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Sample records for m2 m3 m4

  1. Binding properties of nine 4-diphenyl-acetoxy-N-methyl-piperidine (4-DAMP) analogues to M1, M2, M3 and putative M4 muscarinic receptor subtypes.

    OpenAIRE

    Waelbroeck, M.; Camus, J.; Tastenoy, M.; Christophe, J.

    1992-01-01

    1. We compared the binding properties of 4-diphenyl-acetoxy-N-methyl-piperidine methiodide (4-DAMP) and nine analogues of this compound on muscarinic receptors of human neuroblastoma NB-OK1 cells (M1 subtype), rat heart (M2 subtype), rat pancreas (M3 subtype) and to the putative M4 subtype in striatum. 2. The requirements for high affinity binding were somewhat different for the four receptor subtypes. In general, the requirements of M3 receptors were more stringent than for M1, M2 or putativ...

  2. [2 fatal cases of acute myeloid leukemia (M3, M4) during pregnancy].

    Science.gov (United States)

    Aragona, M; Asmundo, A

    1995-04-01

    Two cases of unexpected post-partum death of women with acute leukemia are described. In the first case (1st pregnancy) the diagnosis (acute promyelocytic leukemia: M3) was performed one week before delivery and death occurred 3 days later, because of hemorrhagic and renal DIC complication. Since one month before hospitalization, laboratory exams indicated a serious hematological pathology and no further exams were carried out by the physicians, elements of professional fault were recognized in them, considering that because of the diagnostic omission it was impossible to make an early diagnosis and thus perform to specific therapy, adopted only in the terminal phase. This specific therapy is able to determine remission from most cases of acute promyelocytic leukemia. In the second case (2nd pregnancy) the diagnosis (acute myelomonocytic leukemia: M4) was performed only postmortem because, during the whole pregnancy, no signs of disease were evident. After a few hours from the spontaneous delivery, death occurred as a result of an intractable + hemorrhagic syndrome caused by primary hyperfibrinolysis and repeated episodes of cardiac arrest, without possibility of recognizing it. The medical procedures for this case, both throughout pregnancy and terminal phases, appeared free of censure.

  3. Relativistic electrons high doses at International Space Station and Foton M2/M3 satellites

    Science.gov (United States)

    Dachev, T. P.; Tomov, B.; Matviichuk, Yu.; Dimitrov, Pl.; Bankov, N.

    2009-12-01

    The paper presents observation of relativistic electrons. Data are collected by the Radiation Risk Radiometer-Dosimeters (R3D) B2/B3 modifications during the flights of Foton M2/M3 satellites in 2005 and 2007 as well as by the R3DE instrument at the European Technology Exposure Facility (EuTEF) on the Columbus External Payload Adaptor at the International Space Station (ISS) in the period February 20 - April 28, 2008. On the Foton M2/M3 satellites relativistic electrons are observed more frequently than on the ISS because of higher (62.8°) inclination of the orbit. At both Foton satellites the usual duration of the observations are a few minutes long. On the ISS the duration usually is about 1 min or less. The places of observations of high doses due to relativistic electrons are distributed mainly at latitudes above 50° geographic latitude in both hemispheres on Foton M2/M3 satellites. A very high maximum is found in the southern hemisphere at longitudinal range 0°-60°E. At the ISS the maximums are observed between 45° and 52° geographic latitude in both hemispheres mainly at longitudes equatorward from the magnetic poles. The measured absolute maximums of dose rates generated by relativistic electrons are found to be as follows: 304 μGy h -1 behind 1.75 g cm -2 shielding at Foton M2, 2314 μGy h -1 behind 0.71 g cm -2 shielding at Foton M3 and 19,195 μGy h -1 (Flux is 8363 cm -2 s -1) behind les than 0.4 g cm -2 shielding at ISS.

  4. A picrotoxin-specific conformational change in the glycine receptor M2-M3 loop.

    Science.gov (United States)

    Hawthorne, Rebecca; Lynch, Joseph W

    2005-10-28

    The external loop linking the M2 and M3 transmembrane domains is crucial for coupling agonist binding to channel gating in the glycine receptor chloride channel (GlyR). A substituted cysteine accessibility scan previously showed that glycine activation increased the surface accessibility of 6 contiguous residues (Arg271-Lys276) toward the N-terminal end of the homomeric alpha1 GlyR M2-M3 loop. In the present study we used a similar approach to determine whether the allosteric antagonist, picrotoxin, could impose conformational changes to this domain that cannot be induced by varying agonist concentrations alone. Picrotoxin slowed the reaction rate of a sulfhydryl-containing compound (MTSET) with A272C, S273C, and L274C. Before interpreting this as a picrotoxin-specific conformational change, it was necessary to eliminate the possibility of steric competition between picrotoxin and MTSET. Accordingly, we showed that picrotoxin and the structurally unrelated blocker, bilobalide, were both trapped in the R271C GlyR in the closed state and that a point mutation to the pore-lining Thr6' residue abolished inhibition by both compounds. We also demonstrated that the picrotoxin dissociation rate was linearly related to the channel open probability. These observations constitute a strong case for picrotoxin binding in the pore. We thus conclude that the picrotoxin-specific effects on the M2-M3 loop are mediated allosterically. This suggests that the M2-M3 loop responds differently to the occupation of different binding sites.

  5. Length and amino acid sequence of peptides substituted for the 5-HT3A receptor M3M4 loop may affect channel expression and desensitization.

    Directory of Open Access Journals (Sweden)

    Nicole K McKinnon

    Full Text Available 5-HT3A receptors are pentameric neurotransmitter-gated ion channels in the Cys-loop receptor family. Each subunit contains an extracellular domain, four transmembrane segments (M1, M2, M3, M4 and a 115 residue intracellular loop between M3 and M4. In contrast, the M3M4 loop in prokaryotic homologues is <15 residues. To investigate the limits of M3M4 loop length and composition on channel function we replaced the 5-HT3A M3M4 loop with two to seven alanine residues (5-HT3A-A(n = 2-7. Mutants were expressed in Xenopus laevis oocytes and characterized using two electrode voltage clamp recording. All mutants were functional. The 5-HT EC(50's were at most 5-fold greater than wild-type (WT. The desensitization rate differed significantly among the mutants. Desensitization rates for 5-HT3A-A(2, 5-HT3A-A(4, 5-HT3A-A(6, and 5-HT3A-A(7 were similar to WT. In contrast, 5-HT3A-A(3 and 5-HT3A-A(5 had desensitization rates at least an order of magnitude faster than WT. The one Ala loop construct, 5-HT3A-A(1, entered a non-functional state from which it did not recover after the first 5-HT application. These results suggest that the large M3M4 loop of eukaryotic Cys-loop channels is not required for receptor assembly or function. However, loop length and amino acid composition can effect channel expression and desensitization. We infer that the cytoplasmic ends of the M3 and M4 segments may undergo conformational changes during channel gating and desensitization and/or the loop may influence the position and mobility of these segments as they undergo gating-induced conformational changes. Altering structure or conformational mobility of the cytoplasmic ends of M3 and M4 may be the basis by which phosphorylation or protein binding to the cytoplasmic loop alters channel function.

  6. M2M monitoring terminal based on Cortex-M3%基于Cortex-M3M2M监控终端

    Institute of Scientific and Technical Information of China (English)

    张鑫; 丁志刚; 郑树泉

    2011-01-01

    在对物联网在工业监控领域的应用研究后,针对目前工业监控终端体积大、容量小、功能简单等问题,设计并实现了一种微型化、大容量、强实时、多参数的M2M监控终端.该终端设计了基本的监控模块,且针对不同的应用环境预设了可配和选择模块,使适用范围更广.实现了网络动态配置接口,提高了终端的通用性.并借鉴传统数据采集模式,设计一种数据采集和数据传输优化方案,并对优化算法进行探讨,经应用结果分析,对系统开销、数据传输等指标有显著的改进.%After research of the application of Internet of Things (IOT) in industrial control field, according to the monitoring terminal problems that large volume, low-capacity and simple function, a miniaturized, high-capacity, strong realtime, multi-parameter M2M monitoring terminal was designed and implemented. The terminal designed a basic control module, and the default for different applications and options that could be equipped with modules and applied more broadly. It achieved dynamic configuration of network interfaces and improved the versatility of the terminal. Learning from the traditional mode of data acquisition, the paper devised a prioritization scheme of data acquisition and data transmission, and discussed optimization algorithm. The results of applications show that it is a noticeable improvement in the index of system overhead and data transmission.

  7. IFR safety tests M2 and M3 in TREAT: data and analysis

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, W R; Lo, R K; Bauer, T H; Froehle, P H; Helenberg, H W; Morman, J A; Stanford, G S; Wright, A E

    1985-06-01

    TREAT tests M2 and M3 were performed to obtain information on the characteristics of metal-alloy reactor fuel under slow transient overpower accident conditions, in particular, the margin to cladding breach and the axial self-extrusion of fuel within intact cladding. The tests used U-5Fs fuel pins irradiated to burnup levels of 0.3 at. %, 4.5 at. % and 7.9 at. %. Each pin was located in a separte flowtube and cooled by flowing sodium. In one test, a pin of each burnup was heated to incipient cladding breach. In the other, pins of the medium and high burnup levels wer heated to slightly beyond breach. Pre- and post-failure fuel motions were monitored by the fast-neutron hodoscope. The time and axial location of cladding breach were determined from the test-loop instrumentation. Computations of fuel extrusion and cladding failure are desribed. The models used in the computations include effects of retained fission gas expansion, vaporization of the sodium-bond annulus in low burnup fuel, and cladding-wall thinning by eutectic formation.

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

    Science.gov (United States)

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

    2010-04-01

    To compare the gastroesophageal junction of the human with the pig, M(2) and M(3) receptor densities and the potencies of M(2) and M(3) muscarinic receptor subtype selective antagonists were determined in gastric clasp and sling smooth muscle fibers. Total muscarinic and M(2) receptors are higher in pig than human clasp and sling fibers. M(3) receptors are higher in human compared with pig sling fibers but lower in human compared with pig clasp fibers. Clasp fibers have fewer M(3) 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 M(2) receptors are involved in mediating contraction in pig clasp and sling fibers. Darifenacin potency suggests that M(3) receptors mediate contraction in pig sling fibers and that M(2) and M(3) receptors mediate contraction in pig clasp fibers. Taken together, the data suggest that both M(2) and M(3) muscarinic receptors mediate the contraction in both pig clasp and sling fibers similar to human clasp and sling fibers.

  9. Characterization of the novel positive allosteric modulator, LY2119620, at the muscarinic M(2) and M(4) receptors.

    Science.gov (United States)

    Croy, Carrie H; Schober, Douglas A; Xiao, Hongling; Quets, Anne; Christopoulos, Arthur; Felder, Christian C

    2014-07-01

    The M(4) receptor is a compelling therapeutic target, as this receptor modulates neural circuits dysregulated in schizophrenia, and there is clinical evidence that muscarinic agonists possess both antipsychotic and procognitive efficacy. Recent efforts have shifted toward allosteric ligands to maximize receptor selectivity and manipulate endogenous cholinergic and dopaminergic signaling. In this study, we present the pharmacological characterization of LY2119620 (3-amino-5-chloro-N-cyclopropyl-4-methyl-6-[2-(4-methylpiperazin-1-yl)-2-oxoethoxy] thieno[2,3-b]pyridine-2-carboxamide), a M(2)/M(4) receptor-selective positive allosteric modulator (PAM), chemically evolved from hits identified through a M4 allosteric functional screen. Although unsuitable as a therapeutic due to M(2) receptor cross-reactivity and, thus, potential cardiovascular liability, LY2119620 surpassed previous congeners in potency and PAM activity and broadens research capabilities through its development into a radiotracer. Characterization of LY2119620 revealed evidence of probe dependence in both binding and functional assays. Guanosine 5'-[γ-(35)S]-triphosphate assays displayed differential potentiation depending on the orthosteric-allosteric pairing, with the largest cooperativity observed for oxotremorine M (Oxo-M) LY2119620. Further [(3)H]Oxo-M saturation binding, including studies with guanosine-5'-[(β,γ)-imido]triphosphate, suggests that both the orthosteric and allosteric ligands can alter the population of receptors in the active G protein-coupled state. Additionally, this work expands the characterization of the orthosteric agonist, iperoxo, at the M(4) receptor, and demonstrates that an allosteric ligand can positively modulate the binding and functional efficacy of this high efficacy ligand. Ultimately, it was the M(2) receptor pharmacology and PAM activity with iperoxo that made LY2119620 the most suitable allosteric partner for the M(2) active-state structure recently solved

  10. The Armys M-1 Abrams, M-2/M-3 Bradley, and M-1126 Stryker: Background and Issues for Congress

    Science.gov (United States)

    2016-04-05

    entered service with the Army in 1980; the M-2/M-3 Bradley Fighting Vehicle in 1981; and the Stryker Combat Vehicle in 2001. Under current Army... Under current Army modernization plans, the Army envisions all three vehicles in service with Active and National Guard forces beyond FY2028...Information from this section, unless otherwise noted, is taken from Jane’s Armour and Artillery, 2011-2012, pp.177- 185, and the author’s personal

  11. The surface accessibility of the glycine receptor M2-M3 loop is increased in the channel open state.

    Science.gov (United States)

    Lynch, J W; Han, N L; Haddrill, J; Pierce, K D; Schofield, P R

    2001-04-15

    Mutations in the extracellular M2-M3 loop of the glycine receptor (GlyR) alpha1 subunit have been shown previously to affect channel gating. In this study, the substituted cysteine accessibility method was used to investigate whether a structural rearrangement of the M2-M3 loop accompanies GlyR activation. All residues from R271C to V277C were covalently modified by both positively charged methanethiosulfonate ethyltrimethylammonium (MTSET) and negatively charged methanethiosulfonate ethylsulfonate (MTSES), implying that these residues form an irregular surface loop. The MTSET modification rate of all residues from R271C to K276C was faster in the glycine-bound state than in the unliganded state. MTSES modification of A272C, L274C, and V277C was also faster in the glycine-bound state. These results demonstrate that the surface accessibility of the M2-M3 loop is increased as the channel transitions from the closed to the open state, implying that either the loop itself or an overlying domain moves during channel activation.

  12. NXP出货高速Cortex—M4及Cortex—M3微控制器

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    恩智浦半导体(NXP SemiconductorsN.V.)发布LPC4300数字信号控制器(DSC)——一款高速的ARMCortex—M4微控制器,其速度高达204MHz。LPC4300也是带有Cortex—MO协处理器的双核非对称架构DSC。恩智浦还同时将LPCI800系列的性能提升到180MHz。

  13. [Biological experiments in flights of unmanned space craft Foton-M2 and Foton-M3].

    Science.gov (United States)

    Ilyin, E A

    2013-01-01

    Missions of unmanned spacecraft Foton-M2 (2005) and Foton-M3 (2007) of 16 and 12 days in duration, respectively, provided an opportunity to conduct the Russian/US experiments with snails (Helix lucorum and Helix aspera), newts (Pleurodeles waltli), geckos (Pachydactilus turneri) and microorganisms (Streptomyces lividans 66, E. coli and others). Besides, Foton-M3 carried a Russian experiment with Mongolian gerbils (Meriones unguiculatus). Objectives of the space experiments were to study the micro-g effects on the living systems' behavior, structure and functioning, post-traumatic regeneration of bone and organs, stable inheritance of plasmid pIJ 702, and melanin pigment synthesis by streptomycets. The survey paper presents the major findings of a large team of investigators.

  14. GABA(A) receptor M2-M3 loop secondary structure and changes in accessibility during channel gating.

    Science.gov (United States)

    Bera, Amal K; Chatav, Maya; Akabas, Myles H

    2002-11-08

    The gamma-aminobutyric acid type A (GABA(A)) receptor M2-M3 loop structure and its role in gating were investigated using the substituted cysteine accessibility method. Residues from alpha(1)Arg-273 to alpha(1)Ile-289 were mutated to cysteine, one at a time. MTSET(+) or MTSES(-) reacted with all mutants from alpha(1)R273C to alpha(1)Y281C, except alpha(1)P277C, in the absence and presence of GABA. The MTSET(+) closed-state reaction rate was >1000 liters/mol-s at alpha(1)N274C, alpha(1)S275C, alpha(1)K278C, and alpha(1)Y281C and was <300 liters/mol-s at alpha(1)R273C, alpha(1)L276C, alpha(1)V279C, alpha(1)A280C, and alpha(1)A284C. These two groups of residues lie on opposite sides of an alpha-helix. The fast reacting group lies on a continuation of the M2 segment channel-lining helix face. This suggests that the M2 segment alpha-helix extends about two helical turns beyond alpha(1)N274 (20'), aligned with the extracellular ring of charge. At alpha(1)S275C, alpha(1)V279C, alpha(1)A280C, and alpha(1)A284C the reaction rate was faster in the presence of GABA. The reagents had no functional effect on the mutants from alpha(1)A282C to alpha(1)I289C, except alpha(1)A284C. Access may be sterically hindered possibly by close interaction with the extracellular domain. We suggest that the M2 segment alpha-helix extends beyond the predicted extracellular end of the M2 segment and that gating induces a conformational change in and/or around the N-terminal half of the M2-M3 loop. Implications for coupling ligand-evoked conformational changes in the extracellular domain to channel gating in the membrane-spanning domain are discussed.

  15. Sequence analysis of muscarinic receptors M2 and M4 expression by cultured rat astrocyte cells%星形胶质细胞毒蕈碱样乙酰胆碱受体M2M4亚型基因克隆及序列分析

    Institute of Scientific and Technical Information of China (English)

    张晓娟; 汪海

    2005-01-01

    目的:克隆胶质细胞M2M4受体亚型基因序列,并比较胶质细胞M2M4受体亚型基因序列和蛋白质序列与神经元细胞M2M4受体基因序列和蛋白质序列间的差异.方法:根据神经元细胞M2M4受体基因序列设计出针对M2M4受体基因序列全长的特异性探针,采用RT-PCR方法扩增胶质细胞M2M4受体亚型基因序列,并对其进行克隆测序.结果:通过RT-PCR方法扩增胶质细胞M2M4受体亚型基因序列,与神经元细胞M2M4受体比较,M2受体差异碱基17个,发生氨基酸改变的有8个;M4受体差异碱基3个,发生氨基酸改变的有2个.结论:胶质细胞M2M4受体与神经细胞M2M4受体亚型在基因序列和氨基酸序列上具有明显差异.

  16. Development of a radioligand, [(3)H]LY2119620, to probe the human M(2) and M(4) muscarinic receptor allosteric binding sites.

    Science.gov (United States)

    Schober, Douglas A; Croy, Carrie H; Xiao, Hongling; Christopoulos, Arthur; Felder, Christian C

    2014-07-01

    In this study, we characterized a muscarinic acetylcholine receptor (mAChR) potentiator, LY2119620 (3-amino-5-chloro-N-cyclopropyl-4-methyl-6-[2-(4-methylpiperazin-1-yl)-2-oxoethoxy]thieno[2,3-b]pyridine-2-carboxamide) as a novel probe of the human M2 and M4 allosteric binding sites. Since the discovery of allosteric binding sites on G protein-coupled receptors, compounds targeting these novel sites have been starting to emerge. For example, LY2033298 (3-amino-5-chloro-6-methoxy-4-methyl-thieno(2,3-b)pyridine-2-carboxylic acid cyclopropylamid) and a derivative of this chemical scaffold, VU152100 (3-amino-N-(4-methoxybenzyl)-4,6-dim​ethylthieno[2,3-b]pyridine carboxamide), bind to the human M4 mAChR allosteric pocket. In the current study, we characterized LY2119620, a compound similar in structure to LY2033298 and binds to the same allosteric site on the human M4 mAChRs. However, LY2119620 also binds to an allosteric site on the human M2 subtype. [(3)H]NMS ([(3)H]N-methylscopolamine) binding experiments confirm that LY2119620 does not compete for the orthosteric binding pocket at any of the five muscarinic receptor subtypes. Dissociation kinetic studies using [(3)H]NMS further support that LY2119620 binds allosterically to the M2 and M4 mAChRs and was positively cooperative with muscarinic orthosteric agonists. To probe directly the allosteric sites on M2 and M4, we radiolabeled LY2119620. Cooperativity binding of [(3)H]LY2119620 with mAChR orthosteric agonists detects significant changes in Bmax values with little change in Kd, suggesting a G protein-dependent process. Furthermore, [(3)H]LY2119620 was displaced by compounds of similar chemical structure but not by previously described mAChR allosteric compounds such as gallamine or WIN 62,577 (17-β-hydroxy-17-α-ethynyl-δ-4-androstano[3,2-b]pyrimido[1,2-a]benzimidazole). Our results therefore demonstrate the development of a radioligand, [(3)H]LY2119620 to probe specifically the human M2 and M4 muscarinic

  17. The use of occupation isoboles for analysis of a response mediated by two receptors: M2 and M3 muscarinic receptor subtype-induced mouse stomach contractions.

    Science.gov (United States)

    Braverman, Alan S; Tallarida, Ronald J; Ruggieri, Michael R

    2008-06-01

    Smooth muscle contains multiple muscarinic receptor subtypes, including M2 and M3. M2 receptors outnumber M3 receptors. Based on the potency of subtype selective anticholinergics, contraction is mediated by the M3 subtype. However, results from knockout (KO) mice show that the M2 receptor mediates approximately 45% of the contractile response produced by the M3 receptor. The traditional theory of one receptor mediating a response does not allow assessment of interactions between receptors when more than one receptor participates in a response. Our study was performed using a novel analysis method based on dual receptor occupancy to determine how M2 and M3 receptor subtypes interact to mediate contraction in mouse stomach. Cumulative carbachol concentration contractile responses were determined for wild-type, M2-KO, and M3-KO stomach body smooth muscle. Using affinity constants for carbachol at M2 and M3 cholinergic receptors, the concentration values were converted to fractional receptor occupation. The resulting occupation-effect relations showed maximum effects for the M2 and M3 subtypes, respectively. These occupation-effect relations allow determination of the additive (expected) isobole based on this dual occupancy, thereby providing a curve (mathematically derived) for comparison against the experimentally derived value in wild type. The actual values determined experimentally in the wild type were not statistically significantly different from that predicted by the isobole. This confirms that the interaction between these mutually occupied receptors is additive. The new method of analysis also expands the traditional Schild theory that was based on a single receptor type to which the agonist and antagonist bind.

  18. Quantitation of the Contractile Response Mediated by Two Receptors: M2 and M3 Muscarinic Receptor-Mediated Contractions of Human Gastroesophageal Smooth MuscleS⃞

    Science.gov (United States)

    Braverman, Alan S.; Miller, Larry S.; Vegesna, Anil K.; Tiwana, Mansoor I.; Tallarida, Ronald J.; Ruggieri, Michael R.

    2009-01-01

    Although muscarinic receptors are known to mediate tonic contraction of human gastrointestinal tract smooth muscle, the receptor subtypes that mediate the tonic contractions are not entirely clear. Whole human stomachs with attached esophagus were procured from organ transplant donors. Cholinergic contractile responses of clasp, sling, lower esophageal circular (LEC), midesophageal circular (MEC), and midesophageal longitudinal (MEL) muscle strips were determined. Sling fibers contracted greater than the other fibers. Total, M2 and M3 muscarinic receptor density was determined for each of these dissections by immunoprecipitation. M2 receptor density is greatest in the sling fibers, followed by clasp, LEC, MEC, and then MEL, whereas M3 density is greatest in LEC, followed by MEL, MEC, sling, and then clasp. The potency of subtype-selective antagonists to inhibit bethanechol-induced contraction was calculated by Schild analysis to determine which muscarinic receptor subtypes contribute to contraction. The results suggest both M2 and M3 receptors mediate contraction in clasp and sling fibers. Thus, this type of analysis in which multiple receptors mediate the contractile response is inappropriate, and an analysis method relating dual occupation of M2 and M3 receptors to contraction is presented. Using this new method of analysis, it was found that the M2 muscarinic receptor plays a greater role in mediating contraction of clasp and sling fibers than in LEC, MEC, and MEL muscles in which the M3 receptor predominantly mediates contraction. PMID:19126780

  19. Quantitation of the contractile response mediated by two receptors: M2 and M3 muscarinic receptor-mediated contractions of human gastroesophageal smooth muscle.

    Science.gov (United States)

    Braverman, Alan S; Miller, Larry S; Vegesna, Anil K; Tiwana, Mansoor I; Tallarida, Ronald J; Ruggieri, Michael R

    2009-04-01

    Although muscarinic receptors are known to mediate tonic contraction of human gastrointestinal tract smooth muscle, the receptor subtypes that mediate the tonic contractions are not entirely clear. Whole human stomachs with attached esophagus were procured from organ transplant donors. Cholinergic contractile responses of clasp, sling, lower esophageal circular (LEC), midesophageal circular (MEC), and midesophageal longitudinal (MEL) muscle strips were determined. Sling fibers contracted greater than the other fibers. Total, M(2) and M(3) muscarinic receptor density was determined for each of these dissections by immunoprecipitation. M(2) receptor density is greatest in the sling fibers, followed by clasp, LEC, MEC, and then MEL, whereas M(3) density is greatest in LEC, followed by MEL, MEC, sling, and then clasp. The potency of subtype-selective antagonists to inhibit bethanechol-induced contraction was calculated by Schild analysis to determine which muscarinic receptor subtypes contribute to contraction. The results suggest both M(2) and M(3) receptors mediate contraction in clasp and sling fibers. Thus, this type of analysis in which multiple receptors mediate the contractile response is inappropriate, and an analysis method relating dual occupation of M(2) and M(3) receptors to contraction is presented. Using this new method of analysis, it was found that the M(2) muscarinic receptor plays a greater role in mediating contraction of clasp and sling fibers than in LEC, MEC, and MEL muscles in which the M(3) receptor predominantly mediates contraction.

  20. High Expression, Purification and Characterization of cDNA Encoding M3-M4 Loop in the Essential Subuint of hNMDA Receptor%人NMDA受体主亚基M3-M4环基因片段的高效表达、纯化与鉴定

    Institute of Scientific and Technical Information of China (English)

    张玉梅; 孙长凯; 范明; 李伍举; 刘淑红; 赵杰; 韩大跃; 王嘉玺

    2003-01-01

    用基因工程方法获得人N-甲基-D-天冬氨酸(N-methyl-D-aspartate,NMDA)受体主亚基M3-M4环靶片段,以此为免疫原,用于进一步免疫原性及相关应用研究. 自人脑胶质瘤组织中提取总RNA, 采用RT-PCR扩增出人NMDA受体主亚基M3-M4环的基因片段, 并按照计算机辅助原核表达载体pBV220中外源基因高效表达的数学模型预测方法, 将其进行优化改构. 将目的基因克隆到pBV220中,转化大肠杆菌DH5α,升温诱导表达,从蛋白质水平检测重组体在大肠杆菌中的表达情况, 通过制备性SDS-PAGE 进行纯化, 从相对分子质量、免疫反应性、肽质谱指纹分析等方面进行鉴定. 结果表明,成功构建了人NMDA受体主亚基M3-M4环的原核表达载体(命名为pBV-NR1L3),通过基因优化,实现了高效表达.凝胶扫描分析表达量约占菌体总蛋白29 %,重组肽纯度达95 %以上.

  1. Different pharmacology of N-desmethylclozapine at human and rat M2 and M 4 mAChRs in neocortex.

    Science.gov (United States)

    Gigout, S; Wierschke, S; Dehnicke, C; Deisz, R A

    2015-05-01

    Cholinergic transmission plays a pivotal role in learning, memory and cognition, and disturbances of cholinergic transmission have been implicated in neurological disorders including Alzheimer's disease, epilepsy and schizophrenia. Pharmacological alleviation of these diseases by drugs including N-desmethylclozapine (NDMC), promising in animal models, often fails in patients. We therefore compared the effects of NDMC on glutamatergic and GABAergic transmission in slices from rat and human neocortex. We used carbachol (CCh; an established agonist at metabotropic muscarinic acetylcholine (ACh) receptors (mAChRs)) as a reference. Standard electrophysiological methods including intracellular and field potential recordings were used. In the rat neocortex, NDMC prevented the CCh-induced decrease of GABAA and GABAB receptor-mediated responses but not the CCh-induced increase of the paired-pulse depression. NDMC reduced neither the amplitude of the excitatory postsynaptic potentials (EPSP) nor antagonized the CCh-induced depression of EPSP. In the human neocortex, however, NDMC failed to prevent CCh-induced decrease of the GABAB responses and directly reduced the amplitude of EPSP. These data suggest distinct effects of NDMC in rat and human at M2 and M4 mAChRs underlying presynaptic modulation of GABA and glutamate release, respectively. In particular, NDMC might be a M2 mAChR antagonist in the rat but has no activity at this receptor in human neocortex. However, NDMC has an agonistic effect at M4 mAChR in the human but no such effect in the rat neocortex. The present study confirms that pharmacology at mAChRs can differ between species and emphasizes the need of studies in human tissue.

  2. Classification of Acute Myelogenous Leukemia (AML M2 and AML M3) using Momentum Back Propagation from Watershed Distance Transform Segmented Images

    Science.gov (United States)

    Suryani, Esti; Wiharto; Palgunadi, Sarngadi; Nurcahya Pradana, TP

    2017-01-01

    This study uses image processing to analyze white blood cell with leukemia indicated that includes the identification, analysis of shapes and sizes, as well as white blood cell count indicated the symptoms of leukemia. A case study in this research was blood cells, from the type of leukemia Acute Myelogenous Leukemia (AML), M2 and M3 in particular. Image processing operations used for segmentation by utilizing the color conversion from RGB (Red, Green dab Blue) to obtain white blood cell candidates. Furthermore, the white blood cells candidates are separated by other cells with active contour without edge. WBC (White Blood Cell) results still have intersected or overlap condition. Watershed distance transform method can separate overlap of WBC. Furthermore, the separation of the nucleus from the cytoplasm using the HSI (Hue Saturation Intensity). The further characteristic extraction process is done by calculating the area WBC, WBC edge, roundness, the ratio of the nucleus, the mean and standard deviation of pixel intensities. The feature extraction results are used for training and testing in determining the classification of AML: M2 and M3 by using the momentum backpropagation algorithm. The classification process is done by testing the numeric data input from the feature extraction results that have been entered in the database. K-Fold validation is used to divide the amount of training data and to test the classification of AML M2 and M3. The experiment results of eight images trials, the result, was 94.285% per cell accuracy and 75% per image accuracy

  3. Mucosal immunization with recombinant adenoviral vectors expressing murine gammaherpesvirus-68 genes M2 and M3 can reduce latent viral load

    DEFF Research Database (Denmark)

    Hoegh-Petersen, Mette; Thomsen, Allan R; Christensen, Jan P

    2009-01-01

    of the gammaherpesvirinae speaks against using a similar approach in humans. DNA immunization with plasmids encoding the MHV-68 genes M2 or M3 caused a reduction in either acute or early latent viral load, respectively, but neither immunization had an effect at times later than 14 days post-infection. Adenovirus......-based vaccines are substantially more immunogenic than DNA vaccines and can be applied to induce mucosal immunity. Here we show that a significant reduction of the late viral load in the spleens, at 60 days post-infection, was achieved when immunizing mice both intranasally and subcutaneously with adenoviral...

  4. Value of interphase fluorescence in situ hybridization in diagnosing acute myeloid leukemia M2 and M3%间期荧光原位杂交技术在急性髓系白血病M2M3型诊断中的应用

    Institute of Scientific and Technical Information of China (English)

    许民; 周永安; 赵瑾; 杜苏萌; 吴坚锐

    2008-01-01

    目的 探讨间期荧光原位杂交技术(FISH)在急性髓系白血病(AML)M2M3诊断中的意义.方法 对初治的9例AML-M3、12例AML-M3及10例未能确定M2M3的AML患者,应用FISH和反转录-聚合酶链反应(RT-PCR)检测AMLI/ETO和PML/RARα融合基因,协助诊断和指导治疗.结果 9例AML-M2中AMLI/ETO融合基因阳性率44.4%(4/9);12例AML-M3中PML/RARα融合基因阳性率83.3%(10/12),其中1例AML1/ETO融合基因阳性.确诊为AML-M2;10例AML中AML1/ETO融合基因阳性率30%(3/10),PML/RAR Ot融合基因阳性率50%(5/10),其余2例未检测到以上两种融合基因.结论 FISH是一种敏感、简便的分子遗传学新技术,具有高效、快速、灵敏等优点,对诊断AML的分型具有重要帮助,可进一步指导临床治疗.%Objective To investigate the value of interphase fluorescence in situ hybridization(FISH)technique and the detection of fusion gene in the diagnosis of acute myeloid leukemia(AML)M2 and M3 Methods FISH was used to detect the AML1/ETO fusion gene and/or PML/RARα fusion gene in incipient cases including 9 AML-M2, 12 AML-M3 and 10 AML undetermined as AML-M2 or AML-M3 primarily diagnosed by routine morphology though bone marrow,cytochemical staining and immunophenotyping,which can help diagnose and guide clinical therapy.Results 4 of 9 AML-M2 cases were AML1/ETO positive.Among 12 AML-M3 cases,10 were PML/RARα positive.1 case was detected AML1/ETO fusion gene.In 10 untonfirmed M3 or M2,3 case8 showed AML1/ETO,5 showed PMIJRARot fusion gene and the rest showed neither of the genes.Conclusion As a new technique of the molecular genetics,FISH is accurate, rapid and efficient.It would be of significance not only at diagnosis of AML,but also for subsequent clinical decision-making.

  5. Discovery of Eclipsing Binary Central Stars in the Planetary Nebulae M 3-16, H 2-29 and M 2-19

    CERN Document Server

    Miszalski, B; Moffat, A F J; Parker, Q A; Udalski, A

    2008-01-01

    Progress in understanding the formation and evolution of planetary nebulae (PN) has been restricted by a paucity of well-determined central star masses. To address this deficiency we aim to (i) significantly increase the number of known eclipsing binary central stars of PN (CSPN), and subsequently (ii) directly obtain their masses and absolute dimensions by combining their light-curve parameters with planned radial velocity data. Using photometric data from the third phase of the Optical Gravitational Lensing Experiment (OGLE) we have searched for periodic variability in a large sample of PN towards the Galactic Bulge using Fourier and phase-dispersion minimisation techniques. Among some dozen periodically variable CSPN found, we report here on three new eclipsing binaries: M 3-16, H 2-29 and M 2-19. We present images, confirmatory spectroscopy and light-curves of the systems.

  6. 良性前列腺增生合并膀胱过度活动症患者膀胱黏膜毒蕈碱型胆碱能受体 M2M3亚型的表达及临床意义%Expression and Clinical Significance of Muscarinic Cholinergic Receptor M2 and M3 Subtypes in Patients with Benign Prostatic Hyperplasia and Overactive Bladder

    Institute of Scientific and Technical Information of China (English)

    张进生; 刘春林; 刘良颖; 李玮; 刘宁; 渠渊; 王立茹; 冯超; 吴宗山; 柴军; 张前

    2014-01-01

    Objective-To-investigate-the-changes-and-significance-of-the-expression-of-the-M-2-and-M3-receptors-of-the-urinary-bladder-mucosa-in-patients-with-benign-prostatic-hyperplasia-(-BPH)-and-overactive-bladder-(-OAB)-.-Methods-From-May-2012-to-February-2013,-20-cases-of-BPH-were-studied-on-the-International-Prostate-Syndrome-Scoring-(IPSS),-Quality-Of-Life-(QOL),-OAB-syndrome-scoring-(OABSS),-and-urodynamics.According-to-OABSS-results,-the-patients-were-divided-into-either-BPH-group-(n=9)-or-BPH-and-OAB-group-(n=11).Mucosa-biopsies-under-the-cystoscopy-were-performed-in-all-the-cases-.The-expression-of-M2&M3-receptors-was-assayed-by-reverse-transcription-polymerase-chain-reaction-(-RT-PCR-)-.The-mRNA-expression-levels-of-M-2-&-M3-receptors-were-indicated-by-the--Ct-values.-Results-The-levels-of--Ct-of-M2-&-M3-receptors-were-significantly-lower-in-the-BPH-group-than-those-in-the-BPH-+OAB-group,-respectively-[M2:(-0.154-±0.641)-vs.(0.562-±0.762),-t=-2.241,-P=0.038;M3:(2.534-±0.816)-vs.(3.639-±1.019),-t=-2.630,-P=0.017],-which-implied-that-the-expression-of-M-2-and-M3-receptors-was-higher-in-the-BPH-group-than-that-in-the-BPH-+OAB-group.The-median-ratios-of-M2M3-in-both-groups-were-respectively-6.5206-(2.35-17.33)-and-7.9447-(2.10-23.83)-(Z=-1.102,-P=0.271).In-the-same-group,-the-expression-of-M2-was-higher-than-M3-in-both-groups-(t=-7.776,-P=0.000;t=-8.018,-P=0.000).The-expression-of-M3-receptors-was-negatively-correlated-to-OABSS-(r=-0.466,-P=0.039)-and-QOL-(r=-0.496,-P=0.026).-Conclusions-The-expression-of-M2-and-M3-receptors-is-decreased-and-the-ratio-of-M-2M3-is-increased-in-patients-with-BPH-and-OAB-,-which-may-play-an-important-role-in-the-development-of-OAB.The-decreasing-of-expression-of-M-3-receptor-exacerbates-the-OAB-degree-and-reduces-the-quality-of-patients-’-life.%目的:探讨良性前列腺增生( benign prostatic hyperplasia ,BPH)合并膀胱过度活动症( overactive bladder ,OAB)患者膀胱黏膜

  7. Camera Ready Masters. B/M-1 Resource Assessment. B/M-2 Surveying. B/M-3 Tabulation. B/M-4 Selecting Program Goals. B/M-5 Producing CDU's. Career Planning Support System.

    Science.gov (United States)

    Ohio State Univ., Columbus. Center for Vocational Education.

    This package of camera ready masters is one of a set of twelve documents describing the Career Planning Support System (CPSS) and its use. (CPSS is a comprehensive guidance program management system which (1) provides techniques to improve a high school's career guidance program, (2) focuses on the skills students need to make decisions about and…

  8. 毒蕈碱乙酰胆碱M2/M4受体亚型在调节脊髓背角神经元谷氨酸能递质释放中的作用%Role of muscarinic cholinergic receptor subtypes in regulating glutamatergic synaptic transmission in rat spinal dorsal horn

    Institute of Scientific and Technical Information of China (English)

    杜威; 郭英; 袁维秀

    2013-01-01

    Objective To investigate the role of muscarinic cholinergic receptor (mAChR) subtypes in the regulation of glutamatergic input to the spinal dorsal horn neurons and the possible mechanism.Methods Whole-cell voltage-clamp recordings on acute spinal slice was utilized to investigate the effect of activation of mAChRs and blockade of M2/M4 subtypes on glutamatergic synaptic transmission in rat spinal dorsal horn neurons.Results The nonselective mAChRs agonist oxotremorine-M concentration-dependently decreased the amplitude of monosynaptic and polysynaptic evoked glutamate-mediated excitatory postsynaptic currents (eEPSCs) in most of the neurons.The M2/M4 antagonist himbacine completely blocked the inhibitory effect of oxotremorine-M in 92.3% of monosynaptic and 75% of polysynaptic neurons in the spinal cord slices.In the remaining 16% neurons,himbacine partially blocked the inhibitory effect of oxotremorine-M.Conclusions Activation of mAChRs in the spinal cord attenuates synaptic glutamate release to the dorsal horn neurons mainly through M2 and M4 receptor subtypes,indicating that a presynaptic inhibition in the spinal cord may be involved in the regulation of nociception by the cholinergic system and mAChRs.%目的 研究毒蕈碱胆碱能受体(mAChRs)亚型对脊髓背角感觉神经元谷氨酸能突触传递的调节机制.方法 在急性切取的腰段脊髓切片上,利用全细胞膜片钳法记录mAChRs非特异性激动剂氢化震颤素M(Oxo-M)对脊髓背角浅层神经元谷氨酸能兴奋性突触后电流(eEPSCs)的影响,给予M2/M4受体特异性拮抗剂喜巴辛,观察mAChRs在脊髓背角浅层神经元谷氨酸能递质释放调节过程中的作用.结果 不同浓度Oxo-M使脊髓背角神经元单突触和多突触eEPSCs的幅度显著降低,其抑制强度呈浓度依赖性,喜巴辛可以拮抗Oxo-M对刺激诱发eEPSCs幅度的抑制作用,在记录的25个细胞中,92.3%的单突触细胞和75%的多突触细胞表现为Oxo-M

  9. A novel antiarrhythmic target-M3-R/IKM3

    Institute of Scientific and Technical Information of China (English)

    Bao-fengYANG

    2004-01-01

    The total efficient rate of antiarrhythmic agents is only 30%to 60%, and the compounding problem is the lack of an effective therapy for some serious arrhythmias. Muscarinic receptors have been cloned and subdivided into the five subtypes M1, M2, M3,M4 and M5. And M2 receptors have long been believed to be the only functional subtype of muscarinic acetylcholine receptor (mAChR) in the heart, although recent studies have provided

  10. Characterization of PCS1055, a novel muscarinic M4 receptor antagonist.

    Science.gov (United States)

    Croy, Carrie H; Chan, Wai Y; Castetter, Andrea M; Watt, Marla L; Quets, Anne T; Felder, Christian C

    2016-07-05

    Identification of synthetic ligands selective for muscarinic receptor subtypes has been challenging due to the high sequence identity and structural homology among the five muscarinic acetylcholine receptors. Here, we report the pharmacological characterization of PCS1055, a novel muscarinic M4 receptor antagonist. PCS1055 inhibited radioligand [(3)H]-NMS binding to the M4 receptor with a Ki=6.5nM. Though the potency of PCS1055 is lower than that of pan-muscarinic antagonist atropine, it has better subtype selectivity over previously reported M4-selective reagents such as the muscarinic-peptide toxins (Karlsson et al., 1994; Santiago and Potter, 2001a) at the M1 subtype, and benzoxazine ligand PD102807 at the M3-subtype (Bohme et al., 2002). A detailed head-to-head comparison study using [(3)H]-NMS competitive binding assays characterizes the selectivity profiles of PCS1055 to that of other potent muscarinic-antagonist compounds PD102807, tropicamide, AF-DX-384, pirenzapine, and atropine. In addition to binding studies, the subtype specificity of PCS1055 is also demonstrated by functional receptor activation as readout by GTP-γ-[(35)S] binding. These GTP-γ-[(35)S] binding studies showed that PCS1055 exhibited 255-, 69.1-, 342- and >1000-fold greater inhibition of Oxo-M activity at the M4 versus the M1-, M2(-), M3-or M5 receptor subtypes, respectively. Schild analyses indicates that PCS1055 acts as a competitive antagonist to muscarinic M4 receptor, and confirms the affinity of the ligand to be low nanomolar, Kb=5.72nM. Therefore, PCS1055 represents a new M4-preferring antagonist that may be useful in elucidating the roles of M4 receptor signaling.

  11. The definitive guide to ARM Cortex-M3 and Cortex-M4 processors

    CERN Document Server

    Yiu, Joseph

    2013-01-01

    This book presents the background of the ARM architecture and outlines the features of the processors such as the instruction set, interrupt-handling and also demonstrates how to program and utilize the advanced features available such as the Memory Protection Unit (MPU). Chapters on getting started with IAR, Keil, gcc and CooCox CoIDE tools help beginners develop program codes.  Coverage also includes the important areas of software development such as using the low power features, handling information input/output, mixed language projects with assembly and C, and other advanced topics. Tw

  12. Variant M4 Barrel Characterization

    Science.gov (United States)

    2009-07-01

    in the button broached barrels. 6. Acknowledgments The authors are pleased to acknowledge the sample preparation provided by Mrs. A. Welty , RDAR...Rickard, C., & Welty , A. (2007). Comparison of electroplated chromium coatings applied to M4 and M16 barrels. US Army-ARDEC. 3) Smith, S. B., & Rickard

  13. The muscarinic acetylcholine receptor agonist BuTAC mediates antipsychotic-like effects via the M4 subtype.

    Science.gov (United States)

    Watt, Marla L; Rorick-Kehn, Linda; Shaw, David B; Knitowski, Karen M; Quets, Anne T; Chesterfield, Amy K; McKinzie, David L; Felder, Christian C

    2013-12-01

    The generation of muscarinic acetylcholine receptor (mAChR) subtype-selective compounds has been challenging, requiring use of nonpharmacological approaches, such as genetically engineered animals, to deepen our understanding of the potential that members of the muscarinic receptor subtype family hold as therapeutic drug targets. The muscarinic receptor agonist 'BuTAC' was previously shown to exhibit efficacy in animal models of psychosis, although the particular receptor subtype(s) responsible for such activity was unclear. Here, we evaluate the in vitro functional agonist and antagonist activity of BuTAC using an assay that provides a direct measure of G protein activation. In addition, we employ the conditioned avoidance response paradigm, an in vivo model predictive of antipsychotic activity, and mouse genetic deletion models to investigate which presynaptic mAChR subtype mediates the antipsychotic-like effects of BuTAC. Our results show that, in vitro, BuTAC acts as a full agonist at the M2AChR and a partial agonist at the M1 and M4 receptors, with full antagonist activity at M3- and M5AChRs. In the mouse conditioned avoidance response (CAR) assay, BuTAC exhibits an atypical antipsychotic-like profile by selectively decreasing avoidance responses at doses that do not induce escape failures. CAR results using M2(-/-), M4(-/-), and M2/M4 (M2/M4(-/-)) mice found that the effects of BuTAC were near completely lost in M2/M4(-/-) double-knockout mice and potency of BuTAC was right-shifted in M4(-/-) as compared with wild-type and M2(-/-) mice. The M2/M4(-/-) mice showed no altered sensitivity to the antipsychotic effects of either haloperidol or clozapine, suggesting that these compounds mediate their actions in CAR via a non-mAChR-mediated mechanism. These data support a role for the M4AChR subtype in mediating the antipsychotic-like activity of BuTAC and implicate M4AChR agonism as a potential novel therapeutic mechanism for ameliorating symptoms associated with

  14. The M2 Channel

    DEFF Research Database (Denmark)

    Santner, Paul

    and inhibition mechanisms, drug design studies were recently able to achieve successes in finding new potent inhibitors, some of which are even able to inhibit resistant M2 variants. Effective and robust methods for measuring M2 activity on the other hand are still scarce and tactics to assess the genetic...... barrier of new inhibitors as well as resistance development non-existent. Therefore we developed a fluorescence sensor based assay that directly measures proton conduction (pHlux assay) and combined it with an already established directed evolution selection and screening system of M2 to identify possible...... resistance escape routes from drug inhibition. We thereby were hopefully able to provide a platform for the large-scale evaluation of M2 channel activity, inhibitors and resistance....

  15. Distinct Agonist Regulation of Muscarinic Acetylcholine M2-M3 Heteromers and Their Corresponding Homomers*

    OpenAIRE

    Aslanoglou, Despoina; Alvarez-Curto, Elisa; Marsango, Sara; Milligan, Graeme

    2015-01-01

    Each subtype of the muscarinic receptor family of G protein-coupled receptors is activated by similar concentrations of the neurotransmitter acetylcholine or closely related synthetic analogs such as carbachol. However, pharmacological selectivity can be generated by the introduction of a pair of mutations to produce Receptor Activated Solely by Synthetic Ligand (RASSL) forms of muscarinic receptors. These display loss of potency for acetylcholine/carbachol alongside a concurrent gain in pote...

  16. Homogeneous M2 duals

    CERN Document Server

    Figueroa-O'Farrill, José

    2015-01-01

    Motivated by the search for new gravity duals to M2 branes with $N>4$ supersymmetry --- equivalently, M-theory backgrounds with Killing superalgebra $\\mathfrak{osp}(N|4)$ for $N>4$ --- we classify (except for a small gap) homogeneous M-theory backgrounds with symmetry Lie algebra $\\mathfrak{so}(n) \\oplus \\mathfrak{so}(3,2)$ for $n=5,6,7$. We find that there are no new backgrounds with $n=6,7$ but we do find a number of new (to us) backgrounds with $n=5$. All backgrounds are metrically products of the form $\\operatorname{AdS}_4 \\times P^7$, with $P$ riemannian and homogeneous under the action of $\\operatorname{SO}(5)$, or $S^4 \\times Q^7$ with $Q$ lorentzian and homogeneous under the action of $\\operatorname{SO}(3,2)$. At least one of the new backgrounds is supersymmetric (albeit with only $N=2$) and we show that it can be constructed from a supersymmetric Freund--Rubin background via a Wick rotation. Two of the new backgrounds have only been approximated numerically.

  17. Muscarinic acetylcholine receptor M1 and M3 subtypes mediate acetylcholine-induced endothelium-independent vasodilatation in rat mesenteric arteries.

    Science.gov (United States)

    Tangsucharit, Panot; Takatori, Shingo; Zamami, Yoshito; Goda, Mitsuhiro; Pakdeechote, Poungrat; Kawasaki, Hiromu; Takayama, Fusako

    2016-01-01

    The present study investigated pharmacological characterizations of muscarinic acetylcholine receptor (AChR) subtypes involving ACh-induced endothelium-independent vasodilatation in rat mesenteric arteries. Changes in perfusion pressure to periarterial nerve stimulation and ACh were measured before and after the perfusion of Krebs solution containing muscarinic receptor antagonists. Distributions of muscarinic AChR subtypes in mesenteric arteries with an intact endothelium were studied using Western blotting. The expression level of M1 and M3 was significantly greater than that of M2. Endothelium removal significantly decreased expression levels of M2 and M3, but not M1. In perfused mesenteric vascular beds with intact endothelium and active tone, exogenous ACh (1, 10, and 100 nmol) produced concentration-dependent and long-lasting vasodilatations. In endothelium-denuded preparations, relaxation to ACh (1 nmol) disappeared, but ACh at 10 and 100 nmol caused long-lasting vasodilatations, which were markedly blocked by the treatment of pirenzepine (M1 antagonist) or 4-DAMP (M1 and M3 antagonist) plus hexamethonium (nicotinic AChR antagonist), but not methoctramine (M2 and M4 antagonist). These results suggest that muscarinic AChR subtypes, mainly M1, distribute throughout the rat mesenteric arteries, and that activation of M1 and/or M3 which may be located on CGRPergic nerves releases CGRP, causing an endothelium-independent vasodilatation. Copyright © 2015 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. All rights reserved.

  18. Muscarinic acetylcholine receptor M1 and M3 subtypes mediate acetylcholine-induced endothelium-independent vasodilatation in rat mesenteric arteries

    Directory of Open Access Journals (Sweden)

    Panot Tangsucharit

    2016-01-01

    Full Text Available The present study investigated pharmacological characterizations of muscarinic acetylcholine receptor (AChR subtypes involving ACh-induced endothelium-independent vasodilatation in rat mesenteric arteries. Changes in perfusion pressure to periarterial nerve stimulation and ACh were measured before and after the perfusion of Krebs solution containing muscarinic receptor antagonists. Distributions of muscarinic AChR subtypes in mesenteric arteries with an intact endothelium were studied using Western blotting. The expression level of M1 and M3 was significantly greater than that of M2. Endothelium removal significantly decreased expression levels of M2 and M3, but not M1. In perfused mesenteric vascular beds with intact endothelium and active tone, exogenous ACh (1, 10, and 100 nmol produced concentration-dependent and long-lasting vasodilatations. In endothelium-denuded preparations, relaxation to ACh (1 nmol disappeared, but ACh at 10 and 100 nmol caused long-lasting vasodilatations, which were markedly blocked by the treatment of pirenzepine (M1 antagonist or 4-DAMP (M1 and M3 antagonist plus hexamethonium (nicotinic AChR antagonist, but not methoctramine (M2 and M4 antagonist. These results suggest that muscarinic AChR subtypes, mainly M1, distribute throughout the rat mesenteric arteries, and that activation of M1 and/or M3 which may be located on CGRPergic nerves releases CGRP, causing an endothelium-independent vasodilatation.

  19. Fungicin M4: a narrow spectrum peptide antibiotic from Bacillus licheniformis M-4.

    Science.gov (United States)

    Lebbadi, M; Gálvez, A; Maqueda, M; Martínez-Bueno, M; Valdivia, E

    1994-07-01

    The strain Bacillus licheniformis M-4 produces a 3.4 kDa hydrophilic peptide with antifungal activity, named fungicin M4. Analysis of the purified peptide shows that it contains the amino acids Glu (8), Arg (5), Pro (4), Tyr (8), Val (3), Met (2) and Orn (4). Its inhibitory spectrum is restricted to Microsporum canis CECT 2797, Mucor mucedo CECT 2653, Mucor plumbeus CCM 443, Sporothrix schenckii CECT 2799, Bacillus megaterium and Corynebacterium glutamicum CECT 78. Fungicin M4 exerts biocidal activity on liquid cultures of Sporothrix schenckii CECT 2799.

  20. Guanylpirenzepine distinguishes between neuronal ml and m4 muscarinic receptor subtypes

    Energy Technology Data Exchange (ETDEWEB)

    Monferini, E.; Cereda, E.; Ladinsky, H.; Donetti, A.; Giraldo, E. (Istituto De Angeli S.p.A., Milan (Italy))

    1990-01-01

    Guanylpirenzepine, a polar, non-quaternary analog of pirenzepine, exhibited a novel binding behavior in rat brain regions: in competition binding experiments against (3H)pirenzepine labeling the M1 receptor in membranes from cerebral cortex, hippocampus and striatum, the compound, differently from pirenzepine, displayed heterogeneous binding curves. Computer assisted analysis of these curves, evidenced the existence of two populations of binding sites: a large proportion (84-89%) of high affinity receptors (KH = 64-92 nM) and a remainder with very low affinity (KL = 19-28 microM). Like pirenzepine, guanylpirenzepine showed low affinity for the glandular M3 and the cardiac M2 receptors when (3H)N-methylscopolamine was used to label the receptors in membranes from these two tissues; affinity values for guanylpirenzepine were 1336 and 5790 nM respectively, vs 323 and 683 nM for pirenzepine. We conclude that guanylpirenzepine is able to discriminate between m1 and m4 receptor subtypes and may represent a new tool for deeper studies on muscarinic receptors classification.

  1. Rotational motion of Foton M-4

    Science.gov (United States)

    Abrashkin, V. I.; Voronov, K. E.; Piyakov, I. V.; Puzin, Yu. Ya.; Sazonov, V. V.; Semkin, N. D.; Chebukov, S. Yu.

    2016-07-01

    The actual controlled rotational motion of the Foton M-4 satellite is reconstructed for the mode of single-axis solar orientation. The reconstruction was carried out using data of onboard measurements of vectors of angular velocity and the strength of the Earth's magnetic field. The reconstruction method is based on the reconstruction of the kinematic equations of the rotational motion of a solid body. According to the method, measurement data of both types collected at a certain time interval are processed together. Measurements of the angular velocity are interpolated by piecewise-linear functions, which are substituted in kinematic differential equations for a quaternion that defines the transition from the satellite instrument coordinate system to the inertial coordinate system. The obtained equations represent the kinematic model of the satellite rotational motion. A solution of these equations that approximates the actual motion is derived from the condition of the best (in the sense of the least squares method) match between the measurement data of the strength vector of the Earth's magnetic field and its calculated values. The described method makes it possible to reconstruct the actual rotational satellite motion using one solution of kinematic equations over time intervals longer than 10 h. The found reconstructions have been used to calculate the residual microaccelerations.

  2. The Luminosity Function of M3

    CERN Document Server

    Rood, R T; Paltrinieri, B; Ferraro, F R; Pecci, F F; Dorman, B; Chieffi, A; Straniero, O; Buonanno, R

    1999-01-01

    We present a high precision, large sample luminosity function (LF) for the Galactic globular cluster M3. With a combination of ground based and Hubble Space Telescope data we cover the entire radial extent of the cluster. The observed LF is well fit by canonical standard stellar models from the red giant branch (RGB) tip to below the main sequence turnoff point. Specifically, neither the RGB LF-bump nor subgiant branch LF indicate any breakdown in the standard models. On the main sequence we find evidence for a flat initial mass function and for mass segregation due to the dynamical evolution of the cluster.

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

    CERN Document Server

    Parke, Stephen

    2016-01-01

    The current short baseline reactor experiments, Daya Bay and RENO (Double Chooz) have measured (or are capable of measuring) an effective $\\Delta m^2$ associated with the atmospheric oscillation scale of 0.5 km/MeV in electron anti-neutrino disappearance. In this paper, I compare and contrast the different definitions of such an effective $\\Delta m^2$ and argue that the simple, L/E independent, definition given by $\\Delta m^2_{ee} \\equiv \\cos^2 \\theta_{12} \\Delta m^2_{31}+ \\sin^2 \\theta_{12} \\Delta m^2_{32}$, i.e. "the $\

  4. Getting ready for the real data-taking with M4

    CERN Multimedia

    Giuseppe Mornacchi

    M4 (Milestone 4), the fourth global commissioning period, took place from August 23rd to September 3rd. As for M3, this run included almost all of the ATLAS sub-detectors, with only the Pixels and Cathode Strip Chambers missing, but featured more detector hardware, new releases of offline and online software and many new functions. These are outlined below. The more mature state of systems integration called for a different organization of M4 with respect to M1-M3: following a 2-day setup time, we spent the rest of M4 running formal shifts: two shifts a day (9:00 to 17:00 and 17:00 to 24:00) with a full crew during week days, that is 13 control room desks staffed by at least one shifter each, and a single shift (9:00 to 17:00) with reduced crew of 5-7 people during weekends. While most of the time was dedicated to combined running with cosmics muons, four of the day shifts were dedicated to more technical issues such as: high rate (many kHz) runs, tests related to synchronization (Bunch Counter Reset and Eve...

  5. Structure and dynamics of the M3 muscarinic acetylcholine receptor

    Energy Technology Data Exchange (ETDEWEB)

    Kruse, Andrew C.; Hu, Jianxin; Pan, Albert C.; Arlow, Daniel H.; Rosenbaum, Daniel M.; Rosemond, Erica; Green, Hillary F.; Liu, Tong; Chae, Pil Seok; Dror, Ron O.; Shaw, David E.; Weis, William I.; Wess, Jürgen; Kobilka, Brian K. (Stanford); (NIH); (D.E. Shaw); (Hanyang); (UTSMC)

    2012-03-01

    Acetylcholine, the first neurotransmitter to be identified, exerts many of its physiological actions via activation of a family of G-protein-coupled receptors (GPCRs) known as muscarinic acetylcholine receptors (mAChRs). Although the five mAChR subtypes (M1-M5) share a high degree of sequence homology, they show pronounced differences in G-protein coupling preference and the physiological responses they mediate. Unfortunately, despite decades of effort, no therapeutic agents endowed with clear mAChR subtype selectivity have been developed to exploit these differences. We describe here the structure of the G{sub q/11}-coupled M3 mAChR ('M3 receptor', from rat) bound to the bronchodilator drug tiotropium and identify the binding mode for this clinically important drug. This structure, together with that of the G{sub i/o}-coupled M2 receptor, offers possibilities for the design of mAChR subtype-selective ligands. Importantly, the M3 receptor structure allows a structural comparison between two members of a mammalian GPCR subfamily displaying different G-protein coupling selectivities. Furthermore, molecular dynamics simulations suggest that tiotropium binds transiently to an allosteric site en route to the binding pocket of both receptors. These simulations offer a structural view of an allosteric binding mode for an orthosteric GPCR ligand and provide additional opportunities for the design of ligands with different affinities or binding kinetics for different mAChR subtypes. Our findings not only offer insights into the structure and function of one of the most important GPCR families, but may also facilitate the design of improved therapeutics targeting these critical receptors.

  6. M2M massive wireless access

    DEFF Research Database (Denmark)

    Zanella, Andrea; Zorzi, Michele; Santos, André F.

    2013-01-01

    of the current cellular standards. Here, we provide insights and introduce potential solutions for the cellular radio protocol that will allow the efficient support of Machine-to-Machine (M2M) communications. The paper focuses on the massive aspect of M2M. We will introduce PHY and MAC approaches such as Coded...... and research guidelines for enabling future networks to support efficiently M2M communications....

  7. Transport Coefficients of Black M3-Branes

    CERN Document Server

    Dhuria, Mansi

    2014-01-01

    The local uplift via local SYZ mirror symmetry of (M)N (fractional)D3-branes, and wrapped N_f flavor D7-branes in the presence of a black-hole resulting in a non-Kaehler resolved warped deformed conifold (NKRWDC) in [1], was carried out in [2] and resulted in black M3-branes; the deviation from the ISD condition of G_3 proportional to the square of the resolution parameter, in the limits of [1] and MQGP limit of [2], imposed on (g_s,M,N), can be ignored [3]. The uplift, if valid globally, asymptotes to M5-branes wrapping a two-cycle (homologously an (large) integer sum of two-spheres) in AdS_5xM_6. Interestingly, in the limits of [1]/ [2], assuming the deformation > resolution, by estimating the five SU(3) structure torsion (\\tau) classes W_{1,2,3,4,5} we show that \\tau\\in W_5 in the large-r limit, implying the NKRWDC reduces to a warped Kaehler deformed conifold. Further, the local T^3 of [2] in the large-r limit and the limits of [1] and the `MQGP' limit of [2], satisfies the same conditions as the maximal ...

  8. Formando planetas habitables en estrellas M3

    Science.gov (United States)

    Dugaro, A.; de Elía, G. C.; Brunini, A.

    2016-08-01

    Studies of stellar evolution allow us to infer that the low-mass stars are the most abundant in the galaxy. In the present investigation, we analyze the formation of planetary systems without gas giants around M3-type stars, which have a mass of 0.29 M. In particular, we are interested in studying the terrestrial-like planet formation processes and water delivery in the Habitable Zone (HZ) of those systems. To develop this investigation, we assume massive protoplanetary disks for such stars, which have 5 of the mass of the central star. Once defined the working disk, we use a semi-analytical model, which is able to determine the distribution of planetary embryos and planetesimals at the end of the gaseous phase. Then, these distributions are used as initial conditions for running -body simulations. Due to the stochastic nature of the accretion process, we carry out ten -body simulations in order to analyze the evolution of the planetary systems after the gas dissipation. Our results suggest the efficient formation of terrestrial-like planets in the HZ with a wide range of masses and water contents. The planets formed in the HZ of the system have masses between 0.07 M and 0.15 M and final water contents between 5.4 and 29 by mass. The physical properties of the terrestrial-like planets formed in the HZ of our simulations suggest that they should be able to retain a permanent and substantial atmosphere.

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

    Science.gov (United States)

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

    2016-11-01

    The human placenta comprises a special type of tissue macrophages, the Hofbauer cells (HBC), which exhibit M2 macrophage phenotype. Several subtypes of M2-polarized macrophages (M2a, M2b and M2c) exist in almost all tissues. Macrophage polarization depends on the way of macrophage activation and leads to the expression of specific cell surface markers and the acquisition of specific functions, including tissue remodeling and the promotion of angiogenesis. The placenta is a highly vascularized and rapidly growing organ, suggesting a role of HBC in feto-placental angiogenesis. We here aimed to characterize the specific polarization and phenotype of HBC and investigated the role of HBC in feto-placental angiogenesis. Therefore, HBC were isolated from third trimester placentas and their phenotype was determined by the presence of cell surface markers (FACS analysis) and secretion of cytokines (ELISA). HBC conditioned medium (CM) was analyzed for pro-angiogenic factors, and the effect of HBC CM on angiogenesis, proliferation and chemoattraction of isolated primary feto-placental endothelial cells (fpEC) was determined in vitro Our results revealed that isolated HBC possess an M2 polarization, with M2a, M2b and M2c characteristics. HBC secreted the pro-angiogenic molecules VEGF and FGF2. Furthermore, HBC CM stimulated the in vitro angiogenesis of fpEC. However, compared with control medium, chemoattraction of fpEC toward HBC CM was reduced. Proliferation of fpEC was not affected by HBC CM. These findings demonstrate a paracrine regulation of feto-placental angiogenesis by HBC in vitro Based on our collective results, we propose that the changes in HBC number or phenotype may affect feto-placental angiogenesis. © 2016 Society for Reproduction and Fertility.

  10. Assigning error to an M2 measurement

    Science.gov (United States)

    Ross, T. Sean

    2006-02-01

    The ISO 11146:1999 standard has been published for 6 years and set forth the proper way to measure the M2 parameter. In spite of the strong experimental guidance given by this standard and the many commercial devices based upon ISO 11146, it is still the custom to quote M2 measurements without any reference to significant figures or error estimation. To the author's knowledge, no commercial M2 measurement device includes error estimation. There exists, perhaps, a false belief that M2 numbers are high precision and of insignificant error. This paradigm causes program managers and purchasers to over-specify a beam quality parameter and researchers not to question the accuracy and precision of their M2 measurements. This paper will examine the experimental sources of error in an M2 measurement including discretization error, CCD noise, discrete filter sets, noise equivalent aperture estimation, laser fluctuation and curve fitting error. These sources of error will be explained in their experimental context and convenient formula given to properly estimate error in a given M2 measurement. This work is the result of the author's inability to find error estimation and disclosure of methods in commercial beam quality measurement devices and building an ISO 11146 compliant, computer- automated M2 measurement device and the resulting lessons learned and concepts developed.

  11. Hemopoietic tissue in newts flown aboard Foton M3

    Science.gov (United States)

    Domaratskaya, Elena I.; Almeida, Eduardo; Butorina, Nina N.; Nikonova, Tatyana M.; Grigoryan, Eleonora N.; Poplinskaya, Valentina A.; Souza, Kenneth; Skidmore, Mike

    The effect of 12-day spaceflight aboard the Foton-M3 biosatellite on the hematopoietic tissue of P. waltl newts was studied. These animals used at the same time in regeneration experiments after lens and tail tip amputation. In flight and synchronous groups there were performed video recording, temperature and radiation monitoring and continuous contact (via skin) with thymidine analog BrdU. We took differential blood counts and assessed histologically the liver in the flight (F), basal (BC) and synchronous (SC)control groups of animals. In the peripheral blood, we identified neutrophils, eosinophils, basophils, lymphocytes, and monocytes. Lymphocytes (L) and neutrophils (N) prevailed, accounting for about 60 and 20% of white blood cells, respectively. The spaceflight had no apparent effect on the differential blood count in the F group: neither the L and N contents nor the maturing to mature N - ratio differed from those in the control groups. No significant differences between F, SC and BC groups were observed with respect to the structure of hematopoietic areas and the liver morphology. As in Foton-M2, BrdU labeled cells revealed in blood as well as in the hemopoietic areas of the liver. However, in previous experiments performed at satellites Bion-10 and Foton-M2 the changes in peripheral blood contents were registered in operated F newts, and we supposed it could be the result of additive effects of spaceflight factors and stimulation of reparative potency and stress due to surgical operation. Possibly, the temperature conditions also may provide some influence on blood cell content of newts that belong to poikilothermic animals. Thus, in present experiment F and SC groups were reared in the same temperature regims, whereas it was nearly 3o C differences between SC and F groups exposed on Foton-M2. At the same time as it was found in experiments on Bion-11 and Foton-M2 spaceflight factors did not affect on differential blood counts of intact non

  12. New BMW M3 sports coupe; Neues Sportcoupe M3 von BMW

    Energy Technology Data Exchange (ETDEWEB)

    Biermann, A.; Friedmann, S.; Gehrig, H.; Huebner, W.; Weidhase, U. [Bayerische Motoren Werke AG (BMW), Muenchen (Germany); Koplenig, W. [BMW, Muenchen (Germany). Fachbereich Karosserie

    2000-10-01

    Since 1972 Motorsport (which has been known as BMW M since 1994) has been manufacturing automobiles of exceptionally sporting character on the basis of suitable series-production cars. With its new M3, BMW M continues this tradition. It is a sports coupe based on the latest BMW 3 Series model line. Its sports design embodies the essentials of BMW M's performance philosophy. Both visible and invisible 'highlights' such as the new high-speed driveline rating elevate its longitudinal and lateral driving dynamics to the level of a racing car. We have also succeeded in maintaining the basic car's unlimited suitability for everyday use. The new M3 is therefore a fully-fledged sports car without the typical disadvantages of this type of vehicle. (orig.) [German] Bereits seit 1972 entstehen bei BMW Motorsport (seit 1994 BMW M) auf der Basis von Serienfahrzeugen Automobile mit aussergewoehnlichen sportlichen Eigenschaften. Mit dem neuen M3, abgeleitet von der aktuellen BMW Dreier-Reihe, setzt BMW M diese Tradition fort. Das Sportcoupe erschliesst ueber die weiterentwickelte Hochdrehzahlauslegung eine Fahrdynamik in Laengs- und Querrichtung auf dem Niveau eines Rennsportwagens. Gleichzeitig ist es gelungen, die uneingeschraenkte Alltagstauglichkeit des Basis-Fahrzeugs zu erhalten. Der neue M3 ist somit ein vollwertiger Sportwagen, vermeidet aber dessen typische Nachteile. (orig.)

  13. Muscarinic M3 receptor subtype gene expression in the human heart.

    Science.gov (United States)

    Hellgren, I; Mustafa, A; Riazi, M; Suliman, I; Sylvén, C; Adem, A

    2000-01-20

    The heart is an important target organ for cholinergic function. In this study, muscarinic receptor subtype(s) in the human heart were determined using reverse transcription-polymerase chain reaction. Our results demonstrated muscarinic receptor M2 and M3 subtype RNA in left/right atria/ventricles of donor hearts. Receptor autoradiography analysis using selective muscarinic ligands indicated an absence of M1 receptor subtype in the human heart. The level of muscarinic receptor binding in atria was two to three times greater than in ventricles. Our results suggest that muscarinic receptors in the human heart are of the M2 and M3 subtypes. This is the first report of M3 receptors in the human myocardium.

  14. Tachyonic Anti-M2 Branes

    CERN Document Server

    Bena, Iosif; Kuperstein, Stanislav; Massai, Stefano

    2014-01-01

    We study the dynamics of anti-M2 branes in a warped Stenzel solution with M2 charges dissolved in fluxes by taking into account their full backreaction on the geometry. The resulting supergravity solution has a singular magnetic four-form flux in the near-brane region. We examine the possible resolution of this singularity via the polarization of anti-M2 branes into M5 branes, and compute the corresponding polarization potential for branes smeared on the finite-size four-sphere at the tip of the Stenzel space. We find that the potential has no minimum. We then use the potential for smeared branes to compute the one corresponding to a stack of localized anti-M2 branes, and use this potential to compute the force between two anti-M2 branes at tip of the Stenzel space. We find that this force, which is zero in the probe approximation, is in fact repulsive. This surprising result points to a tachyonic instability of anti-M2 branes in backgrounds with M2 brane charge dissolved in flux.

  15. Multimedia for Art ReTrieval (M4ART)

    NARCIS (Netherlands)

    Broek, E.L. van den; Schouten, T.E.; Kok, T.; Hoenkamp, E.C.M.

    2006-01-01

    The prototype for an online Multimedia for Art ReTrieval (M4ART) system is introduced, that provides entrance to the digitized collection of the National Gallery of the Netherlands (the Rijksmuseum). The current online system of the Rijksmuseum is text-based and requires expert knowledge concerning

  16. Fast rotating Blue Stragglers in the globular cluster M4

    CERN Document Server

    Lovisi, L; Ferraro, F R; Lucatello, S; Lanzoni, B; Dalessandro, E; Beccari, G; Rood, R T; Sills, A; Pecci, F Fusi; Gratton, R; Piotto, G

    2010-01-01

    We have used high resolution spectra obtained with the spectrograph FLAMES at the ESO Very Large Telescope to determine the kinematical properties and the abundance patterns of 20 blue straggler stars (BSSs) in the globular cluster M4. We found that ~ 40% of the measured BSSs are fast rotators (with rotational velocities > 50 km/s). This is the largest frequency of rapidly rotating BSSs ever detected in a globular cluster. In addition, at odds with what has been found in 47 Tucanae, no evidence of carbon and/or oxygen depletion has been revealed in the sample of 11 BSSs for which we were able to measure the abundances. This could be due either to low statistics, or to a different BSS formation process acting in M4.

  17. Studying RR Lyrae Stars in M4 with K2

    Science.gov (United States)

    Kuehn, Charles A.; Drury, Jason; Moskalik, Pawel

    2017-01-01

    Observations by Kepler/K2 have revolutionized the study of RR Lyrae stars by allowing the detection of new phenomena, such as low amplitude additional modes and period doubling, which had not previously been seen from the ground. During its campaign 2, K2 observed the globular cluster M4, providing the first opportunity to study a sizeable group of RR Lyrae stars that belong to a single population; the other RR Lyrae stars that have been observed from space are field stars in the galactic halo and thus belong to an assortment of populations. We present the results of our study of the RR Lyrae variables in M4 from K2 photometry. We have identified additional, low amplitude pulsation modes in the two observed RRc stars. In three RRab stars we have found the Blazhko effect with periods of 16.6 days, 22.4 days, and 44.5 days.

  18. M4AST - A Tool for Asteroid Modelling

    Science.gov (United States)

    Birlan, Mirel; Popescu, Marcel; Irimiea, Lucian; Binzel, Richard

    2016-10-01

    M4AST (Modelling for asteroids) is an online tool devoted to the analysis and interpretation of reflection spectra of asteroids in the visible and near-infrared spectral intervals. It consists into a spectral database of individual objects and a set of routines for analysis which address scientific aspects such as: taxonomy, curve matching with laboratory spectra, space weathering models, and mineralogical diagnosis. Spectral data were obtained using groundbased facilities; part of these data are precompiled from the literature[1].The database is composed by permanent and temporary files. Each permanent file contains a header and two or three columns (wavelength, spectral reflectance, and the error on spectral reflectance). Temporary files can be uploaded anonymously, and are purged for the property of submitted data. The computing routines are organized in order to accomplish several scientific objectives: visualize spectra, compute the asteroid taxonomic class, compare an asteroid spectrum with similar spectra of meteorites, and computing mineralogical parameters. One facility of using the Virtual Observatory protocols was also developed.A new version of the service was released in June 2016. This new release of M4AST contains a database and facilities to model more than 6,000 spectra of asteroids. A new web-interface was designed. This development allows new functionalities into a user-friendly environment. A bridge system of access and exploiting the database SMASS-MIT (http://smass.mit.edu) allows the treatment and analysis of these data in the framework of M4AST environment.Reference:[1] M. Popescu, M. Birlan, and D.A. Nedelcu, "Modeling of asteroids: M4AST," Astronomy & Astrophysics 544, EDP Sciences, pp. A130, 2012.

  19. White Dwarfs in Globular Clusters HST Observations of M4

    CERN Document Server

    Richer, H B; Ibata, R A; Pryor, C E; Bell, R A; Bolte, M; Bond, H E; Harris, W E; Hesser, J E; Holland, S; Ivanans, N; Mandushev, G I; Stetson, P B; Wood, M A; Richer, Harvey B.; Fahlman, Gregory G.; Ibata, Rodrigo A.; Pryor, Carlton; Bell, Roger A.; Bolte, Michael; Bond, Howard E.; Harris, William E.; Hesser, James E.; Holland, Steve; Ivanans, Nicholas; Mandushev, Georgi; Stetson, Peter B.; Wood, Matt A.

    1997-01-01

    Using WFPC2 on the Hubble Space Telescope, we have isolated a sample of 258 white dwarfs (WDs) in the Galactic globular cluster M4. Fields at three radial distances from the cluster center were observed and sizeable WD populations were found in all three. The location of these WDs in the color-magnitude diagram, their mean mass of 0.51($ \\pm 0.03$)M$_{\\odot}$, and their luminosity function confirm basic tenets of stellar evolution theory and support the results from current WD cooling theory. The WDs are used to extend the cluster main-sequence mass function upward to stars that have already completed their nuclear evolution. The WD/red dwarf binary frequency in M4 is investigated and found to be at most a few percent of all the main-sequence stars. The most ancient WDs found are about 9 Gyr old, a level which is set solely by the photometric limits of our data. Even though this is less than the age of M4, we discuss how these cooling WDs can eventually be used to check the turnoff ages of globular clusters a...

  20. The M4 Transmembrane α-Helix Contributes Differently to Both the Maturation and Function of Two Prokaryotic Pentameric Ligand-gated Ion Channels.

    Science.gov (United States)

    Hénault, Camille M; Juranka, Peter F; Baenziger, John E

    2015-10-09

    The role of the outermost transmembrane α-helix in both the maturation and function of the prokaryotic pentameric ligand-gated ion channels, GLIC and ELIC, was examined by Ala scanning mutagenesis, deletion mutations, and mutant cycle analyses. Ala mutations at the M4-M1/M3 interface lead to loss-of-function phenotypes in GLIC, with the largest negative effects occurring near the M4 C terminus. In particular, two aromatic residues at the M4 C terminus form a network of π-π and/or cation-π interactions with residues on M3 and the β6-β7 loop that is essential for both maturation and function. M4-M1/M3 interactions appear to be optimized in GLIC with even subtle structural changes at this interface leading to detrimental effects. In contrast, mutations along the M4-M1/M3 interface of ELIC typically lead to gain-of-function phenotypes, suggesting that these interactions in ELIC are not optimized for channel function. In addition, no cluster of interacting residues involving the M4 C terminus, M3, and the β6-β7 loop was found, suggesting that the M4 C terminus plays little role in ELIC maturation or function. This study shows that M4 makes distinct contributions to the maturation and gating of these two closely related homologs, suggesting that GLIC and ELIC exhibit divergent features of channel function. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. M2M massive wireless access

    DEFF Research Database (Denmark)

    Zanella, Andrea; Zorzi, Michele; Santos, André F.

    2013-01-01

    In order to make the Internet of Things a reality, ubiquitous coverage and low-complexity connectivity are required. Cellular networks are hence the most straightforward and realistic solution to enable a massive deployment of always connected Machines around the globe. Nevertheless, a paradigm...... of the current cellular standards. Here, we provide insights and introduce potential solutions for the cellular radio protocol that will allow the efficient support of Machine-to-Machine (M2M) communications. The paper focuses on the massive aspect of M2M. We will introduce PHY and MAC approaches such as Coded...

  2. Anti-influenza M2e antibody

    Science.gov (United States)

    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.

  3. Anti-influenza M2e antibody

    Energy Technology Data Exchange (ETDEWEB)

    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.

  4. Anti-influenza M2e antibody

    Science.gov (United States)

    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.

  5. HUBBLE SPACE TELESCOPE Photometry of the Globular Cluster M4

    Science.gov (United States)

    Ibata, Rodrigo A.; Richer, Harvey B.; Fahlman, Gregory G.; Bolte, Michael; Bond, Howard E.; Hesser, James E.; Pryor, Carlton; Stetson, Peter B.

    1999-02-01

    This paper presents a detailed description of the acquisition and processing of a large body of imaging data for three fields in the globular cluster M4 taken with the Wide Field and Planetary Camera 2 aboard the Hubble Space Telescope. Analysis with the ALLFRAME package yielded the deepest photometry yet obtained for this cluster. The resulting data set for 4708 stars (positions and calibrated photometry in V, I, and, in two fields, U) spanning approximately six cluster core radii is presented. The scientific analysis is deferred to three companion papers, which investigate the significant white dwarf population discovered and the main-sequence population.

  6. Superconformal indices and M2-branes

    Energy Technology Data Exchange (ETDEWEB)

    Eager, Richard [Kavli Institute for the Physics and Mathematics of the Universe (WPI),University of Tokyo, Kashiwa, Chiba 277-8583 (Japan); Schmude, Johannes [RIKEN Nishina Center, Saitama 351-0198 (Japan)

    2015-12-10

    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.

  7. Superconformal indices and M2-branes

    Science.gov (United States)

    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.

  8. M3 Macrophages Stop Division of Tumor Cells In Vitro and Extend Survival of Mice with Ehrlich Ascites Carcinoma.

    Science.gov (United States)

    Kalish, Sergey; Lyamina, Svetlana; Manukhina, Eugenia; Malyshev, Yuri; Raetskaya, Anastasiya; Malyshev, Igor

    2017-01-26

    BACKGROUND M1 macrophages target tumor cells. However, many tumors produce anti-inflammatory cytokines, which reprogram the anti-tumor M1 macrophages into the pro-tumor M2 macrophages. We have hypothesized that the problem of pro-tumor macrophage reprogramming could be solved by using a special M3 switch phenotype. The M3 macrophages, in contrast to the M1 macrophages, should respond to anti-inflammatory cytokines by increasing production of pro-inflammatory cytokines to retain its anti-tumor properties. Objectives of the study were to form an M3 switch phenotype in vitro and to evaluate the effect of M3 macrophages on growth of Ehrlich ascites carcinoma (EAC) in vitro and in vivo. MATERIAL AND METHODS Tumor growth was initiated by an intraperitoneal injection of EAC cells into C57BL/6J mice. RESULTS 1) The M3 switch phenotype can be programed by activation of M1-reprogramming pathways with simultaneous inhibition of the M2 phenotype transcription factors, STAT3, STAT6, and/or SMAD3. 2) M3 macrophages exerted an anti-tumor effect both in vitro and in vivo, which was superior to anti-tumor effects of cisplatin or M1 macrophages. 3) The anti-tumor effect of M3 macrophages was due to their anti-proliferative effect. CONCLUSIONS Development of new biotechnologies for restriction of tumor growth using in vitro reprogrammed M3 macrophages is very promising.

  9. M3 Macrophages Stop Division of Tumor Cells In Vitro and Extend Survival of Mice with Ehrlich Ascites Carcinoma

    Science.gov (United States)

    Kalish, Sergey; Lyamina, Svetlana; Manukhina, Eugenia; Malyshev, Yuri; Raetskaya, Anastasiya; Malyshev, Igor

    2017-01-01

    Background M1 macrophages target tumor cells. However, many tumors produce anti-inflammatory cytokines, which reprogram the anti-tumor M1 macrophages into the pro-tumor M2 macrophages. We have hypothesized that the problem of pro-tumor macrophage reprogramming could be solved by using a special M3 switch phenotype. The M3 macrophages, in contrast to the M1 macrophages, should respond to anti-inflammatory cytokines by increasing production of pro-inflammatory cytokines to retain its anti-tumor properties. Objectives of the study were to form an M3 switch phenotype in vitro and to evaluate the effect of M3 macrophages on growth of Ehrlich ascites carcinoma (EAC) in vitro and in vivo. Material/Methods Tumor growth was initiated by an intraperitoneal injection of EAC cells into C57BL/6J mice. Results 1) The M3 switch phenotype can be programed by activation of M1-reprogramming pathways with simultaneous inhibition of the M2 phenotype transcription factors, STAT3, STAT6, and/or SMAD3. 2) M3 macrophages exerted an anti-tumor effect both in vitro and in vivo, which was superior to anti-tumor effects of cisplatin or M1 macrophages. 3) The anti-tumor effect of M3 macrophages was due to their anti-proliferative effect. Conclusions Development of new biotechnologies for restriction of tumor growth using in vitro reprogrammed M3 macrophages is very promising. PMID:28123171

  10. M2M在3GPP SA2的研究进展%The Progress of M2M in 3GPP SA2

    Institute of Scientific and Technical Information of China (English)

    杜加懂

    2011-01-01

    With the rapid development of Internet of things,almost all communication standardization organizations put their focus on the standards of M2M.3GPP as the main mobile communication SDO is working hard on research and standards on M2M.Based on the brief introduction of the 3GPP working groups on M2M,this paper mainly introduces the 3GPP SA2 research progress and standardization on M2M.%随着物联网的快速发展,M2M成为各个标准化组织研究和标准制定的工作重点。3GPP作为移动通信技术的主要研究和标准制定者,对M2M的相关研究和标准制定也在加紧进行。本文在介绍3GPP各个工作组的工作情况的基础上,重点介绍了M2M在3GPP在SA2的研究和标准化进展情况。

  11. Genomic standards consortium workshop: metagenomics, metadata and metaanalysis (M3).

    Science.gov (United States)

    Sterk, Peter; Hirschman, Lynette; Field, Dawn; Wooley, John

    2010-01-01

    The M3 workshop has, as its primary focus, the rapidly growing area of metagenomics, including the metadata standards and the meta-analysis approaches needed to organize, process and interpret metagenomics data. The PSB Workshop builds on the first M3 meeting, a Special Interest Group (SIG) meeting at ISMB 2009, organized by the Genomics Standards Consortium.

  12. LOSA-M2 aerosol Raman lidar

    Energy Technology Data Exchange (ETDEWEB)

    Balin, Yu S; Bairashin, G S; Kokhanenko, G P; Penner, I E; Samoilova, S V [V.E. Zuev Institute of Atmospheric Optics, Siberian Branch, Russian Academy of Sciences, Tomsk (Russian Federation)

    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.

  13. Periodic Arrays of M2-Branes

    CERN Document Server

    Jeon, Imtak; Richmond, Paul

    2012-01-01

    We consider periodic arrays of M2-branes in the ABJM model in the spirit of a circle compactification to D2-branes in type IIA string theory. The result is a curious formulation of three-dimensional maximally supersymmetric Yang-Mills theory in terms of fermions, seven transverse scalars, a non-dynamical gauge field and an additional scalar `dual gluon'. Upon further T-duality on a transverse torus we obtain a non-manifest-Lorentz-invariant description of five-dimensional maximally supersymmetric Yang-Mills. Here the additional scalar field can be thought of as the components of a two-form along the torus. This action can be viewed as an M-theory description of M5-branes on ${\\mathbb T}^3$.

  14. The (178m2)Hf Controversy

    Energy Technology Data Exchange (ETDEWEB)

    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.

  15. Evidence of paired M2 muscarinic receptors

    Energy Technology Data Exchange (ETDEWEB)

    Potter, L.T.; Ballesteros, L.A.; Bichajian, L.H.; Ferrendelli, C.A.; Fisher, A.; Hanchett, H.E.; Zhang, R. (Univ. of Miami School of Medicine, FL (USA))

    1991-02-01

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

  16. Inversion of the Focal Mechanisms of the 2014 M4.2 and M4.0 Earthquakes in Rushan,Shandong Using the CAP Method%CAP 方法反演2014年山东乳山 M4.2、M4.0地震震源机制解

    Institute of Scientific and Technical Information of China (English)

    曲均浩; 刘瑞峰; 李金; 李永红; 张芹; 李铂; 吴丹彤

    2014-01-01

    There have been many intensive small earthquakes since the M 3.8 earthquake occurred in Rushan,Shandong on October 1,2013.Two earthquakes(M 4.2 and M 4.0)occurred separately on January 7 and April 4,2014.There have never been so many earthquakes in Rushan.A focal mechanism describes the nature and source rupture process and is an important foundation to un-derstand the stress state of the source region,earthquake faults,and for analyzing the causes of a seismic event.Therefore,seismic interpretation and post-earthquake seismogenic stress distribu-tion mechanisms play very important roles in determining earthquake focal mechanisms.In this study,using waveforms from the Shandong Seismological Network and comparing the synthetic and the observed seismograms,the focal mechanism of the Rushan M 4.2 and M 4.0 earthquakes in 2014 are inverted using the CAP(Cut and paste)method.The results show that the two earth-quakes get their best focal mechanism at 6 km depth,and that the parameters of the nodal planes are similar,belonging to the strike-slip type.At a depth of 6 km,the correlation coefficients of 40 phases of the M 4.2 earthquake greater than 0.7 that were recorded by eight stations are 37,which accounts for 93%.The correlation coefficients greater than 0.9 are 28,accounting for about 70%. Similarly,at a depth of 6 km,the correlation coefficients of 40 phases of the M 4.0 earthquake that were recorded by the eight stations are all greater than 0.7 and the correlation coefficients greater than 0.9 are 31,accounting for about 78%.Therefore,the synthetic seismograms of the two earth-quakes fit the observed seismograms well demonstrating that the inversion results are credible. The focal mechanism shows that the moment magnitude of the M 4.2 earthquake was M W =4.3;one nodal plane has a strike of 290°,rake of 84°,and dip of 22°and the other nodal plane has a strike of 189°,rake of 68°,and dip of 174°.The moment magnitude of the M 4.0 earthquake is M W=4.2,one nodal

  17. M3: Matrix Multiplication on MapReduce

    DEFF Research Database (Denmark)

    Silvestri, Francesco; Ceccarello, Matteo

    2015-01-01

    M3 is an Hadoop library for performing dense and sparse matrix multiplication in MapReduce. The library is based on multi-round algorithms exploiting the 3D decomposition of the problem.......M3 is an Hadoop library for performing dense and sparse matrix multiplication in MapReduce. The library is based on multi-round algorithms exploiting the 3D decomposition of the problem....

  18. Involvement of a subpopulation of neuronal M4 muscarinic acetylcholine receptors in the antipsychotic-like effects of the M1/M4 preferring muscarinic receptor agonist xanomeline

    DEFF Research Database (Denmark)

    Dencker, Ditte; Wörtwein, Gitta; Weikop, Pia;

    2011-01-01

    studies indicate that the M(4) muscarinic cholinergic receptor subtype (mAChR) modulates the activity of the dopaminergic system and that this specific mAChR subtype is involved in mediating the antipsychotic-like effects of xanomeline. A specific neuronal subpopulation that expresses M(4) mAChRs together...... with D(1) dopamine receptors seems to be especially important in modulating dopamine-dependent behaviors. Using mutant mice that lack the M(4) mAChR only in D(1) dopamine receptor-expressing cells (D1-M4-KO), we investigated the role of this neuronal population in the antipsychotic-like effects...

  19. M3D project for simulation studies of plasmas

    Energy Technology Data Exchange (ETDEWEB)

    Park, W.; Belova, E.V.; Fu, G.Y. [Princeton Univ., NJ (United States). Plasma Physics Lab.; Strauss, H.R. [New York Univ., NY (United States); Sugiyama, L.E. [Massachusetts Inst. of Tech., Cambridge, MA (United States)

    1998-12-31

    The M3D (Multi-level 3D) project carries out simulation studies of plasmas of various regimes using multi-levels of physics, geometry, and mesh schemes in one code package. This paper and papers by Strauss, Sugiyama, and Belova in this workshop describe the project, and present examples of current applications. The currently available physics models of the M3D project are MHD, two-fluids, gyrokinetic hot particle/MHD hybrid, and gyrokinetic particle ion/two-fluid hybrid models. The code can be run with both structured and unstructured meshes.

  20. Assembly language programming ARM Cortex-M3

    CERN Document Server

    Mahout, Vincent

    2013-01-01

    ARM designs the cores of microcontrollers which equip most "embedded systems" based on 32-bit processors. Cortex M3 is one of these designs, recently developed by ARM with microcontroller applications in mind. To conceive a particularly optimized piece of software (as is often the case in the world of embedded systems) it is often necessary to know how to program in an assembly language.This book explains the basics of programming in an assembly language, while being based on the architecture of Cortex M3 in detail and developing many examples.It is written for people who have never pr

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

    OpenAIRE

    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 ...

  2. Optimizing Concurrent M3-Transactions: A Fuzzy Constraint Satisfaction Approach

    Directory of Open Access Journals (Sweden)

    Peng LI

    2004-10-01

    Full Text Available Due to the high connectivity and great convenience, many E-commerce application systems have a high transaction volume. Consequently, the system state changes rapidly and it is likely that customers issue transactions based on out-of-date state information. Thus, the potential of transaction abortion increases greatly. To address this problem, we proposed an M3-transaction model. An M3-transaction is a generalized transaction where users can issue their preferences in a request by specifying multiple criteria and optional data resources simultaneously within one transaction. In this paper, we introduce the transaction grouping and group evaluation techniques. We consider evaluating a group of M3-transactions arrived to the system within a short duration together. The system makes optimal decisions in allocating data to transactions to achieve better customer satisfaction and lower transaction failure rate. We apply the fuzzy constraint satisfaction approach for decision-making. We also conduct experimental studies to evaluate the performance of our approach. The results show that the M3-transaction with group evaluation is more resilient to failure and yields much better performance than the traditional transaction model.

  3. Optimizing Concurrent M3-Transactions: A Fuzzy Constraint Satisfaction Approach

    Directory of Open Access Journals (Sweden)

    Peng LI

    2004-10-01

    Full Text Available Due to the high connectivity and great convenience, many E-commerce application systems have a high transaction volume. Consequently, the system state changes rapidly and it is likely that customers issue transactions based on out-of-date state information. Thus, the potential of transaction abortion increases greatly. To address this problem, we proposed an M3-transaction model. An M3-transaction is a generalized transaction where users can issue their preferences in a request by specifying multiple criteria and optional data resources simultaneously within one transaction. In this paper, we introduce the transaction grouping and group evaluation techniques. We consider evaluating a group of M3-transactions arrived to the system within a short duration together. The system makes optimal decisions in allocating data to transactions to achieve better customer satisfaction and lower transaction failure rate. We apply the fuzzy constraint satisfaction approach for decision-making. We also conduct experimental studies to evaluate the performance of our approach. The results show that the M3-transaction with group evaluation is more resilient to failure and yields much better performance than the traditional transaction model.

  4. M3: An Open Model for Measuring Code Artifacts

    NARCIS (Netherlands)

    Izmaylova, A.; Klint, P.; Shahi, A.; Vinju, J.J.

    2013-01-01

    In the context of the EU FP7 project ``OSSMETER'' we are developing an infra-structure for measuring source code. The goal of OSSMETER is to obtain insight in the quality of open-source projects from all possible perspectives, including product, process and community. This is a "white paper" on M3,

  5. Low-lying electronic states of M(3)O(9)(-) and M(3)O(9)(2-) (M = Mo, W).

    Science.gov (United States)

    Li, Shenggang; Dixon, David A

    2007-11-01

    Multiple low-lying electronic states of M(3)O(9)(-) and M(3)O(9)(2-) (M = Mo, W) arise from the occupation of the near-degenerate low-lying virtual orbitals in the neutral clusters. We used density functional theory (DFT) and coupled cluster theory (CCSD(T)) with correlation consistent basis sets to study the structures and energetics of the electronic states of these anions. The adiabatic and vertical electron detachment energies (ADEs and VDEs) of the anionic clusters were calculated with 27 exchange-correlation functionals including one local spin density approximation functional, 13 generalized gradient approximation (GGA) functionals, and 13 hybrid GGA functionals, as well as the CCSD(T) method. For M(3)O(9)(-), CCSD(T) and nearly all of the DFT exchange-correlation functionals studied predict the (2)A(1) state arising from the Jahn-Teller distortion due to singly occupying the degenerate e' orbital to be lower in energy than the (2)A(1)' state arising from singly occupying the nondegenerate a(1)' orbital. For W(3)O(9)(-), the (2)A(1) state was predicted to have essentially the same energy as the (2)A(1)' state at the CCSD(T) level with core-valence correlation corrections included and to be higher in energy or essentially isoenergetic with most DFT methods. The calculated VDEs from the CCSD(T) method are in reasonable agreement with the experimental values for both electronic states if estimates for the corrections due to basis set incompleteness are included. For M(3)O(9)(2-), the singlet state arising from doubly occupying the nondegenerate a(1)' orbital was predicted to be the most stable state for both M = Mo and W. However, whereas M(3)O(9)(2-) was predicted to be less stable than M(3)O(9)(-), W(3)O(9)(2-) was predicted to be more stable than W(3)O(9)(-).

  6. 26 CFR 1.401(m)-4 - Special rules for mergers, acquisitions and similar events. [Reserved

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Special rules for mergers, acquisitions and similar events. 1.401(m)-4 Section 1.401(m)-4 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE.... § 1.401(m)-4 Special rules for mergers, acquisitions and similar events....

  7. Main: 1M2Q [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available 1M2Q トウモロコシ Corn Zea mays L. Casein Kinase Ii, Alpha Chain Name=Ack2; Zea Mays Mole...LVGRHSRKPWLKFMNADNQHLVSPEAIDFLDKLLRYDHQERLTALEAMTHPYFQQVRAAENSRTRA corn_1M2Q.jpg ...

  8. Main: 1M2P [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available 1M2P トウモロコシ Corn Zea mays L. Casein Kinase Ii, Alpha Chain Name=Ack2; Zea Mays Mole...LVGRHSRKPWLKFMNADNQHLVSPEAIDFLDKLLRYDHQERLTALEAMTHPYFQQVRAAENSRTRA corn_1M2P.jpg ...

  9. Main: 1M2R [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available 1M2R トウモロコシ Corn Zea mays L. Casein Kinase Ii, Alpha Chain Name=Ack2; Zea Mays Mole...ELLVDLQDYDYSLDMWSLGCMFAGMIFRKEPFFYGHDNHDQLVKIAKVLGTDGLNVYLNKYRIELDPQLEALVGRHSRKPWLKFMNADNQHLVSPEAIDFLDKLLRYDHQERLTALEAMTHPYFQQVRAAENSRTRA corn_1M2R.jpg ...

  10. M3与M5的MICM鉴别

    Institute of Scientific and Technical Information of China (English)

    索翠平; 李寅; 赵霞

    2003-01-01

    @@ 急性早幼粒细胞自血病(M3型,acute promyelocytic leukemia,APL)和急性单核细胞白血病(M5型,acute monocytic leukemia,AMOL)同属于急性非淋巴细胞白血病.二者在临床与形态上均有相似之处,特别是细颗粒型急性早幼粒细胞白血病(M3b)在形态上更易被误诊为急性单核细胞白血病.但二者的治疗与预后却有很大的区别.在此,结合MICM分型原则对二者加以鉴别,以免造成误诊,导致不应有的后果.

  11. M4 muscarinic receptor knockout mice display abnormal social behavior and decreased prepulse inhibition

    Directory of Open Access Journals (Sweden)

    Koshimizu Hisatsugu

    2012-04-01

    Full Text Available Abstract Background In the central nervous system (CNS, the muscarinic system plays key roles in learning and memory, as well as in the regulation of many sensory, motor, and autonomic processes, and is thought to be involved in the pathophysiology of several major diseases of the CNS, such as Alzheimer's disease, depression, and schizophrenia. Previous studies reveal that M4 muscarinic receptor knockout (M4R KO mice displayed an increase in basal locomotor activity, an increase in sensitivity to the prepulse inhibition (PPI-disrupting effect of psychotomimetics, and normal basal PPI. However, other behaviorally significant roles of M4R remain unclear. Results In this study, to further investigate precise functional roles of M4R in the CNS, M4R KO mice were subjected to a battery of behavioral tests. M4R KO mice showed no significant impairments in nociception, neuromuscular strength, or motor coordination/learning. In open field, light/dark transition, and social interaction tests, consistent with previous studies, M4R KO mice displayed enhanced locomotor activity compared to their wild-type littermates. In the open field test, M4R KO mice exhibited novelty-induced locomotor hyperactivity. In the social interaction test, contacts between pairs of M4R KO mice lasted shorter than those of wild-type mice. In the sensorimotor gating test, M4R KO mice showed a decrease in PPI, whereas in the startle response test, in contrast to a previous study, M4R KO mice demonstrated normal startle response. M4R KO mice also displayed normal performance in the Morris water maze test. Conclusions These findings indicate that M4R is involved in regulation of locomotor activity, social behavior, and sensorimotor gating in mice. Together with decreased PPI, abnormal social behavior, which was newly identified in the present study, may represent a behavioral abnormality related to psychiatric disorders including schizophrenia.

  12. The boundary RSOS \\mathcal{M}(3,5) model

    CERN Document Server

    Deeb, Omar El

    2015-01-01

    We consider the critical non-unitary minimal model {\\cal M}(3,5) with integrable boundaries. We analyze the patterns of zeros of the eigenvalues of the transfer matrix and then determine the spectrum of the critical theory through the Thermodynamic Bethe Ansatz (TBA) equations. We derive these equations for all excitations by solving, the TBA functional equation satisfied by the transfer matrices of the associated A_{4} RSOS lattice model of Forrester and Baxter in Regime III, then determine their corresponding energies. The excitations are classified in terms of (m,n) systems.

  13. 3000m3/h cutter-suction dredge

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    @@ In October 2004, the Fumin 9 3000 m3/h cutter-suction dredge co-designed by the Dutch IHC and Guangzhou Wenchong Shipyard went through a dock usability test and a 25 meter clean water test. The dredge is the largest of its kind in China, and the most advanced and most efficient cutter-suction dredge in the world. The IHC was responsible for the design of the ship till its working design was taken over by Guangzhou Wenchong Shipyard, the builder of the dredge, who had started its construction on October 23, 2003.

  14. Hydraulic supports for polishing TMT M3MP

    Science.gov (United States)

    Hu, Haifei; Qi, Erhui; Cole, Glen; Hu, Haixiang; Luo, Xiao; Ford, Virginia; Zhang, Xuejun

    2016-10-01

    For polishing the ultra-thin TMT M3MP, a polishing support system with 18 hydraulic supports (HS) is introduced. This work focuses on the designing and testing of these HSs. Firstly the design concept of HS system is discussed; then mechanical implementation of the HS structure is carried out, with special consideration of fluid cycling, work pressurization and the weight component. Afterward the piping installation and the de-gas process for the working fluid are implemented. Pressurization and stiffness are well checked before system integration for the single HS unit. Finally the support system is integrated for the polishing process.

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

    Science.gov (United States)

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

    2006-12-15

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

  16. Towards Horizontal Architecture for Autonomic M2M Service Networks

    Directory of Open Access Journals (Sweden)

    Juhani Latvakoski

    2014-05-01

    Full Text Available Today, increasing number of industrial application cases rely on the Machine to Machine (M2M services exposed from physical devices. Such M2M services enable interaction of physical world with the core processes of company information systems. However, there are grand challenges related to complexity and “vertical silos” limiting the M2M market scale and interoperability. It is here expected that horizontal approach for the system architecture is required for solving these challenges. Therefore, a set of architectural principles and key enablers for the horizontal architecture have been specified in this work. A selected set of key enablers called as autonomic M2M manager, M2M service capabilities, M2M messaging system, M2M gateways towards energy constrained M2M asset devices and creation of trust to enable end-to-end security for M2M applications have been developed. The developed key enablers have been evaluated separately in different scenarios dealing with smart metering, car sharing and electric bike experiments. The evaluation results shows that the provided architectural principles, and developed key enablers establish a solid ground for future research and seem to enable communication between objects and applications, which are not initially been designed to communicate together. The aim as the next step in this research is to create a combined experimental system to evaluate the system interoperability and performance in a more detailed manner.

  17. Revisiting the Endocytosis of the M2 Muscarinic Acetylcholine Receptor

    OpenAIRE

    Wymke Ockenga; Ritva Tikkanen

    2015-01-01

    The agonist-induced endocytosis of the muscarinic acetylcholine receptor M2 is different from that of the other members of the muscarinic receptor family. The uptake of the M2 receptor involves the adapter proteins of the β-arrestin family and the small GTPase ADP-ribosylation factor 6. However, it has remained inconclusive if M2 endocytosis is dependent on clathrin or the large GTPase dynamin. We here show by means of knocking down the clathrin heavy chain that M2 uptake upon agonist stimul...

  18. 针对MCU应用的Cortex-M3

    Institute of Scientific and Technical Information of China (English)

    费浙平

    2005-01-01

    传统上MCU领域一直由4/8位架构占据了主导地位,部分采用16位架构,而32位才刚起步,在多数人印象中它还是一种奢侈的高端应用。但近几年这种情况已有了很大变化,越来越多的设计采用32位MCU架构,而ARMCotex—M3的面世也为32位MCU应用带来更多可能。

  19. Acetylcholine acts through M3 muscarinic receptor to activate the EGFR signaling and promotes gastric cancer cell proliferation

    Science.gov (United States)

    Yu, Huangfei; Xia, Hongwei; Tang, Qiulin; Xu, Huanji; Wei, Guoqing; Chen, Ying; Dai, Xinyu; Gong, Qiyong; Bi, Feng

    2017-01-01

    Acetylcholine (ACh), known as a neurotransmitter, regulates the functions of numerous fundamental central and peripheral nervous system. Recently, emerging evidences indicate that ACh also plays an important role in tumorigenesis. However, little is known about the role of ACh in gastric cancer. Here, we reported that ACh could be auto-synthesized and released from MKN45 and BGC823 gastric cancer cells. Exogenous ACh promoted cell proliferation in a does-dependent manner. The M3R antagonist 4-DAMP, but not M1R antagonist trihexyphenidyl and M2/4 R antagonist AFDX-116, could reverse the ACh-induced cell proliferation. Moreover, ACh, via M3R, activated the EGFR signaling to induce the phosphorylation of ERK1/2 and AKT, and blocking EGFR pathway by specific inhibitor AG1478 suppressed the ACh induced cell proliferation. Furthermore, the M3R antagonist 4-DAMP and darifenacin could markedly inhibit gastric tumor formation in vivo. 4-DAMP could also significantly enhance the cytotoxic activity of 5-Fu against the MKN45 and BGC823 cells, and induce the expression of apoptosis-related proteins such as Bax and Caspase-3. Together, these findings indicated that the autocrine ACh could act through M3R and the EGFR signaling to promote gastric cancer cells proliferation, targeting M3R or EGFR may provide us a potential therapeutic strategy for gastric cancer treatment. PMID:28102288

  20. A selfish gene chastened: Tribolium castaneum Medea M4 is silenced by a complementary gene.

    Science.gov (United States)

    Thomson, M Scott

    2014-04-01

    Maternal-effect dominant embryonic arrest (Medea) of Tribolium castaneum are autosomal factors that act maternally to cause the death of any progeny that do not inherit them. This selfish behavior is thought to result from a maternally expressed poison and zygotically expressed antidote. Medea factors and the hybrid incompatibility factor, H, have a negative interaction consistent with complementary genes of the Dobzhansky-Muller model for post-zygotic isolation. This negative interaction may result from H suppression of Medea zygotic antidote, leaving zygotes incompletely protected from maternal poison. I report here a test of the hypothesis that H also suppresses the Medea maternal poison. Viable F1 females were generated from a cross of Medea M4 strain males to H strain females. These females, heterozygous for both M4 and H, failed to express M4 maternal lethal activity when crossed to their male sibs. Transmission of non-M4 homologues from these females was confirmed using a dominant transgenic enhanced green fluorescent protein eye color marker, tightly linked in cis to M4. M4 beetles, lacking H, were selected from the F2 population. Female descendants of these clearly expressed M4 maternal lethal activity, indicating restoration of this activity after H was segregated away. I conclude that H, or a factor tightly linked to H, suppresses Medea M4 maternal poison.

  1. Antipsychotic-induced catalepsy is attenuated in mice lacking the M4 muscarinic acetylcholine receptor

    DEFF Research Database (Denmark)

    Fink-Jensen, Anders; Schmidt, Lene S; Dencker, Ditte

    2011-01-01

    of the striatum, suggesting a role for muscarinic M4 receptors in the motor side effects of antipsychotics, and in the alleviation of these side effects by anticholinergics. Here we investigated the potential role of the muscarinic M4 receptor in catalepsy induced by antipsychotics (haloperidol and risperidone...

  2. The Demand for Divisia M2 in China%中国Divisa M2需求模型

    Institute of Scientific and Technical Information of China (English)

    潘红宇; 邓述慧

    2001-01-01

    本文计算中国Divisa M2指数并对其建立需求模型,研究发现实际Divisa M2 与实际产出存在协整关系,采用误差校正方法建立的动态需求模型具有良好的稳定性。%This paper computes the Divisa M2 in China and makes the money demand model for it. The research finds that the demand for real Divisa M2 is cointegrated with the real output, the short-run model is stable also.

  3. A Survey on M2M Service Networks

    Directory of Open Access Journals (Sweden)

    Juhani Latvakoski

    2014-11-01

    Full Text Available The number of industrial applications relying on the Machine to Machine (M2M services exposed from physical world has been increasing in recent years. Such M2M services enable communication of devices with the core processes of companies. However, there is a big challenge related to complexity and to application-specific M2M systems called “vertical silos”. This paper focuses on reviewing the technologies of M2M service networks and discussing approaches from the perspectives of M2M information and services, M2M communication and M2M security. Finally, a discussion on technologies and approaches potentially enabling future autonomic M2M service networks are provided. According to our conclusions, it is seen that clear definition of the architectural principles is needed to solve the “vertical silo” problem and then, proceeding towards enabling autonomic capabilities for solving complexity problem appears feasible. Several areas of future research have been identified, e.g., autonomic information based services, optimization of communications with limited capability devices, real-time messaging, creation of trust and end to end security, adaptability, reliability, performance, interoperability, and maintenance.

  4. M2 factor of four-petal Gaussian beam

    Institute of Scientific and Technical Information of China (English)

    Zhou Guo-Quan; Fan Yan

    2008-01-01

    Based on the second-order moments,this paper derives an analytical expression of the M2 factor of four-petal Gaussian beam.The results show that the M2 factor is only determined by the beam order n.The corresponding numerical calculations are also given.As the beam order increases,the augment of M2 factor is disciplinary.As the expression of M2 factor is expressed in series form and becomes more complicated,a new concise formula of M2 factor is also presented by using curve fitting of numerical calculations.When 3≤n≤200,the maximum error rate of fitting formula will not exceed 2.6% and the average error rate is 0.28%.This research is helpful to the applications of four-petal Gaussian beam.

  5. M2 polarization enhances silica nanoparticle uptake by macrophages

    Directory of Open Access Journals (Sweden)

    Jessica eHoppstädter

    2015-03-01

    Full Text Available 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: GM-CSF/LPS/IFN-gamma was used to generate primary human M1 cells and M-CSF/IL-10 to differentiate M2 monocyte-derived macrophages. PMA-differentiated THP-1 cells were polarized towards an M1 type by LPS/IFN-gamma and towards M2 by IL-10. Uptake of fluorescent silica nanoparticles (Ø 26 and 41 nm and microparticles (Ø 1.75 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 monocyte-derived macrophages 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 (TAM 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 might also open up therapeutic perspectives allowing to specifically target M2

  6. Magnetic circular dichroism of porphyrin lanthanide M3+ complexes.

    Science.gov (United States)

    Andrushchenko, Valery; Padula, Daniele; Zhivotova, Elena; Yamamoto, Shigeki; Bouř, Petr

    2014-10-01

    Lanthanide complexes exhibit interesting spectroscopic properties yielding many applications as imaging probes, natural chirality amplifiers, and therapeutic agents. However, many properties are not fully understood yet. Therefore, we applied magnetic circular dichroism (MCD) spectroscopy, which provides enhanced information about the underlying electronic structure to a series of lanthanide compounds. The metals in the M(3+) state included Y, La, Eu, Tb, Dy, Ho, Er, Tm, Yb, and Lu; the spectra were collected for selected tetraphenylporphin (TPP) and octaethylporphin (OEP) complexes in chloroform. While the MCD and UV-VIS absorption spectra were dominated by the porphyrin signal, metal binding significantly modulated them. MCD spectroscopy was found to be better suited to discriminate between various species than absorption spectroscopy alone. The main features and trends in the lanthanide series observed in MCD and absorption spectra of the complexes could be interpreted at the Density Functional Theory (DFT) level, with effective core potentials on metal nuclei. The sum over state (SOS) method was used for simulation of the MCD intensities. The combination of the spectroscopy and quantum-chemical computations is important for understanding the interactions of the metals with the organic compounds.

  7. Presynaptic muscarinic M(2) receptors modulate glutamatergic transmission in the bed nucleus of the stria terminalis.

    Science.gov (United States)

    Guo, Ji-Dong; Hazra, Rimi; Dabrowska, Joanna; Muly, E Chris; Wess, Jürgen; Rainnie, Donald G

    2012-03-01

    The anterolateral cell group of the bed nucleus of the stria terminalis (BNST(ALG)) serves as an important relay station in stress circuitry. Limbic inputs to the BNST(ALG) are primarily glutamatergic and activity-dependent changes in this input have been implicated in abnormal behaviors associated with chronic stress and addiction. Significantly, local infusion of acetylcholine (ACh) receptor agonists into the BNST trigger stress-like cardiovascular responses, however, little is known about the effects of these agents on glutamatergic transmission in the BNST(ALG). Here, we show that glutamate- and ACh-containing fibers are found in close association in the BNST(ALG). Moreover, in the presence of the acetylcholinesterase inhibitor, eserine, endogenous ACh release evoked a long-lasting reduction of the amplitude of stimulus-evoked EPSCs. This effect was mimicked by exogenous application of the ACh analog, carbachol, which caused a reversible, dose-dependent, reduction of the evoked EPSC amplitude, and an increase in both the paired-pulse ratio and coefficient of variation, suggesting a presynaptic site of action. Uncoupling of postsynaptic G-proteins with intracellular GDP-β-S, or application of the nicotinic receptor antagonist, tubocurarine, failed to block the carbachol effect. In contrast, the carbachol effect was blocked by prior application of atropine or M(2) receptor-preferring antagonists, and was absent in M(2)/M(4) receptor knockout mice, suggesting that presynaptic M(2) receptors mediate the effect of ACh. Immunoelectron microscopy studies further revealed the presence of M(2) receptors on axon terminals that formed asymmetric synapses with BNST neurons. Our findings suggest that presynaptic M(2) receptors might be an important modulator of the stress circuit and hence a novel target for drug development.

  8. TNF Counterbalances the Emergence of M2 Tumor Macrophages

    Directory of Open Access Journals (Sweden)

    Franz Kratochvill

    2015-09-01

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

  9. TNF counterbalances the emergence of M2 tumor macrophages

    Science.gov (United States)

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

    2015-01-01

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

  10. Multiple Access Technologies for Cellular M 2M Communications

    Institute of Scientific and Technical Information of China (English)

    Mahyar Shirvanimoghaddam; Sarah J. Johnson

    2016-01-01

    This paper reviews the multiple access techniques for machine⁃to⁃machine (M2M) communications in future wireless cellular net⁃works. M2M communications aims at providing the communication infrastructure for the emerging Internet of Things (IoT), which will revolutionize the way we interact with our surrounding physical environment. We provide an overview of the multiple access strategies and explain their limitations when used for M2M communications. We show the throughput efficiency of different multi⁃ple access techniques when used in coordinated and uncoordinated scenarios. Non⁃orthogonal multiple access (NOMA) is also shown to support a larger number of devices compared to orthogonal multiple access techniques, especially in uncoordinated sce⁃narios. We also detail the issues and challenges of different multiple access techniques to be used for M2M applications in cellu⁃lar networks.

  11. Theoretical Assessment of 178m2Hf De-Excitation

    Energy Technology Data Exchange (ETDEWEB)

    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.

  12. Characterization of M2 antibodies in asymptomatic Chinese population

    Institute of Scientific and Technical Information of China (English)

    Xiao-Hua Jiang; Ren-Qian Zhong; Xiao-Yun Fan; Yin Hu; Feng An; Jian-Wen Sun; Xian-Tao Kong

    2003-01-01

    AIM: To investigate the presence of M2 antibodies specific for pdmary biliary cirrhosis (PBC) in asymptomatic Chinese and identify patients with early PBC.METHODS: Enzyme-linked immunosorbent assay (ElISA)tests for M2 antibodies to recombinant protein were performed in 5 011 subjects (age range, 26-85 years; mean age: 45.81±15.02 years) who took an annual physical examination. M2-positive subjects were further analyzed for immunoglobulin (Ig) classes and subclasses of M2 antibodies.Clinical, biochemical and immunological data were obtained for M2-positive subjects. In addition, ultrasonography (US)or endoscopic retrograde cholangio-pancreatography (ERCP)was performed to exclude any disorders other than PBC.RESULTS: M2 antibodies were detected in 8 (0.16%) of the 5 0LL subjects studied. Of the 8 subjects, 7 were female and 1 was male (age range: 40-74 years). An unexplained increase of serum alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (γ-GT) values, often to striking levels,was detected in 4 M2-positive subjects, 3 of them accorded with the diagnostic criteria recommended by the American Association for the Study of Liver Diseases, even though they had no symptoms of PBC (such as fatigue, pruritus or jaundice).Liver biopsy was performed in two M2-positive subjects and the histology was compatible with PBC in both cases.CONCLUSION: Our data, while not assessing the true prevalence of asymptomatic PBC in the general population,suggest that asymptomatic PBC is much more common in China than has been supposed.

  13. M2-Edge Colorings Of Cacti And Graph Joins

    Directory of Open Access Journals (Sweden)

    Czap Július

    2016-02-01

    Full Text Available An edge coloring φ of a graph G is called an M2-edge coloring if |φ(v| ≤ 2 for every vertex v of G, where φ(v is the set of colors of edges incident with v. Let 2(G denote the maximum number of colors used in an M2-edge coloring of G. In this paper we determine 2(G for trees, cacti, complete multipartite graphs and graph joins.

  14. Study of {sup 179}Hf{sup m2} excitation

    Energy Technology Data Exchange (ETDEWEB)

    Vishnevsky, I. N.; Zheltonozhsky, V. A., E-mail: zhelton@kinr.kiev.ua; Savrasov, A. N. [National Academy of Sciences of Ukraine, Institute for Nuclear Research (Ukraine); Mazur, V. M. [National Academy of Sciences of Ukraine, Institute of Electronic Physics (Ukraine)

    2016-12-15

    Isomeric ratios of {sup 179}Hf{sup m2,g} yields in the (γ, n) reaction and the cross section for the {sup 179}Hf{sup m2} population in the (α, p) reaction are measured for the first time at the end-point energies of 15.1 and 17.5 MeV for bremsstrahlung photons and 26 MeV for alpha particles. The results are σ = (1.1 ± 0.11) × 10{sup −27} cm{sup 2} for the {sup 176}Lu(α, p){sup 179}Hf{sup m2} reaction and Y{sub m2}/Y{sub g} = (6.1 ± 0.3) × 10{sup −6} and (3.7 ± 0.2) × 10{sup −6} for the {sup 180}Hf(γ, n){sup 179}Hf{sup m22} reaction at E{sub ep} =15.1 and 17.5 MeV, respectively. The experimental data on the relative {sup 179}Hf{sup m2} yield indicate a single-humped shape of the excitation function for the {sup 180}Hf(γ, n){sup 179}Hf{sup m2} reaction. Simulation is performed using the TALYS-1.4 and EMPIRE-3.2 codes.

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

    Science.gov (United States)

    Ockenga, Wymke; Tikkanen, Ritva

    2015-05-12

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

  16. Revisiting the Endocytosis of the M2 Muscarinic Acetylcholine Receptor

    Directory of Open Access Journals (Sweden)

    Wymke Ockenga

    2015-05-01

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

  17. EFFECT OF Nb ON THE MICROSTRUCTURE AND PROPERTIES OF SPRAY FORMED M3 HIGH SPEED STEEL%Nb对喷射成形M3型高速钢组织和性能的影响

    Institute of Scientific and Technical Information of China (English)

    于一鹏; 黄进峰; 崔华; 蔡元华; 张济山

    2012-01-01

    为了利用NbC的高硬度和高热稳定性,并避免其在凝固过程中的过分长大,采用喷射成形快速凝固技术制备了M3型高速钢和以Nb代V的M3型高速钢.利用SEM,EDX和XRD等方法研究了Nb对喷射成形M3型高速钢沉积态组织的影响;利用SRV高温摩擦磨损试验机和三维白光干涉表面形貌仪研究了Nb对喷射成形M3型高速钢摩擦磨损性能的影响.结果表明,用等原子分数的Nb替代V,可大幅增加沉积态中一次MC型碳化物,减少一次M2C型碳化物,同时由于喷射成形高冷速的作用,使得MC碳化物尺寸减小,分布更弥散;这些MC型碳化物的存在是M3型高速钢的抗磨粒磨损性能提高的主要原因,但其对抗氧化性能并无贡献,在高载荷时抗氧化剥落磨损能力增加不明显;Nb对提高M3高速钢回火稳定性也有明显的作用.%Spray forming with a short process chains has been proven to be a powerful tool for the production of high-alloyed materials. Niobium, as a strong former for the carbide, will mainly form primary MC carbides, such as NbC, which can be formed via the reaction between Nb and C atoms at the beginning of solidification, and it can act as the inoculants and refine the cast structure of steel which can mainly form primary MC carbides. M3 high speed steel with or without Nb addition were prepared via spray forming. The effect of Nb on the microstructure of spray formed M3 high speed steel was investigated by SEM, EDX and XRD methods; the friction performances of these two steels were studied by SRV high temperature tribometer and 3D white-light interfering profilometer. The results show that the amount of primary MC carbides can increase sharply while the reduction of the amount of primary M2C due to the substitution of 2% Nb for 1% V (mass fraction) in M3 high speed steel. For the high cooling rate during the spray forming, the primary MC carbides can be refined and dispersed. Large number of primary MC carbides

  18. A randomized comparison of daunorubicin 90 mg/m2 vs 60 mg/m2 in AML induction

    DEFF Research Database (Denmark)

    Burnett, A. K.; Russell, N. H.; Hills, R. K.

    2015-01-01

    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/m(2) 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...... recommended as a standard of care. However, 60 mg/m(2) is widely used and has never been directly compared with 90 mg/m(2). 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/m(2) or 60 mg/m(2) on days 1, 3, and 5 combined with cytosine arabinoside. All patients then received a second course that included daunorubicin 50 mg/m(2) on days 1, 3, and 5. There was no overall difference in complete...

  19. M$^2$I Communication: From Theoretical Modeling to Practical Design

    CERN Document Server

    Guo, Hongzhi

    2015-01-01

    Wireless communications in complex environments are constrained by lossy media and complicated structures. Magnetic Induction (MI) has been proved to be an efficient solution to extend the communication range. Due to the small coil antenna's physical limitation, however, MI's communication range is still very limited. To this end, Metamaterial-enhanced Magnetic Induction (M$^2$I) communication has been proposed and the theoretical results suggest that it can significantly increase the communication performance, namely, data rate and communication range. Nevertheless, currently, the real implementation of M$^2$I is still a challenge and there is no guideline on design and fabrication of spherical metamaterial. In this paper, we propose a practical design by using a spherical coil array to realize M$^2$I and we prove that it can achieve negative permeability and there exists a resonance condition where the radiated magnetic field can be significantly amplified. The radiation and communication performance are ev...

  20. M4 mAChR-mediated modulation of glutamatergic transmission at corticostriatal synapses.

    Science.gov (United States)

    Pancani, Tristano; Bolarinwa, Caroline; Smith, Yoland; Lindsley, Craig W; Conn, P Jeffrey; Xiang, Zixiu

    2014-04-16

    The striatum is the main input station of the basal ganglia and is extensively involved in the modulation of motivated behavior. The information conveyed to this subcortical structure through glutamatergic projections from the cerebral cortex and thalamus is processed by the activity of several striatal neuromodulatory systems including the cholinergic system. Acetylcholine potently modulates glutamate signaling in the striatum via activation of muscarinic receptors (mAChRs). It is, however, unclear which mAChR subtype is responsible for this modulatory effect. Here, by using electrophysiological, optogenetic, and immunoelectron microscopic approaches in conjunction with a novel, highly selective M4 positive allosteric modulator VU0152100 (ML108) and M4 knockout mice, we show that M4 is a major mAChR subtype mediating the cholinergic inhibition of corticostriatal glutamatergic input on both striatonigral and striatopallidal medium spiny neurons (MSNs). This effect is due to activation of presynaptic M4 receptors, which, in turn, leads to a decrease in glutamate release from corticostriatal terminals. The findings of the present study raise the interesting possibility that M4 mAChR could be a novel therapeutic target for the treatment of neurological and neuropsychiatric disorders involving hyper-glutamatergic transmission at corticostriatal synapses.

  1. M2-F1 on lakebed with pilot Milt Thompson

    Science.gov (United States)

    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

  2. Transport coefficients of black MQGP M3-branes

    Energy Technology Data Exchange (ETDEWEB)

    Dhuria, Mansi [Physical Research Laboratory, Theoretical Physics Division, Ahmedabad (India); Misra, Aalok [Indian Institute of Technology, Department of Physics, Roorkee, Uttaranchal (India)

    2015-01-01

    The Strominger-Yau-Zaslow (SYZ) mirror, in the 'delocalised limit' of Becker et al. (Nucl Phys B 702:207, 2004), of N D3-branes, M fractional D3-branes and N{sub f} flavour D7-branes wrapping a non-compact four-cycle in the presence of a black hole (BH) resulting in a non-Kahler resolved warped deformed conifold (NKRWDC) in Mia et al. (Nucl Phys B 839:187, 2010), was carried out in Dhuria and Misra (JHEP 1311:001, 2013) and resulted in black M3- branes. There are two parts in our paper. In the first we show that in the 'MQGP' limit discussed in Dhuria and Misra (JHEP 1311:001, 2013) a finite g{sub s} (and hence expected to be more relevant to QGP), finite g{sub s}M, N{sub f}, g{sub s}{sup 2}MN{sub f} and very large g{sub s}N, and very small (g,M{sup 2})/(N), we have the following. (i) The uplift, if valid globally (like Dasgupta et al., Nucl Phys B 755:21, 2006) for fractional D3 branes in conifolds, asymptotically goes to M5-branes wrapping a two-cycle (homologously a (large) integer sum of two-spheres) in AdS{sub 5} x M{sub 6}. (ii) Assuming the deformation parameter to be larger than the resolution parameter, by estimating the five SU(3) structure torsion (τ) classes W{sub 1,2,3,4,5} we verify that τ element of W{sub 5} in the large-r limit, implying the NKRWDC reduces to a warped Kahler deformed conifold. (iii) The local T{sup 3} of Dhuria and Misra (JHEP 1311:001, 2013) in the large-r limit satisfies the same conditions as the maximal T{sup 2}-invariant special Lagrangian three-cycle of T*S{sup 3} of Ionel and Min-OO (J Math 52(3), 2008), partly justifying use of SYZ-mirror symmetry in the ''delocalised limit'' of Becker et al. (Nucl Phys B 702:207, 2004) in Dhuria and Misra (JHEP 1311:001, 2013). In the second part of the paper, by either integrating out the angular coordinates of the non-compact four-cycle which a D7-brane wraps around, using the Ouyang embedding, in the DBI action of a D7-brane evaluated at infinite

  3. 4333M4超高压反应管的断裂韧度%Fracture Toughness of Ultrahigh Pressure Reaction Tube Made by 4333M4 Steel

    Institute of Scientific and Technical Information of China (English)

    李铜; 陈进

    2012-01-01

    The critical stress intensity factor Kit: of high strength low alloy steel 4333M4 was determinated through non-standard arch bone bending experiment, and flexibility method was used. Then the tube was assessed by the leak before break criterion. The results showed that the fracture toughness of the steel was measured up to standard of SFAC 98--01 Rev. 2 and the pipe met requirements of leak before break.%通过非标准拱形三点弯曲试样的试验,采用柔度法标定,测定了进口4333M4低合金超高强度钢管材的临界应力强度因子Kzc,并对该超高压反应管进行了先漏后破分析。结果表明:该钢材有较高的断裂韧度,符合SFAC98-01Rev.2《超高压用无缝合金钢管技术条件》的要求,且管材符合先漏后破标准。

  4. International Conference on Harmonisation; guidance on M4 common technical document; availability. Notice.

    Science.gov (United States)

    2001-10-16

    The Food and Drug Administration (FDA) is announcing the availability of guidance entitled "M4 Organization of the Common Technical Document for the Registration of Pharmaceuticals for Human Use" (M4CTD). The guidance was developed under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance, which is being made available simultaneously in four parts (general organization, quality, safety, and efficacy), describes a harmonized format for new product applications (including applications for biotechnology-derived products) for submission to the regulatory authorities in the three ICH regions. The M4 CTD is intended to reduce the time and resources used to compile applications, ease the preparation of electronic submissions, facilitate regulatory reviews and communication with the applicant, and simplify the exchange of regulatory information among regulatory authorities.

  5. Voice-coil technology for the E-ELT M4 Adaptive Unit

    Science.gov (United States)

    Gallieni, D.; Tintori, M.; Mantegazza, M.; Anaclerio, E.; Crimella, L.; Acerboni, M.; Biasi, R.; Angerer, G.; Andrigettoni, M.; Merler, A.; Veronese, D.; Carel, J.-L.; Marque, G.; Molinari, E.; Tresoldi, D.; Toso, G.; Spanó, P.; Riva, M.; Mazzoleni, R.; Riccardi, A.; Mantegazza, P.; Manetti, M.; Morandini, M.; Vernet, E.; Hubin, N.; Jochum, L.; Madec, P.; Dimmler, M.; Koch, F.

    We present our design of the E-ELT M4 Adaptive Unit based on voice-coil driven deformable mirror technology. This technology was developed by INAF-Arcetri, Microgate and ADS team in the past 15 years and it has been adopted by a number of large ground based telescopes as the MMT, LBT, Magellan and lastly the VLT in the frame of the Adaptive Telescope Facility project. Our design is based on contactless force actuators made by permanent magnets glued on the back of the deformable mirror and coils mounted on a stiff reference structure. We use capacitive sensors to close a position loop co-located with each actuator. Dedicated high performance parallel processors are used to implement the local de-centralized control at actuator level and a centralized feed-forward computation of all the actuators forces. This allowed achieving in our previous systems dynamic performances well in line with the requirements of the M4 Adaptive Unit (M4AU) case. The actuator density of our design is in the order of 30-mm spacing for a figure of about 6000 actuators on the M4AU and it allows fulfilling the fitting error and corrections requirements of the E-ELT high order DM. Moreover, our contact-less technology makes the Deformable Mirror tolerant to up 5% actuators failures without spoiling system capability to reach its specified performances, besides allowing large mechanical tolerances between the reference structure and the deformable mirror. Finally, we present the Demonstration Prototype we are building in the frame of the M4AU Phase B study to measure the optical dynamical performances predicted by our design. Such a prototype will be fully representative of the M4AU features, in particular it will address the controllability of two adjacent segments of the 2-mm thick mirror and implement the actuators "brick" modular concept that has been adopted to dramatically improve the maintainability of the final unit.

  6. M2磁带机挑战极限

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    日前安百特(Exabyte)公司宣布,其OEM合作伙伴Cybernetics在对Mammoth-2(M2)磁带机的性能和可靠性测试中取得了创记录的结果,从而加快了M2的商业交付计划。M2磁带机以部门级价格提供了企业级的性能,其容量增加50%,达到60GB,性能提高一倍,传输率达到12MB/s,可在一小时内备份43GB数据(未压缩)。Cybernetics利用该公司为了故意“破坏”磁带机而创建的定制软件对M2进行了测试,包括读/写能力测试、

  7. Dimeric Complexes of Tryptophan with M2+ Metal Ions

    NARCIS (Netherlands)

    Dunbar, R. C.; Steill, J. D.; Polfer, N. C.; Oomens, J.

    2009-01-01

    IRMPD spectroscopy using the FELIX free electron laser and a Fourier transform ICR mass spectrometer was used to characterize the structures of electrosprayed dimer complexes M(2+)Trp(2) of tryptophan with a series of eight doubly charged metal ions, including alkaline earths Ca, Sr, and Ba, and tra

  8. M2e-Based Universal Influenza A Vaccines

    Directory of Open Access Journals (Sweden)

    Lei Deng

    2015-02-01

    Full Text Available 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.

  9. Progress On 58m2 Passive Resonant Ring Laser Gyroscope

    Science.gov (United States)

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

    1986-01-01

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

  10. Correlation of the National Emergency Medicine M4 Clerkship Examination with USMLE Examination Performance

    Directory of Open Access Journals (Sweden)

    Luan E. Lawson

    2015-12-01

    Full Text Available Introduction: Assessment of medical students’ knowledge in clinical settings is complex yet essential to the learning process. Clinical clerkships use various types of written examinations to objectively test medical knowledge within a given discipline. Within emergency medicine (EM, a new national standardized exam was developed to test medical knowledge in this specialty. Evaluation of the psychometric properties of a new examination is an important issue to address during test development and use. Studies have shown that student performance on selected standardized exams will reveal students’ strengths and/or weaknesses, so that effective remedial efforts can be implemented. Our study sought to address these issues by examining the association of scores on the new EM national exam with other standardized exam scores. Methods: From August 2011 to April 2013, average National EM M4 examination scores of fourthyear medical students taken at the end of a required EM clerkship were compiled. We examined the correlation of the National EM M4 examination with the scores of initial attempts of the United States Medical Licensing Exam (USMLE Step 1 and Step 2 Clinical Knowledge (CK examinations. Correlation coefficients and 95% confidence intervals of correlation coefficients are reported. We also examined the association between the national EM M4 examination score, final grades for the EM rotation, and USMLE Step 1 and Step 2 CK scores. Results: 133 students were included in the study and achieved a mean score of 79.5 SD 8.0 on the National EM M4 exam compared to a national mean of 79.7 SD 3.89. The mean USMLE Step 1 score was 226.8 SD 19.3. The mean USMLE Step 2 CK score was 238.5 SD 18.9. National EM M4 examination scores showed moderate correlation with both USMLE Step 1 (mean score=226.8; correlation coefficient=0.50; 95% CI [0.28-0.67] and USMLE Step 2 CK (mean score=238.5; correlation coefficient=0.47; 95% CI [0.25-0.65]. Students scoring

  11. Internal steel structure of M2-F1

    Science.gov (United States)

    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

  12. Effects of Modulating M3 Muscarinic Receptor Activity on Azoxymethane-Induced Liver Injury in Mice

    OpenAIRE

    2013-01-01

    Previously, we reported that azoxymethane (AOM)-induced liver injury is robustly exacerbated in M3 muscarinic receptor (M3R)-deficient mice. We used the same mouse model to test the hypothesis that selective pharmacological modulation of M3R activity regulates the liver injury response. Initial experiments confirmed that giving a selective M3R antagonist, darifenacin, to AOM-treated mice mimicked M3R gene ablation. Compared to vehicle controls, mice treated with the M3R antagonist had reduced...

  13. E Durans Strain M4-5 Isolated From Human Colonic Flora Attenuates Intestinal Inflammation

    DEFF Research Database (Denmark)

    Avram-Hananel, L.; Stock, J.; Parlesak, Alexandr

    2010-01-01

    inflammation, and inhibited colonic transcription of proinflammatory immune factors. The effect of therapeutic treatment alone on these parameters was more moderate but still significant. CONCLUSIONS: We conclude that E durans strain M4 to 5 and its metabolic product butyrate induce significant anti...

  14. Iconic end-users in M4H's organic area development

    NARCIS (Netherlands)

    Meijer, Michaël; Peek, Gert- Joost

    2015-01-01

    This paper present the preliminary findings of a recently started research project on the organic redevelopment strategy of the Rotterdam City Ports organization in the MerweVierhavens area (M4H) and its particular context. An overview of the area and roles of the involved actors is given from the p

  15. Terahertz and M4PP conductivity mapping of large area CVD grown graphene films

    DEFF Research Database (Denmark)

    Buron, Jonas Christian Due; Petersen, Dirch Hjorth; Bøggild, Peter;

    We demonstrate mapping of magnitude and variation of the electrical conductance of large area CVD graphene films by terahertz time-domain spectroscopy (THz-TDS) and micro four-point-probe (M4PP). Non-trivial correlations between results obtained with the two techniques are discussed in relation...

  16. Increased cocaine self-administration in M4 muscarinic acetylcholine receptor knockout mice

    DEFF Research Database (Denmark)

    Schmidt, Lene Sørensen; Thomsen, Morgane; Weikop, Pia

    2011-01-01

    Rationale The reinforcing effects of cocaine are mediated by the mesolimbic dopamine system. Behavioral and neurochemical studies have shown that the cholinergic muscarinic M4 receptor subtype plays an important role in regulation of dopaminergic neurotransmission. Objectives Here we investigated...... of drug addiction...

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

    Directory of Open Access Journals (Sweden)

    Udaya S Rangaswamy

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  19. Syntheses, crystal structure and magnetic properties of Rm+nCo5m+3nB2n

    Institute of Scientific and Technical Information of China (English)

    梁敬魁; 陈怡; 陈小龙

    2001-01-01

    The phase relations at the 600℃ and 700℃ isothermal sections of the ternary systems R-Co-B for R= Nd, Pr and R = Sm, Gd respectively were summarized in this paper. For Rm+ n Co5m+3n B2n, two new types ofcompounds R3Co13B2(R=Pr, Nd, Sm, Gd, Dy, Ho, Er, Y) (m=2, n=1) andR5Co19B6(R=Pr, Nd) (m=2,n = 3 ) were synthesized by utilizing the principle of structural combination. Their crystalstructures and easymagnetization direction were determined by X-ray powder diffraction, and structures were refined by the Rietveldmethod. The Curie temperature Tc, saturation magnetization M8 and anisotropic field HA of the new compounds weremeasured using a vibrating-sample magnetometer, an extraction sample magnetometer and M(H) - H curves of samplesin different magnetization directions respectively. The Tc and Ms of Rm + n Co5 m + 3 n B2n increase with increasing values of mat a given n value. HA increases with an increase in n when m is kept invariable. The effects of the substitution of Ni for Co on the magnetic properties of Nd13 Co15- x Nix B2 were also investigated. It was found that TsR decreased monotonously as the concentration of Ni increased, and at x = 3 the easy magnetization direction becomes axial at room temperature. The relations between crystal structure and magnetic properties of Rm + nCo5m+ 3nB2n and the possible routes of synthesizing permanent magnetic materials are also discussed.

  20. Experiment on an Integrated Ricefish Polyculture System (6 Species, 1- 2 fish/m2 in the Mekong Delta

    Directory of Open Access Journals (Sweden)

    Lan, LM.

    2002-01-01

    Full Text Available Our ricefish polyculture (6 species results at two stocking densities (1 and 2 fish/m2 show that: The water quality in a ricefish polyculture system, such as water temperature (29.1 – 29.0 °C, water pH (6.6 – 6.7, water transparency (18.0 – 20.8 cm, dissolved O2 (4.7 – 4.6 ppm, CO2 (22.8 – 23.1 ppm, COD (11.9 – 12.7 ppm, are similar at both densities and acceptable for the 6 tropical fish species. Ammonium and phosphorus concentrations are statistically higher at 1 fish/m2 (0.4 and 0.2 ppm. The primary productivity is similar for both densities (6.5 – 6.8 g O2/m3/day and suitable for fish culture. The phytoplankton biodiversity is relatively high and at the same level for both treatments (74 – 63 taxa, but the densities of phytoplankton, of zooplankton, and the biomass of zoobenthos are lower at the highest density (2 fish/m2, probably due to a higher predation by fish.The fish yield (808 kg/ha at 2 fish/m2 is higher than at 1 fish/m2 (482 kg/ha. The cost ratio benefit (1.84 and the cost ratio profit (1.81 for farm households at 1 fish/m2 are lower than those values at 2 fish/m2 (2.1 and 2.05 respectively. Regarding the aquaculture extension program, the model of the ricefish polyculture (6 species system with the stocking density of 2 fish/m2 could be extended in the rice fields to improve farmer's income in the Mekong delta.

  1. Activation and dynamic network of the M2 muscarinic receptor

    OpenAIRE

    Miao, Yinglong; Nichols, Sara E.; Gasper, Paul M.; Metzger, Vincent T; McCammon, J. Andrew

    2013-01-01

    G-protein-coupled receptors (GPCRs) mediate cellular responses to various hormones and neurotransmitters and are important targets for treating a wide spectrum of diseases. Although significant advances have been made in structural studies of GPCRs, details of their activation mechanism remain unclear. The X-ray crystal structure of the M2 muscarinic receptor, a key GPCR that regulates human heart rate and contractile forces of cardiomyocytes, was determined recently in an inactive antagonist...

  2. Wilson Loops for M2- and M5-brane spaces

    CERN Document Server

    Quijada, Edward

    2015-01-01

    We calculate the quark and anti-quark interaction energy in different positions in spaces generated by $N$ coincident $M2$- and $M5$-branes. We use the Maldacena-Rey-Yee method for calculating this energy as a function of quark-antiquark separation. We obtain the solution for these problems as integrals of the metric elements. For limiting regimes we find simpler solutions for which some potentials exhibit a confinement behavior.

  3. The BIOPAN experiment MARSTOX II of the FOTON M-3 mission

    Science.gov (United States)

    Rettberg, P.; Moeller, R.; Rabbow, E.; Panitz, C.; Horneck, G.; Meyer, C.; Lammer, H.; Douki, T.; Cadet, J.

    2008-09-01

    The experiment MARSTOX II on FOTON M-3 mission (September 14 - 26, 2007) was a further step in the study of the Responses of Organisms to the Martian Environment (ROME) which already started with first ground-based experiments in Mars simulation chambers and with the space experiment MARSTOX I, flown in 2005 in the ESA facility BIOPAN (Fig. 1) on FOTON M-2. The survivability of bacterial spores of B. subtilis, a well-characterized model system for highly resistant microorganisms, was investigated under the extreme environmental conditions as they exist on the surface of Mars. By use of exterrestrial UV radiation and cut-off filters the photoprotection and potential UV-phototoxicity of different minerals of the Martian soil were investigated.In MARSTOX II two further aspects were addressed (i) the influence of different concentrations of dust in the Martian atmosphere, which change the solar irradiance on the surface significantly compared to vacuum exposure under the same conditions (experiment parts 'DUST MARS' and 'DUST SPACE'), and (ii) the survivability of spores under martian atmosphere and pressure exposed to a mars-like spectral irradiance compared to vacuum exposure under the same conditions (experiment parts 'MIXED MARS' and 'MIXED SPACE') (Fig. 2 and 3). After exposure to space during the FOTON M-3 mission the sample analysis was performed at CEA in Grenoble, F, and at DLR in Cologne, D, together with parallel samples from the corresponding ground control experiment performed in the space simulation facilities at DLR. As biological endpoints in these investigations survival and UV-induced DNAphotoproducts were analysed.From the results of MARSTOX II the following conclusions can be drawn: (i) Spores mixed with martian soil analogue are protected only to a low degree against UV radiation. The protective effect of several defined layers of spores mixed with Martian soil analogue were quantified. (ii) The two investigated martian soil analogues, MRS07 (47

  4. Exception Processing of Cortex-M3%Cortex-M3的异常处理机制研究

    Institute of Scientific and Technical Information of China (English)

    方安平; 蔡俊宇

    2009-01-01

    详细阐述Cortex-M3异常的分类、优先级、进入和退出,以及在Cortex-M3异常处理机制中使用的新技术--迟到(late-arriving)和尾链(tail-chaining);最后,比较Cortex-M3和ARM7异常控制机制的区别,并量化分析迟到和尾链技术在异常处理中的优越性.

  5. VizieR Online Data Catalog: M4 Core Project with HST. Radial velocities (Malavolta+, 2015)

    Science.gov (United States)

    Malavolta, L.; Piotto, G.; Bedin, L. R.; Sneden, C.; Nascimbeni, V.; Sommariva, V.

    2016-07-01

    The spectra for our project were originally used by Sommariva et al. (2009A&A...493..947S) to study the internal velocity dispersion of M4 and to search for spectroscopic binaries. A total of 2771 stars covering colour-magnitude diagram (CMD) positions from the upper RGB to about 1mag fainter than the main-sequence turnoff (TO) luminosity were observed between 2003 and 2009, including 306 new spectra obtained in 2009 and targeting MS stars already observed in the previous epochs. Determination of the M 4 velocity dispersion and binary star fraction were the prime motivators for obtaining these data. Therefore nearly all stars were observed at least twice, and three or more spectra were obtained for nearly 40 per cent of the sample. (2 data files).

  6. M4C9 +(M = Ti, V): New gas phase clusters

    Indian Academy of Sciences (India)

    R Selvan; L Gowrishankar; T Pradeep

    2001-10-01

    New metal-carbon clusters, M4C9 +(M = Ti, V), generated using a combined thermal arc discharge evaporation set-up, have been studied with quadrupole mass spectrometry. Reactivities of these clusters have been investigated by means of association reactions with H2O. Metal-carbon clusters of other compositions have also been studied. We speculate on the mechanism of formation of larger metal-carbon clusters.

  7. Hypoplastic acute myeloid leukemia-M4: A rare case report

    Directory of Open Access Journals (Sweden)

    Harsh Kumar

    2016-01-01

    Full Text Available Hypocellular acute myeloid leukemia (AML is defined as AML with bone marrow cellularity <20%. Hypocellular AML is an infrequent entity. Its frequency ranges between 5% and 12% of all cases of AML. Hypocellular variants of acute leukemia almost always have a myeloid phenotype and usually develop secondary to radiation or chemotherapy. We report a rare case of Hypocellular AML-M4 occurring in a 60-year-old woman who was incidentally found to be positive for HIV.

  8. A Business Case Analysis of the M4/AR-15 Market

    Science.gov (United States)

    2015-09-01

    market . The market analysis was conducted to fill missing gaps on the M4/AR-15 market size, customer demographics , and supplier base. Data was collected...Wesson, 2012). The article also provides data on the rapid growth in the modern sporting rifle market segment . Peters (2012) cites a Freedom Group...types of products generally manufactured in each market . The four main market segments are Small Arms (which will be considered the “Gun segment

  9. Simulation of VANAM M3 test using MELCOR 1.8.3

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Sung Won; Kim, Hee Dong [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1996-07-01

    A standard problem is defined as a comparison between experimental and analytical results in the field of reactor safety research. The detailed comparison of the data permits conclusions for the reliability and precision of computer simulations of postulated accidents and contributions to the development and improvement of reactor safety computer codes. Following a suggestion of the Federal Republic of Germany, the OECD-CSNI agreed to offer the experiment VANAM M3 at the Battelle Model Containment (BMC), an experiment on thermohydraulics and aerosol behavior in a containment, as International Standard Problem No. 37 (ISP 37). The general objectives of the ISP 37 are to analyse the thermohydraulics of a containment atmosphere and the distribution and settlement of aerosol after a high pressure path with depressurization by pressurizer relief valve discharge. Steam condensation at the aerosol particles(condensation in volume) is enhanced by the hygroscopic properties of the aerosol materials, even in case of limited steam supply. The originally small, low-density NaOH particles are converted to solution droplets by steam condensation, the increasing droplet mass significantly enhancing aerosol depletion by gravity settlement. As a result, higher depletion rate have been obtained for the NaOH aerosol than for the SnO{sub 2} aerosol in M2. The MELCOR code, version 1.8.3, has been used for the simulation of this experiment, and the results are compared with the results of other calculations at GRS. The objectives of this report are to contribute to the efficient use of MELCOR code and understanding of the aerosol behavior. 12 tabs., 19 figs., 11 refs. (Author).

  10. The M4RIE library for dense linear algebra over small fields with even characteristic

    CERN Document Server

    Albrecht, Martin R

    2011-01-01

    In this work, we present the M4RIE library which implements efficient algorithms for linear algebra with dense matrices over GF(2^e) for 2 <= 2 <= 10. As the name of the library indicates, it makes heavy use of the M4RI library both directly (i.e., by calling it) and indirectly (i.e., by using its concepts). We provide an open-source GPLv2+ C library for efficient linear algebra over GF(2^e) for e small. In this library we implemented an idea due to Bradshaw and Boothby which reduces matrix multiplication over GF(p^k) to a series of matrix multiplications over GF(p). Furthermore, we propose a caching technique - Newton-John tables - to avoid finite field multiplications which is inspired by Kronrod's method ("M4RM") for matrix multiplication over GF(2). Using these two techniques we provide asymptotically fast triangular solving with matrices (TRSM) and PLE-based Gaussian elimination. As a result, we are able to significantly improve upon the state of the art in dense linear algebra over GF(2^e) with 2 ...

  11. Abundances in a sample of turnoff and subgiant stars in NGC 6121 (M4)

    CERN Document Server

    Spite, Monique; Gallagher, Andrew J; Monaco, Lorenzo; Bonifacio, Piercarlo; Caffau, Elisabetta; Villanova, Sandro

    2016-01-01

    {The aim of this work is to investigate the relations between the abundances of different elements in the globular cluster M4, selected for its uniform deficiency of iron, to explore the best models explaining the pattern of these observed abundances. Moreover, in turnoff stars, the abundances of the elements are not suspected to be affected by internal mixing. In M4, using low and moderate resolution spectra obtained for 91 turnoff (and subgiant) stars with the ESO FLAMES-Giraffe spectrograph, we have extended previous measurements of abundances (of Li, C and Na) to other elements (C, Si, Ca, Sr and Ba), using model atmosphere analysis. We have also studied the influence of the choice of the microturbulent velocity. Firstly, the peculiar turnoff star found to be very Li-rich in a previous paper does not show any other abundance anomalies relative to the other turnoff stars in M4. ~Secondly, an anti-correlation between C and Na has been detected, the slope being significative at more than $3\\sigma$. This rela...

  12. M2-Branes in N = 3 Harmonic Superspace

    Directory of Open Access Journals (Sweden)

    E. Ivanov

    2010-01-01

    Full Text Available We give a brief account of the recently proposed N = 3 superfield formulation of the N = 6, 3D superconformal theory of Aharony et al (ABJM describing a low-energy limit of the system of multiple M2-branes on the AdS4×S7/Zk background. This formulation is given in harmonic N = 3 superspace and reveals a number of surprising new features. In particular, the sextic scalar potential of ABJM arises at the on-shell component level as the result of eliminating appropriate auxiliary fields, while there is no explicit superpotential at the off-shell superfield level.

  13. M2-branes and AdS/CFT

    CERN Document Server

    Klebanov, Igor R

    2009-01-01

    These notes provide a brief introduction to the ABJM theory, the level k U(N) x U(N) superconformal Chern-Simons matter theory which has been conjectured to describe N coincident M2-branes. We discuss its dual formulation in terms of M-theory on AdS_4 x S^7/Z_k and review some of the evidence in favor of the conjecture. We end with a brief discussion of the important role played by the monopole operators.

  14. Superconformal M2-branes and generalized Jordan triple systems

    CERN Document Server

    Nilsson, Bengt E W

    2008-01-01

    Three-dimensional conformal theories with six supersymmetries and SU(4) R-symmetry describing stacks of M2-branes are here proposed to be related to generalized Jordan triple systems. Writing the four-index structure constants in an appropriate form, the Chern-Simons part of the action immediately suggests a connection to such triple systems. In this note we show that the whole theory with six manifest supersymmetries can be naturally expressed in terms of structure constants of generalized Jordan triple systems. We comment on the associated graded Lie algebra, which corresponds to an extension of the gauge group.

  15. The s-process enrichment of the globular clusters M4 and M22

    Energy Technology Data Exchange (ETDEWEB)

    Shingles, Luke J.; Karakas, Amanda I.; Fishlock, Cherie K.; Yong, David; Da Costa, Gary S.; Marino, Anna F. [Research School of Astronomy and Astrophysics, Australian National University, Canberra, ACT 2611 (Australia); Hirschi, Raphael, E-mail: luke.shingles@anu.edu.au [Institute for the Physics and Mathematics of the Universe (WPI), University of Tokyo, 5-1-5 Kashiwanoha, 277-8583 Kashiwa (Japan)

    2014-11-01

    We investigate the enrichment in elements produced by the slow neutron-capture process (s-process) in the globular clusters M4 (NGC 6121) and M22 (NGC 6656). Stars in M4 have homogeneous abundances of Fe and neutron-capture elements, but the entire cluster is enhanced in s-process elements (Sr, Y, Ba, Pb) relative to other clusters with a similar metallicity. In M22, two stellar groups exhibit different abundances of Fe and s-process elements. By subtracting the mean abundances of s-poor from s-rich stars, we derive s-process residuals or empirical s-process distributions for M4 and M22. We find that the s-process distribution in M22 is more weighted toward the heavy s-peak (Ba, La, Ce) and Pb than M4, which has been enriched mostly with light s-peak elements (Sr, Y, Zr). We construct simple chemical evolution models using yields from massive star models that include rotation, which dramatically increases s-process production at low metallicity. We show that our massive star models with rotation rates of up to 50% of the critical (break-up) velocity and changes to the preferred {sup 17}O(α, γ){sup 21}Ne rate produce insufficient heavy s-elements and Pb to match the empirical distributions. For models that incorporate asymptotic giant branch yields, we find that intermediate-mass yields (with a {sup 22}Ne neutron source) alone do not reproduce the light-to-heavy s-element ratios for M4 and M22, and that a small contribution from models with a {sup 13}C pocket is required. With our assumption that {sup 13}C pockets form for initial masses below a transition range between 3.0 and 3.5 M {sub ☉}, we match the light-to-heavy s-element ratio in the s-process residual of M22 and predict a minimum enrichment timescale of between 240 and 360 Myr. Our predicted value is consistent with the 300 Myr upper limit age difference between the two groups derived from isochrone fitting.

  16. A comprehensive survey of M(2)AX phase elastic properties.

    Science.gov (United States)

    Cover, M F; Warschkow, O; Bilek, M M M; McKenzie, D R

    2009-07-29

    M(2)AX phases are a family of nanolaminate, ternary alloys that are composed of slabs of transition metal carbide or nitride (M(2)X) separated by single atomic layers of a main group element. In this combination, they manifest many of the beneficial properties of both ceramic and metallic compounds, making them attractive for many technological applications. We report here the results of a large scale computational survey of the elastic properties of all 240 elemental combinations using first-principles density functional theory calculations. We found correlations revealing the governing role of the A element and its interaction with the M element on the c axis compressibility and shearability of the material. The role of the X element is relatively minor, with the strongest effect seen in the in-plane constants C(11) and C(12). We identify several elemental compositions with extremal properties such as W(2)SnC, which has by far the lowest value of C(44), suggesting potential applications as a high-temperature dry lubricant.

  17. Putative M2 muscarinic receptors of rat heart have high affinity for organophosphorus anticholinesterases

    Energy Technology Data Exchange (ETDEWEB)

    Silveira, C.L.; Eldefrawi, A.T.; Eldefrawi, M.E. (Univ. of Maryland, Baltimore (USA))

    1990-05-01

    The M2 subtype of muscarinic receptor is predominant in heart, and such receptors were reported to be located in muscles as well as in presynaptic cholinergic and adrenergic nerve terminals. Muscarinic receptors of rat heart were identified by the high affinity binding of the agonist (+)-(3H)cis-methyldioxolane ((3H)CD), which has been used to label a high affinity population of M2 receptors. A single population of sites was detected and (3H)CD binding was sensitive to the M2 antagonist himbacine but much less so to pirenzepine, the M1 antagonist. These cardiac receptors had different sensitivities to NiCl2 and N-ethylmaleimide from brain muscarinic receptors, that were also labeled with (3H)CD and considered to be of the M2 subtype. Up to 70% of the (3H)CD-labeled cardiac receptors had high affinities for several organophosphate (OP) anticholinesterases. (3H)CD binding was inhibited by the nerve agents soman, VX, sarin, and tabun, with K0.5 values of 0.8, 2, 20, and 50 nM, respectively. It was also inhibited by echothiophate and paraoxon with K0.5 values of 100 and 300 nM, respectively. The apparent competitive nature of inhibition of (3H)CD binding by both sarin and paraoxon suggests that the OPs bind to the acetylcholine binding site of the muscarinic receptor. Other OP insecticides had lower potencies, inhibiting less than 50% of 5 nM (3H)CD binding by 1 microM of EPN, coumaphos, dioxathion, dichlorvos, or chlorpyriphos. There was poor correlation between the potencies of the OPs in reversibly inhibiting (3H)CD binding, and their anticholinesterase activities and toxicities. Acetylcholinesterases are the primary targets for these OP compounds because of the irreversible nature of their inhibition, which results in building of acetylcholine concentrations that activate muscarinic and nicotinic receptors and desensitize them, thereby inhibiting respiration.

  18. The Extreme Type I Planetary Nebula M2-52

    Directory of Open Access Journals (Sweden)

    M. Peña

    2002-01-01

    Full Text Available Se presentan los resultados obtenidos a partir de espectroscopía de alta resolución de la parte central de la nebulosa planetaria bipolar M2-52 que muestra un tipo morfológico Br. Hemos confirmado que M2-52 es una nebulosa de Tipo I de Peimbert, con un espectro rico en líneas de alto y bajo grado de ionización y un fuerte enriquecimiento de He y N. La composición química del gas ionizado es: He/H = 0:165 0:010, O/H = (2:6 0:5 x 10_4, N/O = 2:3 0:3, Ne/O = 0:37 0:10, Ar/O = (9:2 2:0 x 10_3 y S/O > 2:0 x 10_3. La velocidad de expansión de la nebulosa es, en promedio, de 20 2 km s_1 y varía ligeramente dependiendo del ión considerado. Los iones de menor grado de ionización, N+ y S+, muestran vexp _ 18 km s_1, O++ y He+ muestran vexp _ 20 km s_1, en tanto que He++ y H+ muestran vexp _ 22 km s_1. Es posible que la zona de N+ y S+ esté siendo frenada por el anillo de material molecular encontrado alrededor de la estrella.

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

    Energy Technology Data Exchange (ETDEWEB)

    Naghdi, M. [University of Ilam, Department of Physics, Faculty of Basic Sciences, Ilam (Iran, Islamic Republic of)

    2014-03-15

    We introduce some (anti-) M/D-branes through turning on the corresponding field strengths of the 11- and 10-dimensional supergravity theories over AdS{sub 4} x M{sup 7} {sup vertical} {sup stroke} {sup 6} spaces, where we use S{sup 7}/Z{sub k} and CP{sup 3} for the internal spaces. Indeed, when we add M2/D2-branes on the same directions with the near horizon branes of the Aharony-Bergman-Jafferis- Maldacena model, all symmetries and supersymmetries are preserved trivially. In this case, we obtain a localized object just in the horizon. This normalizable bulk massless scalar mode is a singlet of SO(8) and SU(4) x U(1), and it agrees with a marginal boundary operator of the conformal dimension of Δ{sub +} = 3. However, after performing a special conformal transformation, we see that the solution is localized in the Euclideanized AdS{sub 4} space and is attributable to the included anti-M2/D2-branes, which are also necessary to ensure that there is no back-reaction. The resultant theory now breaks all N = 8, 6 supersymmetries to N = 0, while the other symmetries are so preserved. The dual boundary operator is then set up from the skew-whiffing of the representations 8s and 8v for the supercharges and scalars, respectively, while the fermions remain fixed in 8c of the original theory. Besides, we also address another alternate bulk to boundary matching procedure through turning on one of the gauge fields of the full U(N){sub k} x U(N){sub -k} gauge group along the same lines with a similar situation to the one faced in the AdS{sub 5}/CFT{sub 4} correspondence. The latter approach covers the difficulty already faced with in the bulk-boundary matching procedure for k = 1, 2 as well. (orig.)

  20. M4FT-15LL0806062-LLNL Thermodynamic and Sorption Data FY15 Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    Zavarin, M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Wolery, T. J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2015-08-31

    This progress report (Milestone Number M4FT-15LL0806062) summarizes research conducted at Lawrence Livermore National Laboratory (LLNL) within Work Package Number FT-15LL080606. The focus of this research is the thermodynamic modeling of Engineered Barrier System (EBS) materials and properties and development of thermodynamic databases and models to evaluate the stability of EBS materials and their interactions with fluids at various physicochemical conditions relevant to subsurface repository environments. The development and implementation of equilibrium thermodynamic models are intended to describe chemical and physical processes such as solubility, sorption, and diffusion.

  1. M4FT-16LL080302052-Update to Thermodynamic Database Development and Sorption Database Integration

    Energy Technology Data Exchange (ETDEWEB)

    Zavarin, Mavrik [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Glenn T. Seaborg Inst.. Physical and Life Sciences; Wolery, T. J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Akima Infrastructure Services, LLC; Atkins-Duffin, C. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Global Security

    2016-08-16

    This progress report (Level 4 Milestone Number M4FT-16LL080302052) summarizes research conducted at Lawrence Livermore National Laboratory (LLNL) within the Argillite Disposal R&D Work Package Number FT-16LL08030205. The focus of this research is the thermodynamic modeling of Engineered Barrier System (EBS) materials and properties and development of thermodynamic databases and models to evaluate the stability of EBS materials and their interactions with fluids at various physico-chemical conditions relevant to subsurface repository environments. The development and implementation of equilibrium thermodynamic models are intended to describe chemical and physical processes such as solubility, sorption, and diffusion.

  2. Abundances in a sample of turnoff and subgiant stars in NGC 6121 (M 4)

    Science.gov (United States)

    Spite, M.; Spite, F.; Gallagher, A. J.; Monaco, L.; Bonifacio, P.; Caffau, E.; Villanova, S.

    2016-10-01

    Context. The stellar abundances observed in globular clusters show complex structures, currently not yet understood. Aims: The aim of this work is to investigate the relations between the abundances of different elements in the globular cluster M 4, selected for its uniform deficiency of iron, to explore the best models explaining the pattern of these observed abundances. Moreover, in turnoff stars, the abundances of the elements are not suspected to be affected by internal mixing. Methods: In M 4, using low and moderate resolution spectra obtained for 91 turnoff (and subgiant) stars with the ESO FLAMES-Giraffe spectrograph, we have extended previous measurements of abundances (of Li, C and Na) to other elements (C, Si, Ca, Sr and Ba), using model atmosphere analysis. We have also studied the influence of the choice of the microturbulent velocity. Results: Firstly, the peculiar turnoff star found to be very Li-rich in a previous paper does not show any other abundance anomalies relative to the other turnoff stars in M 4. Secondly, an anti-correlation between C and Na has been detected, the slope being significative at more than 3σ. This relation between C and Na is in perfect agreement with the relation found in giant stars selected below the RGB bump. Thirdly, the strong enrichment of Si and of the neutron-capture elements Sr and Ba, already observed in the giants in M 4, is confirmed. Finally, the relations between Li, C, Na, Sr and Ba constrain the enrichment processes of the observed stars. Conclusions: The abundances of the elements in the turnoff stars appear to be compatible with production processes by massive AGBs, but are also compatible with the production of second generation elements (like Na) and low Li produced by, for example, fast rotating massive stars. Based on observations collected at the European Organisation for Astronomical Research in the Southern Hemisphere under ESO programme 085.D-0537(A).Full Tables 3 and 4 are only available at the

  3. [Effective method of isolating M4-lactate dehydrogenase from rat liver].

    Science.gov (United States)

    Gorbach, Z V; Maglysh, S S; Konovalenko, O V

    1984-01-01

    Lactate dehydrogenase M4-isoform in the homogeneous state was isolated from the rat liver by successive application of sulphate-ammonium fractionation, phosphocellulose ion-exchange chromatography with high-affinity elution of 1 mM NADH and subsequent hydroxyl apatite fractionation. The method permits obtaining the preparation amounts of the enzymic protein with yield 37.5%, specific activity 386.8 units per 1 mg of protein. It is established that 1 mM NAD+, 10 mM pyruvate and 100 mM lactate are also effective as agents of the selective enzyme elution.

  4. Different Characteristics of the Bright Branches of the Globular Clusters M3 and M13

    CERN Document Server

    Cho, D H; Jeon, Y B; Sim, K J; Cho, Dong-Hwan; Lee, Sang-Gak; Jeon, Young-Beom; Sim, Kyung Jin

    2005-01-01

    We carried out wide-field BVI CCD photometric observations of the GCs M3 and M13 using the BOAO 1.8 m telescope equipped with a 2K CCD. We present CMDs of M3 and M13. We have found AGB bumps at V = 14.85 for M3 at V = 14.25 for M13. It is found that AGB stars in M3 are more concentrated near the bump, while those in M13 are scattered along the AGB sequence. We identified the RGB bump of M3 at V = 15.50 and that of M13 at V = 14.80. We have estimated the ratios R and R2 for M3 and M13 and found that of R for M3 is larger than that for M13 while R2's for M3 and M13 are similar when only normal HB stars are used in R and R2 for M13. However, we found that R's for M3 and M13 are similar while R2 for M3 is larger than that for M13 when all the HB stars are included in R and R2 for M13. We have compared the observed RGB LFs of M3 and M13 with the theoretical RGB LF of Bergbusch & VandenBerg at the same radial distances from the cluster centers as used in R and R2 for M3 and M13. We found "extra stars" belonging...

  5. New examples of metalloaromatic Al-clusters: (Al4M4)Fe(CO)3 (M=Li, Na and K) and (Al4M4)2Ni: Rationalization for possible synthesis

    CERN Document Server

    Datta, A; Datta, Ayan; Pati, Swapan K.

    2005-01-01

    Ab-initio calculations reveal that all-metal antiaromatic molecules like Al4M4 (M=Li, Na and K) can be stabilized in half-sandwich complex: (Al4M4)Fe(CO)3 and full-sandwich complexes of the type: (Al4M4)2Ni. The formation of the full-sandwich complex [(Al4M4)2Ni] from its organometallic precursor depends on the stability of the organic-inorganic hybrid (C4H4) Ni (Al4Li4).

  6. Second Parameter Effects in and between M3 and Palomar 3

    CERN Document Server

    Catelan, M; Ferraro, F R

    2001-01-01

    We study the globular clusters M3 and Palomar 3 as a "second parameter (2ndP) pair," showing that: i) M3 has a surprisingly strong *internal* 2ndP; ii) The dispersion in mass on the Pal 3 horizontal branch (HB) is intrinsically very small, leading to the most apparent differences in HB morphology between M3 and Pal 3; iii) Ignoring the difference in HB mass dispersion between M3 and Pal 3, their relative HB types can be accounted for by a fairly small difference in age, of order 0.5-1 Gyr.

  7. Multiple populations along the asymptotic giant branch of the globular cluster M4

    Science.gov (United States)

    Lardo, C.; Salaris, M.; Savino, A.; Donati, P.; Stetson, P. B.; Cassisi, S.

    2017-04-01

    Nearly all Galactic globular clusters host stars that display characteristic abundance anticorrelations, like the O-rich/Na-poor pattern typical of field halo stars, together with O-poor/Na-rich additional components. A recent spectroscopic investigation questioned the presence of O-poor/Na-rich stars amongst a sample of asymptotic giant branch (AGB) stars in the cluster M4, at variance with the spectroscopic detection of a O-poor/Na-rich component along both the cluster red giant branch (RGB) and horizontal branch. This is contrary to what is expected from the cluster horizontal branch morphology and horizontal branch stellar evolution models. Here, we have investigated this issue by employing the CUBI = (U - B) - (B - I) index, that previous studies have demonstrated to be very effective in separating multiple populations along both the RGB and AGB sequences. We confirm previous results that the RGB is intrinsically broad in the V-CUBI diagram, with the presence of two components that nicely correspond to the two populations identified by high-resolution spectroscopy. We find that AGB stars are distributed over a wide range of CUBI values, in close analogy with what is observed for the RGB, demonstrating that the AGB of M4 also hosts multiple stellar populations.

  8. The discovery of an M4+T8.5 binary system

    CERN Document Server

    Burningham, Ben; Leggett, S K; Tinney, C G; Liu, M C; Homeier, D; West, A A; Day-Jones, A; Huélamo, N; Dupuy, T J; Zhang, Z; Murray, D N; Lodieu, N; Navascues, D Barrado y; Folkes, S; Galvez-Ortiz, M C; Jones, H R A; Lucas, P W; Calderon, M Morales; Tamura, M

    2009-01-01

    We report the discovery of a T8.5 dwarf, which is a companion to the M4 dwarf Wolf 940. At a distance of 12.50 (+0.75,-0.67) pc, the angular separation of 32arcsec corresponds to a projected separation of 400 AU. The M4 primary displays no Halpha emission, and we apply the age-activity relations of West et al. to place a lower limit on the age of the system of 3.5 Gyr. Weak Halpha absorption suggests some residual activity and we estimate an upper age limit of 6 Gyr. We apply the relations of Bonfils et al for V-Ks and M_Ks to determine the metallicity, [Fe/H] = -0.06 +/- 0.20 for Wolf~940A, and by extension the T8.5 secondary, Wolf 940B. We have obtained JHK NIRI spectroscopy and JHKL' photometry of Wolf 940B, and use these data, in combination with theoretical extensions, to determine its bolometric flux, Fbol = 1.75 +/- 0.18 E-16 Wm^-2 and thus its luminosity log(L*/Lsun) = -6.07 +/- 0.04. Using the age constraints for the system, and evolutionary structural models of Baraffe et al. we determine Teff = 570...

  9. An aluminium tool for multiple stellar generations in the globular clusters 47 Tuc and M 4

    CERN Document Server

    Carretta, Eugenio; Bragaglia, Angela; D'Orazi, Valentina; Lucatello, Sara

    2012-01-01

    We present aluminium abundances for a sample of about 100 red giant stars in each of the Galactic globular clusters 47 Tuc (NGC 104) and M 4 (NGC 6121). We have derived homogeneous abundances from intermediate-resolution FLAMES/GIRAFFE spectra. Aluminium abundances are from the strong doublet Al I at 8772-8773 A as in previous works done for giants in NGC 6752 and NGC 1851, and nitrogen abundances are extracted from a large number of features of the CN molecules, by assuming a suitable carbon abundance. We added previous homogeneous abundances of O and Na and newly derived abundances of Mg and Si for our samples of 83 stars in M 4 and 116 stars in 47 Tuc to obtain the full set of elements from proton-capture reactions produced by different stellar generations in these clusters. By simultaneously studying the Ne-Na and Mg-Al cycles of H-burning at high temperature our main aims are to understand the nature of the polluters at work in the first generation and to ascertain whether the second generation of cluste...

  10. Sodium-Oxygen anticorrelation among Horizontal Branch Stars in the Globular Cluster M4

    CERN Document Server

    Marino, A F; Milone, A P; Piotto, G; Lind, K; Geisler, D; Stetson, P B

    2010-01-01

    The horizontal branch (HB) morphology of globular clusters (GC) is mainly governed by metallicity. The second parameter problem, well known since the 60's, states that metallicity alone is not enough to describe the observed HB morphology of many GCs. Despite many efforts to resolve this issue, the second parameter phenomenon still remains without a satisfactory explanation. We have analyzed blue, red-HB, and RR-Lyrae stars in the GC M4 and studied their Fe, Na, and O abundances. Our goal is to investigate possible connections between the bimodal HB of M4 and the chemical signatures of the two stellar populations recently discovered among red giants of this cluster. We obtained FLAMES-UVES/GIRAFFE spectra of a sample of 22 stars covering the HB from the red to the blue region. While iron has the same abundance in both the red and blue-HB segment, the red-HB is composed of stars with scaled-solar sodium abundances, while the blue-HB stars are all sodium enhanced and oxygen depleted. The RR-Lyrae are Na-poor, a...

  11. Expression of ETV6 rearrangement in a subject with acute myeloid leukemia-M4Eo

    Institute of Scientific and Technical Information of China (English)

    GAO Na; LI Zhi-hong; DING Bu-tong; CHEN Yun; WANG Yun-shan; QIAO Ying; GUO Nong-jian

    2008-01-01

    @@ Acute myeloid leukemia (AML) M4Eo type is a hematological malignancy with abnormal eosinophilia,which is often accompanied by inv(16).The Ets variant gene 6 (ETV6),mapped to 12p13,is an ETS family transcription factor that is essential for hematopoietic processes,1 The ETV6 gene-involved chromosomal translocations have been found in many hematological malignancies characterized by fusing to a number of different partner genes;mainly coding for tyrosine kinases or transcription factors which are important for the initiation,progress and prognosis of disease.2 In particular,the ETV6 gene has been reported to be fused to ABL in acute lymphocytic leukemias (ALL),3 and chronic myeloid leukemia (CML).4 However,there have been few domestic reports of ETV6 fusion genes,especially in cases of acute leukemia.We investigated 3 cases of AML-M4Eo patients using Split-signal Fluorescence in situ hybridization (FISH) and found one case with a translocation between 12p13 and 1q25 co-occurring with an inv(16).The ETV6/ARG (ABL-related gene) fusion transcript was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR).This is the report of ARG involvement in a translocation in a human malignancy.

  12. X-ray Sources and their Optical Counterparts in the Globular Cluster M4

    CERN Document Server

    Bassa, C; Homer, L; Verbunt, F; Gaensler, B M; Lewin, W H G; Anderson, S F; Margon, B; Kaspi, V M; Van der Klis, M; Bassa, Cees; Pooley, David; Homer, Lee; Verbunt, Frank; Gaensler, Bryan M.; Lewin, Walter H. G.; Anderson, Scott F.; Margon, Bruce; Kaspi, Victoria M.; Klis, Michiel van der

    2004-01-01

    We report on the Chandra X-ray Observatory ACIS-S3 imaging observation of the Galactic globular cluster M4 (NGC 6121). We detect 12 X-ray sources inside the core and 19 more within the cluster half-mass radius. The limiting luminosity of this observation is Lx~10e29 erg/sec for sources associated with the cluster, the deepest X-ray observation of a globular cluster to date. We identify 6 X-ray sources with known objects and use ROSAT observations to show that the brightest X-ray source is variable. Archival data from the Hubble Space Telescope allow us to identify optical counterparts to 16 X-ray sources. Based on the X-ray and optical properties of the identifications and the information from the literature, we classify two (possibly three) sources as cataclysmic variables, one X-ray source as a millisecond pulsar and 12 sources as chromospherically active binaries. Comparison of M4 with 47 Tuc and NGC 6397 suggests a scaling of the number of active binaries in these clusters with the cluster (core) mass.

  13. Monte Carlo Simulations of Star Clusters - V. The globular cluster M4

    CERN Document Server

    Giersz, Mirek

    2008-01-01

    We describe Monte Carlo models for the dynamical evolution of the nearby globular cluster M4. The code includes treatments of two-body relaxation, three- and four-body interactions involving primordial binaries and those formed dynamically, the Galactic tide, and the internal evolution of both single and binary stars. We arrive at a set of initial parameters for the cluster which, after 12Gyr of evolution, gives a model with a satisfactory match to the surface brightness profile, the velocity dispersion profile, and the luminosity function in two fields. We describe in particular the evolution of the core, and find that M4 (which has a classic King profile) is actually a post-collapse cluster, its core radius being sustained by binary burning. We also consider the distribution of its binaries, including those which would be observed as photometric binaries and as radial-velocity binaries. We also consider the populations of white dwarfs, neutron stars, black holes and blue stragglers, though not all channels ...

  14. Design Essentials of 80 m3 Diluted Acetaldehyde Storage Tank%浅谈80 m3稀乙醛储槽设计要点

    Institute of Scientific and Technical Information of China (English)

    白春山; 刘文元

    2009-01-01

    Combination 80 m3 thin acetaldehyde tank design, the paper focused on low-pressure tank-top cans bearing ring, tank walls, tank top and anchor set design and the method of calculating and comparing the general design of storage tanks were introduced.%结合80 m3稀乙醛储槽的设计,着重介绍低压储罐罐顶承压环、罐壁、罐顶以及锚栓设置的设计及其计算方法,并与一般储罐设计进行比较.

  15. Effects of Modulating M3 Muscarinic Receptor Activity on Azoxymethane-Induced Liver Injury in Mice

    Science.gov (United States)

    Khurana, Sandeep; Jadeja, Ravirajsinh; Twadell, William; Cheng, Kunrong; Rachakonda, Vikrant; Saxena, Neeraj; Raufman, Jean-Pierre

    2013-01-01

    Previously, we reported that azoxymethane (AOM)-induced liver injury is robustly exacerbated in M3 muscarinic receptor (M3R)-deficient mice. We used the same mouse model to test the hypothesis that selective pharmacological modulation of M3R activity regulates the liver injury response. Initial experiments confirmed that giving a selective M3R antagonist, darifenacin, to AOM-treated mice mimicked M3R gene ablation. Compared to vehicle controls, mice treated with the M3R antagonist had reduced survival and increased liver nodularity and fibrosis. We next assessed AOM-induced liver injury in mice treated with a selective M3R agonist, pilocarpine. After pilocarpine treatment, stimulation of post-M3R signaling in the liver was evidenced by ERK and AKT activation. In contrast to the damaging effects of the M3R antagonist, administering pilocarpine to AOM-treated mice significantly attenuated hepatic stellate cell activation, collagen deposition, bile ductule proliferation, and liver fibrosis and nodularity. As anticipated from these findings, livers from pilocarpine-treated mice exhibited reduced expression of key players in fibrosis (α1 collagen, α-smooth muscle actin, TGF-β1, PGDF, TGF-β1R, PGDFR) and decreased mRNA levels for molecules that regulate extracellular matrix formation (TIMP-1, TIMP-2, MMP-2, MMP-13). Cleaved caspase-3, nitrotyrosine and BrdU immunostaining provided evidence that pilocarpine treatment reduced hepatocyte apoptosis and oxidative stress, while increasing hepatocyte proliferation. Collectively, these findings identify several downstream mechanisms whereby M3R activation ameliorates toxic liver injury. These novel observations provide a proof-of-principle that selectively stimulating M3R activation to prevent or diminish liver injury is a therapeutic strategy worthy of further investigation. PMID:23707755

  16. Programmable self-assembly of water-soluble organo-heterometallic cages [M12M'4L12] using 3-(3,5-dimethyl-1H-pyrazol-4-yl)pentane-2,4-dione (H2L).

    Science.gov (United States)

    Chen, Zi-Man; Cui, Yu; Jiang, Xuan-Feng; Tong, Jin; Yu, Shu-Yan

    2017-04-11

    A bifunctional ligand H2L featuring primary (pyrazole) and secondary (acetylacetone) coordination sites was preferentially reacted with dimetallic [M2(NO3)2](NO3)2 linkers at the pyrazolyl end of H2L, giving rise to dimetallic corners. Subsequently, the corners serve as the secondary site with M' to form water-soluble organo-heterometallic [M12M'4L12] cages in a stepwise mode.

  17. Multiwavelength photometry in the Globular Cluster M2

    CERN Document Server

    Dalessandro, E; Lanzoni, B; Ferraro, F R; Schiavon, R; Rood, R T

    2009-01-01

    We present a multiwavelength photometric analysis of the globular cluster M2. The data-set has been obtained by combining high-resolution (HST/WFPC2 and ACS) and wide-field (GALEX) space observations and ground based (MEGACAM-CFHT, EMMI-NTT) images. The photometric sample covers the entire cluster extension from the very central regions up to the tidal radius and beyond. It allows an accurate determination of the cluster center of gravity and other structural parameters derived from the star count density profile. Moreover we study the BSS population and its radial distribution. A total of 123 BSS has been selected, and their radial distribution has been found to be bimodal (highly peaked in the center, decreasing at intermediate radii and rising outward), as already found in a number of other clusters. The radial position of the minimum of the BSS distribution is consistent with the radius of avoidance caused by the dynamical friction of massive objects over the cluster age. We also searched for gradients in...

  18. Metric 3-Leibniz algebras and M2-branes

    CERN Document Server

    Méndez-Escobar, Elena

    2010-01-01

    This thesis is concerned with superconformal Chern-Simons theories with matter in 3 dimensions. The interest in these theories is two-fold. On the one hand, it is a new family of theories in which to test the AdS/CFT correspondence and on the other, they are important to study one of the main objects of M-theory (M2-branes). All these theories have something in common: they can be written in terms of 3-Leibniz algebras. Here we study the structure theory of such algebras, paying special attention to a subclass of them that gives rise to maximal supersymmetry and that was the first to appear in this context: 3-Lie algebras. In chapter 2, we review the structure theory of metric Lie algebras and their unitary representations. In chapter 3, we study metric 3-Leibniz algebras and show, by specialising a construction originally due to Faulkner, that they are in one to one correspondence with pairs of real metric Lie algebras and unitary representations of them. We also show a third characterisation for six extreme...

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

    Science.gov (United States)

    DeWolfe, Oliver; Henriksson, Oscar; Rosen, Christopher

    2015-06-01

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

  20. Scale-up of industrial biodiesel production to 40 m3using a liquid lipase formulation

    DEFF Research Database (Denmark)

    Price, Jason; Nordblad, Mathias; Martel, Hannah H.

    2016-01-01

    In this work, we demonstrate the scale-up from an 80 L fed-batch scale to 40 m3 along with the design of a 4 m3continuous process for enzymatic biodiesel production catalysed by NS-40116 (a liquid formulation of a modified Thermomyces lanuginosus lipase). Based on the analysis of actual pilot pla...

  1. Residual stress in a M3:2 PM high speed steel; effect of mechanical loading

    DEFF Research Database (Denmark)

    Højerslev, Christian; Odén, Magnus; Carstensen, Jesper V.;

    2001-01-01

    X-ray lattice strains were investigated in an AISI M3:2 PM high-speed steel in the as heat treated condition and after exposure to alternating mechanical load. The volume changes during heat treatment were monitored with dilatometry. Hardened and tempered AISI M3:2 steel consists of tempered lath...

  2. Desulphurization Technology of Flue Gas for Jinan Steel’s 400 m2 Sinter Methane%济钢400 m2烧结机烟气脱硫技术应用

    Institute of Scientific and Technical Information of China (English)

    周亮; 路亮

    2012-01-01

      结合济钢400 m2烧结机烟气特点,应用旋转喷雾干燥法脱硫技术进行脱硫,采用BOT管理模式,确保达到治污减排的目的,实现经济高效运行,吨矿脱硫成本5元,在线监测SO2排放浓度为60 mg/m3左右。%  Combined with the characters of Sintering flue gas on 400 m2 sinter in Jinan Steel,the Spray Drying Absorption to Desulphurization has been applied and the mode of BOT has been adopted, ensuring the purpose of pollution abatement and economic efficiency operation, its cost is 5 Yuan per ton sinter. On-line monitoring of SO2 emission concentration is about 60 mg/m3.

  3. Tracing differential reddening with Diffuse Interstellar Bands. The globular cluster M 4 as a testbed

    CERN Document Server

    Monreal-Ibero, A; Puspitarini, L; Bonifacio, P; Monaco, L

    2015-01-01

    Diffuse interstellar bands (DIBs) are weak absorption features of interstellar origin present in the optical and infrared spectra of stars. Their use as a tool to trace the structure of the Galactic ISM is gaining relevance in the recent years. Here we present an experiment to test our ability to trace differential reddening on the plane of the sky by using the information relative to the DIB at $\\lambda$6614 extracted from the spectra of cool stars. For that we made use of archive FLAMES data of the globular cluster M4, as well as WISE and Planck images for reference. We found a global positive trend between the distribution of the strength of the DIB, as traced by its equivalent width, and the amount of Galactic reddening, as traced by Planck. This result supports the use of DIBs to trace the small scale structure of the Galactic ISM.

  4. Experimental results and numerical simulations for transonic flow over the ONERA M4R model

    Directory of Open Access Journals (Sweden)

    Marius Gabriel COJOCARU

    2013-06-01

    Full Text Available This paper presents a comparison between experimental results of transonic flow over the ONERA M4R calibration model obtained in the INCAS Trisonic wind tunnel and the numerical results. The first purpose, emphasized in this paper is to compare and validate the computational fluid dynamics (CFD techniques for internal transonic flows and to try to find the most suitable numerical methodology for these flows in both accuracy and computational resources. The second purpose is to develop a general method in experimental data correction and flight Reynolds extrapolation, using numerical simulations for both global and local pressure coefficients, as a replacement for the classical vortex lattices based method. That will be developed in a future paper. Besides the computational work, the periodic wind tunnel calibration is required as a quality insurance operation and a numerical model is developed such that future hardware modifications to be included and their impact to be properly considered.

  5. A Case of Acute Myeloid Leukemia (FAB M2 with Inversion 16 Who Presented with Pelvic Myeloid Sarcoma

    Directory of Open Access Journals (Sweden)

    Mustafa Çakan

    2014-01-01

    Full Text Available Acute leukemias are the most common childhood cancer in all age groups. Acute myeloid leukemias (AML constitute about 15–20% of acute leukemias. Fatigability, pallor, fever, and bleeding are the most common presenting symptoms of AML. Hepatosplenomegaly and lymphadenopathy are commonly encountered during physical examination. In rare instances eruptions due to skin involvement and localized tumor masses (myeloid sarcoma may be found. Myeloid sarcoma is especially seen in AML-M2 subtype. By cytogenetic analysis, in AML-M2 subtype t(8;21 is often seen and it is more probable to find inversion 16 in AML-M4Eos subtype. Herein, we present a 15-year-old girl whose initial symptom was abdominal pain for three days and her pathological sign was a large abdominal mass which was verified by imaging studies and diagnosed as myeloid sarcoma by biopsy. On bone marrow examination, she had diagnosis of AML-M2 and by cytogenetic analysis inversion 16 was positive. She was treated with AML-BFM 2004 protocol and she is being followed up in remission on her ninth month of the maintenance therapy.

  6. Interaction of the M4 Segment with Other Transmembrane Segments Is Required for Surface Expression of Mammalian α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors*

    Science.gov (United States)

    Salussolia, Catherine L.; Corrales, Alexandra; Talukder, Iehab; Kazi, Rashek; Akgul, Gulcan; Bowen, Mark; Wollmuth, Lonnie P.

    2011-01-01

    Ionotropic glutamate receptors (GluRs) are ligand-gated ion channels with a modular structure. The ion channel itself shares structural similarity, albeit an inverted membrane topology, with P-loop channels. Like P-loop channels, prokaryotic GluR subunits (e.g. GluR0) have two transmembrane segments. In contrast, eukaryotic GluRs have an additional transmembrane segment (M4), located C-terminal to the ion channel core. However, the structural/functional significance of this additional transmembrane segment is poorly defined. Although topologically similar to GluR0, mammalian AMPA receptor (GluA1) subunits lacking the M4 segment do not display surface expression. This lack of expression is not due to the M4 segment serving as an anchor to the ligand-binding domain because insertion of an artificial polyleucine transmembrane segment does not rescue surface expression. Specific interactions between M4 and the ligand-binding domain are also unlikely because insertion of polyglycines into the linker connecting them has no deleterious effects on function or surface expression. However, tryptophan and cysteine scanning mutagenesis of the M4 segment, as well as recovery of function in the polyleucine background, defined a unique face of the M4 helix that is required for GluR surface expression. In the AMPA receptor structure, this face forms intersubunit contacts with the transmembrane helices of the ion channel core (M1 and M3) from another subunit within the homotetramer. Thus, our experiments show that a highly specific interaction of the M4 segment with an adjacent subunit is required for surface expression of AMPA receptors. This interaction may represent a mechanism for regulating AMPA receptor biogenesis. PMID:21930708

  7. An allosteric enhancer of M(4) muscarinic acetylcholine receptor function inhibits behavioral and neurochemical effects of cocaine

    DEFF Research Database (Denmark)

    Nielsen, Ditte Dencker; Weikop, Pia; Sørensen, Gunnar

    2012-01-01

    The mesostriatal dopamine system plays a key role in mediating the reinforcing effects of psychostimulant drugs like cocaine. The muscarinic M(4) acetylcholine receptor subtype is centrally involved in the regulation of dopamine release in striatal areas. Consequently, striatal M(4) receptors could...... be a novel target for modulating psychostimulant effects of cocaine....

  8. On M3-transition rates in selected odd-mass nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Lombard, R.J. E-mail: lombard@ipno.in2p3.fr; Vdovin, A.I.; Shirikova, N.Yu.; Sushkov, A.V

    2003-06-02

    The reduced probabilities of M3 transitions are studied in five deformed and three spherical or near-spherical odd-mass nuclei. In deformed nuclei, the states linked by M3 transitions are predominantly of single-quasiparticle nature and the calculations are performed taking into account the single-quasiparticle as well as core-polarization terms in the M3-operator. Whereas in {sup 159}Ho, {sup 175}Yb, and {sup 179}Hf the ratio between theoretical and experimental B(M3) values range from 0.5 to 1.4, the situation is much worse in neutron deficient nuclides {sup 179}W and {sup 183}Pt where the theory used can not explain a very sharp drop of the B(M3) values. In the soft nuclei {sup 121}Cs and {sup 207}Po the states connected by M3 transitions are treated as 'quasiparticle x phonon' states. In {sup 113}Sn, the small 'quasiparticle x phonon' components are not sufficient to compensate vanishing contribution of the dominant quasiparticle component, which shares {delta}l forbidden transitions. Thus, on the whole theoretical description of B(M3) with the present simple models seems to be unsatisfactory. It constitutes a challenging problem both at the level of the nuclear structure and the transition operator.

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

    Science.gov (United States)

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

    2016-03-01

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

  10. Cosmic radiation measurements on the Foton-M4 satellite by passive detectors

    Science.gov (United States)

    Strádi, Andrea; Pálfalvi, József K.; Szabó, Julianna; Pázmándi, Tamás; Ivanova, Olga A.; Shurshakov, Vyacheslav A.

    2017-02-01

    The Russian Foton spacecraft was designed to deliver scientific experiments to low Earth orbit and return them safely to the ground for further analysis. During the 44-d Foton-M4 satellite mission in 2014 several passive cosmic ray detectors were exposed outside (in a single holder) and inside (in 4 locations) the recoverable capsule to study the radiation field. The applied thermoluminescent detectors (TLDs) are more sensitive to the particles with LET under 10 keV μm-1, while the solid state nuclear track detectors (SSNTDs) measure the particles having LET over this value. According to our measurements the average internal absorbed dose rate varied between 374-562 μGy/day for low LET radiation and 40-52 μGy/day for high LET radiation. Outside the capsule the dose rate was much higher, 1078 μGy/day for low LET radiation and 75 μGy/day for high LET radiation. Within the paper the obtained absorbed dose rates has been compared to those measured on the previous Foton-M flights, during the Bion-M1 mission and in the Columbus module of the International Space Station.

  11. An extreme paucity of second population AGB stars in the normal globular cluster M4

    CERN Document Server

    MacLean, B T; De Silva, G M; Lattanzio, J; DOrazi, V; Simpson, J D; Momany, Y

    2016-01-01

    Galactic Globular clusters (GCs) are now known to harbour multiple stellar populations, which are chemically distinct in many light element abundances. It is becoming increasingly clear that asymptotic giant branch (AGB) stars in GCs show different abundance distributions in light elements compared to those in the red giant branch (RGB) and other phases, skewing toward more primordial, field-star-like abundances, which we refer to as subpopulation one (SP1). As part of a larger program targeting giants in GCs, we obtained high-resolution spectra for a sample of 106 RGB and 15 AGB stars in Messier 4 (NGC 6121) using the 2dF+HERMES facility on the Anglo-Australian Telescope. In this Letter we report an extreme paucity of AGB stars with [Na/O] > -0.17 in M4, which contrasts with the RGB that has abundances up to [Na/O] =0.55. The AGB abundance distribution is consistent with all AGB stars being from SP1. This result appears to imply that all subpopulation two stars (SP2; Na-rich, O-poor) avoid the AGB phase. Thi...

  12. A White Light Megaflare on the dM4.5e Star YZ CMi

    CERN Document Server

    Kowalski, Adam F; Holtzman, Jon A; Wisniewski, John P; Hilton, Eric J

    2010-01-01

    On UT 2009 January 16, we observed a white light megaflare on the dM4.5e star YZ CMi as part of a long-term spectroscopic flare-monitoring campaign to constrain the spectral shape of optical flare continuum emission. Simultaneous U-band photometric and 3350A-9260A spectroscopic observations were obtained during 1.3 hours of the flare decay. The event persisted for more than 7 hours and at flare peak, the U-band flux was almost 6 magnitudes brighter than in the quiescent state. The properties of this flare mark it as one of the most energetic and longest-lasting white light flares ever to be observed on an isolated low-mass star. We present the U-band flare energetics and a flare continuum analysis. For the first time, we show convincingly with spectra that the shape of the blue continuum from 3350A to 4800A can be represented as a sum of two components: a Balmer continuum as predicted by the Allred et al radiative hydrodynamic flare models and a T ~ 10,000K blackbody emission component as suggested by many pr...

  13. Bimodality of light and s-elements in M4 (NGC 6121)

    CERN Document Server

    Villanova, Sandro

    2011-01-01

    All Globular Clusters (GCs) studied in detail so far host two or more populations of stars. Theoretical models suggest that the second population is formed from gas polluted by processed material produced by massive stars of the first generation. However the nature of the polluter is a matter of strong debate. Several candidates have been proposed: massive main-sequence stars (fast rotating or binaries), intermediate-mass AGB stars, or SNeII. We studied red giant branch (RGB) stars in the GC M4 (NGC 6121) to measure their chemical signature. We confirm the presence of a bimodal population, first discovered by Marino et al. (2008). The two groups have different C,$^{12}$C/$^{13}$C,N,O,Na content, but share the same Li,C+N+O,Mg,Al,Si,Ca,Ti,Cr,Fe,Ni,Zr,Ba and Eu abundance. Quite surprisingly the two groups differ also in their Y abundance. The absence of a spread in $\\alpha$-elements, Eu and Ba makes SNeII and AGB stars unlikely as polluters. On the other hand, massive main-sequence stars can explain the bimodal...

  14. Hubble space telescope observations of white dwarfs in the globular cluster M4

    CERN Document Server

    Richer, H B; Ibata, R A; Stetson, P B; Bell, R A; Bolte, M; Bond, H E; Harris, W E; Hesser, J E; Mandushev, G I; Pryor, C E; Richer, Harvey B; Fahlman, Gregory G; Ibata, Rodrigo A; Stetson, Peter B; Bell, Roger A; Bolte, Michael; Bond, Howard E; Harris, William E; Hesser, James E; Mandushev, Georgi; Pryor, Carlton

    1995-01-01

    With the Wide Field Planetary Camera 2 (WFPC2) on the Hubble Space Telescope, we have discovered in M4 (NGC 6121, C 1620-264) the first extensive sequence of cooling white dwarfs seen in a globular cluster. Adopting a distance modulus of (m-M)_V = 12.65 and a reddening of E(B-V) = 0.37, we show that the sequence, which extends over 9 < M_U < 13, is comprised of white dwarfs of mass \\sim 0.5 M_{\\odot}. The total mass loss from the present turnoff to the white dwarf sequence is 0.31 M_{\\odot} and the intrinsic dispersion in the mean mass appears to be < 0.05 M_{\\odot}. Both the location of the white dwarf cooling sequence in the cluster color-magnitude diagram and the cumulative luminosity function attest to the basic correctness and completeness of the physics in theoretical models for the upper three magnitudes of the observed white dwarf cooling sequence. To test the theory in globular clusters at cooling ages beyond \\sim 3 \\times 10^8 years will require deeper and more complete data.

  15. Molecular Characterization of a Recombinant Manganese Superoxide Dismutase from Lactococcus lactis M4

    Directory of Open Access Journals (Sweden)

    Boon Hooi Tan

    2014-01-01

    Full Text Available A superoxide dismutase (SOD gene of Lactococcus lactis M4 was cloned and expressed in a prokaryotic system. Sequence analysis revealed an open reading frame of 621 bp which codes for 206 amino acid residues. Expression of sodA under T7 promoter exhibited a specific activity of 4967 U/mg when induced with 1 mM of isopropyl-β-D-thiogalactopyranoside. The recombinant SOD was purified to homogeneity by immobilised metal affinity chromatography and Superose 12 gel filtration chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blot analyses of the recombinant SOD detected a molecular mass of approximately 27 kDa. However, the SOD was in dimer form as revealed by gel filtration chromatography. The purified recombinant enzyme had a pI of 4.5 and exhibited maximal activity at 25°C and pH 7.2. It was stable up to 45°C. The insensitivity of this lactococcal SOD to cyanide and hydrogen peroxide established that it was a MnSOD. Although it has 98% homology to SOD of L. lactis IL1403, this is the first elucidated structure of lactococcal SOD revealing active sites containing the catalytic manganese coordinated by four ligands (H-27, H-82, D-168, and H-172.

  16. COOLING METHOD OF SILUMINA CASTINGS AK15M3 AT VERTICAL CENTRIFUGAL CASTING

    Directory of Open Access Journals (Sweden)

    V. Yu. Stecenko

    2013-01-01

    Full Text Available The way of cooling of castings from silumin AK15M3 is developed at the vertical centrifugal casting, enabling to receive bimetallic blanks with high-disperse eutectic and hypereutectic microstructures and minimal allowance for machining.

  17. Complete Genome Sequence of the Novel Leech Symbiont Mucinivorans hirudinis M3T

    OpenAIRE

    Nelson, Michael C.; Bomar, Lindsey; Graf, Joerg

    2015-01-01

    Mucinivorans hirudinis M3T was isolated from the digestive tract of the medicinal leech, Hirudo verbana, and is the type species of a new genus within the Rikenellaceae. Here, we report the complete annotated genome sequence of this bacterium.

  18. Complete Genome Sequence of the Novel Leech Symbiont Mucinivorans hirudinis M3T.

    Science.gov (United States)

    Nelson, Michael C; Bomar, Lindsey; Graf, Joerg

    2015-02-05

    Mucinivorans hirudinis M3(T) was isolated from the digestive tract of the medicinal leech, Hirudo verbana, and is the type species of a new genus within the Rikenellaceae. Here, we report the complete annotated genome sequence of this bacterium.

  19. Reseach on Business Model of M2M Virtual Opertion%M2M虚拟运营的商业模式研究

    Institute of Scientific and Technical Information of China (English)

    景士颖; 乔新春

    2014-01-01

    M2M市场在未来几年拥有较大的增长空间,随着移动转售业务牌照的发放,M2M将成为虚拟运营商可以切入的具备潜力的市场领域之一。探讨M2M虚拟运营的商业模式,分析国际开展M2M虚拟运营的案例,并给出国内开展M2M虚拟运营的建议。%M2M has more market space for growth in the coming years, with the issuance of mobile resale service license, M2M wil become a potential market area where MVNOs can cut into. This article discusses the business model of M2M virtual operation, analyzes the international M2M MVNO business cases, and gives advices to MNOs and MVNOs on how to provide better M2M services in China.

  20. M2e通用流感疫苗的研究进展%Universal influenza vaccine based on the extracellular domain of M2 protein

    Institute of Scientific and Technical Information of China (English)

    花艳红; 王希良

    2009-01-01

    M2基质蛋白是A型流感病毒膜蛋白,在A型流感病毒的生命周期中,M2具有重要的生物学功能,已成为抗病毒药物研究的靶蛋白.其胞外区M2e(M2 eetodomain,M2e)为24个氨基酸残基,该片段在多病毒株中具有极高的保守性.针对M2e产生IgG型抗体能够防止流感病毒引发的死亡,减少动物模型中流感的发病率.了解有关M2e疫苗的研究进展,以及关于M2e作为A型流感疫苗靶抗原的关键问题很重要.%Matrix protein M2 (M2) is the membrane protein of Influenza A with an extracellular domain of 24 amino acid residues, which is strongly conserved across virus strains. M2 plays an important role in the life cy-cle of the Influenza A virus and has been the target of antiviral drugs. IgG subtype antibodies directed against M2e can prevent death from influenza and reduce morbidity in animal models for influenza disease. This review summarizes the findings on M2e vaccine candidates and addresses some key questions about this Influenza A vaccine target.

  1. Posttranslational modifications of human M3 muscarinic acetylcholine receptor: zooming in its functional implications

    OpenAIRE

    Romero Fernández, Wilber

    2011-01-01

    The human M3 muscarinic acetylcholine receptor (M3R) regulates many important physiological roles in the central and peripheral nervous systems, and it is involved in the pathophysiology of several neurodegenerative and autoimmune diseases, representing attractive potential pharmacological target for intervention. However, the lack of structural information on this receptor hampered the development of new potent antagonist with increased selectivity and lower side effects. Such structural inf...

  2. M3B: A coarse grain model for the simulation of oligosaccharides and their water mixtures.

    Science.gov (United States)

    Goddard, William A.; Cagin, Tahir; Molinero, Valeria

    2003-03-01

    Water and sugar dynamics in concentrated carbohydrate solutions is of utmost importance in food and pharmaceutical technology. Water diffusion in concentrated sugar mixtures can be slowed down many orders of magnitude with respect to bulk water [1], making extremely expensive the simulation of these systems with atomistic detail for the required time-scales. We present a coarse grain model (M3B) for malto-oligosaccharides and their water mixtures. M3B speeds up molecular dynamics simulations about 500-1000 times with respect to the atomistic model while retaining enough detail to be mapped back to the atomistic structures with low uncertainty in the positions. The former characteristic allows the study of water and carbohydrate dynamics in supercooled and polydisperse mixtures with characteristic time scales above the nanosecond. The latter makes M3B well suited for combined atomistic-mesoscale simulations. We present the parameterization of M3B force field for water and a family of technologically relevant glucose oligosaccharides, the alpha-(1->4) glucans. The coarse grain force field is completely parameterized from atomistic simulations to reproduce the density, cohesive energy and structural parameters of amorphous sugars. We will show that M3B is capable to describe the helical character of the higher oligosaccharides, and that the water structure in low moisture mixtures shows the same features obtained with the atomistic and M3B models. [1] R Parker, SG Ring: Carbohydr. Res. 273 (1995) 147-55.

  3. Comparison of the space radiation environment at Foton M3 satellite altitudes and on aircraft altitudes for minimum of solar activity

    Science.gov (United States)

    Ploc, Ondrej; Dachev, Tsvetan; Spurny, Frantisek; Tomov, Borislav; Dimitrov, Plamen; Matviichuk, Yury; Bankov, Nikolay

    The space radiation environments at Foton M3 and aircraft altitudes were measured by using of practically equal silicon detector based on a deposited energy spectrometers in the fall of 2007. The aircraft measurements were performed on commercial flights of CSA airlines, while the Foton M3 measurements were inside of the ESA Biopan 6 experiment. Foton M3 orbit was close to circular between 260 and 289 km altitude and about 63° inclination. The relatively high inclination and small shielding of the detector (0.81 g/cm2 ) allow us to observe doses by electrons in the outer radiation belt as high as 2.3 mGy/hour. The comparison of the total GCR deposited doses for the Foton M3 time interval, which coincides with the absolute cycle 23 minimum of the solar activity is about 15% higher than the measured during the Foton M2 satellite doses in 2005. Comparisons of the latitudinal profiles for ISS in 2001, Foton 2 and 3 satellites and aircrafts show that the ratio of doses is as 1:2:3. Aircraft measurements are characterised through average values of exposure during frequent, statistically well based measurements on the routes Prague - New York. Dose absorbed in Si-detector per flight on these routes was about 8% higher in 2007 than in 2005. Different comparisons with the existing models for the radiation environment on aircraft and spacecraft altitudes are presented in the paper also and discussed.

  4. New M+, M3+-arsenates – the framework structures of AgM3+(HAsO42 (M3+ = Al, Ga and M+GaAs2O7 (M+ = Na, Ag

    Directory of Open Access Journals (Sweden)

    Karolina Schwendtner

    2017-05-01

    Full Text Available The crystal structures of hydrothermally synthesized silver(I aluminium bis[hydrogen arsenate(V], AgAl(HAsO42, silver(I gallium bis[hydrogen arsenate(V], AgGa(HAsO42, silver gallium diarsenate(V, AgGaAs2O7, and sodium gallium diarsenate(V, NaGaAs2O7, were determined from single-crystal X-ray diffraction data collected at room temperature. The first two compounds are representatives of the MCV-3 structure type known for KSc(HAsO42, which is characterized by a three-dimensional anionic framework of corner-sharing alternating M3+O6 octahedra (M = Al, Ga and singly protonated AsO4 tetrahedra. Intersecting channels parallel to [101] and [110] host the Ag+ cations, which are positionally disordered in the Ga compound, but not in the Al compound. The hydrogen bonds are relatively strong, with O...O donor–acceptor distances of 2.6262 (17 and 2.6240 (19 Å for the Al and Ga compounds, respectively. The two diarsenate compounds are representatives of the NaAlAs2O7 structure type, characterized by an anionic framework topology built of M3+O6 octahedra (M = Al, Ga sharing corners with diarsenate groups, and M+ cations (M = Ag hosted in the voids of the framework. Both structures are characterized by a staggered conformation of the As2O7 groups.

  5. 3 800 m3耙吸挖泥船的HVAC设计%HVAC design for a 3 800 m3 trailing suction dredger

    Institute of Scientific and Technical Information of China (English)

    戴菁; 赵骊; 陈维茂

    2007-01-01

    挖泥船的需求量与日俱增,逐渐形成系列船型.通过介绍3 800 m3耙吸挖泥船的HVAC设计系统,与以往挖泥船型比较,以及用户的评价,指出该船的空调系统设计思想和方法上的优点,为后续船提供了有益的参考.

  6. Muscarinic M3 receptors on structural cells regulate cigarette smoke-induced neutrophilic airway inflammation in mice

    NARCIS (Netherlands)

    Kistemaker, Loes E.M.; van Os, Ronald P.; Dethmers-Ausema, Albertina; Bos, I. Sophie T.; Hylkema, Machteld N.; van den Berge, Maarten; Hiemstra, Pieter S; Wess, Jürgen; Meurs, Herman; Kerstjens, Huib A.M.; Gosens, Reinoud

    2015-01-01

    Anticholinergics, blocking the muscarinic M-3 receptor, are effective bronchodilators for patients with chronic obstructive pulmonary disease. Recent evidence from M-3 receptor-deficient mice (M3R-/-) indicates that M-3 receptors also regulate neutrophilic inflammation in response to cigarette smoke

  7. 经典再出发--江淮瑞风M4上市%JAC Launch Reifne in Guangzhou

    Institute of Scientific and Technical Information of China (English)

    于占波

    2016-01-01

    Oct. 12, 2016, JAC held a grand ceremony in front of the Guangzhou Tower, the symbolic scene of Guangzhou city, to launch latest new models of Reifne M4. These new four models of Reifne were priced between 99,800 RMB to 129,800 RMB, which indicated that higher cost-effective quality is still the key to market promotion of Reifne M4.

  8. Degradation of 3-phenoxybenzoic acid by a filamentous fungus Aspergillus oryzae M-4 strain with self-protection transformation.

    Science.gov (United States)

    Zhu, Yuanting; Li, Jianlong; Yao, Kai; Zhao, Nan; Zhou, Kang; Hu, Xinjie; Zou, Likou; Han, Xinfeng; Liu, Aiping; Liu, Shuliang

    2016-11-01

    A novel filamentous fungus M-4 strain was isolated from soy sauce koji and identified as Aspergillus oryzae (Collection number: CGMCC 11645) on the basis of morphological characteristics and internal transcribed spacer sequence. M-4 could degrade 80.62 % of 3-phenoxybenzoic acid (3-PBA; 100 mg L(-1)) within 5 days. 3-PBA degradation occurred in accordance with first-order kinetics. The degradation metabolites of 3-PBA were identified through high-performance liquid chromatography-mass spectrometry (HPLC-MS). Relevant enzymatic activities and substrate utilization were also investigated, which indicated that M-4 could effectively degrade the intermediates of 3-PBA. Base on analysis of these metabolites, a novel biochemical pathway for the degradation of 3-PBA was proposed. There exists a mutual transformation between 3-phenoxy-benzyl alcohol and 3-PBA, which was firstly reported about the degradation of 3-PBA and may be attributed to self-protection transformation of M-4; subsequently, 3-PBA was gradually transformed into phenol, 3-hydroxy-5-phenoxy benzoic acid, protocatechuic acid and gallic acid. The safety of M-4 was evaluated via an acute toxicity test in vivo. The biodegradation ability of M-4 without toxic effects reveals that this fungus may be likely to be used for eliminating 3-PBA from contaminated environment or fermented foods.

  9. DEEP NEAR-IR OBSERVATIONS OF THE GLOBULAR CLUSTER M4: HUNTING FOR BROWN DWARFS

    Energy Technology Data Exchange (ETDEWEB)

    Dieball, A. [Argelander Institut für Astronomie, Helmholtz Institut für Strahlen- und Kernphysik, University of Bonn (Germany); Bedin, L. R. [INAF-Osservatorio Astronomico di Padova, Vicolo dell’Osservatorio 5, I-35122 Padova (Italy); Knigge, C. [Physics and Astronomy, University of Southampton, Southampton SO17 1BJ (United Kingdom); Rich, R. M. [Department of Physics and Astronomy, University of California at Los Angeles, Los Angeles, CA 90095-1562 (United States); Allard, F. [Centre de Recherche Astrophysique de Lyon, UMR 5574: CNRS, Université de Lyon, École Normale Supérieure de Lyon, 46 allée d’Italie, F-69364 Lyon Cedex 07 (France); Dotter, A. [Research School of Astronomy and Astrophysics, Australian National University, Canberra, ACT (Australia); Richer, H. [Department of Physics and Astronomy, University of British Columbia, Vancouver, BC, V6T 1Z1 (Canada); Zurek, D., E-mail: adieball@astro.uni-bonn.de [Department of Astrophysics, American Museum of Natural History, New York, NY 10024 (United States)

    2016-01-20

    We present an analysis of deep Hubble Space Telescope (HST)/Wide Field Camera 3 near-IR (NIR) imaging data of the globular cluster (GC) M4. The best-photometry NIR color–magnitude diagram (CMD) clearly shows the main sequence extending toward the expected end of the hydrogen-burning limit and going beyond this point toward fainter sources. The white dwarf (WD) sequence can be identified. As such, this is the deepest NIR CMD of a GC to date. Archival HST optical data were used for proper-motion cleaning of the CMD and for distinguishing the WDs from brown dwarf (BD) candidates. Detection limits in the NIR are around F110W ≈ 26.5 mag and F160W ≈ 27 mag, and in the optical around F775W ≈ 28 mag. Comparing our observed CMDs with theoretical models, we conclude that we have reached beyond the H-burning limit in our NIR CMD and are probably just above or around this limit in our optical–NIR CMDs. Thus, any faint NIR sources that have no optical counterpart are potential BD candidates, since the optical data are not deep enough to detect them. We visually inspected the positions of NIR sources that are fainter than the H-burning limit in F110W and for which the optical photometry did not return a counterpart. We found in total five sources for which we did not get an optical measurement. For four of these five sources, a faint optical counterpart could be visually identified, and an upper optical magnitude was estimated. Based on these upper optical magnitude limits, we conclude that one source is likely a WD, one source could be either a WD or BD candidate, and the remaining two sources agree with being BD candidates. No optical counterpart could be detected for just one source, which makes this source a good BD candidate. We conclude that we found in total four good BD candidates.

  10. Design of USB smart card reader based on Cortex-M3%基于Cortex-M3的智能卡USB读卡器设计

    Institute of Scientific and Technical Information of China (English)

    李冬霞; 张雪庆

    2010-01-01

    为了提高智能卡系统的通信速度和中断响应速度,设计了基于Cortex-M3和USB接口的智能卡读卡器系统.设计中采用具有ARM Cortex-M3内核的STM32F103R6T6等芯片进行相关的硬件设计,分别使用Keil和Visual C++6.0进行读卡器固件子系统程序和PC端子系统驱动程序开发,在此基础上,专门设计了测试程序用于测试系统的正确性和有效性.实验结果表明,该智能卡读卡器系统可实现计算机与智能卡的准确,高效通信.

  11. Renovation of stirring system in 300m3 L-lysine fermentor%300m3赖氨酸发酵罐搅拌系统改造

    Institute of Scientific and Technical Information of China (English)

    王远海

    2012-01-01

    以加强传质混合为目的提出300m3赖氨酸发酵罐搅拌系统改造方案,采用计算流体力学(CFD)数值模拟方法分析了搅拌系统轴功率、流型、传质混合能力,成功指导了搅拌系统改造,在电流增大的情况下,平均单罐产量提高2.44t,平均糖酸转化率提高约1个百分点.%To strengthen mass transfer and mixing for purpose, the reform scheme of stirring system in 300m3 L-lysine fermentor was proposed, CFD (Computational Fluid Dynamics) numerical simulation was used in analysing shaft power, flow pattern, mass transfer mixing ability of the stirring system, when current increased, the fermentation yield and L-lysine acid conversion rate of sugar was 2.44t and about 1% higher than the fermentor which not renovated.

  12. M3-receptor activation counteracts opioid-mediated apneusis, but the apneusis per se is not necessarily related to an impaired M3 mechanism in rats.

    Science.gov (United States)

    Niwa, Yuka; Haji, Akira

    2011-11-07

    Morphine slows the respiratory cycle due to a predominant prolongation of inspiration (apneusis) by postponing the spontaneous termination of inspiration (inspiratory off-switching). The present study investigates whether the morphine-induced apneusis results from impairment of cholinergic mechanisms in the central respiratory network. The efferent discharge was recorded from the phrenic nerve in artificially ventilated and anesthetized rats with vagotomy. All drugs were injected intravenously. The phrenic nerve displayed an augmenting discharge during inspiration and arrest of discharge during expiration in normal condition. Administration of morphine (0.3-10.0mg/kg) dose-dependently provoked apneusis characterized by a long-lasting, plateau inspiratory discharge of the phrenic nerve. It shortened the expiratory duration. Subsequent administration of physostigmine (0.1mg/kg) restored the morphine-induced apneusis to eupnea with a partial recovery of the augmenting inspiratory discharge. This modification of physostigmine was blocked by a non-specific muscarinic antagonist scopolamine (3.0mg/kg), leading to re-prolongation of inspiration. A similar antagonism was affected by an antagonist of M3 cholinergic receptors, 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, 1.0 and 10.0mg/kg) but not by an antagonist of M1 cholinergic receptors, pirenzepine (1.0 and 10.0mg/kg). These results demonstrate that the activation of endogenous M3 cholinergic mechanisms counteracts the morphine-induced apneusis. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Pharmacological and biological properties of CHOm2 cells transfected with M2-receptor suptype%M2受体cDNA转染CHOm2细胞的某些药理学和生物学特性

    Institute of Scientific and Technical Information of China (English)

    胡雅儿; 施菊; 夏宗勤

    1999-01-01

    转染m1、m2m4 Cdna的CHO细胞膜受体与3H-QNB结合,能给出典型的饱和曲线,Hill系数接近1.单位点竞争结合表明,对PZP抑制能力为CHOm1>CHOm4>CHOm2,对METH抑制强度为CHOm2>CHOm4>CHOm1.与药理学PZP对M1受体的亲和力最高和METH对M2的亲和力最高是一致的.CHOm2对Forskolin和Carbachol影响Camp的结果,证明该M受体亚型信号传导系统的完整性,因此是研究M受体亚型与其信号传导的较好模型,也可用于筛选M受体亚型的药物

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

    Science.gov (United States)

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

    2006-01-09

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

  15. AML-M2 with der(18t(1;18(q2?;p11.3 in addition to t(8;21 and del(9q

    Directory of Open Access Journals (Sweden)

    Bakshi Sonal

    2004-01-01

    Full Text Available We report a case of Acute Myeloid Leukemia with clinical features suggestive of AML-M3 and 46,XX,t(8;21,del(9q,der(18t(1;18 karyotype leading to the final diagnosis AML-M2 in light of t(8;21. The Deletion (9q is a frequent secondary anomaly to the t(8;21(q22;q22 in AML-M2. In addition to these two AML-M2 related rearrangements we also observed der(18t(1;18(q2?;p11.3 which may be an unusual rearrangement. This rearrangement resulted into partial trisomy of chromosome #1(q2? without the loss of any part of chromosome 18, morphologically. Rearrangements of long arm of chromosome 1 that result in complete or partial trisomy for 1q mostly involved the region q25-q32, which may confer a proliferation advantage.

  16. The application of pentaprism scanning technology on the manufacturing of M3MP

    Science.gov (United States)

    Qi, Erhui; Hu, Haixiang; Hu, Haifei; Cole, Glen; Luo, Xiao; Ford, Virginia; Zhang, Xuejun

    2016-10-01

    The PSS (pentaprism scanning system) has advantages of simple structure, needless of reference flat, be able of on-site testing, etc, it plays an important role in large flat reflective mirror's manufacturing, especially the high accuracy testing of low order aberrations. The PSS system measures directly the slope information of the tested flat surface. Aimed at the unique requirement of M3MP, which is the prototype mirror of the tertiary mirror in TMT (Thirty Meter Telescope) project, this paper analyzed the slope distribution of low order aberrations, power and astigmatism, which is very important in the manufacturing process of M3MP. Then the sample route lines of PSS are reorganized and new data process algorism is implemented. All this work is done to improve PSS's measure sensitivity of power and astigmatism, for guiding the manufacturing process of M3MP.

  17. M3 User's Manual. Version 3.0

    Energy Technology Data Exchange (ETDEWEB)

    Laaksoharju, Marcus (Geopoint AB, Sollentuna (Sweden)); Skaarman, Erik (Abscondo Utveckling, Bromma (Sweden)); Gomez, Javier B. (Univ. of Zaragoza (Spain). Geochemical modelling Group); Gurban, Ioana (3D Terra (Canada))

    2006-07-15

    This report describes the Multivariate Mixing and Mass balance calculations (M3). This new method and computer code is developed to trace the mixing and reaction processes in the groundwater. The aim of the M3 concept is to decode the often hidden and complex information gathered in the groundwater analytical data. The manual presents shortly the theory and practice behind the M3 method. The M3 computer code is also presented and emphasis is put on the reference manual. This includes detailed reference to the M3 program's abilities and limitations, installation procedures and all functions and operations that the program can perform. It also describes sample cases of how the program is used to analyse a test data set. This guide is part of the Help Files distributed together with M3. Two accompanying reports cover other aspects: - Concepts, Methods, and Mathematical Formulation, gives a complete description of the mathematical framework of M3 and introduces concepts and methods useful for the end user. - M3 version 3.0: Verification and Validation, gathers a collection of validation and verification exercises, designed to test each part of M3 code and to build confidence in its methodology. The M3 method has been tested and modified over several years. The development work has been supported by the Swedish Nuclear Fuel and Waste Management Company (SKB). The main test site for the model was the underground Aespoe Hard Rock Laboratory (HRL). The examples used in this manual are from a Aespoe international groundwater modelling co-operation project where one of the tools used was M3. The M3 concept has been applied on the data from SKB's site investigation programme and in data from Canada, Japan, Jordan, Gabon and Finland. The groundwater composition is a result of mixing processes and water-rock interaction. Standard groundwater models based on thermodynamic laws may not be applicable in a normal temperature groundwater system where equilibrium with many

  18. A Discussion of the High Energy Density Primary Battery Employed in the FOTON M3 Mission

    Science.gov (United States)

    Bennetti, A.; Reece, D.; Spurrett, R.; Schautz, M.; Green, K.

    2008-09-01

    In 2005, ABSL Space Products (ABSL) was contracted by QinetiQ to deliver the lithium sulfuryl chloride primary battery system for the FOTON M3 ESA (European Space Agency) mission. FOTON M3 was led by the ESA Directorate of Human Spaceflight & Exploration and carried a number of materials science, fluid physics and biology experiments as well as technology demonstration payloads. A number of the experiments required a very high energy density primary battery power source. This battery was manufactured by ABSL, and the mission was successfully completed in September 2007 following a twelve days orbiting in Low Earth Orbit (LEO).

  19. Development of RT-components for the M-3 Strawberry Harvesting Robot

    Science.gov (United States)

    Yamashita, Tomoki; Tanaka, Motomasa; Yamamoto, Satoshi; Hayashi, Shigehiko; Saito, Sadafumi; Sugano, Shigeki

    We are now developing the strawberry harvest robot called “M-3” prototype robot system under the 4th urgent project of MAFF. In order to develop the control software of the M-3 robot more efficiently, we innovated the RT-middleware “OpenRTM-aist” software platform. In this system, we developed 9 kind of RT-Components (RTC): Robot task sequence player RTC, Proxy RTC for image processing software, DC motor controller RTC, Arm kinematics RTC, and so on. In this paper, we discuss advantages of RT-middleware developing system and problems about operating the RTC-configured robotic system by end-users.

  20. 1500 m3立式圆筒形煤仓有限元计算%Finite Element Calculation of 1 500 m3 Vertical Cylindrical Bunker

    Institute of Scientific and Technical Information of China (English)

    汪志福; 陶保林; 孙文红

    2015-01-01

    Large cylindrical bunker is widely used in oil fired steam injection station project.An analysis of stress strength for the design of a 1 500 m3 vertical cylindrical bunker is given.A large general finite element software ANSYS is used to establish a actual size of the finite element nu-merical model,which connected with a coal bunker tank top,tank walls,bearing,cone bottom, consistent with steel support columns,using powerful border simulation and all kinds of applied load function,in a state filled with water + wind + snow + load cases,to calculate and check the various structural parts of coal bunker.The calculated results show that it has sufficient safe-ty margin and reliability.%大型圆筒式煤仓在油田燃煤注汽站工程中应用广泛,对某1500 m3立式圆筒形煤仓进行了应力强度分析。运用有限元软件 ANSYS 建立了与煤仓罐顶、罐壁、支座连接、锥底、支撑钢架以及立柱实际尺寸相一致的有限元数值计算模型,利用软件的边界模拟和各种荷载施加功能,针对煤仓各结构部分,在充水状态+风载荷+雪载荷+地震载荷工况下进行了应力计算和校核,结果表明,此煤仓具有足够的安全裕度及可靠性。

  1. M5-branes on S^2 x M_4: Nahm's Equations and 4d Topological Sigma-models

    CERN Document Server

    Assel, Benjamin; Wong, Jin-Mann

    2016-01-01

    We study the 6d N=(0,2) superconformal field theory, which describes multiple M5-branes, on the product space S^2 x M_4, and suggest a correspondence between a 2d N=(0,2) half-twisted gauge theory on S^2 and a topological sigma-model on the four-manifold M_4. To set up this correspondence, we determine in this paper the dimensional reduction of the 6d N=(0,2) theory on a two-sphere and derive that the four-dimensional theory is a sigma-model into the moduli space of solutions to Nahm's equations, or equivalently the moduli space of k-centered SU(2) monopoles, where k is the number of M5-branes. We proceed in three steps: we reduce the 6d abelian theory to a 5d Super-Yang-Mills theory on I x M_4, with I an interval, then non-abelianize the 5d theory and finally reduce this to 4d. In the special case, when M_4 is a Hyper-Kahler manifold, we show that the dimensional reduction gives rise to a topological sigma-model based on tri-holomorphic maps. Deriving the theory on a general M_4 requires knowledge of the met...

  2. File list: ALL.Myo.50.AllAg.LHCN-M2 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Myo.50.AllAg.LHCN-M2 hg19 All antigens Muscle LHCN-M2 SRX201296,SRX201297,SRX19...3596,SRX193611,SRX201281,SRX201282 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Myo.50.AllAg.LHCN-M2.bed ...

  3. File list: DNS.Myo.10.AllAg.LHCN-M2 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Myo.10.AllAg.LHCN-M2 hg19 DNase-seq Muscle LHCN-M2 SRX201296,SRX201297,SRX19359...6,SRX201281,SRX193611,SRX201282 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Myo.10.AllAg.LHCN-M2.bed ...

  4. File list: ALL.Myo.05.AllAg.LHCN-M2 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Myo.05.AllAg.LHCN-M2 hg19 All antigens Muscle LHCN-M2 SRX201296,SRX201297,SRX19...3596,SRX201281,SRX193611,SRX201282 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Myo.05.AllAg.LHCN-M2.bed ...

  5. File list: DNS.Myo.50.AllAg.LHCN-M2 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Myo.50.AllAg.LHCN-M2 hg19 DNase-seq Muscle LHCN-M2 SRX201296,SRX201297,SRX19359...6,SRX193611,SRX201281,SRX201282 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Myo.50.AllAg.LHCN-M2.bed ...

  6. File list: ALL.Myo.10.AllAg.LHCN-M2 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Myo.10.AllAg.LHCN-M2 hg19 All antigens Muscle LHCN-M2 SRX201296,SRX201297,SRX19...3596,SRX201281,SRX193611,SRX201282 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Myo.10.AllAg.LHCN-M2.bed ...

  7. File list: ALL.Myo.20.AllAg.LHCN-M2 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Myo.20.AllAg.LHCN-M2 hg19 All antigens Muscle LHCN-M2 SRX201296,SRX201297,SRX19...3596,SRX201281,SRX193611,SRX201282 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Myo.20.AllAg.LHCN-M2.bed ...

  8. File list: DNS.Myo.20.AllAg.LHCN-M2 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Myo.20.AllAg.LHCN-M2 hg19 DNase-seq Muscle LHCN-M2 SRX201296,SRX201297,SRX19359...6,SRX201281,SRX193611,SRX201282 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Myo.20.AllAg.LHCN-M2.bed ...

  9. All-trans retinoic acid as a single agent induces complete remission in a patient with acute leukemia of M2a subtype

    Institute of Scientific and Technical Information of China (English)

    陈子兴; 王阳; 王玮; 贡静霞; 薛永权

    2002-01-01

    Objective To present a special case with the karyotype and molecular marker of acute myeloid leukemia (AML)-M2 who was induced to complete remission by all-trans retinoic acid (ATRA) alone.Methods A recently hospitalized young female patient with acute leukemia was initially diagnosed as M3 subtype based on morphological French-American-British (FAB) classification. Karyotype analysis using standard G and R banding techniques and RT-PCR were applied to further define the diagnosis. After primarily cultured bone marrow cells from the iliac aspiration were tested for in vitro induced differentiation, the patient was treated with oral all-trans retinoic acid alone, 60?mg per day until complete remission was achieved. Peripheral blood and bone marrow changes were monitored over the whole treatment course.Results The characteristic chromosomal aberration for M3, the t(15;17) reciprocal translocation, was not found while a t(8;21) translocation was verified. Furthermore, an amplified product of the AML-1/ETO fusion gene instead of the PML/RARα fusion gene was detected by RT-PCR and the diagnosis was corrected from M3 to M2. Primary cultured bone marrow cells can be fully induced to terminal differentiation after 4 days exposure to ATRA. A hematological complete remission was achieved after 40 days treatment with ATRA as a single therapeutic agent, suggesting an alternative pathway mediating ATRA-induced myeloid differentiation. Conclusion A leukemia patient with a subtype other than M3, such as M2 in this case, may also be induced to complete remission by the mechanism of ATRA-induced terminal differentiation. This implies that there may be a pathway other than PML/RARα fusion gene product which mediates ATRA-induced myeloid maturation in leukemia cells.

  10. PPARγ ligands switched high fat diet-induced macrophage M2b polarization toward M2a thereby improving intestinal Candida elimination.

    Directory of Open Access Journals (Sweden)

    Lise Lefèvre

    Full Text Available Obesity is associated with a chronic low-grade inflammation that predisposes to insulin resistance and the development of type 2 diabetes. In this metabolic context, gastrointestinal (GI candidiasis is common. We recently demonstrated that the PPARγ ligand rosiglitazone promotes the clearance of Candida albicans through the activation of alternative M2 macrophage polarization. Here, we evaluated the impact of high fat diet (HFD-induced obesity and the effect of rosiglitazone (PPARγ ligand or WY14643 (PPARα ligand both on the phenotypic M1/M2 polarization of peritoneal and cecal tissue macrophages and on the outcome of GI candidiasis. We demonstrated that the peritoneal macrophages and the cell types present in the cecal tissue from HF fed mice present a M2b polarization (TNF-α(high, IL-10(high, MR, Dectin-1. Interestingly, rosiglitazone induces a phenotypic M2b-to-M2a (TNF-α(low, IL-10(low, MR(high, Dectin-1(high switch of peritoneal macrophages and of the cells present in the cecal tissue. The incapacity of WY14643 to switch this polarization toward M2a state, strongly suggests the specific involvement of PPARγ in this mechanism. We showed that in insulin resistant mice, M2b polarization of macrophages present on the site of infection is associated with an increased susceptibility to GI candidiasis, whereas M2a polarization after rosiglitazone treatment favours the GI fungal elimination independently of reduced blood glucose. In conclusion, our data demonstrate a dual benefit of PPARγ ligands because they promote mucosal defence mechanisms against GI candidiasis through M2a macrophage polarization while regulating blood glucose level.

  11. HST UV Observations of the Cores of M3 and M13

    CERN Document Server

    Ferraro, F R; Pecci, F F; Cacciari, C; Dorman, B; Rood, R T; Ferraro, Francesco R.; Paltrinieri, Barbara; Pecci, Flavio Fusi; Cacciari, Carla; Dorman, Ben; Rood, Robert T.

    1997-01-01

    We present preliminary results from HST/WFPC2 observations of the central regions of the of the Galactic globular clusters M13 and M3. The clusters are almost identical in most respects including chemical composition, but there are dramatic differences in both the horizontal branch (HB) and blue straggler (BSS) populations. The M13 HB has a long blue tail extending 4.5 mag in V, reaching well below the level of the main sequence turn-off. M3 has no such feature. M3 and M13 are thus an extreme case of the ``second parameter problem'' in HB morphology. Also present in the M13 HB are two gaps similar to those seen in the clusters NGC 6752 and NGC 2808. M3 has a specific frequency of BSS three times larger than that of M13. Our results imply that neither age nor cluster density, two popular second parameter candidates, are likely to be responsible for the observed differences.

  12. Experimental Conditions: SE37_S16_M3_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available opes SE37_S16 Blank (80% methanol) SE37_S16_M3 0mg [MassBase ID] MDLC1_43486 SE37_MS1 Metabolites extraction... with 80% methanol and analysis by LC-Orbitrap-MS SE37_DS1 Peak extraction for unlabeled data ...

  13. On the Family of Thue Equation |x3 + mx2y- (m + 3) xy2 + y3 |= k

    Institute of Scientific and Technical Information of China (English)

    XIA Jingbo; CHEN Jianhua; ZHANG Silan

    2006-01-01

    The family of cubic Thue equation which depend on two parameters | x3 + mx2 y- (m+3) xy2 + y3|=k is studied. Using rational approximation, we give a smaller upper bound of the solution of the equation, that is quite better than the present result. Moreover, we study two inequalities |x3 +mx2y- (m+3)xy2 +y3|=k≤2m+3 and |m3 +mm2y- (m+3)my2 + y3 | = k≤(2m+ 3)2 separately. Our result of upper bound make it easy to solve those inequalities by simple method of continuous fraction expansion.

  14. Structural and electronic properties of reduced transition metal oxide clusters, M4O10 and M4O10- (M = Cr, W), from photoelectron spectroscopy and quantum chemical calculations.

    Science.gov (United States)

    Li, Shenggang; Zhai, Hua-Jin; Wang, Lai-Sheng; Dixon, David A

    2012-05-31

    Anion photoelectron spectroscopy and quantum chemical calculations at the density functional theory (DFT), coupled cluster theory (CCSD(T)), and complete active space self-consistent field (CASSCF) theory levels are employed to study the reduced transition metal oxide clusters M(4)O(10)(-) (M = Cr, W) and their neutrals. Photoelectron spectra are obtained at 193 and 157 nm photon energies, revealing very different electronic structures for the Cr versus W oxide clusters. The electron affinity and HOMO-LUMO gap are measured to be 3.68 ± 0.05 and 0.7 eV, respectively, for the Cr(4)O(10) neutral cluster, as compared to 4.41 ± 0.04 and 1.3 eV for W(4)O(10). A comprehensive search is performed to determine the ground-state structures for M(4)O(10) and M(4)O(10)(-), in terms of geometry and electronic states by carefully examining the calculated relative energies at the DFT, CCSD(T), and CASSCF levels. The ground states of Cr(4)O(10) and Cr(4)O(10)(-) have tetrahedral structures similar to that of P(4)O(10) with the anion having a lower symmetry due to a Jahn-Teller distortion. The ground states of W(4)O(10) and W(4)O(10)(-) have butterfly shape structures, featuring two fused five-member rings with a metal-metal multiple bond between the central metal atoms. The much stronger WW bonding than the CrCr bonding is found to be the primary cause for the different ground state structures of the reduced Cr(4)O(10)(0/-) versus W(4)O(10)(0/-) oxide clusters. The photoelectron spectra are assigned by comparing the experimental and theoretical adiabatic and vertical electron detachment energies, further confirming the determination of the ground electronic states of M(4)O(10) and M(4)O(10)(-). The time-dependent DFT method is used to calculate the excitation energies of M(4)O(10). The TD-DFT results in combination with the self-consistently calculated vertical detachment energies for some of the excited states at the DFT and CCSD(T) levels are used to assign the higher energy

  15. Divergent evolution of the M3A family of metallopeptidases in plants.

    Science.gov (United States)

    Kmiec, Beata; Teixeira, Pedro F; Murcha, Monika W; Glaser, Elzbieta

    2016-07-01

    Plants, as stationary organisms, have developed mechanisms allowing them efficient resource reallocation and a response to changing environmental conditions. One of these mechanisms is proteome remodeling via a broad peptidase network present in various cellular compartments including mitochondria and chloroplasts. The genome of the model plant Arabidopsis thaliana encodes as many as 616 putative peptidase-coding genes organized in 55 peptidase families. In this study, we describe the M3A family of peptidases, which comprises four members: mitochondrial and chloroplastic oligopeptidase (OOP), cytosolic oligopeptidase (CyOP), mitochondrial octapeptidyl aminopeptidase 1 (Oct1) and plant-specific protein of M3 family (PSPM3) of unknown function. We have analyzed the evolutionary conservation of M3A peptidases across plant species and the functional specialization of the three distinct subfamilies. We found that the subfamily-containing OOP and CyOP-like peptidases, responsible for oligopeptide degradation in the endosymbiotic organelles (OOP) or in the cytosol (CyOP), are highly conserved in all kingdoms of life. The Oct1-like peptidase subfamily involved in pre-protein maturation in mitochondria is conserved in all eukaryotes, whereas the PSPM3-like protein subfamily is strictly conserved in higher plants only and is of unknown function. Specific characteristics within PSPM3 sequences, i.e. occurrence of a N-terminal transmembrane domain and amino acid changes in distal substrate-binding motif, distinguish PSPM3 proteins from other members of M3A family. We performed peptidase activity measurements to analyze the role of substrate-binding residues in the different Arabidopsis M3A paralogs. © 2016 Scandinavian Plant Physiology Society.

  16. A miniaturized microbial fuel cell with three-dimensional graphene macroporous scaffold anode demonstrating a record power density of over 10 000 W m-3

    Science.gov (United States)

    Ren, Hao; Tian, He; Gardner, Cameron L.; Ren, Tian-Ling; Chae, Junseok

    2016-02-01

    A microbial fuel cell (MFC) is a bio-inspired renewable energy converter which directly converts biomass into electricity. This is accomplished via the unique extracellular electron transfer (EET) of a specific species of microbe called the exoelectrogen. Many studies have attempted to improve the power density of MFCs, yet the reported power density is still nearly two orders of magnitude lower than other power sources/converters. Such a low performance can primarily be attributed to two bottlenecks: (i) ineffective electron transfer from microbes located far from the anode and (ii) an insufficient buffer supply to the biofilm. This work takes a novel approach to mitigate these two bottlenecks by integrating a three-dimensional (3D) macroporous graphene scaffold anode in a miniaturized MFC. This implementation has delivered the highest power density reported to date in all MFCs of over 10 000 W m-3. The miniaturized configuration offers a high surface area to volume ratio and improved mass transfer of biomass and buffers. The 3D graphene macroporous scaffold warrants investigation due to its high specific surface area, high porosity, and excellent conductivity and biocompatibility which facilitates EET and alleviates acidification in the biofilm. Consequently, the 3D scaffold houses an extremely thick and dense biofilm from the Geobacter-enriched culture, delivering an areal/volumetric current density of 15.51 A m-2/31 040 A m-3 and a power density of 5.61 W m-2/11 220 W m-3, a 3.3 fold increase when compared to its planar two-dimensional (2D) control counterparts.A microbial fuel cell (MFC) is a bio-inspired renewable energy converter which directly converts biomass into electricity. This is accomplished via the unique extracellular electron transfer (EET) of a specific species of microbe called the exoelectrogen. Many studies have attempted to improve the power density of MFCs, yet the reported power density is still nearly two orders of magnitude lower than

  17. LEYENDO P4L4BR4S y NÚM3R05

    Directory of Open Access Journals (Sweden)

    Manuel Carreiras

    2008-04-01

    Full Text Available Un aspecto clave en lectura es el proceso de reconocimiento de las letras en las palabras. Dicho proceso tiene un componente de normalización de la información sensorial conforme a unos patrones almacenados. Un ejemplo es que cuando leemos un ítem como M4T3R14L se activa inicialmente el significado de MATERIAL.

  18. Definition and measurement of the beam propagation factor M2 for chromatic laser beams

    Institute of Scientific and Technical Information of China (English)

    Tao Fang; Xin Ye; Jinfu Niu; Jianqiu Xu

    2006-01-01

    The concept of the beam propagation factor M2 is extended for chromatic laser beams. The definition of the beam propagation factor can be generalized with the weighted effective wavelength. Using the new definition of factor M2, the propagation of chromatic beams can be analyzed by the beam propagation factor M2 as same as that of monochromatic beams. A simple method to measure the chromatic beam factor M2 is demonstrated. The chromatic factor M2 is found invariable while the laser beam propagates through the dispersion-free ABCD system.

  19. A subpopulation of neuronal M4 muscarinic acetylcholine receptors plays a critical role in modulating dopamine-dependent behaviors

    DEFF Research Database (Denmark)

    Jeon, Jongrye; Nielsen, Ditte Dencker; Wörtwein, Gitta;

    2010-01-01

    Acetylcholine (ACh) regulates many key functions of the CNS by activating cell surface receptors referred to as muscarinic ACh receptors (M(1)-M(5) mAChRs). Like other mAChR subtypes, the M(4) mAChR is widely expressed in different regions of the forebrain. Interestingly, M(4) mAChRs are coexpres....... Since enhanced central dopaminergic neurotransmission is a hallmark of several severe disorders of the CNS, including schizophrenia and drug addiction, our findings have substantial clinical relevance....

  20. Left-Right Symmetric Model from Geometrical Formulation of Gauge Theory in $M_{4} \\times Z_{2} \\times Z_{2}$

    CERN Document Server

    Konisi, G; Mäki, Z; Nakahara, M

    1999-01-01

    The left-right symmetric model (LRSM) with gauge group $SU(2)_{L} \\times SU(2)_{R} \\times U(1)_{B-L}$ is reconstructed from the geometric formulation of gauge theory in $M_4 \\times Z_2 \\times Z_2$ where $M_4$ is the four-dimensional Minkowski space and $Z_2 \\times Z_2$ the discrete space with four points. The geometrical structure of this model becomes clearer compared with other works based on noncommutative geometry. As a result, the Yukawa coupling terms and the Higgs potential are derived in more restricted forms than in the standard LRSM.

  1. M4/12 package project - development of a package for transport of new MOX fuel in Europe

    Energy Technology Data Exchange (ETDEWEB)

    Kaye, B.R.; Porter, I.; Ashley, P. [BNFL, Warrington, Cheshire (United Kingdom)

    2004-07-01

    BNFL has a requirement to deliver new MOX fuel from the Sellafield MOX Plant (SMP) to its customers in mainland Europe. To satisfy this requirement, a transport system has been developed which complies with national and international regulations and conventions relating to the transport of Category 1 materials. Fundamental to this system is the transport package. BNFL has designed, developed, and is manufacturing a new transport package, the M4/12, This paper gives a brief overview of the overall transport system and then goes on to describe the development of the M4/12 package with particular emphasis on the novel features of the design.

  2. Comparison of Allergenicity at Gly m 4 and Gly m Bd 30K of Soybean after Genetic Modification.

    Science.gov (United States)

    Tsai, Jaw-Ji; Chang, Ching-Yun; Liao, En-Chih

    2017-02-15

    Despite rapid growth of genetically modified (GM) crops, effective evaluations of genetic modification on allergenicity are still lacking. Gly m Bd 30K is cross-reactive with cow's milk protein casein, Gly m 4, and with birch pollen allergen Bet v 1. Here we compared the allergenicity between GM and non-GM soybeans with respect to the foci Gly m 4 and Gly m Bd 30K. Recombinant allergens of Gly m Bd 30K and Gly m 4 were generated and polyclonal antibodies raised to identify these two allergenic components in soybeans. GM soybean was first PCR-confirmed using 35S promoter. A total of 20 soybeans (half GM, half non-GM) obtained from a food market were used to assess their allergenicity based on IgE-binding and histamine release. The concentrations of Gly m Bd 30K and Gly m 4 in soybeans were then determined. Most soybean-allergic patients (9 of 10) showed IgE-positive reactions to the allergen of 30 kDa in molecular weight. That allergen turned out to be Glycine max Gly m Bd 30K based on LC-MS/MS analyses. Gly m Bd 30K is therefore the major allergen in the soybean. An increase in the transcription of both the Gly m 4 (stress-induced protein SAM22) and Gly m Bd 28K (soybean allergen precursor) was found after genetic modification. The protein concentrations of Gly m 4 and Gly m Bd 30K were not statistically significant different between non-GM and GM soybeans. There were also no statistical significances between them in the tests of IgE binding and histamine release. In conclusion, soybeans showed similar concentrations of Gly m Bd 30K and Gly m 4 regardless of genetic modification or absence thereof. The allergenicity of both Gly m Bd 30K and Gly m 4 was therefore not altered after genetic modification. Patients showing hypersensitivity to soybeans and who had pre-existing allergy to birch pollen and cow's milk casein might not further increase their allergic reactions following exposures to the GM soybeans.

  3. Selective activation of M4 muscarinic acetylcholine receptors reverses MK-801-induced behavioral impairments and enhances associative learning in rodents

    DEFF Research Database (Denmark)

    Bubser, Michael; Bridges, Thomas M; Dencker, Ditte;

    2014-01-01

    an antipsychotic drug-like profile in rodents after amphetamine challenge. Previous studies suggest that enhanced cholinergic activity may also improve cognitive function and reverse deficits observed with reduced signaling through the N-methyl-d-aspartate subtype of the glutamate receptor (NMDAR) in the central...... PAMs, enabling a more extensive characterization of M4 actions in rodent models. We used VU0467154 to test the hypothesis that selective potentiation of M4 receptor signaling could ameliorate the behavioral, cognitive, and neurochemical impairments induced by the noncompetitive NMDAR antagonist MK-801...

  4. Antagonism of nucleus accumbens M(2) muscarinic receptors disrupts operant responding for sucrose under a progressive ratio reinforcement schedule.

    Science.gov (United States)

    Cousens, Graham A; Beckley, Jacob T

    2007-07-19

    Diverse cholinergic signaling mechanisms regulate the excitability of striatal principal neurons and modulate striatal-dependent behavior. These effects are mediated, in part, by action at muscarinic receptors (mAChR), subtypes of which exhibit distinct patterns of expression across striatal neuronal populations. Non-selective mAChR blockade within the nucleus accumbens (NAc) has been shown to disrupt operant responding for food and to inhibit food consumption. However, the specific receptor subtypes mediating these effects are not known. Thus, we evaluated effects of intra-NAc infusions of pirenzepine and methoctramine, mAChR antagonisits with distinct binding affinity profiles, on operant responding for sucrose reward under a progressive ratio (PR) reinforcement schedule. Moderate to high doses of methoctramine disrupted operant responding and reduced behavioral breakpoint. In contrast, pirenzepine failed to impact operant performance at any dose tested. Methoctramine failed to affect latencies to complete appetitive-consummatory response sequences or to impact measures of acoustic startle, suggesting that its' disruptive effects on operant behavior were not consequent to gross motor impairment. Since methoctramine has a greater affinity for M(2) receptors compared to pirenzepine, which has a greater relative affinity for M(1) and M(3) receptors, these findings suggest that M(2) mAChRs within the NAc regulate behavioral processes underling the acquisition of reward.

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

    Science.gov (United States)

    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).

  6. Sublingual immunization with M2-based vaccine induces broad protective immunity against influenza.

    Directory of Open Access Journals (Sweden)

    Byoung-Shik Shim

    Full Text Available BACKGROUND: The ectodomain of matrix protein 2 (M2e of influenza A virus is a rationale target antigen candidate for the development of a universal vaccine against influenza as M2e undergoes little sequence variation amongst human influenza A strains. Vaccine-induced M2e-specific antibodies (Abs have been shown to display significant cross-protective activity in animal models. M2e-based vaccine constructs have been shown to be more protective when administered by the intranasal (i.n. route than after parenteral injection. However, i.n. administration of vaccines poses rare but serious safety issues associated with retrograde passage of inhaled antigens and adjuvants through the olfactory epithelium. In this study, we examined whether the sublingual (s.l. route could serve as a safe and effective alternative mucosal delivery route for administering a prototype M2e-based vaccine. The mechanism whereby s.l. immunization with M2e vaccine candidate induces broad protection against infection with different influenza virus subtypes was explored. METHODS AND RESULTS: A recombinant M2 protein with three tandem copies of the M2e (3M2eC was expressed in Escherichia coli. Parenteral immunizations of mice with 3M2eC induced high levels of M2e-specific serum Abs but failed to provide complete protection against lethal challenge with influenza virus. In contrast, s.l. immunization with 3M2eC was superior for inducing protection in mice. In the latter animals, protection was associated with specific Ab responses in the lungs. CONCLUSIONS: The results demonstrate that s.l. immunization with 3M2eC vaccine induced airway mucosal immune responses along with broad cross-protective immunity to influenza. These findings may contribute to the understanding of the M2-based vaccine approach to control epidemic and pandemic influenza infections.

  7. Residual stress in a M3:2 PM high speed steel; effect of mechanical loading

    DEFF Research Database (Denmark)

    Højerslev, Christian; Odén, Magnus; Carstensen, Jesper V.

    2001-01-01

    X-ray lattice strains were investigated in an AISI M3:2 PM high-speed steel in the as heat treated condition and after exposure to alternating mechanical load. The volume changes during heat treatment were monitored with dilatometry. Hardened and tempered AISI M3:2 steel consists of tempered lath...... martensite and the carbides M6C,V8C7 and M23C6. In the as heat treated condition the stress state is triaxial. The primary carbides M6C and V8C7 experience a compressive state of stress. Exposure to an alternating mechanical load, changes the states of stress of V8C7 and tempered martensite, but does...... not appear to change the state of stress in M6C....

  8. The Abundance of Lithium in an AGB Star in the Globular Cluster M3 (NGC 5272)

    CERN Document Server

    Givens, R A

    2016-01-01

    A survey of red giants in the globular cluster M3 with the Hydra multi-object spectrograph on the WIYN 3.5-m telescope indicated a prominent Li I 6707 $\\AA$ feature in the red giant vZ 1050. Follow-up spectroscopy with the ARC 3.5-m telescope confirmed this observation and yielded a derived abundance of A(Li)$_{NLTE}$ = 1.6 $\\pm$ 0.05. In addition, the high oxygen and low sodium abundances measured from the same spectrum suggest that vZ 1050 is a first generation cluster star. The location vZ 1050 above the horizontal branch and blueward of the red giant branch in the cluster's color-magnitude diagram places vZ 1050 on M3's asymptotic giant branch. The likely source for the enhanced lithium abundance is the Cameron-Fowler mechanism operating in vZ 1050 itself.

  9. The Abundance of Lithium in an ABG Star in the Globular Cluster M3 (NGC 5272)

    Science.gov (United States)

    Givens, R. A.; Pilachowski, C. A.

    2016-12-01

    A survey of red giants in the globular cluster M3 with the Hydra multi-object spectrograph on the WIYN 3.5 m telescope indicated a prominent Li i 6707 Å feature in the red giant vZ 1050. Followup spectroscopy with the ARC 3.5 m telescope confirmed this observation and yielded a derived abundance of A(Li)NLTE = 1.6 ± 0.05. In addition, the high oxygen and low sodium abundances measured from the same spectrum suggest that vZ 1050 is a first generation cluster star. The location of vZ 1050 above the horizontal branch and blueward of the red giant branch in the cluster’s color-magnitude diagram places vZ 1050 on M3's asymptotic giant branch. The likely source for the enhanced lithium abundance is the Cameron-Fowler mechanism operating in vZ 1050 itself.

  10. M3A system (2000–2005 – operation and maintenance

    Directory of Open Access Journals (Sweden)

    G. Petihakis

    2006-05-01

    Full Text Available During the Pilot Phase of the Mediterranean Forecasting System (MFSPP (1998–2001 a prototype observing system (Mediterranean Moored Multi-sensor Array – M3A was designed, developed and operated in the Cretan Sea for continuous oceanographic measurements in real time. The main problems encountered were associated with biofouling, underwater and aerial communication and with the design of the surface buoy. In the second phase of the MFS project named Mediterranean Forecasting System Towards Environmental Predictions (MFSTEP (2001–2005, the aim was to solve those problems and to consolidate the M3A. During the approximately five years of operation there were 13 scheduled and 15 emergency visits with a total duration of 65 days. The acquired experience through the maintenance program proved that the continuous observation of a so important system with a relative low cost is feasible.

  11. Cloning and characterization of a novel deletion mutant of heterogeneous nuclear ribonucleoprotein M4 from human dendritic cells

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To identify differentially expressed genes from antigen-stimulated human dendritic cells (DC), subtractive cloning was adopted and more than ten novel genes differentially expressed were cloned. One is a deletion mutant of heterogeneous nuclear ribonucleoprotein (hnRNP) M4 in which the residues from 159 to 197 of hnRNP M4 have been absent. The deletion mutant was shown to be co-expressed with hnRNP M4 in cell lines. The mutant was expressed in antigen-stimulated DC but not in normal DC. Northern blot analysis revealed the presence of a major hnRNP M4 deletion mutant Mrna transcript of 2.4 kilobase with the highest levels in peripheral lymphocytes, lung, liver and spleen. It was also expressed in bone marrow-derived stromal cells (BMSC), BMSC treated with several cytokines but not in BMSC treated with TNF-a. The results revealed a new member of hnRNP family and suggested that hnRNP would participate in antigen process and presentation.

  12. Cloning and characterization of a novel deletion mutant of heterogeneous nuclear ribonucleoprotein M4 from human dendritic cells

    Institute of Scientific and Technical Information of China (English)

    黄欣; 赵忠良; 袁正隆; 张明徽; 朱学军; 陈国友; 曹雪涛

    2000-01-01

    To identify differentially expressed genes from antigen-stimulated human dendritic cells (DC), subtractive cloning was adopted and more than ten novel genes differentially expressed were cloned. One is a deletion mutant of heterogeneous nuclear ribonucleoprotein (hnRNP) M4 in which the residues from 159 to 197 of hnRNP M4 have been absent. The deletion mutant was shown to- be co-expressed with hnRNP M4 in cell lines. The mutant was expressed in antigen-stimulated DC but not in normal DC. Northern blot analysis revealed the presence of a major hnRNP M4 deletion mutant mRNA transcript of 2.4 kilobase with the highest levels in peripheral lymphocytes, lung, liver and spleen. It was also expressed in bone marrow-derived stromal cells (BMSC), BMSC treated with several cytokines but not in BMSC treated with TNF-a. The results revealed a new member of hnRNP family and suggested that hnRNP would participate in antigen process and presentation.

  13. Cloning and characterization of a novel deletion mutant of heterogeneous nuclear ribonucleoprotein M4 from human dendritic cells

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To identify differentially expressed genes from antigen-stimulated human dendritic cells (DC), subtractive cloning was adopted and more than ten novel genes differentially expressed were cloned. One is a deletion mutant of heterogeneous nuclear ribonucleoprotein (hnRNP) M4 in which the residues from 159 to 197 of hnRNP M4 have been absent. The deletion mutant was shown to be co-expressed with hnRNP M4 in cell lines. The mutant was expressed in antigen-stimulated DC but not in normal DC. Northern blot analysis revealed the presence of a major hnRNP M4 deletion mutant mRNA transcript of 2.4 kilobase with the highest levels in peripheral lymphocytes, lung, liver and spleen. It was also expressed in bone marrow-derived stromal cells (BMSC), BMSC treated with several cytokines but not in BMSC treated with TNF-a. The results revealed a new member of hnRNP family and suggested that hnRNP would participate in antigen process and presentation.

  14. 8s, a numerical simulator of the challenging optical calibration of the E-ELT adaptive mirror M4

    Science.gov (United States)

    Briguglio, Runa; Pariani, Giorgio; Xompero, Marco; Riccardi, Armando; Tintori, Matteo; Lazzarini, Paolo; Spanò, Paolo

    2016-07-01

    8s stands for Optical Test TOwer Simulator (with 8 read as in italian 'otto'): it is a simulation tool for the optical calibration of the E-ELT deformable mirror M4 on its test facility. It has been developed to identify possible criticalities in the procedure, evaluate the solutions and estimate the sensitivity to environmental noise. The simulation system is composed by the finite elements model of the tower, the analytic influence functions of the actuators, the ray tracing propagation of the laser beam through the optical surfaces. The tool delivers simulated phasemaps of M4, associated with the current system status: actuator commands, optics alignment and position, beam vignetting, bench temperature and vibrations. It is possible to simulate a single step of the optical test of M4 by changing the system parameters according to a calibration procedure and collect the associated phasemap for performance evaluation. In this paper we will describe the simulation package and outline the proposed calibration procedure of M4.

  15. Quantum corrections to short folded superstring in AdS_3 x S^3 x M^4

    CERN Document Server

    Beccaria, Matteo

    2012-01-01

    We consider integrable superstring theory on AdS_3 x S^3 x M^4 where M^4=T^4 or M^4=S^3 x S^1 with generic ratio of the radii of the two 3-spheres. We compute the one-loop energy of a short folded string spinning in AdS_3 and rotating in S^3. The computation is performed by world-sheet small spin perturbation theory as well as by quantizing the classical algebraic curve characterizing the finite-gap equations. The two methods give equal results up to regularization contributions that are under control. One important byproduct of the calculation is the part of the energy which is due to the dressing phase in the Bethe Ansatz. Remarkably, this contribution E_1^{dressing} turns out to be independent on the radii ratio. In the M^4=T^4 limit, we discuss how E_1^{dressing} relates to a recent proposal for the dressing phase tested in the su(2) sector. We point out some difficulties suggesting that quantization of the AdS_3 classical finite-gap equations could be subtler than the easier AdS_5 x S^5 case.

  16. M3MS-16OR0401086 – Report on NEAMS Workbench Support for MOOSE Applications

    Energy Technology Data Exchange (ETDEWEB)

    Lefebvre, Robert A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Reactor and Nuclear Systems Division; Langley, Brandon R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Reactor and Nuclear Systems Division; Thompson, Adam B. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Reactor and Nuclear Systems Division

    2016-09-23

    This report summarizes the status of the Nuclear Energy Advanced Modeling and Simulation (NEAMS) Workbench from Oak Ridge National Laboratory (ORNL) and the integration of the MOOSE framework. This report marks the completion of NEAMS milestone M3MS-16OR0401086. This report documents the developed infrastructure to support the MOOSE framework applications, the applications’ results, visualization status, the collaboration that facilitated this progress, and future considerations.

  17. New species of Triplocania Roesler with forewing M3 forked (Psocodea: 'Psocoptera': Ptiloneuridae), from Brazil.

    Science.gov (United States)

    Da Silva Neto, Alberto Moreira; Rafael, José Albertino; Aldrete, Alfonso N García

    2014-07-16

    Four new Brazilian species of Triplocania with forewing M3 forked are described and illustrated based on male specimens, namely: Triplocania lamasi n.sp. (Mato Grosso: Brazil), Triplocania mariateresae n.sp. (Rio de Janeiro: Brazil), Triplocania newi n.sp. (Tocantins: Brazil) and Triplocania plaumanni n.sp. (Santa Catarina: Brasil). They differ from all the other species in the genus, in which the males are known, by the hypandrium and phallosome structures.

  18. Increased immunogenicity and protective efficacy of influenza M2e fused to a tetramerizing protein.

    Directory of Open Access Journals (Sweden)

    Anne-Marie Carola Andersson

    Full Text Available The ectodomain of the matrix 2 protein (M2e of influenza A virus represents an attractive target for developing a universal influenza A vaccine, with its sequence being highly conserved amongst human variants of this virus. With the aim of targeting conformational epitopes presumably shared by diverse influenza A viruses, a vaccine (M2e-NSP4 was constructed linking M2e (in its consensus sequence to the rotavirus fragment NSP4(98-135; due to its coiled-coil region this fragment is known to form tetramers in aqueous solution and in this manner we hoped to mimick the natural configuration of M2e as presented in membranes. M2e-NSP4 was then evaluated side-by-side with synthetic M2e peptide for its immunogenicity and protective efficacy in a murine influenza challenge model. Here we demonstrate that M2e fused to the tetramerizing protein induces an accelerated, augmented and more broadly reactive antibody response than does M2e peptide as measured in two different assays. Most importantly, vaccination with M2e-NSP4 caused a significant decrease in lung virus load early after challenge with influenza A virus and maintained its efficacy against a lethal challenge even at very low vaccine doses. Based on the results presented in this study M2e-NSP4 merits further investigation as a candidate for or as a component of a universal influenza A vaccine.

  19. Development, Implementation and Evaluation of an M3 Community Health Curriculum

    Directory of Open Access Journals (Sweden)

    Staci Young, MS

    2004-03-01

    Full Text Available Objectives: This paper describes the development, implementation and evaluation of an M3 community health curriculum that responds to recent changes within the health care finance and delivery system. Methods: The new curriculum was developed based on AAMC recommendations, LCME requirements, a national review of undergraduate community health curricula, and an internal review of the integration of community health concepts in M3 clerkships. Results: The M3 curriculum teaches: 1 the importance of being a community responsive physician; 2 SES factors that influence health; 3 cultural competency; and 4 the role of physicians as health educators. Student evaluations for the first twelve months of implementation indicate that students are most satisfied with presentations and less satisfied with required readings and a patient interview project. Discussion: Most students agree that at the completion of the course they understand what it means to be a community-responsive physician, and they have developed skills to help them become more community responsive. Evaluation tools need to be developed to assess if students’ behavior has changed due to course participation.

  20. Performance of 500 m3 TankCell® at Kevitsa Cu-Ni-PGM concentrator

    Directory of Open Access Journals (Sweden)

    Mattsson Toni

    2016-01-01

    Full Text Available Outotec TankCell e500 flotation cell, with 500 m3 of efficient flotation volume, has been in operation since October 2014 at Kevitsa Cu-Ni-PGM concentrator as the first Cu rougher flotation cell. The 500 m3 flotation cell has proven to provide metallurgical superiority at very low specific power. On average the cell has recovered 71% of copper contained in the flotation feed. The cell has produced the concentrate with the Cu grade equal to 17% Cu. The typical specific power for the cell is around 0.4 kW/m3 (blower power not included. After the start-up of the cell the operating parameters have varied. The mixing speed have varied from 4.9 to 7.0 m/s and the superficial gas velocity from 0.3 to 1.5 cm/s. At various operating parameters the mixing, gas dispersion and metallurgical performance of the cell have been evaluated. In this paper a review of the hydrodynamic and metallurgical performance of the cell is presented. The paper focuses on the interactions of mixing intensity, bubble size and metallurgical performance in industrial application.

  1. Mice Lacking M1 and M3 Muscarinic Acetylcholine Receptors Have Impaired Odor Discrimination and Learning

    Science.gov (United States)

    Chan, Wilson; Singh, Sanmeet; Keshav, Taj; Dewan, Ramita; Eberly, Christian; Maurer, Robert; Nunez-Parra, Alexia; Araneda, Ricardo C.

    2017-01-01

    The cholinergic system has extensive projections to the olfactory bulb (OB) where it produces a state-dependent regulation of sensory gating. Previous work has shown a prominent role of muscarinic acetylcholine (ACh) receptors (mAChRs) in regulating the excitability of OB neurons, in particular the M1 receptor. Here, we examined the contribution of M1 and M3 mAChR subtypes to olfactory processing using mice with a genetic deletion of these receptors, the M1−/− and the M1/M3−/− knockout (KO) mice. Genetic ablation of the M1 and M3 mAChRs resulted in a significant deficit in odor discrimination of closely related molecules, including stereoisomers. However, the discrimination of dissimilar molecules, social odors (e.g., urine) and novel object recognition was not affected. In addition the KO mice showed impaired learning in an associative odor-learning task, learning to discriminate odors at a slower rate, indicating that both short and long-term memory is disrupted by mAChR dysfunction. Interestingly, the KO mice exhibited decreased olfactory neurogenesis at younger ages, a deficit that was not maintained in older animals. In older animals, the olfactory deficit could be restored by increasing the number of new born neurons integrated into the OB after exposing them to an olfactory enriched environment, suggesting that muscarinic modulation and adult neurogenesis could be two different mechanism used by the olfactory system to improve olfactory processing. PMID:28210219

  2. Goldschmidt crater and the Moon's north polar region: Results from the Moon Mineralogy Mapper (M3)

    Science.gov (United States)

    Cheek, L.C.; Pieters, C.M.; Boardman, J.W.; Clark, R.N.; Combe, J.-P.; Head, J.W.; Isaacson, P.J.; McCord, T.B.; Moriarty, D.; Nettles, J.W.; Petro, N.E.; Sunshine, J.M.; Taylor, L.A.

    2011-01-01

    Soils within the impact crater Goldschmidt have been identified as spectrally distinct from the local highland material. High spatial and spectral resolution data from the Moon Mineralogy Mapper (M3) on the Chandrayaan-1 orbiter are used to examine the character of Goldschmidt crater in detail. Spectral parameters applied to a north polar mosaic of M3 data are used to discern large-scale compositional trends at the northern high latitudes, and spectra from three widely separated regions are compared to spectra from Goldschmidt. The results highlight the compositional diversity of the lunar nearside, in particular, where feldspathic soils with a low-Ca pyroxene component are pervasive, but exclusively feldspathic regions and small areas of basaltic composition are also observed. Additionally, we find that the relative strengths of the diagnostic OH/H2O absorption feature near 3000 nm are correlated with the mineralogy of the host material. On both global and local scales, the strongest hydrous absorptions occur on the more feldspathic surfaces. Thus, M3 data suggest that while the feldspathic soils within Goldschmidt crater are enhanced in OH/H2O compared to the relatively mafic nearside polar highlands, their hydration signatures are similar to those observed in the feldspathic highlands on the farside. Copyright 2011 by the American Geophysical Union.

  3. M5-branes on S 2 × M 4: Nahm's equations and 4d topological sigma-models

    Science.gov (United States)

    Assel, Benjamin; Schäfer-Nameki, Sakura; Wong, Jin-Mann

    2016-09-01

    We study the 6d N = (0 , 2) superconformal field theory, which describes multiple M5-branes, on the product space S 2 × M 4, and suggest a correspondence between a 2d N = (0 , 2) half-twisted gauge theory on S 2 and a topological sigma-model on the four-manifold M 4. To set up this correspondence, we determine in this paper the dimensional reduction of the 6d N = (0 , 2) theory on a two-sphere and derive that the four-dimensional theory is a sigma-model into the moduli space of solutions to Nahm's equations, or equivalently the moduli space of k-centered SU(2) monopoles, where k is the number of M5-branes. We proceed in three steps: we reduce the 6d abelian theory to a 5d Super-Yang-Mills theory on I × M 4, with I an interval, then non-abelianize the 5d theory and finally reduce this to 4d. In the special case, when M 4 is a Hyper-Kähler manifold, we show that the dimensional reduction gives rise to a topological sigma-model based on tri-holomorphic maps. Deriving the theory on a general M 4 requires knowledge of the metric of the target space. For k = 2 the target space is the Atiyah-Hitchin manifold and we twist the theory to obtain a topological sigma-model, which has both scalar fields and self-dual two-forms.

  4. The Moon Mineralogy (M3) Imaging Spectrometer: Early Assessment of the Spectral, Radiometric, Spatial and Uniformity Properties

    Science.gov (United States)

    Green, Robert O.; Pieters, C. M.; Boardman, J.; Barr, D.; Bruce, C.; Bousman, J.; Chatterjee, A.; Eastwood, M.; Essandoh, V.; Geier, S.; Glavich, T.; Green, R.; Haemmerle, V.; Hyman, S.; Hovland, L.; Koch, T.; Lee, K.; Lundeen, S.; Motts, E.; Mouroulis, P.; Paulson, S.; Plourde, K.; Racho, C.; Robinson, D.; Rodriquez, J.

    2009-01-01

    The Moon Mineralogy Mapper's (M3) is a high uniformity and high signal-to-noise ratio NASA imaging spectrometer that is a guest instrument on the Indian Chandrayaan-1 Mission to the Moon. The laboratory measured spectral, radiometric, spatial, and uniformity characteristics of the M3 instrument are given. The M3 imaging spectrometer takes advantage of a suite of critical enabling capabilities to achieve its measurement requirement with a mass of 8 kg, power usage of 15 W, and volume of 25X18X12 cm. The M3 detector and spectrometer are cooled by a multi-stage passive cooler. This paper presents early M3 performance assessment results.

  5. Distributed Access Control Based on Proxy Signature in M2M Sensor Networks

    Directory of Open Access Journals (Sweden)

    Lingyu Lee

    2013-05-01

    Full Text Available In this study, we have a research of the distributed access control based on proxy signature in M2M sensor networks M2M sensor networks. As M2M sensor networks are usually deployed in hostile environment, the global communication security of M2M sensor networks is and will continue to be a major concern. Although there are many related works on access control in WSNs (Wireless Sensor Networks, Ad-hoc networks, MANETs (Mobile Ad-hoc Networks and etc., they cannot be applied to M2M sensor networks directly. Motivated by this consideration, we develop a secure and distributed access control scheme based on proxy signature for M2M sensor networks, which provides strong authentication and achieves efficiency. Moreover, security of the proposed technique does not rely on availability of a secure channel.

  6. Increased immunogenicity and protective efficacy of influenza M2e fused to a tetramerizing protein

    DEFF Research Database (Denmark)

    Andersson, Anne-Marie Carola; Håkansson, Kjell Ove; Jensen, Benjamin Anderschou Holbech

    2012-01-01

    by diverse influenza A viruses, a vaccine (M2e-NSP4) was constructed linking M2e (in its consensus sequence) to the rotavirus fragment NSP4(98-135); due to its coiled-coil region this fragment is known to form tetramers in aqueous solution and in this manner we hoped to mimick the natural configuration of M2......The ectodomain of the matrix 2 protein (M2e) of influenza A virus represents an attractive target for developing a universal influenza A vaccine, with its sequence being highly conserved amongst human variants of this virus. With the aim of targeting conformational epitopes presumably shared...... reactive antibody response than does M2e peptide as measured in two different assays. Most importantly, vaccination with M2e-NSP4 caused a significant decrease in lung virus load early after challenge with influenza A virus and maintained its efficacy against a lethal challenge even at very low vaccine...

  7. Solidification microstructure of M2 high speed steel by different casting technologies

    OpenAIRE

    Zhou Xuefeng; Fang Feng; Jiang Jianjing

    2011-01-01

    The present work investigated the solidification microstructure of AISI M2 high speed steel manufactured by different casting technologies, namely iron mould casting and continuous casting. The results revealed that the as-cast structure of the steel was composed of the iron matrix and the M2C eutectic carbide networks, which were greatly refined in the ingot made by continuous casting process, compared with that by the iron mould casting process. M2C eutectic carbides presented variation in ...

  8. M2M Communications for E-Health and Smart Grid: An Industry and Standard Perspective

    OpenAIRE

    Fan, Zhong; Haines, Russell J.; Kulkarni, Parag

    2013-01-01

    An overview of several standardization activities for machine-to-machine (M2M) communications is presented, analyzing some of the enabling technologies and applications of M2M in industry sectors such as Smart Grid and e-Health. This summary and overview of the ongoing work in M2M from the industrial and standardization perspective complements the prevalent academic perspective of such publications to date in this field.

  9. Increased immunogenicity and protective efficacy of influenza M2e fused to a tetramerizing protein

    DEFF Research Database (Denmark)

    Andersson, Anne-Marie Carola; Håkansson, Kjell Ove; Jensen, Benjamin Anderschou Holbech;

    2012-01-01

    The ectodomain of the matrix 2 protein (M2e) of influenza A virus represents an attractive target for developing a universal influenza A vaccine, with its sequence being highly conserved amongst human variants of this virus. With the aim of targeting conformational epitopes presumably shared......e as presented in membranes. M2e-NSP4 was then evaluated side-by-side with synthetic M2e peptide for its immunogenicity and protective efficacy in a murine influenza challenge model. Here we demonstrate that M2e fused to the tetramerizing protein induces an accelerated, augmented and more broadly...

  10. Characteristics of Hebei Xinyue 280m2 sinter project%河北鑫跃280m2烧结机的工艺特点

    Institute of Scientific and Technical Information of China (English)

    宾蓉晖

    2012-01-01

    The process characteristics of bar screen, dust pneumatic conveying, and first mixing de-dusting system were introduced, and the influence on environment protection and energy saving of Hebei Xinyue 280m2 sinter projects were introduced.%介绍了河北鑫跃280m2烧结机工程棒条筛、除尘灰气力输送、一混除尘的工艺特点,以及产生的环保、节能影响.

  11. The M4.5V flare star AF Psc as seen in K2 engineering data

    CERN Document Server

    Ramsay, Gavin

    2014-01-01

    We present the light curve of the little studied flare star AF Psc (M4.5V) obtained using engineering data from the K2 mission. Data were obtained in Long Cadence mode giving an effective exposure of 29 min and nearly 9 d of coverage. A clear modulation on a period of 1.08 d was seen which is the signature of the stellar rotation period. We identify 14 flares in the light curve, with the most luminous flares apparently coming from the same active region. We compare the flare characteristics of AF Psc to two M4V flare stars studied using kepler data. The K2 mission, if given approval, will present a unique opportunity to study the rotation and flare properties of late type dwarf stars with different ages and mass.

  12. Seismicity Pattern Changes before the M = 4.8 Aeolian Archipelago (Italy) Earthquake of August 16, 2010

    Science.gov (United States)

    2014-01-01

    We investigated the seismicity patterns associated with an M = 4.8 earthquake recorded in the Aeolian Archipelago on 16, August, 2010, by means of the region-time-length (RTL) algorithm. This earthquake triggered landslides at Lipari; a rock fall on the flanks of the Vulcano, Lipari, and Salina islands, and some damages to the village of Lipari. The RTL algorithm is widely used for investigating precursory seismicity changes before large and moderate earthquakes. We examined both the spatial and temporal characteristics of seismicity changes in the Aeolian Archipelago region before the M = 4.8 earthquake. The results obtained reveal 6-7 months of seismic quiescence which started about 15 months before the earthquake. The spatial distribution shows an extensive area characterized by seismic quiescence that suggests a relationship between quiescence and the Aeolian Archipelago regional tectonics. PMID:24511288

  13. Vasco da Gama 33000m3耙吸挖泥船

    Institute of Scientific and Technical Information of China (English)

    刘厚恕; 顾洁

    2001-01-01

    The 33000m3 Vasco da Gama was delivered to the owner in 2000, which is the largest trailing suction hopper dredger up to now. The vessel is designed for the following main functions: loading spoil with two side suction pipes at a depth of 45-60m; transporting the spoil at a speed of 16.Skn; dumping spoil through six pairs of bottom doors; self-discharging of spoil via floating pipeline; self-discharging of spoil through bow-jet nozzle; deep dredging at 131m with 5500kW submerged dredge pump. This paper fully described its arrangement, key dredging equipments and major design features,

  14. Deposition of CdTe films under microgravity: Foton M3 mission

    Energy Technology Data Exchange (ETDEWEB)

    Benz, K.W.; Croell, A. [Freiburger Materialforschungszentrum FMF, Albert-Ludwigs-Universitaet Freiburg (Germany); Zappettini, A.; Calestani, D. [CNR Parma, Instituto Materiali Speciali per Elettronica e Magnetismo IMEM, Fontani Parma (Italy); Dieguez, E. [Universidad Autonoma de Madrid (Spain). Departamento de Fisica de Materiales; Carotenuto, L.; Bassano, E. [Telespazio Napoli, Via Gianturco 31, 80146 Napoli (Italy); Fiederle, M.

    2009-10-15

    Experiments of deposition of CdTe films have been carried out under microgravity in the Russian Foton M3 mission. The influence of gravity has been studied with these experiments and compared to the results of simulations. The measured deposition rate could be confirmed by the theoretical results for lower temperatures. For higher temperatures the measured thickness of the deposited films was larger compared to the theoretical data. (copyright 2009 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  15. Postpartum Diagnosis of AML-M3: A Rare Case Report

    Directory of Open Access Journals (Sweden)

    Manjula Biradar

    2016-07-01

    Full Text Available A 27 year old female gravid 2, para 1, presented at 39 weeks of gestation with pain in abdomen going in for labour, and delivered healthy baby. The patient later had post-partum haemorrhage with Prothrombin Time (PT 10min, platelet count 70,000 cells/cumm. Peripheral smear showed shift to left with myeloblasts, promyelocytes. The diagnosis of Acute Myeloid Leukemia (AML was given and advised for bone marrow examination. The diagnosis AML-M3 was confirmed by marrow study. Unfortunately, patient went in for Disseminated Intravascular Coagulation (DIC and died 2 days after the diagnosis.

  16. Lunar Exploration Insights Recognized from Chandrayaan-1 M3 Imaging Spectrometer

    Science.gov (United States)

    Pieters, Carle; Green, Robert O.; Boardman, Joseph

    2016-07-01

    One of the most important lessons learned from the renaissance of lunar exploration over the last decade is that new discoveries and surprises occur with every new mission to the Moon. Although the color of the Moon had been measured using Earth-based telescopes even before Apollo, modern instruments sent to orbit the Moon provide a scope of inquiry unimaginable during the last century. Spacecraft have now been successfully sent to the Moon by six different space agencies from around the world and the number is growing. The Indian Chandrayaan- 1 spacecraft carried a suite of indigenous instruments as well as several guest instruments from other countries, including the Moon Mineralogy Mapper (M-cube) supplied by NASA. Even though Chandrayaan's lifetime in orbit was shortened by technical constraints, M3 provided a taste of the power of near-infrared imaging spectroscopy used for science and exploration at the Moon. Contrary to expectations, the lunar surface was discovered to be hydrated, which is now known to result from solar wind H combining with O of rocks and soil. Surficial hydration was found to be pervasive across the Moon and the limited data hint at both local concentrations and temporal variations. The prime objective of M3 was to characterize lunar mineralogy in a spatial context. Working in tandem with related instruments on JAXA's SELENE, M3 readily recognized and mapped known minerals from mare and highland terrains (pyroxenes, olivine) at high resolution, but also detected diagnostic properties of crystalline plagioclase which, when mapped across a spatial context, enabled the unambiguous identification of a massive crustal layer of plagioclase that clearly resulted from an early magma ocean. An additional surprise came with the discovery of a new rock type on the Moon that had not been recognized in samples returned by Apollo and Luna: a Mg-rich spinel anorthosite associated with material excavated from some of the greatest lunar depths. In

  17. Forsmark Site: M3 modelling and 2D visualisation of the hydrochemical parameters in Forsmark groundwater

    Energy Technology Data Exchange (ETDEWEB)

    Gurban, Ioana (3D Terra (Canada))

    2008-08-15

    This work represents the stage 2.3 of the hydrochemical evaluation and modelling of the Forsmark data. This comprises M3 modelling and 2D visualisation of the data along the boreholes. The following conclusions can be drawn: - M3 modelling helped to summarise and understand the data, by using as variables the major elements and the isotopes delta18O and deltaD. - Previous alternative models and the experience from Forsmark 1.2, 2.1 and 2.2, helped to clarify different previously unsolved issues such as: the use of variables, tests with different endmembers, the use of only groundwater data in order to build a bedrock hydrochemical model. - The visualisation of the mixing proportions along the boreholes helps to understand the distribution of the data in the domain and to check and compare the results of different models; and therefore to chose the model which best describes the measured data. - The different M3 modelling tests resulted in the following conclusions: a) When calculating mixing proportions only samples from the boreholes will be used, b) the altered meteoric end-member which best describes the more shallow groundwater compositions is defined by a representative upper bedrock sample; the Littorina end-member employed the existing modelled compositions; the Deep saline and glacial end-members compositions were tested by means of a feasibility study and employed in the modelling. - Three models were presented. All the models are good and can be used, but the best is to use the one that fits the conceptual model best and the hydrogeochemical understanding. - The use of Littorina, Glacial, Deep Saline and Altered Meteoric end-members makes possible the comparison of different sites such as Laxemar and Forsmark. - All the data used in the M3 modelling and the results of the modelling and visualisation along the boreholes are presented in SKB database SIMON. - The extended data do not affect the results of the modelling of the Forsmark 2.3 dataset (the

  18. Precursory signatures in the radon and geohydrological borehole data for M4.9 Kharsali earthquake of Garhwal Himalaya

    Energy Technology Data Exchange (ETDEWEB)

    Choubey, V.M., E-mail: vchoubey@wihg.res.in [Wadia Institute of Himalayan Geology, 33 General Mahadeo Singh Road, Dehradun 248001 (India); Kumar, Naresh; Arora, B.R. [Wadia Institute of Himalayan Geology, 33 General Mahadeo Singh Road, Dehradun 248001 (India)

    2009-11-01

    Continuous recording of different geophysical parameters incorporated at a single location as a unified effort for earthquake precursory through geodynamical changes initiated for the first time in the Garhwal Himalaya, India. A 68 m deep borehole, penetrating into the water table is operated for continuous radon monitoring along with meteorological/geohydrological observations at two points, one at 10 m (in the air column) and the second one at 50 m (within water column) depths from surface. Preliminary studies reveal diagnostic short duration anomalies in radon concentration recorded few days before the occurrence of a nearby moderate M4.9 earthquake at Kharsali on the 23rd of July, 2007. For nearly half of the year, radon emanation at 10 m depth in the closed air column showed definite pattern of daily variations that may be due to the influence of tidal forces, meteorological and other geodynamical phenomena. This pattern is totally missing during June and July, 2007 when few anomalies for small durations were observed out of which two are unique. These two anomalies exceed 2{sigma} (standard deviation) from average radon concentration in both positive and negative sides. However, its emanation at 50 m depth (water radon) is almost constant throughout the year 2007 except some disturbances observed to the ending of June and during July. These abnormalities in radon emanation and other parameters in the borehole may be considered precursory to the M4.9 Kharsali earthquake of July 23, 2007 having an epicenter distance of 60 km. The empirical relation used for amount of radon anomaly with the epicenter distance predicts an earthquake of M4.6 and M4.7 with the observed anomaly at 10 m and 50 m observation points respectively after taking a 60 km epicenter distance.

  19. Kinetics of Proton Transport into Influenza Virions by the Viral M2 Channel

    NARCIS (Netherlands)

    Ivanovic, Tijana; Rozendaal, Rutger; Floyd, Daniel L.; Popovic, Milos; Oijen, Antoine M. van; Harrison, Stephen C.

    2012-01-01

    M2 protein of influenza A viruses is a tetrameric transmembrane proton channel, which has essential functions both early and late in the virus infectious cycle. Previous studies of proton transport by M2 have been limited to measurements outside the context of the virus particle. We have developed a

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

    Science.gov (United States)

    1966-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

    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…

  3. De novo formal synthesis of (-)-virginiamycin M2 via the asymmetric hydration of dienoates.

    Science.gov (United States)

    Mortensen, Matthew S; Osbourn, Joshua M; O'Doherty, George A

    2007-08-02

    A de novo approach to the formal total synthesis of the macrolide natural product (-)-virginiamycin M2 has been achieved via a convergent approach. The absolute and relative stereochemistry of the nonpeptide portion of (-)-virginiamycin M2 was introduced by two Sharpless asymmetric dihydroxylation reactions.

  4. Solid State NMR Observation of Phenylalanine Residues in M2 Protein from Influenza a Virus

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    @@ The M2 protein from influenza A functions as a proton channel. It has been cloned and over-expressed in Escherchia coli. Large quantities of recombinant protein are purified by Ni2 affinity chromatography. The residues in M2 have been selectively labeled with 15N in an aromatic amino acid autotroph CT19.

  5. Almost optimal distributed M2M multicasting in wireless mesh networks

    DEFF Research Database (Denmark)

    Xin, Qin; Manne, Fredrik; Zhang, Yan

    2012-01-01

    nodes. It is known that the computation of an optimal M2M multicasting schedule isNP-hard. We present a fully distributed deterministic algorithm for such an M2M multicasting problem and analyze its time complexity. We show that if the maximum hop distance between any two out of the k participants is d...

  6. 12 CFR Appendix M2 to Part 226 - Actual Repayment Disclosures

    Science.gov (United States)

    2010-01-01

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

  7. The Mediterranean Moored Multi-sensor Array (M3A: system development and initial results

    Directory of Open Access Journals (Sweden)

    K. Nittis

    Full Text Available Operational forecasting of ocean circulation and marine ecosystem fluctuations requires multi-parametric real-time measurements of physical and biochemical properties. The architecture of a system that is able to provide such measurements from the upper-thermocline layers of the Mediterranean Sea is described here. The system was developed for the needs of the Mediterranean Forecasting System and incorporates state-of-the-art sensors for optical and chemical measurements in the upper 100 m and physical measurements down to 500 m. Independent moorings that communicate via hydro-acoustic modems are hosting the sensors. The satellite data transfer and the large autonomy allow for the operation of the system in any open-ocean site. The system has been in pre-operational use in the Cretan Sea since January 2000. The results of this pilot phase indicate that multi-parametric real-time observations with the M3A system are feasible, if a consistent maintenance and re-calibration program is followed. The main limitations of the present configuration of M3A are related: (a to bio-fouling that primarily affects the turbidity and secondarily affects the other optical sensors, and (b to the limited throughput of the currently used satellite communication system.

    Key words. Atmospheric composition and structure (instruments and techniques. Oceanography: general (ocean prediction Oceanography: physical (upper ocean process

  8. Connexins and M3 Muscarinic Receptors Contribute to Heterogeneous Ca2+ Signaling in Mouse Aortic Endothelium

    Directory of Open Access Journals (Sweden)

    François-Xavier Boittin

    2013-02-01

    Full Text Available Background/Aims: Smooth muscle tone is controlled by Ca2+ signaling in the endothelial layer. Mouse endothelial cells are interconnected by gap junctions made of Connexin40 (Cx40 and Cx37, which allow the exchange of signaling molecules to coordinate their activity. Here, we investigated the role of Cx40 in the endothelial Ca2+ signaling of the mouse aorta. Methods: Ca2+ imaging was performed on intact aortic endothelium from both wild type (Cx40+/+ and Connexin40-deficient (Cx40 -/- mice. Results: Acetylcholine (ACh induced early fast and high amplitude Ca2+ transients in a fraction of endothelial cells expressing the M3 muscarinic receptors. Inhibition of intercellular communication using carbenoxolone or octanol fully blocked the propagation of ACh-induced Ca2+ transients toward adjacent cells in WT and Cx40-/- mice. As compared to WT, Cx40-/- mice displayed a reduced propagation of ACh-induced Ca2+ waves, indicating that Cx40 contributes to the spreading of Ca2+ signals. The propagation of those Ca2+ responses was not blocked by suramin, a blocker of purinergic ATP receptors, indicating that there is no paracrine effect of ATP release on the Ca2+ waves. Conclusions: Altogether our data show that Cx40 and Cx37 contribute to the propagation and amplification of the Ca2+ signaling triggered by ACh in endothelial cells expressing the M3 muscarinic receptors.

  9. HST Observations of Blue Straggler Stars in the Core of the Globular Cluster M3

    CERN Document Server

    Ferraro, F R; Pecci, F F; Cacciari, C; Dorman, B; Rood, R T; Buonanno, R; Corsi, C E; Burgarella, D; Laget, M

    1997-01-01

    The core of the Galactic Globular Cluster M3 (NGC 5272) has been observed with the WFPC2 through the filters F255W, F336W, F555W, and F814W. Using these observations along with a thorough reanalysis of earlier catalogs, we have produced a catalog of blue straggler stars (BSS) spanning the cluster. Earlier studies and the fainter part of our sample suffer severe selection biases. Our analysis is based on a more reliable bright global sample of 122 BSS. We confirm earlier suggestions that the radial BSS distribution in M3 is bimodal. It is strongly peaked in the center, has a clear dip 100--200" from the center, and rises again at larger radii. The observed distribution agrees with the dynamical model of Sigurdsson et al. (1994) which takes into account both star collisions and merging of primordial binaries for the origin of BSS. The observed luminosity functions of BSS in the inner and outer parts of the cluster are different. Interpreting these using the models of Bailyn & Pinsonneault (1995), we suggest...

  10. Scale-up of industrial biodiesel production to 40 m3using a liquid lipase formulation

    DEFF Research Database (Denmark)

    Price, Jason; Nordblad, Mathias; Martel, Hannah H.

    2016-01-01

    In this work, we demonstrate the scale-up from an 80 L fed-batch scale to 40 m3 along with the design of a 4 m3continuous process for enzymatic biodiesel production catalysed by NS-40116 (a liquid formulation of a modified Thermomyces lanuginosus lipase). Based on the analysis of actual pilot plant...... the fed-batch and CSTR cases. Given similar operating conditions, the CSTR operation on average, has a reaction time which is 1.3 times greater than the fed-batch operation. We also showed how the process metrics can be used to quickly estimate the selling price of the enzyme. Assuming a biodiesel selling...... price of 0.6 USD/kg and a one-time use of the enzyme (0.1% (w/woil) enzyme dosage); the enzyme can then be sold for 30 USD/kg which ensures that that the enzyme cost is not more than 5% of the biodiesel revenue. This article is protected by copyright. All rights reserved...

  11. M3A system (2000–2005 – operation and maintenance

    Directory of Open Access Journals (Sweden)

    G. Petihakis

    2007-01-01

    Full Text Available During the pilot phase of the Mediterranean Forecasting System (MFSPP (2000 2003, a prototype observing system (Mediterranean Moored Multi-sensor Array – M3A was designed, developed and operated in the Cretan Sea for continuous oceanographic measurements in real time. The main problems encountered were associated with biofouling, underwater and aerial communication and with the design of the surface buoy. In the second phase of the MFS project named Mediterranean Forecasting System Towards Environmental Predictions (MFSTEP (2003–2005, the aim was to solve those problems and to consolidate the M3A. For the minimisation of biofouling a pilot field study was performed and the techniques of bromine solution and copper shielding were evaluated. Additionally, the oligotrophy of the Aegean Sea dictated the need to ignore factory calibrations and to perform site-specific laboratory calibrations of the sensors. This procedure was proved necessary and produced calibration coefficients that gave results comparable to the measurements obtained with the laboratory analysis method. During the approximately five years of operation, there were 13 scheduled and 15 emergency visits, with a total duration of 65 days. The acquired experience through the maintenance program proved that the continuous observation of such a very important system with a relative low cost is feasible.

  12. Machining risk of beryllium disease and sensitization with median exposures below 2 micrograms/m3.

    Science.gov (United States)

    Kreiss, K; Mroz, M M; Newman, L S; Martyny, J; Zhen, B

    1996-07-01

    We examined the prevalence of beryllium sensitization in relation to work process and beryllium exposure measurements in a beryllia ceramics plant that had operated since 1980. We interviewed 136 employees (97.8% of the workforce), ascertained beryllium sensitization with the beryllium lymphocyte proliferation blood test, and reviewed historical industrial hygiene measurements. Of eight beryllium-sensitized employees (5.9%), six (4.4% of participating employees) had granulomatous disease on transbronchial lung biopsy. Machinists had a sensitization rate of 14.3% compared to a rate of 1.2% among other employees. Machining had significantly higher general area and breathing zone measurements than did other processes in the time period in which most beryllium-sensitized cases had started machining work. Daily weighted average (DWA) estimates of exposure for matching processes also exceeded estimates for other work processes in that time period, with a median DWA of 0.9 microgram/m3. Machining process DWAs accounted for the majority of DWAs exceeding the 2.0 micrograms/m3 OSHA standard, with 8.1% of machining DWAs above the standard. We conclude that lowering machining process-related exposures may be important to lowering risk of beryllium disease.

  13. Role of M2 Muscarinic Receptor in the Airway Response to Methacholine of Mice Selected for Minimal or Maximal Acute Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Juciane Maria de Andrade Castro

    2013-01-01

    Full Text Available Airway smooth muscle constriction induced by cholinergic agonists such as methacholine (MCh, which is typically increased in asthmatic patients, is regulated mainly by muscle muscarinic M3 receptors and negatively by vagal muscarinic M2 receptors. Here we evaluated basal (intrinsic and allergen-induced (extrinsic airway responses to MCh. We used two mouse lines selected to respond maximally (AIRmax or minimally (AIRmin to innate inflammatory stimuli. We found that in basal condition AIRmin mice responded more vigorously to MCh than AIRmax. Treatment with a specific M2 antagonist increased airway response of AIRmax but not of AIRmin mice. The expression of M2 receptors in the lung was significantly lower in AIRmin compared to AIRmax animals. AIRmax mice developed a more intense allergic inflammation than AIRmin, and both allergic mouse lines increased airway responses to MCh. However, gallamine treatment of allergic groups did not affect the responses to MCh. Our results confirm that low or dysfunctional M2 receptor activity is associated with increased airway responsiveness to MCh and that this trait was inherited during the selective breeding of AIRmin mice and was acquired by AIRmax mice during allergic lung inflammation.

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

    Energy Technology Data Exchange (ETDEWEB)

    Ehlert, F.J.; Tran, L.P. (Univ. of California, Irvine (USA))

    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.

  15. M2受体的细胞表征及其运动与心脏、血管M2受体研究进展%Cell Characterization of M2 Receptor and Research Advancement of Exercise Training and Cardiovascular M2 Receptor

    Institute of Scientific and Technical Information of China (English)

    田振军; 杜蕾

    2009-01-01

    目的:探讨M2受体的细胞表征及其运动与心脏、血管M2受体的基础与应用前景.方法:采用文献回顾与前瞻性分析及逻辑推理相结合的方法,跟踪M2受体表征研究进展及其运动与心脏、血管M2受体表征在体育科学领域中的应用.结果与结论:M2受体在心肌、血管平滑肌等细胞上广泛分布,具有重要的生物学功能.不同运动强度和心肌细胞M2受体表征、运动后心率恢复与M2受体基因多态性、心脏运动康复与M2受体表征等的关系密切.积极开展M2受体基因变异与运动前预测心源性死亡风险,运动性心律失常与M2受体表征,运动性心肌损伤引起的心功能紊乱与M2受体表征,基于M2受体靶点的心脏、血管运动康复及其中药有效成份筛选等方面的研究,具有重要的基础研究价值和应用前景.对有效筛选心脏、血管运动康复方案和与M2受体相关药物有效成份具有重大意义.

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

    Science.gov (United States)

    Sankararamakrishnan, R; Samsom, M S

    1994-12-01

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

  17. VARIABILITY STUDIES IN M3 GENERATION IN BLACKGRAM (VIGNA MUNGO (L.HEPPER

    Directory of Open Access Journals (Sweden)

    M P MESHRAM

    2013-12-01

    Full Text Available In the present study, pure line seeds of black gram variety viz. T-9, TPU-4 and one promising genotype AKU-18 was treated with gamma irradiation (15kR, 25kR and 35kR with the objective to assess the variability in M3 generation.. Highest GCV and PCV and high estimates of heritability were recorded for the characters sprouting percentage, number of pods plant-1 and grain yield plant-1 (g. High heritability accompanied with high genetic advance was recorded for number of pods plant-1 governed by additive gene effects and therefore selection based on phenotypic performance will be useful to improve character in future.

  18. Trimble M3 1” and South Nts-362R Total Station Angle Measurement Accuracy Analysis

    Directory of Open Access Journals (Sweden)

    Oleniacz Grzegorz

    2017-03-01

    Full Text Available The main purpose of this study was to obtain information about the actual precision of angle measurements with two instruments (Trimble M3 1 "and South NTS-362R, realizable in given measurement conditions. This object is achieved by using a simplified method of testing instruments contained in the PN-ISO 17123-3 standard [1]. This is a continuation of research described in [2], carried out on the same test base, but this time in a different, less favorable field conditions. The use of the same instrument has created an opportunity to compare and analyze the measurement results. The scope of work includes the measurement and results preparation along with statistical processing of the obtained results for both instruments.

  19. Half lives of spherical proton emitters using density dependent M3Y interaction

    CERN Document Server

    Chowdhury, P R; Basu, D N

    2005-01-01

    The proton radioactivity lifetimes of spherical proton emitters from the ground and the isomeric states are calculated using the microscopic nucleon-nucleus interaction potentials. The daughter nuclei density distributions are folded with a realistic density dependent M3Y effective interaction supplemented by a zero-range pseudo-potential. The density dependence parameters of the interaction are extracted from the nuclear matter calculations. The saturation energy per nucleon used for nuclear matter calculations is determined from the co-efficient of the volume term of Bethe-Weizsacker mass formula which is evaluated by fitting the recent experimental and estimated atomic mass excesses from Audi-Wapstra-Thibault atomic mass table by minimizing the mean square deviation. The quantum mechanical tunneling probability is calculated within the WKB approximation. Spherical charge distributions are used for calculating the Coulomb interaction potentials. These calculations provide good estimates for the observed pro...

  20. Electrodialytic remediation of CCA-treated waste wood in a 2 m3 pilot plant

    DEFF Research Database (Denmark)

    Christensen, Iben Vernegren; Pedersen, Anne Juul; Ottosen, Lisbeth M.;

    2006-01-01

    Waste wood that has been treated with chromated-copper-arsenate (CCA) poses a potential environmental problem due to the content of copper, chromium and arsenic. A pilot plant for electrodialytic remediation of up to 2 m3 wood has been designed and tested and the results are presented here. Several...... fractions. The best remediation efficiency was obtained in an experiment with an electrode distance of 60 cm, and 100 kg wood chips. In this experiment 87% copper, 81% chromium and > 95% arsenic were removed. One other experiment was also analysed for arsenic. In this experiment the distance between...... the working electrodes was 1.5 m and here 95% As was removed. The results showed that arsenic may be the easiest removable of the copper, chromium and arsenic investigated here. This is very encouraging since arsenic is the CCA components of most environmental concern....

  1. Variable Star Status of Two Stars: V204 and I-I-39 in M3

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The star I-I-42 (=vZ1390), a cluster member in M3, located near the red edge of the instability strip of the horizontal branch, was discovered by Roberts and Sandage as a low amplitude variable, it was designated as V204 in the "second catalogue of variable stars in globular clusters", but its coordinates given in all versions of this catalogue are wrong since 1955. We argue that V204 is indeed a low amplitude HB variable star, located near to the red edge of the instability strip, with a period of 0.74785d and an amplitude of about 0.04 mag in V. We also find that the red cluster member star I-I-39 is a low amplitude variable with a period of 1.16d and amplitude of about 0.03 mag in V which might be pulsating at the second overtone.

  2. Modeling of lithium granule injection in NSTX using M3D-C1

    Science.gov (United States)

    Fil, A.; Kolemen, E.; Ferraro, N.; Jardin, S.; Parks, P. B.; Lunsford, R.; Maingi, R.

    2017-05-01

    In this paper, we present simulations of pedestal control by lithium granule injection (LGI) in NSTX. A model for small granule ablation has been implemented in the M3D-C1 code (Jardin et al 2012 Comput. Sci. Discovery 5 014002), allowing the simulation of realistic lithium granule injections. 2D and 3D simulations of Li injections in NSTX H-mode plasmas are performed and the effect of granule size, injection angle and velocity on the pedestal gradient increase is studied. The amplitude of the local pressure perturbation caused by the granules is found to be highly dependent on the solid granule size. Adjusting the granule injection velocity allows one to inject more particles at the pedestal top. 3D simulations show the destabilization of high order MHD modes whose amplitude is directly linked to the localized pressure perturbation, which is found to depend on the toroidal localization of the granule density source.

  3. Designing inhibitors of M2 proton channel against H1N1 swine influenza virus.

    Directory of Open Access Journals (Sweden)

    Qi-Shi Du

    Full Text Available BACKGROUND: M2 proton channel of H1N1 influenza A virus is the target protein of anti-flu drugs amantadine and rimantadine. However, the two once powerful adamantane-based drugs lost their 90% bioactivity because of mutations of virus in recent twenty years. The NMR structure of the M2 channel protein determined by Schnell and Chou (Nature, 2008, 451, 591-595 may help people to solve the drug-resistant problem and develop more powerful new drugs against H1N1 influenza virus. METHODOLOGY: Docking calculation is performed to build the complex structure between receptor M2 proton channel and ligands, including existing drugs amantadine and rimantadine, and two newly designed inhibitors. The computer-aided drug design methods are used to calculate the binding free energies, with the computational biology techniques to analyze the interactions between M2 proton channel and adamantine-based inhibitors. CONCLUSIONS: 1 The NMR structure of M2 proton channel provides a reliable structural basis for rational drug design against influenza virus. 2 The channel gating mechanism and the inhibiting mechanism of M2 proton channel, revealed by the NMR structure of M2 proton channel, provides the new ideas for channel inhibitor design. 3 The newly designed adamantane-based inhibitors based on the modeled structure of H1N1-M2 proton channel have two pharmacophore groups, which act like a "barrel hoop", holding two adjacent helices of the H1N1-M2 tetramer through the two pharmacophore groups outside the channel. 4 The inhibitors with such binding mechanism may overcome the drug resistance problem of influenza A virus to the adamantane-based drugs.

  4. Design of a Cortex-M4 based ultrasonic phased array detection system%基于Cortex-M4的超声相控阵探测系统的设计

    Institute of Scientific and Technical Information of China (English)

    赵连睿; 杨济民; 李振江; 李玉坤

    2013-01-01

    We design an obstacle detection system with ultrasonic phased array detection and the microcontroller Cortex-M4 as a processor. Experiments show that the actual sound field strength of the focal area is greater than that of conventional ultrasonic technology and sound energy is more convergent. Its detection distance is from 0.3 to 5.5 m, and measurement accuracy is ±1 cm. The system is therefore effective and satisfactory.%设计了一种以Cortex-M4微控制器STM32F407为核心,采用超声相控阵技术对障碍物进行探测的系统.实验结果表明,该系统聚焦探测区域的实际声场强度大于常规的超声波技术,声波能量更为集中.系统的探测范围在0.3~5.5m,探测精度±1 cm,稳定性好,准确方便.

  5. 米曲霉Aspergillus oryzae M-4降解己烯雌酚的特性研究%Degradation Characteristics of Diethylstilbestrol by Aspergillus oryzae M-4

    Institute of Scientific and Technical Information of China (English)

    胡凯弟; 邓维琴; 陈树平; 柴先杜; 刘爱平; 卓文杰; 刘书亮

    2016-01-01

    以1株分离自酱油曲的米曲霉(Aspergillus oryzae)M-4为材料,初步研究其降解己烯雌酚(diethylstilbestrol,DES)的特性.米曲霉M-4对DES的降解率与菌体生物量呈正相关,在基础盐培养基(mineral salt medium,MM)中培养9d对100mg/L的DES降解率为93%.动力学研究表明,该菌株降解DES的过程符合一级动力学方程,在所测试的培养温度、初始pH值、底物质量浓度范围内,DES半衰期为1.645~5.295d.培养温度30℃和偏酸性环境有利于其对DES的降解;底物质量浓度越高,其半衰期越长.

  6. CH5M3D: an HTML5 program for creating 3D molecular structures.

    Science.gov (United States)

    Earley, Clarke W

    2013-11-18

    While a number of programs and web-based applications are available for the interactive display of 3-dimensional molecular structures, few of these provide the ability to edit these structures. For this reason, we have developed a library written in JavaScript to allow for the simple creation of web-based applications that should run on any browser capable of rendering HTML5 web pages. While our primary interest in developing this application was for educational use, it may also prove useful to researchers who want a light-weight application for viewing and editing small molecular structures. Molecular compounds are drawn on the HTML5 Canvas element, with the JavaScript code making use of standard techniques to allow display of three-dimensional structures on a two-dimensional canvas. Information about the structure (bond lengths, bond angles, and dihedral angles) can be obtained using a mouse or other pointing device. Both atoms and bonds can be added or deleted, and rotation about bonds is allowed. Routines are provided to read structures either from the web server or from the user's computer, and creation of galleries of structures can be accomplished with only a few lines of code. Documentation and examples are provided to demonstrate how users can access all of the molecular information for creation of web pages with more advanced features. A light-weight (≈ 75 kb) JavaScript library has been made available that allows for the simple creation of web pages containing interactive 3-dimensional molecular structures. Although this library is designed to create web pages, a web server is not required. Installation on a web server is straightforward and does not require any server-side modules or special permissions. The ch5m3d.js library has been released under the GNU GPL version 3 open-source license and is available from http://sourceforge.net/projects/ch5m3d/.

  7. Evaluation of secure capability-based access control in the M2M local cloud platform

    DEFF Research Database (Denmark)

    Anggorojati, Bayu; Prasad, Neeli R.; Prasad, Ramjee

    2016-01-01

    of multiple distributed M2M gateways, creating new challenges in the access control. Some existing access control systems lack in scalability and flexibility to manage access from users or entity that belong to different authorization domains, or fails to provide fine grained and flexible access right...... delegation. Recently, the capability based access control has been considered as method to manage access in the Internet of Things (IoT) or M2M domain. In this paper, the implementation and evaluation of a proposed secure capability based access control in the M2M local cloud platform is presented...

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

    Energy Technology Data Exchange (ETDEWEB)

    Bradbury, Andrew M [Los Alamos National Laboratory; Velappan, Nileena [Los Alamos National Laboratory; Schmidt, Jurgen G [Los Alamos National Laboratory

    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.

  9. Aggregation and Trunking of M2M Traffic via D2D Connections

    DEFF Research Database (Denmark)

    Rigazzi, Giovanni; Kiilerich Pratas, Nuno; Popovski, Petar

    2015-01-01

    Machine-to-Machine (M2M) communications is one of the key enablers of the Internet of Things (IoT). Billions of devices are expected to be deployed in the near future for novel M2M applications demanding ubiquitous access and global connectivity. In order to cope with the massive number of machines......, there is a need for new techniques to coordinate the access and allocate the resources. Although the majority of the proposed solutions are focused on the adaptation of the traditional cellular networks to the M2M traffic patterns, novel approaches based on the direct communication among nearby devices may...

  10. 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

    Science.gov (United States)

    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.

  11. The muscarinic M1/M4 receptor agonist xanomeline exhibits antipsychotic-like activity in Cebus apella monkeys

    DEFF Research Database (Denmark)

    Andersen, Maibritt B; Fink-Jensen, Anders; Peacock, Linda

    2003-01-01

    Xanomeline is a muscarinic M(1)/M(4) preferring receptor agonist with little or no affinity for dopamine receptors. The compound reduces psychotic-like symptoms in patients with Alzheimer's disease and exhibits an antipsychotic-like profile in rodents without inducing extrapyramidal side effects ...... that xanomeline inhibits D-amphetamine- and (-)-apomorphine-induced behavior in Cebus apella monkeys at doses that do not cause EPS. These data further substantiate that muscarinic receptor agonists may be useful in the pharmacological treatment of psychosis....

  12. Sustainable Cost Models for mHealth at Scale: Modeling Program Data from m4RH Tanzania.

    Directory of Open Access Journals (Sweden)

    Emily R Mangone

    Full Text Available There is increasing evidence that mobile phone health interventions ("mHealth" can improve health behaviors and outcomes and are critically important in low-resource, low-access settings. However, the majority of mHealth programs in developing countries fail to reach scale. One reason may be the challenge of developing financially sustainable programs. The goal of this paper is to explore strategies for mHealth program sustainability and develop cost-recovery models for program implementers using 2014 operational program data from Mobile for Reproductive Health (m4RH, a national text-message (SMS based health communication service in Tanzania.We delineated 2014 m4RH program costs and considered three strategies for cost-recovery for the m4RH program: user pay-for-service, SMS cost reduction, and strategic partnerships. These inputs were used to develop four different cost-recovery scenarios. The four scenarios leveraged strategic partnerships to reduce per-SMS program costs and create per-SMS program revenue and varied the structure for user financial contribution. Finally, we conducted break-even and uncertainty analyses to evaluate the costs and revenues of these models at the 2014 user volume (125,320 and at any possible break-even volume.In three of four scenarios, costs exceeded revenue by $94,596, $34,443, and $84,571 at the 2014 user volume. However, these costs represented large reductions (54%, 83%, and 58%, respectively from the 2014 program cost of $203,475. Scenario four, in which the lowest per-SMS rate ($0.01 per SMS was negotiated and users paid for all m4RH SMS sent or received, achieved a $5,660 profit at the 2014 user volume. A Monte Carlo uncertainty analysis demonstrated that break-even points were driven by user volume rather than variations in program costs.These results reveal that breaking even was only probable when all SMS costs were transferred to users and the lowest per-SMS cost was negotiated with telecom partners

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

    Directory of Open Access Journals (Sweden)

    Michael J V White

    Full Text Available 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.

  14. HF183/BFDrev and HumM2 qPCR data

    Data.gov (United States)

    U.S. Environmental Protection Agency — Concentration estimates for HF183/BFDrev and HumM2 qPCR genetic markers in raw sewage collected from 54 geographic locations across the United States. This dataset...

  15. Vanishing Str M2 in the presence of anomalous U A(1)

    Science.gov (United States)

    Lopez, Jorge L.; Nanopoulos, D. V.

    1996-02-01

    We show that the presence of an anomalous U A(1) factor in the gauge group of string-derived models may have the new and important phenomenological consequence of allowing the vanishing of Str M2 in the “shifted” vacuum that results in the process of cancelling the anomalous U A(1). The feasibility of this effect seems to be enhanced by a vanishing vacuum energy, and by a “small” value of Str M2 in the original vacuum. In the class of free-fermionic models with vanishing vacuum energy that we focus on, a necessary condition for this mechanism to be effective is that Str M2 > 0 in the original vacuum. A vanishing Str M2 ameliorates the cosmological constant problem and is a necessary element in the stability of the no-scale mechanism.

  16. Reliable Radio Access for Massive Machine-to-Machine (M2M) Communication

    DEFF Research Database (Denmark)

    Madueño, Germán Corrales

    Machine-to-Machine (M2M) communication is a term that identifies the emerging paradigm of interconnected systems, machines, and things that communicate and collaborate without human intervention. The characteristics of M2M Communications are small payloads and sporadic transmissions, while...... the service requirements can range from massive number of devices to ultra-reliable. This PhD thesis focuses on novel mechanisms to meet these requirements in a variety of wireless systems, from well-established technologies such as cellular networks, to emerging technologies like IEEE 802.11ah. Today...... an overwhelming 89% of the deployed M2M modules are GPRS-based. This motivates us to investigate the potential of GPRS as a dedicated M2M network. We show that by introducing minimal modifications to GPRS operation, a large number of devices can be reliably supported. Surprisingly, even though LTE is seen...

  17. Porous Photocatalytic Membrane Microreactor (P2M2): A new reactor concept for photochemistry

    NARCIS (Netherlands)

    Aran, H.C.; Salamon, D.; Rijnaarts, T.; Mul, G.; Wessling, M.; Lammertink, R.G.H.

    2011-01-01

    In this study, a new membrane microreactor concept for multiphase photocatalytic reactions is demonstrated. Microfabrication, photocatalyst immobilization and surface modification steps were performed to develop a Porous Photocatalytic Membrane Microreactor (P2M2). This concept benefits from a stabl

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

    Science.gov (United States)

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

    2016-12-01

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

  19. Porous Photocatalytic Membrane Microreactor (P2M2): A new reactor concept for photochemistry

    NARCIS (Netherlands)

    Aran, H.C.; Salamon, David; Rijnaarts, Timon; Rijnaarts, T.; Mul, Guido; Wessling, Matthias; Lammertink, Rob G.H.

    2011-01-01

    In this study, a new membrane microreactor concept for multiphase photocatalytic reactions is demonstrated. Microfabrication, photocatalyst immobilization and surface modification steps were performed to develop a Porous Photocatalytic Membrane Microreactor (P2M2). This concept benefits from a

  20. The challenges of M2M massive access in wireless cellular networks

    National Research Council Canada - National Science Library

    Biral, Andrea; Centenaro, Marco; Zanella, Andrea; Vangelista, Lorenzo; Zorzi, Michele

    2015-01-01

    .... Nonetheless, general consensus has been reached upon some specific challenges, such as the need for 5G wireless access networks to support massive access by MTDs, as a consequence of the proliferation of M2M services...

  1. Chemokine Binding Protein M3 of Murine Gammaherpesvirus 68 Modulates the Host Response to Infection in a Natural Host

    Science.gov (United States)

    Hughes, David J.; Kipar, Anja; Leeming, Gail H.; Bennett, Elaine; Howarth, Deborah; Cummerson, Joanne A.; Papoula-Pereira, Rita; Flanagan, Brian F.; Sample, Jeffery T.; Stewart, James P.

    2011-01-01

    Murine γ-herpesvirus 68 (MHV-68) infection of Mus musculus-derived strains of mice is an attractive model of γ-herpesvirus infection. Surprisingly, however, ablation of expression of MHV-68 M3, a secreted protein with broad chemokine-binding properties in vitro, has no discernable effect during experimental infection via the respiratory tract. Here we demonstrate that M3 indeed contributes significantly to MHV-68 infection, but only in the context of a natural host, the wood mouse (Apodemus sylvaticus). Specifically, M3 was essential for two features unique to the wood mouse: virus-dependent inducible bronchus-associated lymphoid tissue (iBALT) in the lung and highly organized secondary follicles in the spleen, both predominant sites of latency in these organs. Consequently, lack of M3 resulted in substantially reduced latency in the spleen and lung. In the absence of M3, splenic germinal centers appeared as previously described for MHV-68-infected laboratory strains of mice, further evidence that M3 is not fully functional in the established model host. Finally, analyses of M3's influence on chemokine and cytokine levels within the lungs of infected wood mice were consistent with the known chemokine-binding profile of M3, and revealed additional influences that provide further insight into its role in MHV-68 biology. PMID:21445235

  2. Chemokine binding protein M3 of murine gammaherpesvirus 68 modulates the host response to infection in a natural host.

    Directory of Open Access Journals (Sweden)

    David J Hughes

    2011-03-01

    Full Text Available Murine γ-herpesvirus 68 (MHV-68 infection of Mus musculus-derived strains of mice is an attractive model of γ-herpesvirus infection. Surprisingly, however, ablation of expression of MHV-68 M3, a secreted protein with broad chemokine-binding properties in vitro, has no discernable effect during experimental infection via the respiratory tract. Here we demonstrate that M3 indeed contributes significantly to MHV-68 infection, but only in the context of a natural host, the wood mouse (Apodemus sylvaticus. Specifically, M3 was essential for two features unique to the wood mouse: virus-dependent inducible bronchus-associated lymphoid tissue (iBALT in the lung and highly organized secondary follicles in the spleen, both predominant sites of latency in these organs. Consequently, lack of M3 resulted in substantially reduced latency in the spleen and lung. In the absence of M3, splenic germinal centers appeared as previously described for MHV-68-infected laboratory strains of mice, further evidence that M3 is not fully functional in the established model host. Finally, analyses of M3's influence on chemokine and cytokine levels within the lungs of infected wood mice were consistent with the known chemokine-binding profile of M3, and revealed additional influences that provide further insight into its role in MHV-68 biology.

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

    Directory of Open Access Journals (Sweden)

    Tanja Buchacher

    Full Text Available 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

  4. Conductrometric, density and thermal measurements of the M2S2O7 (M = Na, K, Rb, Cs) salts

    DEFF Research Database (Denmark)

    Hatem, Gerard; Abdoun, Fatma; Gaune-Escard, Marcelle;

    1998-01-01

    Physico-chemical properties, such as densities, conductivities, enthalpies of phase transitions and melting points, have been measured and summarised for the alkali pyrosulphates Na2S2O7, K2S2O7, Rb2S2O7, CS2S2O7. The densities of the molten pyrosulphates could be expressed by the linear expressi...... rho=A+B(T-T-m) where T-m is the middle temperature of the temperature range measured, i.e. from the melting point and up to 550 degrees C at the maximum. The specific conductivities of the molten pyrosulphates have been expressed by the equation rho=A+B(T-T-m)+C(T-T-m)(2)+ D(T-T-m)(3......) in the temperature range from the melting point and up to 500 degrees C at the maximum. From these measurements also the activation energy for the equivalent conductivity of the alkali cations in the melts could be calculated and compared to the analogous alkalisulphates. By calorimetric investigations of the alkali...... pyrosulphates the temperatures of fusion, the enthalpies and entropies of fusion and possible solid-solid transitions together with the molar heat capacities of the solid and liquid pyrosulphates at 300-800 K, have been obtained and discussed in relation to the conductrometric measurements and the few related...

  5. Segal-Bargmann Transform and Paley-Wiener Theorems on $M(2)$

    Indian Academy of Sciences (India)

    E K Narayanan; Suparna Sen

    2010-04-01

    We study the Segal–Bargmann transform on $M(2)$. The range of this transform is characterized as a weighted Bergman space. In a similar fashion Poisson integrals are investigated. Using a Gutzmer’s type formula we characterize the range as a class of functions extending holomorphically to an appropriate domain in the complexification of $M(2)$. We also prove a Paley–Wiener theorem for the inverse Fourier transform.

  6. Wound Administration of M2-Polarized Macrophages Does Not Improve Murine Cutaneous Healing Responses

    OpenAIRE

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

    2014-01-01

    Macrophages play a crucial role in all stages of cutaneous wound healing responses and dysregulation of macrophage function can result in derailed wound repair. The phenotype of macrophages is influenced by the wound microenvironment and evolves during healing from a more pro-inflammatory (M1) profile in early stages, to a less inflammatory pro-healing (M2) phenotype in later stages of repair. The aim of the current study was to investigate the potential of exogenous administration of M2 macr...

  7. 10D massive type IIA supergravities as the uplift of parabolic M2-brane torus bundles

    Energy Technology Data Exchange (ETDEWEB)

    Garcia del Moral, Maria Pilar [Universidad de Antofagasta (Chile). Dept. de Fisica; Restuccia, Alvaro [Universidad de Antofagasta (Chile). Dept. de Fisica; Universidad Simon Bolivar, Caracas (Venezuela, Bolivarian Republic of). Dept. de Fisica

    2016-04-15

    We remark that the two 10D massive deformations of the N = 2 maximal type IIA supergravity (Romans and HLW supergravity) are associated to the low energy limit of the uplift to 10D of M2-brane torus bundles with parabolic monodromy linearly and non-linearly realized respectively. Romans supergravity corresponds to M2-brane compactified on a twice-punctured torus bundle. (copyright 2015 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  8. A novel M2e based flu vaccine formulation for dogs.

    Directory of Open Access Journals (Sweden)

    Denis Leclerc

    Full Text Available BACKGROUND: The USA 2004 influenza virus outbreak H3N8 in dogs heralded the emergence of a new disease in this species. A new inactivated H3N8 vaccine was developed to control the spread of the disease but, as in humans and swine, it is anticipated that the virus will mutate shift and drift in the dog population. Therefore, there is a need for a vaccine that can trigger a broad protection to prevent the spread of the virus and the emergence of new strains. METHODOLOGY AND PRINCIPAL FINDINGS: The universal M2e peptide is identical in almost all the H3N8 influenza strains sequenced to date and known to infect dogs. This epitope is therefore a good choice for development of a vaccine to provide broad protection. Malva mosaic virus (MaMV nanoparticles were chosen as a vaccine platform to improve the stability of the M2e peptide and increase its immunogenicity in animals. The addition of an adjuvant (OmpC purified from Salmonella typhi membrane in the vaccine formulation increased the immune response directed to the M2e peptide significantly and enlarged the protection to include the heterosubtypic strain of influenza in a mouse model. An optimal vaccine formulation was also shown to be immunogenic in dogs. CONCLUSIONS AND SIGNIFICANCE: The MaMV vaccine platform triggered an improved immune response directed towards the universal M2e peptide. The adjuvant OmpC increased the immune response to the M2e peptide and protection to a heterosubtypic influenza strain that harbors a different M2e peptide in a mouse model. Antibodies generated by the vaccine formulation showed cross-reactivity with M2e peptides derived from influenza strains H9N2, H5N1 and H1N1. The vaccine formulation shows a potential for commercialization of a new M2e based vaccine in dogs.

  9. M2 pyruvate kinase provides a mechanism for nutrient sensing and regulation of cell proliferation.

    Science.gov (United States)

    Morgan, Hugh P; O'Reilly, Francis J; Wear, Martin A; O'Neill, J Robert; Fothergill-Gilmore, Linda A; Hupp, Ted; Walkinshaw, Malcolm D

    2013-04-09

    We show that the M2 isoform of pyruvate kinase (M2PYK) exists in equilibrium between monomers and tetramers regulated by allosteric binding of naturally occurring small-molecule metabolites. Phenylalanine stabilizes an inactive T-state tetrameric conformer and inhibits M2PYK with an IC50 value of 0.24 mM, whereas thyroid hormone (triiodo-L-thyronine, T3) stabilizes an inactive monomeric form of M2PYK with an IC50 of 78 nM. The allosteric activator fructose-1,6-bisphosphate [F16BP, AC50 (concentration that gives 50% activation) of 7 μM] shifts the equilibrium to the tetrameric active R-state, which has a similar activity to that of the constitutively fully active isoform M1PYK. Proliferation assays using HCT-116 cells showed that addition of inhibitors phenylalanine and T3 both increased cell proliferation, whereas addition of the activator F16BP reduced proliferation. F16BP abrogates the inhibitory effect of both phenylalanine and T3, highlighting a dominant role of M2PYK allosteric activation in the regulation of cancer proliferation. X-ray structures show constitutively fully active M1PYK and F16BP-bound M2PYK in an R-state conformation with a lysine at the dimer-interface acting as a peg in a hole, locking the active tetramer conformation. Binding of phenylalanine in an allosteric pocket induces a 13° rotation of the protomers, destroying the peg-in-hole R-state interface. This distinct T-state tetramer is stabilized by flipped out Trp/Arg side chains that stack across the dimer interface. X-ray structures and biophysical binding data of M2PYK complexes explain how, at a molecular level, fluctuations in concentrations of amino acids, thyroid hormone, and glucose metabolites switch M2PYK on and off to provide the cell with a nutrient sensing and growth signaling mechanism.

  10. Organophosphorus pesticides decrease M2 muscarinic receptor function in guinea pig airway nerves via indirect mechanisms.

    Directory of Open Access Journals (Sweden)

    Becky J Proskocil

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  12. M2C Precipitate in Isothermal Tempering of High Co-Ni Alloy Steel

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The ultra-strength alloy steel with high content of Co and Ni is typical tempering martensite steel, and the secondary hardening is accomplished by the precipitation of fine scale alloy carbides with black-white contrast until peak-hardening. The crystal structure of precipitates was well determined as M2C with hexagonal by micro-beam diffraction. Observing in HREM, M2C carbides were shown coherent with the ferrite matrix completely and have their own structure.

  13. Influence of cladding layer field of slab waveguide on M2 factor

    Institute of Scientific and Technical Information of China (English)

    Bin Lin(林斌); Xuejin Wen(文学金); Fuyuan Guo(郭福源)

    2003-01-01

    Based on the theory of semiconductor laser pattern and the non-paraxial vectorial moment theory of lightbeam propagation, the beam quality factor M2 of TE0 propagating mode is analyzed and calculated.The result shows that when both core layer and cladding layer are considered, M2 > 1 is always obtained.Moreover, by analyzing the characteristic of real beams, this result is generalized to the multilayer isotropiclinear slab waveguides.

  14. Effect of organophosphorus insecticides on phosphorylation of the M2 muscarinic acetylcholine receptor

    Institute of Scientific and Technical Information of China (English)

    Shuyin Li; Liming Zou; Carry Pope

    2008-01-01

    BACKGROUND: Organophosphorus insecticides may promote the accumulation of acetylcholine at synapses and the neuromuscular junction by inhibiting acetylcholinesterase activity to cause disturbance of neural signal conduction and induce a toxic reaction. Organophosphorus insecticides may act on M2 muscarinic acetylcholine receptors, whose combination with G proteins is regulated by phosphorylation of G protein-coupled receptor kinase 2.OBJECTIVE: To investigate the effects of organophosphorus insecticides on the phosphorylation of G protein-coupled receptor kinase 2-mediated M2 muscarinic acetylcholine receptors and to reveal other possible actions of organophosphorus insecticides.DESIGN, TIME AND SETTING: An observational study, which was performed in the Central Laboratory of Shenyang Medical College, and Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University from June 2002 to December 2004.METHODS: The M2 muscarinic acetylcholine receptor was extracted and purified from pig brain using affinity chromatography. Subsequently, the purified M2 muscarinic acetylcholine receptor, G protein-coupled receptor kinase 2, and [OP32] ATP were incubated with different concentrations of paraoxon and chlorpyrifos oxon together. The mixture then underwent polyacrylamide gel electrophoresis, and the gel film was dried and radioactively autographed to detect phosphorylation of the M2 muscarinic acetylcholine receptor. Finally, the radio-labeled phosphorylated M2 receptor protein band was excised for counting with an isotope liquid scintillation counter.MAIN OUTCOME MEASURES: Effects of chlorpyrifos oxon, paraoxon, chlorpyrifos, and parathion in different concentrations on the phosphorylation of the M2 muscarinic acetylcholine receptor; effects of chlorpyrifos oxon on the phosphorylation of the adrenergic receptor.CONCLUSION: Different kinds of organophosphorus insecticides have different effects on the phosphorylation of the G protein

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

    OpenAIRE

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

    2013-01-01

    M2 muscarinic acetylcholine receptors modulate cardiac rhythm via regulation of the inward potassium current. To increase our understanding of M2 receptor physiology we used Total Internal Reflection Fluorescence Microscopy to visualize individual receptors at the plasma membrane of transformed CHOM2 cells, a cardiac cell line (HL-1), primary cardiomyocytes and tissue slices from pre- and post-natal mice. Receptor expression levels between individual cells in dissociated cardiomyocytes and he...

  16. The role of exochitinase type A1 in the fungistatic activity of the rhizosphere bacterium Paenibacillus sp. M4

    Directory of Open Access Journals (Sweden)

    Jankiewicz Urszula

    2016-01-01

    Full Text Available The aim of the study was to detect the activity and characterize potentially fungistatic chitinases synthesized by rhizosphere bacteria identified as Paenibacillus sp. M4. Maximum chitinolytic activity was achieved on the fifth day of culturing bacteria in a growth medium with 1% colloidal chitin. Analysis of a zymogram uncovered the presence of four activity bands in the crude bacterial extract. The used three-stage protein purification procedure resulted in a single band of chitinase activity on the zymogram. The purified enzyme exhibited maximum activity at pH 6.5 and temperature 45oC, and thermal stability at 40oC for 4 h. In terms of substrate specificity, it is an exochitinase (chitobiose. The amino acid sequence obtained after mass spectrometry showed similarity to chitinase A1 synthesized by Bacillus circulans. The M4 isolate demonstrated the highest growth inhibiting activity against plant pathogens belonging to the genera Fusarium, Rhizoctonia and Alternaria. Fungistatic activity, although to a somewhat lesser degree, was also demonstrated by purified chitinase. The obtained results confirm the participation of the studied exochitinase in antagonism towards pathogenic molds. However, the lower fungistatic effectiveness of the chitinases points to the synergistic action of different metabolites in biocontrol by these bacteria.

  17. High-resolution CCD spectra of stars in globular clusters. III - M4, M13, and M22

    Science.gov (United States)

    Wallerstein, George; Leep, E. Myckky; Oke, J. B.

    1987-01-01

    Spectra of 0.3 and 0.6 A resolution of stars in M4, M13 and M22 to derive abundances of various atomic species and the CN molecule. For M13, the usual Fe/H ratio and a surprisingly high aluminum abundance is found. The CN lines indicate a larger column density in the oxygen-rich star III-63 than in the oxygen-poor star II-67 by a factor of 10. It appears that II-67 is deficient in C, N, and O by about a factor 3 relative to iron for all three elements. For M4, Fe/H = -1.2 using solar f values derived via the Bell et al. (1976) model. This Fe abundance lies between earlier echelle values and photometric values. For two stars, CN data are obtained that can be understood if there was a slight excess of C/Fe and N/Fe prior to CN cycling and mixing. For M22, a large difference in CN is found between stars III-3 and IV-102. The origin of the CNO elements is discussed in terms of mass loss from an early generation of red giants and possibly Wolf-Rayet stars.

  18. Soluble M3 proteins of murine gammaherpesviruses 68 and 72 expressed in Escherichia coli: analysis of chemokine-binding properties.

    Science.gov (United States)

    Matúšková, R; Pančík, P; Štibrániová, I; Belvončíková, P; Režuchová, I; Kúdelová, M

    2015-12-01

    M3 protein of murine gammaherpesvirus 68 (MHV-68) was identified as a viral chemokine-binding protein 3 (vCKBP-3) capable to bind a broad spectrum of chemokines and their receptors. During both acute and latent infection MHV-68 M3 protein provides a selective advantage for the virus by inhibiting the antiviral and inflammatory response. A unique mutation Asp307Gly was identified in the M3 protein of murine gammaherpesvirus 72 (MHV-72), localized near chemokine-binding domain. Study on chemokine-binding properties of MHV-72 M3 protein purified from medium of infected cells implied reduced binding to some chemokines when compared to MHV-68 M3 protein. It was suggested that the mutation in the M3 protein might be involved in the attenuation of immune response to infection with MHV-72. Recently, Escherichia coli cells were used to prepare native recombinant M3 proteins of murine gammaherpesviruses 68 and 72 (Pančík et al., 2013). In this study, we assessed the chemokine-binding properties of three M3 proteins prepared in E. coli Rosetta-gami 2 (DE3) cells, the full length M3 protein of both MHV-68 and MHV-72 and MHV-68 M3 protein truncated in the signal sequence (the first 24 aa). They all displayed binding activity to human chemokines CCL5 (RANTES), CXCL8 (IL-8), and CCL3 (MIP-1α). The truncated MHV-68 M3 protein had more than twenty times reduced binding activity to CCL5, but only about five and three times reduced binding to CXCL8 and CCL3 when compared to its full length counterpart. Binding of the full length MHV-72 M3 protein to all chemokines was reduced when compared to MHV-68 M3 protein. Its binding to CCL5 and CCL3 was reduced over ten and seven times. However, its binding to CXCL8 was only slightly reduced (64.8 vs 91.8%). These data implied the significance of the signal sequence and also of a single mutation (at aa 307) for efficient M3 protein binding to some chemokines.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    G. Karina Chimal-Ramírez

    2016-01-01

    Full Text Available 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.

  1. Reliable Reporting for Massive M2M Communications with Periodic Resource Pooling

    DEFF Research Database (Denmark)

    Madueño, Germán Corrales; Stefanovic, Cedomir; Popovski, Petar

    2014-01-01

    This letter considers a wireless M2M communication scenario with a massive number of M2M devices. Each device needs to send its reports within a given deadline and with certain reliability, e.g., 99.99%. A pool of resources available to all M2M devices is periodically available for transmission....... The number of transmissions required by an M2M device within the pool is random due to two reasons - random number of arrived reports since the last reporting opportunity and requests for retransmission due to random channel errors. We show how to dimension the pool of M2M-dedicated resources in order...... to guarantee the desired reliability of the report delivery within the deadline. The fact that the pool of resources is used by a massive number of devices allows to base the dimensioning on the central limit theorem. The results are interpreted in the context of LTE, but they are applicable to any M2M...

  2. Study into the Applicability of Laser Beam Quality Factor M2

    Institute of Scientific and Technical Information of China (English)

    YANG Jing; TIAN Xiao-hong; XIN Jian-guo

    2006-01-01

    The applicable condition of single-frequency laser beam quality factor M2 is studied. Any real single-frequency laser beam can be classified as Gaussian mode and non-Gaussian mode according to the transverse field distribution. Non-Gaussian transverse field distribution can be analytically expressed as the sum of Hermite-Gaussian functions. The propagation function and M2 factor expression for non-Gaussian mode can be obtained by the second moment definition of laser beam spot. The analytical results show, the same as that of Gaussian mode, that the propagation function follows the hyperbolic law and the value of M2 factor is a constant for non-Gaussian mode. But, different non-Gaussian field distributions may have the same M2 value. That means M2 factor cannot reflect the quality of non-Gaussian laser beams correctly. We conclude that the M2 factor is applicable only to ideal Gaussian laser beam generated by stable resonators.

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

    Directory of Open Access Journals (Sweden)

    Veluchamy A. Barathi

    2013-09-01

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

  4. Cyclooxygenase-2 inhibition blocks M2 macrophage differentiation and suppresses metastasis in murine breast cancer model.

    Directory of Open Access Journals (Sweden)

    Yi-Rang Na

    Full Text Available Tumor cells are often associated with abundant macrophages that resemble the alternatively activated M2 subset. Tumor-associated macrophages (TAMs inhibit anti-tumor immune responses and promote metastasis. Cyclooxygenase-2 (COX-2 inhibition is known to prevent breast cancer metastasis. This study hypothesized that COX-2 inhibition affects TAM characteristics potentially relevant to tumor cell metastasis. We found that the specific COX-2 inhibitor, etodolac, inhibited human M2 macrophage differentiation, as determined by decreased CD14 and CD163 expressions and increased TNFα production. Several key metastasis-related mediators, such as vascular endothelial growth factor-A, vascular endothelial growth factor-C, and matrix metalloproteinase-9, were inhibited in the presence of etodolac as compared to untreated M2 macrophages. Murine bone marrow derived M2 macrophages also showed enhanced surface MHCII IA/IE and CD80, CD86 expressions together with enhanced TNFα expressions with etodolac treatment during differentiation. Using a BALB/c breast cancer model, we found that etodolac significantly reduced lung metastasis, possibly due to macrophages expressing increased IA/IE and TNFα, but decreased M2 macrophage-related genes expressions (Ym1, TGFβ. In conclusion, COX-2 inhibition caused loss of the M2 macrophage characteristics of TAMs and may assist prevention of breast cancer metastasis.

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

    Science.gov (United States)

    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

  6. Endogenous-Exogenous Money Supply and Trend-Stationary Process of M2——Dynamic growth path analysis of M2%货币供给内生性、外生性与M2退势平稳——M2动态增长路径分析

    Institute of Scientific and Technical Information of China (English)

    徐伟康

    2010-01-01

    本文发现M2是一个退势平稳过程,而非单位根过程.尽管M2具有较强的内生性,但同时也受外生货币政策因素冲击或影响.内生因素和外生因素共同作用使M2围绕一条稳态增长路径上下波动;并且M2偏离稳态增长路径会造成产出波动.于是本文利用2000年至2007年的M2月度数据,分别建立SARMA模型和含月度虚拟变量的组合模型,对这条动态增长路径进行拟合.利用2008年的最新数据评价模型的预测能力时,我们发现M2仍然处在这条动态增长路径上.

  7. CH5M3D: an HTML5 program for creating 3D molecular structures

    Science.gov (United States)

    2013-01-01

    Background While a number of programs and web-based applications are available for the interactive display of 3-dimensional molecular structures, few of these provide the ability to edit these structures. For this reason, we have developed a library written in JavaScript to allow for the simple creation of web-based applications that should run on any browser capable of rendering HTML5 web pages. While our primary interest in developing this application was for educational use, it may also prove useful to researchers who want a light-weight application for viewing and editing small molecular structures. Results Molecular compounds are drawn on the HTML5 Canvas element, with the JavaScript code making use of standard techniques to allow display of three-dimensional structures on a two-dimensional canvas. Information about the structure (bond lengths, bond angles, and dihedral angles) can be obtained using a mouse or other pointing device. Both atoms and bonds can be added or deleted, and rotation about bonds is allowed. Routines are provided to read structures either from the web server or from the user’s computer, and creation of galleries of structures can be accomplished with only a few lines of code. Documentation and examples are provided to demonstrate how users can access all of the molecular information for creation of web pages with more advanced features. Conclusions A light-weight (≈ 75 kb) JavaScript library has been made available that allows for the simple creation of web pages containing interactive 3-dimensional molecular structures. Although this library is designed to create web pages, a web server is not required. Installation on a web server is straightforward and does not require any server-side modules or special permissions. The ch5m3d.js library has been released under the GNU GPL version 3 open-source license and is available from http://sourceforge.net/projects/ch5m3d/. PMID:24246004

  8. Real-time monitoring of genetically modified Chlamydomonas reinhardtii during the Foton M3 space mission

    Science.gov (United States)

    Lambreva, M.; Rea, G.; Antonacci, A.; Serafini, A.; Damasso, M.; Pastorelli, S.; Margonelli, A.; Johanningmeier, U.; Bertalan, I.; Pezzotti, G.; Giardi, M. T.

    2008-09-01

    Long-term space exploration, colonization or habitation requires biological life support systems capable to cope with the deleterious space environment. The use of oxygenic photosynthetic microrganisms is an intriguing possibility mainly for food, O2 and nutraceutical compounds production. The critical points of utilizing plants- or algae-based life support systems are the microgravity and the ionizing radiation, which can influence the performance of these organisms. The aim of the present study was to assess the effects of space environment on the photosynthetic activity of various microrganisms and to select space stresstolerant strains. Photosystem II D1 protein sitedirected and random mutants of the unicellular green alga Chlamydomonas reinhardtii [1] were used as a model system to test and select the amino acid substitutions capable to account for space stress tolerance. We focussed our studies also on the accumulation of the Photosystem II photoprotective carotenoids (the xantophylls violaxanthin, anteraxanthin and zeaxanthin), powerful antioxidants that epidemiological studies demonstrated to be human vision protectors. For this purpose some mutants modified at the level of enzymes involved in the biosynthesis of xanthophylls were included in the study [2]. To identify the consequences of the space environment on the photosynthetic apparatus the changes in the Photosystem II efficiency were monitored in real time during the ESA-Russian Foton- M3 mission in September 2007. For the space flight a high-tech, multicell fluorescence detector, Photo-II, was designed and built by the Centre for Advanced Research in Space Optics in collaboration with Kayser-Italy, Biosensor and DAS. Photo-II is an automatic device developed to measure the chlorophyll fluorescence and to provide a living conditions for several different algae strains (Fig.1). Twelve different C. reinhardti strains were analytically selected and two replications for each strain were brought to space

  9. 2014年河北涿鹿M4.3地震矩张量反演%Seismic Moment Tensor Inversion of 2014 Zhuolu M4.3 Earthquake

    Institute of Scientific and Technical Information of China (English)

    李冬圣; 李文军; 王艳荣; 贾炯; 蔡玲玲; 张从珍

    2016-01-01

    Using Three-component broadband digital waveform data from Hebei Digital Seismograph Net-work,we inversed the seismic moment tensor of Hebei Zhuolu M4.3 earthquake on September 6,2014 in time domain,obtain the optimum solution at the depth of 14km.The results show that the Variance (VR) is 92.2,the Double-couple (Pdc) value is 88,the Compensation linear vector dipole(CLVD) is 12 and the Residual/double-couple (RES/Pdc) is 9.54 × 10-12.The focal mechanism solution is of right-lateral strike-slip type which is consistent with the result from grid method.The seismogenic structure of the earth-quake is discussed combining with geological data and background tectonic of the Zhuolu area.%使用河北省遥测台网记录的三分量宽频带数字波形资料 ,在时间域反演2014年9月6日河北涿鹿 M4. 3地震的矩张量解 ,深度14 km时得到最佳解 ,Variance(VR)为92.2、Double-couple (Pdc)值为88、Compensation linear vector dipole(CLVD)值为12 ,Residual /double-couple(RES/Pdc)达到9.54 × 10-12 ,震源机制解呈右旋走滑 ,与格点尝试法计算结果一致 ,文章结合涿鹿地区的地质资料和构造背景对发震断层进行了讨论.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Andrea M Siegel

    2008-04-01

    Full Text Available 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

  12. The Swift/UVOT Stars Survey. II. RR Lyrae Stars in M 3 and M 15

    CERN Document Server

    Siegel, Michael H; Balzer, Benjamin G; Hagen, Lea M Z

    2015-01-01

    We present the first results of an near-ultraviolet (NUV) survey of RR Lyrae stars from the Ultraviolet Optical Telescope (UVOT) aboard the Swift Gamma-Ray Burst Mission. It is well-established that RR Lyrae have large amplitudes in the far- and near-ultraviolet. We have used UVOT's unique wide-field NUV imaging capability to perform the first systematic NUV survey of variable stars in the Galactic globular clusters M 3 and M 15. We identify 280 variable stars, comprising 275 RR Lyrae, two anomalous Cepheids, one classical Cepheid, one SX Phoenicis star and one possible long-period or irregular variable. Only two of these are new discoveries. We compare our results to previous investigations and find excellent agreement in the periods with significantly larger amplitudes in the NUV. We map out, for the first time, an NUV Bailey diagram from globular clusters, showing the usual loci for fundamental mode RRab and first overtone RRc pulsators. We show the unique sensitivity of NUV photometry to both the temperat...

  13. THE SWIFT UVOT STARS SURVEY. II. RR LYRAE STARS IN M3 AND M15

    Energy Technology Data Exchange (ETDEWEB)

    Siegel, Michael H.; Porterfield, Blair L.; Balzer, Benjamin G.; Hagen, Lea M. Z., E-mail: siegel@astro.psu.edu, E-mail: blp14@psu.edu, E-mail: bgb5080@psu.edu, E-mail: lea.zernow.hagen@gmail.com [Pennsylvania State University, Department of Astronomy, 525 Davey Laboratory, University Park, PA 16802 (United States)

    2015-10-15

    We present the first results of a near-ultraviolet (NUV) survey of RR Lyrae stars from the Ultraviolet Optical Telescope (UVOT) on board the Swift Gamma-ray Burst Mission. It is well-established that RR Lyrae stars have large amplitudes in the far- and near-ultraviolet. We have used UVOT’s unique wide-field NUV imaging capability to perform the first systematic NUV survey of variable stars in the Galactic globular clusters M3 and M15. We identify 280 variable stars, comprised of 275 RR Lyrae, 2 anomalous Cepheids, 1 classical Cepheid, 1 SX Phoenicis star, and 1 possible long-period or irregular variable. Only two of these are new discoveries. We compare our results to previous investigations and find excellent agreement in the periods with significantly larger amplitudes in the NUV. We map out, for the first time, an NUV Bailey diagram from globular clusters, showing the usual loci for fundamental mode RRab and first overtone RRc pulsators. We show the unique sensitivity of NUV photometry to both the temperatures and the surface gravities of RR Lyrae stars. Finally, we show evidence of an NUV period–metallicity–luminosity relationship. Future investigations will further examine the dependence of NUV pulsation parameters on metallicity and Oosterhoff classification.

  14. Molecular Modeling of the M3 Acetylcholine Muscarinic Receptor and Its Binding Site

    Science.gov (United States)

    Martinez-Archundia, Marlet; Cordomi, Arnau; Garriga, Pere; Perez, Juan J.

    2012-01-01

    The present study reports the results of a combined computational and site mutagenesis study designed to provide new insights into the orthosteric binding site of the human M3 muscarinic acetylcholine receptor. For this purpose a three-dimensional structure of the receptor at atomic resolution was built by homology modeling, using the crystallographic structure of bovine rhodopsin as a template. Then, the antagonist N-methylscopolamine was docked in the model and subsequently embedded in a lipid bilayer for its refinement using molecular dynamics simulations. Two different lipid bilayer compositions were studied: one component palmitoyl-oleyl phosphatidylcholine (POPC) and two-component palmitoyl-oleyl phosphatidylcholine/palmitoyl-oleyl phosphatidylserine (POPC-POPS). Analysis of the results suggested that residues F222 and T235 may contribute to the ligand-receptor recognition. Accordingly, alanine mutants at positions 222 and 235 were constructed, expressed, and their binding properties determined. The results confirmed the role of these residues in modulating the binding affinity of the ligand. PMID:22500107

  15. [Gerbil experiment in the flight of spacecraft "Foton-M3"].

    Science.gov (United States)

    Il'in, E A; Smirnov, I A; Soldatov, P E; Orlov, O I

    2009-01-01

    The 12-d mission of Russian spacecraft Foton-M3 in September of 2007 was used as an opportunity to fly an experiment with 12 male gerbils (Meriones unguiculatus) at the age of 4-4.5 mos. and mean body weight of 51.6 grams. Considering the behavior pattern of these animals, selection and preparation of the experimental groups continued in the course of 2.5-3 months. The flight animals were contained in module Kontur-L outfitted with a self-sustained system of life support. In orbit, the animals received a palletized hydrogenous feed. The physiological and hygienic parameters of the gerbil environment during the flight complied with the official standards. Analysis of the video recorded behavior of animals in microgravity showed that virtually throughout the flight they moved chaotically along the cage never attempting to stabilize position catching at the wire netting of the cage. The animals were decapitated in 21-24 hours after landing. The investigations showed that structural and functional changes in gerbil organs and tissues were generally of the same type as in rats following fights of comparable duration. However, some differences between the animals were attributed to the specifics of water turnover in gerbils.

  16. [Handling and maintenance of gerbils during the spacecraft Foton-M3 mission].

    Science.gov (United States)

    Soldatov, P E; Smirnov, I A; Il'in, E A; Gur'eva, T S; Mednikova, E I; Smolenskaia, T S; Lysenko, L A; Kaminskaia, E V

    2009-01-01

    Pressurized low-sized module Kontur with an independent life support system (LSS) was developed by the Institute of Biomedical Problems cooperatively with the Special Design Bureau of Experimental Equipment to house gerbils (Meriones unguiculatus) aboard robotic technology-purpose spacecraft. Design of the module precludes pollution of the environment The fully equipped module weighs 69 kg; average daily power consumption is 62 watts. The environmental parameters for 12 animals flown on Foton-M3 in the period of September 14-26, 2007 were controlled within the following ranges: pO2 - 143-156 mm Hg, (mean 150 mm Hg), pCO2 - 0.76 mm Hg maximum (mean 0.64 mm Hg), temperature - 23-28 degrees C (mean 26.7 degrees C), relative humidity - 29% and 57% at the beginning and end of the flight, respectively (mean 39%). The animals consumed the palletized food prepared of natural products with a moisture content of approx. 20%. The day-night periods were 12 hrs. long. The daytime video recording of the animals went on continuously in the throughout the flight. The experiment showed that the module meets the requirements of experiments with mammals aboard returnable robotic spacecraft and piloted space stations. At the moment, the model is being redesigned for a 30-day BION-M1 mission.

  17. [Glycogen content in gerbil's liver following the spacecraft Foton-M3 mission].

    Science.gov (United States)

    Atiakshin, D A; Bykov, E G; Il'in, E A; Pashkov, A N

    2009-01-01

    Glycogen cytochemistry and distribution in hepatocytes of the classic liver lobules were studied in three groups of gerbils Meriones unguiculatus: vivarium, synchronous control and flown in the 12-d Foton-M3 mission. The control animals were shown to have the central glycogen distribution with a large pool of polysaccharides found in hepatocytes of the pericentral and intermediate lobules and a small pool in the periportal area. Glycogen in hepatocyte plasm was within the physiological norm in the alpha- and beta-granules, typically localized on the cell periphery. Exposure to the spaceflight conditions decreased significantly glycogen concentrations in each functional region of the hepatic lobules and reduced the gradient of polysaccharide distribution from the portal triads toward the central vein. In parallel, high glycogen heterogeneity formed in adjacent hepatocytes and loci. The presence of glycosomes evidenced disturbance of carbohydrates metabolism. In addition, intracellular topography of glycogen granules in cytoplasm was altered. Trends of glycogen in gerbils of the synchronous control were similar to the space flown animals but much less pronounced.

  18. [Jejunum intersticium in mongolian gerbils after the flight on spacecraft Foton-M3].

    Science.gov (United States)

    Atiashkin, D A; Bykov, É G; Il'in, E A; Pashkov, A N

    2012-01-01

    Methods of light optical microscopy were used to explore histoarchitectonics, topography and tinctorial properties of the extracellular phase of fibers of jejunum wall intersticium in Mongolian gerbils following 12-day orbital flight aboard Foton-M3, ground-based simulation of the spaceflight factors in the KONTUR-L facility, and in the group of biological control Postflight destructive changes were found in reticulin fibers (type-III collagen) of villi stroma, intercrypt intersticium and submucosa. Local acidophilia and fiber homogenization formed in type I collagen present in the intestinal subserous layer, muscular layers endomysium and submucose against the background of progressing edema and arterial, venous plethora and lymphostasis. Elastic component of the intersticium was disarranged in the structures of internal elastic membrane of submucous vessels, fragmented and partly reduced. Simulation of the orbital factors, except for microgravity, in the KONTUR-L facility called forth similar, although less often and diffuse, changes in intersticium fibers. The results of examination of intestinal intersticium fibers in the vivarium control gerbils discovered expressed species characters that should be taken into account by investigators, especially when comparing with data obtained from other animal species.

  19. [Rna content of gerbil hepatocytes after the flight aboard space platform Foton-M3].

    Science.gov (United States)

    Atiashkin, D A; Bykov, E G; Il'in, E A; Pashkov, A N

    2010-01-01

    The paper compares and contrasts the results of measuring the hepatocyte cytoplasm area and RNA content in 35 gerbils in three series of experiments, i.e. the vivarium control, modeled space flight (synchronous control) and exposure to the factors of 12-d Foton-M3 orbital flight. Central, intermediate and peripheral zones of hepatic lobes were subjected to histological and histochemical analyses to measure the hepatocyte cytoplasm area; the RNA content was determined from the level of cytoplasm basophilia after azure staining. Cytometric and cytophotometric investigations were performed using image analyzer Video-7-Test-Morpho. In the vivarium animals, hepatocytes with the largest cytoplasm localized predominantly in the intermediate and central zones of the lobes. Judging from the results of microdensitometry, the RNA content was particularly high in binucleate hepatocytes of the intermediate zone. In the synchronous control, hepatocytes tended to grow in size, in the peripheral zone specifically, whereas RNA content was largely equal no matter hepatocyte topography. After space flight, cytoplasm enlargement transcended this process in the vivarium animals. The cytoplasm RNA content along the entire liver parenchyma made a significant decrease equally as compared with the vivarium and synchronous control animals.

  20. Molecular Modeling of the M3 Acetylcholine Muscarinic Receptor and Its Binding Site

    Directory of Open Access Journals (Sweden)

    Marlet Martinez-Archundia

    2012-01-01

    Full Text Available The present study reports the results of a combined computational and site mutagenesis study designed to provide new insights into the orthosteric binding site of the human M3 muscarinic acetylcholine receptor. For this purpose a three-dimensional structure of the receptor at atomic resolution was built by homology modeling, using the crystallographic structure of bovine rhodopsin as a template. Then, the antagonist N-methylscopolamine was docked in the model and subsequently embedded in a lipid bilayer for its refinement using molecular dynamics simulations. Two different lipid bilayer compositions were studied: one component palmitoyl-oleyl phosphatidylcholine (POPC and two-component palmitoyl-oleyl phosphatidylcholine/palmitoyl-oleyl phosphatidylserine (POPC-POPS. Analysis of the results suggested that residues F222 and T235 may contribute to the ligand-receptor recognition. Accordingly, alanine mutants at positions 222 and 235 were constructed, expressed, and their binding properties determined. The results confirmed the role of these residues in modulating the binding affinity of the ligand.

  1. Experimental Study of Ultralight (<300 kg/m3 Foamed Concrete

    Directory of Open Access Journals (Sweden)

    Xianjun Tan

    2014-01-01

    Full Text Available A type of ultralight (<300 kg/m3 foamed concrete (FC, which can be used as a new energy-conservation and environmental-protection building material and is particularly suitable for the thermal-insulation engineering of building external walls, was produced. The influences of different mixing amounts of fly ash, fly ash activator, WC (WC ratio, and foaming agent (FA on the compressive strength of FC were reported. The experimental study indicated that (1 the addition of fly ash reduced the strength of the FC and that the appropriate mixing amount of fly ash in this ultralight FC system should not exceed 45%; (2 with the increasing of fly ash activator, the strength of the FC sample is notably enhanced and the appropriate mixing amount of fly ash activator is 2.5%; (3 the optimized proportion of WC ratio is 0.45, and the FC that was produced according to this proportion has relatively high compressive strength; (4 by increasing the mixing amount of FA, the compressive strength of the FC notably decreases, and the optimal mixing amount of FA in this experiment is 3.5%.

  2. Discovery of a wide planetary-mass companion to the young M3 star GU PSC

    Energy Technology Data Exchange (ETDEWEB)

    Naud, Marie-Eve; Artigau, Étienne; Malo, Lison; Albert, Loïc; Doyon, René; Lafrenière, David; Gagné, Jonathan; Boucher, Anne [Département de physique and Observatoire du Mont-Mégantic, Université de Montréal, Montréal H3C 3J7 (Canada); Saumon, Didier [Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Morley, Caroline V. [Department of Astronomy and Astrophysics, University of California, Santa Cruz, CA 95064 (United States); Allard, France; Homeier, Derek [Centre de Recherche Astrophysique de Lyon, UMR 5574 CNRS, Université de Lyon, École Normale Supérieure de Lyon, 46 Allée d' Italie, F-69364 Lyon Cedex 07 (France); Beichman, Charles A.; Gelino, Christopher R., E-mail: naud@astro.umontreal.ca [Infrared Processing and Analysis Center, MS 100-22, California Institute of Technology, Pasadena, CA 91125 (United States)

    2014-05-20

    We present the discovery of a comoving planetary-mass companion ∼42'' (∼2000 AU) from a young M3 star, GU Psc, a likely member of the young AB Doradus Moving Group (ABDMG). The companion was first identified via its distinctively red i – z color (>3.5) through a survey made with Gemini-S/GMOS. Follow-up Canada-France-Hawaii Telescope/WIRCam near-infrared (NIR) imaging, Gemini-N/GNIRS NIR spectroscopy and Wide-field Infrared Survey Explorer photometry indicate a spectral type of T3.5 ± 1 and reveal signs of low gravity which we attribute to youth. Keck/Adaptive Optics NIR observations did not resolve the companion as a binary. A comparison with atmosphere models indicates T {sub eff} = 1000-1100 K and log g = 4.5-5.0. Based on evolution models, this temperature corresponds to a mass of 9-13 M {sub Jup} for the age of ABDMG (70-130 Myr). The relatively well-constrained age of this companion and its very large angular separation to its host star will allow its thorough characterization and will make it a valuable comparison for planetary-mass companions that will be uncovered by forthcoming planet-finder instruments such as Gemini Planet Imager and SPHERE 9.

  3. Magnetic and dynamical photospheric disturbances observed during an M3.2 solar flare

    CERN Document Server

    Kuckein, C; Sainz, R Manso

    2015-01-01

    This letter reports on a set of full-Stokes spectropolarimetric observations in the near infrared He I 10830 A spectral region covering the pre-, flare, and post-flare phases of an M3.2 class solar flare. The flare originated on 2013 May 17 and belonged to active region NOAA 11748. We detected strong He I 10830 A emission in the flare. The red component of the He I triplet peaks at an intensity ratio to the continuum of about 1.86. During the flare, He I Stokes V is substantially larger and appears reversed compared to the usually larger Si I Stokes V profile. The photospheric Si I inversions of the four Stokes profiles reveal the following: (1) the magnetic field strength in the photosphere decreases or is even absent during the flare phase, as compared to the pre-flare phase. However, this decrease is not permanent. After the flare the magnetic field recovers its pre-flare configuration in a short time (i.e., in 30 minutes after the flare). (2) In the photosphere, the line-of-sight velocities show a regular...

  4. GRAVITAS : General Relativistic Astrophysics VIa Timing And Spectroscopy: An ESA M3 mission proposal

    CERN Document Server

    Nandra, Kirpal; Fabian, Andy; Strueder, Lothar; Willingale, Richard; Watson, Mike; Jonker, Peter; Kunieda, Hideyo; Miniutti, Giovanni; Motch, Christian; Predehl, Peter

    2011-01-01

    GRAVITAS is an X-ray observatory, designed and optimised to address the ESA Cosmic Vision theme of "Matter under extreme conditions". It was submitted as a response to the call for M3 mission proposals. The concept centres around an X-ray telescope of unprecedented effective area, which will focus radiation emitted from close to the event horizon of black holes or the surface of neutron stars. To reveal the nature and behaviour of matter in the most extreme astrophysical environments, GRAVITAS targets a key feature in the X-ray spectra of compact objects: the iron Kalpha line at ~6.5 keV. The energy, profile, and variability of this emission line, and the properties of the surrounding continuum emission, shaped by General Relativity (GR) effects, provide a unique probe of gravity in its strong field limit. Among its prime targets are hundreds of supermassive black holes in bright Active Galactic Nuclei (AGN), which form the perfect laboratory to help understand the physical processes behind black hole growth....

  5. Overtone and multi-mode RR Lyrae stars in the globular cluster M3

    CERN Document Server

    Jurcsik, J; Hajdu, G; Sódor, Á; Nuspl, J; Kolenberg, K; Fűrész, G; Moór, A; Kun, E; Pál, A; Bakos, J; Kelemen, J; Kovács, T; Kriskovics, L; Sárneczky, K; Szalai, T; Szing, A; Vida, K

    2015-01-01

    The overtone and multi-mode RR Lyrae stars in the globular cluster M3 are studied using a 200-d long, $B,V$ and $I_{\\mathrm C}$ time-series photometry obtained in 2012. 70\\% of the 52 overtone variables observed show some kind of multi-periodicity (additional frequency at ${f_{0.61}}={f_{\\mathrm {1O}}}/0.61$ frequency ratio, Blazhko effect, double/multi-mode pulsation, period doubling). A signal at 0.587 frequency ratio to the fundamental-mode frequency is detected in the double-mode star, V13, which may be identified as the second radial overtone mode. If this mode-identification is correct, than V13 is the first RR Lyrae star showing triple-mode pulsation of the first three radial modes. Either the Blazhko effect or the ${f_{0.61}}$ frequency (or both of these phenomena) appear in 7 double-mode stars. The $P_{\\mathrm{1O}}/P_{\\mathrm{F}}$ period ratio of RRd stars showing the Blazhko effect are anomalous. A displacement of the main frequency component at the fundamental-mode with the value of modulation freq...

  6. Discovery of a wide planetary-mass companion to the young M3 star GU Psc

    CERN Document Server

    Naud, Marie-Eve; Malo, Lison; Albert, Loïc; Doyon, René; Lafrenière, David; Gagné, Jonathan; Saumon, Didier; Morley, Caroline V; Allard, France; Homeier, Derek; Beichman, Charles A; Gelino, Christopher R; Boucher, Anne

    2014-01-01

    We present the discovery of a co-moving planetary-mass companion ~42" (~2000 AU) from a young M3 star, GU Psc, likely member of the young AB Doradus Moving Group (ABDMG). The companion was first identified via its distinctively red i - z color (> 3.5) through a survey made with Gemini-S/GMOS. Follow-up Canada-France-Hawaii Telescope/WIRCam near-infrared (NIR) imaging, Gemini-N/GNIRS NIR spectroscopy and Wide-field Infrared Survey Explorer photometry indicate a spectral type of T3.5+-1 and reveal signs of low gravity which we attribute to youth. Keck/Adaptive Optics NIR observations did not resolve the companion as a binary. A comparison with atmosphere models indicates Teff = 1000-1100 K and logg = 4.5-5.0. Based on evolution models, this temperature corresponds to a mass of 9-13 MJup for the age of ABDMG (70-130 Myr). The relatively well-constrained age of this companion and its very large angular separation to its host star will allow its thorough characterization and will make it a valuable comparison for ...

  7. THE CLUSTER AGES EXPERIMENT (CASE). V. ANALYSIS OF THREE ECLIPSING BINARIES IN THE GLOBULAR CLUSTER M4

    Energy Technology Data Exchange (ETDEWEB)

    Kaluzny, J.; Rozyczka, M.; Krzeminski, W.; Pych, W. [Nicolaus Copernicus Astronomical Center, Bartycka 18, 00-716 Warsaw (Poland); Thompson, I. B.; Burley, G. S.; Shectman, S. A. [Observatories of the Carnegie Institution of Washington, 813 Santa Barbara Street, Pasadena, CA 91101-1292 (United States); Dotter, A. [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); Rucinski, S. M., E-mail: jka@camk.edu.pl, E-mail: mnr@camk.edu.pl, E-mail: wk@camk.edu.pl, E-mail: batka@camk.edu.pl, E-mail: pych@camk.edu.pl, E-mail: ian@obs.carnegiescience.edu, E-mail: burley@obs.carnegiescience.edu, E-mail: shec@obs.carnegiescience.edu, E-mail: aaron.dotter@gmail.com, E-mail: rucinski@astro.utoronto.ca [Department of Astronomy and Astrophysics, David Dunlap Observatory, University of Toronto PO Box 360, Richmond Hill, ON L4C 4Y6 (Canada)

    2013-02-01

    We use photometric and spectroscopic observations of the eclipsing binaries V65, V66, and V69 in the field of the globular cluster M4 to derive masses, radii, and luminosities of their components. The orbital periods of these systems are 2.29, 8.11, and 48.19 days, respectively. The measured masses of the primary and secondary components (M{sub p} and M{sub s} ) are 0.8035 {+-} 0.0086 and 0.6050 {+-} 0.0044 M{sub Sun} for V65, 0.7842 {+-} 0.0045 and 0.7443 {+-} 0.0042 M{sub Sun} for V66, and 0.7665 {+-} 0.0053 and 0.7278 {+-} 0/0048 M{sub Sun} for V69. The measured radii (R{sub p} and R{sub s} ) are 1.147 {+-} 0.010 and 0.6110 {+-} 0.0092 R{sub Sun} for V66, 0.9347 {+-} 0.0048 and 0.8298 {+-} 0.0053 R{sub Sun} for V66, and 0.8655 {+-} 0.0097 and 0.8074 {+-} 0.0080 R{sub Sun} for V69. The orbits of V65 and V66 are circular, whereas that of V69 has an eccentricity of 0.38. Based on systemic velocities and relative proper motions, we show that all three systems are members of the cluster. We find that the distance to M4 is 1.82 {+-} 0.04 kpc-in good agreement with recent estimates based on entirely different methods. We compare the absolute parameters of V66 and V69 with two sets of theoretical isochrones in mass-radius and mass-luminosity diagrams, and for assumed [Fe/H] = -1.20, [{alpha}/Fe] = 0.4, and Y = 0.25 we find the most probable age of M4 to be between 11.2 and 11.3 Gyr. Color-magnitude diagram (CMD) fitting with the same parameters yields an age close to, or slightly in excess of, 12 Gyr. However, considering the sources of uncertainty involved in CMD fitting, these two methods of age determination are not discrepant. Age and distance determinations can be further improved when infrared eclipse photometry is obtained.

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

    Science.gov (United States)

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

    1998-02-27

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

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

    Science.gov (United States)

    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.

  10. M2 macrophages induce EMT through the TGF-β/Smad2 signaling pathway.

    Science.gov (United States)

    Zhu, Liangying; Fu, Xiao; Chen, Xiang; Han, Xiaodong; Dong, Ping

    2017-09-01

    IPF is characterized by fibroblast accumulation, collagen deposition, and ECM remodeling, with myofibroblasts believed to be the effector cell type. Myofibroblasts develop due to EMT of lung alveolar epithelial cells, which can be induced by TGF-β. M2 macrophages, a macrophage subpopulation, secrete large amounts of TGF-β. To clarify the relationship between IPF, EMT, TGF-β, and M2 macrophages, a bleomycin-induced pulmonary fibrosis mouse model was used. Seventeen days after mice were treated with bleomycin, the successful establishment of a pulmonary fibrosis model was confirmed by HE stain and Masson's trichrome stain. We found evidence in support of EMT, such as elevated protein levels of α-SMA in lung tissue and decreased levels of E-cadherin and CK-18. Additionally, increased TGF-β levels and TGF-β/Smad2 signaling activation was observed. Macrophages were recruited to pulmonary alveoli. Alveolar macrophages were phenotyped and identified as M2 macrophages, with up-regulated CD206 on the cell surfaces. For in vitro studies, we treated RAW 264.7 cells with IL-4 for 24 h, and the cells were then utilized as M2 macrophages. TGF-β levels increased significantly in the culture supernatant. Forty-eight hours after lung epithelial cells (MLE-12) were co-cultured with the M2 macrophages, the expression of α-SMA increased, and E-cadherin and CK-18 decreased. When a TGF-β receptor inhibitor, LY2109761 was used, the EMT induced by M2 macrophages was blocked. In conclusion, we demonstrated that M2 macrophages induce EMT through the TGF-β/Smad2 signaling pathway. © 2017 International Federation for Cell Biology.

  11. Granulocytic Sarcoma by AML M4eo (inv16 after Allogeneic Stem Cell Transplantation without Bone Marrow Involvement

    Directory of Open Access Journals (Sweden)

    Stephan Zaenker

    2011-01-01

    Full Text Available Granulocytic sarcoma (GS represents a rare type of extramedullar manifestation from the acute myeloid leukaemia (AML. We report the case of a patient with recurrences of AML M4eo leukaemia in the uterus and the small intestine at 3 and 5 years, respectively, after matched related peripheral blood stem cell transplantation (PBSCT. The patient underwent the withdrawal of immunosuppression, hysterectomy, and local irradiation at first relapse, as well as systemic chemotherapy and donor lymphocyte infusions at second recurrence, inducing a second and third complete remission, respectively. At year six after transplantation, the patient experienced disease progression by meningeosis leukaemia to which she succumbed despite intrathecal chemotherapy. Following allogeneic stem cell transplantation, awareness for atypical manifestations of granulocytic sarcoma appears prudent, the cellular immunotherapy should aim at immunological disease control.

  12. The muscarinic M1/M4 receptor agonist xanomeline exhibits antipsychotic-like activity in Cebus apella monkeys

    DEFF Research Database (Denmark)

    Andersen, Maibritt B; Fink-Jensen, Anders; Peacock, Linda

    2003-01-01

    Xanomeline is a muscarinic M(1)/M(4) preferring receptor agonist with little or no affinity for dopamine receptors. The compound reduces psychotic-like symptoms in patients with Alzheimer's disease and exhibits an antipsychotic-like profile in rodents without inducing extrapyramidal side effects......, stereotypies and arousal as well as apomorphine-induced stereotypies and arousal in drug-naive Cebus apella monkeys. Xanomeline did not induce EPS but vomiting occurred in some monkeys at high doses, in accordance with emetic events observed in Alzheimer patients following xanomeline administration. Even when...... that xanomeline inhibits D-amphetamine- and (-)-apomorphine-induced behavior in Cebus apella monkeys at doses that do not cause EPS. These data further substantiate that muscarinic receptor agonists may be useful in the pharmacological treatment of psychosis....

  13. Lithium abundance in the globular cluster M4: from the turn-off to the red giant branch bump

    Science.gov (United States)

    Mucciarelli, A.; Salaris, M.; Lovisi, L.; Ferraro, F. R.; Lanzoni, B.; Lucatello, S.; Gratton, R. G.

    2011-03-01

    We present Li and Fe abundances for 87 stars in the globular cluster M4, obtained by using high-resolution spectra collected with GIRAFFE at the Very Large Telescope. The targets range from the turn-off up to the red giant branch bump. The Li abundance in the turn-off stars is uniform, with an average value equal to A(Li)= 2.30 ± 0.02 dex (σ= 0.10 dex), consistent with the upper envelope of Li content measured in other globular clusters and in the halo field stars, confirming also for M4 the discrepancy with the primordial Li abundance predicted by Wilkinson Microwave Anisotropy Probe+ big bang nucleosynthesis (WMAP+BBNS). The global behaviour of A(Li) as a function of the effective temperature allows us to identify the two main drops in the Li evolution due to the first dredge-up and to the extra-mixing episode after the red giant branch bump. The measured iron content of M4 results to [Fe/H]=-1.10 ± 0.01 dex (σ= 0.07 dex), with no systematic offsets between dwarf and giant stars. The behaviour of the Li and Fe abundances along the entire evolutionary path is incompatible with theoretical models including pure atomic diffusion, pointing out that an additional turbulent mixing below the convective region needs to be taken into account, able to inhibit the atomic diffusion. The measured value of A(Li) and its homogeneity in the turn-off stars allow us to put strong constraints on the shape of the Li profile inside the M4 turn-off stars. The global behaviour of A(Li) with the effective temperature can be reproduced with different pristine Li abundances, depending on the kind of adopted turbulent mixing. One cannot reproduce the global trend that starts from the WMAP+BBNS A(Li) and adopts the turbulent mixing described by Richard, Michaud & Richer with the same efficiency as that used by Korn et al. to explain the Li content in NGC 6397. In fact, such a solution is not able to well reproduce simultaneously the Li abundance observed in turn-off and red giant branch

  14. 英特尔蓝图大曝光 65纳米赛扬M 4XX系列

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    英特尔目前正准备发布主频为233GHz的Core Duo芯片T2700,其产品路线图包括速度更快的Core Solo芯片,快速低压的Core Duos和超低压Core Duo芯片,后者的主频为1.06GHz代号为U2500。此外,赛扬(Celoron)M 4XX也被纳入了英特尔最新的产品路线圈,这是一款从65纳米制程的Core Solo肃离下来的单核产品。

  15. Observations of the Ultraviolet-bright Star Y453 in the Globular Cluster M4 (NGC 6121)

    Science.gov (United States)

    Dixon, William V.; Chayer, Pierre; Latour, Marilyn; Miller Bertolami, Marcelo Miguel; Benjamin, Robert A.

    2017-09-01

    We present a spectral analysis of the UV-bright star Y453 in M4. Model fits to the star’s optical spectrum yield {T}{eff} ∼ 56,000 K. Fits to the star’s FUV spectrum, obtained with the Cosmic Origins Spectrograph on board the Hubble Space Telescope, reveal it to be considerably hotter, with {T}{eff} ∼ 72,000 K. We adopt {T}{eff} = 72,000 ± 2000 K and {log}g = 5.7 ± 0.2 as our best-fit parameters. Scaling the model spectrum to match the star’s optical and near-infrared magnitudes, we derive a mass {M}* =0.53+/- 0.24 {M}ȯ and luminosity {log}L/{L}ȯ =2.84+/- 0.05, consistent with the values expected of an evolved star in a globular cluster. Comparing the star with post-horizontal-branch evolutionary tracks, we conclude that it most likely evolved from the blue horizontal branch, departing the asymptotic giant branch before third dredge-up. It should thus exhibit the abundance pattern (O-poor and Na-rich) characteristic of the second-generation (SG) stars in M4. We derive the star’s photospheric abundances of He, C, N, O, Si, S, Ti, Cr, Fe, and Ni. CNO abundances are roughly 0.25 dex greater than those of the cluster’s SG stars, while the Si and S abundances match the cluster values. Abundances of the iron-peak elements (except for iron itself) are enhanced by 1–3 dex. Rather than revealing the star’s origin and evolution, this pattern reflects the combined effects of diffusive and mechanical processes in the stellar atmosphere.

  16. Tumor type M2 pyruvate kinase expression in gastric cancer,colorectal cancer and controls

    Institute of Scientific and Technical Information of China (English)

    Bo Zhang; Jian-Ying Chen; Dao-Da Chen; Guo-Bin Wang; Ping Shen

    2004-01-01

    AIM: Tumor formation is generally linked to an expansion of glycolytic phosphometabolite pools and aerobic glycolytic flux rates. To achieve this, tumor cells generally overexpress a special glycolytic isoenzyme, termed pyruvate kinase type M2. The present study was designed to evaluate the use of a new tumor marker, tumor M2-PK, in discriminating gastrointestinal cancer patients from healthy controls, and to compare with the reference tumor markers CEA and CA72-4.METHODS: The concentration of tumor M2-PK in body fluids could be quantitatively determined by a commercially available enzyme-linked immunosorbent assay (ELISA)-kit (ScheBo(R) Tech, Giessen, Germany). By using this kit, the tumor M2-PK concentration was measured in EDTA-plasma of 108 patients. For the healthy blood donors a cut-off value of 15 U/mL was evaluated, which corresponded to 90% specificity. Overall 108 patients were included in this study, 54 patients had a histological confirmed gastric cancer, 54 patients colorectal cancer, and 20 healthy volunteers served as controls.RESULTS: The cut-off value to discriminate patients from controls was established at 15 U/mL for tumor M2-PK. The mean tumor M2-PK concentration of gastric cancer was 26.937 U/mL. According to the TNM stage system, the mean tumor M2-PK concentration of stage Ⅰ was 16.324 U/mL, of stage Ⅱ 15.290 U/mL, of stage Ⅲ 30.289 U/mL, of stage Ⅳ127.31 U/mL, of non-metastasis 12.854 U/mL and of metastasis 35.711 U/mL. The mean Tumor M2-PK concentration of colorectal cancer was 30.588 U/mL. According to the Dukes stage system, the mean tumor M2-PK concentration of Dukes A was 16.638 U/mL, of Dukes B 22.070 U/mL, and of Dukes C 48.024 U/mL, of non-metastasis 19.501 U/mL, of metastasis 49.437 U/mL. The mean tumor M2-PK concentration allowed a significant discrimination of colorectal cancers (30.588 U/mL) from controls (10.965 U/mL) (P<0.01), and gastric cancer (26.937 U/mL) from controls (10.965 U/mL)(P<0.05). The overall

  17. Role of the M2 muscarinic receptor pathway in lidocaine-induced potentiation of the relaxant response to atrial natriuretic peptide in bovine tracheal smooth muscle.

    Science.gov (United States)

    Yunoki, Motonari; Nakahara, Tsutomu; Mitani, Akiko; Sakamoto, Kenji; Ishii, Kunio

    2003-01-01

    We earlier reported that lidocaine augments the relaxation and accumulation of guanosine 3',5'-cyclic monophosphate produced by atrial natriuretic peptide (ANP) in bovine tracheal smooth muscle contracted with methacholine. However, the mechanism of that augmentation remains to be elucidated. In this study, we examined the role of muscarinic receptor-mediated signalling in the potentiation of ANP-induced relaxation by lidocaine. Lidocaine (100 micro M) augmented the relaxant responses to ANP in methacholine (0.3 microM)-contracted bovine tracheal smooth muscle but had no effect on the relaxant effects of ANP in preparations contracted with 100 micro M histamine. Treatment of tracheal preparations with methoctramine (0.03 microM), an M2 muscarinic receptor antagonist, enhanced ANP-induced relaxation and this treatment abolished the synergistic action of lidocaine on ANP. In radioligand-binding experiments, lidocaine concentration dependently displaced the specific binding of [3H]- N-methyl scopolamine to cloned human M2 and M3 muscarinic receptors expressed in Chinese hamster ovary cells. These results suggest that lidocaine acts as an M2 muscarinic receptor antagonist, thereby potentiating the relaxant responses to ANP in the bovine tracheal smooth muscle contracted with muscarinic receptor agonists.

  18. Technological Transformation Practice of 105 m2 Sintering Machine%105 m2烧结机技术改造实践

    Institute of Scientific and Technical Information of China (English)

    白玮

    2015-01-01

    山钢股份莱芜分公司炼铁厂对3台105 m2烧结机进行了一系列技术改造,包括烧结熔剂破碎工艺优化,配料自动化控制系统改造,混合料温度提升,混合机筒体衬板及安装改造,烧结机漏风治理,单辊篦板保护帽改造等。改造后,烧结机作业率98.02%,烧结矿合格率98.19%,产量355.9万t。%A series of technological transformation for three 105 m2 sintering machines in Laiwu branch iron works has been made. That include to optimize sintering flux crushing process and transform automatic batching control, increase the temperature of mixture, reform of mixing machine barrel lining board and installation, control the air leakage of sinter, transform the single and grate plate protective cap. The sintering machine operating rate reached 98.02%, sinter and the qualified rate can reach 98.19%, sinter yield reached 355.9 million tons.

  19. 羊八井50m2 RPC地毯性能研究%Study on the Performance of YBJ 50m2 RPC Carpet

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    利用羊八井50m2 RPC地毯(YBJ-ARGO实验原型)的测试数据对其性能进行了分析研究,包括原初粒子方位角分布、天顶角分布、地毯的角分辨、探测时间系统误差对方位角分布的正弦调制、探测时间系统误差的离线修正、几何不对称的小型地毯探测器上原初粒子到达方向重建误差造成的方位角分布的不均匀性等.%The characteristics of a 50m2 RPC carpet(prototype of YBJ-ARGO experiment)was analyzed using its test run data.A correction method of the systematic time error is suggested,and non-uniform azimuthal angle distribution possibly due to direction reconstruction error on an asymmetric carpet is reported.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    Du, Yongzhao; Fu, Yuqing; Zheng, Chaoying

    2017-02-01

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

  2. Differential Roles of M1 and M2 Microglia in Neurodegenerative Diseases.

    Science.gov (United States)

    Tang, Yu; Le, Weidong

    2016-03-01

    One of the most striking hallmarks shared by various neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease (AD), and amyotrophic lateral sclerosis, is microglia-mediated neuroinflammation. Increasing evidence indicates that microglial activation in the central nervous system is heterogeneous, which can be categorized into two opposite types: M1 phenotype and M2 phenotype. Depending on the phenotypes activated, microglia can produce either cytotoxic or neuroprotective effects. In this review, we focus on the potential role of M1 and M2 microglia and the dynamic changes of M1/M2 phenotypes that are critically associated with the neurodegenerative diseases. Generally, M1 microglia predominate at the injury site at the end stage of disease, when the immunoresolution and repair process of M2 microglia are dampened. This phenotype transformation is very complicated in AD due to the phagocytosis of regionally distributed β-amyloid (Aβ) plaque and tangles that are released into the extracellular space. The endogenous stimuli including aggregated α-synuclein, mutated superoxide dismutase, Aβ, and tau oligomers exist in the milieu that may persistently activate M1 pro-inflammatory responses and finally lead to irreversible neuron loss. The changes of microglial phenotypes depend on the disease stages and severity; mastering the stage-specific switching of M1/M2 phenotypes within appropriate time windows may provide better therapeutic benefit.

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

    Science.gov (United States)

    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.

  4. Three-dimensional numerical simulation of M2 internal tides in the Luzon Strait

    Institute of Scientific and Technical Information of China (English)

    LI Bingtian; CAO Anzhou; LV Xianqing

    2015-01-01

    A three-dimensional isopycnic-coordinate internal tidal model is employed to investigate the generation, propagation, vertical structure and energy conversion of M2 internal tides in the Luzon Strait (LS) with mooring observations. Simulated results, especially the tidal current amplitudes, agree well with observations, demonstrating the reasonability and accuracy of the model. Results indicate that M2 internal tides mainly propagate into three directions horizontally, i.e., eastward towards the western Pacific Ocean, westward towards the Dongsha Island and southwestward towards the South China Sea Basin. In the horizontal direction, tidal current amplitudes decrease as distance increases away from the LS; in the vertical direction, they show an obvious decreasing tendency with depth. Between the double ridges of the LS, a clockwise gyre of M2 baroclinic energy flux appears, which is caused by reflections of M2 internal tides at supercritical topographies, and resonance of M2 internal tides happens along 19.5° and 21.5°N due to the heights and separation distance of the double ridges. The total energy conversion in the LS is about 14.20 GW.

  5. Estimates of global M2 internal tide energy fluxes using TOPEX/POSEIDON altimeter data

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yanwei; LIANG Xinfeng; TIAN Jiwei; YANG Lifen

    2009-01-01

    TOPEX/POSEIDON altimeter data from October 1992 to June 2002 are used to calculate the global barotropic M2 tidal currents using long-term tidal harmonic analysis. The tides calculated agree well with ADCP data obtained from the South China Sea (SCS). The maximum tide velocities along the semi-major axis and semi-minor axis can be computed from the tidal ellipse. The global distribution of M2 internal tide vertical energy flux from the sea bottom is calculated based on a linear internal wave generation model. The global vertical energy flux of M2 internal tide is 0.96 TW, with 0.36 TW in the Pacific, 0.31 TW in the Atlantic and 0.29 TW in the Indian Ocean, obtained in this study. The total horizontal energy flux of M2 internal tide radiating into the open ocean from the lateral boundaries is 0.13 TW, with 0.06 TW in the Pacific, 0.04TW in the Atlantic, and 0.03 TW in the Indian Ocean. The result shows that the principal lunar semi-diurnal tide M2 provides enough energy to maintain the large-scale thermohaline circulation of the ocean.

  6. Dynamic Environmental/Economic Scheduling for Microgrid Using Improved MOEA/D-M2M

    Directory of Open Access Journals (Sweden)

    Xin Li

    2016-01-01

    Full Text Available The environmental/economic dynamic scheduling for microgrids (MGs is a complex multiobjective optimization problem, which usually has dynamic system parameters and constraints. In this paper, a biobjective optimization model of MG scheduling is established. And various types of microsources (like the conventional sources, various types of renewable sources, etc., electricity markets, and dynamic constraints are considered. A recently proposed MOEA/D-M2M framework is improved (I-MOEA/D-M2M to solve the real-world MG scheduling problems. In order to deal with the constraints, the processes of solutions sorting and selecting in the original MOEA/D-M2M are revised. In addition, a self-adaptive decomposition strategy and a modified allocation method of individuals are introduced to enhance the capability of dealing with uncertainties, as well as reduce unnecessary computational work in practice and meet the time requirements for the dynamic optimization tasks. Thereafter, the proposed I-MOEA/D-M2M is applied to the independent MG scheduling problems, taking into account the load demand variation and the electricity price changes. The simulation results by MATLAB show that the proposed method can achieve better distributed fronts in much less running time than the typical multiobjective evolutionary algorithms (MOEAs like the improved strength Pareto evolutionary algorithm (SPEA2 and the nondominated sorting genetic algorithm II (NSGAII. Finally, I-MOEA/D-M2M is used to solve a 24-hour MG dynamic operation scheduling problem and obtains satisfactory results.

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

    Science.gov (United States)

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

    2017-01-01

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

  8. Wireless Access Control with Smart Antenna for M2M Communications

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    Sankararamakrishnan, R; Sansom, M S

    1995-11-01

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

  10. The challenges of M2M massive access in wireless cellular networks

    Directory of Open Access Journals (Sweden)

    Andrea Biral

    2015-02-01

    Full Text Available The next generation of communication systems, which is commonly referred to as 5G, is expected to support, besides the traditional voice and data services, new communication paradigms, such as Internet of Things (IoT and Machine-to-Machine (M2M services, which involve communication between Machine-Type Devices (MTDs in a fully automated fashion, thus, without or with minimal human intervention. Although the general requirements of 5G systems are progressively taking shape, the technological issues raised by such a vision are still partially unclear. Nonetheless, general consensus has been reached upon some specific challenges, such as the need for 5G wireless access networks to support massive access by MTDs, as a consequence of the proliferation of M2M services. In this paper, we describe the main challenges raised by the M2M vision, focusing in particular on the problems related to the support of massive MTD access in current cellular communication systems. Then we analyze the most common approaches proposed in the literature to enable the coexistence of conventional and M2M services in the current and next generation of cellular wireless systems. We finally conclude by pointing out the research challenges that require further investigation in order to provide full support to the M2M paradigm.

  11. Prophylactic and therapeutic activity of fully human monoclonal antibodies directed against Influenza A M2 protein

    Directory of Open Access Journals (Sweden)

    Gwerder Myriam

    2009-12-01

    Full Text Available Abstract Influenza virus infection is a prevalent disease in humans. Antibodies against hemagglutinin have been shown to prevent infection and hence hemagglutinin is the major constituent of current vaccines. Antibodies directed against the highly conserved extracellular domain of M2 have also been shown to mediate protection against Influenza A infection in various animal models. Active vaccination is generally considered the best approach to combat viral diseases. However, passive immunization is an attractive alternative, particularly in acutely exposed or immune compromized individuals, young children and the elderly. We recently described a novel method for the rapid isolation of natural human antibodies by mammalian cell display. Here we used this approach to isolate human monoclonal antibodies directed against the highly conserved extracellular domain of the Influenza A M2 protein. The identified antibodies bound M2 peptide with high affinities, recognized native cell-surface expressed M2 and protected mice from a lethal influenza virus challenge. Moreover, therapeutic treatment up to 2 days after infection was effective, suggesting that M2-specific monoclonals have a great potential as immunotherapeutic agents against Influenza infection.

  12. MAGNETIC AND DYNAMICAL PHOTOSPHERIC DISTURBANCES OBSERVED DURING AN M3.2 SOLAR FLARE

    Energy Technology Data Exchange (ETDEWEB)

    Kuckein, C. [Leibniz-Institut für Astrophysik Potsdam (AIP), An der Sternwarte 16, D-14482, Potsdam (Germany); Collados, M.; Sainz, R. Manso, E-mail: ckuckein@aip.de [Instituto de Astrofísica de Canarias (IAC), Vía Láctea s/n, E-38205, La Laguna, Tenerife (Spain)

    2015-02-01

    This Letter reports on a set of full-Stokes spectropolarimetric observations in the near-infrared He i 10830 Å spectral region covering the pre-flare, flare, and post-flare phases of an M3.2 class solar flare. The flare originated on 2013 May 17 and belonged to active region NOAA 11748. We detected strong He i 10830 Å emission in the flare. The red component of the He i triplet peaks at an intensity ratio to the continuum of about 1.86. During the flare, He i Stokes V is substantially larger and appears reversed compared to the usually larger Si i Stokes V profile. The photospheric Si i inversions of the four Stokes profiles reveal the following: (1) the magnetic field strength in the photosphere decreases or is even absent during the flare phase, as compared to the pre-flare phase. However, this decrease is not permanent. After the flare, the magnetic field recovers its pre-flare configuration in a short time (i.e., 30 minutes after the flare). (2) In the photosphere, the line of sight velocities show a regular granular up- and downflow pattern before the flare erupts. During the flare, upflows (blueshifts) dominate the area where the flare is produced. Evaporation rates of ∼10{sup −3} and ∼10{sup −4} g cm{sup −2} s{sup −1} have been derived in the deep and high photosphere, respectively, capable of increasing the chromospheric density by a factor of two in about 400 s.

  13. Signal transduction by M3 muscarinic acetylcholine receptor in prostate cancer

    Science.gov (United States)

    GUO, LIQIANG; LIU, YUQIANG; DING, ZHIBO; SUN, WENDONG; YUAN, MINGZHEN

    2016-01-01

    The present study aimed to investigate the potential mechanisms used during signal transduction by M3 muscarinic acetylcholine receptor (CHRM3) in prostate cancer. The microarray datasets of GSE3325, including 5 clinically localized primary prostate cancers and 4 benign prostate tissues, were downloaded from the Gene Expression Omnibus database. The differentially-expressed genes (DEGs) in primary prostate cancer tissues compared with benign controls were screened using the Limma package. Gene Ontology and pathway enrichment analyses were performed using the Database for Annotation Visualization and Integrated Discovery. Next, a protein-protein interaction (PPI) network was constructed. Additionally, microRNAs (miRNAs) associated with DEGs were predicted and miRNA-target DEG analysis was performed using a Web-based Gene Set Analysis Toolkit. Finally, the PPI network and the miRNA-target DEG network were integrated using Cytoscape. In total, 224 DEGs were screened in the prostate cancer tissues, including 113 upregulated and 111 downregulated genes. CHRM3 and epidermal growth factor (EGF) were enriched in the regulation of the actin cytoskeleton. EGF and v-myc avian myelocytomatosis viral oncogene homolog (Myc) were enriched in the mitogen-activated protein kinase (MAPK) signaling pathway. EGF with the highest degree of connectivity was the hub node in the PPI network, and miR-34b could interact with Myc directly in the miRNA-target DEG network. EGF and Myc may exhibit significant roles in the progression of prostate cancer via regulation of the actin cytoskeleton and the MAPK signaling pathway. CHRM3 may activate these two pathways in prostate cancer progression. Thus, these two key factors and pathways may be crucial mechanisms during signal transduction by CHRM3 in prostate cancer. PMID:26870222

  14. Agronomic Characterization of Wheat Mutants (Triticum aestivum of M3 Generation Planted in Sukabumi

    Directory of Open Access Journals (Sweden)

    Laela Sari

    2016-11-01

    Full Text Available The purpose of this study was to identify the selection criteria to obtain a superior mutant derived from the wheat plants of such varieties as Dewata, Selayar and Alibey, adaptive in medium land. The analysis of agronomic growth characters showed a significantly effect on a growth percentage of the initial growth (8 mutants, flowering time (1 mutant, panicle stem length (15 mutants, number of panicles (7 mutants, the number of grains per panicle (8 mutants, grain weight observed (8 mutants, grain weight per genotype (6 mutants, leaf area (2 mutants and leaf greenness (5 mutants. The effects on the characters of ripe time, harvest, panicle length and plant height were not significant. The mutants of Dewata, Selayar and Alibey could be selected based on the characters of panicle stem length, number of grains per panicle and grain weight per observation because these characters generated more mutants than the other characters. The correlation analysis between the characters of growth and yield components of wheat mutants showed that the number of grains per panicle was positively correlated with the grain weight observed, while the length of panicle stem was positively correlated with grain weight per genotype, number of panicles and leaf area. Hopefully some mutants produced could adapt to the tropical medium land, thus adding to the diversity of wheat germplasm in Indonesia, thereby reducing the import of wheat to Indonesia.How to CiteSari, L., Purwito, A., Sopandie, D., Purnamaningsih, R. & Sudarmonowati, E. (2016. Agronomic Characterization of Wheat Mutants (Triticum aestivum of M3 Generation Planted in Sukabumi. Biosaintifika: Journal of Biology & Biology Education, 8(3, 353-361. 

  15. Remote compositional analysis of lunar olivine-rich lithologies with Moon Mineralogy Mapper (M3) spectra

    Science.gov (United States)

    Isaacson, P.J.; Pieters, C.M.; Besse, S.; Clark, R.N.; Head, J.W.; Klima, R.L.; Mustard, J.F.; Petro, N.E.; Staid, M.I.; Sunshine, J.M.; Taylor, L.A.; Thaisen, K.G.; Tompkins, S.

    2011-01-01

    A systematic approach for deconvolving remotely sensed lunar olivine-rich visible to near-infrared (VNIR) reflectance spectra with the Modified Gaussian Model (MGM) is evaluated with Chandrayaan-1 Moon Mineralogy Mapper (M 3) spectra. Whereas earlier studies of laboratory reflectance spectra focused only on complications due to chromite inclusions in lunar olivines, we develop a systematic approach for addressing (through continuum removal) the prominent continuum slopes common to remotely sensed reflectance spectra of planetary surfaces. We have validated our continuum removal on a suite of laboratory reflectance spectra. Suites of olivine-dominated reflectance spectra from a small crater near Mare Moscoviense, the Copernicus central peak, Aristarchus, and the crater Marius in the Marius Hills were analyzed. Spectral diversity was detected in visual evaluation of the spectra and was quantified using the MGM. The MGM-derived band positions are used to estimate the olivine's composition in a relative sense. Spectra of olivines from Moscoviense exhibit diversity in their absorption features, and this diversity suggests some variation in olivine Fe/Mg content. Olivines from Copernicus are observed to be spectrally homogeneous and thus are predicted to be more compositionally homogeneous than those at Moscoviense but are of broadly similar composition to the Moscoviense olivines. Olivines from Aristarchus and Marius exhibit clear spectral differences from those at Moscoviense and Copernicus but also exhibit features that suggest contributions from other phases. If the various precautions discussed here are weighed carefully, the methods presented here can be used to make general predictions of absolute olivine composition (Fe/Mg content). Copyright ?? 2011 by the American Geophysical Union.

  16. Magnetic and electronic transport properties of the monophosphate tungsten bronze (PO 2) 4(WO 3) 2 m, m = 2

    Science.gov (United States)

    Teweldemedhin, Z. S.; Ramanujachary, K. V.; Greenblatt, M.

    1991-11-01

    Large plate-like dark-brown crystals of monophosphate tungsten bronze (PO 2) 4(WO 3) 2 m, m = 2 or PWO 5 were prepared by reacting stoichiometric mixtures of P 2O 5, WO 3, and W at 1200°C. The temperature dependence of electrical resistivity along each of the three unique crystallographic axes of a single crystal shows semiconducting behavior down to 50 K with an activation energy of ˜0.084 eV. The room temperature resistivitity along the direction of corner sharing WO 6 octahedra is 5 × 10 -3 Ω · cm and about one to two orders of magnitude lower than along other unique directions, which implies quasi one-dimensional behavior. The magnetization study made on a batch of crystals in the temperature range of 2 to 300 K is indicative of antiferromagnetic ordering with a maximum at 15 K. An earlier theoretical study on the band electronic structure of (PO 2) 4(WO 3) 4 predicted both localized and delocalized electrons in narrow and dispersive bands, respectively. The observed magnetic moment of PWO 5 is consistent with the theoretical prediction, but the observed semiconductivity behavior is not. The difference in the observed electronic transport properties of PWO 5 from that of theoretically predicted behavior, as well as the anomalous magnetic and transport properties compared to the higher members of the series of the monophosphate tungsten bronzes {(PO 2) 4(WO 3) 2 m, m = 4, 6}, is discussed in terms of the unique structure of PWO 5.

  17. M2-KK6 System in ABJM Theory : Fuzzy $S^3$ and Wrapped KK6

    CERN Document Server

    Huang, Wung-Hong

    2011-01-01

    We study the properties of M2-KK6 solution in ABJM membrane theory. First, we find a new kind of BPS solution which has six coordinates, contrasts to our previous solutions which have four coordinates. Next, we argue that, after wrapping 2 sphere the new solution may correspond to the previous solution of four coordinates. We analyze the properties therein and conclude that M2-branes described in ABJM theory could expand into fuzzy three sphere plus a wrapped 2 sphere near the KK6 core. Especially, we show in detail how the fuzzy 3-sphere could arise in these solutions and discuss the property of wrapped KK6 and its relation to M5-brane. We also analyze the fluctuation of the M2-KK6 solution and see that it is U(1) field theory.

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

    Energy Technology Data Exchange (ETDEWEB)

    Sepehri, Alireza, E-mail: alireza.sepehri@uk.ac.ir [Faculty of Physics, Shahid Bahonar University, P.O. Box 76175, Kerman (Iran, Islamic Republic of); Research Institute for Astronomy and Astrophysics of Maragha (RIAAM), Maragha (Iran, Islamic Republic of); Faizal, Mir, E-mail: f2mir@uwaterloo.ca [Department of Physics and Astronomy, University of Waterloo, Waterloo, ON, N2L 3G1 (Canada); Setare, Mohammad Reza, E-mail: rezakord@ipm.ir [Department of Science, Campus of Bijar, University of Kurdistan, Bijar (Iran, Islamic Republic of); Ali, Ahmed Farag, E-mail: afali@fsu.edu [Department of Physics, Florida State University, Tallahassee, FL 32306 (United States); Department of Physics, Faculty of Science, Benha University, Benha 13518 (Egypt)

    2016-05-15

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

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

    Science.gov (United States)

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

    2016-10-04

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

  20. Aggregation and Trunking of M2M Traffic via D2D Connections

    DEFF Research Database (Denmark)

    Rigazzi, Giovanni; Kiilerich Pratas, Nuno; Popovski, Petar

    2015-01-01

    , there is a need for new techniques to coordinate the access and allocate the resources. Although the majority of the proposed solutions are focused on the adaptation of the traditional cellular networks to the M2M traffic patterns, novel approaches based on the direct communication among nearby devices may......Machine-to-Machine (M2M) communications is one of the key enablers of the Internet of Things (IoT). Billions of devices are expected to be deployed in the near future for novel M2M applications demanding ubiquitous access and global connectivity. In order to cope with the massive number of machines...... generated packets is performed by a user device, which aggregates the machine-type data, supplements it with its own data and transmits all of them to the Base Station. We observe a fundamental trade-off between latency and the transmit power needed to deliver the aggregate traffic, in a sense that lower...

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    Sankararamakrishnan, R; Sansom, M S

    1995-12-27

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

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

    Directory of Open Access Journals (Sweden)

    Palmer MB

    2014-11-01

    Full Text Available Matthew B Palmer,1 Alfred A Vichot,2 Lloyd G Cantley,2 Gilbert W Moeckel1 1Department of Pathology, Yale University School of Medicine, New Haven, CT, USA; 2Department of Medicine, Yale University School of Medicine, New Haven, CT, USA Abstract: 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. Keywords: macrophages, acute kidney injury, CD163, HLA-DR, CD68, electron microscopy

  5. Functional analysis of the stress-inducible soybean calmodulin isoform-4 (GmCaM-4) promoter in transgenic tobacco plants.

    Science.gov (United States)

    Park, Hyeong Cheol; Kim, Man Lyang; Kang, Yun Hwan; Jeong, Jae Cheol; Cheong, Mi Sun; Choi, Wonkyun; Lee, Sang Yeol; Cho, Moo Je; Kim, Min Chul; Chung, Woo Sik; Yun, Dae-Jin

    2009-04-30

    The transcription of soybean (Glycine max) calmodulin isoform-4 (GmCaM-4) is dramatically induced within 0.5 h of exposure to pathogen or NaCl. Core cis-acting elements that regulate the expression of the GmCaM-4 gene in response to pathogen and salt stress were previously identified, between -1,207 and -1,128 bp, and between -858 and -728 bp, in the GmCaM-4 promoter. Here, we characterized the properties of the DNA-binding complexes that form at the two core cis-acting elements of the GmCaM-4 promoter in pathogen-treated nuclear extracts. We generated GUS reporter constructs harboring various deletions of approximately 1.3-kb GmCaM-4 promoter, and analyzed GUS expression in tobacco plants transformed with these constructs. The GUS expression analysis suggested that the two previously identified core regions are involved in inducing GmCaM-4 expression in the heterologous system. Finally, a transient expression assay of Arabidopsis protoplasts showed that the GmCaM-4 promoter produced greater levels of GUS activity than did the CaMV35S promoter after pathogen or NaCl treatments, suggesting that the GmCaM-4 promoter may be useful in the production of conditional gene expression systems.

  6. Interaction of Tacrine at M1 and M2 Cholinoceptors in Guinea Pig Brain

    Science.gov (United States)

    1993-01-01

    using the selective M, and M2 antagonists [3H]- pirenzepine ([3H]PZ) and [3H]AF-DX 384. The dissocia- tion constants were 0.36 nmol/I for the M...nmol/I) at 25*C with 200 ml homogenate made nist [3H]- pirenzepine ([3HJPZ) [4, 5] and the up to 2 ml with buffer. The incubation period was 2 h...tion constant; nH = Hill coefficient; n = number of experiments. pirenzepine indicate that its affinity for the T"M. 2. Dissociation constants for [3H

  7. CEMS-investigations of AISI M2 steel after nitrogen plasma immersion ion implantation

    Energy Technology Data Exchange (ETDEWEB)

    Uglov, V.V. E-mail: info@research.bsu.unibel.by; Kholmetskii, A.L.; Kuleshov, A.K.; Fedotova, J.A.; Rusalsky, D.P.; Khodasevich, V.V.; Ruebenbauer, K.; Richter, E.; Guenzel, R.; Parascandola, S

    1999-01-02

    Plasma-immersion ion implantation (PIII) and high-current ion implantation (HCII) of nitrogen into M2 steel were carried out. The formation of a multilayer system consisting of a surface layer of austenite on top of {epsilon}-Fe{sub 3}N nitride precipitates was manifested in M2 steel after PIII. HCII forms a thick (more than 14 {mu}m) layer with {epsilon}-Fe{sub 3}N precipitates. Apparently, the formation of the austenite layer after PIII is connected with a local tempering of the steel surface by the pulsed nitrogen ion beam.

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

    Science.gov (United States)

    Bera, Amal K; Akabas, Myles H

    2005-10-21

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

  9. 广雅SUNDAY三期7500元/m2起发售

    Institute of Scientific and Technical Information of China (English)

    张雷

    2008-01-01

    本报讯 6月22日,SUNDAY三期发售,此前已有近300名买家进行购买登记,而发展商把300多套货量一并推出,以最低价格7000元/m2,最高也不超过1万元/m2的诱人价格,且发售当天买家可享受95折优惠。

  10. Peculiarities of lens and tail regeneration detected in newts after spaceflight aboard Foton M3

    Science.gov (United States)

    Grigoryan, Eleonora N.; Almeida, Eduardo; Poplinskaya, Valentina; Novikova, Julia; Domaratskaya, Elena; Aleinikova, Karina; Souza, Kenneth; Skidmore, Mike; Grigoryan, Eleonora N.

    In September 2007 the joint, 12 day long experiment was carried out aboard Russian satellite Foton M3. The goal of the experiment was to study eye lens, tail and forelimb toe regeneration in adult 16 newts (Pl. waltl.) operated 10 days before taking-off. In spaceflight and synchronous ground control we used video recording, temperature and irradiation control, as well as constant availability of thymidine analog BrdU for its absorption via animals' skin. New techniques allowed us to analyze animals' behavior in hyperand microgravity periods of time, to take proper account of spaceflight factors, and measure accumulated pools of DNA-synthesizing cells in regenerating tissues. All tissue specimens obtained from animals were isolated in the day of landing and then prepared for morphological, immunochemical and molecular investigations. Synchronous control was shifted for two days and reproduced flight conditions except changes of gravity influence. As a result in flown animals as compared with synchronous ground control we found lens regeneration of 0.5-1 stage speeded up and an increased BrdU+ (S-phase) cell number in eye cornea, growth zone, limbus and newly forming lens. These features of regeneration were accompanied by an increase of FGF2 expression in eye growth zone and heat shock protein (HSP90) induction purely in retinal macroglial cells of regenerating eyes. Toe regeneration rate was equal and achieved the stage of accomplished healing of amputation area in both groups - "flown" and control animals. We found no essential differences in tail regeneration rate and tail regenerate sizes in the newts exposed to space and on ground. In both groups tail regeneration reached the stage IV-V when tail length and square were around 4.4 mm and 15.5 mm2, correspondingly. However we did observe remarkable changes of tail regenerate form and some of pigmentation. Computer morphometrical analysis showed that only in ground control animals the evident dorso

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

    Science.gov (United States)

    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

  12. Spectroscopy and Photometry of Multiple Populations along the Asymptotic Giant Branch of NGC 2808 and NGC 6121 (M4)

    Science.gov (United States)

    Marino, A. F.; Milone, A. P.; Yong, D.; Da Costa, G.; Asplund, M.; Bedin, L. R.; Jerjen, H.; Nardiello, D.; Piotto, G.; Renzini, A.; Shetrone, M.

    2017-07-01

    We present a photometric and spectroscopic study of multiple populations along the asymptotic giant branch (AGB) of the intermediate-metallicity globular clusters (GCs) NGC 2808 and NGC 6121 (M4). Chemical abundances of O, Na, Mg, Al, Si, Ca, Sc, Ti, V, Cr, Fe, Co, Ni, Zn, Y, and Ce in AGB stars from high-resolution FLAMES+UVES@VLT spectra are reported for both clusters. Our spectroscopic results have been combined with multiwavelength photometry from the Hubble Space Telescope UV survey of Galactic GCs and ground-based photometry, as well as proper motions derived by combining stellar positions from ground-based images and Gaia DR1. Our analysis reveals that the AGBs of both clusters host multiple populations with different chemical compositions. In M4, we have identified two main populations of stars with different Na/O content lying on distinct AGBs in the {m}{{F}438{{W}}} versus {C}{{F}275{{W}},{{F}}336{{W}},{{F}}438{{W}}} and the V versus {C}{{U},{{B}},{{I}}} pseudo-color-magnitude diagrams. In the more massive and complex GC NGC 2808, three groups of stars with different chemical abundances occupy different locations on the so-called “chromosome map” photometric diagram constructed for AGB stars. The spectroscopic + photometric comparison of stellar populations along the AGB and the red giants of this GC suggests that the AGB hosts stellar populations with a range in helium abundances from primordial to high contents of Y˜ 0.32. By contrast, from our data set, there is no evidence for stars with extreme helium abundance (Y˜ 0.38) on the AGB, suggesting that the most He-rich stars of NGC 2808 do not reach this phase. Based on observations collected at the European Organisation for Astronomical Research in the Southern Hemisphere under ESO programs 093.D-0789 and 094.D-0455 and on observations with the NASA/ESA Hubble Space Telescope, obtained at the Space Telescope Science Institute, which is operated by AURA, Inc., under NASA contract NAS 5-26555.

  13. Recent Development of QCD Factorization for B-> M1 M2

    CERN Document Server

    Yang, Deshan

    2010-01-01

    After briefly introducing the framework of QCD factorization for B-> M1 M2 in the language of the Soft-Collinear Effective Theory, we firstly address the recent efforts on higher-order radiative corrections in QCD factorization. Then we discuss some phenomenologies in B-> V V within the framework of QCD factorization.

  14. Kinetics of proton transport into influenza virions by the viral M2 channel.

    Directory of Open Access Journals (Sweden)

    Tijana Ivanovic

    Full Text Available M2 protein of influenza A viruses is a tetrameric transmembrane proton channel, which has essential functions both early and late in the virus infectious cycle. Previous studies of proton transport by M2 have been limited to measurements outside the context of the virus particle. We have developed an in vitro fluorescence-based assay to monitor internal acidification of individual virions triggered to undergo membrane fusion. We show that rimantadine, an inhibitor of M2 proton conductance, blocks the acidification-dependent dissipation of fluorescence from a pH-sensitive virus-content probe. Fusion-pore formation usually follows internal acidification but does not require it. The rate of internal virion acidification increases with external proton concentration and saturates with a pK(m of ∼4.7. The rate of proton transport through a single, fully protonated M2 channel is approximately 100 to 400 protons per second. The saturating proton-concentration dependence and the low rate of internal virion acidification derived from authentic virions support a transporter model for the mechanism of proton transfer.

  15. Tramadol differentially regulates M1 and M2 macrophages from human umbilical cord blood.

    Science.gov (United States)

    Zhang, Jun; Chen, Liang; Sun, Yunyun; Li, Yuanhai

    2017-03-17

    Tramadol is an analgesic drug and relieves pain through activating μ-opioid receptors and inhibiting serotonin and noradrenaline reuptake. Emerging evidence shows that it also stimulates immune cells, including NK cells, splenocytes, and lymphocytes, and elevates IL-2 production. However, it remains unknown whether and how tramadol directly affects macrophages. To answer these questions, we collected human umbilical cord blood, isolated macrophages, and examined their responses to tramadol. Although tramadol did not alter resting macrophages and the antigen-presenting function in lipopolysaccharide-activated macrophages, it regulated M1 and M2 macrophages, which are, respectively, transformed by IFN-γ and IL-4. Interestingly, tramadol inhibits production and secretion of cytokines in M1 macrophages, but facilitates the production of inflammation-responding molecules, synthesized in M2 macrophages. We also found that STAT6 cascade pathway in M2 macrophages was significantly enhanced by tramadol. Therefore, this study reveals that tramadol regulates inflammation by inhibiting M1 macrophages (killing process), but promoting the function of M2 macrophages (healing process).

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

    Science.gov (United States)

    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.

  17. NO EVIDENCE FOR A ROLE OF MUSCARINIC M(2) RECEPTORS IN FUNCTIONAL ANTAGONISM IN BOVINE TRACHEA

    NARCIS (Netherlands)

    ROFFEL, AF; MEURS, H; ELZINGA, CRS; ZAAGSMA, J

    1 The functional antagonism between methacholine- or histamine-induced contraction and beta-adrenoceptor-mediated relaxation was evaluated in bovine tracheal smooth muscle in vitro. In addition, the putative contribution of muscarinic M(2) receptors mediating inhibition of beta-adrenoceptor-induced

  18. Solidification microstructure of M2 high speed steel by different casting technologies

    Directory of Open Access Journals (Sweden)

    Zhou Xuefeng

    2011-08-01

    Full Text Available The present work investigated the solidification microstructure of AISI M2 high speed steel manufactured by different casting technologies, namely iron mould casting and continuous casting. The results revealed that the as-cast structure of the steel was composed of the iron matrix and the M2C eutectic carbide networks, which were greatly refined in the ingot made by continuous casting process, compared with that by the iron mould casting process. M2C eutectic carbides presented variation in their morphologies and growth characteristics in the ingots by both casting methods. In the ingot by iron mould casting, they have a plate-like morphology and grow anisotropically. However, in the ingot made by continuous casting, the carbides evolved into the fiber-like shape that exhibited little characteristics of anisotropic growth. It was noticed that the fiber-like M2C was much easier to decompose and spheroidize after heated, as a result, the carbides refined remarkably, compared with the case of plate-like carbides in the iron mould casting ingot.

  19. Modifications to 25m2 target-aligned research Heliostat mirror panels

    CSIR Research Space (South Africa)

    Roos, TH

    2009-09-01

    Full Text Available Several heliostat mirror panels of the CSIR 25m2 target-aligned heliostat suffered corrosion-related failure, prompting a panel redesign. Two test samples of the new design were subjected to mechanical and thermal cycling tests in an attempt...

  20. Molecular mechanisms that regulate the macrophage M1/M2 polarization balance

    Directory of Open Access Journals (Sweden)

    Nan eWang

    2014-11-01

    Full Text Available 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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2017-01-01

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

  3. Comparison of Plasma Tu-M2-PK and CA19-9 in Pancreatic Cancer

    DEFF Research Database (Denmark)

    Joergensen, Maiken Thyregod; Heegaard, Niels H H; Schaffalitzky de Muckadell, Ove B

    2009-01-01

    because of suspicion of pancreatic cancer. Of these, 51 patients had their conditions diagnosed as PDAC, whereas this diagnosis was ruled out in 52 after 12 months of follow-up. The performance of Tu-M2-PK was compared with that of CA19-9 using cutoff values 15 and 37 U/mL, respectively. RESULTS...

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

    Energy Technology Data Exchange (ETDEWEB)

    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 (Stanford-MED); (Kyoto); (Gakushuin); (Kyushu)

    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.

  5. Experimental Conditions: SE37_S16_M2_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available opes SE37_S16 Blank (80% methanol) SE37_S16_M2 0mg [MassBase ID] MDLC1_43485 SE37_MS1 Metabolites extraction... with 80% methanol and analysis by LC-Orbitrap-MS SE37_DS1 Peak extraction for unlabeled data ...

  6. Serine is a natural ligand and allosteric activator of pyruvate kinase M2

    NARCIS (Netherlands)

    Chaneton, Barbara; Hillmann, Petra; Zheng, Liang; Martin, Agnes C. L.; Maddocks, Oliver D. K.; Chokkathukalam, Achuthanunni; Coyle, Joseph E.; Jankevics, Andris; Holding, Finn P.; Vousden, Karen H.; Frezza, Christian; O'Reilly, Marc; Gottlieb, Eyal

    2012-01-01

    Cancer cells exhibit several unique metabolic phenotypes that are critical for cell growth and proliferation(1). Specifically, they overexpress the M2 isoform of the tightly regulated enzyme pyruvate kinase (PKM2), which controls glycolytic flux, and are highly dependent on de novo biosynthesis of s

  7. Massive M2M Access with Reliability Guarantees in LTE Systems

    DEFF Research Database (Denmark)

    Madueño, Germán Corrales; Kiilerich Pratas, Nuno; Stefanovic, Cedomir

    2015-01-01

    Machine-to-Machine (M2M) communications are one of the major drivers of the cellular network evolution towards 5G systems. One of the key challenges is on how to provide reliability guarantees to each accessing device in a situation in which there is a massive number of almost-simultaneous arrivals...

  8. Medroxyprogesterone acetate drives M2 macrophage differentiation toward a phenotype of decidual macrophage.

    Science.gov (United States)

    Tsai, Yung-Chieh; Tseng, Joseph T; Wang, Chia-Yih; Su, Mei-Tsz; Huang, Jyun-Yuan; Kuo, Pao-Lin

    2017-09-05

    M1 macrophage differentiation plays a crucial role in enhanced inflammation during pregnancy, which may lead to pregnancy complications. Therefore, modulation of macrophage differentiation toward the M2 phenotype is desirable to ensure a successful pregnancy. Medroxyprogesterone acetate (MPA) is a potent progestin with an anti-inflammatory property, but its effect on macrophage differentiation is unknown. This study aimed to examine whether MPA can induce an M2 macrophage differentiation by using the human monocytes cell line THP-1 or primary monocytes. THP-1 cells were primed with phorbol-12-myristate-13 acetate (PMA) to initiate macrophage differentiation. By incubating with MPA, the cells (denoted as MPA-pTHP-1) underwent M2 macrophage differentiation with downregulations of CD11c, IL-1β and TNF-α, and upregulations of CD163 and IL-10; while cells incubated with progesterone (P4) did not show the M2 phenotype. Primary monocytes treated with MPA also had the same M2 phenotype. Moreover, M1 macrophages derived from IFN-γ/LPS-treated THP-1 cells, which had high levels of IL-1b and iNOS, and low levels of IL-10 and IDO, were reversed to the M2 phenotype by the MPA treatment. We also found that the MPA-pTHP-1 promoted the decidualization of endometrial stromal cells and the invasion of trophoblast cells. To mimic conditions of exposure to various pathogens, MPA-pTHP-1 cells were stimulated by different types of TLR ligands. We found they produced lower levels of IL-1β and TNF-α, as well as a higher level of IL-10, compared to untreated cells. Finally, we found the level of phosphorylated ERK in the MPA-pTHP-1 cells was increased, but its IL-10 production was suppressed by either the progesterone/glucocorticoid antagonist (Mifepristone) or MEK inhibitor (U0126). Taken together, MPA could drive monocyte differentiation toward an M2 phenotype that mimics decidual macrophages. This finding holds great potential to combat chronic endometrial inflammation

  9. The M 4 Core Project with HST - V. Characterizing the PSFs of WFC3/UVIS by focus★

    Science.gov (United States)

    Anderson, J.; Bedin, L. R.

    2017-09-01

    As part of the astrometric Hubble Space Telescope (HST) large program GO-12911, we conduct an in-depth study to characterize the point spread function (PSF) of the Uv-VISual channel of the Wide Field Camera 3 (WFC3), as a necessary step to achieve the astrometric goals of the program. We extracted a PSF from each of the 589 deep exposures taken through the F467M filter over the course of a year and find that the vast majority of the PSFs lie along a 1-D locus that stretches continuously from one side of focus, through optimal focus, to the other side of focus. We constructed a focus-diverse set of PSFs and find that with only five medium-bright stars in an exposure it is possible to pin down the focus level of that exposure. We show that the focus-optimized PSF does a considerably better job fitting stars than the average 'library' PSF, especially when the PSF is out of focus. The fluxes and positions are significantly improved over the 'library' PSF treatment. These results are beneficial for a much broader range of scientific applications than simply the program at hand, but the immediate use of these PSFs will enable us to search for astrometric wobble in the bright stars in the core of the globular cluster M 4, which would indicate a dark, high-mass companion, such as a white dwarf, neutron star or black hole.

  10. Kepler Flares. IV. A Comprehensive Analysis of the Activity of the dM4e Star GJ 1243

    Science.gov (United States)

    Silverberg, Steven M.; Kowalski, Adam F.; Davenport, James R. A.; Wisniewski, John P.; Hawley, Suzanne L.; Hilton, Eric J.

    2016-10-01

    We present a comprehensive study of the active dM4e star GJ 1243. We use previous observations and ground-based echelle spectroscopy to determine that GJ 1243 is a member of the Argus association of field stars, suggesting it is ∼ 30{--}50 {{Myr}} old. We analyze 11 months of 1 minute cadence data from Kepler, presenting Kepler flare frequency distributions, as well as determining correlations between flare energy, amplitude, duration, and decay time. We find that the exponent α of the power-law flare energy distribution varies in time, primarily due to completeness of sample and the low frequency of high-energy flares. We also find a deviation from a single power law at high energy. We use ground-based spectroscopic observations that were simultaneous with the Kepler data to provide simultaneous photometric and spectroscopic analysis of three low-energy flares, the lowest-energy dMe flares with detailed spectral analysis to date on any star. The spectroscopic data from these flares extend constraints for radiative hydrodynamic flare models to a lower energy regime than has previously been studied. We use this simultaneous spectroscopy and Kepler photometry to develop approximate conversions from the Kepler bandpass to the traditional U and B bands. This conversion will be a critical factor in comparing any Kepler flare analyses to the canon of previous ground-based flare studies.

  11. The M4 Core Project with HST - IV. Internal Kinematics from Accurate Radial Velocities of 2771 Cluster Members

    CERN Document Server

    Malavolta, L; Bedin, L R; Sneden, C; Nascimbeni, V; Sommariva, V

    2015-01-01

    We present a detailed study of the internal kinematics of the Galactic Globular Cluster M 4 (NGC 6121), by deriving the radial velocities from 7250 spectra for 2771 stars distributed from the upper part of the Red Giant Branch down to the Main Sequence. We describe new approaches to determine the wavelength solution from day-time calibrations and to determine the radial velocity drifts that can occur between calibration and science observations when observing with the GIRAFFE spectrograph at VLT. Two techniques to determine the radial velocity are compared, after a qualitative description of their advantages with respect to other commonly used algorithm, and a new approach to remove the sky contribution from the spectra obtained with fibre-fed spectrograph and further improve the radial velocity precision is presented. The average radial velocity of the cluster is $\\langle v \\rangle = 71.08 \\pm 0.08$ km s$^{-1}$ with an average dispersion of $\\mu_{v_c} = 3.97$ km s$^{-1}$. Using the same dataset and the same ...

  12. Kepler Flares IV: A Comprehensive Analysis of the Activity of the dM4e Star GJ 1243

    CERN Document Server

    Silverberg, Steven M; Davenport, James R A; Wisniewski, John P; Hawley, Suzanne L; Hilton, Eric J

    2016-01-01

    We present a comprehensive study of the active dM4e star GJ 1243. We use previous observations and ground-based echelle spectroscopy to determine that GJ 1243 is a member of the Argus association of field stars, suggesting it is $\\sim 30-50$ Myr old. We analyze eleven months of 1-minute cadence data from Kepler, presenting Kepler flare frequency distributions, as well as determining correlations between flare energy, amplitude, duration, and decay time. We find that the exponent $\\alpha$ of the power-law flare energy distribution varies in time, primarily due to completeness of sample and the low frequency of high-energy flares. We also find a deviation from a single power law at high energy. We use ground-based spectroscopic observations simultaneous with the Kepler data to provide simultaneous photometric and spectroscopic analysis of three low-energy flares, the lowest-energy dMe flares with detailed spectral analysis to date on any star. The spectroscopic data from these flares extend constraints for radi...

  13. Synthesis, structure and properties of {M4O4} cubanes containing nickel(II) and cobalt(II).

    Science.gov (United States)

    Isele, Katharina; Gigon, Fabienne; Williams, Alan F; Bernardinelli, Gérald; Franz, Patrick; Decurtins, Silvio

    2007-01-21

    A survey of the crystal structures containing simple {M4O4} cubane units is reported. It shows that the average M-M distance in these complexes is relatively constant for a given metal ion M. The structures are all distorted from the idealised cube to a T(d) structure, and most show a further distortion which, however, usually maintains some elements of symmetry. A system for classifying the different types of ligand in these complexes is proposed. Two new cubanes of cobalt(II) and nickel(II) with the ligand (R,R)-bis-1,2-(1-methylbenzimidazol-2-yl)ethane-1,2-diol, (R,R)- or its enantiomer have been isolated and the crystal structure of the cobalt(II) complex confirms the cubane structure. Electronic, CD and (1)H NMR spectra and magnetic susceptibility data are reported. The magnetic data for these and other compounds in the literature are discussed in terms of the structural parameters.

  14. Chemotherapy toxicity in gynecologic cancer patients with a body surface area (BSA)>2 m2.

    Science.gov (United States)

    Schwartz, Joanna; Toste, Beth; Dizon, Don S

    2009-07-01

    Although many clinicians practice empiric dose reduction to prevent toxicity, it is unknown whether obese patients given chemotherapy dosed according to actual body weight (ABW) experience excess toxicity. At our institution, cancer patients receive chemotherapy dosed by ABW unless on a protocol capping doses at a maximum body surface area (BSA). We compared toxicities and dose modifications between women with a BSA>2 m(2) on uncapped versus capped paclitaxel as part of adjuvant paclitaxel/carboplatin for gynecologic malignancy. In this retrospective study, women with a BSA>2 m(2) treated with paclitaxel (P) and carboplatin (C) for endometrial and ovarian cancer between January 1999 and July 2007 were identified using the chemotherapy database. Records were reviewed for patient age, BSA, diagnosis, stage, standardized and actual doses for each cycle, adverse drug reactions, and dosing modifications. Statistical comparisons were made using Fisher's exact test. We identified 59 women with BSA>2 m(2) on adjuvant P/C for endometrial and ovarian cancers. 50 received paclitaxel dosed by ABW and 9 received paclitaxel capped at a BSA of 2 m(2). There were no statistically significant differences in rates of toxicity or dose modification. Obese women with a BSA>2 m(2) on paclitaxel dosed by ABW do not experience excess toxicity in comparison to women on paclitaxel capped at a maximum BSA or women in published trials of adjuvant P/C. Empiric dose reduction is unnecessary and may result in suboptimal treatment of obese patients. However, as this was a retrospective review, more research is needed to make definitive recommendations on this topic.

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

    Science.gov (United States)

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

    2014-01-01

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

  16. Study on phylogenetic relationships, variability, and correlated mutations in M2 proteins of influenza virus A.

    Directory of Open Access Journals (Sweden)

    Ly Le

    Full Text Available M2 channel, an influenza virus transmembrane protein, serves as an important target for antiviral drug design. There are still discordances concerning the role of some residues involved in proton transfer as well as the mechanism of inhibition by commercial drugs. The viral M2 proteins show high conservativity; about 3/4 of the positions are occupied by one residue in over 95%. Nine M2 proteins from the H3N2 strain and possibly two proteins from H2N2 strains make a phylogenic cluster closely related to 2RLF. The variability range is limited to 4 residues/position with one exception. The 2RLF protein stands out by the presence of 2 serines at the positions 19 and 50, which are in most other M2 proteins occupied by cysteines. The study of correlated mutations shows that there are several positions with significant mutational correlation that have not been described so far as functionally important. That there are 5 more residues potentially involved in the M2 mechanism of action. The original software used in this work (Consensus Constructor, SSSSg, Corm, Talana is freely accessible as stand-alone offline applications upon request to the authors. The other software used in this work is freely available online for noncommercial purposes at public services on bioinformatics such as ExPASy or NCBI. The study on mutational variability, evolutionary relationship, and correlated mutation presented in this paper is a potential way to explain more completely the role of significant factors in proton channel action and to clarify the inhibition mechanism by specific drugs.

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

    Directory of Open Access Journals (Sweden)

    Christina Camell

    Full Text Available Several studies have implicated fatty-acids as inflammatory regulators, suggesting that there may be a direct role for common dietary fatty-acids in regulating innate immune cells. In humans, a single high-fat meal increases systemic cytokines and leukocytes. In mice, short term high-fat feeding increases adipose tissue (AT leukocytes and alters the inflammatory profile of AT macrophages. We have seen that short term high fat feeding to C57BL/6J male mice increases palmitic and oleic acid within AT depots, but oleic acid increase is highest in the mesenteric AT (MAT. In vitro, oleic acid increases M2 macrophage markers (CD206, MGL1, and ARG1 in a murine macrophage cell line, while addition of palmitic acid is able to inhibit that increase. Three day supplementation of a chow diet, with oleic acid, induced an increase in M2 macrophage markers in the MAT, but not in the epididymal AT. We tested whether increases in M2 macrophages occur during short term ad lib feeding of a high fat diet, containing oleic acid. Experiments revealed two distinct populations of macrophages were altered by a three day high milk-fat diet. One population, phenotypically intermediate for F4/80, showed diet-induced increases in CD206, an anti-inflammatory marker characteristic of M2 macrophages intrinsic to the AT. Evidence for a second population, phenotypically F4/80(HICD11b(HI macrophages, showed increased association with the MAT following short term feeding that is dependent on the adhesion molecule, ICAM-1. Collectively, we have shown that short term feeding of a high-fat diet changes two population of macrophages, and that dietary oleic acid is responsible for increases in M2 macrophage polarization.

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

    Science.gov (United States)

    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

  19. SAP is required for the development of innate phenotype in H2-M3-restricted CD8+ T cells1

    Science.gov (United States)

    Bediako, Yaw; Bian, Yao; Zhang, Hong; Cho, Hoonsik; Stein, Paul L.; Wang, Chyung-Ru

    2012-01-01

    H2-M3-restricted T cells have a pre-activated surface phenotype, rapidly expand and produce cytokines upon stimulation and as such, are classified as innate T cells. Unlike most innate T cells, M3-restricted T cells also express CD8αβ co-receptors and a diverse TCR repertoire: hallmarks of conventional MHC Ia-restricted CD8+ T cells. Although iNKT cells are also innate lymphocytes, they are selected exclusively on hematopoietic cells (HC), while M3-restricted T cells can be selected on either hematopoietic or thymic epithelial cells (TEC). Moreover, their phenotypes differ depending on what cells mediate their selection. Though there is a clear correlation between selection on HC and development of innate phenotype, the underlying mechanism remains unclear. SAP is required for the development of iNKT cells and mediates signals from SLAM receptors that are exclusively expressed on HC. Based on their dual selection pathway, M3-restricted T cells present a unique model for studying the development of innate T cell phenotype. Using both polyclonal and transgenic mouse models we demonstrate that while M3-restricted T cells are capable of developing in the absence of SAP, SAP is required for HC-mediated selection, development of pre-activated phenotype and heightened effector functions of M3-restricted T cells. These findings are significant because they directly demonstrate the need for SAP in HC-mediated acquisition of innate T cell phenotype and suggest that due to their SAP-dependent HC-mediated selection, M3-restricted T cells develop a pre-activated phenotype and an intrinsic ability to proliferate faster upon stimulation, allowing for an important role in the early response to infection. PMID:23041566

  20. Discovery and SAR of a novel series of potent, CNS penetrant M4 PAMs based on a non-enolizable ketone core: Challenges in disposition.

    Science.gov (United States)

    Wood, Michael R; Noetzel, Meredith J; Tarr, James C; Rodriguez, Alice L; Lamsal, Atin; Chang, Sichen; Foster, Jarrett J; Smith, Emery; Chase, Peter; Hodder, Peter S; Engers, Darren W; Niswender, Colleen M; Brandon, Nicholas J; Wood, Michael W; Duggan, Mark E; Conn, P Jeffrey; Bridges, Thomas M; Lindsley, Craig W

    2016-09-01

    This Letter describes the chemical optimization of a novel series of M4 PAMs based on a non-enolizable ketone core, identified from an MLPCN functional high-throughput screen. The HTS hit was potent, selective and CNS penetrant; however, the compound was highly cleared in vitro and in vivo. SAR provided analogs for which M4 PAM potency and CNS exposure were maintained; yet, clearance remained high. Metabolite identification studies demonstrated that this series was subject to rapid, and near quantitative, reductive metabolism to the corresponding secondary alcohol metabolite that was devoid of M4 PAM activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. 1750m3高炉煤气除尘改造及TRT发电技术的应用%De-dusting System Improvement and TRT Technology Application on the 1750m3 Blast Furnaces

    Institute of Scientific and Technical Information of China (English)

    曹海刚; 许强

    2012-01-01

    介绍了济钢2座1750m3高炉煤气湿法改干法涂尘及TRT发电的主体设备、主要技术参数及取得的经济效益。%On the two 1750m3 blast furnaces of Jinan Iron and Steel Co., the wet BFG de-ducting system is replaced with the dry de-dusting system and the TRT generation unit is installed. These equipment and their technical data and economic benefits are presented.

  2. Horizontal-Branch Models and the Second-Parameter Effect. IV. The Case of M3 and Palomar 3

    CERN Document Server

    Catelan, M; Rood, R T

    2001-01-01

    We present a detailed analysis of the "second-parameter pair" of globular clusters M3 (NGC 5272) and Palomar 3. Our main results can be summarized as follows: i) The horizontal-branch (HB) morphology of M3 is significantly bluer in its inner regions (observed with the Hubble Space Telescope) than in the cluster outskirts (observed from the ground), i.e., M3 has an internal second parameter. Most plausibly the mass loss on the red giant branch (RGB) has been more efficient in the inner than in the outer regions of the cluster. ii) The dispersion in mass of the Pal 3 HB is found to be very small -- consistent with zero -- and we argue that this is unlikely to be due to a statistical fluctuation. It is this small mass dispersion that leads to the most apparent difference in the HB morphologies of M3 and Pal 3. iii) The relative HB types of M3 and Pal 3, as measured by mean colors or parameters involving the number of blue, variable, and red HB stars, can easily be accounted for by a fairly small difference in ag...

  3. Genetic environments of the transferable plasmid-mediated blaCTX-M-3 gene in Serratia marcescens isolates.

    Science.gov (United States)

    Chu, Pei-Yu; Peng, Chien-Fang

    2014-01-01

    In this study, genetic environments of the transferable plasmid-mediated blaCTX-M-3 gene were characterized among 14 isolates of cefotaxime-resistant Serratia marcescens using PCR and BLAST DNA sequence analysis. A total of 3 types of genetic architectures in the regions surrounding this blaCTX-M-3 gene were identified. Type I architecture was characterized by the presence of a complete insertion sequence of tnpA-ISEcp1, identified as interrupting a reverse IS26 sequence in the upstream region of the blaCTX-M-3 gene. A reverse-directional orf477 fragment was located downstream of the blaCTX-M-3 gene, which was in the same direction of the mucA gene. A common region containing the orf513 element was located upstream of the mucA gene. Moreover, a copy of the 3'-CS2 element was located immediately upstream of the orf513 element. A novel complex class 1 integron was characterized by the presence of the dfrA19 gene, which was flanked by two copies of class 1 integrons. This is the first report to describe the dfrA19 gene within a novel complex class 1 integron in S. marcescens isolates from Taiwan. This novel complex class 1 integron structure was located distantly upstream of the blaCTX-M-3 gene.

  4. Hypocholesterolemic effects of Kluyveromyces marxianus M3 isolated from Tibetan mushrooms on diet-induced hypercholesterolemia in rat

    Directory of Open Access Journals (Sweden)

    Yuanhong Xie

    2015-06-01

    Full Text Available To investigate the effects of Kluyveromyces marxianus M3 isolated from Tibetan mushrooms on diet-induced hypercholesterolemia in rats, female Wistar rats were fed a high-cholesterol diet (HCD for 28 d to generate hyperlipidemic models. Hyperlipidemic rats were assigned to four groups, which were individually treated with three different dosages of K. marxianus M3+HCD or physiological saline+HCD via oral gavage for 28 d. The total cholesterol (TC, triglycerides (TG, high-density lipoprotein cholesterol (HDL-C, and low-density lipoprotein cholesterol (LDL-C levels in the serum and liver of the rats were measured using commercially available enzyme kits. In addition, the liver morphology was also examined using hematoxylin and eosin staining and optical microscopy. According to our results, the serum and liver TC, TG, LDL-C levels and atherogenic index (AI were significantly decreased in rats orally administered K. marxianus M3 (p <0.01, and the HDL-C levels and anti atherogenic index (AAI were significantly increased (p <0.01 compared to the control group. Moreover, K. marxianus M3 treatment also reduced the build-up of lipid droplets in the liver and exhibited normal hepatocytes, suggesting a protective effect of K. marxianus M3 in hyperlipidemic rats.

  5. Hypocholesterolemic effects of Kluyveromyces marxianus M3 isolated from Tibetan mushrooms on diet-induced hypercholesterolemia in rat.

    Science.gov (United States)

    Xie, Yuanhong; Zhang, Hongxing; Liu, Hui; Xiong, Lixia; Gao, Xiuzhi; Jia, Hui; Lian, Zhengxing; Tong, Nengsheng; Han, Tao

    2015-06-01

    To investigate the effects of Kluyveromyces marxianus M3 isolated from Tibetan mushrooms on diet-induced hypercholesterolemia in rats, female Wistar rats were fed a high-cholesterol diet (HCD) for 28 d to generate hyperlipidemic models. Hyperlipidemic rats were assigned to four groups, which were individually treated with three different dosages of K. marxianus M3+HCD or physiological saline+HCD via oral gavage for 28 d. The total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels in the serum and liver of the rats were measured using commercially available enzyme kits. In addition, the liver morphology was also examined using hematoxylin and eosin staining and optical microscopy. According to our results, the serum and liver TC, TG, LDL-C levels and atherogenic index (AI) were significantly decreased in rats orally administered K. marxianus M3 (p <0.01), and the HDL-C levels and anti atherogenic index (AAI) were significantly increased (p <0.01) compared to the control group. Moreover, K. marxianus M3 treatment also reduced the build-up of lipid droplets in the liver and exhibited normal hepatocytes, suggesting a protective effect of K. marxianus M3 in hyperlipidemic rats.

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

    Science.gov (United States)

    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

  7. Macrophage polarisation: an immunohistochemical approach for identifying M1 and M2 macrophages.

    Directory of Open Access Journals (Sweden)

    Mário Henrique M Barros

    Full Text Available 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

  8. Potent neutralization of influenza A virus by a single-domain antibody blocking M2 ion channel protein.

    Directory of Open Access Journals (Sweden)

    Guowei Wei

    Full Text Available Influenza A virus poses serious health threat to humans. Neutralizing antibodies against the highly conserved M2 ion channel is thought to offer broad protection against influenza A viruses. Here, we screened synthetic Camel single-domain antibody (VHH libraries against native M2 ion channel protein. One of the isolated VHHs, M2-7A, specifically bound to M2-expressed cell membrane as well as influenza A virion, inhibited replication of both amantadine-sensitive and resistant influenza A viruses in vitro, and protected mice from a lethal influenza virus challenge. Moreover, M2-7A showed blocking activity for proton influx through M2 ion channel. These pieces of evidence collectively demonstrate for the first time that a neutralizing antibody against M2 with broad specificity is achievable, and M2-7A may have potential for cross protection against a number of variants and subtypes of influenza A viruses.

  9. Comprehensive photometric study of an extremely low mass ratio deep contact binary in the globular cluster M 4

    Science.gov (United States)

    Li, Kai; Hu, Shaoming; Chen, Xu; Guo, Difu

    2017-10-01

    A comprehensive photometric study and an investigation of the orbital period variation of V53 in the globular cluster M 4 are presented. The photometric study reveals that the mass ratio and the contact degree of V53 are q ˜ 0.078 and f ˜ 69%, respectively. The observed variation in the light curve can be explained by adjusting the spot parameters. V53 belongs to extreme mass ratio (q ≤ 0.25), deep contact (f ≥ 50%) binaries, and its mass ratio is close to the minimum mass ratio predicted by theoretical studies, making it a potential object for studying the evolution of binaries and the formation of blue stragglers and FK Com-type stars. The orbital period of V53 shows a long-term decrease at a rate of dp/dt = 5.89(±0.02) × 10-8 d yr-1. This secular period decrease may be caused by the combination of mass transfer from the more massive component to the less massive component and an angular momentum loss via magnetic braking. As this mass transfer and angular momentum loss continues, V53 will ultimately evolve into a single fast-rotation star. By studying the statistics of all the contact binaries in globular clusters that have been analyzed, we found a possible correlation between the contact degree and whether or not a contact binary is a blue straggler. A contact binary is likely to become a blue straggler when its fill-out factor is more than 46.25(±2.05)%. More samples should be introduced to confirm this preliminary result in the future.

  10. Retinoic acid prevents virus-induced airway hyperreactivity and M2 receptor dysfunction via anti-inflammatory and antiviral effects

    OpenAIRE

    Moreno-Vinasco, Liliana; Verbout, Norah G.; Fryer, Allison D.; Jacoby, David B.

    2009-01-01

    Inhibitory M2 muscarinic receptors on airway parasympathetic nerves normally limit acetylcholine release. Viral infections decrease M2 receptor function, increasing vagally mediated bronchoconstriction. Since retinoic acid deficiency causes M2 receptor dysfunction, we tested whether retinoic acid would prevent virus-induced airway hyperreactivity and prevent M2 receptor dysfunction. Guinea pigs infected with parainfluenza virus were hyperreactive to electrical stimulation of the vagus nerves,...

  11. High temperature EPR study of the M3Fe4V6O24 (M = Cu, Zn, Mg and Mn

    Directory of Open Access Journals (Sweden)

    Guskos Niko

    2016-09-01

    Full Text Available Electron paramagnetic resonance (EPR spectra of M3Fe4V6O24 (M = Cu, Zn, Mg and Mn compounds in high temperature range (293 K to 493 K have been investigated. The role of magnetic (Cu, Mn and non-magnetic (Zn, Mg ions in M3Fe4V6O24 structure in formation of magnetic resonance spectra was studied. Temperature dependence of EPR parameters: resonance field, linewidth and integrated intensity were examined. Similarities and differences in temperature behavior of these parameters has been discussed in terms of different relaxation mechanisms and magnetic interactions in the spin systems. An important role of additional magnetic ions (M = Mn or Cu in the M3Fe4V6O24 structure has been identified and its consequences considered.

  12. A Novel MLC Scheme with M2-QAM Constellations over AWGN and Rayleigh Fading Channels

    Institute of Scientific and Technical Information of China (English)

    YUANDongfeng; ZHANGPeng; WayneE.Stark

    2003-01-01

    Optimal multilevel codes (MLC) with M2-QAM constellations are considered with focus on both AWGN and Rayleigh fading channels. With the proposition of three new set partitioning rules for M2-QAM constellations, a novel simplified MLC scheme with a very simple MSD (Multistage decoding) structure comes into being, which is operated on the capacity rule. Compared with traditional MLC/MSD scheme the new MLC/MSD structure greatly reduces the calculation of the individual capacities in MLC system because the new set partitioning rules ensure the independency of two dimensions symbols. Furthermore the new MLC/MSD system cannot enhance any performance loss and the time delay is just 1/2 of that with traditional partitioning rules. As an example 64-QAM constellation with three new set partitioning rules are provided. Their performance is simulated over AWGN and Rayleigh fading channels by choosing BCH codes as the component codes.

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

    Science.gov (United States)

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

    2017-03-01

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

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

    Science.gov (United States)

    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.

  15. The Mont Blanc mystery solved? A $m^2=-0.28 keV^2$ neutrino

    CERN Document Server

    Ehrlich, Robert

    2016-01-01

    Evidence is presented in support of a hypothesis made in 2013 predicting the existence of a tachyonic neutrino mass eigenstate doublet having $m^2\\approx -0.2 keV^2$ with $\\Delta m^2=1 eV^2.$ The evidence is based primarily on the puzzling LSD (Mont Blanc) neutrino burst observed on February 23, 1987, which the hypothesis thoroughly explains, with additional support from the Kamiokande-II events recorded on the same day. The probability of the null hypothesis, i.e., that background fluctuations can explain the noted features of the two data sets is estimated to be $4.2\\sigma$ (Mont Blanc), and $3.7\\sigma$ (K-II). Such a controversial hypothesis as a tachyonic neutrino requires absolutely definitive proof, and there may exist a test based on observing the neutrino spectrum from diffuse supernovae that could supply it.

  16. Unveiling the structure of the planetary nebula M 2-48 Kinematics and physical conditions

    CERN Document Server

    López-Martin, L; Esteban, C; Vázquez, R; Raga, A C; Torrelles, J M; Miranda, L F; Meaburn, J; Olguin, L

    2002-01-01

    The kinematics and physical conditions of the bipolar planetary nebula M 2-48 are analysed from high and low dispersion long-slit spectra. Previous CCD narrow-band optical observations have suggested that this nebula is mainly formed by a pair of symmetric bow-shocks, an off-center semi-circular shell, and an internal bipolar structure. The bipolar outflow has a complex structure, characterised by a series of shocked regions located between the bright core and the polar tips. There is an apparent kinematic discontinuity between the bright bipolar core and the outer regions. The fragmented ring around the bright bipolar region presents a low expansion velocity and could be associated to ejection in the AGB-PN transition phase, although its nature remains unclear. The chemical abundances of the central region are derived, showing that M 2-48 is a Type I planetary nebula (PN).

  17. Zebrafish M2 muscarinic acetylcholine receptor: cloning, pharmacological characterization, expression patterns and roles in embryonic bradycardia

    OpenAIRE

    Hsieh, Dennis Jine-Yuan; Liao, Ching-Fong

    2002-01-01

    A zebrafish M2 muscarinic acetylcholine receptor (mAChR) gene was cloned. It encodes 495 amino acids in a single exon. The derived amino acid sequence is 73.5% identical to its human homologue.Competitive binding studies of the zebrafish M2 receptor and [3H]-NMS gave negative log dissociation constants (pKi) for each antagonist as follows: atropine (9.16)>himbacine (8.05)⩾4-DAMP (7.83)>AF-DX 116 (7.26)⩾pirenzepine (7.18)⩾tropicamide (6.97)⩾methoctramine (6.82)⩾p-F-HHSiD (6.67)>carbachol (5.20...

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

    Energy Technology Data Exchange (ETDEWEB)

    Aali-Javanangrouh, M.; Rezaei-Aghdam, A. [Azarbaijan Shahid Madani University, Department of Physics, Faculty of Science, Tabriz (Iran, Islamic Republic of)

    2016-11-15

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

  19. Soft X-Ray Magneto-optical Faraday Effect around Ni M2,3 Edges

    Institute of Scientific and Technical Information of China (English)

    CHEN Kai; CUI Ming-Qi; YAN Fen; ZHAO Jia; SUN Li-Juan; ZHENG Lei; MA Chen-Yan; XI Shi-So; ZHAO Yi-Dong

    2008-01-01

    @@ We present magneto-optical (MO) Faraday spectra measured around the M2,3 edges (60-70eV) of Ni films at the Beijing Synchrotron Radiation Facility (BSRF).A polarization analysis of the final state of the transmitted radiation from the Ni film is employed to determine the Faraday rotation at the edges.The MO effect becomes resonantly enhanced at the M2,3 edges,and accordingly large values for the rotation angle β of 1.85 ± 0.19°for this ferromagnetic Ni film with thickness of 31 nm are measured. Without the magnetic field,the azimuthal angles do not shift; with parallel and antiparallel magnetic field the rotation angles shift in the opposite way and they are symmetrical.The uncertainty of Faraday rotation angles mainly comes from the data fitting and the state change of the beamline when the angles are measured.

  20. Epitope Mapping of Avian Influenza M2e Protein: Different Species Recognise Various Epitopes.

    Directory of Open Access Journals (Sweden)

    Noor Haliza Hasan

    Full Text Available 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.

  1. Seamless communication in supply chains based on M2M technology

    OpenAIRE

    Walid Moneimne; Marcin Hajdul; Szymon Mikołajczak

    2016-01-01

    Background: Access to information is the key element in the successful and efficient organization of transport & logistic processes. The importance of real-time access to information is confirmed by a panel workshop carried out with support of design thinking methodology. There are two ways of gaining access to the right information - manual, where human agency is needed and fully automatic, where new M2M technology is implemented. Implementation of such technology improves seamless commu...

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

    Science.gov (United States)

    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

  3. Power Aware Mobility Management of M2M for IoT Communications

    Directory of Open Access Journals (Sweden)

    Awais Ahmad

    2015-01-01

    Full Text Available Machine-to-Machine (M2M communications framework is evolving to sustain faster networks with the potential to connect millions of devices in the following years. M2M is one of the essential competences for implementing Internet of Things (IoT. Therefore, various organizations are now focusing on enhancing improvements into their standards to support M2M communications. Thus, Heterogeneous Mobile Ad Hoc Network (HetMANET can normally be considered appropriate for M2M challenges. These challenges incorporated when a mobile node (MN selects a target network in an energy efficient scanning for efficient handover. Therefore, to cope with these constraints, we proposed a vertical handover scheme for handover triggering and selection of an appropriate network. The proposed scheme is composed of two phases. Firstly, the MNs perform handover triggering based on the optimization of the Receive Signal Strength (RSS from an access point/base station (AP/BS. Secondly, the network selection process is performed by considering the cost and energy consumption of a particular application during handover. Moreover, if there are more networks available, then the MN selects the one provided with the highest quality of service (QoS. The decision regarding the selection of available networks is made on three metrics, that is, cost, energy, and data rate. Furthermore, the selection of an AP/BS of the selected network is made on five parameters: delay, jitter, Bit Error Rate (BER, communication cost, and response time. The numerical and experimental results are compared in the context of energy consumption by an MN, traffic management on an AP/BS, and QoS of the available networks. The proposed scheme efficiently optimizes the handoff related parameters, and it shows significant improvement in the existing models used for similar purpose.

  4. Description of $^{178}$Hf$^{m2}$ in the constrained relativistic mean field theory

    CERN Document Server

    Wei, Zhang; Shuang-Quan, Zhang

    2009-01-01

    The properties of the ground state of $^{178}$Hf and the isomeric state $^{178}$Hf$^{m2}$ are studied within the adiabatic and diabatic constrained relativistic mean field (RMF) approaches. The RMF calculations reproduce well the binding energy and the deformation for the ground state of $^{178}$Hf. Using the ground state single-particle eigenvalues obtained in the present calculation, the lowest excitation configuration with $K^\\pi=16^+$ is found to be $\

  5. M2Align: parallel multiple sequence alignment with a multi-objective metaheuristic.

    Science.gov (United States)

    Zambrano-Vega, Cristian; Nebro, Antonio J; García-Nieto, José; Aldana Montes, José F

    2017-05-24

    Multiple Sequence Alignment (MSA) is an NP-complete optimization problem found in computational biology, where the time complexity of finding an optimal alignment raises exponentially along with the number of sequences and their lengths. Additionally, to assess the quality of a MSA, a number of objectives can be taken into account, such as maximizing the sum-of-pairs, maximizing the totally conserved columns, minimizing the number of gaps, or maximizing structural information based scores such as STRIKE. An approach to deal with MSA problems is to use multi-objective metaheuristics, which are non-exact stochastic optimization methods that can produce high quality solutions to complex problems having two or more objectives to be optimized at the same time. Our motivation is to provide a multi-objective metaheuristic for MSA that can run in parallel taking advantage of multi-core based computers. The software tool we propose, called M2Align (Multi-objective Multiple Sequence Alignment), is a parallel and more efficient version of the three-objective optimizer for sequence alignments MO-SAStrE, able of reducing the algorithm computing time by exploiting the computing capabilities of common multicore CPU clusters. Our performance evaluation over datasets of the benchmark BAliBASE (v3.0) shows that significant time reductions can be achieved by using up to 20 cores. Even in sequential executions, M2Align is faster than MO-SAStrE, thanks to the encoding method used for the alignments. M2Align is an open source project hosted in GitHub, where the source code and sample datasets can be freely obtained: https://github.com/KhaosResearch/M2Align. antonio@lcc.uma.es. Supplementary data are available at Bioinformatics online.

  6. Granulin exacerbates lupus nephritis via enhancing macrophage M2b polarization.

    Directory of Open Access Journals (Sweden)

    Xi Chen

    Full Text Available BACKGROUND AND AIMS: Lupus nephritis (LN, with considerable morbidity and mortality, is one of the most severe manifestations of systemic lupus erythematosus (SLE. Yet, the pathogenic mechanisms of LN have not been clearly elucidated, and efficient therapies are still in great need. Granulin (GRN, a multifunctional protein linked to inflammatory diseases, has recently been reported to correlate with the disease activity of autoimmune diseases. However, the role of GRN in the pathogenic process of LN still remains obscure. In this study, we explored its potential role and underlying mechanism in the pathogenesis of LN. METHODOLOGY/PRINCIPAL FINDINGS: We found that serum GRN levels were significantly up-regulated and were positively correlated with the severity of LN. Overexpression of GRN in vivo by transgenic injection remarkably exacerbated LN, whereas down-regulation of GRN with shRNA ameliorated LN, firmly demonstrating the critical role of GRN in the pathogenesis of LN. Notably, macrophage phenotype analysis revealed that overexpression of GRN could enhance macrophage polarization to M2b, a key mediator of the initiation and progression of LN. On the contrary, down-regulation of GRN resulted in impaired M2b differentiation, thus ameliorating LN. Moreover, we found that MAPK signals were necessary for the effect of GRN on macrophage M2b polarization. CONCLUSION/SIGNIFICANCE: We first demonstrated that GRN could aggravate lupus nephritis (LN via promoting macrophage M2b polarization, which might provide insights into the pathogenesis of LN as well as potential therapeutic strategies against LN.

  7. Regional outbreak of CTX-M-2 β-lactamase-producing Proteus mirabilis in Japan.

    Science.gov (United States)

    Nakano, Ryuichi; Nakano, Akiyo; Abe, Michiko; Inoue, Matsuhisa; Okamoto, Ryoichi

    2012-12-01

    Proteus mirabilis is a common cause of urinary tract infection. Wild-type P. mirabilis strains are usually susceptible to penicillins and cephalosporins, but occurrences of P. mirabilis producing extended-spectrum β-lactamases (ESBLs) have been recently reported. Here, we surveyed the prevalence of cefotaxime resistance among P. mirabilis strains at seven different hospitals in Kanagawa Prefecture, Japan, and investigated their molecular epidemiology to explain the mechanism of their spread. The prevalence of cefotaxime resistance among P. mirabilis increased annually, from 10.1 % in 1998 to 23.1 % in 2003, and increased drastically in 2004, exceeding 40 %. We collected 105 consecutive and non-duplicate cefotaxime-resistant P. mirabilis isolates (MIC 16 to >256 µg ml(-1)) from these hospitals from June 2004 to May 2005 and characterized their profile. PCR and sequence analysis revealed that all resistant strains produced exclusively CTX-M-2 β-lactamase. PFGE analysis identified 47 banding patterns with 83 % or greater similarity. These results indicated that a regional outbreak of P. mirabilis producing CTX-M-2 β-lactamase has occurred in Japan and suggest that the epidemic spread occurred within and across hospitals and communities by extended clonal strains. Plasmid analysis revealed that 44.8 % of plasmids harboured by bla(CTX-M-2) isolates had common profiles, encoding ISEcp1, IS26 and Int1, and belonged to incompatibility group T. Spread of the resistant isolates in Japan resulted from dissemination of narrow-host-range plasmids of the IncT group encoding bla(CTX-M-2). These findings indicate the rapidly developing problem of treating the species to prevent dissemination of ESBL producers.

  8. Performance Analysis of SNR-Based HDAF M2M Cooperative Networks

    Directory of Open Access Journals (Sweden)

    Lingwei Xu

    2015-01-01

    Full Text Available The lower bound on outage probability (OP of mobile-to-mobile (M2M cooperative networks over N-Nakagami fading channels is derived for SNR-based hybrid decode-amplify-forward (HDAF relaying. The OP performance under different conditions is evaluated through numerical simulation to verify the accuracy of the analysis. These results show that the fading coefficient, number of cascaded components, relative geometric gain, and power-allocation are important parameters that influence this performance.

  9. M2 Proton Channel: Toward a Model of a Primitive Proton Pump

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  11. Study of the solidification of M2 high speed steel Laser Cladding coatings

    Directory of Open Access Journals (Sweden)

    Candel, J. J.

    2013-10-01

    Full Text Available High speed steel laser cladding coatings are complex because cracks appear and the hardness is lower than expected. In this paper AISI M2 tool steel coatings on medium carbon AISI 1045 steel substrate have been manufactured and after Laser Cladding (LC processing it has been applied a tempering heat treatment to reduce the amount of retained austenite and to precipitate secondary carbides. The study of metallurgical transformations by Scanning Electron Microscopy (SEM and Electron Back Scattered Diffraction (EBSD shows that the microstructure is extremely fine and complex, with eutectic transformations and MC, M2C and M6C precipitation. Therefore, after the laser coating is necessary to use post-weld heat treatments.Los recubrimientos de acero rápido por Laser Cladding (LC son complejos porque aparecen fisuras y la dureza es menor a la esperada. En este trabajo se han fabricado recubrimientos de acero AISI M2 sobre acero al carbono AISI 1045 y tras el procesado por láser, se han revenido para reducir la cantidad de austenita retenida y precipitar carburos secundarios. El estudio de las transformaciones metalúrgicas con Microscopía Electrónica de Barrido (MEB y Difracción de Electrones Retrodispersados (EBSD muestra que la microestructura es extremadamente fina y compleja, presenta transformaciones eutécticas y precipitación de carburos MC, M2C y M6C. Por tanto, tras el recubrimiento por láser es necesario recurrir a tratamientos térmicos post-soldeo.

  12. Study of the solidification of M2 high speed steel Laser Cladding coatings

    OpenAIRE

    Candel Bou, Juan Jose; Franconetti Rodríguez, Patricia; Amigó Borrás, Vicente

    2013-01-01

    [EN] High speed steel laser cladding coatings are complex because cracks appear and the hardness is lower than expected. In this paper AISI M2 tool steel coatings on medium carbon AISI 1045 steel substrate have been manufactured and after laser cladding (LC) processing it has been applied a tempering heat treatment to reduce the amount of retained austenite and to precipitate secondary carbides. The study of metallurgical transformations by scanning electron microscopy (SEM) and backscattered...

  13. Expression of the M3 Muscarinic Receptor on Orexin Neurons that Project to the Rostral Ventrolateral Medulla.

    Science.gov (United States)

    Dai, Yu-Wen E; Lee, Yen-Hsien; Chen, Jennifer Y S; Lin, Yen-Kuang; Hwang, Ling-Ling

    2016-05-01

    Activation of central cholinergic receptors causes a pressor response in rats, and the hypothalamus is important for this response. Projections from hypothalamic orexin neurons to the rostral ventrolateral medulla (RVLM) are involved in sympatho-excitation of the cardiovascular system. A small population of orexin neurons is regulated by cholinergic inputs through M3 muscarinic acetylcholine receptor (M3 R). To elucidate whether the M3 R on orexin neurons is involved in cardiosympathetic regulation through the RVLM, we examined the presence of the M3 R on retrograde-labeled RVLM-projecting orexin neurons. The retrograde tracer was unilaterally injected into the RVLM. Within the hypothalamus, retrograde-labeled neurons were located predominantly ipsilateral to the injection side. In the anterior hypothalamus (-1.5 to -2.3 mm to the bregma), retrograde-labeled neurons were densely distributed in the paraventricular nuclei and scattered in the retrochiasmatic area. At -2.3 to -3.5 mm from the bregma, labeled neurons were located in the regions where orexin neurons were situated, that is, the tuberal lateral hypothalamic area, perifornical area, and dorsomedial nuclei. Very few retrograde-labeled neurons were observed in the hypothalamus at -3.5 to -4.5 mm from the bregma. About 19.5% ± 1.6% of RVLM-projecting neurons in the tuberal hypothalamus were orexinergic. The M3 R was present on 18.7% ± 3.0% of RVLM-projecting orexin neurons. Injection of a muscarinic agonist, oxotremorine, in the perifornical area resulted in a pressor response, which was attenuated by a pretreatment of atropine. We conclude that cholinergic inputs to orexin neurons may be involved in cardiosympathetic regulation through the M3 R on the orexin neurons that directly project to the RVLM.

  14. 不定方程m~4x(x+1)(x+2)(x+3)=(m~4-1)y(y+1)(y+2)(y+3)的整数解%Solutions of Diophantine Equation m~4x(x+1)(x+2)(x+3)=(m~4-1)y(y+1)(y+2)(y+3)

    Institute of Scientific and Technical Information of China (English)

    郑惠

    2012-01-01

    运用初等方法对不定方程ax(x+1)(x+2)(x+3)=by(y+1)(y+2)(y+3)的整数解进行了研究,得到了当a=m4,b=m4-1时方程的非负整数解仅有(x,y)=(0,0)。%The solution of Diophantine eqeation ax(x+1)(x+2)(x+3)=by(y+1)(y+2)(y+3) is discussed by using elementary methods.It is proved that the eqution has only non-negative integer solution(x,y)=(0,0) when a=m4,b=m4-1.

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

    Science.gov (United States)

    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

  16. Parthenolide Relieves Pain and Promotes M2 Microglia/Macrophage Polarization in Rat Model of Neuropathy

    Directory of Open Access Journals (Sweden)

    Katarzyna Popiolek-Barczyk

    2015-01-01

    Full Text Available Neuropathic pain treatment remains a challenge because pathomechanism is not fully understood. It is believed that glial activation and increased spinal nociceptive factors are crucial for neuropathy. We investigated the effect of parthenolide (PTL on the chronic constriction injury to the sciatic nerve (CCI-induced neuropathy in rat. We analyzed spinal changes in glial markers and M1 and M2 polarization factors, as well as intracellular signaling pathways. PTL (5 µg; i.t. was preemptively and then daily administered for 7 days after CCI. PTL attenuated the allodynia and hyperalgesia and increased the protein level of IBA1 (a microglial/macrophage marker but did not change GFAP (an astrocyte marker on day 7 after CCI. PTL reduced the protein level of M1 (IL-1β, IL-18, and iNOS and enhanced M2 (IL-10, TIMP1 factors. In addition, it downregulated the phosphorylated form of NF-κB, p38MAPK, and ERK1/2 protein level and upregulated STAT3. In primary microglial cell culture we have shown that IL-1β, IL-18, iNOS, IL-6, IL-10, and TIMP1 are of microglial origin. Summing up, PTL directly or indirectly attenuates neuropathy symptoms and promotes M2 microglia/macrophages polarization. We suggest that neuropathic pain therapies should be shifted from blanketed microglia/macrophage suppression toward maintenance of the balance between neuroprotective and neurotoxic microglia/macrophage phenotypes.

  17. Parthenolide Relieves Pain and Promotes M2 Microglia/Macrophage Polarization in Rat Model of Neuropathy.

    Science.gov (United States)

    Popiolek-Barczyk, Katarzyna; Kolosowska, Natalia; Piotrowska, Anna; Makuch, Wioletta; Rojewska, Ewelina; Jurga, Agnieszka M; Pilat, Dominika; Mika, Joanna

    2015-01-01

    Neuropathic pain treatment remains a challenge because pathomechanism is not fully understood. It is believed that glial activation and increased spinal nociceptive factors are crucial for neuropathy. We investigated the effect of parthenolide (PTL) on the chronic constriction injury to the sciatic nerve (CCI)-induced neuropathy in rat. We analyzed spinal changes in glial markers and M1 and M2 polarization factors, as well as intracellular signaling pathways. PTL (5 µg; i.t.) was preemptively and then daily administered for 7 days after CCI. PTL attenuated the allodynia and hyperalgesia and increased the protein level of IBA1 (a microglial/macrophage marker) but did not change GFAP (an astrocyte marker) on day 7 after CCI. PTL reduced the protein level of M1 (IL-1β, IL-18, and iNOS) and enhanced M2 (IL-10, TIMP1) factors. In addition, it downregulated the phosphorylated form of NF-κB, p38MAPK, and ERK1/2 protein level and upregulated STAT3. In primary microglial cell culture we have shown that IL-1β, IL-18, iNOS, IL-6, IL-10, and TIMP1 are of microglial origin. Summing up, PTL directly or indirectly attenuates neuropathy symptoms and promotes M2 microglia/macrophages polarization. We suggest that neuropathic pain therapies should be shifted from blanketed microglia/macrophage suppression toward maintenance of the balance between neuroprotective and neurotoxic microglia/macrophage phenotypes.

  18. Parthenolide Relieves Pain and Promotes M2 Microglia/Macrophage Polarization in Rat Model of Neuropathy

    Science.gov (United States)

    Popiolek-Barczyk, Katarzyna; Kolosowska, Natalia; Makuch, Wioletta; Rojewska, Ewelina; Jurga, Agnieszka M.; Pilat, Dominika

    2015-01-01

    Neuropathic pain treatment remains a challenge because pathomechanism is not fully understood. It is believed that glial activation and increased spinal nociceptive factors are crucial for neuropathy. We investigated the effect of parthenolide (PTL) on the chronic constriction injury to the sciatic nerve (CCI)-induced neuropathy in rat. We analyzed spinal changes in glial markers and M1 and M2 polarization factors, as well as intracellular signaling pathways. PTL (5 µg; i.t.) was preemptively and then daily administered for 7 days after CCI. PTL attenuated the allodynia and hyperalgesia and increased the protein level of IBA1 (a microglial/macrophage marker) but did not change GFAP (an astrocyte marker) on day 7 after CCI. PTL reduced the protein level of M1 (IL-1β, IL-18, and iNOS) and enhanced M2 (IL-10, TIMP1) factors. In addition, it downregulated the phosphorylated form of NF-κB, p38MAPK, and ERK1/2 protein level and upregulated STAT3. In primary microglial cell culture we have shown that IL-1β, IL-18, iNOS, IL-6, IL-10, and TIMP1 are of microglial origin. Summing up, PTL directly or indirectly attenuates neuropathy symptoms and promotes M2 microglia/macrophages polarization. We suggest that neuropathic pain therapies should be shifted from blanketed microglia/macrophage suppression toward maintenance of the balance between neuroprotective and neurotoxic microglia/macrophage phenotypes. PMID:26090236

  19. Access Control in IoT/M2M - Cloud Platform

    DEFF Research Database (Denmark)

    Anggorojati, Bayu

    and quality of life. This paradigm, which is often called Internet of Things (IoT) or Machine-to-Machine (M2M), will provide an unprecedented opportunity to create applications and services that go far beyond the mere purpose of each participant. Many studies on the both technical and social aspects of IoT...... of a system can be accessed by other parties by means of a set of access policies. For an IoT system such as Radio Frequency Identification (RFID) that collects huge amounts of RFID events data and may store it in the cloud storage for tracking purpose, access control to such data becomes a critical point...... management in RFID system is of paramount importance. A distributed cloud platform approach for the IoT/M2M, which consists of a set of IoT/M2M gateways, is introduced to cope with some inherent issues of IoT network which is highly heterogeneous and distributed in nature. As aresult, access control becomes...

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

    Science.gov (United States)

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

    Directory of Open Access Journals (Sweden)

    Yashaswini Kannan

    2016-08-01

    Full Text Available 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.

  2. Fasciola hepatica tegumental antigens indirectly induce an M2 macrophage-like phenotype in vivo.

    Science.gov (United States)

    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.

  3. Characterization of the hrpZ gene from Pseudomonas syringae pv. maculicolaM2

    Science.gov (United States)

    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

  4. RESTful M2M Gateway for Remote Wireless Monitoring for District Central Heating Networks

    Directory of Open Access Journals (Sweden)

    Bo Cheng

    2014-11-01

    Full Text Available 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.

  5. β-elemene inhibits tumor-promoting effect of M2 macrophages in lung cancer.

    Science.gov (United States)

    Yu, Xiaomu; Xu, Maoyi; Li, Na; Li, Zongjuan; Li, Hongye; Shao, Shujuan; Zou, Kun; Zou, Lijuan

    2017-08-19

    Macrophages in tumor are mostly M2-polarized and have been reported to promote tumorigenesis, which are also defined as tumor-associated macrophages (TAMs). β-elemene has therapeutic effects against several cancers, however, it remains unknown whether β-elemene could inhibit cancer by targeting TAMs. Herein, we examined the effect of β-elemene on macrophages to elucidate a novel mechanism of β-elemene in tumor therapy. We showed that the conditioned medium of M2 macrophages promoted lung cancer cells to migration, invasion and epithelial mesenchymal transition, which could be inhibited by β-elemene. Moreover, β-elemene regulated the polarization of macrophages from M2 to M1. β-elemene also inhibited the proliferation, migration, invasion of lung cancer cells and enhanced its radiosensitivity. These results indicate β-elemene suppresses lung cancer by regulating both macrophages and lung cancer cells, it is a promising drug for combination with chemotherapy or radiotherapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Tumor-derived interleukin-1 promotes lymphangiogenesis and lymph node metastasis through M2-type macrophages.

    Directory of Open Access Journals (Sweden)

    Kosuke Watari

    Full Text Available Tumors formed by a highly metastatic human lung cancer cell line are characterized by activated signaling via vascular endothelial growth factor (VEGF-C through its receptor (VEGFR-3 and aggressive lymph node metastasis. In this study, we examined how these highly metastatic cancers acquired aggressive lymph node metastasis. Compared with their lower metastatic counterparts, the highly metastatic tumors formed by this cell line expressed higher amounts of interleukin (IL-1α, with similarly augmented expression of IL-1α and IL-1β by tumor stromal cells and of VEGF-A and VEGF-C by tumor-associated macrophages. These tumor-associated macrophages were mainly of the M2 type. Administration of a macrophage-targeting drug suppressed the production of these potent angiogenic and lymphangiogenic factors, resulting in decreased tumor growth, angiogenesis, lymphangiogenesis, and lymph node metastasis. In Matrigel plug assays, the highly metastatic cells formed tumors that were extensively infiltrated by M2-type macrophages and exhibited enhanced angiogenesis and lymphangiogenesis. All of these responses were suppressed by the IL-1 receptor (IL-1R antagonist anakinra. Thus, the IL-1α-driven inflammatory activation of angiogenesis and lymphangiogenesis seems to provide a highly metastatic tumor microenvironment favorable for lymph node metastasis through cross-talk with macrophages. Accordingly, the IL-1R/M2-type macrophage axis may be a good therapeutic target for patients with this form of lung cancer.

  7. Tumor-derived interleukin-1 promotes lymphangiogenesis and lymph node metastasis through M2-type macrophages.

    Science.gov (United States)

    Watari, Kosuke; Shibata, Tomohiro; Kawahara, Akihiko; Sata, Ken-ichi; Nabeshima, Hiroshi; Shinoda, Ai; Abe, Hideyuki; Azuma, Koichi; Murakami, Yuichi; Izumi, Hiroto; Takahashi, Takashi; Kage, Masayoshi; Kuwano, Michihiko; Ono, Mayumi

    2014-01-01

    Tumors formed by a highly metastatic human lung cancer cell line are characterized by activated signaling via vascular endothelial growth factor (VEGF)-C through its receptor (VEGFR-3) and aggressive lymph node metastasis. In this study, we examined how these highly metastatic cancers acquired aggressive lymph node metastasis. Compared with their lower metastatic counterparts, the highly metastatic tumors formed by this cell line expressed higher amounts of interleukin (IL)-1α, with similarly augmented expression of IL-1α and IL-1β by tumor stromal cells and of VEGF-A and VEGF-C by tumor-associated macrophages. These tumor-associated macrophages were mainly of the M2 type. Administration of a macrophage-targeting drug suppressed the production of these potent angiogenic and lymphangiogenic factors, resulting in decreased tumor growth, angiogenesis, lymphangiogenesis, and lymph node metastasis. In Matrigel plug assays, the highly metastatic cells formed tumors that were extensively infiltrated by M2-type macrophages and exhibited enhanced angiogenesis and lymphangiogenesis. All of these responses were suppressed by the IL-1 receptor (IL-1R) antagonist anakinra. Thus, the IL-1α-driven inflammatory activation of angiogenesis and lymphangiogenesis seems to provide a highly metastatic tumor microenvironment favorable for lymph node metastasis through cross-talk with macrophages. Accordingly, the IL-1R/M2-type macrophage axis may be a good therapeutic target for patients with this form of lung cancer.

  8. Extracellular mycobacterial DnaK polarizes macrophages to the M2-like phenotype.

    Directory of Open Access Journals (Sweden)

    Rafael L Lopes

    Full Text Available Macrophages are myeloid cells that play an essential role in inflammation and host defense, regulating immune responses and maintaining tissue homeostasis. Depending on the microenvironment, macrophages can polarize to two distinct phenotypes. The M1 phenotype is activated by IFN-γ and bacterial products, and displays an inflammatory profile, while M2 macrophages are activated by IL-4 and tend to be anti-inflammatory or immunosupressive. It was observed that DnaK from Mycobacterium tuberculosis has immunosuppressive properties, inducing a tolerogenic phenotype in dendritic cells and MDSCs, contributing to graft acceptance and tumor growth. However, its role in macrophage polarization remains to be elucidated. We asked whether DnaK was able to modulate macrophage phenotype. Murine macrophages, derived from bone marrow, or from the peritoneum, were incubated with DnaK and their phenotype compared to M1 or M2 polarized macrophages. Treatment with DnaK leads macrophages to present higher arginase I activity, IL-10 production and FIZZ1 and Ym1 expression. Furthermore, DnaK increased surface levels of CD206. Importantly, DnaK-treated macrophages were able to promote tumor growth in an allogeneic melanoma model. Our results suggest that DnaK polarizes macrophages to the M2-like phenotype and could constitute a virulence factor and is an important immunomodulator of macrophage responses.

  9. The outer envelopes of globular clusters - I. NGC 7089 (M2)

    Science.gov (United States)

    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.

  10. The Outer Envelopes of Globular Clusters. I. NGC 7089 (M2)

    CERN Document Server

    Kuzma, P B; Mackey, A D; Roderick, T A

    2016-01-01

    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 $\\sim 60^{\\prime}$ ($\\sim 210$ 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 $\\gamma = -2.2 \\pm 0.2$, and contains approximately $1.6\\%$ 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...

  11. Moldeo por inyección del acero rápido M2

    Directory of Open Access Journals (Sweden)

    Ruiz-Román, J. M.

    1996-12-01

    Full Text Available The purpose of this work is to study the feasibility of Powder Injection Molding in order to obtain M2 High Speed Steels with higher performances than those obtained by conventional P/M. With this object trials have been carried out in order to optimize all the process steps (mixing, injection, debinding and sintering, and to evaluate the mechanical properties (hardness and transverse tensile strengh of the manufactured M2 HSS sample.

    Se estudia la viabilidad de la tecnología de Moldeo por Inyección de Polvos (MIM en la fabricación con acero rápido M2 a fin de obtener componentes de este material de prestaciones superiores a las que se consiguen mediante métodos convencionales pulvimetalúrgicos. Los ensayos realizados se han dirigido a optimizar los parámetros de la eliminación del ligante y de la sinterización, con objeto de controlar el contenido de carbono y la densidad final de las piezas, así como evitar la aparición de los defectos típicos de esta tecnología.

  12. Measurement of M2-Curve for Asymmetric Beams by Self-Referencing Interferometer Wavefront Sensor

    Directory of Open Access Journals (Sweden)

    Yongzhao Du

    2016-11-01

    Full Text Available For asymmetric laser beams, the values of beam quality factor M x 2 and M y 2 are inconsistent if one selects a different coordinate system or measures beam quality with different experimental conditionals, even when analyzing the same beam. To overcome this non-uniqueness, a new beam quality characterization method named as M2-curve is developed. The M2-curve not only contains the beam quality factor M x 2 and M y 2 in the x-direction and y-direction, respectively; but also introduces a curve of M x α 2 versus rotation angle α of coordinate axis. Moreover, we also present a real-time measurement method to demonstrate beam propagation factor M2-curve with a modified self-referencing Mach-Zehnder interferometer based-wavefront sensor (henceforth SRI-WFS. The feasibility of the proposed method is demonstrated with the theoretical analysis and experiment in multimode beams. The experimental results showed that the proposed measurement method is simple, fast, and a single-shot measurement procedure without movable parts.

  13. Conformational variability of the glycine receptor M2 domain in response to activation by different agonists.

    Science.gov (United States)

    Pless, Stephan A; Dibas, Mohammed I; Lester, Henry A; Lynch, Joseph W

    2007-12-07

    Models describing the structural changes mediating Cys loop receptor activation generally give little attention to the possibility that different agonists may promote activation via distinct M2 pore-lining domain structural rearrangements. We investigated this question by comparing the effects of different ligands on the conformation of the external portion of the homomeric alpha1 glycine receptor M2 domain. Conformational flexibility was assessed by tethering a rhodamine fluorophore to cysteines introduced at the 19' or 22' positions and monitoring fluorescence and current changes during channel activation. During glycine activation, fluorescence of the label attached to R19'C increased by approximately 20%, and the emission peak shifted to lower wavelengths, consistent with a more hydrophobic fluorophore environment. In contrast, ivermectin activated the receptors without producing a fluorescence change. Although taurine and beta-alanine were weak partial agonists at the alpha1R19'C glycine receptor, they induced large fluorescence changes. Propofol, which drastically enhanced these currents, did not induce a glycine-like blue shift in the spectral emission peak. The inhibitors strychnine and picrotoxin elicited fluorescence and current changes as expected for a competitive antagonist and an open channel blocker, respectively. Glycine and taurine (or beta-alanine) also produced an increase and a decrease, respectively, in the fluorescence of a label attached to the nearby L22'C residue. Thus, results from two separate labeled residues support the conclusion that the glycine receptor M2 domain responds with distinct conformational changes to activation by different agonists.

  14. Seamless communication in supply chains based on M2M technology

    Directory of Open Access Journals (Sweden)

    Walid Moneimne

    2016-12-01

    Full Text Available Background: Access to information is the key element in the successful and efficient organization of transport & logistic processes. The importance of real-time access to information is confirmed by a panel workshop carried out with support of design thinking methodology. There are two ways of gaining access to the right information - manual, where human agency is needed and fully automatic, where new M2M technology is implemented. Implementation of such technology improves seamless communication during transport execution and allows real-time access to needed information. The aim of the paper is to evaluate the influence of the effectiveness of using M2M technology and traditional way of communication as well as data gathering in order to ensure seamless communication in the supply chain. Methods: Survey, design thinking, desk research and real case study results were used in the paper. Results and conclusions: Seamless communication and implementation of M2M technology within the whole supply (including modes of transport and transport units chain is a backbone of the lean and reliable digital supply chain.

  15. Study and Implementation of Floating-point Operations Based on Cortex-M3 Core%Cortex-M3内核浮点型运算的研究与实现

    Institute of Scientific and Technical Information of China (English)

    梅静静; 王申良

    2011-01-01

    通过分析Cortex-M3内核的结构与浮点型格式,充分利用Cortex-M3内核中的分支预测、单周期乘法、硬件除法等众多功能强大的特性,使用Thumb-2指令集实现了单精度浮点型的加、减、乘、除与比较运算,并给出了加减法运算的流程图和除法运算的源程序.%By analyzing the Cortex-M3 core structure and floating-point format, this paper uses the Thumb-2 instruction set to achieve addition, subtraction, multiplication, division and comparison operations of single-precision floating-point numbers, making full use of such powerful features of Cortex-M3 core as branch prediction, single-cycle multiplication and hardware division. The flow chart of addition and subtraction operations, as well as the source program of division operation, is provided.

  16. TREATMENT OF ABNORMAL TEMPERATURE RISE OF 1 800 m3 BF HEARTH%宣钢1800 m3高炉炉缸温度异常升高的处理

    Institute of Scientific and Technical Information of China (English)

    武建新; 匡祎

    2014-01-01

    This paper is aimed at the abnormal temperature rise of the 1800m3 BF hearth carbon bricks . Through correct diagnosis of furnace body corrosion condition , such measures are taken as increasing tita-nium load into the furnace , enhancing cooling intensity , enhancing tap -hole maintenance to guarantee tap-hole depth , changing field on time while tapping and so on , many hidden safety troubles are elimi-nated , and long-time and smooth operation of the 1 800 m3 BF is guaranteed .%针对2013年1月16日宣钢1800 m3高炉炉缸碳砖温度大幅度异常升高。通过正确诊断炉体侵蚀状况,采取提高入炉钛负荷、提高冷却强度、加强铁口维护保证铁口深度、出铁及时倒场等多项护炉措施,消除了安全隐患,保证了1800 m3高炉炉况长期稳定顺行。

  17. M3(Au,Ge)19 and M(3.25)(Au,Ge)18 (M = Ca, Yb): distinctive phase separations driven by configurational disorder in cubic YCd6-type derivatives.

    Science.gov (United States)

    Lin, Qisheng; Corbett, John D

    2010-05-17

    Exploratory syntheses in the M-Au-Ge (M = Ca, Yb) systems have led to the discovery of two cleanly separated non-stoichiometric phases M(3)Au(approximately 14.4)Ge(approximately 4.6) (I) and M(3.25)Au(approximately 12.7)Ge(approximately 5.3) (II). Single crystal X-ray studies reveal that both (space group Im3) feature body-centered-cubic packing of five-shell multiply endohedral clusters that resemble those in the parent YCd(6) (= Y(3)Cd(18)) and are akin to approximate phases in other quasicrystal systems. However, differences resulting from various disorders in these are distinctive. The innermost cluster in the M(3)Au(approximately 14.4)Ge(approximately 4.6) phase (I) remains a disordered tetrahedron, as in the YCd(6) parent. In contrast, its counterpart in the electron-richer M(3.25)Au(approximately 12.7)Ge(approximately 5.3) phase (II) is a "rattling" M atom. The structural differentiations between I and II exhibit strong correlations between lattice parameters, cluster sizes, particular site occupancies, and valence electron counts.

  18. Clinical significance of blood and fecal tumor M2-pyruvate kinase expression in patients with colorectal cancer%结直肠癌患者血清、粪便中M2-PK表达的临床意义

    Institute of Scientific and Technical Information of China (English)

    李勇; 王俊江

    2011-01-01

    目的 探讨结直肠癌患者血清和粪便中肿瘤M2型丙酮酸激酶(M2-PK)表达的临床意义.方法 收集44例结直肠癌患者和22名健康人血液和粪便标本,采用ELISA方法检测tumor M2-PK表达水平.结果 血清M2-PK和粪便M2-PK对结直肠癌的诊断的敏感性分别为59.1%、63.6%,特异性分别为86.4%、81.8%.血清M2 -PK和粪便M2-PK的吻合度有统计学意义.结论 血清和粪便tumor M2-PK的检测对结直肠癌的诊断有重要价值,值得进一步研究.%Objective To evaluate the clinical significance of blood and fecal expression of tumor M2-pyruvate kinase (Tumor M2-PK) in patients with colorectal cancer. Methods With 22 healthy subjects as controls, 44 patients with CRC were examined for tumor M2-PK in serum and fecal samples using a sandwich enzyme immunoassay. Results The sensitivity of serum and fecal tumor M2-PK for detecting CRC was 59.1% and 63.6% with a specificity of 86.4% and 81.8%, respectively. The serum and fecal levels of tumor M2-PK showed a significant correlation in CRC patients. Conclusions Tumor M2-PK has good sensitivity and specificity in the diagnosis of CRC.

  19. Source parameters of a M4.8 and its accompanying repeating earthquakes off Kamaishi, NE Japan: Implications for the hierarchical structure of asperities and earthquake cycle

    Science.gov (United States)

    Uchida, N.; Matsuzawa, T.; Ellsworth, W.L.; Imanishi, K.; Okada, T.; Hasegawa, A.

    2007-01-01

    We determine the source parameters of a M4.9 ?? 0.1 'characteristic earthquake' sequence and its accompanying microearthquakes at ???50 km depth on the subduction plate boundary offshore of Kamaishi, NE Japan. The microearthquakes tend to occur more frequently in the latter half of the recurrence intervals of the M4.9 ?? 0.1 events. Our results show that the microearthquakes are repeating events and they are located not only around but also within the slip area for the 2001 M4.8 event. From the hierarchical structure of slip areas and smaller stress drops for the microearthquakes compared to the M4.8 event, we infer the small repeating earthquakes rupture relatively weak patches in and around the slip area for the M4.8 event and their activity reflects a stress concentration process and/or change in frictional property (healing) at the area. We also infer the patches for the M4.9 ?? 0.1 and other repeating earthquakes undergo aseismic slip during their interseismic period. Copyright 2007 by the American Geophysical Union.

  20. Thermal testing results of an electroformed nickel secondary (M2) mirror

    Science.gov (United States)

    Smith, David R.; Gale, David M.; Cabrera Cuevas, Lizeth; Lucero Álvarez, Maribel; Castro Santos, David; Olmos Tapia, Arak

    2016-07-01

    To support higher-frequency operation, the Large Millimeter Telescope/Gran Telescopio Milimetrico (or LMT/GTM) is replacing its existing monolithic aluminum secondary mirror (M2). The new mirror is a segmented design based on the same electroformed nickel reflector panel technology that is already in use for the primary reflector segments. While the new M2 is lighter and has better surface accuracy than the original mirror, the electroformed panels are more sensitive to high temperatures. During the design phase, concerns were raised over the level of temperature increase that could occur at M2 during daytime observations. Although the panel surface is designed to scatter visible light, the LMT primary mirror is large enough to cause substantial solar heating, even at significant angular separation from the Sun. To address these concerns, the project conducted a series of field tests, within the constraint of having minimum impact on night time observations. The supplier sent two coupon samples of a reflector panel prepared identically to their proposed M2 surface. Temperature sensors were mounted on the samples and they were temporarily secured to the existing M2 mirror at different distances from the center. The goal was to obtain direct monitoring of the surface temperature under site thermal conditions and the concentration effects from the primary reflector. With the sensors installed, the telescope was then commanded to track the Sun with an elevation offset. Initially, elevation offsets from as far as 40 degrees to as close as 6 degrees were tested. The 6 degree separation test quickly passed the target maximum temperature and the telescope was returned to a safer separation. Based on these initial results, a second set of tests was performed using elevation separations from 30 degrees to 8 degrees. To account for the variability of site conditions, the temperature data were analyzed using multiple metrics. These metrics included maximum temperature, final