WorldWideScience

Sample records for m-2 s-1 pa-1

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

    Science.gov (United States)

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

    2017-01-01

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

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

    CERN Document Server

    Lashkevich, Michael

    2014-01-01

    In the framework of the algebraic approach to form factors in two-dimensional integrable models of quantum field theory we consider the reduction of the sine-Gordon model to the $\\Phi_{13}$\\=/perturbation of minimal conformal models of the $M(2,2s+1)$ series. We find in an algebraic form the condition of compatibility of local operators with the reduction. We propose a construction that make it possible to obtain reduction compatible local operators in terms of screening currents. As an application we obtain exact multiparticle form factors for the compatible with the reduction conserved currents $T_{\\pm2k}$, $\\Theta_{\\pm(2k-2)}$, which correspond to the spin $\\pm(2k-1)$ integrals of motion, for any positive integer~$k$. Furthermore, we obtain all form factors of the operators $T_{2k}T_{-2l}$, which generalize the famous $T\\bar T$ operator. The construction is analytic in the $s$ parameter and, therefore, makes sense in the sine-Gordon theory.

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

    Energy Technology Data Exchange (ETDEWEB)

    Lashkevich, Michael [Landau Institute for Theoretical Physics,1a prospekt Akademika Semenova, 142432 Chernogolovka (Russian Federation); Moscow Institute of Physics and Technology,9 Institutsky per., 141707 Dolgoprudny (Russian Federation); Kharkevich Institute for Information Transmission Problems,19 Bolshoy Karetny per., 127994 Moscow (Russian Federation); Pugai, Yaroslav [Landau Institute for Theoretical Physics,1a prospekt Akademika Semenova, 142432 Chernogolovka (Russian Federation); Moscow Institute of Physics and Technology,9 Institutsky per., 141707 Dolgoprudny (Russian Federation)

    2015-04-23

    In the framework of the algebraic approach to form factors in two-dimensional integrable models of quantum field theory we consider the reduction of the sine-Gordon model to the Φ{sub 13}-perturbation of minimal conformal models of the M(2,2s+1) series. We find in an algebraic form the condition of compatibility of local operators with the reduction. We propose a construction that make it possible to obtain reduction compatible local operators in terms of screening currents. As an application we obtain exact multiparticle form factors for the compatible with the reduction conserved currents T{sub ±2k}, Θ{sub ±(2k−2)}, which correspond to the spin ±(2k−1) integrals of motion, for any positive integer k. Furthermore, we obtain all form factors of the operators T{sub 2k}T{sub −2l}, which generalize the famous TT̄ operator. The construction is analytic in the s parameter and, therefore, makes sense in the sine-Gordon theory.

  4. High Frequency of cagA and vacA s1a/m2 Genotype among Helicobacter pylori Infected Gastric Biopsies of Pakistani Children

    Directory of Open Access Journals (Sweden)

    Ahmed, S.

    2011-01-01

    Full Text Available The vacuolating cytotoxin VacA and cytotoxin associated gene product CagA, encoded by vacA and cagA are major virulence determinants associated with pathogenesis of Helicobacter pylori. The presence and prevalence of two major H. pylori virulence associated genes among gastric biopsies of Pakistani children were investigated in the current study. Fifty one gastric biopsy specimens of children were analysed for 16S rRNA, vacA and cagA genes using PCR. The results showed that 21 (41.2% biopsies were positive for H. pylori as determined by 16S rRNA PCR. In the 21 H. pylori positive gastric biopsies, 19 (90.5% showed vacA s1a, 1 (4.75% was vacA s1b and 1 (4.75% was vacA s2 whereas, 5 (23.8% were vacA m1 and 16 (76.2% were vacA m2. None of the H. pylori positive biopsies carried vacA s1c subtype. The cagA gene was found in 13 (61.9% of H. pylori infected biopsies and different vacA combinations were found with or without cagA gene. H. pylori was detected with high frequency of cagA while vacA s1a and vacA m2 regions with vacA s1a/m2 genotype were predominant in H. pylori infected gastric biopsies of children.

  5. Relationship between Helicobacter pylori vacA s1m2 and intestinal metaplasia of gastric mucosa in gastropathic patients%幽门螺杆菌vacA s1m2基因型与胃黏膜肠上皮化生关系

    Institute of Scientific and Technical Information of China (English)

    薄威; 王旭光; 张忠; 王翠芳; 吴璠

    2016-01-01

    目的 探讨幽门螺杆菌(H.pylori) vacA s1m2基因型与胃黏膜肠上皮化生(IM)的关系,为萎缩性胃炎治疗及胃癌预防提供依据.方法 选取H.pylori阳性胃镜活检的石蜡包埋标本271例,包括浅表性胃炎76例(伴IM18例)、萎缩性胃炎56例(伴IM 37例)和胃溃疡139例(伴IM 30例);提取标本中DNA,经巢式PCR方法及琼脂糖凝胶电泳对H pylori的细胞空泡毒素基因(vacA)基因型进行检测.结果 萎缩性胃炎组中vacA s1m2亚型的检出率为53.6% (30/56),明显高于浅表性胃炎组和胃溃疡组;在271例H.pylori阳性病例中,伴IM组vacA s1 m2亚型检出率为62.4%(53/85),明显高于无IM组;萎缩性胃炎病例中伴IM组vacA s1 m2亚型检出率为75.7%(28/37),明显高于无IM组,同时高于浅表性胃炎伴IM组和胃溃疡伴IM组.结论 幽门螺杆菌vacA s1m2基因型与胃黏膜肠上皮化生密切相关,vacA s1m2基因型幽门螺杆菌为萎缩性胃炎相关高致病性菌株.

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

    Science.gov (United States)

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

    2014-01-01

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

  7. Data of evolutionary structure change: 1PA1A-2PA5B [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1PA1A-2PA5B 1PA1 2PA5 A B ----KLEFMEMEKEFEQIDKSG--SWAAIYQDIRHEASD...IFEDTNLKLTLISEDIKSYYTVRQLELENLTTQETREILHFHYTTWPDFGVPESPASFLNFLFKVRESGSLSPE---HGPVVVHDSAGIGRSGTFCLADTCLLLMDKR...HHHH-------------HHHHH - 0 1PA...1 A 1PA1A IDKSG--SWAAI...ne>ILE CA 308 2PA5 B 2PA

  8. Strategies for improved rhamnolipid production by Pseudomonas aeruginosa PA1.

    Science.gov (United States)

    Soares Dos Santos, Alexandre; Pereira, Nei; Freire, Denise M G

    2016-01-01

    Rhamnolipids are biosurfactants with potential for diversified industrial and environmental uses. The present study evaluated three strategies for increasing the production of rhamnolipid-type biosurfactants produced by Pseudomonas aeruginosa strain PA1. The influence of pH, the addition of P. aeruginosa spent culture medium and the use of a fed-batch process were examined. The culture medium adjusted to pH 7.0 was the most productive. Furthermore, the pH of the culture medium had a measurable effect on the ratio of synthesized mono- and dirhamnolipids. At pH values below 7.3, the proportion of monorhamnolipids decreased from 45 to 24%. The recycling of 20% of the spent culture medium in where P. aeruginosa was grown up to the later stationary phase was responsible for a 100% increase in rhamnolipid volumetric productivity in the new culture medium. Finally, the use of fed-batch operation under conditions of limited nitrogen resulted in a 3.8-fold increase in the amount of rhamnolipids produced (2.9 g L(-1)-10.9 g L(-1)). These results offer promising pathways for the optimization of processes for the production of rhamnolipids.

  9. Processing of FENDL-PA/1.1

    Energy Technology Data Exchange (ETDEWEB)

    Mann, F.M.; Lessor, D.E.; Carter, L.L.

    1994-02-01

    The Fusion Evaluated Nuclear Data Library (FENDL) is an evaluated nuclear data library based upon the best evaluations from the world community. The library is maintained by the Nuclear Data Section of the International Atomic Energy Agency (IAEA). However, before the data can be used in computer codes, it must be processed into the appropriate format. The library containing the transmutation (or activation) cross sections that are part of FENDL is designated as FENDL-PA (P designating pointwise). The evaluations in Version 1.1 of this activation library were selected in the following two steps. For the most important reactions ({approximately}250), consultants to the IAEA compared evaluations submitted for consideration with experimental data. These evaluations included those from ENDF/B, JEF, BROND, JENDL, as well as ``complete`` activation libraries, such as EAF and REAC. The consultants then chose the ``best`` evaluation for each of the reactions. The evaluations for the remaining ({approximately}12,000) reactions were taken from EAF-3. The pointwise FENDL-PA/1.1 activation library was processed into two formats. Continuous energy format as used by the Monte Carlo neutron/photon transport code MCNP. ASCII 175 group multigroup format as used by the transmutation code REAC*2/3.

  10. 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....

  11. Orion Launch Abort System (LAS) Propulsion on Pad Abort 1 (PA-1)

    Science.gov (United States)

    Jones, Daniel S.

    2015-01-01

    This presentation provides a concise overview of the highly successful Orion Pad Abort 1 (PA-1) flight test, and the three rocket motors that contributed to this success. The primary purpose of the Orion PA-1 flight was to help certify the Orion Launch Abort System (LAS), which can be utilized in the unlikely event of an emergency on the launchpad or during mission vehicle ascent. The PA-1 test was the first fully integrated flight test of the Orion LAS, one of the primary systems within the Orion Multi-Purpose Crew Vehicle (MPCV). The Orion MPCV is part of the architecture within the Space Launch System (SLS), which is being designed to transport astronauts beyond low-Earth orbit for future exploration missions. Had the Orion PA-1 flight abort occurred during launch preparations for a real human spaceflight mission, the PA-1 LAS would have saved the lives of the crew. The PA-1 flight test was largely successful due to the three solid rocket motors of the LAS: the Attitude Control Motor (ACM); the Jettison Motor (JM); and the Abort Motor (AM). All three rocket motors successfully performed their required functions during the Orion PA-1 flight test, flown on May 6, 2010 at the White Sands Missile Range in New Mexico, culminating in a successful demonstration of an abort capability from the launchpad.

  12. The Orion Pad Abort 1 (PA-1) Flight Test: A Propulsion Success

    Science.gov (United States)

    Jones, Daniel S.

    2015-01-01

    This poster provides a concise overview of the highly successful Orion Pad Abort 1 (PA-1) flight test, and the three rocket motors that contributed to this success. The primary purpose of the Orion PA-1 flight was to help certify the Orion Launch Abort System (LAS), which can be utilized in the unlikely event of an emergency on the launchpad or during mission vehicle ascent. The PA-1 test was the first fully integrated flight test of the Orion LAS, one of the primary systems within the Orion Multi-Purpose Crew Vehicle (MPCV). The Orion MPCV is part of the architecture within the Space Launch System (SLS), which is being designed to transport astronauts beyond low-Earth orbit for future exploration missions. Had the Orion PA-1 flight abort occurred during launch preparations for a real human spaceflight mission, the PA-1 LAS would have saved the lives of the crew. The PA-1 flight test was largely successful due to the three solid rocket motors of the LAS: the Attitude Control Motor (ACM); the Jettison Motor (JM); and the Abort Motor (AM). All three rocket motors successfully performed their required functions during the Orion PA-1 flight test, flown on May 6, 2010 at the White Sands Missile Range in New Mexico, culminating in a successful demonstration of an abort capability from the launchpad.

  13. PTIP associated protein 1, PA1, is an independent prognostic factor for lymphnode negative breast cancer.

    Directory of Open Access Journals (Sweden)

    Takashi Takeshita

    Full Text Available Pax transactivation domain interacting protein (PTIP associated protein 1, PA1, was a newly found protein participating in the modulation of transactivity of nuclear receptor super family members such as estrogen receptor (ER, androgen receptor (AR and glucocorticoid receptor (GR. Breast cancer is one of the most life threatening diseases for women and has tight association with estrogen and ER. This study was performed to understand the function of PA1 in breast cancer. The expression of PA1 had been evaluated in a total of 344 primary invasive breast cancer samples and examined the relationship with clinical output, relapse free survival (RFS, breast cancer-specific survival (BCSS. PA1 expression was observed in both nucleus and cytoplasm, however, appeared mainly in nuclear. PA1 nuclear expression was correlated with postmenopausal (P = 0.0097, smaller tumor size (P = 0.0025, negative Ki67 (P = 0.02, positive AR (P = 0.049 and positive ERβ (P = 0.0020. Kaplan-Meier analysis demonstrated PA1 nuclear positive cases seemed to have a longer survival than negative ones for RFS (P = 0.023 but not for BCSS (P = 0.23. In the Cox hazards model, PA1 nuclear protein expression proved to be a significant prognostic univariate parameter for RFS (P = 0.03, but not for BCSS (P = 0.20. In addition, for those patients without lymphnode metastasis PA1 was found to be an independent prognostic factor for RFS (P = 0.025, which was verified by univariate and multivariate analyses. These investigations suggested PA1 expression could be a potential prognostic indicator for RFS in breast cancer.

  14. Pea Albumin 1 Subunit b (PA1b), a Promising Bioinsecticide of Plant Origin.

    OpenAIRE

    Corinne Royer; Vanessa Eyraud; Lamis Karaki; Frédéric Gressent; Pedro Da Silva

    2011-01-01

    International audience; PA1b (Pea Albumin 1, subunit b) is a peptide extract from pea seeds showing significant insecticidal activity against certain insects, such as cereal weevils (genus Sitophilus), the mosquitoes Culex pipiens and Aedes aegyptii, and certain species of aphids. PA1b has great potential for use on an industrial scale and for use in organic farming: it is extracted from a common plant; it is a peptide (and therefore suitable for transgenic applications); it can withstand man...

  15. 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.

  16. 广谱抗菌肽——片球菌素pediocin PA-1%Pediocin PA-1, a wide-spectrum bacteriocin from lactic acid bacteria

    Institute of Scientific and Technical Information of China (English)

    吕燕妮

    2011-01-01

    Pediocin PA-1 is a broad-spectrum lactic acid bacteria bacteriocin that shows a particularly strong activity against Listeria monocytogenes, a foodborne pathogen of special concern among the food industrys. This antimicrobial peptide is the most extensively studied class Ⅱa bacteriocin, and it has been sufficiently well characterized to be used as a food biopreservative. This review focuses on the progress that have been made in the elucidations of its structure and mode of action, includes an overview of its applications in food systems. In the future, protein engineering, genetic engineering and chemical synthesis may lead to the development of new antimicrobial peptides with improved properties, based on some features of the pediocin PA-1 molecule.%片球菌素PA-1是一种广谱的乳酸菌细菌素,它对食品工业中的腐败菌单核细胞增生李斯特氏菌有强烈的抑制作用,是Ⅱa类细菌素中研究最深入的一种抗菌肽,具有很好的作为食品生物防腐剂开发的应用前景。对近年来关于片球菌素PA-1的结构、作用方式及在食品中的应用作一综述,并对其未来的应用前景,在蛋白质工程、基因工程和化学合成方面进行性质改进做出了展望。

  17. Pea Albumin 1 Subunit b (PA1b, a Promising Bioinsecticide of Plant Origin

    Directory of Open Access Journals (Sweden)

    Corinne Royer

    2011-12-01

    Full Text Available PA1b (Pea Albumin 1, subunit b is a peptide extract from pea seeds showing significant insecticidal activity against certain insects, such as cereal weevils (genus Sitophilus, the mosquitoes Culex pipiens and Aedes aegyptii, and certain species of aphids. PA1b has great potential for use on an industrial scale and for use in organic farming: it is extracted from a common plant; it is a peptide (and therefore suitable for transgenic applications; it can withstand many steps of extraction and purification without losing its activity; and it is present in a seed regularly consumed by humans and mammals without any known toxicity or allergenicity. The potential of this peptide to limit pest damage has stimulated research concerning its host range, its mechanism of action, its three-dimensional structure, the natural diversity of PA1b and its structure–function relationships.

  18. Pea Albumin 1 subunit b (PA1b), a promising bioinsecticide of plant origin.

    Science.gov (United States)

    Gressent, Frédéric; Da Silva, Pedro; Eyraud, Vanessa; Karaki, Lamis; Royer, Corinne

    2011-12-01

    PA1b (Pea Albumin 1, subunit b) is a peptide extract from pea seeds showing significant insecticidal activity against certain insects, such as cereal weevils (genus Sitophilus), the mosquitoes Culex pipiens and Aedes aegyptii, and certain species of aphids. PA1b has great potential for use on an industrial scale and for use in organic farming: it is extracted from a common plant; it is a peptide (and therefore suitable for transgenic applications); it can withstand many steps of extraction and purification without losing its activity; and it is present in a seed regularly consumed by humans and mammals without any known toxicity or allergenicity. The potential of this peptide to limit pest damage has stimulated research concerning its host range, its mechanism of action, its three-dimensional structure, the natural diversity of PA1b and its structure-function relationships.

  19. Data of evolutionary structure change: 1K9PA-1CNPA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1K9PA-1CNPA 1K9P 1CNP A A -ACPLDQAIGLLVAIFHKYSGREGDKHTLSKKELKELIQ...D>1K9P A 1K9PA IGSKL-QDAEI 1CNP A 1CNPA VAL CA 413 -13.432999610900879 15.65699958801269...5 50.41999816894531 rallel> 0.11400000005960464 0.9580000042915344 <

  20. Expression of lactococcin A and pediocin PA-1 in heterologous hosts

    NARCIS (Netherlands)

    Chikindas, M.L.; Venema, K.; Ledeboer, A.M.; Venema, G.; Kok, Jan

    Pediocin PA-1 production, immunity and secretion are specified by a cluster of four genes in Pediococcus acidilactici PAC1.0. The production by, secretion of, and immunity to lactococcin A of Lactococcus lactis are also determined by four genes. Here, expression of the pediocin operon in Lactococcus

  1. Pediocin PA-1, a wide-spectrum bacteriocin from lactic acid bacteria

    NARCIS (Netherlands)

    Rodriguez, JM; Martinez, MI; Kok, J

    2002-01-01

    Pediocin PA-1 is a broad-spectrum lactic acid bacteria bacteriocin that shows a particularly strong activity against Listeria monocytogenes, a foodborne pathogen of special concern among the food industries. This antimicrobial peptide is the most extensively studied class IIa (or pediocin family)

  2. Pediocin PA-1, a wide-spectrum bacteriocin from lactic acid bacteria

    NARCIS (Netherlands)

    Rodriguez, JM; Martinez, MI; Kok, J

    2002-01-01

    Pediocin PA-1 is a broad-spectrum lactic acid bacteria bacteriocin that shows a particularly strong activity against Listeria monocytogenes, a foodborne pathogen of special concern among the food industries. This antimicrobial peptide is the most extensively studied class IIa (or pediocin family) ba

  3. Pediocin PA-1, a wide-spectrum bacteriocin from lactic acid bacteria

    NARCIS (Netherlands)

    Rodriguez, JM; Martinez, MI; Kok, J

    2002-01-01

    Pediocin PA-1 is a broad-spectrum lactic acid bacteria bacteriocin that shows a particularly strong activity against Listeria monocytogenes, a foodborne pathogen of special concern among the food industries. This antimicrobial peptide is the most extensively studied class IIa (or pediocin family) ba

  4. Pediocin PA-1 and a pediocin producing Lactobacillus plantarum strain do not change the HMA rat microbiota

    DEFF Research Database (Denmark)

    Bernbom, Nete; Jelle, N.B.; Brogren, C.-H.

    2009-01-01

    The bacteriocin pediocin PA-1 has potential use as a food biopreservative, and understanding its effect on the commensal gut microbiota is important for assessment of consumer risks associated with the use of biopreservative cultures. Effects of ingested (i) pediocin PA-1 producing Lactobacillus...... in the faeces after ingestion. Pediocin PA-1 did not mediate changes of the rat microbiota, and a biological assay indicated that the bacteriocin was degraded or inactivated during passage through the intestine....

  5. Expression and biological activity of the cystine knot bioinsecticide PA1b (Pea Albumin 1 Subunit b).

    Science.gov (United States)

    Eyraud, Vanessa; Karaki, Lamis; Rahioui, Isabelle; Sivignon, Catherine; Da Silva, Pedro; Rahbé, Yvan; Royer, Corinne; Gressent, Frédéric

    2013-01-01

    The PA1b (Pea Albumin 1, subunit b) peptide is an entomotoxin extract from Legume seeds with lethal activity on several insect pests, such as mosquitoes, some aphids and cereal weevils. This 37 amino-acid cysteine-rich peptide has been, until now, obtained by biochemical purification or chemical synthesis. In this paper, we present our results for the transient production of the peptide in Nicotiana benthamiana by agro-infiltration, with a yield of about 35 µg/g of fresh leaves and maximum production 8 days after infiltration. PA1b is part of the PA1 gene which, after post-translational modifications, encodes two peptides (PA1b and PA1a). We show that transforming tobacco with the PA1b cDNA alone does not result in production of the toxin and, in fact, the entire cDNA is necessary, raising the question of the role of PA1a. We constructed a PA1-cassette, allowing for the quick "cut/paste" of different PA1b mutants within a conserved PA1 cDNA. This cassette enabled us to produce the six isoforms of PA1b which exist in pea seeds. Biological tests revealed that all the isoforms display similar activity, with the exception of one which is inactive. The lack of activity in this isoform led us to conclude that the amphiphilic nature of the peptide is necessary for activity. The possible applications of this expression system for other cysteine-rich biomolecules are discussed.

  6. Expression and biological activity of the cystine knot bioinsecticide PA1b (Pea Albumin 1 Subunit b.

    Directory of Open Access Journals (Sweden)

    Vanessa Eyraud

    Full Text Available The PA1b (Pea Albumin 1, subunit b peptide is an entomotoxin extract from Legume seeds with lethal activity on several insect pests, such as mosquitoes, some aphids and cereal weevils. This 37 amino-acid cysteine-rich peptide has been, until now, obtained by biochemical purification or chemical synthesis. In this paper, we present our results for the transient production of the peptide in Nicotiana benthamiana by agro-infiltration, with a yield of about 35 µg/g of fresh leaves and maximum production 8 days after infiltration. PA1b is part of the PA1 gene which, after post-translational modifications, encodes two peptides (PA1b and PA1a. We show that transforming tobacco with the PA1b cDNA alone does not result in production of the toxin and, in fact, the entire cDNA is necessary, raising the question of the role of PA1a. We constructed a PA1-cassette, allowing for the quick "cut/paste" of different PA1b mutants within a conserved PA1 cDNA. This cassette enabled us to produce the six isoforms of PA1b which exist in pea seeds. Biological tests revealed that all the isoforms display similar activity, with the exception of one which is inactive. The lack of activity in this isoform led us to conclude that the amphiphilic nature of the peptide is necessary for activity. The possible applications of this expression system for other cysteine-rich biomolecules are discussed.

  7. Pseudomonas aeruginosa bacteriophage PA1Ø requires type IV pili for infection and shows broad bactericidal and biofilm removal activities.

    Science.gov (United States)

    Kim, Shukho; Rahman, Marzia; Seol, Sung Yong; Yoon, Sang Sun; Kim, Jungmin

    2012-09-01

    We isolated a new lytic Pseudomonas aeruginosa phage that requires type IV pili for infection. PA1Ø has a broad bactericidal spectrum, covering Gram-positive and Gram-negative bacteria, and can eradicate biofilm cells. PA1Ø may be developed as a therapeutic agent for biofilm-related mixed infections with P. aeruginosa and Staphylococcus aureus.

  8. Chimeras of mature pediocin PA-1 fused to the signal peptide of enterocin P permits the cloning, production, and expression of pediocin PA-1 in Lactococcus lactis.

    Science.gov (United States)

    Martín, María; Gutiérrez, Jorge; Criado, Raquel; Herranz, Carmen; Cintas, Luis M; Hernández, Pablo E

    2007-12-01

    Chimeras of pediocin PA-1 (PedA-1), a bacteriocin produced by Pediococcus acidilactici PLBH9, fused to the signal peptide of enterocin P (EntP), a sec-dependent bacteriocin produced by Enterococcus faecium P13, permitted the production of PedA-1 in Lactococcus lactis. Chimeric genes encoding the EntP signal peptide (SP(entP)) fused to mature PedA-1 (pedA), with or without its immunity gene (pedB), were cloned into the expression vector pMG36c to generate the recombinant plasmids pMPP9 (SP(entP):pedA) and pMPP14i (SP(entP):pedA + pedB). Transformation of competent L. lactis subsp. lactis IL1403, L. lactis subsp. cremoris NZ9000, and L. lactis subsp. lactis DPC5598 with the recombinant plasmids has permitted the detection and quantitation of PedA-1 and the coproduction of nisin A and PedA-1 in supernatants of producer cells with specific anti-PedA-1 antibodies and a noncompetitive indirect enzyme-linked immunosorbent assay. Recombinant L. lactis hosts carrying pMPP9 or pMPP14i displayed antimicrobial activity, suggesting that mature PedA-1 fused to SP(EntP) is the minimum requirement for the synthesis, processing, and secretion of biologically active PedA-1 in L. lactis. However, the production and antimicrobial activity of the PedA-1 produced by L. lactis was lower than that produced by the P. acidilactici control strains.

  9. Rapid and efficient purification method for small, hydrophobic, cationic bacteriocins : Purification of lactococcin B and pediocin PA-1

    NARCIS (Netherlands)

    Venema, Koen; Chikindas, Michael L.; Seegers, Jos F.M.L.; Haandrikman, Alfred J.; Leenhouts, Kees J.; Venema, Gerard; Kok, Jan

    1997-01-01

    The bacteriocins lactococcin B and pediocin PA 1 were purified by ethanol precipitation, preparative isoelectric focusing, and ultrafiltration. The procedure reproducibly leads to high final yields in comparison to the generally low yields obtained by column chromatography. Specifically, during isoe

  10. Rapid and efficient purification method for small, hydrophobic, cationic bacteriocins : Purification of lactococcin B and pediocin PA-1

    NARCIS (Netherlands)

    Venema, Koen; Chikindas, Michael L.; Seegers, Jos F.M.L.; Haandrikman, Alfred J.; Leenhouts, Kees J.; Venema, Gerard; Kok, Jan

    The bacteriocins lactococcin B and pediocin PA 1 were purified by ethanol precipitation, preparative isoelectric focusing, and ultrafiltration. The procedure reproducibly leads to high final yields in comparison to the generally low yields obtained by column chromatography. Specifically, during

  11. Fusion expression of pedA gone to obtain biologically active pediocin PA-1 in Escherichia coli

    Institute of Scientific and Technical Information of China (English)

    Shan-na LIU; Ye HAN; Zhi-jiang ZHOU

    2011-01-01

    Two heterologous expression systems using thioredoxin (trxA) as a gene fusion part in Eschenchia coli weredeveloped to produce recombinant pediocin PA-1. Pediocin PA-1 structural gene pedA was isolated from Pediococcusacidi/actici PA003 by the method of polymerase chain reaction (PCR), then cloned into vector pET32a(+), and expressedas thioredoxin-PedA fusion protein in the host strain E. coil BL21 (DE3). The fusion protein was in the form of inclusionbody and was refolded before purification by nickel-iminodiacetic acid (Ni-IDA) agarose resin column. Biological activity ofrecombinant pediocin PA-1 was analyzed after cleavage of the fusion protein by enterokinase. Agar diffusion test re-vealed that 512-arbitrary unit (AU) recombinant pediocin PA-1 was obtained from 1 ml culture medium of E. coli(pPA003PED1) using Listeda monocytogenes as the indicator strain. Thioredoxin-PedA fusion gene was further clonedinto pET20b(+). Thioredoxin-PedA fusion protein was detected in both the periplasmic and cytoplasmic spaces. Therecombinant pediocin PA-1 from the soluble fraction attained 384 AU from 1 ml culture medium of E. coli (pPA003PED2).Therefore, biologically active pediocin PA-1 could be obtained by these two hybrid gene expression methods.

  12. Improved antimicrobial activities of synthetic-hybrid bacteriocins designed from enterocin E50-52 and pediocin PA-1.

    Science.gov (United States)

    Tiwari, Santosh Kumar; Sutyak Noll, Katia; Cavera, Veronica L; Chikindas, Michael L

    2015-03-01

    Two hybrid bacteriocins, enterocin E50-52/pediocin PA-1 (EP) and pediocin PA-1/enterocin E50-52 (PE), were designed by combining the N terminus of enterocin E50-52 and the C terminus of pediocin PA-1 and by combining the C terminus of pediocin PA-1 and the N terminus of enterocin E50-52, respectively. Both hybrid bacteriocins showed reduced MICs compared to those of their natural counterparts. The MICs of hybrid PE and EP were 64- and 32-fold lower, respectively, than the MIC of pediocin PA-1 and 8- and 4-fold lower, respectively, than the MIC of enterocin E50-52. In this study, the effect of hybrid as well as wild-type (WT) bacteriocins on the transmembrane electrical potential (ΔΨ) and their ability to induce the efflux of intracellular ATP were investigated. Enterocin E50-52, pediocin PA-1, and hybrid bacteriocin PE were able to dissipate ΔΨ, but EP was unable to deplete this component. Both hybrid bacteriocins caused a loss of the intracellular concentration of ATP. EP, however, caused a faster efflux than PE and enterocin E50-52. Enterocin E50-52 and hybrids PE and EP were active against the Gram-positive and Gram-negative bacteria tested, such as Micrococcus luteus, Salmonella enterica serovar Enteritidis 20E1090, and Escherichia coli O157:H7. The hybrid bacteriocins designed and described herein are antimicrobial peptides with MICs lower those of their natural counterparts. Both hybrid peptides induce the loss of intracellular ATP and are capable of inhibiting Gram-negative bacteria, and PE dissipates the electrical potential. In this study, the MIC of hybrid bacteriocin PE decreased 64-fold compared to the MIC of its natural peptide counterpart, pediocin PA-1. Inhibition of Gram-negative pathogens confers an additional advantage for the application of these peptides in therapeutics.

  13. Immunopotentiator from Pantoea agglomerans 1 (IP-PA1) Promotes Murine Hair Growth and Human Dermal Papilla Cell Gene Expression.

    Science.gov (United States)

    Wakame, Koji; Okawa, Hiroshi; Komatsu, Ken-Ich; Nakata, Akifumi; Sato, Keisuke; Ingawa, Hiroyuki; Kohchi, Chie; Nishizawa, Takashi; Soma, Gen-Ichiro

    2016-07-01

    The lipopolysaccharide (LPS)-like compound derived from Pantoea agglomerans (immunopotentiator from Pantoea agglomerans 1 (IP-PA1)) has been used not only as dietary supplement or cosmetic for humans, but also by Japanese veterinarians as an anti-tumor, anti-allergy, "keep a fine coat of fur" and hair growth-promoting functional food for dogs and cats. In the present study, we focused on the hair growth-promoting effects of IP-PA1 on a hair-shaved animal model and its mechanism of action. We also investigated its potential on gene expression after stimulating human dermal papilla cells with IP-PA1. The hair on the back of a C3H/HeN mouse was shaved and IP-PA1 was orally administered or applied to the skin. The status of hair growth was observed and recorded for 14 days. Skin was collected and histological tissue examination was performed with respect to hair growth status using hematoxylin and eosin staining. After IP-PA1 administration (2 and 10 μg/ml) to human dermal papilla cell culture system for 24 h, fibroblast growth factor-7 (FGF-7) and vascular endothelial growth factor (VEGF) mRNA expression were measured using real-time polymerase chain reaction (PCR) analysis. IP-PA1, when given orally, showed a tendency to promote hair growth in mice. In addition, skin application also significantly promoted hair growth, while histopathological examinations further demonstrated hair elongation from dermal papilla cells. In the human dermal papilla cell culture system, significant FGF-7 and VEGF mRNA expressions were observed (p<0.05). An underlying mechanism of gene expression by which IP-PA1 promotes hair growth was suggested to be different from that of medicine and traditional hair tonics, such as minoxidil and adenosine. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  14. Production of biosurfactants from Pseudomonas aeruginosa PA 1 isolated in oil environments

    Directory of Open Access Journals (Sweden)

    Santa Anna L.M.

    2002-01-01

    Full Text Available The potential production of rhamnolipid-type biosurfactants is assessed based on the development of a fermentative process with a strain of Pseudomonas aeruginosa PA1, which was isolated from oil production wastewater in the Northeast of Brazil. These production of molecules using different carbon (n-hexadecane, paraffinic oil, glycerol and babassu oil and nitrogen sources (NaNO3, (NH42SO4 and CH4N2O was studied. The best results were obtained when using glycerol as substrate. A C/N ratio of 60/1 and use of sodium nitrate as nitrogen source resulted in higher production of the rhamnolipid, expressed by rhamnose (3.16 g/L and by the yield in relation to biomass (Yp/x = 0.70 g/g. Additionally, physical-chemical characteristics of the spent broth with and without cells were studied, providing a low critical micelle concentration of 19 mg/L and toxicity values of 13 and 13.8 mg/L using two test organisms, the micro crustacean Daphnia similis and the bacterium Vibrio fisheri (Microtox, respectively.

  15. Pediocin PA-1, a Bacteriocin from Pediococcus acidilactici PAC1.0, Forms Hydrophilic Pores in the Cytoplasmic Membrane of Target Cells

    NARCIS (Netherlands)

    Chikindas, Michael L.; García-Garcerá, Maria J.; Driessen, Arnold J.M.; Ledeboer, Aat M.; Nissen-Meyer, Jon; Nes, Ingolf F.; Abee, Tjakko; Konings, Wilhelmus; Venema, Gerhardus

    1993-01-01

    Pediocin PA-1 is a bacteriocin which is produced by Pediococcus acidilactici PAC1.0. We demonstrate that pediocin PA-1 kills sensitive Pediococcus cells and acts on the cytoplasmic membrane. In contrast to its lack of impact on immune cells, pediocin PA-1 dissipates the transmembrane electrical

  16. Pediocin PA-1, a Bacteriocin from Pediococcus acidilactici PAC1.0, Forms Hydrophilic Pores in the Cytoplasmic Membrane of Target Cells

    NARCIS (Netherlands)

    Chikindas, Michael L.; García-Garcerá, Maria J.; Driessen, Arnold J.M.; Ledeboer, Aat M.; Nissen-Meyer, Jon; Nes, Ingolf F.; Abee, Tjakko; Konings, Wilhelmus; Venema, Gerhardus

    1993-01-01

    Pediocin PA-1 is a bacteriocin which is produced by Pediococcus acidilactici PAC1.0. We demonstrate that pediocin PA-1 kills sensitive Pediococcus cells and acts on the cytoplasmic membrane. In contrast to its lack of impact on immune cells, pediocin PA-1 dissipates the transmembrane electrical pote

  17. Enhanced production of pediocin PA-1 in wild nisin- and non-nisin-producing Lactococcus lactis strains of dairy origin

    NARCIS (Netherlands)

    Reviriego, C.; Fernandez, L.; Kuipers, O. P.; Kok, J.; Rodriguez, J. M.

    In this work, heterologous production of pediocin PA-1 in Lactococcus lactis ESI 153 and ESI 515 (Nis+), two strains selected because of their technological properties for cheesemaking, was achieved after transformation with plasmids pMC117, pRK119 and pCNC1, which contain the complete pediocin

  18. Microcin V Production in Lactobacillus plantarum LB-B1 Using Heterologous Leader Peptide from Pediocin PA-1.

    Science.gov (United States)

    Ma, Xiayin; Wang, Guohong; Li, Dan; Hao, Yanling

    2016-03-01

    Lactobacillus strains producing bacteriocins have attracted highly attention as probiotic cultures in animal nutrition since the use of antibiotics was forbidden in the livestock industry. Lactobacillus plantarum LB-B1 isolated from the fermented dairy product can produce pediocin PA-1, which has a strong inhibition of Listeria but hardly any influence on Gram-negative spoilage agents. In this work, L. plantarum LB-B1 was selected as the host to express microcin V using the leader peptide of pediocin PA-1. Well-diffusion assay combined with Tricine-SDS-polyacrylamide gel showed that microcin V could be successfully expressed and secreted in L. plantarum LB-B1. Meanwhile, the production of microcin V did not affect the secretion of pediocin PA-1. It is worthwhile noted that the supernatant from L. plantarum 8148-ColV had a more effective inhibition of Listeria than that from the control strain L. plantarum 8148. Furthermore, this supernatant also unexpectedly produced antibacterial activity against Staphylococcus aureus. Taken altogether, these results suggested that pediocin PA-1 and microcin V in the supernatant could generate synergistic effect, which not only enhanced the antibacterial ability but also expanded the antibacterial spectrum. Therefore, the recombinant strain has a great potential application as a probiotic to reduce the level of enteric pathogens in livestock industry.

  19. Simple and rapid purification of pediocin PA-1 from Pediococcus pentosaceous NCDC 273 suitable for industrial application.

    Science.gov (United States)

    Vijay Simha, B; Sood, S K; Kumariya, Rashmi; Garsa, Anita Kumari

    2012-10-12

    The use of pediocins as food additives or drugs requires a simple and rapid method by which large quantities of homogeneous pediocin are produced at industrial level. Two centrifugation steps required during initial stages of purification i.e. separation of cells from fermentation broth and collection of precipitates after ammonium sulphate precipitation are the major bottlenecks for their large scale purification. In the present work, pediocin production by a new a dairy strain, Pediococcus pentosaceous NCDC 273 (identical to pediocin PA-1 at nucleotide sequence level), was found to be optimum at initial pH of 6.0 and 7.0 of basal MRS supplemented with 20 g/l of glucose or lactose at 20 and 24 h, respectively. Immobilization of cells through entrapment in alginate-xanthan gum gel beads with chitosan coating resulted in negligible cell release during fermentation. Thus, the cell free extract was directly collected through decantation, avoiding the need of centrifugation step at this stage. Subsequent ammonium sulphate precipitation at isoelectric point of pediocin PA-1 (8.85), using magnetic stirrer at high speed (approx. 1200 rpm), resulted in forceful deposition of precipitates on the wall of precipitation beaker allowing their collection using a spatula, avoiding centrifugation step at this stage also. Further purification using cation-exchange chromatography resulted in yield of 134.4% with more than 320 fold purification with the specific activity of 19×10⁵ AU/mg. The collection of single peak of pediocin at 41.9min in RP-HPLC, overlapping with standard pediocin PA-1, resulted in yield of 1.15 μg from 20 μl of sample applied. The overlapping of RP-HPLC peak and SDS-PAGE band corresponding to 4.6 kDa, confirmed the purity and identity of pediocin 273 as pediocin PA-1.

  20. 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 $\

  1. 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....

  2. Enantioselective degradation and unidirectional chiral inversion of 2-phenylbutyric acid, an intermediate from linear alkylbenzene, by Xanthobacter flavus PA1

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yishan; Han, Ping [School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong (China); Li, Xiao-yan; Shih, Kaimin [Department of Civil Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong (China); Gu, Ji-Dong, E-mail: jdgu@hkucc.hku.hk [School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong (China); The Swire Institute of Marine Science, The University of Hong Kong, Shek O, Cape d' Aguilar, Hong Kong (China)

    2011-09-15

    Highlights: {yields} We isolated a Xanthobacter flavus strain PA1 utilizing the racemic 2-PBA and the single enantiomers as the sole source of carbon and energy. {yields} Both (R) and (S) forms of enantiomers can be degraded in a sequential manner in which the (S) disappeared before the (R) form. {yields} The biochemical degradation pathway involves an initial oxidation of the alkyl side chain before aromatic ring cleavage. - Abstract: Microbial degradation of the chiral 2-phenylbutyric acid (2-PBA), a metabolite of surfactant linear alkylbenzene sulfonates (LAS), was investigated using both racemic and enantiomer-pure compounds together with quantitative stereoselective analyses. A pure culture of bacteria, identified as Xanthobacter flavus strain PA1 isolated from the mangrove sediment of Hong Kong Mai Po Nature Reserve, was able to utilize the racemic 2-PBA as well as the single enantiomers as the sole source of carbon and energy. In the presence of the racemic compounds, X. flavus PA1 degraded both (R) and (S) forms of enantiomers to completion in a sequential manner in which the (S) enantiomer disappeared much faster than the (R) enantiomer. When the single pure enantiomer was supplied as the sole substrate, a unidirectional chiral inversion involving (S) enantiomer to (R) enantiomer was evident. No major difference was observed in the degradation intermediates with either of the individual enantiomers when used as the growth substrate. Two major degradation intermediates were detected and identified as 3-hydroxy-2-phenylbutanoic acid and 4-methyl-3-phenyloxetan-2-one, using a combination of liquid chromatography-mass spectrometry (LC-MS), and {sup 1}H and {sup 13}C nuclear magnetic resonance (NMR) spectroscopy. The biochemical degradation pathway follows an initial oxidation of the alkyl side chain before aromatic ring cleavage. This study reveals new evidence for enantiomeric inversion catalyzed by pure culture of environmental bacteria and emphasizes the

  3. 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.

  4. 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.

  5. New mode of action for a knottin protein bioinsecticide: pea albumin 1 subunit b (PA1b) is the first peptidic inhibitor of V-ATPase.

    Science.gov (United States)

    Chouabe, Christophe; Eyraud, Vanessa; Da Silva, Pedro; Rahioui, Isabelle; Royer, Corinne; Soulage, Christophe; Bonvallet, Robert; Huss, Markus; Gressent, Frédéric

    2011-10-21

    PA1b (for pea albumin 1 subunit b) is a plant bioinsecticide lethal to several pests that are important in agriculture or human health. PA1b belongs to the inhibitory cystine knot family or knottin family. Originating from a plant (the garden pea) commonly eaten by humans without any known toxic or allergic effects, PA1b is a candidate for transgenic applications and is one of the most promising biopesticides for pest control. Using whole-cell patch-clamp techniques on Sf9 PA1b-sensitive lepidopteran insect cells, we discovered that PA1b reversibly blocked ramp membrane currents in a dose-dependent manner (EC(50) = 0.52 μM). PA1b had the same effect as bafilomycin, a specific inhibitor of the vacuolar proton pump (V-type H(+)-ATPase), and the PA1b-sensitive current depended on the internal proton concentration. Biochemical assays on purified V-ATPase from the lepidopteran model Manduca sexta showed that PA1b inhibited the V(1)V(0)-type H(+)-ATPase holoenzyme activity (IC(50) ∼ 70 nM) by interacting with the membrane-bound V(0) part of the V-ATPase. V-ATPase is a complex protein that has been studied increasingly because of its numerous physiological roles. In the midgut of insects, V-ATPase activity is essential for energizing nutrient absorption, and the results reported in this work explain the entomotoxic properties of PA1b. Targeting V-ATPase is a promising means of combating insect pests, and PA1b represents the first peptidic V-ATPase inhibitor. The search for V-ATPase inhibitors is currently of great importance because it has been demonstrated that V-ATPase plays a role in so many physiological processes.

  6. 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.

  7. 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.

  8. 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...

  9. 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.

  10. 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.

  11. 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.

  12. Cloning, expression, and nucleotide sequence of genes involved in production of pediocin PA-1, and bacteriocin from Pediococcus acidilactici PAC1.0.

    Science.gov (United States)

    Marugg, J D; Gonzalez, C F; Kunka, B S; Ledeboer, A M; Pucci, M J; Toonen, M Y; Walker, S A; Zoetmulder, L C; Vandenbergh, P A

    1992-01-01

    The production of pediocin PA-1, a small heat-stable bacteriocin, is associated with the presence of the 9.4-kbp plasmid pSRQ11 in Pediococcus acidilactici PAC1.0. It was shown by subcloning of pSRQ11 in Escherichia coli cloning vectors that pediocin PA-1 is produced and, most probably, secreted by E. coli cells. Deletion analysis showed that a 5.6-kbp SalI-EcoRI fragment derived from pSRQ11 is required for pediocin PA-1 production. Nucleotide sequence analysis of this 5.6-kbp fragment indicated the presence of four clustered open reading frames (pedA, pedB, pedC, and pedD). The pedA gene encodes a 62-amino-acid precursor of pediocin PA-1, as the predicted amino acid residues 19 to 62 correspond entirely to the amino acid sequence of the purified pediocin PA-1. Introduction of a mutation in pedA resulted in a complete loss of pediocin production. The pedB and pedC genes, encoding proteins of 112 and 174 amino acid residues, respectively, are located directly downstream of the pediocin structural gene. Functions could not be assigned to their gene products; mutation analysis showed that the PedB protein is not involved in pediocin PA-1 production. The mutation analysis further revealed that the fourth gene, pedD, specifying a relatively large protein of 724 amino acids, is required for pediocin PA-1 production in E. coli. The predicted pedD protein shows strong similarities to several ATP-dependent transport proteins, including the E. coli hemolysin secretion protein HlyB and the ComA protein, which is required for competence induction for genetic transformation in Streptococcus pneumoniae.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1514784

  13. Simultaneous bioremediation and biodetection of mercury ion through surface display of carboxylesterase E2 from Pseudomonas aeruginosa PA1.

    Science.gov (United States)

    Yin, Kun; Lv, Min; Wang, Qiaoning; Wu, Yixuan; Liao, Chunyang; Zhang, Weiwei; Chen, Lingxin

    2016-10-15

    Mercury is a toxic heavy metal and presents significant threats to organisms and natural ecosystems. Recently, the mercury remediation as well as its detection by environmental-friendly biotechnology has received increasing attention. In this study, carboxylesterase E2 from mercury-resistant strain Pseudomonas aeruginosa PA1 has been successfully displayed on the outer membrane of Escherichia coli Top10 bacteria to simultaneously adsorb and detect mercury ion (Hg(2+)). The transmission electron microscopy analysis shows that Hg(2+) can be absorbed by carboxylesterase E2 and accumulated on the outer membrane of surface-displayed E. coli bacteria. The adsorption of Hg(2+) followed a physicochemical, equilibrated and saturatable mechanism, which well fits the traditional Langmuir adsorption model. The surface-displayed system can be regenerated through regulating pH values. As its activity can be inhibited by Hg(2+), carboxylesterase E2 has been used to detect the concentration of Hg(2+) in water samples. The developed surface display system will be of great potential in the simultaneous bioremediation and biodetection of environmental mercury pollution. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. 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.

  15. 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.

  16. The interaction of the bioinsecticide PA1b (Pea Albumin 1 subunit b) with the insect V-ATPase triggers apoptosis.

    Science.gov (United States)

    Eyraud, Vanessa; Balmand, Séverine; Karaki, Lamis; Rahioui, Isabelle; Sivignon, Catherine; Delmas, Agnès F; Royer, Corinne; Rahbé, Yvan; Da Silva, Pedro; Gressent, Frédéric

    2017-07-07

    PA1b (Pea Albumin 1, subunit b) peptide is an entomotoxin, extracted from Legume seeds, with a lethal activity towards several insect pests, such as mosquitoes, some aphids and cereal weevils. This toxin acts by binding to the subunits c and e of the plasma membrane H(+)-ATPase (V-ATPase) in the insect midgut. In this study, two cereal weevils, the sensitive Sitophilus oryzae strain WAA42, the resistance Sitophilus oryzae strain ISOR3 and the insensitive red flour beetle Tribolium castaneum, were used in biochemical and histological experiments to demonstrate that a PA1b/V-ATPase interaction triggers the apoptosis mechanism, resulting in insect death. Upon intoxication with PA1b, apoptotic bodies are formed in the cells of the insect midgut. In addition, caspase-3 enzyme activity occurs in the midgut of sensitive weevils after intoxication with active PA1b, but not in the midgut of resistant weevils. These biochemical data were confirmed by immuno-histochemical detection of the caspase-3 active form in the midgut of sensitive weevils. Immuno-labelling experiments also revealed that the caspase-3 active form and V-ATPase are close-localized in the insect midgut. The results concerning this unique peptidic V-ATPase inhibitor pave the way for the utilization of PA1b as a promising, more selective and eco-friendly insecticide.

  17. 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.

  18. 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 ${\\mathbb T}^3$.

  19. 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.

  20. Heterologous Processing and Export of the Bacteriocins Pediocin PA-1 and Lactococcin A in Lactococcus Lactis : A Study with Leader Exchange

    NARCIS (Netherlands)

    Chikindas, M.; Emond, E.; Haandrikman, A.J.; Kok, J.; Leenhouts, K.; Pandian, S.; Venema, Gerhardus; Venema, K.

    2010-01-01

    The bacteriocins pediocin PA-1 and lactococcin A are synthesized as precursors carrying N-terminal extensions with a conserved cleavage site preceded by two glycine residues in positions -2 and -1. Each bacteriocin is translocated through the cytoplasmic membrane by an integral membrane protein of

  1. 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.

  2. 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 ...

  3. 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 ...

  4. 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 ...

  5. Main: S1FSORPL21 [PLACE

    Lifescience Database Archive (English)

    Full Text Available S1FSORPL21 S000215 19-August-2004 (last modified) kehi S1F binding site (S1 site) i...in downregulating RPL21 promoter activity (Lagrange et al., 1993); See S000211 (SITE1SORPS1), S000166 (S2FSOR

  6. [A comparative study of S-1 plus cisplatin and S-1 plus weekly cisplatin for unresectable gastric cancer].

    Science.gov (United States)

    Kemmochi, Takeshi; Egawa, Tomohisa; Sato, Aya; Umakoshi, Tomoko; Ito, Yasuhiro; Nagashima, Atsushi; Makino, Hiroyuki; Yamamuro, Wataru

    2012-11-01

    Clinical efficacy and safety were analyzed in patients with unresectable gastric cancer receiving S-1 plus CDDP(CS) therapy or S-1 plus weekly CDDP (w-CS) therapy as first-line treatment between April 2007 and December 2010. Fifteen patients received CS therapy and 17 received w-CS therapy. CS therapy was used according to the SPIRITS regimen, and w-CS therapy of S-1 80 mg/(m2·day) was administered for 2 weeks followed by a 1-week rest, with CDDP 20 mg/m2 being injected intravenously on days 1 and 8. In the CS therapy group and w-CS therapy group, the overall response rates were 33.3% and 70.1%, the median overall survival periods were 135 and 174 days (p=0.113), and the median follow- up times were 196 and 352 days (p=0.196), respectively. The w-CS therapy group showed less adverse events than did the CS therapy group. This study suggested that the w-CS regimen is a useful treatment modality showing clinical efficacy and safety for unresectable gastric cancer.

  7. 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.

  8. 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...

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. Helicobacter pylori vacA s1a and s1b alleles from clinical isolates from different regions of Chile show a distinct geographic distribution

    Institute of Scientific and Technical Information of China (English)

    MI Díaz; A Kirberg; E Hebel; J Fierro; R Bravo; F Siegel; G Leon; G Klapp; A Venegas; A Valdivia; P Martínez; JL Palacios; P Harris; J Novales; E Garrido; D Valderrama; C Shilling

    2005-01-01

    AIM: To establish the most common vacA alleles in Helicobacter pylori(H pylori) strains isolated from Chilean patients and its relationship with gastritis and gastroduodenal ulcers.METHODS: Two hundred and forty five H pylori clinical isolates were obtained from 79 biopsies from Chilean infected patients suffering from gastrointestinal diseases. An average of 2-3 strains per patient was isolated and the vacA genotype was analyzed by PCR and 3% agarose electrophoresis. Some genotypes were checked by DNA sequencing.RESULTS: The most prevalent vacA genotype inChilean patients was s1b m1 (76%), followed by s1a m1 (21%). In contrast, the s2 m2 genotype was scarcely represented (3%).The s1b m1 genotype was found most frequently linked to gastropathies (P<0.05) rather than ulcers. Ulcers were found more commonly in male and older patients. Curiously, patients living in cities located North and far South of Santiago, the capital and largest Chilean city, carried almost exclusively strains with the s1b m1 genotype. In contrast, patients from Santiago and cities located South of Santiago carried strains with either one or both s1a m1 and s1b m1 genotypes.Regarding the s2 m2 genotype, comparison with GenBank sequences revealed that Chilean s2 sequence was identical to those of Australian, American, and Colombian strains but quite different from those of Alaska and India.CONCLUSION: Differences in geographic distribution of the s and m vaccA alleles in Chile and a relationship of s1b m1 genotype with gastritis were found. Sequence data in part support a hispanic origin for the vacA genotype.Asymmetric distribution of genotypes s1b m1 and s2 m2recedes H Pyloristrain distribution in Spain and Portugal.

  14. PA1b, a plant peptide, induces intracellular [Ca2+] in- crease via Ca2+ influx through the L-type Ca2+ channel and triggers secretion in pancreatic β cells

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Using alginic acid to adsorb polypeptides at pH 2.7, we isolated a peptide pea albumin 1b (PA1b) from pea seeds. The PA1b is a single chain peptide consisting of 37 amino acid residues with 6 cysteines which constitutes the cystine-knot structure. Using microfluorometry and patch clamp techniques, we found that PA1b significantly elevated the intracellular calcium level ([Ca2+ ]i) and elicited membrane capacitance increase in the primary rat pancreatic β cells. The PA1b effect on [Ca2+]i elevation was abolished in the absence of extracellular Ca2+ or in the presence of L-type Ca2+ channel blocker, ni- modipine. Interestingly, we found that PA1b significantly depolarized membrane potential, which could lead to the opening of voltage-dependent L-type Ca2+ channels and influx of extracellular Ca2+, and then evoke robust secretion. In this study we identified the plant peptide PA1b which is capable of affecting the excitability and function of mammalian pancreatic β cell.

  15. PA1b, a plant peptide, induces intracellular [Ca2+] increase via Ca2+ influx through the L-type Ca2+ channel and triggers secretion in pancreatic β cells

    Institute of Scientific and Technical Information of China (English)

    HU ZhiTao; DUN XinPeng; ZHANG Ming; ZHU HongLiang; XIE Li; WU ZhengXing; CHEN ZhengWang; XU Tao

    2007-01-01

    Using alginic acid to adsorb polypeptides at pH 2.7, we isolated a peptide pea albumin 1b (PA1b) from pea seeds. The PA1b is a single chain peptide consisting of 37 amino acid residues with 6 cysteines which constitutes the cystine-knot structure. Using microfluorometry and patch clamp techniques, we found that PA1b significantly elevated the intracellular calcium level ([Ca2+]i) and elicited membrane capacitance increase in the primary rat pancreatic β cells. The PA1b effect on [Ca2+]i elevation was abolished in the absence of extracellular Ca2+ or in the presence of L-type Ca2+ channel blocker, nimodipine. Interestingly, we found that PA1b significantly depolarized membrane potential, which could lead to the opening of voltage-dependent L-type Ca2+ channels and influx of extracellular Ca2+, and then evoke robust secretion. In this study we identified the plant peptide PA1b which is capable of affecting the excitability and function of mammalian pancreatic β cell.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Characterization of leucocin B-KM432Bz from Leuconostoc pseudomesenteroides isolated from boza, and comparison of its efficiency to pediocin PA-1.

    Directory of Open Access Journals (Sweden)

    Kahina Maya Makhloufi

    Full Text Available A bacteriocin-producing bacterium was isolated from boza and identified as Leuconostoc pseudomesenteroides KM432Bz. The antimicrobial peptide was purified and shown to be identical to other class IIa bacteriocins: leucocin A from Leuconostoc gelidum UAL-187 and Leuconostoc pseudomesenteroides QU15 and leucocin B from Leuconostoc carnosum Ta11a. The bacteriocin was named leucocin B-KM432Bz. Leucocin B-KM432Bz gene cluster encodes the bacteriocin precursor (lcnB, the immunity protein (lcnI and the dedicated export machinery (lcnD and lcnE. A gene of unknown and non-essential function (lcnC, which is interrupted by an insertion sequence of the IS30 family, is localized between lcnB and lcnD. The activity of leucocin B-KM432Bz requires subunit C of the EII(t Man mannose permease, which is the receptor for entry into target cells. The determination of the minimum inhibitory concentrations revealed the lowest values for leucocin B-KM432Bz over Listeria strains, with 4 to 32 fold better efficiency than pediocin PA-1.

  6. Multi-wavelength view of an M2.2 Solar Flare on 26 November 2000

    CERN Document Server

    Chandra, R; Rani, S; Maurya, R A

    2016-01-01

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

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

    Science.gov (United States)

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

    2017-02-01

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

  8. A 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...

  9. 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...

  10. Randomized study comparing full dose monotherapy (S-1 followed by irinotecan) and reduced dose combination therapy (S-1/oxaliplatin followed by S-1/irinotecan) as initial therapy for older patients with metastatic colorectal cancer: NORDIC 9.

    Science.gov (United States)

    Winther, Stine Braendegaard; Österlund, Pia; Berglund, Åke; Glimelius, Bengt; Qvortrup, Camilla; Sorbye, Halfdan; Pfeiffer, Per

    2017-08-16

    Metastatic colorectal cancer (mCRC) is a disease of older age, but there is a relative lack of knowledge about effects of chemotherapy in older patients as they are under-represented in clinical trials. Little data can guide whether the strategy in older mCRC patients should be a sequential full-dose monotherapy chemotherapy approach or a dose-reduced combination chemotherapy approach. The oral 5FU prodrug S-1 seems to have less side effects than capecitabine and should be an optimal drug for older patients, but few data are available. Improved geriatric assessments are needed to select which older patients should receive therapy. The NORDIC 9 trial is a Nordic multicenter randomized phase II study comparing full dose monotherapy (S-1 30 mg/m(2) twice daily days 1-14 every 3 weeks, followed by second line irinotecan 250-350 mg/m(2) iv day 1 every 3 weeks or 180-250 mg/m(2) iv day 1 every 2 weeks) with reduced dose combination therapy (S-1 20 mg/m(2) days 1-14 + oxaliplatin 100 mg/m(2) iv day 1 every 3 weeks, followed by second line S-1 20 mg/m(2) days 1-14 + irinotecan 180 mg/m(2) day 1 every 3 week) for older patients (≥70 years) with mCRC who are not candidates for full-dose standard combination therapy. Additional bevacizumab (7.5 mg/kg) is optional in first-line. Blood samples and tumor tissue will be collected to investigate predictive markers. Geriatric screening tools (G-8, VES-13, Timed-Up-and-Go and Handgrip strength), Charlson Comorbidty Index and quality of life (EORTC QLQ-C30) will be evaluated as predictors of efficacy and toxicity. The target sample size is 150 patients. The primary endpoint is progression-free survival and secondary endpoints are time-to-failure of strategy, overall survival, response rate, toxicity, and correlations between biomarkers, pre-treatment characteristics and geriatric assessments. The study will add knowledge on how to treat older mCRC patients who are not candidates for standard combination therapy

  11. 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

  12. Identification of benzoxazole analogs as novel, S1P(3) sparing S1P(1) agonists.

    Science.gov (United States)

    Deng, Guanghui; Meng, Qinghua; Liu, Qian; Xu, Xuesong; Xu, Qiongfeng; Ren, Feng; Guo, Taylor B; Lu, Hongtao; Xiang, Jia-Ning; Elliott, John D; Lin, Xichen

    2012-06-15

    A novel series of benzoxazole-derived S1P(1) agonists were designed based on scaffold hopping molecular design strategy combined with computational approaches. Extensive SAR studies led to the discovery of compound 17d as a selective S1P(1) agonist (over S1P(3)) with high CNS penetration and favorable DMPK properties. 17d also demonstrated in vivo pharmacological efficacy to reduce blood lymphocyte in mice after oral administration.

  13. 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、

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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...

  1. 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.

  2. 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.

  3. Restless legs syndrome mimicking S1 radiculopathy.

    Science.gov (United States)

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

    2016-01-01

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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

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

    Science.gov (United States)

    Pálfalvi, J K; Szabó, J; Dudás, B

    2007-01-01

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

  9. Clinical Study of S-1 Plus Oxaliplatin Versus S-1 Plus Cisplatin as First-Line Treatment for Elderly Patients with Advanced Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Deng-feng BO

    2015-12-01

    Full Text Available Abstract Objective: To explore the efficacy and safety of S-1 plus oxaliplatin versus S-1 plus cisplatin as the first-line treatment for elderly patients with advanced gastric cancer. Methods: A total of 60 patients with advanced gastric cancer admitted in Xi’an Yanliang Railway Hospital from Jan., 2011 to Oct., 2013 were selected as study objects and randomly divided into 2 groups: S1 plus oxaliplatin group (SOX group, 30 cases and S1 plus cisplatin group (SP group, 30 cases. SOX group were given intravenous drip of 130 mg/m2 oxaliplatin for 2 h on d1. And S-1 was also given according to body surface area: body surface area <1.25 m2, 40 mg once; 1.25-1.5 m2, 60 mg once; >1.5, 28 d as 1 cycle. SP group was administered with intravenous drip of 25 mg/m2 cisplatin during d1-d3. Treatment was discontinued until the occurrence of disease progression or patients’ intolerance to chemotherapy. Results: SOX group was non-inferior to SP group in overall response rate (ORR (53.3% vs. 43.3%, disease control rate (DCR (83.3% vs. 80.0%, median progression-free survival (PFS (7.0 vs. 6.0 months and median overall survival (OS (11.0 vs. 10.5 months. However, the difference was statistical significant in the rate of increased KPS score (86.7% vs. 46.7%, χ2=10.800, P=0.001 and the rate of increased FACT-G score (73.3% vs. 36.7%, χ2=8.148, P=0.004. The main toxic and side effects of two groups was hematological toxicity. There was no degree III-IV toxic and side effects occurring in non hematological toxicity in two groups. The main toxic effect was peripheral neuritis in SOX group, and nausea and vomiting and renal dysfunction in SP group, and there were statistical differences in the above toxic and side effects between two groups (P<0.05. Conclusion: SOX regimen is as safe and effective as SP regimen for elderly patients with advanced gastric cancer, with better quality of life and less toxic and side effects.

  10. 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.)

  11. Integrable KdV Hierarchies on $T^2=S^1\\times S^1$

    CERN Document Server

    Sedra, M B

    2007-01-01

    Following our previous works on extended higher spin symmetries on the torus we focus in the present contribution to make a setup of the integrable KdV hierarchies on $T^{2} = S^{1} \\times S^{1}$. Actually two particular systems are considered, namely the KdV and the Burgers non linear integrable model associated to currents of conformal weights (2, 2) and (1, 1) respectively. One key steps towards proving the integrability of these systems is to find their Lax pair operators. This is explicitly done and a mapping between the two systems is discussed.

  12. MANAJEMEN PEMBELAJARAN S1 KEPERAWATAN STIKES YOGYAKARTA

    Directory of Open Access Journals (Sweden)

    Teti Indriati Kastuti

    2014-10-01

    Full Text Available Penelitian ini bertujuan untuk mendeskripsikan manajemen pembelajaran dilihat dari segi pe-rencanaan, pelaksanaan, dan evaluasi kurikulum di S1 Keperawatan STIKES Yogyakarta. Penelitian ini merupakan penelitian deskriptif dengan pendekatan kualitatif. Subjek penelitian adalah Pembantu Ketua I, III, dosen, kepala bagain akademik, perpustakaan, laboratorium, dan mahasiswa. Data peneli-tian dikumpulkan melalui wawancara, observasi, dan studi dokumentasi. Dianalisis secara kualitatif dengan menggunakan teknik analisis interaktif model Miles dan Huberman. Hasil penelitian bahwa perencanaan pembelajaran: 1 rumusan kompetensi pendukung dan lainnya tidak terjabarkan dalam elemen kompetensi; 2 proses pembelajaran memerlukan team teaching. Pelaksanaan pembelajaran: 1 pembinaan motivasi belajar mahasiswa masih ada dosen yang mengajar berdasarkan mood; 2 bahan ajar dimanfaatkan dengan baik untuk mencapai tujuan instruksional pembelajaran; 3 bimbing-an dan konseling pada saat pengisian KRS; 4 masih ada dosen yang mengganti jadwal. Evaluasi pembelajaran: 1 penamaan mata kuliah IKD 1 dan 2, yang menunjukkan prerequisite, kenyataannya tidak berhubungan; 2 evaluasi dosen  sebatas pelaksanaan administratif. Kata kunci: manajemen, kurikulum, pembelajaran, keperawatan

  13. Fast, low-ionization emission regions of the planetary nebula M2-42

    CERN Document Server

    Danehkar, A; Steffen, W

    2016-01-01

    Spatially resolved observations of the planetary nebula M2-42 (PN G008.2-04.8) obtained with the Wide Field Spectrograph on the Australian National University 2.3 m telescope have revealed the remarkable features of bipolar collimated jets emerging from its main structure. Velocity-resolved channel maps derived from the [N II] $\\lambda$6584 emission line disentangle different morphological components of the nebula. This information is used to develop a three-dimensional morpho-kinematic model, which consists of an equatorial dense torus and a pair of asymmetric bipolar outflows. The expansion velocity of about 20 km s$^{-1}$ is measured from the spectrum integrated over the main shell. However, the deprojected velocities of the jets are found to be in the range of 80-160 km s$^{-1}$ with respect to the nebular center. It is found that the mean density of the collimated outflows, 595 $\\pm$ 125 cm$^{-3}$, is five times lower than that of the main shell, 3150 cm$^{-3}$, whereas their singly ionized nitrogen and ...

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

    CERN Document Server

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

    2015-01-01

    We present results from spectroscopic observations with the Michigan/Magellan Fiber System (M2FS) of $147$ stellar targets along the line of sight to the newly-discovered `ultrafaint' stellar systems Tucana 2 (Tuc 2) and Grus 1 (Gru 1). Based on simultaneous estimates of line-of-sight velocity and stellar-atmospheric parameters, we identify 8 and 7 stars as probable members of Tuc 2 and and Gru 1, respectively. Our sample for Tuc 2 is sufficient to resolve an internal velocity dispersion of $8.6_{-2.7}^{+4.4}$ km s$^{-1}$ about a mean of $-129.1_{-3.5}^{+3.5}$ km s$^{-1}$ (solar rest frame), and to estimate a mean metallicity of [Fe/H]= $-2.23_{-0.12}^{+0.18}$. These results place Tuc 2 on chemodynamical scaling relations followed by dwarf galaxies, suggesting a dominant dark matter component with dynamical mass $2.7_{-1.3}^{+3.1}\\times 10^6$ $\\mathrm{M}_{\\odot}$ enclosed within the central $\\sim 160$ pc, and dynamical mass-to-light ratio $1900_{-900}^{+2200}$ $\\mathrm{M}_{\\odot}/L_{V,\\odot}$. For Gru 1 we es...

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

    Science.gov (United States)

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

    2016-08-01

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

  16. 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...

  17. 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...

  18. 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.

  19. Main: S1FBOXSORPS1L21 [PLACE

    Lifescience Database Archive (English)

    Full Text Available S1FBOXSORPS1L21 S000223 10-May-1998 (last modified) kehi S1F box conserved both in ...e element; Might play a role in downregulating RPS1 and RPL21 promoter activity (Lagrange et al., 1993); See S000211 (SITE1SOR...PS1), S000215 (S1FSORPL21); S1F; S1F box; S1F-box; S1; plastid protein; RPS1; RPL21; leaf; negative; spinach (Spinacia oleracea) ATGGTA ...

  20. Pharmacokinetic evaluation of novel oral fluorouracil antitumor drug S-1 in Chinese cancer patients

    Institute of Scientific and Technical Information of China (English)

    Zhi-xiang ZHUANG; Hong ZHU; Ji WANG; Min-gao ZHU; Hui WANG; Wang-yang PU; Hua-hui BIAN

    2013-01-01

    Aim:S-1 is an oral anticancer fluoropyrimidine formulation consisting of tegafur,5-chloro-2,4-dihydroxypyridine and potassium oxonate.The aim of this study was to evaluate the pharmacokinetics and bioequivalence of a newly developed generic formulation of S-1 in Chinese cancer patients in comparison with the branded reference formulation of S-1.Methods:A single-dose,randomized-sequence,open-label,two-way self-crossover study was conducted in 30 Chinese cancer patients.The subjects alternatively received the two formulations (40 mg/m2,po) with a 7-d interval.Plasma concentrations of FT,CDHP,Oxo,and 5-Fu were determined using LC-MS/MS.Pharmacokinetic parameters,including C Tmax,t1/2,AUC0-t,and AUC0-∞ were determined using non-compartmental models with DAS2.0 software.Bioequivalence of the two formulations were to be evaluated according to 90% Cls for the log-transformed ratios of AUC and Cmax of S-1.Adverse events were evaluated through monitoring the symptom,physical and laboratory examinations,ECGs and subject interviews.Results:The mean values of Cmax,AUC0-t,and AUC0-∞ of FT,5-Fu,CDHP,and Oxo for the two formulations had no significant differences.The 90% Cls for natural log-transformed ratios of C AUC0-t,and AUC0-∞ were within the predetermined bioequivalence acceptance limits.A total of 11 mild adverse events,including fatigue,nausea and vomiting,anorexia,diarrhea and myelosuppression,were observed,and no serious and special adverse events were found.Conclusion:The newly developed generic formulation and reference formulation of S-1 have similar pharmacokinetics with one dose (40 mg/m2) in Chinese cancer patients.Both the formulations of S-1 are well tolerated.

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

    Science.gov (United States)

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

    2015-01-01

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

  2. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Fujii, Yasuyuki, E-mail: y.fujii@po.rd.taisho.co.jp [Department of Molecular Function and Pharmacology Laboratories, Taisho Pharmaceutical Co. Ltd., 1-403 Saitama, Saitama 331-9530 (Japan); Ueda, Yasuji; Ohtake, Hidenori; Ono, Naoya; Takayama, Tetsuo; Nakazawa, Kiyoshi [Department of Molecular Function and Pharmacology Laboratories, Taisho Pharmaceutical Co. Ltd., 1-403 Saitama, Saitama 331-9530 (Japan); Igarashi, Yasuyuki [Laboratory of Biomembrane and Biofunctional Chemistry, Hokkaido University, Sapporo, Hokkaido 060-0812 (Japan); Goitsuka, Ryo [Division of Development and Aging, Research Institute for Biological Sciences, Tokyo University of Science, Noda, Chiba 278-0022 (Japan)

    2012-03-23

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

  4. 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.

  5. 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.

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

    Science.gov (United States)

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

    2017-02-01

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

  7. Cohomology of the Schro¨dinger Algebra S (1)

    Institute of Scientific and Technical Information of China (English)

    Yue Zhu WU; Xiao Qing YUE; Lin Sheng ZHU

    2014-01-01

    We explicitly compute the first and second cohomology groups of the Schr¨odinger algebra S(1) with coeffi cients in the trivial module and the finite-dimensional irreducible modules. We also show that the first and second cohomology groups of S(1) with coeffi cients in the universal enveloping algebras U (S (1)) (under the adjoint action) are infinite dimensional.

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

    Science.gov (United States)

    Gräler, Markus H

    2010-01-01

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

  9. 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.

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

    Science.gov (United States)

    Lima, F. W. S.

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

  11. Resonating Valence Bond states for low dimensional S=1 antiferromagnets

    Science.gov (United States)

    Liu, Zheng-Xin; Zhou, Yi; Ng, Tai-Kai

    2014-03-01

    We study S = 1 spin liquid states in low dimensions. We show that the resonating-valence-bond (RVB) picture of S = 1 / 2 spin liquid state can be generalized to S = 1 case. For S = 1 system, a many-body singlet (with even site number) can be decomposed into superposition of products of two-body singlets. In other words, the product states of two-body singlets, called the singlet pair states (SPSs), are over complete to span the Hilbert space of many-body singlets. Furthermore, we generalized fermionic representation and the corresponding mean field theory and Gutzwiller projected stats to S = 1 models. We applied our theory to study 1D anti-ferromagnetic bilinear-biquadratic model and show that both the ground states (including the phase transition point) and the excited states can be understood excellently well within the framework. Our method can be applied to 2D S = 1 antiferromagnets.

  12. Main: O2F2BE2S1 [PLACE

    Lifescience Database Archive (English)

    Full Text Available coxin, the maize b-32 genes and the AP-1 pseudopalindrome; O2; opaque-2; be2S1; seed; Brazil nut tree (Bertholletia excelsa) GCCACCTCAT ... ...O2F2BE2S1 S000163 17-May-1998 (last modified) kehi opaque-2 recognition site F2 in Bertholletia excelsa (Bra...zil nut tree) 2S storage protein gene (be2S1); O2 protein binds to F1, F2 and F3 se

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

    Science.gov (United States)

    2010-04-01

    ... prior regulation provisions of § 1.414(s)-1T. (See § 1.414(s)-1T as contained in the CFR edition revised... to the extent necessary to satisfy the requirements of 29 CFR 2530.204-2(d) (regarding double... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Definition of compensation. 1.414(s)-1 Section...

  14. Main: O2F3BE2S1 [PLACE

    Lifescience Database Archive (English)

    Full Text Available quences of be2S1 promoter; F3 is hybrid of A/G box; O2; opaque-2; be2S1; seed; Brazil nut tree (Bertholletia excelsa) TCCACGTACT ... ...O2F3BE2S1 S000164 17-May-1998 (last modified) kehi opaque-2 recognition site F3 in Bertholletia excelsa (Bra...zil nut tree) 2S storage protein gene (be2S1); O2 protein binds to F1, F2 and F3 se

  15. Main: O2F1BE2S1 [PLACE

    Lifescience Database Archive (English)

    Full Text Available quences of be2S1 promoter; F1 is hybrid C/G box; O2; opaque-2; be2S1; F1; seed; Brazil nut tree (Bertholletia excelsa); TCCACGTCGA ... ...O2F1BE2S1 S000162 17-May-1998 (last modified) kehi opaque-2 recognition site F1 in Bertholletia excelsa (Bra...zil nut tree) 2S storage protein gene (be2S1); O2 protein binds to F1, F2 and F3 se

  16. 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。

  17. 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 ...

  18. 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 ...

  19. 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 ...

  20. 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 ...

  1. 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 ...

  2. 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 ...

  3. 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 ...

  4. 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.

  5. Inhibition of skeletal muscle S1-myosin ATPase by peroxynitrite.

    Science.gov (United States)

    Tiago, Teresa; Simão, Sónia; Aureliano, Manuel; Martín-Romero, Francisco Javier; Gutiérrez-Merino, Carlos

    2006-03-21

    Exposure of myosin subfragment 1 (S1) to 3-morpholinosydnonimine (SIN-1) produced a time-dependent inhibition of the F-actin-stimulated S1 Mg(2+)-ATPase activity, reaching 50% inhibition with 46.7 +/- 8.3 microM SIN-1 for 8.7 microM S1, that is, at a SIN-1/S1 molar ratio of approximately 5.5. The inhibition was due to the peroxynitrite produced by SIN-1 decomposition because (1) decomposed SIN-1 was found to have no effect on S1 ATPase activity, (2) addition of SIN-1 in the presence of superoxide dismutase and catalase fully prevented inhibition by SIN-1, and (3) micromolar pulses of chemically synthesized peroxynitrite produced inhibition of F-actin-stimulated S1 Mg(2+)-ATPase activity. In parallel, SIN-1 produced the inhibition of the nonphysiological Ca(2+)-dependent and K(+)/EDTA-dependent S1 ATPase activity of S1 and, therefore, suggested that the inhibition of F-actin-stimulated S1 Mg(2+)-ATPase activity is produced by the oxidation of highly reactive cysteines of S1 (Cys(707) and Cys(697)), located close to the catalytic center. This point was further confirmed by the titration of S1 cysteines with 5,5'-dithiobis(2-nitrobenzoic acid) and by the parallel decrease of Cys(707) labeling by 5-(iodoacetamido)fluorescein, and it was reinforced by the fact that other common protein modifications produced by peroxynitrite, for example, protein carbonyl and nitrotyrosine formation, were barely detected at the concentrations of SIN-1 that produced more than 50% inhibition of the F-actin-stimulated S1 Mg(2+)-ATPase activity. Differential scanning calorimetry of S1 (untreated and treated with different SIN-1 concentrations) pointed out that SIN-1, at concentrations that generate micromolar peroxynitrite fluxes, impaired the ability of ADP.V(1) to induce the intermediate catalytic transition state and also produced the partial unfolding of S1 that leads to an enhanced susceptibility of S1 to trypsin digestion, which can be fully protected by 2 mM GSH.

  6. 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.

  7. 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).

  8. 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.

  9. Localization on $AdS_2\\times S^1$

    CERN Document Server

    David, Justin R; Gupta, Rajesh Kumar; Narain, Kumar

    2016-01-01

    Conformal symmetry relates the metric on $AdS_2 \\times S^{1}$ to that of $S^3$. This implies that under a suitable choice of boundary conditions for fields on $AdS_2$ the partition function of conformal field theories on these spaces must agree which makes $AdS_2 \\times S^{1}$ a good testing ground to study localization on non-compact spaces. We study supersymmetry on $AdS_2\\times S^1$ and determine the localizing Lagrangian for ${\\cal N}=2$ supersymmetric Chern-Simons theory on $AdS_2\\times S^1$. We evaluate the partition function of ${\\cal N}=2$ supersymmetric Chern-Simons theory on $AdS_2 \\times S^1$ using localization, where the radius of $S^1$ is $q$ times that of $AdS_2$. With boundary conditions on $AdS_2\\times S^1$ which ensure that all the physical fields are normalizable and lie in the space of square integrable wave functions in $AdS_2$, the result for the partition function precisely agrees with that of the theory on the $q$-fold covering of $S^3$.

  10. Epson EMP-S1投影机的升级产品EMP-S1H

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    EMP-S1是Epson公司推出的1款颇具影响力的经济型投影机,2004年5月Epson推出了EMP-S1的升级产品EMP-S1H。EMP.S1H在原有EMP-S1投影机的基础上亮度提高到了1400流明,同时对比度也提高到500:1,对比度的提高使图像层次感更好,影像更富有质感。

  11. 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.

  12. 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.

  13. 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...

  14. 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 ...

  15. 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.

  16. Assignment of Isodoublet of 23S1 Meson Nonet

    Institute of Scientific and Technical Information of China (English)

    FENG Xue-Chao; JIANG Feng-Chun

    2007-01-01

    Inserting the masses of some states, which have been established in the experiments or the theory of lattice QCD, we investigate the mass of the isodoublet of the 23S1 meson nonet. The agreement results, 1567 ± 22.6 MeV and 1576.8 MeV, are given by two different approaches. We suggest that the assignment of 23S1 meson nonet should be re-examined in future experiments.

  17. 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...

  18. 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.

  19. Magellan/M2FS Spectroscopy of Galaxy Clusters: Stellar Population Model and Application to Abell 267

    Science.gov (United States)

    Tucker, Evan; Walker, Matthew G.; Mateo, Mario; Olszewski, Edward W.; Bailey, John I., III; Crane, Jeffrey D.; Shectman, Stephen A.

    2017-09-01

    We report the results of a pilot program to use the Magellan/M2FS spectrograph to survey the galactic populations and internal kinematics of galaxy clusters. For this initial study, we present spectroscopic measurements for 223 quiescent galaxies observed along the line of sight of the galaxy cluster Abell 267 (z∼ 0.23). We develop a Bayesian method for modeling the integrated light from each galaxy as a simple stellar population, with free parameters that specify the redshift ({v}{los}/c) and characteristic age, metallicity ([{Fe}/{{H}}]), alpha-abundance ([α /{Fe}]), and internal velocity dispersion ({σ }{int}) for individual galaxies. Parameter estimates derived from our 1.5 hr observation of A267 have median random errors of {σ }{v{los}}=20 {km} {{{s}}}-1, {σ }{Age}=1.2 {Gyr}, {σ }[{Fe/{{H}}]}=0.11 {dex}, {σ }[α /{Fe]}=0.07 {dex}, and {σ }{σ {int}}=20 {km} {{{s}}}-1. In a companion paper, we use these results to model the structure and internal kinematics of A267.

  20. S-1 in combination with docetaxel and oxaliplatin in patients with advanced gastro-esophageal adenocarcinoma: two parallel phase 1/2a studies.

    Science.gov (United States)

    Pfeiffer, Per; Qvortrup, Camilla; Krogh, Merete; Schoennemann, Katrine; Vestermark, Lene W; Jensen, Helle A; Bjerregaard, Jon K

    2017-01-01

    Docetaxel in combination with cisplatin and 5-fluorouracil (5-FU) is one of several standard chemotherapy regimens for patients with advanced gastro-esophageal adenocarcinoma (aGEA) in Europe. To enable outpatient treatment, we evaluated the maximum tolerated dose (MTD), recommended dose (RD), dose limiting toxicity (DLT) and safety of docetaxel in combination with oxaliplatin (O) and S-1 (DOS) in Caucasian patients with aGEA. We present final results of two parallel phase 1/2a studies (3 + 3 design). Escalating doses of docetaxel and S-1 with fixed dose O were given for 18 weeks every second week (DOS2w) or every third week (DOS3w) followed by S-1 maintenance therapy. Thirty-four patients (18 in DOS2w and 16 in DOS3w) were enrolled between October 2013 and June 2015. Median age was 65 years (range 49-78). DLT was most often febrile neutropenia. Most common severe non-hematological adverse events were diarrhea (9%) and fatigue (6%). The RD of DOS3w was: docetaxel 50 mg/m(2), O 100 mg/m(2) and S-1 25 mg/m(2) twice daily and of DOS2w was: docetaxel 40 mg/m(2), O 70 mg/m(2) and S-1 35 mg/m(2) twice daily. Overall, response rate was 56%; median progression-free survival was 9.1 months; and median overall survival was 13.2 months in 34 patients. At the RD, DOS2w and DOS3w showed an acceptable safety profile in patients with aGEA. Clinical trials ID: NCT-01928524 and EudraCT 2012-005187-10.

  1. 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

  2. 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.

  3. 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.

  4. 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…

  5. 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.

  6. 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.

  7. 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...

  8. 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...

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

    Science.gov (United States)

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

    2006-07-15

    Novel series of sphingosine-1-phosphate (S1P) receptor agonists were developed through a systematic SAR aimed to achieve high selectivity for a single member of the S1P family of receptors, S1P1. The optimized structure represents a highly S1P1-selective and efficacious agonist: S1P1/S1P2, S1P1/S1P3, S1P1/S1P4>10,000-fold, S1P1/S1P5>600-fold, while EC50 (S1P1) effect.

  10. 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.

  11. Improvement of S-1 photocathode shelf life stability. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Fitts, R.W.

    1977-03-01

    The purpose of this program was to stabilize sensitivity of S-1 photocathodes in C73435AG high speed image converters. Variations in bulb pre- and post-heating and in aging were investigated using partial tube assemblies consisting of the cathode bulb half of the standard tube. Successful processing of stable S-1 photocathodes in partial tubes led to adapting the schedules to complete tube assemblies. Five tubes processed on this contract yielded high but unstable photocathode sensitivity. Continued testing of tubes being made to fill customer orders shows that control of tube heating and cooling, together with careful control of evaporated cesium, can yield stable S-1 photocathodes. Additional experimentation is required to optimize a schedule yielding consistently stable photocathodes.

  12. In vivo analysis of the Notch receptor S1 cleavage.

    Directory of Open Access Journals (Sweden)

    Robert J Lake

    Full Text Available A ligand-independent cleavage (S1 in the extracellular domain of the mammalian Notch receptor results in what is considered to be the canonical heterodimeric form of Notch on the cell surface. The in vivo consequences and significance of this cleavage on Drosophila Notch signaling remain unclear and contradictory. We determined the cleavage site in Drosophila and examined its in vivo function by a transgenic analysis of receptors that cannot be cleaved. Our results demonstrate a correlation between loss of cleavage and loss of in vivo function of the Notch receptor, supporting the notion that S1 cleavage is an in vivo mechanism of Notch signal control.

  13. 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.

  14. 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.

  15. 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.

  16. In situ production of pediocin PA-1 like bacteriocin by different genera of lactic acid bacteria in soymilk fermentation and evaluation of sensory properties of the fermented soy curd.

    Science.gov (United States)

    Devi, Sundru Manjulata; Ramaswamy, Asha Mysore; Halami, Prakash M

    2014-11-01

    The lactic acid bacteria (LAB) are found to produce bacteriocins with enhanced nutritive properties in the fermented foods. In the present study, the ability of LAB cultures (Pediococcus acidilactici NCIM 5424, Enterococcus faecium NCIM 5423 and Lactobacillus plantarum Acr2) to produce pediocin PA-1 like bacteriocin was evaluated during soymilk fermentation. The isolates E. faecium NCIM 5423 and Lb. plantarum Acr2 were able to produce bacteriocin as well as ferment soymilk within 6 h of incubation. Upon plating the cultures E. faecium NCIM 5423 and Lb. plantarum Acr2 in soymilk were found to be viable even after 15 days of storage at 4 °C. No significant variation was observed in the viable counts of E. faecium NCIM 5423 and Lb. plantarum Acr2 (P>0.05). The effect of crude bacteriocin on Listeria cells was evidenced through scanning electron microscope (SEM) photographs wherein cell membrane damage was observed. On co-cultivation of E. faecium NCIM 5423 and Lb. plantarum Acr2 individually with Listeria monocytogenes ScottA a decrease in the Listeria count was observed within 24 h of incubation. However, during co-cultivation of ScottA with P. acidilactici NCIM 5424, no significant difference was observed in the viable counts (P>0.05). The pH, titratable acidity, pediocin activity, anti-oxidant property and sensory attributes for E. faecium NCIM 5423 were studied. It was observed that E. faecium NCIM 5423 fermented soymilk had an acceptable sensory score during storage period. Hence, such culture can be an ideal starter for development of functional foods with longer shelf life.

  17. 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...

  18. 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.

  19. 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...

  20. Anomalous Dispersion of the S1 Lamb Mode

    Directory of Open Access Journals (Sweden)

    Faiz Ahmad

    2013-01-01

    Full Text Available The S1 mode of the Lamb spectrum of an isotropic plate exhibits negative group velocity in a narrow frequency domain. This anomalous behavior is explained analytically by examining the slope of each mode first in its initial state and then near its turning points.

  1. Emerging role of S-1 in gastric cancer

    Directory of Open Access Journals (Sweden)

    Eriseld Krasniqi

    2015-01-01

    Full Text Available Gastric cancer remains one of the most important malignancies worldwide in terms of incidence and mortality. The treatment is based on the combination of local surgery and radiation therapy as well as systemic chemotherapy and targeted molecules. Fluoropyrimidines and particularly 5-fluorouracil (FU represent still the backbone for gastric cancer chemotherapy and new molecular versions of this molecule have been brought to clinical practice in order to improve benefits and reduce adverse effects. S-1 is an oral prodrug of 5-FU, which has demonstrated high effectiveness for gastric cancer treatment and a favorable safety profile. Currently, there are geographic differences in the treatment of gastric cancer and in the use of S-1, which is a mainstay of gastric cancer management in Eastern countries, but is not part of the standard care in the rest of the world. In this review, we gathered data from phase I, II, and III trials of S-1 in gastric cancer, in order to define its real benefit-risk ratio and assess whether geographic differences in S-1 use are justified by unchangeable factors.

  2. Spin diffusion in anisotropic Heisenberg chains: S{>=}1/2

    Energy Technology Data Exchange (ETDEWEB)

    Huber, D.L., E-mail: huber@src.wisc.edu [Physics Department, University of Wisconsin-Madison, 1150 University Avenue, Madison WI 53706 (United States)

    2012-11-01

    In this paper, we investigate spin diffusion in Heisenberg chains with uniaxial nearest-neighbor interactions. The approach followed is based on an analysis of the infinite-temperature longitudinal spin density and spin current correlation functions. For S=1/2, exact results are presented for the time-dependent correlation functions in the XY limit. Away from this limit, the second and fourth moments of the Fourier transform of the spin density correlation function provide information about spin dynamics for arbitrary values of the spin. The moments are used in an assessment of the accuracy of the Gaussian approximation for the spin diffusion constant for S=1/2. The general behavior of the Gaussian approximation when S>1/2 is discussed, and numerical results for the spin diffusion constant are presented for S=1/2, 1, 3/2, 2 and in the classical limit. A moment-based criterion for the boundary in reciprocal space between diffusive and non-diffusive dynamics that applies to arbitrary values of the spin is presented.

  3. 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.

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

    Science.gov (United States)

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

    2016-01-15

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

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

    Science.gov (United States)

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

    2016-08-01

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

  6. 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.

  7. 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...

  8. 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.

  9. 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...

  10. 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

  11. 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.

  12. 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

  13. 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...

  14. 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

  15. 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.

  16. 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...

  17. 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)

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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...

  6. 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.

  7. 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.

  8. 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...

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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

  16. Spatially frustrated S = 1 Heisenberg antiferromagnet with single ion anisotropy

    Science.gov (United States)

    Pires, A. S. T.

    2016-10-01

    Using the SU(3) Schwinger boson formalism, I study the S = 1 square lattice Heisenberg antiferromagnet, at zero temperature, with spatially anisotropic nearest-neighbor couplings frustrated by a next-nearest neighbor interaction and single ion anisotropy. The phase diagram at zero temperature is presented. My calculations show two magnetically ordered phases separated by a quantum-disordered region for all values of the anisotropy.

  17. The Global S_1 Tide in Earth's Nutation

    Science.gov (United States)

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

    2016-05-01

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

  18. Osmo-, thermo- and ethanol- tolerances of Saccharomyces cerevisiae S1

    Directory of Open Access Journals (Sweden)

    Sandrasegarampillai Balakumar

    2012-03-01

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

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

    Science.gov (United States)

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

    2015-12-01

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

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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...

  2. 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.

  3. 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.

  4. 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.

  5. QCD corrections to inclusive $\\Delta S=1,2$ transitions

    OpenAIRE

    Jamin, Matthias

    1994-01-01

    The talk summarises a calculation of the two-point functions for $\\Delta S=1$ current-current and QCD-penguin operators, as well as for the $\\Delta S=2$ operator, at the next-to-leading order. The size of the gluonic corrections to current-current operators is large, providing a qualitative understanding of the observed enhancement in $\\Delta I=1/2$ transitions. In the $\\Delta S=2$ sector the QCD corrections are quite moderate ($\\approx -20\\%$). This work has been done in collaboration with A...

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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。

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

    Science.gov (United States)

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

    2011-07-01

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

  13. M2M monitoring terminal based on Cortex-M3%基于Cortex-M3的M2M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.

  14. 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

  15. 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.

  16. 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.

  17. 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).

  18. 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.

  19. 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

  20. 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.

  1. 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...

  2. 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.

  3. 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.

  4. 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

  5. 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...

  6. 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.

  7. 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 ...

  8. 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

  9. 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...

  10. The S1 ← S0 fluorescence excitation spectrum and structure of propanal in the S1 excited electronic state.

    Science.gov (United States)

    Godunov, I A; Yakovlev, N N; Terentiev, R V; Maslov, D V; Abramenkov, A V

    2016-06-01

    We have obtained and analyzed the S1 ← S0 fluorescence excitation spectra of jet-cooled propanal-h1 (CH3CH2CHO) and -d1 (CH3CH2CDO). Using the results of theoretical studies of the structure of propanal molecule in the S1 lowest excited singlet electronic state, we have assigned the bands of both spectra to the vibronic transitions of the cis conformer (in the S0 ground electronic state) to the 1 and 3 conformers (in the S1 state) differed by the angle of the C2H5 ethyl group rotation around the central C-C bond. The origins of the 1 ← cis and 3 ← cis electronic transitions have been observed at 29 997 and 30 075 cm(-1) for propanal-h1 and at 30 040 and 30 115 cm(-1) for propanal-d1, respectively. The high activity of torsional (C2H5 ethyl groups) and inversional (CCHO/CCDO carbonyl fragments) vibrations and the intensity distribution of the bands in torsional sequences (passing through maximum) are in agreement with the theoretical prediction that the S1 ← S0 electronic excitation of the cis conformer causes (after geometrical relaxation) the pyramidalization of carbonyl fragments and the rotation of ethyl groups around the central C-C bond. A number of energy levels have been found for torsional and inversional vibrations, and also fundamentals of ν10 (CCO bend) and ν13 (CCC bend) for the both 1 and 3 conformers of propanal-h1 and -d1 have been found. Then the "experimental" potential functions of inversion for the pair of the 1 and 3 conformers have been determined. The heights of potential barriers to inversion and the angle values corresponding to the minima of potential functions of inversion are 900 cm(-1) and 35° for propanal-h1 and 820 cm(-1) and 34° for propanal-d1, respectively.

  11. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Takeshita, Harunori [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Kitano, Masayasu, E-mail: mkitano6@hyo-med.ac.jp [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Iwasaki, Tsuyoshi [Department of Pharmacy, Hyogo University of Health Sciences, 1-3-6 Minatojima Kobe, Hyogo 650-8530 (Japan); Kitano, Sachie; Tsunemi, Sachi; Sato, Chieri; Sekiguchi, Masahiro; Azuma, Naoto [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Miyazawa, Keiji [Discovery Research III, Research and Development, Kissei Pharmaceutical Company, 4365-1 Hodakakashiwara, Azumino, Nagano 399-8304 (Japan); Hla, Timothy [Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, 1300 York Avenue, Box 69, NY 10065 (United States); Sano, Hajime [Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan)

    2012-03-09

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

  13. 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.

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

    Science.gov (United States)

    Gorbatsevich, Vladimir V.

    2007-10-01

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

  20. Dynamical instability in the S =1 Bose-Hubbard model

    Science.gov (United States)

    Asaoka, Rui; Tsuchiura, Hiroki; Yamashita, Makoto; Toga, Yuta

    2016-01-01

    We study the dynamical instabilities of superfluid flows in the S =1 Bose-Hubbard model. The time evolution of each spin component in a condensate is calculated based on the dynamical Gutzwiller approximation for a wide range of interactions, from a weakly correlated regime to a strongly correlated regime near the Mott-insulator transition. Owing to the spin-dependent interactions, the superfluid flow of the spin-1 condensate decays at a different critical momentum from a spinless case when the interaction strength is the same. We furthermore calculate the dynamical phase diagram of this model and clarify that the obtained phase boundary has very different features depending on whether the average number of particles per site is even or odd. Finally, we analyze the density and spin modulations that appear in association with the dynamical instability. We find that spin modulations are highly sensitive to the presence of a uniform magnetic field.

  1. Inverse Supersymmetry Breaking in S1 × R3

    Directory of Open Access Journals (Sweden)

    Vasilis Oikonomou

    2010-03-01

    Full Text Available In this paper, we study the influence of hard supersymmetry breaking terms in a N = 1, d = 4 supersymmetric model, in S1 × R3 spacetime topology. It is shown that when the radius of the compact dimension is large supersymmetry is unbroken, and dynamically breaks as the radius decreases. We point out that this resembles the inverse symmetry breaking of continuous symmetries at finite temperature (however, in the case of supersymmetry, the role of the temperature is played by the compact dimension’s radius. Furthermore, we also find a universality in the dependence of the critical length Lc as a function of a coupling g3, after comparing all cases.

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

    Science.gov (United States)

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

    2011-01-01

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

  3. S-1 project. Volume I. Architecture. 1979 annual report

    Energy Technology Data Exchange (ETDEWEB)

    1979-01-01

    The US Navy is one of the world's largest users of digital computing equipment having a procurement cost of at least $50,000, and is the single largest such computer customer in the Department of Defense. Its projected acquisition plan for embedded computer systems during the first half of the 80s contemplates the installation of over 10,000 such systems at an estimated cost of several billions of dollars. This expenditure, though large, is dwarfed by the 85 billion dollars which DOD is projected to spend during the next half-decade on computer software, the near-majority of which will be spent by the Navy; the life-cycle costs of the 700,000+ lines of software for a single large Navy weapons systems application (e.g., AEGIS) have been conservatively estimated at most of a billion dollars. The S-1 Project is dedicated to realizing potentially large improvements in the efficiency with which such very large sums may be spent, so that greater military effectiveness may be secured earlier, and with smaller expenditures. The fundamental objectives of the S-1 Project's work are first to enable the Navy to be able to quickly, reliably and inexpensively evaluate at any time what is available from the state-of-the-art in digital processing systems and what the relevance of such systems may be to Navy data processing applications: and second to provide reference prototype systems to support possible competitive procurement action leading to deployment of such systems.

  4. Discovery of potent 3,5-diphenyl-1,2,4-oxadiazole sphingosine-1-phosphate-1 (S1P1) receptor agonists with exceptional selectivity against S1P2 and S1P3.

    Science.gov (United States)

    Li, Zhen; Chen, Weirong; Hale, Jeffrey J; Lynch, Christopher L; Mills, Sander G; Hajdu, Richard; Keohane, Carol Ann; Rosenbach, Mark J; Milligan, James A; Shei, Gan-Ju; Chrebet, Gary; Parent, Stephen A; Bergstrom, James; Card, Deborah; Forrest, Michael; Quackenbush, Elizabeth J; Wickham, L Alexandra; Vargas, Hugo; Evans, Rose M; Rosen, Hugh; Mandala, Suzanne

    2005-10-06

    A class of 3,5-diphenyl-1,2,4-oxadiazole based compounds have been identified as potent sphingosine-1-phosphate-1 (S1P1) receptor agonists with minimal affinity for the S1P2 and S1P3 receptor subtypes. Analogue 26 (S1P1 IC50 = 0.6 nM) has an excellent pharmacokinetics profile in the rat and dog and is efficacious in a rat skin transplant model, indicating that S1P3 receptor agonism is not a component of immunosuppressive efficacy.

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

    Science.gov (United States)

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

    2016-01-27

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

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

    Science.gov (United States)

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

    2009-07-01

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

  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. [Combination chemotherapy of S-1, docetaxel and CDDP produces a remarkable response in a patient with metastases of supraclavicular lymph nodes and gingival carcinoma of the mandible].

    Science.gov (United States)

    Ishii, Shoichiro; Ueda, Takashi; Higuchi, Masataka; Mima, Takashi; Yakushiji, Noboru

    2010-09-01

    We report a 53-year-old female patient with an unresectable metastasis to the supraclavicular lymph node from a primary gingival carcinoma of the mandible. The patient had a history of tongue carcinoma and had undergone a radical neck dissection for the treatment of gingival carcinoma. She underwent combined chemotherapy consisting of S-1 (80 mg on days 1-14, followed by a 7-day rest), docetaxel (35mg/m2 by intravenous infusion on days 1 and 8), and CDDP (10mg/m2 by intravenous infusion on days 1 and 8) every 3 weeks. After three courses of the above chemotherapy regimen, a computerized tomography examination revealed a complete response. The patient did not experience any severe side effects during the course of chemotherapy. Combined S-1, docetaxel, and CDDP chemotherapy can thus be effective for unresectable recurrences of oral cancer in lymph nodes.

  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. 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.

  12. 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.

  13. 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...

  14. Selecting against S1P3 enhances the acute cardiovascular tolerability of 3-(N-benzyl)aminopropylphosphonic acid S1P receptor agonists.

    Science.gov (United States)

    Hale, Jeffrey J; Doherty, George; Toth, Leslie; Mills, Sander G; Hajdu, Richard; Keohane, Carol Ann; Rosenbach, Mark; Milligan, James; Shei, Gan-Ju; Chrebet, Gary; Bergstrom, James; Card, Deborah; Forrest, Michael; Sun, Shu-Yu; West, Sarah; Xie, Huijuan; Nomura, Naomi; Rosen, Hugh; Mandala, Suzanne

    2004-07-01

    Structurally modified 3-(N-benzylamino)propylphosphonic acid S1P receptor agonists that maintain affinity for S1P1, and have decreased affinity for S1P3 are efficacious, but exhibit decreased acute cardiovascular toxicity in rodents than do nonselective agonists.

  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. Involvement of Sphingosine 1-Phosphate (S1P) Receptor Type 1 and Type 4 in Migratory Response of Mouse T Cells toward S1P

    Institute of Scientific and Technical Information of China (English)

    Hirofumi Matsuyuki; Yasuhiro Maeda; Kazuhiro Yano; Kunio Sugahara; Kenji Chiba; Takayuki Kohno; Yasuyuki Igarashi

    2006-01-01

    Sphingosine 1-phosphate (S1P), a pleiotropic lysophospholipid, regulates signal transduction pathway via Gprotein-coupled receptors termed S1P1-5 in several types of the cells including lymphocytes. Higher levels of S1P4 mRNA as well as S1P1 mRNA are expressed in lymphoid tissues such as the spleen, thymus, lymph nodes, and Payer's patches. In contrast to S1P1 that plays an essential role in lymphocyte egress, little is known about the role of S1P4 in immune system. In this study, we found that S1P at 10 to 100 nM significantly induced the cell migration and the significant levels of S1P1 and S1P4 mRNA were expressed in mouse CD4 T cells, D10.G4.1 mouse Th2 cells,and EL-4.IL-2 mouse thymoma cells. In D10.G4.1 and EL-4.IL-2 cells, S1P-induced migration was almost completely inhibited by pretreatment with pertussis toxin, Clostoridium difficile toxin B, and (S)-enantiomer of FTY720-phosphate, a potent agonist at S1P1 and S1P4. The members of the Rho family small GTPase, Cdc42 and Rac were activated by S1P stimulation in these cells. The transfection with dominant negative or constitutively active forms of Cdc42 and Rac revealed that the activation of both Cdc42 and Rac is essential for S1P-induced migration of these cells. The immunoprecipitation assays using CHO cells co-expressing both S1P4 and S1P1 receptors indicated that S1P4 and S1P1 are associated on the cell surface. These results suggest that the association of S1P4 and S1P1 plays an important role in migratory response of mouse T cells toward S1P.

  16. 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.

  17. Confinement on $R^{3}\\times S^{1}$: continuum and lattice

    CERN Document Server

    Ogilvie, Michael C

    2014-01-01

    There has been substantial progress in understanding confinement in a class of four-dimensional SU(N) gauge theories using semiclassical methods. These models have one or more compact directions, and much of the analysis is based on the physics of finite-temperature gauge theories. The topology $R^{3}\\times S^{1}$ has been most often studied, using a small compactification circumference $L$ such that the running coupling $g^{2}\\left(L\\right)$ is small. The gauge action is modified by a double-trace Polyakov loop deformation term, or by the addition of periodic adjoint fermions. The additional terms act to preserve $Z(N)$ symmetry and thus confinement. An area law for Wilson loops is induced by a monopole condensate. In the continuum, the string tension can be computed analytically from topological effects. Lattice models display similar behavior, but the theoretical analysis of topological effects is based on Abelian lattice duality rather than on semiclassical arguments. In both cases the key step is reducin...

  18. Will Comet ISON (C/2012 S1) Survive Perihelion?

    Science.gov (United States)

    Knight, Matthew M.; Walsh, Kevin J.

    2013-10-01

    On 2013 November 28 Comet ISON (C/2012 S1) will pass by the Sun with a perihelion distance of 2.7 solar radii. Understanding the possible outcomes for the comet's response to such a close passage by the Sun is important for planning observational campaigns and for inferring ISON's physical properties. We present new numerical simulations and interpret them in context with the historical track record of comet disruptions and of sungrazing comet behavior. Historical data suggest that sizes below ~200 m are susceptible to destruction by sublimation driven mass loss, while we find that for ISON's perihelion distance, densities lower than 0.1 g cm-3 are required to tidally disrupt a retrograde or non-spinning body. Such low densities are substantially below the range of the best-determined comet nucleus densities, though dynamically new comets such as ISON have few measurements of physical properties. Disruption may occur for prograde rotation at densities up to 0.7 g cm-3, with the chances of disruption increasing for lower density, faster prograde rotation, and increasing elongation of the nucleus. Given current constraints on ISON's nucleus properties and the typically determined values for these properties among all comets, we find tidal disruption to be unlikely unless other factors (e.g., spin-up via torquing) affect ISON substantially. Whether or not disruption occurs, the largest remnant must be big enough to survive subsequent mass loss due to sublimation in order for ISON to remain a viable comet well after perihelion.

  19. Will Comet ISON (C/2012 S1) Survive Perihelion?

    CERN Document Server

    Knight, Matthew M

    2013-01-01

    On 2013 November 28 Comet ISON (C/2012 S1) will pass by the Sun with a perihelion distance of 2.7 solar radii. Understanding the possible outcomes for the comet's response to such a close passage by the Sun is important for planning observational campaigns and for inferring ISON's physical properties. We present new numerical simulations and interpret them in context with the historical track record of comet disruptions and of sungrazing comet behavior. Historical data suggest that sizes below ~200 m are susceptible to destruction by sublimation driven mass loss, while we find that for ISON's perihelion distance, densities lower than 0.1 g cm^-3 are required to tidally disrupt a retrograde or non-spinning body. Such low densities are substantially below the range of the best-determined comet nucleus densities, though dynamically new comets such as ISON have few measurements of physical properties. Disruption may occur for prograde rotation at densities up to 0.7 g cm^-3, with the chances of disruption increas...

  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

  1. First Global Climate Model Simulations of the M2 Pliocene Glacial

    Science.gov (United States)

    Dolan, A.; Haywood, A.; Hunter, S. J.; Tindall, J.; Valdes, P. J.

    2013-12-01

    The Pliocene Epoch (5.2 to 2.6 Ma) and specifically the PRISM interval (3.0 to 3.3 Ma) have frequently been targeted to investigate warm intervals in Earth history (e.g. Haywood et al., 2013). However, climate variability within the Pliocene is often overlooked. Although not as dramatic as the glacial and interglacial cycles that typified the Pleistocene, the Pliocene also exhibited climate variability and periods which were apparently cooler than modern (Lisiecki and Raymo, 2005). Of particular interest is the major cooling event that occurred around 3.3 Ma during Marine Isotope Stage (MIS) M2. This 'Pliocene glacial' punctuates an otherwise relatively warm background climate and has been referred to as a failed attempt of the climate to reach a full glacial state (De Schepper et al., 2009; Haug and Tiedemann, 1998). The onset of full Northern Hemisphere (NH) glaciation finally occurred at the end of the Pliocene (~ 2.75 Ma). Although numerous temperature reconstructions from around the world's oceans tend to capture the MIS M2 cooling event, the exact nature of M2 remains enigmatic. Sea level records vary but suggest a maximum sea level drop of ~65 m compared to modern, which in itself is significant enough to necessitate the growth of a NH ice sheet (Dwyer and Chandler, 2009). Previous ice sheet modelling suggests that ~8 m sea level equivalent (SLE) ice could be stored on Antarctica (Pollard and DeConto, 2009) and this larger ice sheet (compared to modern) is potentially supported by the increase in ice-rafted debris (IRD) found offshore of East Antarctica during this time (Passchier, 2011). IRD in the North Atlantic would suggest the presence of an ice sheet on Greenland (e.g. Kleiven et al., 2002), but the locations of other ice caps in the NH are not determined due to the destructive nature of subsequent Pleistocene ice sheet advances. Moreover, recent evidence questions whether the climate in the NH was favourable at all for the initiation of ice sheets

  2. Sphingosine 1 Phosphate (S1P) Receptors 1 and 2 Coordinately Induce Osteoblast Migration Through S1P Activation of Complementary Kinase Pathways

    DEFF Research Database (Denmark)

    Quint, Patrick; Ruan, Ming; Pederson, Larry

    2013-01-01

    to sites of bone resorption as an initial step in replacing lost bone. In this study we investigated the mechanisms by which S1P stimulates mesenchymal (skeletal) stem cell (MSC) chemotaxis. S1P treatment of MSC activated RhoA GTPase, but this small G protein did not contribute to migration. Rather, two S1...... metabolism, it is crucial to determine the mechanisms by which osteoclasts and osteoblast precursors interact and contribute to coupling. We showed osteoclasts produce the chemokine sphingosine 1 phosphate (S1P), which stimulates osteoblast migration. Thus, osteoclast-derived S1P may recruit osteoblasts...

  3. Dale Reed with model in front of M2-F1

    Science.gov (United States)

    1967-01-01

    Dale Reed with a model of the M2-F1 in front of the actual lifting body. Reed used the model to show the potential of the lifting bodies. He first flew it into tall grass to test stability and trim, then hand-launched it from buildings for longer flights. Finally, he towed the lifting-body model aloft using a powered model airplane known as the 'Mothership.' A timer released the model and it glided to a landing. Dale's wife Donna used a 9 mm. camera to film the flights of the model. Its stability as it glided--despite its lack of wings--convinced Milt Thompson and some Flight Research Center engineers including the center director, Paul Bikle, that a piloted lifting body was possible. The lifting body concept evolved in the mid-1950s as researchers considered alternatives to ballistic reentries of piloted space capsules. The designs for hypersonic, wingless vehicles were on the boards at NASA Ames and NASA Langley facilities, while the US Air Force was gearing up for its Dyna-Soar program, which defined the need for a spacecraft that would land like an airplane. Despite favorable research on lifting bodies, there was little support for a flight program. Dryden engineer R. Dale Reed was intrigued with the lifting body concept, and reasoned that some sort of flight demonstration was needed before wingless aircraft could be taken seriously. In February 1962, he built a model lifting body based upon the Ames M2 design, and air-launched it from a radio controlled 'mothership.' Home movies of these flights, plus the support of research pilot Milt Thompson, helped pursuade the facilities director, Paul Bikle, to give the go-ahead for the construction of a full-scale version, to be used as a wind-tunnel model and possibly flown as a glider. Comparing lifting bodies to space capsules, an unofficial motto of the project was, 'Don't be Rescued from Outer Space--Fly Back in Style.' The construction of the M2-F1 was a joint effort by Dryden and a local glider manufacturer, the

  4. Carboxyl- and amino-functionalized polystyrene nanoparticles differentially affect the polarization profile of M1 and M2 macrophage subsets.

    Science.gov (United States)

    Fuchs, Ann-Kathrin; Syrovets, Tatiana; Haas, Karina A; Loos, Cornelia; Musyanovych, Anna; Mailänder, Volker; Landfester, Katharina; Simmet, Thomas

    2016-04-01

    Macrophages are key regulators of innate and adaptive immune responses. Exposure to microenvironmental stimuli determines their polarization into proinflammatory M1 and anti-inflammatory M2 macrophages. M1 exhibit high expression of proinflammatory TNF-α and IL-1β, and M2 promote tissue repair, but likewise support tumor growth and cause immune suppression by expressing IL-10. Thus, the M1/M2 balance critically determines tissue homeostasis. By using carboxyl- (PS-COOH) and amino-functionalized (PS-NH2) polystyrene nanoparticles, the effects of surface decoration on the polarization of human macrophages were investigated. The nanoparticles did not compromise macrophage viability nor did they affect the expression of the M1 markers CD86, NOS2, TNF-α, and IL-1β. By contrast, in M2, both nanoparticles impaired expression of scavenger receptor CD163 and CD200R, and the release of IL-10. PS-NH2 also inhibited phagocytosis of Escherichia coli by both, M1 and M2. PS-COOH did not impair phagocytosis by M2, but increased protein mass in M1 and M2, TGF-β1 release by M1, and ATP levels in M2. Thus, nanoparticles skew the M2 macrophage polarization without affecting M1 markers. Given the critical role of the M1 and M2 polarization for the immunological balance in patients with cancer or chronic inflammation, functionalized nanoparticles might serve as tools for reprogramming the M1/M2 polarization.

  5. M2-F3 In-flight Launch from B-52

    Science.gov (United States)

    1971-01-01

    This photo shows the M2-F3 Lifting Body being launched from NASA's B-52 mothership at the NASA Flight Research Center (FRC--now the Dryden Flight Research Center), Edwards, California. A fleet of lifting bodies flown at the FRC from 1963 to l975 demonstrated the ability of pilots to maneuver and safely land a wingless vehicle designed to fly back to Earth from space and be landed like an aircraft at a pre-determined site. Early flight testing of the M2-F1 and M2-F2 lifting body reentry configurations had validated the concept of piloted lifting body reentry from space. When the M2-F2 crashed on May 10, 1967, valuable information had already been obtained and was contributing to new designs. NASA pilots said the M2-F2 had lateral control problems, so when the M2-F2 was rebuilt at Northrop and redesignated the M2-F3, it was modified with an additional third vertical fin -- centered between the tip fins -- to improve control characteristics. First flight of the M2-F3, with NASA pilot Bill Dana at the controls, was June 2, 1970. The modified vehicle exhibited much better lateral stability and control characteristics than before, and only three glide flights were necessary before the first powered flight on Nov. 25, 1970. Over the next 26 missions, the M2-F3 reached a top speed of l,064 mph (Mach 1.6). Highest altitude reached by vehicle was 7l,500 feet on Dec. 20, 1972, the date of its last flight, with NASA pilot John Manke at the controls. NASA donated The M2-F3 vehicle to the Smithsonian Institute in December 1973. It is currently hanging in the Air and Space Museum along with the X-15 aircraft number 1, which was its hangar partner from 1965 to 1969. NASA B-52, Tail Number 008, is an air launch carrier aircraft, 'mothership,' as well as a research aircraft platform that has been used on a variety of research projects. The aircraft, a 'B' model built in 1952 and first flown on June 11, 1955, is the oldest B-52 in flying status and has been used on some of the most

  6. Long-term results of definitive concurrent chemoradiotherapy using S-1 in the treatment of geriatric patients with esophageal cancer

    Directory of Open Access Journals (Sweden)

    Lv S

    2016-09-01

    Full Text Available Shiliang Lv, Min Fang, Jia Yang, Wenming Zhan, Yongshi Jia, Hong’en Xu, Tao Song Department of Radiotherapy, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang, People’s Republic of China Objective: The aim of this study was to investigate the efficiency and safety of using S-1 as monotherapy and maintenance therapy combined with definitive concurrent radiotherapy for elderly patients with esophageal cancer.Patients and methods: From January 2009 to December 2010, 68 elderly patients were included. Radiotherapy was delivered with a daily fraction of 1.8–2.0 Gy to a total radiation dose of 54.0–60.0 Gy. Preplanned concurrent S-1 (80 mg/m2/d was given on days 1–14, every 3 weeks. After concurrent chemoradiotherapy, maintenance S-1 was repeated up to four cycles.Results: The median age of the enrolled patients was 76 years (range: 70–88 years, and the clinical stages were stage I (two patients, stage II (24 patients, stage III (28 patients, and stage IV (14 patients. A total of 51 (75.0% patients finished treatment on schedule, with a median of five cycles of S-1, in which 35 (51.5% patients achieved complete response. The median follow-up time was 42.7 months, and the median overall survival (OS and progression-free survival (PFS times were 25.7 months and 21.5 months, respectively. The 1-year, 3-year, and 5-year OS and PFS rates were 70.6%, 41.8%, and 25.9% and 68.1%, 32.9%, and 15.9%, respectively. Grade ≥3 neutropenia and leukopenia were found in 14 patients and 13 patients, respectively. The most common nonhematologic toxicity was esophagitis including six patients and one patient with grades 3 and 4, respectively. Multivariate analysis revealed that cycles of S-1 and complete response were strong factors for OS and PFS.Conclusion: For geriatric patients with esophageal cancer, S-1 as monotherapy and maintenance chemotherapy in combination with definitive concurrent radiation therapy yielded satisfactory

  7. Pharmacological effects of mitraphylline from Uncaria tomentosa in primary human monocytes: Skew toward M2 macrophages.

    Science.gov (United States)

    Montserrat-de la Paz, S; de la Puerta, R; Fernandez-Arche, A; Quilez, A M; Muriana, F J G; Garcia-Gimenez, M D; Bermudez, B

    2015-07-21

    Uncaria tomentosa (Willdenow ex Roemer & Schultes) DC. (Rubiaceae) is a Peruvian thorny liana, commonly known as "cat׳s claw", and traditionally used in folk medicine to deal with several inflammatory diseases. Mitraphylline (MTP) is the most abundant pentacyclic oxindolic alkaloid (POA) from U. Tomentosa and has been reported to modify the inflammatory response. Herein, we have sought to identify the mechanisms underlying this modulatory effect of MTP on primary human monocytes and its ability to regulate differentiation processes on human primary monocyte and monocyte-derived macrophages. In vitro studies with human primary monocytes and monocyte-derived macrophages were performed. Monocytes and M0 macrophages were exposed to MTP (25μM) and LPS (100ng/mL). M0 macrophages were polarized to M1 and M2 phenotypes in the absence or presence of MTP. The activation state of monocytes/macrophages was assessed by flow cytometry, gene expression and protein analysis of different specific markers. In human primary monocytes, the incubation of MTP for 24h reduced the number of classical (CD14(++)CD16(-)) and intermediate (CD14(++)CD16(+)) subsets when compared to untreated or LPS-treated cells. MTP also reduced the chemotactic capacity of human primary monocytes. In addition, MTP promoted the polarization of M0 macrophages toward an anti-inflammatory M2 phenotype, the abrogation of the release of pro-inflammatory cytokines such as TNFα, IL-6 or IL-1β, as well as the restoration of markers for M2 macrophages in LPS-treated M1 macrophages. Our results suggest that MTP may be a key modulator for regulating the plasticity of monocytes/macrophages and the attenuation of the inflammatory response. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Bile acid-induced arrhythmia is mediated by muscarinic M2 receptors in neonatal rat cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Siti H Sheikh Abdul Kadir

    Full Text Available BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP is a common disease affecting up to 5% of pregnancies and which can cause fetal arrhythmia and sudden intrauterine death. We previously demonstrated that bile acid taurocholate (TC, which is raised in the bloodstream of ICP, can acutely alter the rate and rhythm of contraction and induce abnormal calcium destabilization in cultured neonatal rat cardiomyocytes (NRCM. Apart from their hepatic functions bile acids are ubiquitous signalling molecules with diverse systemic effects mediated by either the nuclear receptor FXR or by a recently discovered G-protein coupled receptor TGR5. We aim to investigate the mechanism of bile-acid induced arrhythmogenic effects in an in-vitro model of the fetal heart. METHODS AND RESULTS: Levels of bile acid transporters and nuclear receptor FXR were studied by quantitative real time PCR, western blot and immunostaining, which showed low levels of expression. We did not observe functional involvement of the canonical receptors FXR and TGR5. Instead, we found that TC binds to the muscarinic M(2 receptor in NRCM and serves as a partial agonist of this receptor in terms of inhibitory effect on intracellular cAMP and negative chronotropic response. Pharmacological inhibition and siRNA-knockdown of the M(2 receptor completely abolished the negative effect of TC on contraction, calcium transient amplitude and synchronisation in NRCM clusters. CONCLUSION: We conclude that in NRCM the TC-induced arrhythmia is mediated by the partial agonism at the M(2 receptor. This mechanism might serve as a promising new therapeutic target for fetal arrhythmia.

  9. Interleukin-17 induces an atypical M2-like macrophage subpopulation that regulates intestinal inflammation.

    Directory of Open Access Journals (Sweden)

    Kenichiro Nishikawa

    Full Text Available Interleukin 17 (IL-17 is a pleiotropic cytokine that acts on both immune and non-immune cells and is generally implicated in inflammatory and autoimmune diseases. Although IL-17 as well as their source, mainly but not limited to Th17 cells, is also abundant in the inflamed intestine, the role of IL-17 in inflammatory bowel disease remains controversial. In the present study, by using IL-17 knockout (KO mice, we investigated the role of IL-17 in colitis, with special focus on the macrophage subpopulations. Here we show that IL-17KO mice had increased susceptibility to DSS-induced colitis which was associated with decrease in expression of mRNAs implicated in M2 and/or wound healing macrophages, such as IL-10, IL-1 receptor antagonist, arginase 1, cyclooxygenase 2, and indoleamine 2,3-dioxygenase. Lamina propria leukocytes from inflamed colon of IL-17KO mice contained fewer CD11b+Ly6C+MHC Class II+ macrophages, which were derived, at least partly, from blood monocytes, as compared to those of WT mice. FACS-purified CD11b+ cells from WT mice, which were more abundant in Ly6C+MHC Class II+ cells, expressed increased levels of genes associated M2/wound healing macrophages and also M1/proinflammatory macrophages. Depletion of this population by topical administration of clodronate-liposome in the colon of WT mice resulted in the exacerbation of colitis. These results demonstrate that IL-17 confers protection against the development of severe colitis through the induction of an atypical M2-like macrophage subpopulation. Our findings reveal a previously unappreciated mechanism by which IL-17 exerts a protective function in colitis.

  10. Towards Efficient Mobile M2M Communications: Survey and Open Challenges

    Science.gov (United States)

    Pereira, Carlos; Aguiar, Ana

    2014-01-01

    Machine-to-Machine (M2M) communications enable networked devices and services to exchange information and perform actions seamlessly without the need for human intervention. They are viewed as a key enabler of the Internet of Things (IoT) and ubiquitous applications, like mobile healthcare, telemetry, or intelligent transport systems. We survey existing work on mobile M2M communications, we identify open challenges that have a direct impact on performance and resource usage efficiency, especially the impact on energy efficiency, and we review techniques to improve communications. We review the ETSI standard and application protocols, and draw considerations on the impact of their use in constrained mobile devices. Nowadays, smartphones are equipped with a wide range of embedded sensors, with varied local and wide area connectivity capabilities, and thus they offer a unique opportunity to serve as mobile gateways for other more constrained devices with local connectivity. At the same time, they can gather context data about users and environment from the embedded sensors. These capabilities may be crucial for mobile M2M applications. Finally, in this paper, we consider a scenario where smartphones are used as gateways that collect and aggregate data from sensors in a cellular network. We conclude that, in order for their use to the feasible in terms of a normal depletion time of a smartphone's battery, it is a good advice to maximize the collection of data necessary to be transmitted from nearby sensors, and maximize the intervals between transmissions. More research is required to devise energy efficient transmission methods that enable the use of smartphones as mobile gateways. PMID:25333291

  11. Towards Efficient Mobile M2M Communications: Survey and Open Challenges

    Directory of Open Access Journals (Sweden)

    Carlos Pereira

    2014-10-01

    Full Text Available Machine-to-Machine (M2M communications enable networked devices and services to exchange information and perform actions seamlessly without the need for human intervention. They are viewed as a key enabler of the Internet of Things (IoT and ubiquitous applications, like mobile healthcare, telemetry, or intelligent transport systems. We survey existing work on mobile M2M communications, we identify open challenges that have a direct impact on performance and resource usage efficiency, especially the impact on energy efficiency, and we review techniques to improve communications. We review the ETSI standard and application protocols, and draw considerations on the impact of their use in constrained mobile devices. Nowadays, smartphones are equipped with a wide range of embedded sensors, with varied local and wide area connectivity capabilities, and thus they offer a unique opportunity to serve as mobile gateways for other more constrained devices with local connectivity. At the same time, they can gather context data about users and environment from the embedded sensors. These capabilities may be crucial for mobile M2M applications. Finally, in this paper, we consider a scenario where smartphones are used as gateways that collect and aggregate data from sensors in a cellular network. We conclude that, in order for their use to the feasible in terms of a normal depletion time of a smartphone’s battery, it is a good advice to maximize the collection of data necessary to be transmitted from nearby sensors, and maximize the intervals between transmissions. More research is required to devise energy efficient transmission methods that enable the use of smartphones as mobile gateways.

  12. Structural basis for tumor pyruvate kinase M2 allosteric regulation and catalysis.

    Science.gov (United States)

    Dombrauckas, Jill D; Santarsiero, Bernard D; Mesecar, Andrew D

    2005-07-12

    Four isozymes of pyruvate kinase are differentially expressed in human tissue. Human pyruvate kinase isozyme M2 (hPKM2) is expressed in early fetal tissues and is progressively replaced by the other three isozymes, M1, R, and L, immediately after birth. In most cancer cells, hPKM2 is once again expressed to promote tumor cell proliferation. Because of its almost ubiquitous presence in cancer cells, hPKM2 has been designated as tumor specific PK-M2, and its presence in human plasma is currently being used as a molecular marker for the diagnosis of various cancers. The X-ray structure of human hPKM2 complexed with Mg(2+), K(+), the inhibitor oxalate, and the allosteric activator fructose 1,6-bisphosphate (FBP) has been determined to a resolution of 2.82 A. The active site of hPKM2 is in a partially closed conformation most likely resulting from a ligand-induced domain closure promoted by the binding of FBP. In all four subunits of the enzyme tetramer, a conserved water molecule is observed on the 2-si face of the prospective enolate and supports the hypothesis that a proton-relay system is acting as the proton donor of the reaction (1). Significant structural differences among the human M2, rabbit muscle M1, and the human R isozymes are observed, especially in the orientation of the FBP-activating loop, which is in a closed conformation when FBP is bound. The structural differences observed between the PK isozymes could potentially be exploited as unique structural templates for the design of allosteric drugs against the disease states associated with the various PK isozymes, especially cancer and nonspherocytic hemolytic anemia.

  13. Towards efficient mobile M2M communications: survey and open challenges.

    Science.gov (United States)

    Pereira, Carlos; Aguiar, Ana

    2014-10-20

    Machine-to-Machine (M2M) communications enable networked devices and services to exchange information and perform actions seamlessly without the need for human intervention. They are viewed as a key enabler of the Internet of Things (IoT) and ubiquitous applications, like mobile healthcare, telemetry, or intelligent transport systems. We survey existing work on mobile M2M communications, we identify open challenges that have a direct impact on performance and resource usage efficiency, especially the impact on energy efficiency, and we review techniques to improve communications. We review the ETSI standard and application protocols, and draw considerations on the impact of their use in constrained mobile devices. Nowadays, smartphones are equipped with a wide range of embedded sensors, with varied local and wide area connectivity capabilities, and thus they offer a unique opportunity to serve as mobile gateways for other more constrained devices with local connectivity. At the same time, they can gather context data about users and environment from the embedded sensors. These capabilities may be crucial for mobile M2M applications. Finally, in this paper, we consider a scenario where smartphones are used as gateways that collect and aggregate data from sensors in a cellular network. We conclude that, in order for their use to the feasible in terms of a normal depletion time of a smartphone's battery, it is a good advice to maximize the collection of data necessary to be transmitted from nearby sensors, and maximize the intervals between transmissions. More research is required to devise energy efficient transmission methods that enable the use of smartphones as mobile gateways.

  14. Sistemas de gestión de sensores mediante tecnologías M2M

    OpenAIRE

    Miguel Heredero, Miguel de

    2014-01-01

    En el proyecto se lleva a cabo un estudio práctico sobre dos escenarios donde intervienen dispositivos relacionados con el Internet de las cosas. También se puede situar como una solución de comunicación M2M. Comunicación máquina a máquina implica un sistema central que es capaz de conectarse con otros sistemas en varios lugares. La conexión permite que el sistema central recoja o envíe datos a cada lugar remoto para su procesamiento. El primer escenario consta de la configuración y montaj...

  15. Resonant Photoemission and M_{2,3}-Absorption Spectra in Nickel Dichloride

    Science.gov (United States)

    Igarashi, J.

    Ni 3p-resonant photoemission and Ni M_{2,3}-absorption spectra are calculated in detail on a cluster of (NiCl_6)^{4-} with the use of the transition matrix elements evaluated on the Herman-Skillman potential in Ni atom. Overall spectral shape agrees well with experiment, allowing a determination of the parameters which characterize Ni 3d and Cl 3p states. Resonance behavior is discussed near the Ni 3p-core level photothreshold. The resonant enhancement is found to be larger for the peak with higher binding energy in the d^7-multiplets.

  16. 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.

  17. Atmospheric Turbulence Measurements With the Automatic Mini UAV 'M2AV Carolo'

    Science.gov (United States)

    Bange, J.; van den Kroonenberg, A. C.; Spieß, T.; Buschmann, M.; Krüger, L.; Heindorf, A.; Vörsmann, P.

    2007-05-01

    The limitations of manned airborne meteorological measurements led to the development of an autonomously operating mini aircraft, the Meteorological Mini-UAV (M2AV), at the Institute of Aerospace Systems, Technical University of Braunschweig, Germany. The task was to develop, test and verify a meteorological sensor package as payload for an already available automatic carrier aircraft, the UAV 'Carolo T200', which operates autonomously i.e. without remote control. The M2AV is a self constructed model aircraft with two electrically powered engines and a wingspan of two meters. The maximum take-off weight is 4.5~kg (the M2AV is therefore classified as an model plane which simplifies authority issues), including 1.5~kg of payload. It is hand-launched which makes operation of the aircraft easy. With an endurance of approximately 50 minutes, the range accounts for 60 km at a cruising speed of 20~m/s. The M2AV is capable of performing turbulence measurements (wind vector, temperature and humidity) within the troposphere and offers an economic component during meteorological campaigns. The meteorological sensors are mounted on a noseboom to minimise the aircraft's influence on the measurements and to position the sensors closely to each other. Wind is measured via a small five-hole probe, an inertia measurement unit and GPS. The flight mission (waypoints, altitudes, airspeed) is planned and assigned to the aircraft before the semi- automatic launch. The flight is only controlled by the on-board autopilot system which only communicates with a ground station (laptop PC) for the exchange of measured data and command updates like new waypoints etc. The talk gives details on the technical items, calibration and first missions. Results from first field experiments like the LAUNCH-2005 campaign near Berlin are used for data quality assessment by comparison with simultaneous lidar and sodar measurements. An in situ comparison with the highly accurate helicopter-borne turbulence

  18. $SU(N)$ BPS Monopoles in $\\mathcal{M}^2\\times S^2$

    OpenAIRE

    2015-01-01

    We extend the investigation of BPS saturated t'Hooft-Polyakov monopoles in $\\mathcal{M}^{2}\\times S^{2}$ to the general case of $SU(N)$ gauge symmetry. This geometry causes the resulting $N-1$ coupled non-linear ordinary differential equations for the $N-1$ monopole profiles to become autonomous. One can also define a flat limit in which the curvature of the background metric is arbitrarily small but the simplifications brought in by the geometry remain. We prove analytically that non-trivial...

  19. An M/M/2 Queueing System with Heterogeneous Servers Including One with Working Vacation

    Directory of Open Access Journals (Sweden)

    A. Krishnamoorthy

    2012-01-01

    Full Text Available This paper analyzes an M/M/2 queueing system with two heterogeneous servers, one of which is always available but the other goes on vacation in the absence of customers waiting for service. The vacationing server, however, returns to serve at a low rate as an arrival finds the other server busy. The system is analyzed in the steady state using matrix geometric method. Busy period of the system is analyzed and mean waiting time in the stationary regime computed. Conditional stochastic decomposition of stationary queue length is obtained. An illustrative example is also provided.

  20. Clinical experience with autologous M2 macrophages in children with severe cerebral palsy.

    Science.gov (United States)

    Chernykh, Elena R; Kafanova, Marina Yu; Shevela, Ekaterina Ya; Sirota, Sergei I; Adonina, Elena I; Sakhno, Lyudmila V; Ostanin, Alexander A; Kozlov, Vladimir V

    2014-01-01

    Stem cell-based therapy is considered to be a new approach for the treatment of cerebral palsy (CP). Given the potent anti-inflammatory activity and high regenerative potential of M2 macrophages, these cells may be an alternative source for cell transplantation. To evaluate the safety and efficacy of autologous M2 macrophages, we conducted a pilot clinical trial in 21 children with severe CP. The primary outcome measure was safety, which included assessment of mortality of any cause, immediate adverse reactions, and serious adverse effects and comorbidities during 5-year follow-up. The secondary outcome measure was functional improvement in Gross Motor Function Measure (66-item GMFM) test, Peabody Developmental Motor Scale-Fine Motor (PDMS-FM) test, Ashworth scale, MRC scale, and an easy-to-understand questionnaire for evaluation of cognitive functions in our modification. Intradural injection of M2 cells (in mean dose of 0.8 × 10(6)/kg) into the lumbar spinal area did not induce any serious adverse events. No cases of mortality, psychomotor worsening, exacerbation of seizures, and long-term comorbidities, including tumors, were observed during a 5-year follow-up. After 3 months, GMFM score increased from 13.7 ± 7.8 to 58.6 ± 14.6, PDMS-FM score improved from 0.76 ± 0.42 to 5.05 ± 0.97, and the Ashworth score decreased from 3.8 ± 0.21 to 3.3 ± 0.24. Along with gross and fine motor function enhancement, an improvement of cognitive activity (from 1.62 ± 0.41 to 4.05 ± 0.64, according to questionnaire assessment) and reduction of seizure syndrome were registered as well. The neurological improvements did not diminish during the 5-year follow-up period. The data obtained suggest that cell therapy based on M2 macrophages is safe, does not induce early adverse effects and long-term comorbidities, and is accompanied with a significant improvement of motor and cognitive activities in severe CP patients. This manuscript is

  1. Joint TAS and Power Allocation for SDF Relaying M2M Cooperative Networks

    Directory of Open Access Journals (Sweden)

    Lingwei Xu

    2016-01-01

    Full Text Available The outage probability (OP performance of multiple-relay-based selective decode-and-forward (SDF relaying mobile-to-mobile (M2M networks with transmit antenna selection (TAS over N-Nakagami fading channels is investigated. The exact closed-form expressions for OP of the optimal and suboptimal TAS schemes are derived. The power allocation problem is formulated for performance optimization. Then, the OP performance under different conditions is evaluated through numerical simulations to verify the analysis. The simulation results showed that optimal TAS scheme has a better OP performance than suboptimal TAS scheme. Further, the power allocation parameter has an important influence on the OP performance.

  2. EcoM2 web portal: Collecting empirical data and supporting companies' ecodesign implementation and management

    DEFF Research Database (Denmark)

    Pigosso, Daniela Cristina Antelmi; McAloone, Tim C.; Rozenfeld, Henrique

    2013-01-01

    of strengths and limitations; and the establishment of strategic roadmaps for improved ecodesign implementation. This paper describes the development of the EcoM2 web portal, which will allow for the framework to be tested on greater numbers of companies and at the same time to provide a quick diagnosis...... of their current ecodesign maturity profile. Analyses of the collected data will allow the establishment of patterns on ecodesign implementation in regards to criteria such as sector and size of companies and the improvement of empirical knowledge on ecodesign implementation and best practices....

  3. Strategic Thinking of the Internet of Things and M2M Services

    Institute of Scientific and Technical Information of China (English)

    Qi Qingzhong

    2010-01-01

    @@ Editor' s Desk: The Internet of Things is an important part of the emerging high-tech industry and has been recognized as one of the important technologies for addressing global financial crisis and revitalizing the economy. Therefore, at the beginning of the new year, we are honored to have invited Mr. Samuel Qi (Qi Qingzhong), a famous Chinese communication technology expert and GM of Shanghai Symphony Telecommunications Co., Ltd., to give his views on the development strategy of the Internet of Things and Machine to Machine (M2M) Communications.

  4. M2型巨噬细胞的研究进展

    Institute of Scientific and Technical Information of China (English)

    罗冲; 杨锡强

    2010-01-01

    @@ 目前根据巨噬细胞活化状态及功能不同大致分为2种,即M1和M2型巨噬细胞[1-2].M1细胞即为经典活化巨噬细胞(classically activated macrophages,CAM),具有吞噬杀菌,释放炎症介质,提呈抗原和启动适应性免疫应答的功能,是机体抵御外物的重要防线[3].

  5. Split-course chemoradiotherapy with S-1, a novel oral fluorouracil, and cisplatin for distant metastases of oesophageal cancer stage IVb

    Directory of Open Access Journals (Sweden)

    Iwase H

    2017-01-01

    Full Text Available Objectives: To evaluate the efficacy and safety of split-course chemoradiotherapy with S-1, a novel oral fluorouracil, together with cisplatin in patients with distant oesophageal cancer stage IVb metastasis. Methods: Forty-one patients with distant oesophageal cancer metastasis and performance status 0 or 1 received split-course chemoradiotherapy with S-1 and cisplatin. All 41 patients were reviewed retrospectively. Chemoradiotherapy comprised two courses of 30-Gy radiotherapy over three weeks plus daily oral S-1 (70mg/m2/day for two weeks and a 24 h cisplatin infusion (70mg/m2 on Day 8, with a two week interval between the two courses. Results: The most frequent adverse events (AEs were grade 3 and 4 neutropenia (29.2%, thrombocytopenia (9.8%, and anaemia (7.3%. Non-haematological AEs were generally mild. AEs in the initial course of chemoradiotherapy remitted during the second interval week. Overall, the complete response rate was 22.0% and endoscopic complete response rate for primary lesion was 65.9%. Thirty-one patients (75.6% became asymptomatic and regained normal swallowing function. The overall median survival time was 12 months. Conclusion: This retrospective investigation showed that split-course chemoradiotherapy with S-1 and cisplatin had an encouraging safety profile together with good efficacy. Potentially, this regimen may become a standard for distant metastasis of oesophageal cancer stage IVb.

  6. Distinct interneuron types express m2 muscarinic receptor immunoreactivity on their dendrites or axon terminals in the hippocampus.

    Science.gov (United States)

    Hájos, N; Papp, E C; Acsády, L; Levey, A I; Freund, T F

    1998-01-01

    In previous studies m2 muscarinic acetylcholine receptor-immunoreactive interneurons and various types of m2-positive axon terminals have been described in the hippocampal formation. The aim of the present study was to identify the types of interneurons expressing m2 receptor and to examine whether the somadendritic and axonal m2 immunostaining labels the same or distinct cell populations. In the CA1 subfield, neurons immunoreactive for m2 have horizontal dendrites, they are located at the stratum oriens/alveus border and have an axon that project to the dendritic region of pyramidal cells. In the CA3 subfield and the hilus, m2-positive neurons are multipolar and are scattered in all layers except stratum lacunosum-moleculare. In stratum pyramidale of the CA1 and CA3 regions, striking axon terminal staining for m2 was observed, surrounding the somata and axon initial segments of pyramidal cells in a basket-like manner. The co-localization of m2 with neurochemical markers and GABA was studied using the "mirror" technique and fluorescent double-immunostaining at the light microscopic level and with double-labelling using colloidal gold-conjugated antisera and immunoperoxidase reaction (diaminobenzidine) at the electron microscopic level. GABA was shown to be present in the somata of most m2-immunoreactive interneurons, as well as in the majority of m2-positive terminals in all layers. The calcium-binding protein parvalbumin was absent from practically all m2-immunoreactive cell bodies and dendrites. In contrast, many of the terminals synapsing on pyramidal cell somata and axon initial segments co-localized parvalbumin and m2, suggesting a differential distribution of m2 receptor immunoreactivity on the axonal and somadendritic membrane of parvalbumin-containing basket and axo-axonic cells. The co-existence of m2 receptors with the calcium-binding protein calbindin and the neuropeptides cholecystokinin and vasoactive intestinal polypeptide was rare throughout the

  7. M2 macrophages or IL-33 treatment attenuate ongoing Mycobacterium tuberculosis infection

    Science.gov (United States)

    Piñeros, A. R.; Campos, L. W.; Fonseca, D. M.; Bertolini, T. B.; Gembre, A. F.; Prado, R. Q.; Alves-Filho, J. C.; Ramos, S. G.; Russo, M.; Bonato, V. L. D.

    2017-01-01

    The protective effects of mycobacterial infections on lung allergy are well documented. However, the inverse relationship between tuberculosis and type 2 immunity is still elusive. Although type 1 immunity is essential to protection against Mycobacterium tuberculosis it might be also detrimental to the host due to the induction of extensive tissue damage. Here, we determined whether lung type 2 immunity induced by allergen sensitization and challenge could affect the outcome of M. tuberculosis infection. We used two different protocols in which sensitization and allergen challenge were performed before or after M. tuberculosis infection. We found an increased resistance to M. tuberculosis only when allergen exposure was given after, but not before infection. Infected mice exposed to allergen exhibited lower bacterial load and cellular infiltrates in the lungs. Enhanced resistance to infection after allergen challenge was associated with increased gene expression of alternatively activated macrophages (M2 macrophages) and IL-33 levels. Accordingly, either adoptive transfer of M2 macrophages or systemic IL-33 treatment was effective in attenuating M. tuberculosis infection. Notably, the enhanced resistance induced by allergen exposure was dependent on IL-33 receptor ST2. Our work indicates that IL-33 might be an alternative therapeutic treatment for severe tuberculosis. PMID:28128217

  8. Some results on 4~m2~n designs with clear two-factor interaction components

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Clear effects criterion is one of the important rules for selecting optimal fractional factorial designs,and it has become an active research issue in recent years.Tang et al.derived upper and lower bounds on the maximum number of clear two-factor interactions(2fi’s) in 2n-(n-k) fractional factorial designs of resolutions III and IV by constructing a 2n-(n-k) design for given k,which are only restricted for the symmetrical case.This paper proposes and studies the clear effects problem for the asymmetrical case.It improves the construction method of Tang et al.for 2n-(n-k) designs with resolution III and derives the upper and lower bounds on the maximum number of clear two-factor interaction components(2fic’s) in 4m2n designs with resolutions III and IV.The lower bounds are achieved by constructing specific designs.Comparisons show that the number of clear 2fic’s in the resulting design attains its maximum number in many cases,which reveals that the construction methods are satisfactory when they are used to construct 4m2n designs under the clear effects criterion.

  9. Feedback mechanisms between M2 macrophages and Th17 cells in colorectal cancer patients.

    Science.gov (United States)

    Mao, Hui; Pan, Fei; Guo, Hongxia; Bu, Fangfang; Xin, Tong; Chen, Shukun; Guo, Yajun

    2016-09-01

    IL-17 and IL-22 are linked to the development of intestinal inflammation and colorectal cancer (CRC). However, the maintenance of IL-17 and IL-22 production, as well as the cell type (Th17) that mediates these cytokines in CRC patients, remains unknown. To examine this, untreated CRC patients and healthy controls were recruited in this study. We first observed that CRC patients contained significantly elevated levels of IL-17- and IL-22-producing CD4(+) T cells. The vast majority of IL-22-expressing CD4(+) T cells also expressed IL-17. We then found that the production of both IL-17 and IL-22 required support from autologous monocytes, since the depletion of monocytes significantly downregulated IL-17 and IL-22 secretion. Naive T cells from CRC patients did not secrete IL-17 or IL-22 initially, but long-term coculture with autologous monocytes significantly upregulated IL-17 and IL-22 production in an IL-6-dependent manner. Blockade of IL-6 significantly reduced the levels of both IL-17 and IL-22. We then observed that CD163(+) M2 macrophages were the main contributor of IL-6. Interestingly, incubation of monocytes with CCR4(+)CCR6(+) Th17 cells resulted in significantly higher levels of CD163(+) macrophages as well as higher IL-6 secretion, than incubation with non-Th17 CD4(+) T cells. Together, our study discovered a positive feedback mechanism between Th17 and M2 macrophages in CRC patients.

  10. An improved radiosynthesis of the muscarinic M2 radiopharmaceutical, [{sup 18}F]FP-TZTP

    Energy Technology Data Exchange (ETDEWEB)

    Oosten, Erik M. van [Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6 (Canada); PET Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada); Wilson, Alan A.; Stephenson, Karin A. [PET Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada); Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada); Mamo, David C. [PET Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada); Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada); Geriatric Mental Health Program, Centre for Addiction and Mental Health, 1001 Queen Street West, Toronto, Ontario, M6J 1H4 (Canada); Pollock, Bruce G.; Mulsant, Benoit H. [Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada); Geriatric Mental Health Program, Centre for Addiction and Mental Health, 1001 Queen Street West, Toronto, Ontario, M6J 1H4 (Canada); Yudin, Andrei K. [Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6 (Canada); Houle, Sylvain [PET Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada); Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada); Vasdev, Neil [PET Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada); Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada)], E-mail: neil.vasdev@camhpet.ca

    2009-04-15

    The radioligand 3-(4-(3-[{sup 18}F]fluoropropylthio)-1,2,5-thiadiazol-3-yl)-1-methyl-1,2,5, 6-tetrahydropyridine ([{sup 18}F]FP-TZTP) is an agonist with specificity towards subtype 2 of muscarinic acetylcholine (M2) receptors. It is currently the only radiotracer available for imaging M2 receptors in human subjects with positron emission tomography. The present study reports on an improved method for the synthesis of [{sup 18}F]FP-TZTP, automated using a GE TRACERlab{sup TM} FX{sub FN} radiosynthesis module. A key facet was the use of a new precursor, 3-(4-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)-1,2,5-thiadiazol-3-ylthio) propyl 4-methylbenzenesulfonate. The precursor was fluorinated via nucleophilic displacement of the tosyloxy group by potassium cryptand [{sup 18}F]fluoride (K[{sup 18}F]/K{sub 222}) in CH{sub 3}CN at 80 deg. C for 5 min, and purified by HPLC. Formulated [{sup 18}F]FP-TZTP was prepared in an uncorrected radiochemical yield of 29{+-}4%, with a specific activity of 138{+-}41 GBq/{mu}mol (3732{+-}1109 mCi/{mu}mol) at the end of synthesis (35 min; n=3). This methodology offers higher yields, faster synthesis times, an optimized precursor, and simpler automation than previously reported.

  11. ISOMP: An Instant Service-Orchestration Mobile M2M Platform

    Directory of Open Access Journals (Sweden)

    Cholhong Im

    2016-01-01

    Full Text Available Smartphones have greater computing power than ever before, providing convenient applications to improve our lives. In general, people find it difficult to locate suitable applications and implementing new applications often requires professional skills. In this paper, we propose a new service platform that facilitates the implementation of new applications by composing prebuilt components that provide the context information of mobile devices such as location and contacts. Our platform introduces an innovative concept named context collaboration, in which smartphones exchange context information with each other, which in turn is used to deduct useful inferences. The concept is realized by instant orchestration, which assembles some components and implements a composite component. The interactive communication interface helps a mobile device to communicate with other devices using open APIs, such as SOAP and HTTP (REST. The platform also works in heterogeneous environments, for example, between Android and iOS operating systems. Throughout the platform, mobile devices can act as smart M2M machines with context awareness, enabling intelligent tasks on behalf of users. Our platform will open up a new and innovative pathway for both enhanced mobile context awareness and M2M, which is expected to be a fundamental feature of the next generation of mobile devices.

  12. Some results on 4m2n designs with clear two-factor interaction components

    Institute of Scientific and Technical Information of China (English)

    ZHAO ShengLi; ZHANG RunChu; LIU MinQian

    2008-01-01

    Clear effects criterion is one of the important rules for selecting optimal fractional factorial designs, and it has become an active research issue in recent years.Tang et al. derived upper and lower bounds on the maximum number of clear two-factor interactions (2fi's) in 2n-(n-k)fractional factorial designs of resolutions Ⅲ and Ⅳ by constructing a 2n-(n-k) design for given k, which are only restricted for the symmetrical case. This paper proposes and studies the clear effects problem for the asymmetrical case. It improves the construction method of Tang et al. for 2n-(n-k)designs with resolution Ⅲ and derives the upper and lower bounds on the maximum number of clear two-factor interaction components(2fic's) in 4m2n designs with resolutions Ⅲ and Ⅳ. The lower bounds are achieved by constructing specific designs. Comparisons show that the number of clear 2fic's in the resulting design attains its maximum number in many cases, which reveals that the construction methods are satisfactory when they are used to construct 4m2n designs under the clear effects criterion.

  13. Machine to machine (M2M) technology in demand responsive commercial buildings

    Energy Technology Data Exchange (ETDEWEB)

    Watson, David S.; Piette, Mary Ann; Sezgen, Osman; Motegi, Naoya; ten Hope, Laurie

    2004-08-01

    Machine to Machine (M2M) is a term used to describe the technologies that enable computers, embedded processors, smart sensors, actuators and mobile devices to communicate with one another, take measurements and make decisions--often without human intervention. M2M technology was applied to five commercial buildings in a test. The goal was to reduce electric demand when a remote price signal rose above a predetermine price. In this system, a variable price signal was generated from a single source on the Internet and distributed using the meta-language, XML (Extensible Markup Language). Each of five commercial building sites monitored the common price signal and automatically shed site-specific electric loads when the price increased above predetermined thresholds. Other than price signal scheduling, which was set up in advance by the project researchers, the system was designed to operate without human intervention during the two-week test period. Although the buildings responded to the same price signal, the communication infrastructures used at each building were substantially different. This study provides an overview of the technologies used at each building site, the price generator/server, and each link in between. Network architecture, security, data visualization and site-specific system features are characterized. The results of the test are discussed, including: functionality at each site, measurement and verification techniques, and feedback from energy managers and building operators. Lessons learned from the test and potential implications for widespread rollout are provided.

  14. Mid-infrared imaging of the bipolar planetary nebula M2-9 from SOFIA

    Energy Technology Data Exchange (ETDEWEB)

    Werner, M. W.; Sahai, R.; Davis, J.; Livingston, J. [Jet Propulsion Laboratory, California Institute of Technology, 4800 Oak Grove Drive, Pasadena, CA 91107 (United States); Lykou, F. [Institute for Astronomy, University of Vienna, Turkenschanzstrasse 17, A-1180, Vienna (Austria); DE Buizer, J. [USRA SOFIA Science Center, M/S 211-3, NASA Ames Research Center, Moffett Field, CA 94035 (United States); Morris, M. R. [Division of Astronomy, P.O. Box 951547, UCLA, Los Angeles, CA 90095 (United States); Keller, L. [Department of Physics, Ithaca College, Ithaca, NY 14850 (United States); Adams, J.; Gull, G.; Henderson, C.; Herter, T.; Schoenwald, J., E-mail: Michael.W.Werner@jpl.nasa.gov [Department of Astronomy, Cornell University, Ithaca, NY 14853 (United States)

    2014-01-10

    We have imaged the bipolar planetary nebula M2-9 using SOFIA's FORCAST instrument in six wavelength bands between 6.6 and 37.1 μm. A bright central point source, unresolved with SOFIA's ∼4''-5'' beam, is seen at each wavelength, and the extended bipolar lobes are clearly seen at 19.7 μm and beyond. The photometry between 10 and 25 μm is well fit by the emission predicted from a stratified disk seen at large inclination, as has been proposed for this source by Lykou et al. and by Smith and Gehrz. The principal new results in this paper relate to the distribution and properties of the dust that emits the infrared radiation. In particular, a considerable fraction of this material is spread uniformly through the lobes, although the dust density does increase at the sharp outer edge seen in higher resolution optical images of M2-9. The dust grain population in the lobes shows that small (<0.1 μm) and large (>1 μm) particles appear to be present in roughly equal amounts by mass. We suggest that collisional processing within the bipolar outflow plays an important role in establishing the particle size distribution.

  15. DAMPAK KETIDAKSTABILAN NILAI TUKAR RUPIAH TERHADAP PERMINTAAN UANG M2 DI INDONESIA

    Directory of Open Access Journals (Sweden)

    Etty Puji Lestari

    2008-12-01

    Full Text Available This article attempts to estimate demand for M2 money in Indonesia using time series non-stationary technique in 1997.1 - 2006.4. There are four methods are used in research, first, VAR estimation used to forecast model which have interaction of data time series. Second, function impulse response to see response from every variable to structural innovation of the other variables at the same time. Third, variance decomposition to know dissociating variation change of shock from each variable to other variables in model. Fourth method, ADL ECM to see long-range adjustment in variable, before and after addition of variable. The result, there are non-stationary condition in the time series data in the research. Result of VAR estimation show that there is no causality relation two ways among fifth of variable. From impulse, response known that response of M2 variable to other variable very fluctuative but finally the condition will return to stabilize.

  16. Mid-Infrared Imaging of the Bipolar Planetary Nebula M2-9 from SOFIA

    CERN Document Server

    Werner, M W; Davis, J; Livingston, J; Lykou, F; de Buizer, J; Morris, M R; Keller, L; Adams, J; Gull, G; Henderson, C; Herter, T; Schoenwald, J

    2013-01-01

    We have imaged the bipolar planetary nebula M2-9 using SOFIA's FORCAST instrument in six wavelength bands between 6.6 and 37.1 $\\mu m$. A bright central point source, unresolved with SOFIA's $\\sim$ 4${''}$-to-5${''}$ beam, is seen at each wavelength, and the extended bipolar lobes are clearly seen at 19.7 $\\mu m$ and beyond. The photometry between 10 and 25 $\\mu m$ is well fit by the emission predicted from a stratified disk seen at large inclination, as has been proposed for this source by Lykou et al and by Smith and Gehrz. The principal new results in this paper relate to the distribution and properties of the dust that emits the infrared radiation. In particular, a considerable fraction of this material is spread uniformly through the lobes, although the dust density does increase at the sharp outer edge seen in higher resolution optical images of M2-9. The dust grain population in the lobes shows that small ($$ 1 $\\mu m$) particles appear to be present in roughly equal amounts by mass. We suggest that co...

  17. A Rare Cytogenetic Presentation of Acute Myeloid Leukemia (AML-M2

    Directory of Open Access Journals (Sweden)

    Hanumanthappa Vijay Raghavendra

    2012-12-01

    Full Text Available Acute myeloid leukemia (AML with t(8;21(q22;q22 generating the AML1/ETO fusion gene on 8q22 is a distinct type of AML t(8;21 category (WHO/AML-M2 (FAB, generally associated with a favourable prognosis. Variant additional chromosomal abnormalities are frequently reported. We report three adult cases of this category with unusual karyotype. Bone marrow cytogenetics of case no. 1: 45,X,-Y, t(8;21(q13;q22 with a novel breakpoint of chromosome 8 at (q13. Case no. 2: 46,X,t(X;2(q22;q37,t(3;7(q21;q36,t(5;14(p15;q11,del(8(q22 a complex rearrangement without the involvement of chromosome 21. Case no. 3: 49,XX,+5, t(8;21(q22;q22, +16, +der(21t(8;21(q22;q22 with additional der(21. Endometrial in this case which was positive for myeloperoxidase (MPO and CD117 conforming the AML infiltration. All are morphologically AML with t(8;21. Relevant literature in cytogenetic of AML-M2 is reviewed. The molecular mechanism involved in unusual rearrangements and clinical significance of them are subjected for further studies

  18. Anti-Inflammatory Strategy for M2 Microglial Polarization Using Retinoic Acid-Loaded Nanoparticles

    Directory of Open Access Journals (Sweden)

    Marta Machado-Pereira

    2017-01-01

    Full Text Available Inflammatory mechanisms triggered by microglial cells are involved in the pathophysiology of several brain disorders, hindering repair. Herein, we propose the use of retinoic acid-loaded polymeric nanoparticles (RA-NP as a means to modulate microglia response towards an anti-inflammatory and neuroprotective phenotype (M2. RA-NP were first confirmed to be internalized by N9 microglial cells; nanoparticles did not affect cell survival at concentrations below 100 μg/mL. Then, immunocytochemical studies were performed to assess the expression of pro- and anti-inflammatory mediators. Our results show that RA-NP inhibited LPS-induced release of nitric oxide and the expression of inducible nitric oxide synthase and promoted arginase-1 and interleukin-4 production. Additionally, RA-NP induced a ramified microglia morphology (indicative of M2 state, promoting tissue viability, particularly neuronal survival, and restored the expression of postsynaptic protein-95 in organotypic hippocampal slice cultures exposed to an inflammatory challenge. RA-NP also proved to be more efficient than the free equivalent RA concentration. Altogether, our data indicate that RA-NP may be envisioned as a promising therapeutic agent for brain inflammatory diseases.

  19. Allosteric regulation of pyruvate kinase M2 isozyme involves a cysteine residue in the intersubunit contact.

    Science.gov (United States)

    Ikeda, Y; Noguchi, T

    1998-05-15

    Pyruvate kinase M2 isozyme mutants with amino acid substitutions in the subunit interface were prepared and characterized. The substitutions were made in the allosteric M2 isozyme by the corresponding residues of the nonallosteric M1 isozyme to identify the residue involved in the allosteric effects. The replacement of Cys-423 by Leu led to substantial loss of both homotropic and heterotropic allosteric effects while the substitutions at Phe-389, Arg-398, Ala-401, Pro-402, Thr-408, and Ile-427 did not. The altered kinetic properties of the Cys-423-substituted mutant resulted from the shift of the allosteric transition toward the active R-state since the mutant exhibits the allosteric properties in the presence of an allosteric inhibitor, L-phenylalanine. The inverse correlation between the hydrophobicity of residue 423 and the extent of stabilization of the R-state was found by analysis of mutants with un-ionizable amino acids at position 423. Furthermore, the modification of Cys-423 with methyl methanethiosulfonate led to a shift of the allosteric transition toward the R-state, probably the result of increased hydrophobicity of the residue. These results suggest that Cys-423 is involved in the allosteric regulation of the enzyme through hydrophobic interactions.

  20. Supersymmetric M2-branes with Englert fluxes, and the simple group PSL(2, 7)

    Energy Technology Data Exchange (ETDEWEB)

    Fre, Pietro [Dipartimento di Fisica, Universita di Torino (Italy); INFN - Sezione di Torino (Italy); National Research Nuclear University MEPhI, (Moscow Engineering Physics Institute), Moscow (Russian Federation)

    2016-06-15

    A new class is introduced of M2-branes solutions of d=11 supergravity that include internal fluxes obeying Englert equation in 7-dimensions. A simple criterion for the existence of Killing spinors in such backgrounds is established. Englert equation is viewed as the generalization to d=7 of Beltrami equation defined in d=3 and it is treated accordingly. All 2-brane solutions of minimal d=7 supergravity can be uplifted to d=11 and have N≥4 supersymmetry. It is shown that the simple group PSL(2,7) is crystallographic in d=7 having an integral action on the A7 root lattice. By means of this point-group and of the T{sup 7} torus obtained quotiening R{sup 7} with the A7 root lattice we were able to construct new M2 branes with Englert fluxes and N≤4. In particular we exhibit here an N=1 solution depending on 4-parameters and admitting a large non abelian discrete symmetry, namely G{sub 21}≡

  1. Exact relations between M2-brane theories with and without Orientifolds

    CERN Document Server

    Honda, Masazumi

    2015-01-01

    We study partition functions of low-energy effective theories of M2-branes, whose type IIB brane constructions include orientifolds. We mainly focus on circular quiver superconformal Chern-Simons theory on S^3, whose gauge group is O(2N+1)x USp(2N)x ... x O(2N+1)x USp(2N). This theory is a natural generalization of N=5 ABJM theory with the gauge group O(2N+1)_{2k}x USp(2N)_{-k}. We find that the partition function of this type of theory has a simple relation to the one of the M2-brane theories without the orientifolds, whose gauge group is U(N)x ... x U(N). By using this relation, we determine an exact form of the grand partition function of the O(2N+1)_2 x USp(2N)_{-1} ABJM theory, where its supersymmetry is expected to enhance to N=6. As another interesting application, we discuss that our result gives a natural physical interpretation of a relation between grand partition functions of the U(N+1)_4 x U(N)_{-4} ABJ theory and U(N)_2 x U(N)_{-2} ABJM theory, recently conjectured by Grassi-Hatsuda-Marino. We a...

  2. Decisive disappearance search at high Δ m2 with monoenergetic muon neutrinos

    Science.gov (United States)

    Axani, S.; Collin, G.; Conrad, J. M.; Shaevitz, M. H.; Spitz, J.; Wongjirad, T.

    2015-11-01

    "KPipe" is a proposed experiment which will study muon neutrino disappearance for a sensitive test of the Δ m2˜1 eV2 anomalies, possibly indicative of one or more sterile neutrinos. The experiment is to be located at the J-PARC Materials and Life Science Experimental Facility's spallation neutron source, which represents the world's most intense source of charged kaon decay-at-rest monoenergetic (236 MeV) muon neutrinos. The detector vessel, designed to measure the charged-current interactions of these neutrinos, will be 3 m in diameter and 120 m long, extending radially at a distance of 32 to 152 m from the source. This design allows a sensitive search for νμ disappearance associated with currently favored light sterile neutrino models and features the ability to reconstruct the neutrino oscillation wave within a single, extended detector. The required detector design, technology, and costs are modest. The KPipe measurements will be robust since they depend on a known energy neutrino source with low expected backgrounds. Further, since the measurements rely only on the measured rate of detected events as a function of distance, with no required knowledge of the initial flux and neutrino interaction cross section, the results will be largely free of systematic errors. The experimental sensitivity to oscillations, based on a shape-only analysis of the L /E distribution, will extend an order of magnitude beyond present experimental limits in the relevant high-Δ m2 parameter space.

  3. Meteorological profiling of the lower troposphere using the research UAV "M2AV Carolo"

    Directory of Open Access Journals (Sweden)

    F. Beyrich

    2010-11-01

    Full Text Available Vertical profiles of temperature, humidity and wind up to a height of 1500 m a.g.l. (above ground level were measured with the automatically operating small unmanned research aircraft M2AV (Meteorological Mini Aerial Vehicle during the LITFASS-2009 (LIndenberg-To-Falkenberg: Aircraft, Scintillometer and large-eddy Simulation experiment. The campaign took place in July 2009 over the heterogeneous landscape around the Meteorologcial Observatory Lindenberg – Richard-Aßmann-Observatory in the eastern part of Germany. Due to a high vertical resolution of about 10 cm the M2AV data show details of the turbulent structure of the atmospheric boundary layer (ABL. One profile takes about 10–15 min allowing for a continuous monitoring of certain phases of ABL development by successive ascents and descents during one flight (50–60 min duration. Two case studies of measurements performed during the morning and evening ABL transition periods are discussed in detail. Comparison of the aircraft-based temperature, humidity and wind profiles with tower, sodar/RASS, wind profiler/RASS, radiosoundings and microwave radiometer profiler measurements show good agreement taking into account the different sampling strategies of these measurement systems.

  4. Myeloid PTEN deficiency protects livers from ischemia reperfusion injury by facilitating M2 macrophage differentiation.

    Science.gov (United States)

    Yue, Shi; Rao, Jianhua; Zhu, Jianjun; Busuttil, Ronald W; Kupiec-Weglinski, Jerzy W; Lu, Ling; Wang, Xuehao; Zhai, Yuan

    2014-06-01

    Although the role of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in regulating cell proliferation is well established, its function in immune responses remains to be fully appreciated. In the current study, we analyzed myeloid-specific PTEN function in regulating tissue inflammatory immune response in a murine liver partial warm ischemia model. Myeloid-specific PTEN knockout (KO) resulted in liver protection from ischemia reperfusion injury (IRI) by deviating the local innate immune response against ischemia reperfusion toward the regulatory type: expression of proinflammatory genes was selectively decreased and anti-inflammatory IL-10 was simultaneously increased in ischemia reperfusion livers of PTEN KO mice compared with those of wild-type (WT) mice. PI3K inhibitor and IL-10-neutralizing Abs, but not exogenous LPS, recreated liver IRI in these KO mice. At the cellular level, Kupffer cells and peritoneal macrophages isolated from KO mice expressed higher levels of M2 markers and produced lower TNF-α and higher IL-10 in response to TLR ligands than did their WT counterparts. They had enhanced Stat3- and Stat6-signaling pathway activation, but diminished Stat1-signaling pathway activation, in response to TLR4 stimulation. Inactivation of Kupffer cells by gadolinium chloride enhanced proinflammatory immune activation and increased IRI in livers of myeloid PTEN KO mice. Thus, myeloid PTEN deficiency protects livers from IRI by facilitating M2 macrophage differentiation.

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

    Science.gov (United States)

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

    2016-01-01

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

  6. Thermal Decomposition of Anhydrous Alkali Metal Dodecaborates M2B12H12 (M = Li, Na, K

    Directory of Open Access Journals (Sweden)

    Liqing He

    2015-11-01

    Full Text Available Metal dodecaborates M2/nB12H12 are regarded as the dehydrogenation intermediates of metal borohydrides M(BH4n that are expected to be high density hydrogen storage materials. In this work, thermal decomposition processes of anhydrous alkali metal dodecaborates M2B12H12 (M = Li, Na, K synthesized by sintering of MBH4 (M = Li, Na, K and B10H14 have been systematically investigated in order to understand its role in the dehydrogenation of M(BH4n. Thermal decomposition of M2B12H12 indicates multistep pathways accompanying the formation of H-deficient monomers M2B12H12−x containing the icosahedral B12 skeletons and is followed by the formation of (M2B12Hzn polymers. The decomposition behaviors are different with the in situ formed M2B12H12 during the dehydrogenation of metal borohydrides.

  7. Asscessment of the clinical value of CK-M2 and oligosaccharide protein inserum from patients with gastric carcinoma

    Institute of Scientific and Technical Information of China (English)

    Gui Lan Zhao; Jie Lin; Shu You Peng; Qi Yun Li; Fan Zhou; Xian Sheng Chen; Xin You Xie; Yi Xiong Zheng

    2000-01-01

    AIM To evaluate the clinical value of creatine kinase macroisoenzyme type 2 (CK-M2) and oligosaccharideprotein (OP) in serum from patients with gastric carcinoma (GC).METHODS Serum level of CK-M2 was detected by agar gel electrophoresis. OP concentration was measuredby an enzyme immunoassay.RESULTS Serum levels of CK-M2 and OP in 57 cases of GC were significantly higher than those in 51 caseswith gastric precancerous lesion and 28 controls. The diagnostic sensitivity and specificity for GC with CK-M2 was 56.10% and 98.63% respectively. CK-M2 and OP were not associated with histologic type and degreeof differentiation.CONCLUSION These results suggest that CK-M2 may serve as a marker to diagnose GC, and the specificityis higher, whereas OP is not more significant for GC diagnosis, but it could be a useful indicator forevaluation the status of body immune.

  8. D2M2 Dredged-Material Disposal Management Model. User’s Manual

    Science.gov (United States)

    1984-07-01

    small disposal system is shown as Fig. 2. Nodes I and 2 represent the Pedricktown North disposal site, nodes 3 and 4 represent the Pedrick - town...and transferred to the Pedrick - town North site is represented by flow in the arc originating at node 4 and terminating in node 2. The arc originating...material deposited in the Pedrick - town North site in all periods prior to the current period [S(1, T - 1) of Eq. 2]. The storage arc originating at node 2

  9. Ramsey Number of K2,s+1 vs. K1,n%关于K2,s+1 VS,K1,n的Ramsey数

    Institute of Scientific and Technical Information of China (English)

    秦大伟; 沈大鹏

    2007-01-01

    It is shown that the Ramsey number r(K2,s+1, K1,n) ≤ n + √sn+ (s + 3)/2 + o(1) for large n, and r(K2,s+1, K1,n)∈{(q-1)2/s+1,-(q-1)2/s+2},wheren: (q-1)2/s-q+2 and q is a prime power such that s|(q - 1).

  10. The SphKs/S1P/S1PR1 axis in immunity and cancer: more ore to be mined.

    Science.gov (United States)

    Jin, Lei; Liu, Wei-Ren; Tian, Meng-Xin; Fan, Jia; Shi, Ying-Hong

    2016-04-29

    Over the past two decades, huge amounts of research were launched to understand the functions of sphingosine. Many pathways were uncovered that convey the relative functions of biomacromolecules. In this review, we discuss the recent advances of the role of the SphKs/S1P/S1PR1 axis in immunity and cancer. Finally, we investigate the therapeutic potential of new drugs that target S1P signaling in cancer therapy.

  11. Subcellular redistribution of m2 muscarinic acetylcholine receptors in striatal interneurons in vivo after acute cholinergic stimulation.

    Science.gov (United States)

    Bernard, V; Laribi, O; Levey, A I; Bloch, B

    1998-12-01

    The purpose of our work was to investigate how the cholinergic environment influences the targeting and the intracellular trafficking of the muscarinic receptor m2 (m2R) in vivo. To address this question, we have used immunohistochemical approaches at light and electron microscopic levels to detect the m2R in control rats and rats treated with muscarinic receptor agonists. In control animals, m2Rs were located mostly at postsynaptic sites at the plasma membrane of perikarya and dendrites of cholinergic and NPY-somatostatin interneurons as autoreceptors and heteroreceptors, respectively. Presynaptic receptors were also detected in boutons. The m2Rs were usually detected at extrasynaptic sites, but they could be found rarely in association with symmetrical synapses, suggesting that the cholinergic transmission mediated by m2R occurs via synaptic and nonsynaptic mechanisms. The stimulation of muscarinic receptors with oxotremorine provoked a dramatic alteration of m2R compartmentalization, including endocytosis with a decrease of the density of m2R at the membrane (-63%) and an increase of those associated with endosomes (+86%) in perikarya. The very strong increase of m2R associated with multivesicular bodies (+732%) suggests that oxotremorine activated degradation. The slight increase in the Golgi apparatus (+26%) suggests that the m2R stimulation had an effect on the maturation of m2R. The substance P receptor located at the membrane of the same neurons was unaffected by oxotremorine. Our data demonstrate that cholinergic stimulation dramatically influences the subcellular distribution of m2R in striatal interneurons in vivo. These events may have key roles in controlling abundance and availability of muscarinic receptors via regulation of receptor endocytosis, degradation, and/or neosynthesis. Further, the control of muscarinic receptor trafficking may influence the activity of striatal interneurons, including neurotransmitter release and/or electric activity.

  12. Hypothalamic S1P/S1PR1 axis controls energy homeostasis in Middle-Aged Rodents: the reversal effects of physical exercise

    Science.gov (United States)

    Silva, Vagner Ramon Rodrigues; Katashima, Carlos Kiyoshi; Bueno Silva, Carla G.; Lenhare, Luciene; Micheletti, Thayana Oliveira; Camargo, Rafael Ludemann; Ghezzi, Ana Carolina; Camargo, Juliana Alves; Assis, Alexandre Moura; Tobar, Natalia; Morari, Joseane; Razolli, Daniela S.; Moura, Leandro Pereira; Pauli, José Rodrigo; Cintra, Dennys Esper; Velloso, Lício Augusto; Saad, Mario J.A; Ropelle, Eduardo Rochete

    2017-01-01

    Recently, we demonstrated that the hypothalamic S1PR1/STAT3 axis plays a critical role in the control of food consumption and energy expenditure in rodents. Here, we found that reduction of hypothalamic S1PR1 expression occurs in an age-dependent manner, and was associated with defective thermogenic signaling and weight gain. To address the physiological relevance of these findings, we investigated the effects of chronic and acute exercise on the hypothalamic S1PR1/STAT3 axis. Chronic exercise increased S1PR1 expression and STAT3 phosphorylation in the hypothalamus, restoring the anorexigenic and thermogenic signals in middle-aged mice. Acutely, exercise increased sphingosine-1-phosphate (S1P) levels in the cerebrospinal fluid (CSF) of young rats, whereas the administration of CSF from exercised young rats into the hypothalamus of middle-aged rats at rest was sufficient to reduce the food intake. Finally, the intracerebroventricular (ICV) administration of S1PR1 activators, including the bioactive lipid molecule S1P, and pharmacological S1PR1 activator, SEW2871, induced a potent STAT3 phosphorylation and anorexigenic response in middle-aged rats. Overall, these results suggest that hypothalamic S1PR1 is important for the maintenance of energy balance and provide new insights into the mechanism by which exercise controls the anorexigenic and thermogenic signals in the central nervous system during the aging process. PMID:28039439

  13. Impaired atrial M(2)-cholinoceptor function in obesity-related hypertension.

    Science.gov (United States)

    Pelat, M; Verwaerde, P; Merial, C; Galitzky, J; Berlan, M; Montastruc, J L; Senard, J M

    1999-11-01

    The aim of this study was to investigate the activity of the parasympathetic limb of the baroreflex arch in a canine model of obesity-related hypertension. Twelve male beagle dogs were randomized into 2 groups. Six dogs were fed with normal canine food and 6 were submitted to a 10-week high-fat diet (HFD). We have evaluated the consequences of HFD on heart rate (HR) and blood pressure (BP) circadian cycles and methylscopolamine dose-response curves. Binding of [(3)H]-AF-DX 384 and adenylyl cyclase activity were investigated to determine the density and functionality of M(2)-cholinoceptors on right atrial membranes from control and HFD dogs. HFD induced a significant increase in body weight (15+/-1 vs 12+/-1 kg), systolic BP (161+/-5 vs 145+/-4 mm Hg), diastolic BP (92+/-3 vs 79+/-2 mm Hg), and HR (96+/-4 vs 81+/-3 bpm). Circadian rhythms of HR and BP observed in the baseline period were abolished after 9 weeks of HFD. After propranolol (1 mg/kg) pretreatment, the dose of methylscopolamine able to induce 50% maximum tachycardia was significantly increased after 9 weeks of HFD (7.4+/-0.3 vs 4.7+/-0.1 microg/kg). In the control group, the experimental period failed to modify these parameters. The numbers of M(2)-cholinoceptors measured in right atrial membranes were significantly lower in HFD than in control groups (54+/-6 vs 27+/-6 fmol/mg protein). The ability of carbachol to inhibit isoproterenol-stimulated adenylyl cyclase activity was significantly lower in HFD than in control groups (IC(50)=47+/-12 vs 6.4+/-1.4 micromol/L). However, the basal activity of adenylyl cyclase was unchanged by HFD. HFD decreases M(2)-cholinoceptor number and function in cardiomyocytes. This could explain the abolition of circadian rhythm of HR and the changes in chronotropic effect brought about by methylscopolamine.

  14. The Creation and Destruction of Hf-178m2 Isomer by Neutron Interaction

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, Hsiao-Hua [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); TechSource, Inc. Los Alamos, NM (United States); Talbert, Willard L. [TechSource, Inc. Los Alamos, NM (United States); Ward, Tom [TechSource, Inc. Los Alamos, NM (United States)

    2017-03-06

    The property of the isomer state in 178m2Hf was an interesting topic in nuclear structure studies during the time period 1970 to 1980. The state at 2.446 MeV with spin and parity Kπ = 16+, has a half-life of 31 years. The isomer is described as a four-quasi-particle state. The K forbidden deexcitatiion by gamma emission is the reason for long half-life. During 1980, the isomer became a troublesome issue for radiation safety workers, because this isomer can also be produced in the first wall of a fussion reactor containing tungsten and also in a tungsten beam stop of a high-energy accelerator.

  15. Spaceflight Effects on Hemopoiesis of Lower Vertebrates Flown on Foton-M2

    Science.gov (United States)

    Domaratskaya, E. I.; Payushina, O. V.; Butorina, M. N.; Nikonova, T. M.; Grigorian, E. N.; Mitashov, V. I.; Tairbekov, M. G.; Almeida, E.; Khrushchov, N. G.

    2006-01-01

    Intact and operated newts Pleumdeles waltl flown on Foton-M2 for 16 days were used to study the effects of spaceflight as well as tail amputation and lensectomy on their hemopoiesis. The flight did not produce noticeable changes in the peripheral blood of nonoperated newts. However, in operated animals, the number of lymphocytes increased whereas that of neutrophils decreased. There were no morphological differences in hemopoietic organs (liver and spleen) between flown non-operated and operated animals or their controls. However, in both non-operated and operated newts the liver weight and the number of hemopoietic cells in it increased. In contrast to nonoperated newts, space-flown mammals typically showed significant changes in blood cell counts. Experiments with BrdU incorporation revealed labeled cells in the hemopoietic area of the liver as well as in blood and spleen. This observation gives evidence that the BrdU label can be used to study proliferation of hemopoietic cells.

  16. Energies and E1, M2 transition rates for Mo XXX

    CERN Document Server

    Hu, Feng; Mei, Maofei; Yang, Jiamin

    2016-01-01

    Based on relativistic wavefunctions from multiconfigurational Dirac-Hartree-Fock (MCDHF) and configuration interaction calculations, energy levels, radiative rates, and wavelengths are evaluated for all levels of 3s$^2$3p, 3s3p$^2$, 3s$^2$3d, 3p$^3$, 3s3p3d, 3p$^2$3d and 3s3d$^2$ configurations of Al-like Molybdenum ion (Mo XXX). Transition probabilities are reported for E1 and M2 transitions from the ground level. The valence-valence and core-valence correlation effects are accounted for in a systematic way. Breit interactions and quantum electrodynamics effects are estimated in subsequent relativistic configuration interaction calculations. Comparisons are made with the available data in the literature and good agreement has been found which confirms the reliability of our results.

  17. Dy$^{3+}$-activated M$_2$SiO$_4$ (M $=$ Ba, Mg, Sr)-type phosphors

    Indian Academy of Sciences (India)

    ESRA ÖZTÜRK; ERKUL KARACAOGLU

    2017-02-01

    The alkaline orthosilicates of M$_2$SiO$_4$ (M $=$ Ba, Mg, Sr) activated with Dy$^{3+}$ and co-doped with Ho$^{3+}$ are prepared through conventional solid-state method, i.e., mixing and grinding of solid form precursors followedby high-temperature heat treatments of several hours in furnaces, generally under open atmosphere and investigated by X-ray diffraction (XRD) to get phase properties and photoluminescence (PL) analysis to get luminescenceproperties. The thermal behaviours of well-mixed samples were determined by differential thermal analysis (DTA)/thermogravimetry (TG). The PL spectra show that the 478 and 572nm maximum emission bands are attributed, respectively, to ${}^{4}$F$_{9/2}$ $\\to$ ${}^{6}$H$_{15/2}$ and ${}^{4}$F$_{9/2}$ $\\to$ ${}^{6}$H$_{13/2}$ transitions of Dy$^{3+}$ ions.

  18. Thermoelectric Performance of the MXenes M2CO2 (M = Ti, Zr, or Hf)

    KAUST Repository

    Gandi, Appala

    2016-02-21

    We present the first report in which the thermoelectric properties of two-dimensional MXenes are calculated by considering both the electron and phonon transport. Specifically, we solve the transport equations of the electrons and phonons for three MXenes, M2CO2, where M = Ti, Zr, or Hf, in order to evaluate the effect of the metal M on the thermoelectric performance. The lattice contribution to the thermal conductivity, obtained from the phonon life times, is found to be lowest in Ti2CO2 and highest in Hf2CO2 in the temperature range from 300 K to 700 K. The highest figure of merit is predicted for Ti2CO2 . The heavy mass of the electrons due to flat conduction bands results in a larger thermopower in the case of n-doping in these compounds.

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

    Science.gov (United States)

    1963-01-01

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

  20. Spaceflight Effects on Hemopoiesis of Lower Vertebrates Flown on Foton-M2

    Science.gov (United States)

    Domaratskaya, E. I.; Payushina, O. V.; Butorina, M. N.; Nikonova, T. M.; Grigorian, E. N.; Mitashov, V. I.; Tairbekov, M. G.; Almeida, E.; Khrushchov, N. G.

    2006-01-01

    Intact and operated newts Pleumdeles waltl flown on Foton-M2 for 16 days were used to study the effects of spaceflight as well as tail amputation and lensectomy on their hemopoiesis. The flight did not produce noticeable changes in the peripheral blood of nonoperated newts. However, in operated animals, the number of lymphocytes increased whereas that of neutrophils decreased. There were no morphological differences in hemopoietic organs (liver and spleen) between flown non-operated and operated animals or their controls. However, in both non-operated and operated newts the liver weight and the number of hemopoietic cells in it increased. In contrast to nonoperated newts, space-flown mammals typically showed significant changes in blood cell counts. Experiments with BrdU incorporation revealed labeled cells in the hemopoietic area of the liver as well as in blood and spleen. This observation gives evidence that the BrdU label can be used to study proliferation of hemopoietic cells.

  1. Carrier Current Line Systems Technologies in M2M Architecture for Wireless Communication

    Directory of Open Access Journals (Sweden)

    Hua-Ching Chen

    2016-01-01

    Full Text Available This paper investigates the Carrier Current Line Systems (CCLS technologies of Machine to Machine (M2M architecture which applied for mobile station coverage working with metro, high speed railway, and subway such as analysis for public transport of an indoor transition system. It is based on the theory and practical engineering principle which provide guidelines and formulas for link budget design to help designers fully control and analyze the single output power of uplink and downlink between Fiber Repeaters (FR and mobile station as well as base station. Finally, the results of this leakage cable system are successfully applied to indoor coverage design for metro rapid transit system which are easily installed cellular over fiber solutions for WCDMA/LTE access is becoming Ubiquitous Network to Internet of Thing (IOT real case hierarchy of telecommunication.

  2. Large-scale, realistic laboratory modeling of M2 internal tide generation at the Luzon Strait

    CERN Document Server

    Mercier, Matthieu J; Helfrich, Karl; Sommeria, Joël; Viboud, Samuel; Didelle, Henri; Saidi, Sasan; Dauxois, Thierry; Peacock, Thomas

    2015-01-01

    The complex double-ridge system in the Luzon Strait in the South China Sea (SCS) is one of the strongest sources of internal tides in the oceans, associated with which are some of the largest amplitude internal solitary waves on record. An issue of debate, however, has been the specific nature of their generation mechanism. To provide insight, we present the results of a large-scale laboratory experiment performed at the Coriolis platform. The experiment was carefully designed so that the relevant dimensionless parameters, which include the excursion parameter, criticality, Rossby, and Froude numbers, closely matched the ocean scenario. The results advocate that a broad and coherent weakly nonlinear, three-dimensional, M2 internal tide that is shaped by the overall geometry of the double-ridge system is radiated into the South China Sea and subsequently steepens, as opposed to being generated by a particular feature or localized region within the ridge system.

  3. Nonmetabolic functions of pyruvate kinase isoform M2 in controlling cell cycle progression and tumorigenesis

    Institute of Scientific and Technical Information of China (English)

    Zhimin Lu

    2012-01-01

    Pyruvate kinase catalyzes the rate-limiting final step of glycolysis,generating adenosine triphosphate (ATP) and pyruvate.The M2 tumor-specific isoform of pyruvate kinase (PKM2) promotes glucose uptake and lactate production in the presence of oxygen,known as aerobic glycolysis or the Warburg effect.As recently reported in Nature,PKM2,besides its metabolic function,has a nonmetabolic function in the direct control of cell cycle progression by activating β-catenin and inducing expression of the β-catenin downstream gene CCND1 (encoding for cyclin D1).This nonmetabolic function of PKM2 is essential for epidermal growth factor receptor (EGFR) activation-induced tumorigenesis.

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

    Science.gov (United States)

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

    2013-05-01

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

  5. A Decisive Disappearance Search at High-$\\Delta m^2$ with Monoenergetic Muon Neutrinos

    CERN Document Server

    Axani, S; Conrad, JM; Shaevitz, MH; Spitz, J; Wongjirad, T

    2015-01-01

    "KPipe" is a proposed experiment which will study muon neutrino disappearance for a sensitive test of the $\\Delta m^2\\sim1 \\mathrm{eV}^2$ anomalies, possibly indicative of one or more sterile neutrinos. The experiment is to be located at the J-PARC Materials and Life Science Facility's spallation neutron source, which represents the world's most intense source of charged kaon decay-at-rest monoenergetic (236 MeV) muon neutrinos. The detector vessel, designed to measure the charged current interactions of these neutrinos, will be 3 m in diameter and 120 m long, extending radially at a distance of 32 m to 152 m from the source. This design allows a sensitive search for $\

  6. Structure and Abrasive Wear of Composite HSS M2/WC Coating

    Directory of Open Access Journals (Sweden)

    S. F. Gnyusov

    2012-01-01

    Full Text Available Features of phase-structure formation and abrasive wear resistance of composite coatings “WC-M2 steel” worn against tungsten monocarbide have been investigated. It was established that adding 20 wt.% WC to the deposited powder mixture leads to the increase in M6C carbide content. These carbides show a multimodal size distribution consisting of ~5.9 μm eutectic carbides along the grain boundaries, ~0.25 μm carbides dispersed inside the grains. Also a greater amount of metastable austenite (~88 vol.% is found. The high abrasive wear resistance of these coatings is provided by γ→α′-martensitic transformation and multimodal size distribution of reinforcing particles.

  7. 一种面向物联网的M2M通信解决方案%A M2M Communication Solution for the Internet of Things

    Institute of Scientific and Technical Information of China (English)

    王群; 钱焕延

    2012-01-01

    On the basis of analysis of the M2M system architecture and working principle,using the advantages of NAT traversal technology for IoT,this paper proposed a M2M communication solution with user authentication function based on STUN and STUNT agreement.The experiments showed that communication and management between M2M nodes in the IoT could be achieved simply by embedding the STUN Client and the STUNT Client module into M2M devices without changing the original network structure.%在分析了M2M系统体系结构和工作原理的基础上,利用NAT穿越技术在物联网中的应用优势,提出了一种基于STUN和STUNT协议的、具有用户身份认证功能的M2M通信方案.经过实验测试,该方案不需要改变原有网络结构,只需要在M2M设备中嵌入STUN Client和STUNT Client模块,就能够实现物联网中不同M2M节点之间的通信与管理.

  8. The navigational experiments on microgravitational space platform “FOTON-M2

    Science.gov (United States)

    Belokonov, Igor V.; Semkin, Nikolay D.

    2009-06-01

    This paper presents the review of results of the navigating experiments which have been carried out during flight of microgravitational space platform (MSP) Foton-M2 in May-June 2005. The brief characteristic of the created MIRAGE-M equipment consisting from magnitometric system and satellite radionavigation receiver is given. The measurements have allowed to restore unguided MSP movement and to estimate a level of microaccelerations (microgravitations) onboard during flight, and have provided precision time-position binding of the research experiments. The data from the equipments transmitted on the telemetering channel have allowed testing the information technologies of virtual support of experiments in space. Flight testing of the equipment has allowed make a conclusion on usefulness of accommodation onboard the small-sized auxiliary navigating system focused for work with users of research experiments. The experiments on MSP Foton-M2 are the development of experiments with MIRAGE equipment carried out in 1999 during flight time of MSP Foton-12 [N.D. Semkin, V.V. Ivanov, V.I. Abrushkin, V.L. Balakin, I.V. Belokonov, K.E. Voronov, The experiments with magnetic fields formed by technical equipment inside Foton-12 spacecraft: the results of the MIRAGE experiments, in: Proceedings of International Conference "Scientific and Technological Experiments on Russian Foton/Bion Recoverable Satellites: Results, Problems and Outlooks", 25-30 June 2000, pp. 116-122; V.L. Balakin, I.V. Belokonov, V.V. Ivanov, "Determination of motion of spacecraft Foton-12 as a result of magnetic fields measurement in MIRAGE experiment", pp. 231-238 (published in the same place)]. Paper is executed within the framework of the grant of the Russian Fund of Fundamental Researches 06-08-00244.

  9. Inverse agonist activity of pirenzepine at M2 muscarinic acetylcholine receptors.

    Science.gov (United States)

    Daeffler, L; Schmidlin, F; Gies, J P; Landry, Y

    1999-03-01

    1. The intrinsic properties of muscarinic ligands were studied through their binding properties and their abilities to modulate the GTPase activity of G proteins coupled to muscarinic M2 receptors in pig atrial sarcolemma. 2. Competition binding experiments were performed with [3H]-oxotremorine-M to assess the affinity of receptors coupled to G proteins (R*), with [3H]-N-methylscopolamine ([3H]-NMS) to estimate the affinities of coupled and uncoupled receptors (R*+R) and with [3H]-NMS in the presence of GppNHp to assess the affinity of uncoupled receptors (R). 3. The ranking of Ki values for the agonist carbachol was R*pirenzepine was R*>R*+R>R (174, 155, 115 nM), suggesting inverse agonism. 4. The Vmax of the basal high affinity GTPase activity of pig atrial sarcolemma was increased by mastoparan and decreased by GPAnt-2 indicating the relevance of this activity to G proteins coupled to receptors (R*). The K(M) value (0.26-0.33 microM) was not modified by mastoparan or GPAnt-2. 5. Carbachol increased the Vmax of GTP hydrolysis (EC50 8.1+/-0.3 microM), whereas atropine and AF-DX 116, up to 1 mM, did not modify it. Pirenzepine decreased the Vmax of GTP hydrolysis (EC50 77.5+/-10.3 microM). This effect was enhanced when KCI was substituted for NaCl (EC50 11.0+/-0.8 microM) and was antagonized by atropine and AF-DX 116 (IC50 0.91+/-0.71 and 197+/-85 nM). 6. Pirenzepine is proposed as an inverse agonist and atropine and AF-DX 116 as neutral antagonists at the muscarinic M2 receptor.

  10. M2Di: Concise and efficient MATLAB 2-D Stokes solvers using the Finite Difference Method

    Science.gov (United States)

    Räss, Ludovic; Duretz, Thibault; Podladchikov, Yury Y.; Schmalholz, Stefan M.

    2017-02-01

    Recent development of many multiphysics modeling tools reflects the currently growing interest for studying coupled processes in Earth Sciences. The core of such tools should rely on fast and robust mechanical solvers. Here we provide M2Di, a set of routines for 2-D linear and power law incompressible viscous flow based on Finite Difference discretizations. The 2-D codes are written in a concise vectorized MATLAB fashion and can achieve a time to solution of 22 s for linear viscous flow on 10002 grid points using a standard personal computer. We provide application examples spanning from finely resolved crystal-melt dynamics, deformation of heterogeneous power law viscous fluids to instantaneous models of mantle flow in cylindrical coordinates. The routines are validated against analytical solution for linear viscous flow with highly variable viscosity and compared against analytical and numerical solutions of power law viscous folding and necking. In the power law case, both Picard and Newton iterations schemes are implemented. For linear Stokes flow and Picard linearization, the discretization results in symmetric positive-definite matrix operators on Cartesian grids with either regular or variable grid spacing allowing for an optimized solving procedure. For Newton linearization, the matrix operator is no longer symmetric and an adequate solving procedure is provided. The reported performance of linear and power law Stokes flow is finally analyzed in terms of wall time. All MATLAB codes are provided and can readily be used for educational as well as research purposes. The M2Di routines are available from Bitbucket and the University of Lausanne Scientific Computing Group website, and are also supplementary material to this article.

  11. [Prognostic impact of loss of sex chromosomes in children with acute myeloid leukemia subtype M2].

    Science.gov (United States)

    Jia, Yue-Ping; Zuo, Ying-Xi; Lu, Ai-Dong; Zhang, Le-Ping; Liu, Gui-Lan

    2015-02-01

    To study the relationship between loss of sex chromosomes and prognosis in children with acute myeloid leukemia (AML) M2 subtype. According to cytogenetic characteristics, 106 children with AML were divided into three groups: patients with normal karyotype (Group A, n=26), patients with abnormal karyotype who had no loss of sex chromosomes (Group B, n=52), and patients with abnormal karyotype who had loss of sex chromosomes (Group C, n=28). Prognosis was compared between the three groups. The 5-year event-free survival (EFS) rates of Groups A, B, and C were (38.9±11.2)%, (59.3±7.3)%, and (66.5±10.5)%, respectively; the EFS of Group C was significantly higher than that of Group A (P=0.035). The 5-year overall survival (OS) rates of Groups A, B, and C were (54.3±13.5)%, (68.1±7.7)%, and (77.9±9.8)%, respectively (P>0.05). The 5-year EFS of 58 patients with t(8;21) was (63.3±7.3)%, significantly higher than that of patients with normal karyotype (P=0.015). All the 28 cases in Group C had t(8;21), and their 5-year EFS was not significantly different from that of patients with t(8;21) in Group B (P>0.05). Loss of sex chromosomes is a favorable karyotype in children with AML M2 subtype and the patients in this group mostly have t(8;21). Why loss of sex chromosomes indicates a favorable prognosis is probably because it is accompanied by t(8;21) in the patients.

  12. Microwave and magnetic (M2 proteomics of a mouse model of mild traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Teresa M. Evans

    2014-06-01

    Full Text Available Short-term increases in oxidative stress and decreases in motor function, including debilitating effects on balance and motor control, can occur following primary mild traumatic brain injuries (mTBI. However, the long-term effects on motor unit impairment and integrity as well as the molecular mechanisms underlying secondary injuries are poorly understood. We hypothesized that changes in central nervous system-specific protein (CSP expression might correlate to these long-term effects. To test our hypothesis, we longitudinally assessed a closed-skull mTBI mouse model, vs. sham control, at 1, 7, 30, and 120 days post-injury. Motor impairment was determined by rotarod and grip strength performance measures, while motor unit integrity was determined using electromyography. Relative protein expression was determined by microwave and magnetic (M2 proteomics of ipsilateral brain tissue, as previously described. Isoprostane measurements were performed to confirm a primary oxidative stress response. Decoding the relative expression of 476 ± 56 top-ranked proteins for each specimen revealed statistically significant changes in the expression of two well-known CSPs at 1, 7 and 30 days post-injury: P < 0.001 for myelin basic protein (MBP and p < 0.05 for myelin associated glycoprotein (MAG. This was confirmed by Western blot. Moreover, MAG, αII-spectrin (SPNA2 and neurofilament light (NEFL expression at 30 days post-injury were directly related to grip strength (p < 0.05. While higher-powered studies of larger cohorts merit further investigation, this study supports the proof-of-concept that M2 proteomics is a rapid method to quantify putative protein biomarkers and therapeutic targets of mTBI and suggests the feasibility of CSP expression correlations to long-term effects on motor impairment.

  13. S-1 induced secondary acute erythroid leukemia with a chromosome inv(12)(p13;q13)

    Institute of Scientific and Technical Information of China (English)

    Kensuke Matsumoto; Akira Kitanaka; Makiko Uemura; Fusako Waki; Tetsuya Fukumoto; Hiroaki Ohnishi; Yoshitsugu Kubota; Toshihiko Ishida

    2011-01-01

    Adjuvant chemotherapy by S-1 following gastrectomy is considered standard treatment in Japan. Analysis of follow-up data have proved the efficacy of S-1 administration,and that hematological adverse events were relatively rare. PPyrimidine anti-metabolites, including S-1, have shown relatively lower risks for secondary hematological malignancies in comparison to alkylating agents and topoisomerase-Ⅱ inhibitors. We here report a case of therapy-related leukemia after S-1 administration. A patient who had received S-1as the sole adjuvant chemotherapy was diagnosed with acute erythroid leukemia. To the best of our knowledge, our patient represents the first report of S-1 induced acute leukemia.

  14. S-1 monotherapy versus S-1 combination therapy in gemcitabine-refractory advanced pancreatic cancer: A meta-analysis (PRISMA) of randomized control trials.

    Science.gov (United States)

    Zhong, Sheng; Qie, Shuai; Yang, Liu; Yan, Qi; Ge, Linna; Wang, Zhongfeng

    2017-07-01

    Pancreatic cancer (PC) is one of the most lethal digestive system tumors. Most new cases are diagnosed based on metastasis or local aggression and are known as "advanced PC." Recently, studies investigating S-1 have indicated that it has a better clinical curative effect on PC. We conducted a meta-analysis to evaluate the efficacy and safety of S-1 monotherapy compared with S-1 combination regimens in patients with gemcitabine (GEM)-refractory PC. Trials published between 1978 and 2016 were identified by an electronic search of public databases (Medline, Embase, and the Cochrane Library). All prospective studies were independently identified by 2 authors for inclusion. The response rate (RR), progression-free and overall survival (PFS and OS, respectively), and the primary toxicities were extracted for the meta-analysis. Four randomized controlled trials consisting of 623 patients were included in the analysis, among which 315 patients underwent S-1 monotherapy and 308 patients underwent S-1 combination therapy. The pooled data showed a significantly higher response rate and longer PFS in the S-1 combination group than in the S-1 monotherapy group (RR, 1.75; 95% confidence interval [CI], 1.19-2.57; P = .005 and hazard ration [HR], 0.75; 95% CI, 0.62-0.91; P = .005). There were no significant differences in OS or adverse events. Compared with the S-1 monotherapy group, the S-1 combination group had a higher response rate and longer PFS. Both groups had few adverse events, which were balanced between the groups. The subgroup analysis suggested that S-1 combination regimens with leucovorin or irinotecan (CPT-11) provided promising efficacy. These promising combination regimens should be considered for patients with advanced PC who choose S-1 as their second-line therapy.

  15. A prokaryotic S1P lyase degrades extracellular S1P in vitro and in vivo: implication for treating hyperproliferative disorders.

    Directory of Open Access Journals (Sweden)

    Andrea Huwiler

    Full Text Available Sphingosine-1-phosphate (S1P regulates a broad spectrum of fundamental cellular processes like proliferation, death, migration and cytokine production. Therefore, elevated levels of S1P may be causal to various pathologic conditions including cancer, fibrosis, inflammation, autoimmune diseases and aberrant angiogenesis. Here we report that S1P lyase from the prokaryote Symbiobacterium thermophilum (StSPL degrades extracellular S1P in vitro and in blood. Moreover, we investigated its effect on cellular responses typical of fibrosis, cancer and aberrant angiogenesis using renal mesangial cells, endothelial cells, breast (MCF-7 and colon (HCT 116 carcinoma cells as disease models. In all cell types, wild-type StSPL, but not an inactive mutant, disrupted MAPK phosphorylation stimulated by exogenous S1P. Functionally, disruption of S1P receptor signaling by S1P depletion inhibited proliferation and expression of connective tissue growth factor in mesangial cells, proliferation, migration and VEGF expression in carcinoma cells, and proliferation and migration of endothelial cells. Upon intravenous injection of StSPL in mice, plasma S1P levels rapidly declined by 70% within 1 h and then recovered to normal 6 h after injection. Using the chicken chorioallantoic membrane model we further demonstrate that also under in vivo conditions StSPL, but not the inactive mutant, inhibited tumor cell-induced angiogenesis as an S1P-dependent process. Our data demonstrate that recombinant StSPL is active under extracellular conditions and holds promise as a new enzyme therapeutic for diseases associated with increased levels of S1P and S1P receptor signaling.

  16. HDL-associated ApoM is anti-apoptotic by delivering sphingosine 1-phosphate to S1P1 & S1P3 receptors on vascular endothelium.

    Science.gov (United States)

    Ruiz, Mario; Okada, Hiromi; Dahlbäck, Björn

    2017-02-08

    High-density Lipoprotein (HDL) attenuates endothelial cell apoptosis induced by different cell-death stimuli such as oxidation or growth factor deprivation. HDL is the main plasma carrier of the bioactive lipid sphingosine 1-phosphate (S1P), which it is a signaling molecule that promotes cell survival in response to several apoptotic stimuli. In HDL, S1P is bound to Apolipoprotein M (ApoM), a Lipocalin that is only present in around 5% of the HDL particles. The goal of this study is to characterize ApoM-bound S1P role in endothelial apoptosis protection and the signaling pathways involved. Human umbilical vein endothelial cells (HUVEC) cultures were switched to serum/grow factor deprivation medium to induce apoptosis and the effect caused by the addition of ApoM and S1P analyzed. The addition of HDL(+ApoM) or recombinant ApoM-bound S1P promoted cell viability and blocked apoptosis, whereas HDL(-ApoM) had no protective effect. Remarkably, S1P exerted a more potent anti-apoptotic effect when carried by ApoM as compared to albumin, or when added as free molecule. Mechanistically, cooperation between S1P1 and S1P3 was required for the HDL/ApoM/S1P-mediated anti-apoptotic ability. Furthermore, AKT and ERK phosphorylation was also necessary to achieve the anti-apoptotic effect of the HDL/ApoM/S1P complex. Altogether, our results indicate that ApoM and S1P are key elements of the anti-apoptotic activity of HDL and promote optimal endothelial function.

  17. 基于文献研究的M2与房价关系分析%Studying in the relationship between M2 and the real estate price

    Institute of Scientific and Technical Information of China (English)

    彭捷剑; 王振营

    2013-01-01

      In the literature studying the relationship between M2 and the real estate price, most of them using the intermediate target of M2 included the supply of credit and rate of interest to analyze the intermediate target’s effect on the real estate price . Also, the real estate price indexes have much different connotation. Most of the documents can prove the contribution of M2 to the real estate price rising, but others show the opposite conclusion or week correlation . This article based on collecting the relevant documents applies direct channel and indirect channel to analyze the effect of M2 on the real estate price. M2 affecting the real estate price is the direct channel ,while M2 affecting the variables such as real estate price rate of interest the supply of credit ,literature review which cause the real estate price changing is the indirect channel .%  在M2与房价关系研究的文献中,多数体现为M2的信贷量、利率等中介指标对房价的影响;并且所采用的房价指标内涵有着较大不同,多数文献研究的结论是M2将会推高房价,但也有一部分研究得出房价会影响M2或者是两者之间相关性不大的结论。本文基于对M2与房价关系研究的文献的梳理,通过直接和间接两种途径分析M2对房地产价格的影响:直接途径是M2直接作用于房价;间接途径是M2通过影响利率、信贷量、基础货币量、市场预期等变量进而影响房价。

  18. Phase I dose-finding study of S1 in combination with docetaxel and oxaliplatin (DOS) as first-line therapy in patients with advanced gastro-esophageal cancer

    DEFF Research Database (Denmark)

    Weber Vestermark, Lene; Jensen, H. A.; Schoennemann, K. R.

    2015-01-01

    -14) every 3 weeks for a maximum of 6 cycles followed by maintenance therapy with S-1 monotherapy (2 x 30 mg/m2/days 1-14) until progression. Toxicity was evaluated according to NCIC-CTC 4.0. DLT was defined as non-hematological toxicity grade > 3 or febrile neutropenia and evaluated after the first course...... confirmed tolerability of DOS. 7/13 evaluable patients obtained PR; 3 had PD before 6 cycles of DOS; 5 pts continue DOS. Conclusions: For standard therapy and for further development we recommend DOS at dose level 2 (D 50 mg/m2 day 1; O 100 mg/m2 day 1 and S-1 25 mg/m2 x 2 day 1-14 every 3 weeks). DOS......Background: S-1 (Teysuno) was developed to provide more efficacious and safer oral delivery of 5-FU (F) or capecitabine. Recently S-1 in combination with cisplatin (C) was approved in Europe for the treatment of advanced gastro-esophageal cancer (aGEC). Addition of docetaxel (D) to F or CF has...

  19. A phase Ⅱ trial of oxaliplatin plus S-1 as a first-line chemotherapy for patients with advanced gastric cancer

    Institute of Scientific and Technical Information of China (English)

    YANG Lin; SONG Yan; ZHOU Ai-ping; QIN Qiong; CHI Yihebali; HUANG Jing; WANG Jin-wan

    2013-01-01

    Background Palliative chemotherapy has been shown to have a survival benefit for patients with recurrent or metastatic gastric cancer.We conducted a Phase Ⅱ trial to determine the efficacy and safety of S-1 plus oxaliplatin (SOX regimen) as first-line chemotherapy for patients with unresectable locally advanced or metastatic gastric cancer.Methods Eligible patients had measurable lesions and no previous history of chemotherapy (except adjuvant chemotherapy).Oxaliplatin was administered intravenously at a dose of 130 mg/m2 on day 1.S-1 was administered orally in doses of 80,100,or 120 mg/d according to body surface areas of <1.25 m2,1.25-1.5 m2,or >1.5 m2 respectively;the total dose was divided into two daily doses on days 1-14.Treatments were repeated every 3 weeks until disease progression or intolerable toxicity occurred.Results Forty-three patients were enrolled in the study.All were assessable for efficacy and adverse events.The objective response and disease control rates were 55.8% and 76.7% respectively.The median follow-up time was 16.5 months.The median progression-free survival time was 7 months (95% Cl,5.8-8.2 months) and the median overall survival time was 16.5 months (95% Cl,9.7-23.3 months).The one-year survival rate was 54.2%.Major adverse reactions were grade 3/4 neutropenia (9.3%) and thrombocytopenia (20.9%).Conclusion The SOX regimen with oxaliplatin at a dose of 130 mg/m2 was found to be effective and safe as a first-line chemotherapy in Chinese patients with advanced gastric cancer.

  20. Chemical and Biological Properties of S-1-Propenyl-ʟ-Cysteine in Aged Garlic Extract

    Directory of Open Access Journals (Sweden)

    Yukihioro Kodera

    2017-03-01

    Full Text Available S-1-Propenyl-ʟ-cysteine (S1PC is a stereoisomer of S-1-Propenyl-ʟ-cysteine (SAC, an important sulfur-containing amino acid that plays a role for the beneficial pharmacological effects of aged garlic extract (AGE. The existence of S1PC in garlic preparations has been known since the 1960’s. However, there was no report regarding the biological and/or pharmacological activity of S1PC until 2016. Recently, we performed a series of studies to examine the chemical, biological, pharmacological and pharmacokinetic properties of S1PC, and obtained some interesting results. S1PC existed only in trace amounts in raw garlic, but its concentration increased almost up to the level similar of SAC through aging process of AGE. S1PC showed immunomodulatory effects in vitro and in vivo, and reduced blood pressure in a hypertensive animal model. A pharmacokinetic study revealed that S1PC was readily absorbed after oral administration in rats and dogs with bioavailability of 88–100%. Additionally, S1PC had little inhibitory influence on human cytochrome P450 activities, even at a concentration of 1 mM. Based on these findings, S1PC was suggested to be another important, pharmacologically active and safe component of AGE similar to SAC. In this review, we highlight some results from recent studies on S1PC and discuss the potential medicinal value of S1PC.

  1. Chemical and Biological Properties of S-1-Propenyl-l-Cysteine in Aged Garlic Extract.

    Science.gov (United States)

    Kodera, Yukihioro; Ushijima, Mitsuyasu; Amano, Hirotaka; Suzuki, Jun-Ichiro; Matsutomo, Toshiaki

    2017-03-31

    S-1-Propenyl-l-cysteine (S1PC) is a stereoisomer of S-1-Propenyl-l-cysteine (SAC), an important sulfur-containing amino acid that plays a role for the beneficial pharmacological effects of aged garlic extract (AGE). The existence of S1PC in garlic preparations has been known since the 1960's. However, there was no report regarding the biological and/or pharmacological activity of S1PC until 2016. Recently, we performed a series of studies to examine the chemical, biological, pharmacological and pharmacokinetic properties of S1PC, and obtained some interesting results. S1PC existed only in trace amounts in raw garlic, but its concentration increased almost up to the level similar of SAC through aging process of AGE. S1PC showed immunomodulatory effects in vitro and in vivo, and reduced blood pressure in a hypertensive animal model. A pharmacokinetic study revealed that S1PC was readily absorbed after oral administration in rats and dogs with bioavailability of 88-100%. Additionally, S1PC had little inhibitory influence on human cytochrome P450 activities, even at a concentration of 1 mM. Based on these findings, S1PC was suggested to be another important, pharmacologically active and safe component of AGE similar to SAC. In this review, we highlight some results from recent studies on S1PC and discuss the potential medicinal value of S1PC.

  2. The phylogeny of C/S1 bZIP transcription factors reveals a shared algal ancestry and the pre-angiosperm translational regulation of S1 transcripts

    NARCIS (Netherlands)

    Peviani, Alessia; Lastdrager, Jeroen; Hanson, Johannes; Snel, Berend

    2016-01-01

    Basic leucine zippers (bZIPs) form a large plant transcription factor family. C and S1 bZIP groups can heterodimerize, fulfilling crucial roles in seed development and stress response. S1 sequences also harbor a unique regulatory mechanism, termed Sucrose-Induced Repression of Translation (SIRT). Th

  3. Dysfunctional muscarinic M(2) autoreceptors in vagally induced bronchoconstriction of conscious guinea pigs after the early allergic reaction

    NARCIS (Netherlands)

    TenBerge, REJ; Krikke, M; Teisman, ACH; Roffel, AF; Zaagsma, J

    1996-01-01

    We studied the function of autoinhibitory muscarinic M(2) receptors on vagal nerve endings in the airways of conscious, unrestrained, ovalbumin-sensitized guinea pigs after the early and late allergic reaction. For this purpose, the effects of the selective muscarinic M(2) receptor antagonist gallam

  4. Effect of S1P5 on proliferation and migration of human esophageal cancer cells

    OpenAIRE

    Hu, Wei-Min; Li, Li; Jing, Bao-Qian; Zhao, Yong-Sheng; Wang, Chao-Li; Feng, Li; Xie, Yong-En

    2010-01-01

    AIM: To investigate the sphingosine 1-phosphate (S1P) receptor expression profile in human esophageal cancer cells and the effects of S1P5 on proliferation and migration of human esophageal cancer cells.

  5. Fusion to chicken C3d enhances the immunogenicity of the M2 protein of avian influenza virus

    Directory of Open Access Journals (Sweden)

    Zhang Li

    2010-05-01

    Full Text Available Abstract Background Current vaccines to avian influenzae virus (AIV, a highly contagious disease of birds, need to be constantly updated due to the high level of variation in the target antigens. Therefore, a vaccine that could induce broad cross protection against AIV is required. The M2 membrane protein is structurally conserved amongst AIV subtypes but tends in induce a poor immune response, whereas C3d has been shown in many species to enhance immunogenicity. In this study, we investigated the potential of M2-avian C3d fusion proteins to provide effective immunity. Results We fused chicken complement C3d to sM2 (M2 protein with the transmembrane region deleted of AIV and expressed four fusion proteins, GST (Glutathione S-transferase tagged proteins in pGEX expression vector -C3d-sM2, GST-C3d-L2-sM2, GST-C3d-L1-C3d-sM2 and GST-C3d-L1-C3d-L2-sM2 were used to immunize mice. In addition, Specific pathogen free (SPF chickens were inoculated with the plasmids pcDNA-sM2, pcDNA-C3d-L1-C3d-L2-sM2, GST-sM2 and GST-C3d-L1-C3d-L2-sM2. The immune response was monitored by an enzyme-linked immunosorbent assay (ELISA for sM2 antibody, and all the test animals were challenged with A/chicken/Bei Jing/WD9/98 (H9N2 virus. Results revealed that the anti-sM2 antibody in mice and chickens vaccinated with these proteins was higher than the nonfused forms of sM2, the GST-C3d-L1-C3d-L2-sM2 groups have conferred the highest 30% and 20% protection ratio in mice and chickens respectively. In addition, the pcDNA-C3d-L1-C3d-L2-sM2 also enhances the antibody responses to sM2 compared to pcDNA-sM2 in chickens, and acquired 13.3% protection ratio. Conclusion These results indicated that chicken C3d enhanced the humoral immunity against AIV M2 protein either fused proteins expressed by the prokaryotic system or with the DNA vaccine. Nevertheless, in view of the poor protection ratio for these animals, we speculated that this is not a worthy developing of vaccine in these

  6. Acinar Cell Carcinoma of the Pancreas: A Possible Role of S-1 as Chemotherapy for Acinar Cell Carcinoma. A Case Report

    Directory of Open Access Journals (Sweden)

    Tameyoshi Yamamoto

    2012-01-01

    Full Text Available Context Acinar cell carcinoma of the pancreas is a rare malignancy, accounting for 1-2% of pancreatic exocrine malignancies. This rarity makes it difficult to standardize a protocol of treatment for acinar cell carcinoma. Case report A 71-year-old male without any particular past history was referred to our institute with abdominal distention and mild liver dysfunction. Computed tomography (CT revealed a cystic lesion with a diameter of 3.5 cm, which originated from the neck of pancreas and had solid nodules inside. Several nodules were demonstrated surrounding the cystic tumor. Laparotomy and histological study demonstrated peritoneal dissemination of acinar cell carcinoma. The patient was treated with S-1 monotherapy (80 mg/m2 for four weeks with a two-week interval as one cycle. After one cycle of S-1 monotherapy, CT demonstrated remarkable shrinkage of the main tumor and disappearance of the nodules on the peritoneum. The patient underwent a radical distal pancreatectomy. The patient was then treated with 16 cycles of S-1 monotherapy after the radical pancreatectomy and remains without any recurrence of the disease two years later. Conclusion Initially inoperable acinar cell carcinoma was treated by monotherapy using S-1, resulting in curative operation and two years disease free survival post operation. S-1 might be more effective on acinar cell carcinoma, rather than gemcitabine

  7. Moesin controls clathrin-mediated S1PR1 internalization in T cells.

    Directory of Open Access Journals (Sweden)

    Akira Nomachi

    Full Text Available The lipid mediator sphingosine 1-phosphate (S1P regulates a wide range of cellular activities, including vascular maturation, angiogenesis, and immune-cell trafficking. Among the five known receptors for S1P (S1PR1-S1PR5, S1PR1 is a critical regulator of lymphocyte trafficking: its signaling is required for lymphocyte egress from lymphoid organs, while its down-modulation by agonist-induced internalization is a prerequisite for lymphocyte entry into lymphoid organs from the bloodstream. Despite the importance of S1PR1 down-regulation in determining lymphocyte behavior, the molecular mechanism of its internalization in lymphocytes has not been defined. Here we show that agonist-induced S1PR1 internalization in T cells occurs via clathrin-mediated endocytosis and is regulated by moesin, an ezrin-radixin-moesin (ERM family member. In S1P-stimulated T cells, S1PR1 relocalized within clathrin-coated vesicles (CCVs and early endosomes, and S1PR1 internalization was blocked when clathrin was pharmacologically inhibited. Stimulating moesin-deficient T cells with S1P failed to induce S1PR1 internalization and CCV formation. Furthermore, treating moesin-deficient mice with FTY720, an S1P receptor agonist known to internalize S1PR1, caused delayed lymphopenia, and lymphocytes isolated from FTY720-treated moesin-deficient mice still responded to S1P ex vivo in chemotaxis assays. These results reveal a novel role for moesin in regulating clathrin-dependent S1PR1 internalization through CCV formation.

  8. HDL-S1P: cardiovascular functions, disease-associated alterations, and therapeutic applications.

    Science.gov (United States)

    Levkau, Bodo

    2015-01-01

    Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid contained in High-density lipoproteins (HDL) and has drawn considerable attention in the lipoprotein field as numerous studies have demonstrated its contribution to several functions inherent to HDL. Some of them are partly and some entirely due to the S1P contained in HDL (HDL-S1P). Despite the presence of over 1000 different lipids in HDL, S1P stands out as it possesses its own cell surface receptors through which it exercises key physiological functions. Most of the S1P in human plasma is associated with HDL, and the amount of HDL-S1P influences the quality and quantity of HDL-dependent functions. The main binding partner of S1P in HDL is apolipoprotein M but others may also exist particularly under conditions of acute S1P elevations. HDL not only exercise functions through their S1P content but have also an impact on genuine S1P signaling by influencing S1P bioactivity and receptor presentation. HDL-S1P content is altered in human diseases such as atherosclerosis, coronary artery disease, myocardial infarction, renal insufficiency and diabetes mellitus. Low HDL-S1P has also been linked to impaired HDL functions associated with these disorders. Although the pathophysiological and molecular reasons for such disease-associated shifts in HDL-S1P are little understood, there have been successful approaches to circumvent their adverse implications by pharmacologically increasing HDL-S1P as means to improve HDL function. This mini-review will cover the current understanding of the contribution of HDL-S1P to physiological HDL function, its alteration in disease and ways for its restoration to correct HDL dysfunction.

  9. HDL-S1P: cardiovascular functions, disease-associated alterations, and therapeutic applications

    Science.gov (United States)

    Levkau, Bodo

    2015-01-01

    Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid contained in High-density lipoproteins (HDL) and has drawn considerable attention in the lipoprotein field as numerous studies have demonstrated its contribution to several functions inherent to HDL. Some of them are partly and some entirely due to the S1P contained in HDL (HDL-S1P). Despite the presence of over 1000 different lipids in HDL, S1P stands out as it possesses its own cell surface receptors through which it exercises key physiological functions. Most of the S1P in human plasma is associated with HDL, and the amount of HDL-S1P influences the quality and quantity of HDL-dependent functions. The main binding partner of S1P in HDL is apolipoprotein M but others may also exist particularly under conditions of acute S1P elevations. HDL not only exercise functions through their S1P content but have also an impact on genuine S1P signaling by influencing S1P bioactivity and receptor presentation. HDL-S1P content is altered in human diseases such as atherosclerosis, coronary artery disease, myocardial infarction, renal insufficiency and diabetes mellitus. Low HDL-S1P has also been linked to impaired HDL functions associated with these disorders. Although the pathophysiological and molecular reasons for such disease-associated shifts in HDL-S1P are little understood, there have been successful approaches to circumvent their adverse implications by pharmacologically increasing HDL-S1P as means to improve HDL function. This mini-review will cover the current understanding of the contribution of HDL-S1P to physiological HDL function, its alteration in disease and ways for its restoration to correct HDL dysfunction. PMID:26539121

  10. Turbulent Fluxes of Sensible Heat Measured by Research UAV 'M2AV Carolo'

    Science.gov (United States)

    Martin, S.; Bange, J.

    2009-09-01

    Research aircraft equipped for turbulence measurements in the atmospheric boundary layer (ABL) are suitable platforms to measure area-representative mean values and statistical moments of second order - like variance, spectral distribution and turbulent fluxes - in situ i.e. without the use of any theoretical assumptions. Since manned research aircraft are expensive the use of small unmanned aerial vehicle (UAV) or mini aerial vehicles (MAV) is attractive. Such research UAV are able to measure vertical profiles of the lower troposphere, for instance. The next, more challenging league is the measurement of the turbulent fluctuations of the wind vector and simultaneously at least one scalar quantity in order to calculate turbulent fluxes using eddy covariance. To do this, fast and accurate sensors are required, with small weight, small dimensions and small power consumption, in order to be operated on a small research UAV. Beside absolute and relative measurement accuracy, the response time of the sensors has to be short (in the order of several 10 Hz) to resolve turbulent eddies also in stable stratification (i.e. sub-metre range). Since light, small and fast sensors for air humidity and trace gases are not available currently, the first step is to measure the vertical flux of sensible heat H. Beside a slow (about 1 Hz) water vapour sensor, the automatically operating meteorological mini aerial vehicles (M2AV) are equipped with two temperature sensors and a wind measurement unit. One of the temperature sensors is slow but offers a high absolute accuracy, while the fast sensor (up to 100 Hz) has a high relative accuracy but is unstable in time. The two signals are blended using a complementary filter. The wind vector can be calculated using the inertial velocity (aircraft speed relative to the earth) and the true airspeed (aircraft speed relative to the airflow). The true airspeed of M2AV is computed from five-hole-probe pressure measurements whereas the aircraft

  11. The clinically-tested S1P receptor agonists, FTY720 and BAF312, demonstrate subtype-specific bradycardia (S1P₁ and hypertension (S1P₃ in rat.

    Directory of Open Access Journals (Sweden)

    Ryan M Fryer

    Full Text Available Sphingosine-1-phospate (S1P and S1P receptor agonists elicit mechanism-based effects on cardiovascular function in vivo. Indeed, FTY720 (non-selective S1P(X receptor agonist produces modest hypertension in patients (2-3 mmHg in 1-yr trial as well as acute bradycardia independent of changes in blood pressure. However, the precise receptor subtypes responsible is controversial, likely dependent upon the cardiovascular response in question (e.g. bradycardia, hypertension, and perhaps even species-dependent since functional differences in rodent, rabbit, and human have been suggested. Thus, we characterized the S1P receptor subtype specificity for each compound in vitro and, in vivo, the cardiovascular effects of FTY720 and the more selective S1P₁,₅ agonist, BAF312, were tested during acute i.v. infusion in anesthetized rats and after oral administration for 10 days in telemetry-instrumented conscious rats. Acute i.v. infusion of FTY720 (0.1, 0.3, 1.0 mg/kg/20 min or BAF312 (0.5, 1.5, 5.0 mg/kg/20 min elicited acute bradycardia in anesthetized rats demonstrating an S1P₁ mediated mechanism-of-action. However, while FTY720 (0.5, 1.5, 5.0 mg/kg/d elicited dose-dependent hypertension after multiple days of oral administration in rat at clinically relevant plasma concentrations (24-hr mean blood pressure = 8.4, 12.8, 16.2 mmHg above baseline vs. 3 mmHg in vehicle controls, BAF312 (0.3, 3.0, 30.0 mg/kg/d had no significant effect on blood pressure at any dose tested suggesting that hypertension produced by FTY720 is mediated S1P₃ receptors. In summary, in vitro selectivity results in combination with studies performed in anesthetized and conscious rats administered two clinically tested S1P agonists, FTY720 or BAF312, suggest that S1P₁ receptors mediate bradycardia while hypertension is mediated by S1P₃ receptor activation.

  12. MUC1-C oncoprotein regulates glycolysis and pyruvate kinase M2 activity in cancer cells.

    Directory of Open Access Journals (Sweden)

    Michio Kosugi

    Full Text Available Aerobic glycolysis in cancer cells is regulated by multiple effectors that include Akt and pyruvate kinase M2 (PKM2. Mucin 1 (MUC1 is a heterodimeric glycoprotein that is aberrantly overexpressed by human breast and other carcinomas. Here we show that transformation of rat fibroblasts by the oncogenic MUC1-C subunit is associated with Akt-mediated increases in glucose uptake and lactate production, consistent with the stimulation of glycolysis. The results also demonstrate that the MUC1-C cytoplasmic domain binds directly to PKM2 at the B- and C-domains. Interaction between the MUC1-C cytoplasmic domain Cys-3 and the PKM2 C-domain Cys-474 was found to stimulate PKM2 activity. Conversely, epidermal growth factor receptor (EGFR-mediated phosphorylation of the MUC1-C cytoplasmic domain on Tyr-46 conferred binding to PKM2 Lys-433 and inhibited PKM2 activity. In human breast cancer cells, silencing MUC1-C was associated with decreases in glucose uptake and lactate production, confirming involvement of MUC1-C in the regulation of glycolysis. In addition, EGFR-mediated phosphorylation of MUC1-C in breast cancer cells was associated with decreases in PKM2 activity. These findings indicate that the MUC1-C subunit regulates glycolysis and that this response is conferred in part by PKM2. Thus, the overexpression of MUC1-C oncoprotein in diverse human carcinomas could be of importance to the Warburg effect of aerobic glycolysis.

  13. FAST, LOW-IONIZATION EMISSION REGIONS OF THE PLANETARY NEBULA M2-42

    Energy Technology Data Exchange (ETDEWEB)

    Danehkar, A.; Parker, Q. A. [Department of Physics and Astronomy, Macquarie University, Sydney, NSW 2109 (Australia); Steffen, W., E-mail: ashkbiz.danehkar@cfa.harvard.edu [Instituto de Astronomía, Universidad Nacional Autónoma de México, C.P.22860, Ensenada (Mexico)

    2016-02-15

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

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

    Science.gov (United States)

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

    2006-01-01

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

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

    Science.gov (United States)

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

    2006-01-01

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

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

    Science.gov (United States)

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

    2016-01-29

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

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

    Directory of Open Access Journals (Sweden)

    Carmen Chak-Lui Wong

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

  18. On the spectral properties of multi-branes, M2 and M5 branes

    Energy Technology Data Exchange (ETDEWEB)

    Garcia del Moral, M.P. [Departamento de Fisica, Universidad de Oviedo, Calvo Sotelo 18, 33007, Oviedo (Spain); Restuccia, A. [Departamento de Fisica, Universidad de Antofagasta, Aptdo 02800 (Chile); Departamento de Fisica, Universidad Simon Bolivar, Apartado 89000, Caracas 1080-A (Venezuela)

    2011-07-01

    In this note we summarize some of the properties found in [1-3]. We characterize spectral properties of the quantum mechanical hamiltonian of theories with fermionic degrees of freedom beyond semiclassical approximation. We obtain a general class of bosonic polynomial potentials for which the Schroeedinger operator has a discrete spectrum. This class includes all the scalar potentials in membrane, 5-brane, p-branes, multiple M2 branes, BLG and ABJM theories. We also give a sufficient condition for discreteness of the spectrum for supersymmmetric and non supersymmetric theories with a fermionic contribution. We characterize then the spectral properties of different theories: the BMN matrix model, the supermembrane with central charges and a bound state of N D2 with m D0. We show that, while the first two models have a purely discrete spectrum with finite multiplicity, the latter has a continuous spectrum starting from a constant given in terms of the monopole charge. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  19. Carbon and nitrogen abundances of stellar populations in the globular cluster M 2

    CERN Document Server

    Lardo, C; Mucciarelli, A; Milone, A P

    2012-01-01

    We present CH and CN index analysis and C and N abundance calculations based on the low-resolution blue spectra of red giant branch (RGB) stars in the Galactic globular cluster NGC 7089 (M 2). Our main goal is to investigate the C-N anticorrelation for this intermediate metallicity cluster. The data were collected with DOLORES, the multiobject, low-resolution facility at the Telescopio Nazionale Galileo. Spectroscopic data were coupled with UV photometry obtained during the spectroscopic run. We found a considerable star-to-star variation in both A(C) and A(N) at all luminosities for our sample of 35 targets. These abundances appear to be anticorrelated, with a hint of bimodality in the C content for stars with luminosities below the RBG bump (V~15.7), while the range of variations in N abundances is very large and spans almost ~ 2 dex. We find additional C depletion as the stars evolve off the RGB bump, in fairly good agreement with theoretical predictions for metal-poor stars in the course of normal stellar...

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

    Science.gov (United States)

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

    2016-06-01

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

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

    Science.gov (United States)

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

    2003-01-01

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

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

    Science.gov (United States)

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

    2016-06-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-08-26

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

  4. Expansion parallax for the compact planetary nebula M2-43

    Directory of Open Access Journals (Sweden)

    L. Guzmán

    2006-01-01

    Full Text Available Presentamos observaciones de alta calidad en radiocontinuo hechas a 3.6 cm con el Very Large Array en dos épocas hacia la nebulosa planetaria M2-43. La comparación de las dos épocas, obtenidas con una separación de 4.07 años, muestra claramente la expansión de la nebulosa planetaria con una velocidad angular de 0.61_0.09 mas año_1. Suponiendo que la velocidad de expansión en el plano del cielo (determinada de estas mediciones y la velocidad de expansión en la línea de visión (determinada a partir de espectroscopía óptica disponible en la literatura son iguales, encontramos una distancia de 6.9 1.5 kpc a la nebulosa planetaria. Esta es la mayor distancia a una nebulosa planetaria medida hasta ahora con esta técnica.

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

    Science.gov (United States)

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

    2015-10-01

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

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

    Science.gov (United States)

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

    2016-08-25

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

  7. Acid activation mechanism of the influenza A M2 proton channel.

    Science.gov (United States)

    Liang, Ruibin; Swanson, Jessica M J; Madsen, Jesper J; Hong, Mei; DeGrado, William F; Voth, Gregory A

    2016-10-24

    The homotetrameric influenza A M2 channel (AM2) is an acid-activated proton channel responsible for the acidification of the influenza virus interior, an important step in the viral lifecycle. Four histidine residues (His37) in the center of the channel act as a pH sensor and proton selectivity filter. Despite intense study, the pH-dependent activation mechanism of the AM2 channel has to date not been completely understood at a molecular level. Herein we have used multiscale computer simulations to characterize (with explicit proton transport free energy profiles and their associated calculated conductances) the activation mechanism of AM2. All proton transfer steps involved in proton diffusion through the channel, including the protonation/deprotonation of His37, are explicitly considered using classical, quantum, and reactive molecular dynamics methods. The asymmetry of the proton transport free energy profile under high-pH conditions qualitatively explains the rectification behavior of AM2 (i.e., why the inward proton flux is allowed when the pH is low in viral exterior and high in viral interior, but outward proton flux is prohibited when the pH gradient is reversed). Also, in agreement with electrophysiological results, our simulations indicate that the C-terminal amphipathic helix does not significantly change the proton conduction mechanism in the AM2 transmembrane domain; the four transmembrane helices flanking the channel lumen alone seem to determine the proton conduction mechanism.

  8. Desensitization of human muscarinic acetylcholine receptor m2 subtypes is caused by their sequestration/internalization.

    Science.gov (United States)

    Tsuga, H; Kameyama, K; Haga, T

    1998-10-01

    Desensitization of human muscarinic acetylcholine receptor m2 subtypes (hm2 receptors) stably expressed in chinese hamster ovary cells was measured as decreases in the carbamylcholine-stimulated [35S]GTPgammaS binding activity in membrane preparations after pre-treatment of cells with carbamylcholine. The extent of carbamylcholine-stimulated [35S]GTPgammaS binding activity was found to decrease to 64% following pretreatment of cells with 10 microM carbamylcholine for 30 min, and under the same conditions 51-59% of hm2 receptors were sequestered/internalized as assessed by decreases in the [3H]N-methylscopolamine binding activity on the cell surface. A similar reduction in the carbamylcholine-stimulated [35S]GTPgammaS binding activity was observed by pretreatment of cells with 5 nM propylbenzylylcholine mustard, which irreversibly bound to and inactivated 58% of the hm2 receptors. When the cells were pretreated with 10 microM carbamylcholine in the presence of 0.32 M sucrose, which is known to inhibit clathrin-mediated endocytosis, no sequestration/internalization of hm2 receptors was observed, and the extent of carbamylcholine-stimulated [35S]GTPgammaS binding activity did not change. These results indicate that desensitization of hm2 receptors may be caused by reduction of receptor number on the cell surface through sequestration/internalization rather than by loss of the function of receptors.

  9. 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.

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

    Science.gov (United States)

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

    2006-01-01

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

  11. Combination therapy with docetaxel and S-1 as a first-line treatment in patients with advanced or recurrent gastric cancer: a retrospective analysis

    Directory of Open Access Journals (Sweden)

    Yoshida Kazuhiro

    2010-05-01

    Full Text Available Abstract Background We performed a single-institution retrospective study to evaluate the efficacy and toxicities of combination therapy with docetaxel and S-1 in patients with advanced or recurrent gastric cancer. Methods Eighty-six patients with advanced or recurrent gastric cancer were enrolled. Patients received docetaxel, 40 mg/m2, on day 1 and oral S-1, 80 mg/m2/day, on days 1 to 14 every 3 weeks. Results All 84 patients were assessable for response. The overall response rate was 52.4% (44/84 and the disease control rate was 96.4% (81/84. Median time to progression (TTP and overall survival (OS were 6.5 (95% CI, 4.8-8.1 months and 15.1 months (95% CI, 11.7-18.5 months, respectively. The major toxicities were neutropenia, leukopenia, alopecia and anorexia. Grade 3 or 4 hematologic toxicities included neutropenia in 31 patients (36.0%, leukopenia in 27 (31.7%, febrile neutropenia in four (4.7%, and anemia in one (1.2%. Other grade 3 toxicities included anorexia in five patients (5.8%, and stomatitis, diarrhea and nausea in one each (1.2%. There was one treatment-related death (1.2%. Conclusion The combination of docetaxel and S-1 had good clinical activity with acceptable toxicity in patients with advanced or recurrent gastric cancer.

  12. A case of bone metastasis of colon cancer that markedly responded to S-1/CPT-11 combination chemotherapy and became curable by resection

    Directory of Open Access Journals (Sweden)

    Masuda Hideki

    2006-01-01

    Full Text Available Abstract Background An oral combined fluoropyrimidine anticancer drug, tegafur/gimeracil/oteracil potassium (S-1, has recently been used alone or in combination for colon cancer. Case presentation The patient was a 42-year-old man with sigmoid colon cancer with direct invasion of the urinary bladder and multiple costal metastases. A diagnosis of T4, M1, stage IV sigmoid colon cancer was made, and curative resection was considered impossible. S-1 at 50 mg/m2 was administered by oral route from day 1 to day 14. Irinotecan (CPT-11 at 40 mg/m2 was administered by intravenous day 1 and 15. This treatment was followed by 2 weeks absent period, and repeated every 4 weeks. Six cycles of administration were performed in total. Following this treatment, the multiple costal metastases resolved. Down-staging to T3, M0, stage IIA was achieved, and curative resection was judged to be possible. Conclusion Occasional cases in which S-1/CPT-11 therapy was effective have been recently reported. The patient's tumor became resectable despite the discovery of colon cancer associated with bone metastasis at the initial examination, offering hope for cancer patients.

  13. Discovery of Potential M2 Channel Inhibitors Based on the Amantadine Scaffold via Virtual Screening and Pharmacophore Modeling

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    Ly Le

    2011-12-01

    Full Text Available The M2 channel protein on the influenza A virus membrane has become the main target of the anti-flu drugs amantadine and rimantadine. The structure of the M2 channel proteins of the H3N2 (PDB code 2RLF and 2009-H1N1 (Genbank accession number GQ385383 viruses may help researchers to solve the drug-resistant problem of these two adamantane-based drugs and develop more powerful new drugs against influenza A virus. In the present study, we searched for new M2 channel inhibitors through a combination of different computational methodologies, including virtual screening with docking and pharmacophore modeling. Virtual screening was performed to calculate the free energies of binding between receptor M2 channel proteins and 200 new designed ligands. After that, pharmacophore analysis was used to identify the important M2 protein-inhibitor interactions and common features of top binding compounds with M2 channel proteins. Finally, the two most potential compounds were determined as novel leads to inhibit M2 channel proteins in both H3N2 and 2009-H1N1 influenza A virus.

  14. Discovery of potential M2 channel inhibitors based on the amantadine scaffold via virtual screening and pharmacophore modeling.

    Science.gov (United States)

    Tran, Linh; Choi, Sy Bing; Al-Najjar, Belal O; Yusuf, Muhammad; Wahab, Habibah A; Le, Ly

    2011-12-08

    The M2 channel protein on the influenza A virus membrane has become the main target of the anti-flu drugs amantadine and rimantadine. The structure of the M2 channel proteins of the H3N2 (PDB code 2RLF) and 2009-H1N1 (Genbank accession number GQ385383) viruses may help researchers to solve the drug-resistant problem of these two adamantane-based drugs and develop more powerful new drugs against influenza A virus. In the present study, we searched for new M2 channel inhibitors through a combination of different computational methodologies, including virtual screening with docking and pharmacophore modeling. Virtual screening was performed to calculate the free energies of binding between receptor M2 channel proteins and 200 new designed ligands. After that, pharmacophore analysis was used to identify the important M2 protein-inhibitor interactions and common features of top binding compounds with M2 channel proteins. Finally, the two most potential compounds were determined as novel leads to inhibit M2 channel proteins in both H3N2 and 2009-H1N1 influenza A virus.

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

    Science.gov (United States)

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

    2016-05-01

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

  16. Construction and expression of a humanized M2 autoantigen trimer and its application in the diagnosis of primary biliary cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Xiao-Hua Jiang; Ren-Qian Zhong; Sheng-Qian Yu; Yin Hu; Weng-Weng Li; Xian-Tao Kong

    2003-01-01

    AIM: To construct and express a humanized M2 autoantigen trimer designated as BPO and to apply it in the diagnosis of primary biliary cirrhosis (PBC). METHODS: cDNA fragments encoding M2-reactive epitopes of pyruvate dehydrogenase complex Ez (PDCE2), branched chain 2-oxo-acid dehydrogenase complex E2 (BCOADC-E2) and 2-oxo-glutarate dehydrogenase complex E2 (OGDC-E2) were amplified with PCR using total RNA extracted from human peripheral mononuclear blood cells. The fragments were cloned into the plasmid vector pQE-30 and then transferred into E. coliM15 (pREP4) for expression, which was induced by isopropylthio-β-Dgalactoside. The expressed recombinant BPO protein was demonstrated by SDS-PAGE, Western-blotting and Immunoabsorption test, its antigenic reactivity and specificity were identified with seven M2-positive sera confirmed at Euroimmun Research Center (Germany).Using the purified BPO, M2 antibodies in sera from patients with PBC and other liver related diseases were detected with ELISA. RESULTS: The expressed BPO was observed with both antigenic reactivity and specificity of M2 autoantigens. The determination of M2 antibodies by BPO with ELISA was more sensitive than using the Euroimmun's kit with the coefficients of variation less than 10 % in both interassay and intraassay.With the newly established method, M2 antibodies were found in 100 % (20/20) of patients with PBC. Six cases of liver disease with unknown etiology and 1 patient with drug induced liver injury had detectable levels of serum M2antibodies. There were also 2 patients with autoimmune cholangitis and 1 with autoimmune hepatitis showing M2-antibody positive. CONCLUSION: Compared with the routine immunofluorescenoe assay and commercially available assay kit using porcine heart mitochondrial protein as the antigen, the detection system established in the present study shows higher sensitivity and specificity and may be used as a powerful tool for the diagnosis of PBC.

  17. tM2-PK蛋白在结直肠癌中的表达及临床意义%The expression and clinical signification of tM2-PK in colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    喻鑫; 刘弋

    2014-01-01

    Objective To investigate the expression and clinical signification of tumor M2 pyruvate kinase in pa-tients with CRC, and to try to find a reliable and atraumatic method to predict the progress and pronosis in the CRC. Methods ELISA method was used to determine the serum levels of tM2-PK in 68 patients with CRC,40 pa-tients with colorectal polyps and 40 cases of normal subjects; immunohistochemistry ( IHC ) methods were respec-tively used to detect the expression of tM2-PK in tissues. Results ① The level of serum tM2-PK in patients with CRC was significantly higher than the group of patients with polyps and the normal subjects ( P<0.05 ) . The serum tM2-PK levels was closely correlated to tumor size and Duke stage.②The positive rate of tissue tM2-PK was signif-icantly higher in CRC than in colorectal polyps and normal subjects ( P<0.05 ) . Tissue tM2-PK levels was closely correlated to tumor size,Duke stage and differentiation grade. ③Serum tM2-PK levels was correlated to tissue tM2-PK levels (r=0.357,P=0.003). Conclusion Combined detection of expression of tM2-PK can provide the basis theory for the diagnosis and prognosis evaluation of CRC.%目的研究肿瘤型丙酮酸激酶( tM2-PK)在结直肠癌( CRC)患者中的表达及相关性,为CRC的早期诊断、预后判断和治疗后随访,寻求一种简便可靠、无创的检测方法。方法分别应用免疫组化( IHC )法和酶联免疫吸附( ELISA )法检测68例CRC患者癌组织和术前血清tM2-PK水平,并与40例结直肠息肉患者和40例健康体检者作比较。结果① CRC组血清tM2-PK水平明显高于结直肠息肉组、正常组(P<0.05),其表达与肿瘤大小、Duke分期均显著相关;②CRC组织中tM2-PK阳性表达率明显高于结直肠息肉组织和癌旁正常组织(P<0.05),其表达与肿瘤大小、分化程度、Duke分期均显著相关;③血清与癌组织的tM2-PK水平密切相关(r =0.357,P =0.003)。结论摇血清和癌组织tM2-PK 测定对CRC 诊

  18. Measurement of anti-mitochondria M2 antibodies in 1039 patients with cryptogenic hepatitis%1039例隐源性肝炎患者AMA-M2抗体的筛查

    Institute of Scientific and Technical Information of China (English)

    张玮; 王磊; 王奕; 王俐琼; 杜慧慧; 李青梅

    2012-01-01

    Objective To investigate the presence of AMA -M2 antibodies in 1039 patients with cryptogenic hepatitis. Methods M2 antibodies were tested by ELISA. Results M2 antibodies were detected in 81 (7.9% )of the 1039 patients;Of the 81 cases,57 were female and 24 were male,and the mean age was 53.0 ± 14.8 year old,and 78 patients were diagnosed as PBC;The most common symptoms were fatigue (74.4%,58/78), jaundice (61.5%, 48/78 )and skin itching (37.2% ,29/78); Besides, 39 (50.0% ) patients were with ANA positive,and 14 (18.0%) with anti-SSA/Ro positive. Conclusion On the diagnosis of the disease,the detection of serum antimitochondrial autoantibodies (AMA) is an important indicator. The detection of AMA-M2 is important for early diagnosis of patients with PBC.%目的 在1039例隐源性肝炎患者中筛查AMA-M2抗体,对男性和女性的M2抗体滴度、M2抗体阳性患者和M2抗体阴性患者的免疫指标、PBC患者的临床表现等进行统计分析,以早期诊断PBC.方法 采用ELISA法检测M2抗体滴度.结果 在1039例隐源性肝炎患者中,81例(7.9%)M2抗体阳性,其中57例为女性,24例为男性,平均年龄53.0±14.8岁;在78例PBC患者中,乏力(74.4%,58/78)、黄疸(61.5%,48/78)和皮肤瘙痒(37.2%,29/78)多见;合并ANA阳性者39例(50.0%,39/78),合并抗-SSA/Ro抗体阳性14例(17.9%,14/78).结论 AMAs的检测是诊断原发性胆汁性肝硬化的重要指标,检测M2抗体有助于早期诊断PBC.

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

    Science.gov (United States)

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

    2016-01-01

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

  20. miR-122 targets pyruvate kinase M2 and affects metabolism of hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Angela M Liu

    Full Text Available In contrast to normal differentiated cells that depend on mitochondrial oxidative phosphorylation for energy production, cancer cells have evolved to utilize aerobic glycolysis (Warburg's effect, with benefit of providing intermediates for biomass production. MicroRNA-122 (miR-122 is highly expressed in normal liver tissue regulating a wide variety of biological processes including cellular metabolism, but is reduced in hepatocellular carcinoma (HCC. Overexpression of miR-122 was shown to inhibit cancer cell proliferation, metastasis, and increase chemosensitivity, but its functions in cancer metabolism remains unknown. The present study aims to identify the miR-122 targeted genes and to investigate the associated regulatory mechanisms in HCC metabolism. We found the ectopic overexpression of miR-122 affected metabolic activities of HCC cells, evidenced by the reduced lactate production and increased oxygen consumption. Integrated gene expression analysis in a cohort of 94 HCC tissues revealed miR-122 level tightly associated with a battery of glycolytic genes, in which pyruvate kinase (PK gene showed the strongest anti-correlation coefficient (Pearson r = -0.6938, p = <0.0001. In addition, reduced PK level was significantly associated with poor clinical outcomes of HCC patients. We found isoform M2 (PKM2 is the dominant form highly expressed in HCC and is a direct target of miR-122, as overexpression of miR-122 reduced both the mRNA and protein levels of PKM2, whereas PKM2 re-expression abrogated the miR-122-mediated glycolytic activities. The present study demonstrated the regulatory role of miR-122 on PKM2 in HCC, having an implication of therapeutic intervention targeting cancer metabolic pathways.

  1. Molecular Cloning, Characterization, and Expression of Cuc m 2, a Major Allergen in Cucumis melo

    Directory of Open Access Journals (Sweden)

    Mojtaba Sankian

    2013-05-01

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

  2. miR-122 targets pyruvate kinase M2 and affects metabolism of hepatocellular carcinoma.

    Science.gov (United States)

    Liu, Angela M; Xu, Zhi; Shek, Felix H; Wong, Kwong-Fai; Lee, Nikki P; Poon, Ronnie T; Chen, Jinfei; Luk, John M

    2014-01-01

    In contrast to normal differentiated cells that depend on mitochondrial oxidative phosphorylation for energy production, cancer cells have evolved to utilize aerobic glycolysis (Warburg's effect), with benefit of providing intermediates for biomass production. MicroRNA-122 (miR-122) is highly expressed in normal liver tissue regulating a wide variety of biological processes including cellular metabolism, but is reduced in hepatocellular carcinoma (HCC). Overexpression of miR-122 was shown to inhibit cancer cell proliferation, metastasis, and increase chemosensitivity, but its functions in cancer metabolism remains unknown. The present study aims to identify the miR-122 targeted genes and to investigate the associated regulatory mechanisms in HCC metabolism. We found the ectopic overexpression of miR-122 affected metabolic activities of HCC cells, evidenced by the reduced lactate production and increased oxygen consumption. Integrated gene expression analysis in a cohort of 94 HCC tissues revealed miR-122 level tightly associated with a battery of glycolytic genes, in which pyruvate kinase (PK) gene showed the strongest anti-correlation coefficient (Pearson r = -0.6938, p = <0.0001). In addition, reduced PK level was significantly associated with poor clinical outcomes of HCC patients. We found isoform M2 (PKM2) is the dominant form highly expressed in HCC and is a direct target of miR-122, as overexpression of miR-122 reduced both the mRNA and protein levels of PKM2, whereas PKM2 re-expression abrogated the miR-122-mediated glycolytic activities. The present study demonstrated the regulatory role of miR-122 on PKM2 in HCC, having an implication of therapeutic intervention targeting cancer metabolic pathways.

  3. Effect of alphas1-casein ( CSN1S1) genotype on milk CSN1S1 content in Malagueña and Murciano-Granadina goats.

    Science.gov (United States)

    Caravaca, Francisco; Amills, Marcel; Jordana, Jordi; Angiolillo, Antonella; Agüera, Pastora; Aranda, Cristina; Menéndez-Buxadera, Alberto; Sánchez, Alfonso; Carrizosa, Juan; Urrutia, Baltasar; Sànchez, Armand; Serradilla, Juan Manuel

    2008-11-01

    There is substantial evidence showing that the polymorphism of the goat alphas1-casein (CSN1S1) gene has a major effect on milk protein, casein and fat content as well as on cheese yield. However, its influence on the synthesis rate of CSN1S1 has been less studied, with measurements only available in French breeds. In this article, we have measured milk CSN1S1 content in 89 Malagueña and 138 Murciano-Granadina goats with 305 and 460 phenotypic registers, respectively. In the Malagueña breed, average values of CSN1S1 content estimated for BB, BF, EE and FF genotypes were 6.94+/-0.38, 5.36+/-0.22, 4.58+/-0.13 and 3.98+/-0.27 g/l, respectively, being all significantly different (Pgene polymorphism on the synthesis rate of the corresponding protein.

  4. M2M communication technology and its application in the intelligrid%M2M通信技术及其在智能电网中的应用

    Institute of Scientific and Technical Information of China (English)

    钟少恒

    2013-01-01

      M2M通信是近年来随着物联网的兴起和发展而得到长足发展的下一代无线通信技术。该技术的发展和普及为智能电网功能的扩展和实现奠定了基础。文章介绍了M2M技术的发展历史和技术特色,探索了M2M通信在智能电网,特别是家庭区域网络的应用前景,同时指出了M2M通信技术目前所面临的问题和挑战。%With the rise and development of IOT, machine-to-machine (M2M) communications is a next generation wireless communications which has significant development. The development and popularization of the technology lay a foundation for the function extension and realization of the intelligrid. The development history and technical features are introduced. The development trend of the M2M communications in intelligrid, especially in home area network is explored. At the same time, the current problems and challenge of the technology is pointed out.

  5. Cost-effectiveness analysis of gemcitabine, S-1 and gemcitabine plus S-1 for treatment of advanced pancreatic cancer based on GEST study.

    Science.gov (United States)

    Zhou, Jing; Zhao, Rongce; Wen, Feng; Zhang, Pengfei; Tang, Ruilei; Du, Zedong; He, Xiaofeng; Zhang, Jian; Li, Qiu

    2015-04-01

    Gemcitabine (GEM) alone, S-1 alone and gemcitabine plus S-1 (GS) have shown a marginal clinical benefit for the treatment of advanced pancreatic cancer. However, there is no clearly defined optimal cost-effectiveness treatment. The objective of this study was to assess the cost-effectiveness of GEM alone, S-1 alone and GS for the treatment of advanced pancreatic cancer based on GEST study for public payers. A decision model compared GEM alone, S-1 alone and GS. Primary base case data were identified using the GEST study and the literatures. Costs were estimated from West China Hospital, Sichuan University, China, and incremental cost-effectiveness ratios (ICERs) were calculated. Survival benefits were reported in quality-adjusted life-months (QALMs). Sensitive analyses were performed by varying potentially modifiable parameters of the model. The base case analysis showed that the GEM cost $21,912 and yielded survival of 6.93 QALMs, S-1 cost $19,371 and yielded survival of 7.90 QALMs and GS cost $22,943 and yielded survival of 7.46 QALMs in the entire treatment. The one-way sensitivity analyses showed that the ICER of S-1 was driven mostly by the S-1 group utility score of stable state compared with GEM, and the GEM group utility score of progressed state played a key role on the ICER of GS compared with GEM. S-1 represents an attractive cost-effective treatment for advanced pancreatic cancer, given the favorable cost per QALM and improvement in clinical efficacy, especially the limited available treatment options.

  6. Post-marketing Safety Evaluation of S-1 in Patients with Inoperable or Recurrent Breast Cancer: Especially in Patients Treated with S-1 + Trastuzumab

    OpenAIRE

    Saito, Yuki; Oshitanai, Risa; Terao, Mayako; Terada, Mizuho; Tsuda, Banri; Okamura, Takuho; Suzuki, Yasuhiro; Tokuda, Yutaka

    2011-01-01

    Objective The purpose of this study was to assess the safety of S-1 in Japanese in inoperable or recurrent breast cancer patients. Methods A prospective post-marketing surveillance was performed at 313 sites in Japan in patients with inoperable or recurrent breast cancer treated with S-1. We examined 1361 patients between January 2006 and December 2007 with regard to the incidence of adverse drug reactions graded by the Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Resu...

  7. Post-marketing safety evaluation of S-1 in patients with inoperable or recurrent breast cancer: especially in patients treated with S-1 + trastuzumab.

    Science.gov (United States)

    Saito, Yuki; Oshitanai, Risa; Terao, Mayako; Terada, Mizuho; Tsuda, Banri; Okamura, Takuho; Suzuki, Yasuhiro; Tokuda, Yutaka

    2011-09-01

    The purpose of this study was to assess the safety of S-1 in Japanese in inoperable or recurrent breast cancer patients. A prospective post-marketing surveillance was performed at 313 sites in Japan in patients with inoperable or recurrent breast cancer treated with S-1. We examined 1361 patients between January 2006 and December 2007 with regard to the incidence of adverse drug reactions graded by the Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. At least one adverse drug reaction was encountered by 858 patients, with an overall incidence of 63.0% (858/1361). The incidence of Grade 3 or higher adverse drug reactions in a descending order was 14.7% (200/1361). In this study, the most common combination drug was trastuzumab. The overall incidence of adverse drug reactions was 63.5% (431/679 patients) in patients treated with S-1 alone, and 55.9% (66/118 patients) in patients treated with S-1 + trastuzumab. Monotherapy with S-1 or combination therapy with S-1 + trastuzumab was well tolerated for inoperable or recurrent breast cancer patients.

  8. Study on the Clinical Application Value of the tM2-PK in the colorectal cancer%tM2-PK 在结直肠癌的应用价值临床研究

    Institute of Scientific and Technical Information of China (English)

    叶红

    2016-01-01

    Objective To study the tumor pyruvate kinase (tM2-PK)expression and its relationship with clinico-pathological characteristics of colorectal cancer in patients with colorectal cancer.Methods 49 cases of colorectal cancer patients for the study,next to the immunohistochemistry cancer tissue and cancer tissue tM2-PK expression and cancer research organizations tM2-PK and serum tM2-PK levels in patients with correlation analysis tM2-PK colorectal cancer patients with pathological relationship.Results 49 cases of tissue tM2-PK positive rate of colorectal cancer in patients with cancer and adjacent tissues respectively 81.6%,42.9%,there was significant difference (P 0.05)at different ages,gender,and different degrees of differentiation on tM2-PK positive rate;40 cases of colorectal cancer cancer tissues tM2-PK-positive pa-tients,with an average score 7.53 ± 1.94,serum concentrations tM2-PK 26.59 ± 10.24,a positive correlation,r =0.876,P =0.0015,statistically significant (P <0.05).Conclusion tM2-PK in the early diagnosis of colorectal cancer, as well as assess the prognosis of the disease and has good prospects.%目的:研究肿瘤型丙酮酸激酶(tM2-PK)在结直肠癌患者表达情况及其与结直肠癌临床病理特征的关系。方法以49例结直肠癌患者为研究对象,免疫组化检测癌组织以及癌旁组织 tM2-PK 表达情况,并研究癌组织 tM2-PK 与患者血清 tM2-PK 水平相关性,分析 tM2-PK 与结直肠癌患者病理特征关系。结果49例结直肠癌患者癌组织与癌旁组织 tM2-PK 阳性率分别为81.6%、42.9%,两者存在统计学差异(P <0.05);结直肠癌组织最大Φ≥5 cm结直肠癌 tM2-PK 阳性率高于最大Φ<5 cm 结直肠癌,在 TNM 分期中Ⅲ+Ⅳ期 tM2-PK 阳性率高于Ⅰ+Ⅱ期,不同Duck 分期上 C+D 期 tM2-PK 阳性率高于 A+B 期;在不同年龄、性别以及不同分化程度上 tM2-PK 阳性率无统计学差异(P >0.05);40

  9. Effect of RE-Al-N on Structures and Properties of M2 Cast High Speed Steel

    Institute of Scientific and Technical Information of China (English)

    符寒光; 杜建铭; 蒋志强; 邢建东

    2003-01-01

    M2 cast high speed steel was inoculated by addition of rare earth(RE)-Al-N, network eutectic carbides were eliminated, matrix microstructures were refined and the segregation of tungsten and molybdenum elements was relieved. In the condition that the hardness does not decrease, impact toughness obviously increases. Quenching at 1180 ℃ and three-times tempering at 560 ℃, the hardness of M2 cast high speed steel is 65~66 HRC, and impact toughness reaches 21.3 J*cm- 2. Modified M2 cast high speed steel has excellent thermal fatigue resistance and high temperature wear resistance. Roller made in modified M2 cast high speed steel has excellent service effect when it is used in slit rolling mill of hot rolling bar mill.

  10. Down-regulated expression of NPM1 in IMS-M2 cell line by (-)-epigallocatechin-3-gallate

    Institute of Scientific and Technical Information of China (English)

    Hoang Thanh Chi; Bui Thi Kim Ly; Hoang Anh Vu; Yuko Sato; Phu Chi Dung; Phan Thi Xinh

    2014-01-01

    Objective: To investigate the inhibited effect of epigallocatechin-3-gallate (EGCG) on the expression of NPM1 in IMS-M2 cells harboring the NPM1 mutations.Methods:Cell proliferation assay was performed to test the effects of EGCG on cell growth of IMS-M2 cells harboring the NPM1 mutations. Western blot analysis were performed to test the protein expression of NPM1, AKT, those associated with apoptosis. Results: EGCG can down-regulate the expression of NPM1 in IMS-M2 cells harboring the NPM1 mutations. Moreover, EGCG also suppressed the cell proliferation and induced apoptosis in IMS-M2 cells.Conclusions:The results suggested that EGCG could be considered as a reagent for treatment of AML patients with NPM1 mutations.

  11. Bariatric Orthopaedics: Total Knee Arthroplasty in Super-obese Patients (BMI > 50 kg/m2). Survivorship and Complications

    National Research Council Canada - National Science Library

    Naziri, Qais; Issa, Kimona; Malkani, Arthur L; Bonutti, Peter M; Harwin, Steven F; Mont, Michael A

    2013-01-01

    Some studies have suggested that patients who are super obese (BMI > 50 kg/m2) may have poorer outcomes and more frequent complications when undergoing TKA compared with those who have lower BMI, however, the literature on this is...

  12. 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.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    OpenAIRE

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

    2015-01-01

    The heart hosts tissue resident macrophages which are capable of modulating cardiac inflammation and function by multiple mechanisms. At present, the consequences of phenotypic diversity in macrophages in the heart are incompletely understood. The contribution of cardiac M2-polarized macrophages to the resolution of inflammation and repair response following myocardial infarction remains to be fully defined. In this study, the role of M2 macrophages was investigated utilising a specific CSF-1...

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

    Science.gov (United States)

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

    2016-03-04

    Currently approved influenza vaccines predominantly protect through antibodies directed against the highly variable glycoprotein hemagglutinin (HA), necessitating annual redesign and formulation based on epidemiological prediction of predominant circulating strains. More conserved influenza protein sequences, such as the ectodomain of the influenza M2 protein, or M2e, show promise as a component of a universal influenza A vaccine, but require a Th1-biased immune response for activity. Recently, recombinant, bacterially derived outer membrane vesicles (OMVs) demonstrated potential as a platform to promote a Th1-biased immune response to subunit antigens. Here, we engineer three M2e-OMV vaccines and show that all elicit strong IgG titers, with high IgG2a:IgG1 ratios, in BALB/c mice. Additionally, the administration of one M2e-OMV construct containing tandem heterologous M2e peptides (M2e4xHet-OMV) resulted in 100% survival against lethal doses of the mouse-adapted H1N1 influenza strain PR8. Passive transfer of antibodies from M2e4xHet-OMV vaccinated mice to unvaccinated mice also resulted in 100% survival to challenge, indicating that protection is driven largely via antibody-mediated immunity. The potential mechanism through which M2e-OMVs initiated the immune response was explored and it was found that the constructs triggered TLR1/2, TLR4, and TLR5. Our data indicate that OMVs have potential as a platform for influenza A vaccine development due to their unique adjuvant profile and intrinsic pathogen-mimetic nature. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. 胃癌组织中ENO1、M2-PK蛋白表达及其临床意义%Expressions and Clinical Significances of ENO1 and M2-PK in Gastric Cancer

    Institute of Scientific and Technical Information of China (English)

    倪田根; 祝秉东; 周欣; 王娜; 曾峰; 关泉林

    2011-01-01

    目的:探讨胃癌组织中烯醇化酶-α(enolase-α,ENO1)、肿瘤型丙酮酸激酶(tumor M2 pyruvate kinase,M2-PK)的表达、相互关系及临床病理学意义.方法:应用免疫组织化学SP染色方法分别对55例胃癌组织和23例胃良性病变组织切片染色,观察胃癌组织和良性病变组织ENO1、M2-PK的表达情况及分析两者临床病理关系.结果:胃癌组织中ENO1阳性表达率为67.3% (37/55),明显高于胃良性病变组30.4%(7/23)(P<0.01),其表达与胃癌分化程度、浸润深度、淋巴结转移及TNM分期均显著相关(均P<0.05).M2-PK在胃癌组织中的阳性表达率为78.2%(43/55),明显高于胃良性病变组织39.1%(9/23) (P<0.01),其表达与胃癌分化程度、浸润深度均显著相关(均P<0.05).胃癌组织中ENO1与M2-PK的表达呈正相关(r=0.5729,P<0.05).结论:ENO1和M2-PK的表达上调与胃癌的发生、发展可能有关,联合检测两种蛋白在肿瘤组织中的表达,对临床判断胃癌的预后有一定的指导意义.%Objective: To investigate the expression and clinicopathotogical significance of enolase-a (ENO1) and tumor M2 pyruvate kinase (M2-PK) in gastric cancer. Methods: The expression of ENO1 and M2-PK in 55 paraffin-embedded specimens of gastric cancer and 23 paraffin-embedded specimens of benign gastric tissue was detected by S-P immunohistochemistry. The correlation of ENO1 expression to M2-PK. Expression, and their correlations to the clinicophathologic features of gastric cancer were analyzed. Results: The positive rate of ENO1 was significantly higher in gastric cancer than in benign gastric tissue (67.3% vs . 30.4%, P<0.01) , and closely related to differentiation grade ( P<0.01) , depth of invasion (P<0.01), lymph node metastasis (P<0.05) and TNM staging( P<0. 05),The positive rate of M2-PK. Was significantly higher in gastric cancer than in benign gastric tissue (78.2%vs . 39,1%, P<0.01) , and closely related to differentiation grade ( P0

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

    Science.gov (United States)

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

    2013-07-01

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

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

    Science.gov (United States)

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

    2015-10-01

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

  19. 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.

  20. On Use of the Variable Zagreb vM2 Index in QSPR: Boiling Points of Benzenoid Hydrocarbons

    Directory of Open Access Journals (Sweden)

    Albin Jurić

    2004-12-01

    Full Text Available The variable Zagreb vM2 index is introduced and applied to the structure-boiling point modeling of benzenoid hydrocarbons. The linear model obtained (thestandard error of estimate for the fit model Sfit=6.8 oC is much better than thecorresponding model based on the original Zagreb M2 index (Sfit=16.4 oC. Surprisingly,the model based on the variable vertex-connectivity index (Sfit=6.8 oC is comparable tothe model based on vM2 index. A comparative study with models based on the vertex-connectivity index, edge-connectivity index and several distance indices favours modelsbased on the variable Zagreb vM2 index and variable vertex-connectivity index.However, the multivariate regression with two-, three- and four-descriptors givesimproved models, the best being the model with four-descriptors (but vM2 index is notamong them with Sfit=5 oC, though the four-descriptor model contaning vM2 index isonly slightly inferior (Sfit=5.3 oC.

  1. Research on Autoantibodies Against Myocardial β1-adrenergic and M2 Cholinergic Receptors in Patients With Chronic Keshan Disease

    Institute of Scientific and Technical Information of China (English)

    Han Zhenhua; Niu Xiaolin; Ren Fuxian

    2006-01-01

    Objectives To explore the relationship between serum autoantibodies against myocardial β1-adrenergic, M2-cholinergic receptors and chronic Keshan disease (CKD). Methods The second extracellular loops of β1 and M2 receptors on human cardiomyocytes were used as the antigens.Enzyme linked immunosorbent assay (ELISA) was applied to determine serum autoantibodies against myocardial β1 and M2 receptors in 32 CKD patients. 31 healthy subjects from endemic area were selected as the control. Results Positive rate of autoantibodies against myocardial β1 adrenergic (51.3%, 17/32) and M2cholinergic (56.3% , 18/32) receptors weresignificantly higher than those in the control (9.7%, 3/31; 12.9%, 4/31) (both P < 0.01). Both positive rate and titers of above autoantibodies in NYHA Ⅱ~Ⅲ CKD patients were significantly higher than those in NYHA Ⅳ , demonstrating an apparently positive correlation between serum antibodies against myocardial β1 and M2 receptors (r=0.95). Conclusions Autoantibodies against myocardial β1 and M2 receptors were found in sera of CKD patients; distribution of positive rate and titers of the autoantibodies in CKD patients in various NYHA classes of cardiac function are significantly different.

  2. Research Pilot Milt Thompson in M2-F2 Aircraft Attached to B-52 Mothership

    Science.gov (United States)

    1966-01-01

    NASA research pilot Milt Thompson sits in the M2-F2 'heavyweight' lifting body research vehicle before a 1966 test flight. The M2-F2 and the other lifting-body designs were all attached to a wing pylon on NASA's B-52 mothership and carried aloft. The vehicles were then drop-launched and, at the end of their flights, glided back to wheeled landings on the dry lake or runway at Edwards AFB. The lifting body designs influenced the design of the Space Shuttle and were also reincarnated in the design of the X-38 in the 1990s. NASA B-52, Tail Number 008, is an air launch carrier aircraft, 'mothership,' as well as a research aircraft platform that has been used on a variety of research projects. The aircraft, a 'B' model built in 1952 and first flown on June 11, 1955, is the oldest B-52 in flying status and has been used on some of the most significant research projects in aerospace history. Some of the significant projects supported by B-52 008 include the X-15, the lifting bodies, HiMAT (highly maneuverable aircraft technology), Pegasus, validation of parachute systems developed for the space shuttle program (solid-rocket-booster recovery system and the orbiter drag chute system), and the X-38. The B-52 served as the launch vehicle on 106 X-15 flights and flew a total of 159 captive-carry and launch missions in support of that program from June 1959 to October 1968. Information gained from the highly successful X-15 program contributed to the Mercury, Gemini, and Apollo human spaceflight programs as well as space shuttle development. Between 1966 and 1975, the B-52 served as the launch aircraft for 127 of the 144 wingless lifting body flights. In the 1970s and 1980s, the B-52 was the launch aircraft for several aircraft at what is now the Dryden Flight Research Center, Edwards, California, to study spin-stall, high-angle-of attack, and maneuvering characteristics. These included the 3/8-scale F-15/spin research vehicle (SRV), the HiMAT (Highly Maneuverable Aircraft

  3. Use of M2e ELISAs for longitudinal surveillance of commercial poultry in Indonesia vaccinated against highly pathogenic avian influenza.

    Science.gov (United States)

    Wibowo, Michael Haryadi; Tarigan, Simson; Sumarningsih; Artanto, Sidna; Indriani, Risa; Anggoro, Dito; Putra, Cahyaditya Pratama; Idris, Syafrison; Untari, Tri; Asmara, Widya; Tabbu, Charles Rangga; Ignjatovic, Jagoda

    2017-11-01

    In countries where highly pathogenic avian influenza virus (HPAIV) H5N1 is endemic and controlled by vaccination, post-vaccination serological monitoring is essential to differentiate vaccinated poultry from those that are infected. The objectives of this study were to validate two experimental ELISAs that detect antibodies raised against the M2e protein of avian influenza virus that can be used for DIVA purposes. Results from the sM2e and tM2e ELISAs were compared with other conventional tests for the detection of H5N1influenza virus (virus isolation and RT-PCR) using samples collected from 16 commercial flocks in Indonesia. These comprised vaccinated layers aged between 18 and 68 weeks old that were sampled at ten-weekly intervals. A small number of sera were positive in sM2e and tM2e ELISA, 14 (0.6%) and 17 (0.7%) respectively, with low OD420 (0.1-0.3), but only 4 sera were positive in both tests. At the flock level, the incidence of M2e positive sera was low (4%), well below previously established minimum of 40% for an HPAIV H5N1-infected flock. Conventional M and H5 gene RT-PCRs indicated that none of 16 flocks were infected at any time during the study. No virus was isolated from any of the 480 pooled swab samples, except from one, for which the combined data analysis suggest to be the result of a laboratory cross-contamination. Clinical disease, mortalities or reduction in production performance, indicative of field H5N1 challenge, were not observed either in any of the flocks. Birds from two surveyed flocks, challenged in the laboratory with an Indonesian HPAIV H5N1 developed M2e antibodies in 50% and 55% of surviving birds with OD420 in the range of 0.35-1.47 in tM2e ELISA, confirming the validity of the criteria established for use of M2e ELISA for DIVA purposes. Overall these results showed that the tM2e ELISA could be a useful monitoring tool to ascertain freedom from H5N1 infections in vaccinated commercial poultry. Copyright © 2017 Elsevier B.V. All

  4. Functions of pyruvate kinase M2 in tumorigenesis%丙酮酸激酶M2型在肿瘤发生过程中的作用

    Institute