4, 5 that were Y123 (YBa2 Cu3O7-x), Y134 (YBa3Cu4O9-x), Y145 (YBa4Cu5O11-x), Y156 (YBa5Cu6O13-x), by solid state reaction with the Y2O3, BaCO3 and CuO as the beginning materials. The calcination temperature was 950°C and varied the sintering temperature to be 950°C and 980°C. The resistivity measurement by four-point-probe technique showed that the Tconset of Y123, Y134, Y145, Y156 were at 97, 93, 91, 85 K, respectively. The XRD and Rietveld full-profile analysis method were used and found that the crystal structure was in the orthorhombic with Pmmm space group with the ratio c/a were 3.0, 4.0, 5.0 and 6.0 for Y123, Y134, Y145 and Y156, respectively. The oxygen content was characterized by Iodometric titration. The (Cu3+/Cu2+ and Oxygen content) were (0.28, 6.83), (0.19, 8.81), (0.13, 10.79), (0.16, 12.92) of Y123, Y134, Y145, Y156, respectively. We also found that the increasing of sintering temperature has reduced the oxygen content and the critical temperature of all samples.

  18. Molecular cloning, characterization, and expression of Cuc m 2, a major allergen in Cucumis melo

    PubMed Central

    Sankian, Mojtaba; Mahmoudi, Mahmoud; Varasteh, Abdol-Reza

    2013-01-01

    Background: Several studies reported the clinical features of IgE-mediated hypersensitivity after ingestion of melon. Melon allergy is a common IgE-mediated fruit allergy in Iran. This prompted us to investigate immunochemical and molecular properties of the major allergen in melon fruit, to compare the IgE-binding capacity of the natural protein with the recombinant allergen, and to determine cross-reactivity of the major allergen with closely-related allergens from other plants displaying clinical cross-reactivity with melon. Methods: Identification and molecular characterization of the major melon allergen were performed using IgE immunoblotting, allergen-specific ELISA, affinity-based purifications, cross-inhibition assays, cloning, and expression of the allergen in Escherichia coli. Results: Melon profilin was identified and isolated as a major IgE-binding component and designated as Cuc m 2. Sequencing corresponding cDNA revealed an open reading frame of 363 bp coding for 131 amino acid residues and two fragments of 171 bp and 383 bps for the 5’and 3’ UTRs, respectively. Significant cross-reactivity was found between melon profilin and Cynodon dactylon, tomato, peach, and grape profilins in cross-inhibition assays. Although the highest degree of amino acid identity was revealed with watermelon profilin, there was no significant cross-reactivity between melon and watermelon profilins. Conclusion: Melon profilin is the major IgE-binding component in melon extract, and the recombinant and natural forms exhibited similar IgE-binding capacities. A part of the fruit-fruit and pollen-fruit cross-reactions could be explained by the presence of this conserved protein; however, sequence homology provides insufficient information to predict IgE cross-reactivity of profilins. PMID:26989709

  19. Disability Affects the 6-Minute Walking Distance in Obese Subjects (BMI>40 kg/m2)

    PubMed Central

    Donini, Lorenzo Maria; Poggiogalle, Eleonora; Mosca, Veronica; Pinto, Alessandro; Brunani, Amelia; Capodaglio, Paolo

    2013-01-01

    Introduction In obese subjects, the relative reduction of the skeletal muscle strength, the reduced cardio-pulmonary capacity and tolerance to effort, the higher metabolic costs and, therefore, the increased inefficiency of gait together with the increased prevalence of co-morbid conditions might interfere with walking. Performance tests, such as the six-minute walking test (6MWT), can unveil the limitations in cardio-respiratory and motor functions underlying the obesity-related disability. Therefore the aims of the present study were: to explore the determinants of the 6-minute walking distance (6MWD) and to investigate the predictors of interruption of the walk test in obese subjects. Methods Obese patients [body mass index (BMI)>40 kg/m2] were recruited from January 2009 to December 2011. Anthropometry, body composition, specific questionnaire for Obesity-related Disabilities (TSD-OC test), fitness status and 6MWT data were evaluated. The correlation between the 6MWD and the potential independent variables (anthropometric parameters, body composition, muscle strength, flexibility and disability) were analysed. The variables which were singularly correlated with the response variable were included in a multivariated regression model. Finally, the correlation between nutritional and functional parameters and test interruption was investigated. Results 354 subjects (87 males, mean age 48.5±14 years, 267 females, mean age 49.8±15 years) were enrolled in the study. Age, weight, height, BMI, fat mass and fat free mass indexes, handgrip strength and disability were significantly correlated with the 6MWD and considered in the multivariate analysis. The determination coefficient of the regression analysis ranged from 0.21 to 0.47 for the different models. Body weight, BMI, waist circumference, TSD-OC test score and flexibility were found to be predictors of the 6MWT interruption. Discussion The present study demonstrated the impact of disability in obese subjects

  20. Facilitation of memory storage by the acetylcholine M2 muscarinic receptor antagonist AF-DX 116.

    PubMed

    Baratti, C M; Opezzo, J W; Kopf, S R

    1993-07-01

    Post-training administration of the acetylcholine muscarinic M2 presynaptic receptor antagonist AF-DX 116 (0.1-10.0 mg/kg, ip), facilitated 48 h retention, in male Swiss mice, of a one-trial step-through inhibitory avoidance task. The dose-response curve was an inverted U. AF-DX 116 did not increase the retention latencies of mice that had not received a footshock during training. The influence of AF-DX 116 (1 mg/kg, ip) on retention was time-dependent, which suggests that the drug facilitated memory storage. The memory facilitation induced by AF-DX 116 (1 mg/kg, ip) was prevented by atropine (0.5 mg/kg, ip) administered after training, but 10 min prior to AF-DX 116 treatment. In contrast, neither methylatropine (0.5 mg/kg, ip), a peripherally acting muscarinic receptor blocker, nor mecamylamine (5 mg/kg, ip) or hexamethonium (5 mg/kg, ip), two cholinergic nicotinic receptor antagonists, prevented the effects of post-training AF-DX 116 on retention. Low subeffective doses of the central acting anticholinesterase physostigmine (35 micrograms/kg, ip), administered immediately after training, and AF-DX 116 (0.1 mg/kg, ip), given 10 min after training, acted synergistically to improve retention. The effects of AF-DX 116 (0.1 mg/kg, ip) were not influenced by the peripherally acting anticholinesterase neostigmine (35 micrograms/kg, ip). Considered together, these findings suggest that the activation of a muscarinic cholinergic presynaptic inhibitory mechanism, probably by increasing brain acetylcholine release, may modulate the activity of post-training processes involved in memory storage.

  1. The M2 Proton Channel of Influenza Virus: How Does It Work?

    NASA Technical Reports Server (NTRS)

    Pohorille, Andrew; Wilson, Michael; Schweighofer, Karl; Fonda, Mark (Technical Monitor)

    2002-01-01

    The transport of protons across membranes is an essential process for both bioenergetics of modem cells and the origins of cellular life. All living systems make use of proton gradients across cell walls to convert environmental energy into a high-energy chemical compound, adenosine triphosphate (ATR), synthesized from adenosine diphosphate. ATR, in turn, is used as a source of energy to drive many cellular reactions. The ubiquity of this process in biology suggests that even the earliest cellular systems were relying on proton gradient for harvesting environmental energy needed to support their survival and growth. In contemporary cells, proton transfer is assisted by large, complex proteins embedded in membranes. The issue addressed in this study was: how the same process can be accomplished with the aid of similar, but much simpler molecules that could have existed in the protobiological milieu? The model system used in the study contained a bilayer membrane made of phospholipid, dimyristoylphosphatidylcholine (DMPC), which is a good model of the biological membranes focusing cellular boundaries. Both sides of the bilayer were surrounded by water which simulated the environment inside and outside the cell. Embedded in the membrane was a fragment of the Influenza-A M2 protein and enough sodium counterions to maintain system neutrality. This protein has been shown to exhibit remarkably high rates of proton transport and, therefore, is an excellent model to study the formation of proton gradients across membranes. The Influenza M2 protein is 97 amino acids in length, but a fragment 25 amino acids long, which contains a transmembrane domain of 19 amino acids flanked by 3 amino acids on each side, is sufficient to transport protons. Four identical protein fragments, each folded into a helix, aggregate to form small channels spanning the membrane. Protons are conducted through a narrow pore in the middle of the channel in response to applied voltage. This channel is

  2. 3d-modelling workflows for trans-nationally shared geological models - first approaches from the project GeoMol

    NASA Astrophysics Data System (ADS)

    Rupf, Isabel

    2013-04-01

    To meet the EU's ambitious targets for carbon emission reduction, renewable energy production has to be strongly upgraded and made more efficient for grid energy storage. Alpine Foreland Basins feature a unique geological inventory which can contribute substantially to tackle these challenges. They offer a geothermal potential and storage capacity for compressed air, as well as space for underground storage of CO2. Exploiting these natural subsurface resources will strongly compete with existing oil and gas claims and groundwater issues. The project GeoMol will provide consistent 3-dimensional subsurface information about the Alpine Foreland Basins based on a holistic and transnational approach. Core of the project GeoMol is a geological framework model for the entire Northern Molasse Basin, complemented by five detailed models in pilot areas, also in the Po Basin, which are dedicated to specific questions of subsurface use. The models will consist of up to 13 litho-stratigraphic horizons ranging from the Cenozoic basin fill down to Mesozoic and late Paleozoic sedimentary rocks and the crystalline basement. More than 5000 wells and 28 000 km seismic lines serve as input data sets for the geological subsurface model. The data have multiple sources and various acquisition dates, and their interpretations have gone through several paradigm changes. Therefore, it is necessary to standardize the data with regards to technical parameters and content prior to further analysis (cf. Capar et al. 2013, EGU2013-5349). Each partner will build its own geological subsurface model with different software solutions for seismic interpretation and 3d-modelling. Therefore, 3d-modelling follows different software- and partner-specific workflows. One of the main challenges of the project is to ensure a seamlessly fitting framework model. It is necessary to define several milestones for cross border checks during the whole modelling process. Hence, the main input data set of the

  3. Busulfan 12 mg/kg plus melphalan 140 mg/m2 versus melphalan 200 mg/m2 as conditioning regimens for autologous transplantation in newly diagnosed multiple myeloma patients included in the PETHEMA/GEM2000 study

    PubMed Central

    Lahuerta, Juan José; Mateos, Maria Victoria; Martínez-López, Joaquin; Grande, Carlos; de la Rubia, Javier; Rosiñol, Laura; Sureda, Anna; García-Laraña, José; Díaz-Mediavilla, Joaquín; Hernández-García, Miguel T.; Carrera, Dolores; Besalduch, Joan; de Arriba, Felipe; Oriol, Albert; Escoda, Lourdes; García-Frade, Javier; Rivas-González, Concepción; Alegre, Adrían; Bladé, Joan; San Miguel, Jesús F.

    2010-01-01

    Background The aim of this study was to compare the long-term safety and efficacy of oral busulfan 12 mg/kg plus melphalan 140 mg/m2 and melphalan 200 mg/m2 as conditioning regimens for autologous stem cell transplantation in newly diagnosed patients with multiple myeloma in the GEM2000 study. Design and Methods The first 225 patients received oral busulfan 12 mg/kg plus melphalan 140 mg/m2; because of a high frequency of veno-occlusive disease, the protocol was amended and a further 542 patients received melphalan 200 mg/m2. Results Engraftment and hospitalization times were similar in both groups. Oral busulfan 12 mg/kg plus melphalan 140 mg/m2 resulted in higher transplant-related mortality (8.4% versus 3.5%; P=0.002) due to the increased frequency of veno-occlusive disease in this group. Response rates were similar in both arms. With respective median follow-ups of 72 and 47 months, the median progression-free survival was significantly longer with busulfan plus melphalan (41 versus 31 months; P=0.009), although survival was similar to that in the melphalan 200 mg/m2 group. However, access to novel agents as salvage therapy after relapse/progression was significantly lower for patients receiving busulfan plus melphalan (43%) than for those receiving melphalan 200 mg/m2 (58%; P=0.01). Conclusions Conditioning with oral busulfan 12 mg/kg plus melphalan 140 mg/m2 was associated with longer progression-free survival but equivalent survival to that achieved with melphalan 200 mg/m2 but this should be counterbalanced against the higher frequency of veno-occlusive disease-related deaths. This latter fact together with the limited access to novel salvage therapies in patients conditioned with oral busulfan 12 mg/kg plus melphalan 140 mg/m2 may explain the absence of a survival difference. Oral busulfan was used in the present study; use of the intravenous formulation may reduce toxicity and result in greater efficacy, and warrants further investigation in myeloma

  4. Gas-phase NMR spectra of cyclohexene are consistent with a barrier to ring inversion of less than 30 kJ mol -1

    NASA Astrophysics Data System (ADS)

    Suarez, Cristina; Tafazzoli, Mohsen; True, Nancy S.

    1992-08-01

    1H NMR spectra of gaseous cyclohexene at 7.05 T and 195 K do not show line broadening attributable to axial-equatorial proton exchange, indicating that the Gibbs energy of activation, Δ G‡, is less than 30 kJ mol -1, considerably lower than the 43 kJ mol -1 barrier recently determined from a vibrational analysis.

  5. Recombinant M2e outer membrane vesicle vaccines protect against lethal influenza A challenge in BALB/c mice.

    PubMed

    Rappazzo, C Garrett; Watkins, Hannah C; Guarino, Cassandra M; Chau, Annie; Lopez, Jody L; DeLisa, Matthew P; Leifer, Cynthia A; Whittaker, Gary R; Putnam, David

    2016-03-01

    Currently approved influenza vaccines predominantly protect through antibodies directed against the highly variable glycoprotein hemagglutinin (HA), necessitating annual redesign and formulation based on epidemiological prediction of predominant circulating strains. More conserved influenza protein sequences, such as the ectodomain of the influenza M2 protein, or M2e, show promise as a component of a universal influenza A vaccine, but require a Th1-biased immune response for activity. Recently, recombinant, bacterially derived outer membrane vesicles (OMVs) demonstrated potential as a platform to promote a Th1-biased immune response to subunit antigens. Here, we engineer three M2e-OMV vaccines and show that all elicit strong IgG titers, with high IgG2a:IgG1 ratios, in BALB/c mice. Additionally, the administration of one M2e-OMV construct containing tandem heterologous M2e peptides (M2e4xHet-OMV) resulted in 100% survival against lethal doses of the mouse-adapted H1N1 influenza strain PR8. Passive transfer of antibodies from M2e4xHet-OMV vaccinated mice to unvaccinated mice also resulted in 100% survival to challenge, indicating that protection is driven largely via antibody-mediated immunity. The potential mechanism through which M2e-OMVs initiated the immune response was explored and it was found that the constructs triggered TLR1/2, TLR4, and TLR5. Our data indicate that OMVs have potential as a platform for influenza A vaccine development due to their unique adjuvant profile and intrinsic pathogen-mimetic nature. PMID:26827663

  6. Systemic and Cardiac Depletion of M2 Macrophage through CSF-1R Signaling Inhibition Alters Cardiac Function Post Myocardial Infarction.

    PubMed

    Leblond, Anne-Laure; Klinkert, Kerstin; Martin, Kenneth; Turner, Elizebeth C; Kumar, Arun H; Browne, Tara; Caplice, Noel M

    2015-01-01

    The heart hosts tissue resident macrophages which are capable of modulating cardiac inflammation and function by multiple mechanisms. At present, the consequences of phenotypic diversity in macrophages in the heart are incompletely understood. The contribution of cardiac M2-polarized macrophages to the resolution of inflammation and repair response following myocardial infarction remains to be fully defined. In this study, the role of M2 macrophages was investigated utilising a specific CSF-1 receptor signalling inhibition strategy to achieve their depletion. In mice, oral administration of GW2580, a CSF-1R kinase inhibitor, induced significant decreases in Gr1lo and F4/80hi monocyte populations in the circulation and the spleen. GW2580 administration also induced a significant depletion of M2 macrophages in the heart after 1 week treatment as well as a reduction of cardiac arginase1 and CD206 gene expression indicative of M2 macrophage activity. In a murine myocardial infarction model, reduced M2 macrophage content was associated with increased M1-related gene expression (IL-6 and IL-1β), and decreased M2-related gene expression (Arginase1 and CD206) in the heart of GW2580-treated animals versus vehicle-treated controls. M2 depletion was also associated with a loss in left ventricular contractile function, infarct enlargement, decreased collagen staining and increased inflammatory cell infiltration into the infarct zone, specifically neutrophils and M1 macrophages. Taken together, these data indicate that CSF-1R signalling is critical for maintaining cardiac tissue resident M2-polarized macrophage population, which is required for the resolution of inflammation post myocardial infarction and, in turn, for preservation of ventricular function.

  7. Potential recombinant vaccine against influenza A virus based on M2e displayed on nodaviral capsid nanoparticles

    PubMed Central

    Yong, Chean Yeah; Yeap, Swee Keong; Ho, Kok Lian; Omar, Abdul Rahman; Tan, Wen Siang

    2015-01-01

    Influenza A virus poses a major threat to human health, causing outbreaks from time to time. Currently available vaccines employ inactivated viruses of different strains to provide protection against influenza virus infection. However, high mutation rates of influenza virus hemagglutinin (H) and neuraminidase (N) glycoproteins give rise to vaccine escape mutants. Thus, an effective vaccine providing protection against all strains of influenza virus would be a valuable asset. The ectodomain of matrix 2 protein (M2e) was found to be highly conserved despite mutations of the H and N glycoproteins. Hence, one to five copies of M2e were fused to the carboxyl-terminal end of the recombinant nodavirus capsid protein derived from Macrobrachium rosenbergii. The chimeric proteins harboring up to five copies of M2e formed nanosized virus-like particles approximately 30 nm in diameter, which could be purified easily by immobilized metal affinity chromatography. BALB/c mice immunized subcutaneously with these chimeric proteins developed antibodies specifically against M2e, and the titer was proportional to the copy numbers of M2e displayed on the nodavirus capsid nanoparticles. The fusion proteins also induced a type 1 T helper immune response. Collectively, M2e displayed on the nodavirus capsid nanoparticles could provide an alternative solution to a possible influenza pandemic in the future. PMID:25897220

  8. Potential recombinant vaccine against influenza A virus based on M2e displayed on nodaviral capsid nanoparticles.

    PubMed

    Yong, Chean Yeah; Yeap, Swee Keong; Ho, Kok Lian; Omar, Abdul Rahman; Tan, Wen Siang

    2015-01-01

    Influenza A virus poses a major threat to human health, causing outbreaks from time to time. Currently available vaccines employ inactivated viruses of different strains to provide protection against influenza virus infection. However, high mutation rates of influenza virus hemagglutinin (H) and neuraminidase (N) glycoproteins give rise to vaccine escape mutants. Thus, an effective vaccine providing protection against all strains of influenza virus would be a valuable asset. The ectodomain of matrix 2 protein (M2e) was found to be highly conserved despite mutations of the H and N glycoproteins. Hence, one to five copies of M2e were fused to the carboxyl-terminal end of the recombinant nodavirus capsid protein derived from Macrobrachium rosenbergii. The chimeric proteins harboring up to five copies of M2e formed nanosized virus-like particles approximately 30 nm in diameter, which could be purified easily by immobilized metal affinity chromatography. BALB/c mice immunized subcutaneously with these chimeric proteins developed antibodies specifically against M2e, and the titer was proportional to the copy numbers of M2e displayed on the nodavirus capsid nanoparticles. The fusion proteins also induced a type 1 T helper immune response. Collectively, M2e displayed on the nodavirus capsid nanoparticles could provide an alternative solution to a possible influenza pandemic in the future. PMID:25897220

  9. Elastin-Derived Peptides Promote Abdominal Aortic Aneurysm Formation by Modulating M1/M2 Macrophage Polarization.

    PubMed

    Dale, Matthew A; Xiong, Wanfen; Carson, Jeffrey S; Suh, Melissa K; Karpisek, Andrew D; Meisinger, Trevor M; Casale, George P; Baxter, B Timothy

    2016-06-01

    Abdominal aortic aneurysm is a dynamic vascular disease characterized by inflammatory cell invasion and extracellular matrix degradation. Damage to elastin in the extracellular matrix results in release of elastin-derived peptides (EDPs), which are chemotactic for inflammatory cells such as monocytes. Their effect on macrophage polarization is less well known. Proinflammatory M1 macrophages initially are recruited to sites of injury, but, if their effects are prolonged, they can lead to chronic inflammation that prevents normal tissue repair. Conversely, anti-inflammatory M2 macrophages reduce inflammation and aid in wound healing. Thus, a proper M1/M2 ratio is vital for tissue homeostasis. Abdominal aortic aneurysm tissue reveals a high M1/M2 ratio in which proinflammatory cells and their associated markers dominate. In the current study, in vitro treatment of bone marrow-derived macrophages with EDPs induced M1 macrophage polarization. By using C57BL/6 mice, Ab-mediated neutralization of EDPs reduced aortic dilation, matrix metalloproteinase activity, and proinflammatory cytokine expression at early and late time points after aneurysm induction. Furthermore, direct manipulation of the M1/M2 balance altered aortic dilation. Injection of M2-polarized macrophages reduced aortic dilation after aneurysm induction. EDPs promoted a proinflammatory environment in aortic tissue by inducing M1 polarization, and neutralization of EDPs attenuated aortic dilation. The M1/M2 imbalance is vital to aneurysm formation. PMID:27183603

  10. Effect of Fe-chelating complexes on a novel M2FC performance with ferric chloride and ferricyanide catholytes.

    PubMed

    Chung, Kyungmi; Lee, Ilgyu; Han, Jong-In

    2012-01-01

    As an effort to better utilize the microbial fuel cell (MFC) technology, we previously proposed an innovative MFC system named M2FC consisting of ferric-based MFC part and ferrous-based fuel cell (FC) part. In this reactor, ferric ion, the catholyte in the MFC part, was efficiently regenerated by the FC part with the generation of additional electricity. When both units were operated separately, the ferric-based MFC part produced approximately 1360 mW m(-2) of power density with FeCl(3) as catholyte and Fe-citrate as anolyte. The ferrous-based FC part with FeCl(3) as catholyte and Fe-EDTA as anolyte displayed the highest power density (1500 mW m(-2)), while that with ferricyanide as catholyte and Fe-noligand as anolyte had the lowest power density (380 mW m(-2)). The types of catholytes and chelating complexes as anolyte were found to play important roles in the reduction of ferric ions and oxidation of ferrous ion. Linear sweep voltammetry results supported that the cathode electrolytes were electrically active and these agreed well with the M2FC reactor performance. These results clearly showed that ligands played critical role in the efficiency and rate for recycling iron ion and thus the M2FC performance.

  11. Comparison of human and porcine gastric clasp and sling fiber contraction by M2 and M3 muscarinic receptors

    PubMed Central

    Vegesna, Anil K.; Braverman, Alan S.; Miller, Larry S.; Tallarida, Ronald J.; Tiwana, Mansoor I.; Khayyam, Umar

    2010-01-01

    To compare the gastroesophageal junction of the human with the pig, M2 and M3 receptor densities and the potencies of M2 and M3 muscarinic receptor subtype selective antagonists were determined in gastric clasp and sling smooth muscle fibers. Total muscarinic and M2 receptors are higher in pig than human clasp and sling fibers. M3 receptors are higher in human compared with pig sling fibers but lower in human compared with pig clasp fibers. Clasp fibers have fewer M3 receptors than sling fibers in both humans and pigs. Similar to human clasp fibers, pig clasp fibers contract significantly less than pig sling fibers. Analysis of the methoctramine Schild plot suggests that M2 receptors are involved in mediating contraction in pig clasp and sling fibers. Darifenacin potency suggests that M3 receptors mediate contraction in pig sling fibers and that M2 and M3 receptors mediate contraction in pig clasp fibers. Taken together, the data suggest that both M2 and M3 muscarinic receptors mediate the contraction in both pig clasp and sling fibers similar to human clasp and sling fibers. PMID:20133950

  12. On M2 tidal amplitude enhancement in the Taiwan Strait and its asymmetry in the cross-strait direction

    NASA Astrophysics Data System (ADS)

    Yu, Haiqing; Yu, Huaming; Ding, Yang; Wang, Lu; Kuang, Liang

    2015-10-01

    Enhanced M2 tidal amplitude in the Taiwan Strait (TS) and asymmetric M2 tidal amplitude in the cross-strait direction have been found and reproduced in numerical simulations. In this study, Finite Volume Coastal Ocean Model (FVCOM) is applied to investigate the mechanisms behind these features. Model results show that the linear interaction of waves from the East China Sea (ECS) and the Luzon Strait (LS) can explain the formation of the co-amplitude and co-phase lines of the M2 tide in the nodal point area, while the waves from the ECS dominate the tidal motion in the TS according to a basic linear wave superposition. Model simulation also show that wave reflection and transition occur when the M2 tidal waves from the ECS propagate through the TS and encounter an sharply deepened topography. The interaction of these induced reflection waves and the incident waves from the ECS is the main cause for the enhanced M2 tidal amplitude in the TS. The distribution of the sharply deepened topography, rather than the Coriolis effect, is the main reason for the asymmetry of the M2 tidal amplitude in the cross-strait direction in the TS. These findings provide some references for tidal dynamics in other areas, especially where long waves propagate through the shallow water to the deep sea.

  13. Investigation of the Annexin A5 M2 haplotype in 500 white European couples who have experienced recurrent spontaneous abortion.

    PubMed

    Demetriou, Charalambos; Abu-Amero, Sayeda; White, Shawnelle; Peskett, Emma; Markoff, Arseni; Stanier, Philip; Moore, Gudrun E; Regan, Lesley

    2015-11-01

    Annexin A5 is a placental anti-coagulant protein that contains four nucleotide substitutions (M2 haplotype) in its promoter. This haplotype is a risk factor for recurrent spontaneous abortion (RSA). The influence of the M2 haplotype in the gestational timing of spontaneous abortions, paternal risk and relationships with known risk factors were investigated. European couples (n = 500) who had experienced three or more consecutive spontaneous abortions, and two fertile control groups, were selected for this study. The allele frequency of M2 was significantly higher among patients who had experienced early RSA than among controls (P = 0.002). No difference was found between controls and patients who had undergone late spontaneous abortions. No difference was found between patients who had experienced RSA who had a live birth or no live births, or between patients who were positive or negative for known risk factors. Male and female partners in each group had similar allele frequencies of M2. The M2 haplotype is a risk factor for early spontaneous abortions, before the 12th week of gestation, and confers about the same relative risk to carriers of both sexes. Having one or more M2 allele(s) in combination with other risk factors further increases the RSA risk.

  14. On use of the variable Zagreb vM2 index in QSPR: boiling points of benzenoid hydrocarbons.

    PubMed

    Nikolić, Sonja; Milicević, Ante; Trinajstić, Nenad; Jurić, Albin

    2004-12-31

    The variable Zagreb (v)M(2) index is introduced and applied to the structure-boiling point modeling of benzenoid hydrocarbons. The linear model obtained (the standard error of estimate for the fit model S(fit)=6.8 degrees C) is much better than the corresponding model based on the original Zagreb M2 index (S(fit)=16.4 degrees C). Surprisingly,the model based on the variable vertex-connectivity index (S(fit)=6.8 degrees C) is comparable to the model based on (v)M2 index. A comparative study with models based on the vertex-connectivity index, edge-connectivity index and several distance indices favours models based on the variable Zagreb (v)M2 index and variable vertex-connectivity index.However, the multivariate regression with two-, three- and four-descriptors gives improved models, the best being the model with four-descriptors (but (v)M2 index is not among them) with S(fit)=5 degrees C, though the four-descriptor model contaning (v)M2 index is only slightly inferior (S(fit)=5.3 degrees C).

  15. Classification of a Haemophilus influenzae ABC Transporter HI1470/71 through Its Cognate Molybdate Periplasmic Binding Protein, MolA

    SciTech Connect

    Tirado-Lee, Leidamarie; Lee, Allen; Rees, Douglas C.; Pinkett, Heather W.

    2014-10-02

    molA (HI1472) from H. influenzae encodes a periplasmic binding protein (PBP) that delivers substrate to the ABC transporter MolB{sub 2}C{sub 2} (formerly HI1470/71). The structures of MolA with molybdate and tungstate in the binding pocket were solved to 1.6 and 1.7 {angstrom} resolution, respectively. The MolA-binding protein binds molybdate and tungstate, but not other oxyanions such as sulfate and phosphate, making it the first class III molybdate-binding protein structurally solved. The {approx}100 {mu}M binding affinity for tungstate and molybdate is significantly lower than observed for the class II ModA molybdate-binding proteins that have nanomolar to low micromolar affinity for molybdate. The presence of two molybdate loci in H. influenzae suggests multiple transport systems for one substrate, with molABC constituting a low-affinity molybdate locus.

  16. M-M bond-stretching energy landscapes for M2(dimen)4(2+) (M = Rh, Ir; dimen = 1,8-diisocyanomenthane) complexes.

    PubMed

    Hunter, Bryan M; Villahermosa, Randy M; Exstrom, Christopher L; Hill, Michael G; Mann, Kent R; Gray, Harry B

    2012-06-18

    Isomers of Ir(2)(dimen)(4)(2+) (dimen = 1,8-diisocyanomenthane) exhibit different Ir-Ir bond distances in a 2:1 MTHF/EtCN solution (MTHF = 2-methyltetrahydrofuran). Variable-temperature absorption data suggest that the isomer with the shorter Ir-Ir distance is favored at room temperature [K = ∼8; ΔH° = -0.8 kcal/mol; ΔS° = 1.44 cal mol(-1) K(-1)]. We report calculations that shed light on M(2)(dimen)(4)(2+) (M = Rh, Ir) structural differences: (1) metal-metal interaction favors short distances; (2) ligand deformational-strain energy favors long distances; (3) out-of-plane (A(2u)) distortion promotes twisting of the ligand backbone at short metal-metal separations. Calculated potential-energy surfaces reveal a double minimum for Ir(2)(dimen)(4)(2+) (∼4.1 Å Ir-Ir with 0° twist angle and ∼3.6 Å Ir-Ir with ±12° twist angle) but not for the rhodium analogue (∼4.5 Å Rh-Rh with no twisting). Because both the ligand strain and A(2u) distortional energy are virtually identical for the two complexes, the strength of the metal-metal interaction is the determining factor. On the basis of the magnitude of this interaction, we obtain the following results: (1) a single-minimum (along the Ir-Ir coordinate), harmonic potential-energy surface for the triplet electronic excited state of Ir(2)(dimen)(4)(2+) (R(e,Ir-Ir) = 2.87 Å; F(Ir-Ir) = 0.99 mdyn Å(-1)); (2) a single-minimum, anharmonic surface for the ground state of Rh(2)(dimen)(4)(2+) (R(e,Rh-Rh) = 3.23 Å; F(Rh-Rh) = 0.09 mdyn Å(-1)); (3) a double-minimum (along the Ir-Ir coordinate) surface for the ground state of Ir(2)(dimen)(4)(2+) (R(e,Ir-Ir) = 3.23 Å; F(Ir-Ir) = 0.16 mdyn Å(-1)).

  17. OBSERVATIONS OF THE MAGNETIC RECONNECTION SIGNATURE OF AN M2 FLARE ON 2000 MARCH 23

    SciTech Connect

    Li Leping; Zhang Jun E-mail: zjun@ourstar.bao.ac.c

    2009-09-20

    Multiwavelength observations of an M 2.0 flare event on 2000 March 23 in the NOAA active region 8910 provide us a good chance to study the detailed structure and dynamics of the magnetic reconnection region. In the process of the flare, extreme-ultraviolet (EUV) loops displayed two types of sideward motions upon a loop-top hard X-ray source with average velocities of 75 and 25.6 km s{sup -1}, respectively. Meanwhile, a part of the loops disappeared and new post-flare loops formed. We consider these two motions to be the observational evidence of reconnection inflow, and find an X-shaped structure upon the post-flare loops during the period of the second motion. Two separations of the flare ribbons are associated with these two sideward motions, with average velocities of 3.3 and 1.3 km s{sup -1}, respectively. The sideward motions of the EUV loops and the separations of the flare ribbons are temporally consistent with two peaks of the X-ray flux. This indicates that there are two types of magnetic reconnection in the process of the flare. Using the observation of photospheric magnetic field, the velocities of the sideward motions, and the separations, we deduce the corresponding coronal magnetic field strength to be about 13.2-15.2 G, and estimate the reconnection rates to be 0.05 and 0.02 for these two magnetic reconnection processes, respectively. Besides the sideward motions of EUV loops and the separations of flare ribbons, we also observe motions of bright points upward and downward along the EUV loops with velocities ranging from 45.4 to 556.7 km s{sup -1}, which are thought to be the plasmoids accelerated in the current sheet and ejected upward and downward when magnetic reconnection occurs and energy releases. A cloud of bright material flowing outward from the loop-top hard X-ray source with an average velocity of 51 km s{sup -1} in the process of the flare may be accelerated by the tension force of the newly reconnected magnetic field lines. All the

  18. Magellan/M2FS Spectroscopy of the Reticulum 2 Dwarf Spheroidal Galaxy

    NASA Astrophysics Data System (ADS)

    Walker, Matthew G.; Mateo, Mario; Olszewski, Edward W.; Bailey, John I., III; Koposov, Sergey E.; Belokurov, Vasily; Evans, N. Wyn

    2015-08-01

    We present results from spectroscopic observations with the Michigan/Magellan Fiber System (M2FS) of 182 stellar targets along the line of sight (LOS) to the newly discovered “ultrafaint” object Reticulum 2 (Ret 2). For 37 of these targets, the spectra are sufficient to provide simultaneous estimates of LOS velocity ({v}{los}, median random error {δ }{v{los}}=1.4 km s‑1), effective temperature ({T}{eff}, {δ }{T{eff}}=478 K), surface gravity ({log}g, {δ }{logg}=0.63 dex), and iron abundance ([{Fe}/{{H}}], {δ }[{Fe/{{H}}]}=0.47 dex). We use these results to confirm 17 stars as members of Ret 2. From the member sample we estimate a velocity dispersion of {σ }{v{los}}= {3.6}-0.7+1.0 km s‑1 about a mean of < {v}{los}> = {64.3}-1.2+1.2 km s‑1 in the solar rest frame (∼ -90.9 km s‑1 in the Galactic rest frame), and a metallicity dispersion of {σ }[{Fe/{{H}}]} = {0.49}-0.14+0.19 dex about a mean of < [{Fe}/{{H}}]> = -{2.58}-0.33+0.34. These estimates marginalize over possible velocity and metallicity gradients, which are consistent with zero. Our results place Ret 2 on chemodynamical scaling relations followed by the Milky Way’s dwarf-galactic satellites. Under assumptions of dynamic equilibrium and negligible contamination from binary stars—both of which must be checked with deeper imaging and repeat spectroscopic observations—the estimated velocity dispersion suggests a dynamical mass of M({R}{{h}})≈ 5{R}{{h}}{σ }{v{los}}{}2/(2G) = {2.4}-0.8+1.4× {10}5 {M}ȯ enclosed within projected halflight radius {R}{{h}}∼ 32 pc, with mass-to-light ratio ≈ 2M({R}{{h}})/{L}V = {467}-168+286 in solar units. This paper presents data gathered with the Magellan Telescopes at Las Campanas Observatory, Chile.

  19. PREFACE: 10th International Conference on Materials and Mechanisms of Superconductivity (M2S-X)

    NASA Astrophysics Data System (ADS)

    Greene, L. H.; Zhu, J.-X.; Wang, H.; Meen, J.; Lorenz, B.; Dong, X. L.; dela Cruz, C. R.; Carlson, E.; Bud'ko, S. L.; Bauer, E.; Paglione, J.

    2013-07-01

    The 2012 Materials and Mechanisms of Superconductivity Conference (M2S 2012), which occurs every three years, brought together world experts and young scientists to discuss open questions in the fundamental physics and applications of superconductors, and to disseminate the latest theoretical and experimental research results in superconductors and related novel materials. This conference of 600 participants acted as a valuable training ground in this technologically important area. We focused on key unanswered questions in high-temperature cuprate superconductors, high-temperature iron-based superconductors, topological superconductors, organic superconductors, and heavy-electron superconductors. The discovery of new materials and novel technological applications for electronic devices and for energy transmission and storage was emphasized. There were special sessions on superconductivity and energy, and outreach sessions, and an evening public lecture. There were also junior researcher symposia interspersed within the conference, thus providing an ideal environment for advanced graduate students and postdoctoral researchers to explore the latest theoretical and experimental methods used to investigate challenging questions in the physics of materials as it relates to both fundamental science and technological applications. These proceedings are an archival testament to the excitement in the field and provide a valuable snapshot of the cutting-edge research of 2012. We hope this will be a valuable resource to active researchers in the field as well as an encouraging volume to excite new researchers to the ever-growing, multifaceted field of superconductivity. We thank Bernd Lorenz and his Publications Committee for their tremendously creative and diligent work in putting this volume together. This Conference would not have been possible without the tireless work of our Program Committee, Chaired by Rick Greene and Co-Chaired by Mike Norman. Becky McDuffee, our

  20. Synthesis, EPR and luminescent properties of YAlO3:Fe3+ (0.1-0.9 mol%) nanopowders

    NASA Astrophysics Data System (ADS)

    Premkumar, H. B.; Nagabhushana, H.; Sharma, S. C.; Daruka Prasad, B.; Nagabhushana, B. M.; Rao, J. L.; Chakradhar, R. P. S.

    A simple and inexpensive combustion method was used to prepare Fe3+ doped YAlO3 perovskite within few minutes at low temperature (400 ± 10 °C). This might be useful in lowering the cost of the material. The final products were well characterized by various spectroscopic techniques such as PXRD, SEM, TEM, FTIR and UV-Visible. The average crystallite size was estimated from the broadening of the PXRD peaks and found to be in the range 45-90 nm, the results were in good agreement with the W-H plots and TEM. The crystallites show dumbbell shape, agglomerated particles with different size. The TL glow curves of 1-5 kGy γ-irradiated YAlO3:Fe3+ (0.1 mol%) nanopowder warmed at a heating rate of 3 °C s-1 records a single glow peak at ∼260 °C. The kinetic parameters namely activation energy (E), order of kinetics (b) and frequency factor (s) were determined at different gamma doses using the Chens glow peak shape method and the results were discussed in detail. The photoluminescence spectra for Fe3+ (0.1-0.9 mol%) doped YAlO3 records the lower energy band at 720 nm (4T1 (4G) → 6A1 (6S)) and the intermediate band located at 620 nm (4T2 (4G) → 6A1 (6S)) with the excitation of 378 nm. The higher energy band located at 514 nm was associated to 4E + 4A1 (4G) → 6A1 (6S) transition. The resonance signals at g values 7.6, 4.97, 4.10, 2.94, 2.33 and 1.98 were observed in EPR spectra of Fe3+ (0.1-0.9 mol%) doped YAlO3 recorded at room temperature. The g values indicate that the iron ions were in trivalent state and distorted octahedral site symmetry was observed.

  1. Exploration des mécanismes de repliement des protéines par dynamique moléculaire

    NASA Astrophysics Data System (ADS)

    Gilquin, B.

    2005-11-01

    Comment se replient les protéines? Cette question est ancienne. En introduction nous rappellerons ce qu'est le paradoxe de Levinthal et comment on est passé de la notion de chemin de repliement à la notion de paysage énergétique. Les simulations de dynamique moléculaire ont permis d'aborder la compréhension du processus de repliement au niveau atomique. Cependant l'échelle de temps des processus de repliement (de l'ordre de la milliseconde) n'est pas accessible aux simulations numériques (de l'ordre de la nanoseconde). Plusieurs auteurs ont donc proposé de simuler le dépliement des protéines par dynamique moléculaire. En admettant le principe de micro-réversibilité l'étude du processus de dépliement renseigne sur celui de repliement. Cependant, il est nécessaire d'accélérer le dépliement en introduisant un biais afin que les états dépliées soient accessibles aux échelles de temps des simulations. Nous présenterons un exemple de ce qui a été réalise dans le cas de l'étude de protéines de petite taille suivant un repliement simple, globalement à deux états. Nous présenterons ensuite ce que nous avons réalisé dans le cas d'une protéine de taille plus importante et pour laquelle le processus de repliement est plus complexe car il existe un intermédiaire transitoire de repliement. C'est le cas du lysozyme pour lequel les simulations de dépliement permettent d'accéder au mécanisme atomique de repliement et de comprendre pourquoi des mutants de cette protéine se replient plus lentement et forment des fibres amyloïdiques. Ainsi les intermédiaires de repliement seraient à l'origine de formes pathogènes des protéines observées dans les maladies neuro-dégéneratives. Enfin nous montrerons comment à partir de plusieurs simulations longues de dynamique moléculaire, le paysage énergétique pour de petites protéines peut être calculé.

  2. Excitação e fotoabsorção de moléculas interestelares no ultra violeta

    NASA Astrophysics Data System (ADS)

    Rodrigues, A. M. F.; Boechat-Roberty, H. M.; Souza, G. B.; Turci, C. C.

    2003-08-01

    O estudo dos processos de excitação, fotoabsorção e ionização molecular nas nuvens interestelar, permite a análise dos processos químicos, como a formação e destruição de moléculas, até mesmo daquelas que dão origem à vida. Acredita-se que as moléculas como CS2, NH3, CO2 e N2O estão presentes nas nuvens onde são formadas as estrelas e seus sistemas planetários. Estas moléculas são congeladas na superfície de objetos densos, como aqueles encontrados na Nuvem de Oort do nosso Sistema Solar. Quando esses objetos (cometas) desprendem-se dessa região, aproximam-se do Sol, sofrem a interação da radição Ultra Violeta (UV), passam à fase gasosa e são bombardeados por íons e elétrons presentes nos ventos solares. Obtivemos os espectros de fotoabsorção do CS2, NH3 e N2O na faixa do UV, convertendo espectros de Perda de Energia de Elétrons, medidos no menor ângulo de espalhamento e na energia de impacto de 1000 eV. Destes espectros determinamos os valores de força de oscilador (f) e de seção de choque absolutas na faixa de 500 a 2000 Å. Para tal, estudamos e comparamos dois diferentes métodos de conversão. Neste trabalho também geramos muitos dados moleculares como, valores absolutos de seção de choque elástica em função do ângulo de espalhamento e a distribuição de força do oscilador generalizada (df/dE) em função da energia de excitação para diversos ângulos de espalhamento. Comparando nossos espectros de fotoabsorção com o espectro da atmosfera de Júpiter, obtido pelo Telescópio Espacial Hubble, logo após o impacto do cometa Shoemaker-Levy 9, confirmamos a presença do CS2 e da amônia.

  3. Development of a candidate influenza vaccine based on virus-like particles displaying influenza M2e peptide into the immunodominant region of hepatitis B core antigen: Broad protective efficacy of particles carrying four copies of M2e.

    PubMed

    Tsybalova, Liudmila M; Stepanova, Liudmila A; Kuprianov, Victor V; Blokhina, Elena A; Potapchuk, Marina V; Korotkov, Alexander V; Gorshkov, Andrey N; Kasyanenko, Marina A; Ravin, Nikolai V; Kiselev, Oleg I

    2015-06-26

    A long-term objective when designing influenza vaccines is to create one with broad cross-reactivity that will provide effective control over influenza, no matter which strain has caused the disease. Here we summarize the results from an investigation into the immunogenic and protective capacities inherent in variations of a recombinant protein, HBc/4M2e. This protein contains four copies of the ectodomain from the influenza virus protein M2 (M2e) fused within the immunodominant loop of the hepatitis B virus core antigen (HBc). Variations of this basic design include preparations containing M2e from the consensus human influenza virus; the M2e from the highly pathogenic avian A/H5N1 virus and a combination of two copies from human and two copies from avian influenza viruses. Intramuscular delivery in mice with preparations containing four identical copies of M2e induced high IgG titers in blood sera and bronchoalveolar lavages. It also provoked the formation of memory T-cells and antibodies were retained in the blood sera for a significant period of time post immunization. Furthermore, these preparations prevented the death of 75-100% of animals, which were challenged with lethal doses of virus. This resulted in a 1.2-3.5 log10 decrease in viral replication within the lungs. Moreover, HBc particles carrying only "human" or "avian" M2e displayed cross-reactivity in relation to human (A/H1N1, A/H2N2 and A/H3N2) or A/H5N1 and A(H1N1)pdm09 viruses, respectively; however, with the particles carrying both "human" and "avian" M2e this effect was much weaker, especially in relation to influenza virus A/H5N1. It is apparent from this work that to quickly produce vaccine for a pandemic it would be necessary to have several variations of a recombinant protein, containing four copies of M2e (each one against a group of likely influenza virus strains) with these relevant constructs housed within a comprehensive collection Escherichia coli-producers and maintained ready for use.

  4. Defining the dose of gemtuzumab ozogamicin in combination with induction chemotherapy in acute myeloid leukemia: a comparison of 3 mg/m2 with 6 mg/m2 in the NCRI AML17 Trial

    PubMed Central

    Burnett, Alan; Cavenagh, Jamie; Russell, Nigel; Hills, Robert; Kell, Jonathan; Jones, Gail; Nielsen, Ove Juul; Khwaja, Asim; Thomas, Ian; Clark, Richard

    2016-01-01

    Arecent source data meta-analysis of randomized trials in adults assessing the immunoconjugate gemtuzumab ozogamicin combined with standard chemotherapy in acute myeloid leukemia showed a significant survival benefit in patients without an adverse karyotype. It is not clear whether the optimal dose should be 3 mg/m2 or 6 mg/m2. In this study, we randomized 788 patients to a single dose of gemtuzumab ozogamicin 3 mg/m2 or 6 mg/m2 with the first course of induction therapy. We found that the rate of complete remission was higher with 3 mg/m2 [82% vs. 76%; odds ratio 1.46 (1.04–2.06); P=0.03], but this was balanced by a higher rate of complete remission with incomplete peripheral blood count recovery in the 6 mg/m2 treatment (10% vs. 7%) resulting in similar overall response rate [89% vs. 86%; hazard ratio 1.34 (0.88–2.04); P=0.17]. There was no overall difference in relapse or survival at four years between the arms: 46% vs. 54%; hazard ratio 1.17 (0.94–1.45), P=0.5, and 50% versus 47%; hazard ratio 1.10 (0.90–1.34), P=0.3, respectively. The 30- and 60-day mortality was significantly higher in the 6 mg/m2 recipients: 7% versus 3%; hazard ratio 2.07 (1.11–3.87), P=0.02, and 9% versus 5%; hazard ratio 1.99 (1.17–3.39), P=0.01, respectively, which in addition was associated with a higher rate of veno-occlusive disease (5.6% vs. 0.5%; P<0.0001). Our conclusion from this trial is that there is no advantage in using a single dose of 6 mg/m2 of gemtuzumab ozogamicin in combination with induction chemotherapy when compared with a 3 mg/m2 dose, with respect to response, disease-free and overall survival, either overall, or in any disease subgroup. (AML17 was registered as ISRCTN55675535.) PMID:26921360

  5. Spherically shaped active transducer based on proton-irradiated vinylidene fluoride-trifluoroethylene 70/30 mol % copolymer

    SciTech Connect

    Lau, S.T.; Chan, H.L.W.; Choy, C.L.; Cheung, W.Y.; Wong, S.P.

    2006-05-15

    Spherically shaped active transducers using proton-irradiated vinylidene fluoride-trifluoroethylene 70/30 mol % copolymer films as the active elements are described. The copolymer films prepared by hot compression molding were irradiated with a high energy proton over a broad dose range (20-250 Mrad). The electrostrictive and piezoelectric responses of the copolymer have been characterized before subsequent transducer fabrication. The performances of the focused transducers constructed with a 4 mm aperture size and epoxy backing were evaluated under dc bias voltages. The transducers with focal lengths of 17.4-19.0 mm and a center frequency of 19 MHz display a broad bandwidth up to 94%. Besides, the transmitting output of the transducers increases with the dc bias voltage. For the copolymer active element irradiated at a proton dose of 107 Mrad, the transducer shows the highest transmitting voltage response of 1.34 kPa/V.

  6. Distribution of the PBC-specific- (M2) and the naturally-occurring mitochondrial antigen- (NOMAg) systems in plants.

    PubMed Central

    Lang, P; Klein, R; Becker, E W; Berg, P A

    1992-01-01

    In previous studies it was demonstrated that antibodies in sera from patients with primary biliary cirrhosis (PBC) and their relatives can recognize two different antigen systems in the ATPase fraction prepared from beef heart mitochondria, namely the PBC-related M2- and the naturally occurring mitochondrial antigen (NOMAg)-related epitopes. Since separation of these two antigen systems could not be achieved using mammalian mitochondria, mitochondria from a wide spectrum of plants were analysed with respect to the presence of mitochondrial antigens. Mitochondria from 29 species of plants were prepared and tested by ELISA and Western blot using marker sera from patients with PBC reacting in the Western blot with M2a,b,c,d (alpha-ketoacid-dehydrogenase complex) and NOMAg-specific sera recognizing the three major epitopes epsilon, zeta, and eta at 65, 61 and 58 kD. Naturally occurring mitochondrial antibody (NOMA)-positive marker sera reacted in the ELISA with mitochondria from all plants, and the zeta/eta positive sera gave also a positive reaction at 61/58 kD in the Western blot while the epsilon epitope could not be visualized by this method. In contrast, the M2 antigen was detected preferentially in lower plants such as algae, fungi, and ferns. Analysing these data with respect to the evolution of proteins one would have to assume that the M2 antigen was lost in most higher plants or underwent some structural alterations. Furthermore, considering the fact that the M2- and the NOMAg-related epitopes could be only partially separated, i.e. there were no plant mitochondria showing only M2 but no NOMAg, one could speculate that anti-M2 antibodies are derived from the pool of naturally occurring antibodies. Images Fig. 2 PMID:1281057

  7. Contact-dependent carcinoma aggregate dispersion by M2a macrophages via ICAM-1 and β2 integrin interactions

    PubMed Central

    Dang, Truong-Minh; Tu, Ting-Yuan; Leong Penny, Hwei-Xian; Wong, Siew-Cheng; Kamm, Roger D.; Thiery, Jean-Paul

    2015-01-01

    Tumor-associated macrophages (TAMs) can constitute up to 50% of the tumor mass and have strong implications in tumor progression and metastasis. Macrophages are plastic and can polarize to various subtypes that differ in terms of surface receptor expression as well as cytokine and chemokine production and effector function. Conventionally, macrophages are grouped into two major subtypes: the classically activated M1 macrophages and the alternatively activated M2 macrophages. M1 macrophages are pro-inflammatory, promote T helper (Th) 1 responses, and show tumoricidal activity, whereas M2 macrophages contribute to tissue repair and promote Th2 responses. Herein, we present a microfluidic system integrating tumor cell aggregates and subtypes of human monocyte-derived macrophages in a three-dimensional hydrogel scaffold, in close co-culture with an endothelial monolayer to create an in vitro tumor microenvironment. This platform was utilized to study the role of individual subtypes of macrophages (M0, M1, M2a, M2b and M2c) in human lung adenocarcinoma (A549) aggregate dispersion, as a representation of epithelial-mesenchymal transition (EMT). A significant difference was observed when M2a macrophages were in direct contact with or separated from A549 aggregates, suggesting a possible mechanism for proximity-induced, contact-dependent dissemination via ICAM-1 and integrin β2 interactions. Indeed, M2a macrophages tended to infiltrate and release cells from carcinoma cell aggregates. These findings may help in the development of immunotherapies based on enhancing the tumor-suppressive properties of TAMs. PMID:26231039

  8. Contact-dependent carcinoma aggregate dispersion by M2a macrophages via ICAM-1 and β2 integrin interactions.

    PubMed

    Bai, Jing; Adriani, Giulia; Dang, Truong-Minh; Tu, Ting-Yuan; Penny, Hwei-Xian Leong; Wong, Siew-Cheng; Kamm, Roger D; Thiery, Jean-Paul

    2015-09-22

    Tumor-associated macrophages (TAMs) can constitute up to 50% of the tumor mass and have strong implications in tumor progression and metastasis. Macrophages are plastic and can polarize to various subtypes that differ in terms of surface receptor expression as well as cytokine and chemokine production and effector function. Conventionally, macrophages are grouped into two major subtypes: the classically activated M1 macrophages and the alternatively activated M2 macrophages. M1 macrophages are pro-inflammatory, promote T helper (Th) 1 responses, and show tumoricidal activity, whereas M2 macrophages contribute to tissue repair and promote Th2 responses. Herein, we present a microfluidic system integrating tumor cell aggregates and subtypes of human monocyte-derived macrophages in a three-dimensional hydrogel scaffold, in close co-culture with an endothelial monolayer to create an in vitro tumor microenvironment. This platform was utilized to study the role of individual subtypes of macrophages (M0, M1, M2a, M2b and M2c) in human lung adenocarcinoma (A549) aggregate dispersion, as a representation of epithelial-mesenchymal transition (EMT). A significant difference was observed when M2a macrophages were in direct contact with or separated from A549 aggregates, suggesting a possible mechanism for proximity-induced, contact-dependent dissemination via ICAM-1 and integrin β2 interactions. Indeed, M2a macrophages tended to infiltrate and release cells from carcinoma cell aggregates. These findings may help in the development of immunotherapies based on enhancing the tumor-suppressive properties of TAMs. PMID:26231039

  9. Generation of New M2e-HA2 Fusion Chimeric Peptide to Development of a Recombinant Fusion Protein Vaccine

    PubMed Central

    Ameghi, Ali; Baradaran, Behzad; Aghaiypour, Khosrow; Barzegar, Abolfazl; Pilehvar-Soltanahmadi, Yones; Moghadampour, Masood; Taghizadeh, Morteza; Zarghami, Nosratollah

    2015-01-01

    Purpose: The purpose was to design a new construction containing influenza virus (H1N1) M2e gene and HA2 gene by bioinformatics approach, cloning the construct in to Escherichia coli and produce M2e-HA2 peptide. Methods: The procedure was done by virus cultivation in SPF eggs, hemagglutination assay (HA), RNA isolation, RT-PCR, primers designed (DNAMAN 4 and Oligo7), virtual fusion construction translation (ExPASy), N-Glycosylated sites prediction (Ensemblegly-Iowa), complete open reading frame (ORF), stop codon studied (NCBI ORF Finder), rare codon determination (GenScript), Solvent accessibility of epitopes (Swiss-PdbViewer), antigenic sites prediction (Protean), fusion PCR of M2e-HA2 gene, sequence analysis, nested PCR, gel electrophoresis, double digestion of pET22b(+) plasmid and the fusion construct, ligation of them, transformation of the ligated vector (pET22b-M2e-HA2) to E.coli (BL21), mass culture the cloned bacterium ,induction the expression by isopropyl-beta-D-thiogalactopyranoside (IPTG), sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), purification the fusion peptide by Ni-NTA column, western blot to verify the purification. Results: In this study we developed a new approach for fusion of Influenza virus M2e (96 nucleotides) and HA2 (663 nucleotides) genes based on fusion PCR strategy and produced a fused fragment with 793 nucleotides. The construct was successfully cloned and expressed. Conclusion: This construct is a 261 amino acid chimeric fusion peptide with about 30 KD molecular weight. According on the latest information; this is the first case of expression and purification M2e-HA2 fusion chimeric peptide, which could be used for development of a recombinant M2e-HA2 fusion protein vaccine. PMID:26793615

  10. Ovarian cancer stem cells induce the M2 polarization of macrophages through the PPARγ and NF-κB pathways.

    PubMed

    Deng, Xinchao; Zhang, Ping; Liang, Tingting; Deng, Suye; Chen, Xiaojie; Zhu, Lin

    2015-08-01

    Increasing evidence suggests an association between cancer stem cells and the tumor microenvironment. Ovarian cancer stem cell (OCSC) factors can influence the tumor microenvironment and prognosis. However, the effects of OCSCs on macrophage M1/M2 polarization are not yet completely understood. In the present study, we evaluated the effects of OCSCs on macrophage M1/M2 polarization. In addition, we investigated whether the activation of the peroxisome proliferator-activated receptor γ (PPARγ)/nuclear factor-κB (NF-κB) pathway is involved in these effects, thus modulating the M1/M2 differentiation of monocytes into macrophages. The expression levels of markers of the M1 state, such as tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS) and CD86, as well as those of markers of M2 activation, such as mannose receptor (MR), interleukin (IL)-10 and arginase-1 (Arg-1), were measured by RT-qPCR. We found that the OCSCs promoted the M2 polarization of Raw264.7 macrophages by upregulating the expression of MR, IL-10 and Arg-1, while the expression levels of M1 macrophages markers, including TNF-α, iNOS and CD86 were suppressed. In addition, treatment with OCSCs activated PPARγ and suppressed NF-κB in the Raw264.7 cells. Furthermore, the PPARγ, antagonist GW9662, attenuated the promoting effects of OCSCs on the M2 polarization of macrophages. To the best of our knowledge, the findings of the present study, provide the first evidence that OCSCs promote the M2 polarization of macrophages through the PPARγ/NF-κB pathway.

  11. Porphyromonas gingivalis Lipopolysaccharide Weakly Activates M1 and M2 Polarized Mouse Macrophages but Induces Inflammatory Cytokines

    PubMed Central

    Holden, James A.; Attard, Troy J.; Laughton, Katrina M.; Mansell, Ashley; O'Brien-Simpson, Neil M.

    2014-01-01

    Porphyromonas gingivalis is associated with chronic periodontitis, an inflammatory disease of the tooth's supporting tissues. Macrophages are important in chronic inflammatory conditions, infiltrating tissue and becoming polarized to an M1 or M2 phenotype. As responses to stimuli differ between these phenotypes, we investigated the effect of P. gingivalis lipopolysaccharide (LPS) on M1 and M2 macrophages. M1 and M2 polarized macrophages were produced from murine bone marrow macrophages (BMMϕ) primed with gamma interferon (IFN-γ) or interleukin-4 (IL-4), respectively, and incubated with a low or high dose of P. gingivalis LPS or control TLR2 and TLR4 ligands. In M1-Mϕ, the high dose of P. gingivalis LPS (10 μg/ml) significantly increased the expression of CD40, CD86, inducible nitric oxide synthase, and nitric oxide secretion. The low dose of P. gingivalis LPS (10 ng/ml) did not induce costimulatory or antibacterial molecules but did increase the secretion of IL-1α, IL-6, IL-12p40, IL-12p70, and tumor necrosis factor alpha (TNF-α). P. gingivalis LPS marginally increased the expression of CD206 and YM-1, but it did enhance arginase expression by M2-Mϕ. Furthermore, the secretion of the chemokines KC, RANTES, eotaxin, and MCP-1 from M1, M2, and nonpolarized Mϕ was enhanced by P. gingivalis LPS. TLR2/4 knockout macrophages combined with the TLR activation assays indicated that TLR2 is the main activating receptor for P. gingivalis LPS and whole cells. In conclusion, although P. gingivalis LPS weakly activated M1-Mϕ or M2-Mϕ compared to control TLR ligands, it induced the secretion of inflammatory cytokines, particularly TNF-α from M1-Mϕ and IL-10 from M2-Mϕ, as well as chemotactic chemokines from polarized macrophages. PMID:25047849

  12. Sequence analysis and expression of the M1 and M2 matrix protein genes of hirame rhabdovirus (HIRRV)

    USGS Publications Warehouse

    Nishizawa, T.; Kurath, G.; Winton, J.R.

    1997-01-01

    We have cloned and sequenced a 2318 nucleotide region of the genomic RNA of hirame rhabdovirus (HIRRV), an important viral pathogen of Japanese flounder Paralichthys olivaceus. This region comprises approximately two-thirds of the 3' end of the nucleocapsid protein (N) gene and the complete matrix protein (M1 and M2) genes with the associated intergenic regions. The partial N gene sequence was 812 nucleotides in length with an open reading frame (ORF) that encoded the carboxyl-terminal 250 amino acids of the N protein. The M1 and M2 genes were 771 and 700 nucleotides in length, respectively, with ORFs encoding proteins of 227 and 193 amino acids. The M1 gene sequence contained an additional small ORF that could encode a highly basic, arginine-rich protein of 25 amino acids. Comparisons of the N, M1, and M2 gene sequences of HIRRV with the corresponding sequences of the fish rhabdoviruses, infectious hematopoietic necrosis virus (IHNV) or viral hemorrhagic septicemia virus (VHSV) indicated that HIRRV was more closely related to IHNV than to VHSV, but was clearly distinct from either. The putative consensus gene termination sequence for IHNV and VHSV, AGAYAG(A)(7), was present in the N-M1, M1-M2, and M2-G intergenic regions of HIRRV as were the putative transcription initiation sequences YGGCAC and AACA. An Escherichia coli expression system was used to produce recombinant proteins from the M1 and M2 genes of HIRRV. These were the same size as the authentic M1 and M2 proteins and reacted with anti-HIRRV rabbit serum in western blots. These reagents can be used for further study of the fish immune response and to test novel control methods.

  13. Telmisartan prevention of LPS-induced microglia activation involves M2 microglia polarization via CaMKKβ-dependent AMPK activation.

    PubMed

    Xu, Yuan; Xu, Yazhou; Wang, Yurong; Wang, Yunjie; He, Ling; Jiang, Zhenzhou; Huang, Zhangjian; Liao, Hong; Li, Jia; Saavedra, Juan M; Zhang, Luyong; Pang, Tao

    2015-11-01

    Brain inflammation plays an important role in the pathophysiology of many psychiatric and neurological diseases. During brain inflammation, microglia cells are activated, producing neurotoxic molecules and neurotrophic factors depending on their pro-inflammatory M1 and anti-inflammatory M2 phenotypes. It has been demonstrated that Angiotensin II type 1 receptor blockers (ARBs) ameliorate brain inflammation and reduce M1 microglia activation. The ARB telmisartan suppresses glutamate-induced upregulation of inflammatory genes in cultured primary neurons. We wished to clarify whether telmisartan, in addition, prevents microglia activation through polarization to an anti-inflammatory M2 phenotype. We found that telmisartan promoted M2 polarization and reduced M1 polarization in LPS-stimulated BV2 and primary microglia cells, effects partially dependent on PPARγ activation. The promoting effects of telmisartan on M2 polarization, were attenuated by an AMP-activated protein kinase (AMPK) inhibitor or AMPK knockdown, indicating that AMPK activation participates on telmisartan effects. Moreover, in LPS-stimulated BV2 cells, telmisartan enhancement of M2 gene expression was prevented by the inhibitor STO-609 and siRNA of calmodulin-dependent protein kinase kinase β (CaMKKβ), an upstream kinase of AMPK. Furthermore, telmisartan enhanced brain AMPK activation and M2 gene expression in a mouse model of LPS-induced neuroinflammation. In addition, telmisartan reduced the LPS-induced sickness behavior in this in vivo model, and this effect was prevented by prior administration of an AMPK inhibitor. Our results indicate that telmisartan can be considered as a novel AMPK activator, suppressing microglia activation by promoting M2 polarization. Telmisartan may provide a novel, safe therapeutic approach to treat brain disorders associated with enhanced inflammation.

  14. Probing the stability of the M2(Benzene)3 M = Fe, Co, and Ni structures upon electron attachment (deletion) and solvated iron clusters by benzene molecules: Fe2(Benzene)4

    NASA Astrophysics Data System (ADS)

    Flores, Raul; Cortes, Hector F.; Castro, Miguel

    2016-01-01

    Rice-ball (RB) and multiple decker sandwich (MDS) structures of clusters containing transition metal atoms and benzene (Bz) molecules, [M2Bz3]±1 M = Fe, Co, and Ni were studied by means of density functional theory all-electron calculations including dispersion correction as in the BPW91-D2 method. A RB geometry was identified for the ground state (GS) of neutral Fe2Bz3. However, consistent with reported experimental results, RB and MDS structures may occur for the Fe2Bz3- ion. The RB and MDS isomers of Co2Bz3 are degenerate; they have comparable ionization energies; this finding is in agreement with the experimental results, where two isomers were identified also. Experiment and theory suggest that the Co2Bz3- ion has similar geometry, MDS, as the neutral parent. RB and MDS motifs are degenerate for both Ni2Bz3 and Ni2Bz3+ . A RB form is predicted for Ni2Bz3- . In the GS of Fe2Bz4 one benzene molecule was found in the outer region of the RB Fe2Bz3 subcluster; it presents a binding energy (D0) of 4.6 kcal/mol, being originated from weak van der Waals forces. Thus, bridging the internal ligands, the fourth molecule has solvent behavior in the singlet Fe2Bz4 GS. Likewise, 3 + 1 MDS isomers of Fe2Bz4 were found at higher energies, ≈ 13.1 kcal/mol, from the GS. In Fe2Bz4-, the RB motif yields the GS with a D0 of 6.7 kcal/mol for the solvent unit. Having a D0 of 9.0 kcal/mol for such moiety the MDS Fe2Bz4- ion is near in energy (3.6 kcal/mol) to the Fe2Bz4- GS. The GS has an electron affinity (EA) of 0.40 eV. Notably, the MDS isomer has a larger EA (0.83 eV). The outer molecule in the 3 + 1 RB GS is stabilized by a network of dipole Cδ--Hδ+-Cδ- interactions, formed between the external (internal) hydrogen atoms and the π-electrons of the internal (external) benzene rings. Dipole C-Hintδ+-Cextδ- interactions predominate in the 3 + 1 MDS isomers.

  15. Synthesis and In Vitro Evaluation of Novel Nortropane Derivatives as Potential Radiotracers for Muscarinic M2 Receptors

    PubMed Central

    Knol, Remco J. J.; van den Bos, Jan C.; Janssen, Anton G. M.; de Bruin, Kora; van Eck-Smit, Berthe L. F.; Booij, Jan

    2011-01-01

    Disturbances of the cerebral cholinergic neurotransmitter system are present in neurodegenerative disorders. SPECT or PET imaging, using radiotracers that selectively target muscarinic receptor subtypes, may be of value for in vivo evaluation of such conditions. 6β-acetoxynortropane, a potent muscarinic M2 receptor agonist, has previously demonstrated nanomolar affinity and high selectivity for this receptor. Based on this compound we synthesized four nortropane derivatives that are potentially suitable for SPECT imaging of the M2 receptor. 6β-acetoxynortropane and the novel derivatives were tested in vitro for affinity to the muscarinic M1−3 receptors. The original 6β-acetoxynortropane displayed high affinity (Ki = 70–90 nM) to M2 receptors and showed good selectivity ratios to the M1 (65-fold ratio) and the M3 (70-fold ratio) receptors. All new derivatives showed reduced affinity to the M2 subtype and loss of subtype selectivity. It is therefore concluded that the newly synthesized derivatives are not suitable for human SPECT imaging of M2 receptors. PMID:21755053

  16. Role of Microglial M1/M2 Polarization in Relapse and Remission of Psychiatric Disorders and Diseases

    PubMed Central

    Nakagawa, Yutaka; Chiba, Kenji

    2014-01-01

    Psychiatric disorders such as schizophrenia and major depressive disorder were thought to be caused by neurotransmitter abnormalities. Patients with these disorders often experience relapse and remission; however the underlying molecular mechanisms of relapse and remission still remain unclear. Recent advanced immunological analyses have revealed that M1/M2 polarization of macrophages plays an important role in controlling the balance between promotion and suppression in inflammation. Microglial cells share certain characteristics with macrophages and contribute to immune-surveillance in the central nervous system (CNS). In this review, we summarize immunoregulatory functions of microglia and discuss a possible role of microglial M1/M2 polarization in relapse and remission of psychiatric disorders and diseases. M1 polarized microglia can produce pro-inflammatory cytokines, reactive oxygen species, and nitric oxide, suggesting that these molecules contribute to dysfunction of neural network in the CNS. Alternatively, M2 polarized microglia express cytokines and receptors that are implicated in inhibiting inflammation and restoring homeostasis. Based on these aspects, we propose a possibility that M1 and M2 microglia are related to relapse and remission, respectively in psychiatric disorders and diseases. Consequently, a target molecule skewing M2 polarization of microglia may provide beneficial therapies for these disorders and diseases in the CNS. PMID:25429645

  17. Role of the tumor suppressor ARF in macrophage polarization: Enhancement of the M2 phenotype in ARF-deficient mice.

    PubMed

    Herranz, Sandra; Través, Paqui G; Luque, Alfonso; Hortelano, Sonsoles

    2012-11-01

    The ARF locus is frequently inactivated in human cancer. The oncosuppressor ARF has indeed been described as a general sensor for different situation of cellular stress. We have previously demonstrated that ARF deficiency severely impairs inflammatory responses in vitro and in vivo, establishing a role for ARF in the regulation of innate immunity. The aim of the present work was to get further insights into the immune functions of ARF and to evaluate its possible contribution to the polarization of macrophages toward the M1 or M2 phenotype. Our results demonstrate that resting Arf(-/-) macrophages express high levels of Ym1 and Fizz-1, two typical markers of alternatively-activated macrophages (M2). Additionally, Arf(-/-) peritoneal macrophages showed an impaired response to lipopolysaccharide (a classical inducer of M1 polaryzation) and a reduced production of pro-inflammatory cytokines/chemokines. Moreover, upon stimulation with interleukin-4 (IL-4), an inducer of the M2 phenotype, well established M2 markers such as Fizz-1, Ym1 and arginase-1 were upregulated in Arf(-/-) as compared with wild type macrophages. Accordingly, the cytokine and chemokine profile associated with the M2 phenotype was significantly overexpressed in Arf(-/-) macrophages responding to IL-4. In addition, multiple pro-angiogenic factors such as VEGF and MMP-9 were also increased. In summary, these results indicate that ARF contributes to the polarization and functional plasticity of macrophages.

  18. Long-Lasting Cross-Protection Against Influenza A by Neuraminidase and M2e-based immunization strategies

    PubMed Central

    Schotsaert, Michael; Ysenbaert, Tine; Smet, Anouk; Schepens, Bert; Vanderschaeghe, Dieter; Stegalkina, Svetlana; Vogel, Thorsten U.; Callewaert, Nico; Fiers, Walter; Saelens, Xavier

    2016-01-01

    There is mounting evidence that in the absence of neutralizing antibodies cross-reactive T cells provide protection against pandemic influenza viruses. Here, we compared protection and CD8+ T cell responses following challenge with H1N1 2009 pandemic and H3N2 viruses of mice that had been immunized with hemagglutinin (HA), neuraminidase (NA) and the extracellular domain of matrix protein 2 (M2e) fused to a virus-like particle (VLP). Mice were challenged a first time with a sublethal dose of H1N1 2009 pandemic virus and, four weeks later, challenged again with an H3N2 virus. Mice that had been vaccinated with HA, NA, NA + M2e-VLP and HA + NA + M2e-VLP were protected against homologous H1N1 virus challenge. Challenged NA and NA + M2e-VLP vaccinated mice mounted CD8+ T cell responses that correlated with protection against secondary H3N2 challenge. HA-vaccinated mice were fully protected against challenge with homologous H1N1 2009 virus, failed to mount cross-reactive CD8+ T cells and succumbed to the second challenge with heterologous H3N2 virus. In summary, NA- and M2e-based immunity can protect against challenge with (homologous) virus without compromising the induction of robust cross-reactive CD8+ T cell responses upon exposure to virus. PMID:27072615

  19. MicroRNA 21 is a homeostatic regulator of macrophage polarization and prevents prostaglandin E2-mediated M2 generation.

    PubMed

    Wang, Zhuo; Brandt, Stephanie; Medeiros, Alexandra; Wang, Soujuan; Wu, Hao; Dent, Alexander; Serezani, C Henrique

    2015-01-01

    Macrophages dictate both initiation and resolution of inflammation. During acute inflammation classically activated macrophages (M1) predominate, and during the resolution phase alternative macrophages (M2) are dominant. The molecular mechanisms involved in macrophage polarization are understudied. MicroRNAs are differentially expressed in M1 and M2 macrophages that influence macrophage polarization. We identified a role of miR-21 in macrophage polarization, and found that cross-talk between miR-21 and the lipid mediator prostaglandin E2 (PGE2) is a determining factor in macrophage polarization. miR-21 inhibition impairs expression of M2 signature genes but not M1 genes. PGE2 and its downstream effectors PKA and Epac inhibit miR-21 expression and enhance expression of M2 genes, and this effect is more pronounced in miR-21-/- cells. Among potential targets involved in macrophage polarization, we found that STAT3 and SOCS1 were enhanced in miR-21-/- cells and further enhanced by PGE2. We found that STAT3 was a direct target of miR-21 in macrophages. Silencing the STAT3 gene abolished PGE2-mediated expression of M2 genes in miR-21-/- macrophages. These data shed light on the molecular brakes involved in homeostatic macrophage polarization and suggest new therapeutic strategies to prevent inflammatory responses.

  20. Different roles for M1 and M2 receptors within perirhinal cortex in object recognition and discrimination.

    PubMed

    Bartko, Susan J; Winters, Boyer D; Saksida, Lisa M; Bussey, Timothy J

    2014-04-01

    Recognition and discrimination of objects and individuals are critical cognitive faculties in both humans and non-human animals, and cholinergic transmission has been shown to be essential for both of these functions. In the present study we focused on the role of M1 and M2 muscarinic receptors in perirhinal cortex (PRh)-dependent object recognition and discrimination. The selective M1 antagonists pirenzepine and the snake toxin MT-7, and a selective M2 antagonist, AF-DX 116, were infused directly into PRh. Pre-sample infusions of both pirenzepine and AF-DX 116 significantly impaired object recognition memory in a delay-dependent manner. However, pirenzepine and MT-7, but not AF-DX 116, impaired oddity discrimination performance in a perceptual difficulty-dependent manner. The findings indicate distinct functions for M1 and M2 receptors in object recognition and discrimination.

  1. Magic-angle-spinning NMR of the drug resistant S31N M2 proton transporter from influenza A.

    PubMed

    Andreas, Loren B; Eddy, Matthew T; Chou, James J; Griffin, Robert G

    2012-05-01

    We report chemical shift assignments of the drug-resistant S31N mutant of M2(18-60) determined using 3D magic-angle-spinning (MAS) NMR spectra acquired with a (15)N-(13)C ZF-TEDOR transfer followed by (13)C-(13)C mixing by RFDR. The MAS spectra reveal two sets of resonances, indicating that the tetramer assembles as a dimer of dimers, similar to the wild-type channel. Helicies from the two sets of chemical shifts are shown to be in close proximity at residue H37, and the assignments reveal a difference in the helix torsion angles, as predicted by TALOS+, for the key resistance residue N31. In contrast to wild-type M2(18-60), chemical shift changes are minimal upon addition of the inhibitor rimantadine, suggesting that the drug does not bind to S31N M2.

  2. Magic angle spinning NMR investigation of influenza A M2(18-60): support for an allosteric mechanism of inhibition.

    PubMed

    Andreas, Loren B; Eddy, Matthew T; Pielak, Rafal M; Chou, James; Griffin, Robert G

    2010-08-18

    The tetrameric M2 proton channel from influenza A virus conducts protons at low pH and is inhibited by aminoadamantyl drugs such as amantadine and rimantadine (Rmt). We report magic angle spinning NMR spectra of POPC and DPhPC membrane-embedded M2(18-60), both apo and in the presence of Rmt. Similar line widths in the spectra of apo and bound M2 indicate that Rmt does not have a significant impact on the dynamics or conformational heterogeneity of this construct. Substantial chemical shift changes for many residues in the transmembrane region support an allosteric mechanism of inhibition. An Rmt titration supports a binding stoichiometry of >1 Rmt molecule per channel and shows that nonspecific binding or changes in membrane composition are unlikely sources of the chemical shift changes. In addition, doubling of spectral lines in all of the observed samples provides evidence that the channel assembles with twofold symmetry.

  3. M2SR, a novel live single replication influenza virus vaccine, provides effective heterosubtypic protection in mice.

    PubMed

    Sarawar, Sally; Hatta, Yasuko; Watanabe, Shinji; Dias, Peter; Neumann, Gabriele; Kawaoka, Yoshihiro; Bilsel, Pamuk

    2016-09-30

    Despite the annual public health burden of seasonal influenza and the continuing threat of a global pandemic posed by the emergence of highly pathogenic/pandemic strains, conventional influenza vaccines do not provide universal protection, and exhibit suboptimal efficacy rates, even when they are well matched to circulating strains. To address the need for a highly effective universal influenza vaccine, we have developed a novel M2-deficient single replication vaccine virus (M2SR) that induces strong cross-protective immunity against multiple influenza strains in mice. M2SR is able to infect cells and expresses all viral proteins except M2, but is unable to generate progeny virus. M2SR generated from influenza A/Puerto Rico/8/34 (H1N1) protected mice against lethal challenge with influenza A/Puerto Rico/8/34 (H1N1, homosubtypic) and influenza A/Aichi/2/1968 (H3N2, heterosubtypic). The vaccine induced strong systemic and mucosal antibody responses of both IgA and IgG classes. Strong virus-specific T cell responses were also induced. Following heterologous challenge, significant numbers of IFN-γ-producing CD8 T cells, with effector or effector/memory phenotypes and specific for conserved viral epitopes, were observed in the lungs of vaccinated mice. A substantial proportion of the CD8 T cells expressed Granzyme B, suggesting that they were capable of killing virus-infected cells. Thus, our data suggest that M2-deficient influenza viruses represent a promising new approach for developing a universal influenza vaccine. PMID:27595896

  4. Pomegranate juice polyphenols induce a phenotypic switch in macrophage polarization favoring a M2 anti-inflammatory state.

    PubMed

    Aharoni, Saar; Lati, Yoni; Aviram, Michael; Fuhrman, Bianca

    2015-01-01

    It was documented that pomegranate has anti-inflammatory effects. In this study, we investigated a direct effect of pomegranate juice (PJ) and its polyphenols on macrophage inflammatory phenotype. In vitro, PJ and its major polyphenols dose-dependently attenuated macrophage response to M1 proinflammatory activation in J774.A1 macrophage-like cell line. This was evidenced by a significant decrease in TNFα and IL-6 secretion in response to stimulation by IFNγ and Lipopolysaccharide. In addition, PJ and punicalagin dose-dependently promoted the macrophages toward a M2 anti-inflammatory phenotype, as determined by a significant increase in the spontaneous secretion of IL-10. In mice, supplementation with dietary PJ substantially inhibited the M2 to M1 macrophage phenotypic shift associated with age, toward a favorable anti-inflammatory M2 phenotype. This effect was also reflected in the mice atherosclerotic plaques, as evaluated by the distinct expression of arginase isoforms. PJ consumption inhibited the increment of arginase II (Arg II, M1) mRNA expression during aging, and maintained the levels of Arg I (M2) expression similar to those in young mice aorta. This study demonstrates, for the first time, that pomegranate polyphenols directly suppress macrophage inflammatory responses and promote M1 to M2 switch in macrophage phenotype. Furthermore, this study indicates that PJ consumption may inhibit the progressive proinflammatory state in the aorta along atherosclerosis development with aging, due to a switch in macrophage phenotype from proinflammatory M1 to anti-inflammatory M2.

  5. Activation of Epidermal Growth Factor Receptor in Macrophages Mediates Feedback Inhibition of M2 Polarization and Gastrointestinal Tumor Cell Growth.

    PubMed

    Zhao, Gang; Liu, Liping; Peek, Richard M; Hao, Xishan; Polk, D Brent; Li, Hui; Yan, Fang

    2016-09-23

    EGF receptor (EGFR) in tumor cells serves as a tumor promoter. However, information about EGFR activation in macrophages in regulating M2 polarization and tumor development is limited. This study aimed to investigate the effects of EGFR activation in macrophages on M2 polarization and development of gastrointestinal tumors. IL-4, a cytokine to elicit M2 polarization, stimulated release of an EGFR ligand, HB-EGF, and transactivation and down-regulation of EGFR in Raw 264.7 cells and peritoneal macrophages from WT mice. Knockdown of HB-EGF in macrophages inhibited EGFR transactivation by IL-4. IL-4-stimulated STAT6 activation, Arg1 and YM1 gene expression, and HB-EGF production were further enhanced by inhibition of EGFR activity in Raw 264.7 cells using an EGFR kinase inhibitor and in peritoneal macrophages from Egfr(wa5) mice with kinase inactive EGFR and by knockdown of EGFR in peritoneal macrophages from Egfr(fl/fl) LysM-Cre mice with myeloid cell-specific EGFR deletion. Chitin induced a higher level of M2 polarization in peritoneal macrophages in Egfr(fl/fl) LysM-Cre mice than that in Egfr(fl/fl) mice. Accordingly, IL-4-conditioned medium stimulated growth and epithelial-to-mesenchymal transition in gastric epithelial and colonic tumor cells, which were suppressed by that from Raw 264.7 cells with HB-EGF knockdown but promoted by that from Egfr(wa5) and Egfr(fl/fl) LysM-Cre peritoneal macrophages. Clinical assessment revealed that the number of macrophages with EGFR expression became less, indicating decreased inhibitory effects on M2 polarization, in late stage of human gastric cancers. Thus, IL-4-stimulated HB-EGF-dependent transactivation of EGFR in macrophages may mediate inhibitory feedback for M2 polarization and HB-EGF production, thereby inhibiting gastrointestinal tumor growth.

  6. Annexin A5 Promoter Haplotype M2 Is Not a Risk Factor for Recurrent Pregnancy Loss in Northern Europe

    PubMed Central

    Rull, Kristiina; Christiansen, Ole B.; Nielsen, Henriette S.; Laan, Maris

    2015-01-01

    Introduction Annexin A5 is an essential component of placental integrity that may potentially mediate susceptibility to phenotypes of compromised pregnancy. A promoter haplotype termed M2 of the coding gene ANXA5 has been implicated in various pregnancy complications such as preeclampsia and recurrent pregnancy loss (RPL), however with inconclusive results. Study subjects and methods A retrospective case-control study combining resequencing and restriction fragment length polymorphism (RFLP) analysis was undertaken in 313 women with unexplained RPL and 214 fertile women from Estonia and Denmark to estimate the RPL disease risk of the M2 haplotype in Northern Europe. Comparative prevalence of the studied ANXA5 genetic variants in human populations was estimated based on the 1000 Genomes Project (n = 675, whole-genome sequencing data) and the KORA S3 500K dataset of South German samples (n = 1644, genome-wide genotyping data). Results Minor allele frequency of common polymorphisms in ANXA5 promoter was up to two-fold lower among Estonian RPL subjects than fertile controls. The M2 haplotype was not associated with RPL and a trend for decreased prevalence was observed among RPL patients compared to controls both in Estonia (8.1% vs 15.2%, respectively) and Denmark (9.7% vs 12.6%). The high M2 prevalence in fertile controls was consistent with estimations for European and East Asian populations (9.6%-16.0%). Conclusions This study cautions to consider the M2 haplotype as a deterministic factor in early pregnancy success because: i) no RPL disease risk was associated with the haplotype in two clinically well-characterized RPL case-control study samples, ii) high prevalence of the haplotype among fertile controls and world-wide populations is inconsistent with the previously proposed severe impact on early pregnancy success, iii) weak impact of M2 haplotype on the production of ANXA5 protein has been established by others. PMID:26135579

  7. 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

  8. Chronic Opisthorchis viverrini Infection and Associated Hepatobiliary Disease Is Associated with Iron Loaded M2-like Macrophages

    PubMed Central

    Sripa, Banchob

    2014-01-01

    Chronic Opisthorchis viverrini-induced hepatobiliary disease is associated with significant leukocyte infiltration, including activated macrophages; however, the polarization of infiltrating macrophages remains to be fully characterized. In this study, we characterized macrophage polarization and phenotype in chronic O. viverrini-induced hepatobiliary disease in humans and hamsters using gene expression and histochemical analysis. Chronic O. viverrini infection and associated hepatobiliary diseases were associated with iron loaded M2-like macrophages in both humans and hamsters. This study provides suggestive evidence that iron loaded M2-like macrophages promote hepatobiliary disease in chronic O. viverrini infection. PMID:25548425

  9. Structural and Dynamic Mechanisms for the Function and Inhibition of the M2 Proton Channel From Influenza A Virus

    PubMed Central

    Wang, Jun; Qiu, Jade Xiaoyan; Soto, Cinque; DeGrado, William F.

    2011-01-01

    The M2 proton channel from influenza A virus, a prototype for a class of viral ion channels known as viroporins, conducts protons along a chain of water molecules and ionizable side chains, including His37. Recent studies highlight a delicate interplay between protein folding, proton binding and proton conduction through the channel. Drugs inhibit proton conduction by binding to an aqueous cavity adjacent to M2’s proton-selective filter, thereby blocking access of proton to the filter, and altering the energetic landscape of the channel and the energetics of proton-binding to His37. PMID:21247754

  10. Cristallisation, syncristallisation, et alliages moléculaires entre le lorazépam et l'oxazépam

    NASA Astrophysics Data System (ADS)

    Mascherpa-Corral, D.; Mascherpa, G.; Chauvet, A.

    1993-04-01

    Le polymorphisme et pseudopolymorphisme du lorazépam et oxazépam ont été étudiés par analyse thermique, calorimétrie différentielle à balayage et diffraction de rayons X. Deux formes polymorphes du lorazépam et plusieurs mono et hemisolvates ont été isolés à partir de recristallisation dans divers soivants. Aucun polymorphisme ni solvate n'a été mis en évidence avec l'oxazépam. Les paramètres cristallographiques des phases isolées ont été déterminées. A 160 et 203°C, le lorazépam et l'oxazépam perdent respectivement une molécule d'eau pour donner après réarrangement la quinazolinecarboxaldéhyde correspondante. La syncristallisation des deux benzodiazépines dans le benzène conduit à des alliages moléculaires à miscibilité totale à l'état solide dans tout le domaine de concentration entre l'exazépam el la forme α du lorazépam, elle n'est que partielle avec la forme β. Thermal analysis, differential scanning calorimetry, and X-ray diffraction were carried out to study the polymorphism and pseudopolymorphism of lorazepam and oxazepam. Two polymorphic forms of lorazepam and several mono- or hemisolvates were obtained after recrystallization from various solvents. No polymorphic form or solvate has been found for oxazepam. The crystallographic parameters of these new phases were determined. Lorazepam and oxazepam can lose a molecule of water at 160 and 203°C, respectively, and rearrange to quinazolinecarboxaldehyde. Mixed crystals of the two benzodiazepines, after recrystallization from benzene, lead to molecular alloys with complete solid solubility between oxazepam and the α-form of lorazepam over the whole range of composition but only to partial solubility with the β-form of lorazepam.

  11. Y{sub 2}O{sub 3}:Eu{sup 3+} (5 mol%) with Ag nanoparticles prepared by citrate precursor

    SciTech Connect

    Ferrari, J.L.; Cebim, M.A.; Pires, A.M.; Couto dos Santos, M.A.

    2010-09-15

    Y{sub 2}O{sub 3}:Eu{sup 3+} (5 mol% Eu{sup 3+}) and Y{sub 2}O{sub 3}:Eu{sup 3+} (5 mol% Eu{sup 3+}) containing 1 mol% of Ag nanoparticles were prepared by heat treatment of a viscous resin obtained via citrate precursor. TEM and EDS analyses showed that Y{sub 2}O{sub 3}:Eu{sup 3+} (5 mol% Eu{sup 3+}) is formed by nanoparticles with an average size of 12 nm, which increases to 30 nm when Ag is present because the effect of metal induced crystallization occurs. Ag nanoparticles with a size of 9 nm dispersed in Y{sub 2}O{sub 3}:Eu{sup 3+} (5 mol% Eu{sup 3+}) were obtained and the surface plasmon effect on Ag nanoparticles was observed. The emission around 612 nm assigned to the Eu{sup 3+} ({sup 5}D{sub 0{yields}}{sup 7}F{sub 2}) transition enhanced when the Ag nanoparticles were present in the Y{sub 2}O{sub 3}:Eu{sup 3+} luminescent material. - Graphical abstract: The presence of Ag nanoparticles together Y{sub 2}O{sub 3}:Eu{sup 3+} 5 mol% phosphor showed to affect directly the optical and crystallinity of the material. Luminescence spectra show directly the effect observed.

  12. Catechin-based procyanidins from Peumus boldus Mol. aqueous extract inhibit Helicobacter pylori urease and adherence to adenocarcinoma gastric cells.

    PubMed

    Pastene, Edgar; Parada, Víctor; Avello, Marcia; Ruiz, Antonieta; García, Apolinaria

    2014-11-01

    In this work, the anti-Helicobacter pylori effect of an aqueous extract from dried leaves of Peumus boldus Mol. (Monimiaceae) was evaluated. This extract displayed high inhibitory activity against H. pylori urease. Therefore, in order to clarify the type of substances responsible for such effect, a bioassay-guided fractionation strategy was carried out. The active compounds in the fractions were characterized through different chromatographic methods (RP-HPLC; HILIC-HPLC). The fraction named F5 (mDP = 7.8) from aqueous extract was the most active against H. pylori urease with an IC50  = 15.9 µg gallic acid equivalents (GAE)/mL. HPLC analysis evidenced that F5 was composed mainly by catechin-derived proanthocyanidins (LC-MS and phloroglucinolysis). The anti-adherent effect of boldo was assessed by co-culture of H. pylori and AGS cells. Both the aqueous extract and F5 showed an anti-adherent effect in a concentration-dependent manner. An 89.3% of inhibition was reached at 2.0 mg GAE/mL of boldo extract. In conjunction, our results suggest that boldo extract has a potent anti-urease activity and anti-adherent effect against H. pylori, properties directly linked with the presence of catechin-derived proanthocyanidins. PMID:24853276

  13. Transferability of cucumber microsatellite markers used for phylogenetic analysis and population structure study in bottle gourd (Lagenaria siceraria (Mol.) Standl.).

    PubMed

    Bhawna; Abdin, M Z; Arya, L; Verma, M

    2015-02-01

    Improved breeding for developing fruit quality in bottle gourd (Lagenaria siceraria (Mol.) Standl.) necessitates knowledge regarding its genetic diversity. To achieve this, a set of 108 locus-specific SSR markers has been developed in bottle gourd by cross-species transferability from 995 mapped Cucumis sativus SSR markers. During screening, 280 primer pairs amplified in the bottle gourd germplasm, which were further evaluated in a diverse set of 42 lines, resulting in 19 polymorphic, 89 monomorphic, 15 with multiple bands, and the rest 157 showed no or very non-specific amplification. The 19 polymorphic primer pairs produced a total of 54 alleles. Gene diversity, Shannon's information index, and Nei's coefficient of differentiation were calculated suggesting a moderate genetic variation at the species level. A model-based population structure analysis divided these germplasm into two subpopulations. This marker set will be applicable for evaluating the genetic structure for association mapping, DNA fingerprinting, and mounting linkage maps and will be a practical tool set for further genetics. This study provides one of the first quantitative views of population genetic variation in bottle gourd. PMID:25471016

  14. Catechin-based procyanidins from Peumus boldus Mol. aqueous extract inhibit Helicobacter pylori urease and adherence to adenocarcinoma gastric cells.

    PubMed

    Pastene, Edgar; Parada, Víctor; Avello, Marcia; Ruiz, Antonieta; García, Apolinaria

    2014-11-01

    In this work, the anti-Helicobacter pylori effect of an aqueous extract from dried leaves of Peumus boldus Mol. (Monimiaceae) was evaluated. This extract displayed high inhibitory activity against H. pylori urease. Therefore, in order to clarify the type of substances responsible for such effect, a bioassay-guided fractionation strategy was carried out. The active compounds in the fractions were characterized through different chromatographic methods (RP-HPLC; HILIC-HPLC). The fraction named F5 (mDP = 7.8) from aqueous extract was the most active against H. pylori urease with an IC50  = 15.9 µg gallic acid equivalents (GAE)/mL. HPLC analysis evidenced that F5 was composed mainly by catechin-derived proanthocyanidins (LC-MS and phloroglucinolysis). The anti-adherent effect of boldo was assessed by co-culture of H. pylori and AGS cells. Both the aqueous extract and F5 showed an anti-adherent effect in a concentration-dependent manner. An 89.3% of inhibition was reached at 2.0 mg GAE/mL of boldo extract. In conjunction, our results suggest that boldo extract has a potent anti-urease activity and anti-adherent effect against H. pylori, properties directly linked with the presence of catechin-derived proanthocyanidins.

  15. MOL-D: A Collisional Database and Web Service within the Virtual Atomic and Molecular Data Center

    NASA Astrophysics Data System (ADS)

    Vujčič, V.; Jevremović, D.; Mihajlov, A. A.; Ignjatović, Lj. M.; Srećković, V. A.; Dimitrijević, M. S.; Malović, M.

    2015-12-01

    MOL-D database is a collection of cross-sections and rate coefficients for specific collisional processes and a web service within the Serbian Virtual Observatory (SerVO) and the Virtual Atomic and Molecular Data Center (VAMDC). This database contains photo-dissociation cross-sections for the individual ro-vibrational states of the diatomic molecular ions and rate coefficients for the atom-Rydberg atom chemi-ionization and inverse electron-ion-atom chemi-recombination processes. At the moment it contains data for photodissociation cross-sections of hydrogen H2+ and helium He2+ molecular ions and the corresponding averaged thermal photodissociation cross-sections. The ro-vibrational energy states and the corresponding dipole matrix elements are provided as well. Hydrogen and helium molecular ion data are important for calculation of solar and stellar atmosphere models and for radiative transport, as well as for kinetics of other astrophysical and laboratory plasma (i.e. early Universe).

  16. Effect of heat treatment on deformation and mechanical properties of 8 mol% yttria-stabilized zirconia by Berkovich nanoindentation

    NASA Astrophysics Data System (ADS)

    Mao, W. G.; Luo, J. M.; Dai, C. Y.; Shen, Y. G.

    2015-05-01

    The effect of thermal treatment on the elasto-plastic transition and mechanical properties of air plasma-sprayed 8 mol% Y2O3-stabilized ZrO2 (8YSZ) thermal barrier coatings was studied by nanoindentation test at ultra-low loads with a Berkovich indenter. The area contact function of the indenter was calibrated repeatedly under nano-scales, and the indenter tip radius was estimated under different indentation depths, respectively. Owing to the heterogeneous and porous microstructure, the scatter of all collected experimental data was analyzed by Weibull statistic method. It is interesting to observe that the hardness exhibits an apparent reverse indentation size effect under very small depths. The Young's modulus of 8YSZ varies with ranging from 213 to 246 GPa due to the sintering effect. True hardness of 8YSZ increases from as-received 72.9 GPa to a top value 79.7 GPa under 100 thermal cycles, and then slightly decreases from this value to 75.5 GPa under 175 thermal cycles. The pure elastic and elasto-plastic indentation curves were obtained by adjusting the indentation load magnitude. The elasto-plastic transition and resolved shear stress fields were discussed carefully from the use of energetic models and Hertzian contact theory.

  17. Effect of high-pressure torsion deformation on surface properties and biocompatibility of Ti-50.9 mol. %Ni alloys.

    PubMed

    Awang Shri, Dayangku Noorfazidah; Tsuchiya, Koichi; Yamamoto, Akiko

    2014-06-01

    Ti-50.9 mol. %Ni was subjected to high-pressure torsion (HPT) deformation for different number of rotations (N) of 0.25, 0.5, 1, 5, and 10. The structural changes induced by HPT were analyzed using x-ray diffractometer (XRD). The surfaces of the samples before and after cell culture were characterized using x-ray photoelectron spectroscopy (XPS). The biocompatibility of the samples was evaluated based on a colony formation assay, nickel ion release, and protein adsorption behavior. XRD analysis revealed the occurrence of grain refinement, phase transformation, and amorphization in the TiNi samples by HPT deformation due to high dislocation density. The changes in chemical composition and thickness of the passive film formed on the surface observed in XPS analysis reveals improvement in the stability of the passive film by HPT deformation. The microstructural change due to the deformation was found to influence the biocompatibility behaviors of TiNi. Plating efficiency and protein adsorption were found to be higher when the samples are in stress-induced martensitic or amorphous state. HPT deformation was found to alter the surface behavior of the TiNi, which effectively reduced the Ni ion release and improved its biocompatibility. PMID:24985211

  18. Détermination assistée par ordinateur de la structure des molécules organiques

    NASA Astrophysics Data System (ADS)

    Nuzillard, J.-M.

    1998-02-01

    Nuclear Magnetic Resonance spectroscopy offers the unique possibility of accessing proximity relationships between atoms by means of chemical shift correlation experiments. Structure determination of small molecules has become thus much simpler. Computer programs can use directly correlation information for structure analysis. The use and operation mechanism of such a program, LSD (Logic for Structure Determination) are presented. The example compound is gibberellic acid, a natural product. La spectroscopie de Résonance Magnétique Nucléaire offre un moyen unique de déterminer des relations de proximité entre atomes par le biais des expériences de corrélation. L'analyse structurale de petites molécules organiques s'en trouve extrêmement facilitée. Des programmes informatiques peuvent utiliser directement les informations de corrélation pour déduire des structures. Le fonctionnement et l'usage d'un tel programme, LSD (Logic for Structure Determination), sont détaillés sur un exemple, l'acide gibberellique.

  19. COMPLETE SUPPRESSION OF THE M=2/N-1 NEOCLASSICAL TEARING MODE USING ELECTRON CYCLOTRON CURRENT DRIVE ON DIII-D

    SciTech Connect

    PETTY,CC; LAHAYE,LA; LUCE,TC; HUMPHREYS,DA; HYATT,AW; PRATER,R; STRAIT,EJ; WADE,MR

    2003-03-01

    A271 COMPLETE SUPPRESSION OF THE M=2/N-1 NEOCLASSICAL TEARING MODE USING ELECTRON CYCLOTRON CURRENT DRIVE ON DIII-D. The first suppression of the important and deleterious m=2/n=1 neoclassical tearing mode (NTM) is reported using electron cyclotron current drive (ECCD) to replace the ''missing'' bootstrap current in the island O-point. Experiments on the DIII-D tokamak verify the maximum shrinkage of the m=2/n=1 island occurs when the ECCD location coincides with the q = 2 surface. The DIII-D plasma control system is put into search and suppress mode to make small changes in the toroidal field to find and lock onto the optimum position, based on real time measurements of dB{sub {theta}}/dt, for complete m=2/n=1 NTM suppression by ECCD. The requirements on the ECCD for complete island suppression are well modeled by the modified Rutherford equation for the DIII-D plasma conditions.

  20. Paraoxonase 2 Induces a Phenotypic Switch in Macrophage Polarization Favoring an M2 Anti-Inflammatory State

    PubMed Central

    Koren-Gluzer, Marie; Rosenblat, Mira; Hayek, Tony

    2015-01-01

    Inflammatory processes are involved in atherosclerosis development. Macrophages play a major role in the early atherogenesis, and they are present in the atherosclerotic lesion in two phenotypes: proinflammatory (M1) or anti-inflammatory (M2). Paraoxonase 2 (PON2) is expressed in macrophages, and it was shown to protect against atherosclerosis. Thus, the aim of our study was to analyze the direct effect of PON2 on macrophage inflammatory phenotypes. Ex vivo studies were performed with murine peritoneal macrophages (MPM) harvested from control C57BL/6 and PON2-deficient (PON2KO) mice. PON2KO MPM showed an enhanced proinflammatory phenotype compared to the control, both in the basal state and following M1 activation by IFNγ and lipopolysaccharide (LPS). In parallel, PON2KO MPM also showed reduced anti-inflammatory responses in the basal state and also following M2 activation by IL-4. Moreover, the PON2-null MPM demonstrated enhanced phagocytosis and reactive oxygen species (ROS) production in the basal state and following M1 activation. The direct effect of PON2 was shown by transfecting human PON2 (hPON2) into PON2KO MPM. PON2 transfection attenuated the macrophages' response to M1 activation and enhanced M2 response. These PON2 effects were associated with attenuation of macrophages' abilities to phagocyte and to generate ROS. We conclude that PON2 promotes an M1 to M2 switch in macrophage phenotypes. PMID:26779262