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Sample records for m1 m2 isomers

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

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    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.

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

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    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.

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

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    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

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

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    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.

  5. Differential Roles of M1 and M2 Microglia in Neurodegenerative Diseases.

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    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.

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

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    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. 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.

  8. Molecular mechanisms that regulate the macrophage M1/M2 polarization balance

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    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.

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

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    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

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

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    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.

  11. Tramadol differentially regulates M1 and M2 macrophages from human umbilical cord blood.

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    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).

  12. Macrophage polarisation: an immunohistochemical approach for identifying M1 and M2 macrophages.

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    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

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

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    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.

  14. Anti-CD47 Treatment Stimulates Phagocytosis of Glioblastoma by M1 and M2 Polarized Macrophages and Promotes M1 Polarized Macrophages In Vivo.

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    Michael Zhang

    Full Text Available Tumor-associated macrophages (TAMs represent an important cellular subset within the glioblastoma (WHO grade IV microenvironment and are a potential therapeutic target. TAMs display a continuum of different polarization states between antitumorigenic M1 and protumorigenic M2 phenotypes, with a lower M1/M2 ratio correlating with worse prognosis. Here, we investigated the effect of macrophage polarization on anti-CD47 antibody-mediated phagocytosis of human glioblastoma cells in vitro, as well as the effect of anti-CD47 on the distribution of M1 versus M2 macrophages within human glioblastoma cells grown in mouse xenografts. Bone marrow-derived mouse macrophages and peripheral blood-derived human macrophages were polarized in vitro toward M1 or M2 phenotypes and verified by flow cytometry. Primary human glioblastoma cell lines were offered as targets to mouse and human M1 or M2 polarized macrophages in vitro. The addition of an anti-CD47 monoclonal antibody led to enhanced tumor-cell phagocytosis by mouse and human M1 and M2 macrophages. In both cases, the anti-CD47-induced phagocytosis by M1 was more prominent than that for M2. Dissected tumors from human glioblastoma xenografted within NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice and treated with anti-CD47 showed a significant increase of M1 macrophages within the tumor. These data show that anti-CD47 treatment leads to enhanced tumor cell phagocytosis by both M1 and M2 macrophage subtypes with a higher phagocytosis rate by M1 macrophages. Furthermore, these data demonstrate that anti-CD47 treatment alone can shift the phenotype of macrophages toward the M1 subtype in vivo.

  15. Anti-CD47 Treatment Stimulates Phagocytosis of Glioblastoma by M1 and M2 Polarized Macrophages and Promotes M1 Polarized Macrophages In Vivo

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    Kahn, Suzana A.; Azad, Tej D.; Gholamin, Sharareh; Xu, Chelsea Y.; Liu, Jie; Achrol, Achal S.; Richard, Chase; Sommerkamp, Pia; Schoen, Matthew Kenneth; McCracken, Melissa N.; Majeti, Ravi; Weissman, Irving; Mitra, Siddhartha S.; Cheshier, Samuel H.

    2016-01-01

    Tumor-associated macrophages (TAMs) represent an important cellular subset within the glioblastoma (WHO grade IV) microenvironment and are a potential therapeutic target. TAMs display a continuum of different polarization states between antitumorigenic M1 and protumorigenic M2 phenotypes, with a lower M1/M2 ratio correlating with worse prognosis. Here, we investigated the effect of macrophage polarization on anti-CD47 antibody-mediated phagocytosis of human glioblastoma cells in vitro, as well as the effect of anti-CD47 on the distribution of M1 versus M2 macrophages within human glioblastoma cells grown in mouse xenografts. Bone marrow-derived mouse macrophages and peripheral blood-derived human macrophages were polarized in vitro toward M1 or M2 phenotypes and verified by flow cytometry. Primary human glioblastoma cell lines were offered as targets to mouse and human M1 or M2 polarized macrophages in vitro. The addition of an anti-CD47 monoclonal antibody led to enhanced tumor-cell phagocytosis by mouse and human M1 and M2 macrophages. In both cases, the anti-CD47-induced phagocytosis by M1 was more prominent than that for M2. Dissected tumors from human glioblastoma xenografted within NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice and treated with anti-CD47 showed a significant increase of M1 macrophages within the tumor. These data show that anti-CD47 treatment leads to enhanced tumor cell phagocytosis by both M1 and M2 macrophage subtypes with a higher phagocytosis rate by M1 macrophages. Furthermore, these data demonstrate that anti-CD47 treatment alone can shift the phenotype of macrophages toward the M1 subtype in vivo. PMID:27092773

  16. Prospect of triggering the 178m2Hf isomer and the role of resonance conversion

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    Karpeshin, F. F.; Trzhaskovskaya, M. B.; Zhang, J.

    2009-03-01

    A mechanism of triggering the 12.7keV E3 transition, based on the new decay mode of the 31y isomer via resonance internal conversion and emission of a 1.4keV X-ray quantum, is considered. Actually, this decay mode was observed previously in the decay of 45- and 46-fold ions of 125Te . For the purpose of triggering, the atomic radiative vertex has to be induced by resonance radiation. This mechanism makes triggering by an order of magnitude more efficient than triggering a bare nucleus, and is achieved at a lower combination frequency. An experiment is proposed for the direct observation of the new decay mode. This also offers a new way of resonance scattering of these X-rays. Triggering through higher-lying 2573 and 2805keV states is also considered. The results are extended to the general problem of triggering. The main obstacle for enhancing the efficiency is a high internal conversion rate. For this reason, shape isomers with low multipole order -- E1 , M1 , and with a high enough energy of triggering transition are of interest for triggering. The partial ionization of the outer electrons will also help. The same recommendations hold for triggering isomers in laser-produced plasma.

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

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    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.

  18. 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

  19. Haemophilus ducreyi-induced interleukin-10 promotes a mixed M1 and M2 activation program in human macrophages.

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    Li, Wei; Katz, Barry P; Spinola, Stanley M

    2012-12-01

    During microbial infection, macrophages are polarized to classically activated (M1) or alternatively activated (M2) cells in response to microbial components and host immune mediators. Proper polarization of macrophages is critical for bacterial clearance. To study the role of macrophage polarization during Haemophilus ducreyi infection, we analyzed a panel of macrophage surface markers in skin biopsy specimens of pustules obtained from experimentally infected volunteers. Lesional macrophages expressed markers characteristic of both M1 and M2 polarization. Monocyte-derived macrophages (MDM) also expressed a mixed M1 and M2 profile of surface markers and cytokines/chemokines upon infection with H. ducreyi in vitro. Endogenous interleukin 10 (IL-10) produced by infected MDM downregulated and enhanced expression of several M1 and M2 markers, respectively. Bacterial uptake, mediated mainly by class A scavenger receptors, and activation of mitogen-activated protein kinase and phosphoinositide 3-kinase signaling pathways were required for H. ducreyi-induced IL-10 production in MDM. Compared to M1 cells, IL-10-polarized M2 cells displayed enhanced phagocytic activity against H. ducreyi and similar bacterial killing. Thus, IL-10-modulated macrophage polarization may contribute to H. ducreyi clearance during human infection.

  20. Different roles for M1 and M2 receptors within perirhinal cortex in object recognition and discrimination.

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    Bartko, Susan J; Winters, Boyer D; Saksida, Lisa M; Bussey, Timothy J

    2014-04-01

    Recognition and discrimination of objects and individuals are critical cognitive faculties in both humans and non-human animals, and cholinergic transmission has been shown to be essential for both of these functions. In the present study we focused on the role of M1 and M2 muscarinic receptors in perirhinal cortex (PRh)-dependent object recognition and discrimination. The selective M1 antagonists pirenzepine and the snake toxin MT-7, and a selective M2 antagonist, AF-DX 116, were infused directly into PRh. Pre-sample infusions of both pirenzepine and AF-DX 116 significantly impaired object recognition memory in a delay-dependent manner. However, pirenzepine and MT-7, but not AF-DX 116, impaired oddity discrimination performance in a perceptual difficulty-dependent manner. The findings indicate distinct functions for M1 and M2 receptors in object recognition and discrimination.

  1. Role of Microglial M1/M2 Polarization in Relapse and Remission of Psychiatric Disorders and Diseases

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    Yutaka Nakagawa

    2014-11-01

    Full Text Available Psychiatric disorders such as schizophrenia and major depressive disorder were thought to be caused by neurotransmitter abnormalities. Patients with these disorders often experience relapse and remission; however the underlying molecular mechanisms of relapse and remission still remain unclear. Recent advanced immunological analyses have revealed that M1/M2 polarization of macrophages plays an important role in controlling the balance between promotion and suppression in inflammation. Microglial cells share certain characteristics with macrophages and contribute to immune-surveillance in the central nervous system (CNS. In this review, we summarize immunoregulatory functions of microglia and discuss a possible role of microglial M1/M2 polarization in relapse and remission of psychiatric disorders and diseases. M1 polarized microglia can produce pro-inflammatory cytokines, reactive oxygen species, and nitric oxide, suggesting that these molecules contribute to dysfunction of neural network in the CNS. Alternatively, M2 polarized microglia express cytokines and receptors that are implicated in inhibiting inflammation and restoring homeostasis. Based on these aspects, we propose a possibility that M1 and M2 microglia are related to relapse and remission, respectively in psychiatric disorders and diseases. Consequently, a target molecule skewing M2 polarization of microglia may provide beneficial therapies for these disorders and diseases in the CNS.

  2. 替米沙坦对小鼠巨噬细胞 M1M2亚型极化的影响%Effect of Telmisartan on mice macrophage M1/M2 polarization

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    邢亦明; 胡泽平; 王邦宁; 周青; 汪渊

    2016-01-01

    Objective To investigate the effect of Telmisartan on the M1 /M2 polarization of mice macrophage . Methods Mice macrophage was induced to M1 /M2 polarization by LPS +IFN-γand IL-4 respectively, and tested by immunofluorescence.Meanwhile cells were treated with 0.1,1,10 μmol /L Telmisartan,blank control group and vehicle control group were established at the same time .The biomarkers iNOS and Arg Ⅰ were tested by Western blot, and the cytokines IL-6 and IL-10 were tested by ELISA assay.Results The biomarker iNOS and IL-6,secre-ted by M1 macrophage, were apparently increased in the macrophages induced by LPS +IFN-γ.However, after be-ing treated with Telmisartan,the expressions of iNOS and IL-6 were obviously decreased(P <0.05), as the concen-tration higher the expression lower .While, the expression of Arg I and IL-10, which represented the M2 macro-phage, increased ( P <0.05).Conclusion Telmisartan can inhibit the M1 polarization of mice macrophage RAW264.7 induced by LPS and IFN-γand transform M1 macrophage polarization to M2 macrophage polarization.%目的探讨替米沙坦对小鼠巨噬细胞 M1M2亚型极化的影响。方法分别用脂多糖(LPS)联合干扰素-γ(IFN-γ)和白介素-4(IL-4)诱导小鼠巨噬细胞 M1M2型极化,用免疫荧光法检测极化结果。在 M1型巨噬细胞中分别加入0.1、1、10μmol/L 替米沙坦,同时设立空白对照组及溶剂对照组,Western blot 法检测各组巨噬细胞亚型标志物诱导性一氧化氮合酶(iNOS)和精氨酸酶Ⅰ(Arg Ⅰ)的表达情况, ELISA 法检测各组培养液上清中 IL-6、IL-10表达情况。结果在 LPS +IFN-γ诱导的小鼠巨噬细胞中 M1型巨噬细胞标志物 iNOS、IL-6的表达水平明显升高,替米沙坦干预后,各干预组 M1型巨噬细胞标志物 iNOS、IL-6的表达水平下降(P <0.05),随着替米沙坦浓度的增加而降低,而代表 M2型巨噬细胞标志物的 Arg

  3. M1 and M2 macrophage recruitment during tendon regeneration induced by amniotic epithelial cell allotransplantation in ovine.

    Science.gov (United States)

    Mauro, Annunziata; Russo, Valentina; Di Marcantonio, Lisa; Berardinelli, Paolo; Martelli, Alessandra; Muttini, Aurelio; Mattioli, Mauro; Barboni, Barbara

    2016-04-01

    Recently, we have demonstrated that ovine amniotic epithelial cells (oAECs) allotransplanted into experimentally induced tendon lesions are able to stimulate tissue regeneration also by reducing leukocyte infiltration. Amongst leukocytes, macrophages (Mφ) M1 and M2 phenotype cells are known to mediate inflammatory and repairing processes, respectively. In this research it was investigated if, during tendon regeneration induced by AECs allotransplantation, M1Mφ and M2Mφ phenotype cells are recruited and differently distributed within the lesion site. Ovine AECs treated and untreated (Ctr) tendons were explanted at 7, 14, and 28 days and tissue microarchitecture was analyzed together with the distribution and quantification of leukocytes (CD45 positive), Mφ (CD68 pan positive), and M1Mφ (CD86, and IL12b) and M2Mφ (CD206, YM1 and IL10) phenotype related markers. In oAEC transplanted tendons CD45 and CD68 positive cells were always reduced in the lesion site. At day 14, oAEC treated tendons began to recover their microarchitecture, contextually a reduction of M1Mφ markers, mainly distributed close to oAECs, and an increase of M2Mφ markers was evidenced. CD206 positive cells were distributed near the regenerating areas. At day 28 oAECs treated tendons acquired a healthy-like structure with a reduction of M2Mφ. Differently, Ctr tendons maintained a disorganized morphology throughout the experimental time and constantly showed high values of M1Mφ markers. These findings indicate that M2Mφ recruitment could be correlated to tendon regeneration induced by oAECs allotransplantation. Moreover, these results demonstrate oAECs immunomodulatory role also in vivo and support novel insights into their allogeneic use underlying the resolution of tendon fibrosis.

  4. Macrophages Undergo M1-to-M2 Transition in Adipose Tissue Regeneration in a Rat Tissue Engineering Model.

    Science.gov (United States)

    Li, Zhijin; Xu, Fangfang; Wang, Zhifa; Dai, Taiqiang; Ma, Chao; Liu, Bin; Liu, Yanpu

    2016-10-01

    Macrophages are involved in the full processes of tissue healing or regeneration and play an important role in the regeneration of a variety of tissues. Although recent evidence suggests the role of different macrophage phenotypes in adipose tissue expansion, metabolism, and remodeling, the spectrum of macrophage phenotype in the adipose tissue engineering field remains unknown. The present study established a rat model of adipose tissue regeneration using a tissue engineering chamber. Macrophage phenotypes were assessed during the regenerative process in the model. Neo-adipose tissue was generated 6 weeks after implantation. Macrophages were obvious in the chamber constructs 3 days after implantation, peaked at day 7, and significantly decreased thereafter. At day 3, macrophages were predominantly M1 macrophages (CCR7+), and there were few M2 macrophages (CD206+). At day 7, the percentage of M2 macrophages significantly increased and remained stable at day 14. M2 macrophages became the predominant macrophage population at 42 days. Enzyme-linked immunosorbent assay demonstrated transition of cytokines from pro-inflammatory to anti-inflammatory, which was consistent with the transition of macrophage phenotype from M1 to M2. These results showed distinct transition of macrophage phenotypes from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 in adipose tissue regeneration in our tissue engineering model. This study provides new insight into macrophage phenotype transition in the regeneration of adipose tissue.

  5. Occurrence of aflatoxins M(1) and M(2) in milk commercialized in Ribeirão Preto-SP, Brazil.

    Science.gov (United States)

    Garrido, N S; Iha, M H; Santos Ortolani, M R; Duarte Fávaro, R M

    2003-01-01

    Aflatoxins are toxic metabolites found in foods and feeds. When ruminants eat foodstuffs containing aflatoxins B(1) and B(2), these toxins are metabolized and excreted as aflatoxin M(1) and M(2) in milk. The aim was to determine the incidence of these aflatoxins in commercial milk collected from supermarkets in Ribeirão Preto-SP, Brazil, and consisting of 60 ultrahigh temperature (UHT) milk samples and 79 pasteurized milk samples. The milk samples were analysed according to method 986.16 of AOAC International. None of the milk samples analysed were contaminated with aflatoxin M(2), and aflatoxin M(1) was detected in 29 (20.9%) of samples in the range 50-240 ng l(-1). The results show that despite a high occurrence of aflatoxin M(1) in commercial pasteurized and UHT milk sold in Ribeirão Preto in 1999 and 2000, the contamination level of these toxins could not be considered a serious public health problem according to MERCOSUR Technical Regulations. However, levels in 20.9% of the milk samples exceeded the concentration of 50 ng l(-1) permitted by the European Union. Although it is not necessary to continue monitoring the incidence and levels of aflatoxins M(1) and M(2) in milk samples, surveillance could be appropriate.

  6. Active vitamin D prevents podocyte injury via regulation of macrophage M1 and M2 phenotype in diabetic nephropathy rats

    Institute of Scientific and Technical Information of China (English)

    郭银凤

    2014-01-01

    Objective To investigate the effect of active vitamin D(VD)on macrophage M1 and M2 phenotype and its role in protecting podocyte impairment in diabetic nephropathy(DN).Methods Diabetes mellitus rats were established by intraperitoneal injection with streptozocin.Rats were randomly divided into four groups:normal-1(NC-1,n=8),normal-2(NC-2,n=8,normal rats treated with calcitriol 0.1μg·kg-1·d-1by gavages),

  7. Differential effects of m1 and m2 receptor antagonists in perirhinal cortex on visual recognition memory in monkeys.

    Science.gov (United States)

    Wu, Wei; Saunders, Richard C; Mishkin, Mortimer; Turchi, Janita

    2012-07-01

    Microinfusions of the nonselective muscarinic antagonist scopolamine into perirhinal cortex impairs performance on visual recognition tasks, indicating that muscarinic receptors in this region play a pivotal role in recognition memory. To assess the mnemonic effects of selective blockade in perirhinal cortex of muscarinic receptor subtypes, we locally infused either the m1-selective antagonist pirenzepine or the m2-selective antagonist methoctramine in animals performing one-trial visual recognition, and compared these scores with those following infusions of equivalent volumes of saline. Compared to these control infusions, injections of pirenzepine, but not of methoctramine, significantly impaired recognition accuracy. Further, similar doses of scopolamine and pirenzepine yielded similar deficits, suggesting that the deficits obtained earlier with scopolamine were due mainly, if not exclusively, to blockade of m1 receptors. The present findings indicate that m1 and m2 receptors have functionally dissociable roles, and that the formation of new visual memories is critically dependent on the cholinergic activation of m1 receptors located on perirhinal cells. Published by Elsevier Inc.

  8. M1, M2 Growth Scissors:Causes, Influence and Countermeasures%M1M2月度同比增速剪刀差:成因、影响与应对

    Institute of Scientific and Technical Information of China (English)

    娄飞鹏

    2016-01-01

    Since October 2015, the monthly growth rate of M1 exceeds M2 again and continues till today, and during this period the scissors are gradually expanding. This is because monetary expansion brings more capital precipitation, but increasing liquidity doesn't effectively flow to the real economy in recent years. There are different effects of the M1 and M2 scissors on macroeconomic between long-term and short-term. To effectively cope with the M1 and M2 scissors, we need to reduce investment and financing costs and improve the efficiency of investment and financing; promote the healthy development of the real estate market and expand the main types of investment channels; flexible use of various macro-control policies, through policy coordination to improve control effect.%从2015年10月起,我国M1M2月度同比增速剪刀差现象再次出现并延续至今,且剪刀差在逐步扩大。这次剪刀差的出现是近几年来货币扩张带来较多的资金沉淀,增加了流动性,但充裕的流动性并未有效流向实体经济所致。剪刀差的持续存在对宏观经济长短期走势存在不同的影响。为有效应对剪刀差,需要降低实体经济投融资成本,提高投融资效率;推动房地产市场健康发展,扩大各类主体的投资渠道;灵活运用各种宏观调控政策,通过政策配合提高调控效果。

  9. Solvothermal synthesis and characterization of a novel selenidoantimonate: [M1(C4H13N3)2]n [M2Sb2Se5]n(M1- Mn、 Co, M2 = Zn、 Cd)%溶剂热法合成新型锑硒化合物[M1(C4H13N3)2]n[M2Sb2Se5]n(M1=Mn、Co,M2=Zn、Cd)及结构

    Institute of Scientific and Technical Information of China (English)

    姜浩; 王欣; 盛天录; 胡胜民; 傅瑞标; 温跃红; 沈超君; 袁宁; 吴新涛

    2011-01-01

    以二乙烯三胺为模板剂,通过溶剂热法制备了一种新型有机无机杂化锑硒化合物:[M1(C4H13N3)2]n[M2Sb2Se5]n(M1=Mn、Co,M2=Zn、Cd).相比传统的有机无机杂化锑硒化合物,过渡金属Zn和Cd参与了这种化合物主框架的构建,使化合物的主框架由传统的SbSex单元转变为Zn(Cd)SbSe5的配位单元.据我们所知,这是第一次合成出Zn和Cd参与SbSex骨架配位的有机无机杂化锑硒化合物.同时,由于结构中CdSe4和ZnSe4单元的存在,使得该化合物表现出荧光性质.这种化合物的出现,使得我们有可能通过相同的途径合成出一系列具有该类型结构特征,在发光领域有潜在应用前景的新型锑硒化合物.%A novel inorganic-organic hybrid selenidoantimonate material, [M1(C4Hi3N3)2]n[M2Sb2Se5]n (M1= Mn,Co M2= Zn, Cd), was synthesized by solvothermal reaction. Dien(diethylenetriamine) was used as a templatedirected reagent. Until now, this compound, to the best of our knowledge, is the first selenidoantimonate, in which zinc and cadmium incorporated into the SbSe3 framework, leading to the formation of ZnSbSe5 and CdSbSe5.Furthermore, because of the ZnSe4 and CdSe4 units in the framework, all the compounds exhibit emission of fluorescence. By the same way, it is possible to synthesize series of compounds with similar novel structure and potential application value in luminescence area.

  10. Classification of M1/M2-polarized human macrophages by label-free hyperspectral reflectance confocal microscopy and multivariate analysis.

    Science.gov (United States)

    Bertani, Francesca R; Mozetic, Pamela; Fioramonti, Marco; Iuliani, Michele; Ribelli, Giulia; Pantano, Francesco; Santini, Daniele; Tonini, Giuseppe; Trombetta, Marcella; Businaro, Luca; Selci, Stefano; Rainer, Alberto

    2017-08-21

    The possibility of detecting and classifying living cells in a label-free and non-invasive manner holds significant theranostic potential. In this work, Hyperspectral Imaging (HSI) has been successfully applied to the analysis of macrophagic polarization, given its central role in several pathological settings, including the regulation of tumour microenvironment. Human monocyte derived macrophages have been investigated using hyperspectral reflectance confocal microscopy, and hyperspectral datasets have been analysed in terms of M1 vs. M2 polarization by Principal Components Analysis (PCA). Following PCA, Linear Discriminant Analysis has been implemented for semi-automatic classification of macrophagic polarization from HSI data. Our results confirm the possibility to perform single-cell-level in vitro classification of M1 vs. M2 macrophages in a non-invasive and label-free manner with a high accuracy (above 98% for cells deriving from the same donor), supporting the idea of applying the technique to the study of complex interacting cellular systems, such in the case of tumour-immunity in vitro models.

  11. Association of m1 and m2 muscarinic receptor proteins with asymmetric synapses in the primate cerebral cortex: morphological evidence for cholinergic modulation of excitatory neurotransmission.

    OpenAIRE

    Mrzljak, L; Levey, A I; Goldman-Rakic, P S

    1993-01-01

    Muscarinic m1 receptors traditionally are considered to be postsynaptic to cholinergic fibers, while m2 receptors are largely presynaptic receptors associated with axons. We have examined the distribution of these receptor proteins in the monkey cerebral cortex and obtained results that are at odds with this expectation. Using immunohistochemistry with specific antibodies to recombinant m1 and m2 muscarinic receptor proteins, we have demonstrated that both m1 and m2 receptors are prominently ...

  12. Activation of the α7 nicotinic receptor promotes lipopolysaccharide-induced conversion of M1 microglia to M2

    Science.gov (United States)

    Zhang, Qichun; Lu, Ying; Bian, Huimin; Guo, Liwei; Zhu, Huaxu

    2017-01-01

    The α7 subtype of the nicotinic acetylcholine receptor (α7 nAChR) plays an essential role in the cholinergic anti-inflammatory pathway that regulates macrophage/microglia function in inflammation. Similar to M1 and M2 macrophages, M1 and M2 microglia exhibit pro-inflammation and anti-inflammation properties, respectively. In the present study, we analyzed function-associated phenotypes to detect the transformation of microglia with activation of α7 nAChRs. We used lentivirus-mediated shRNA to knockdown the expression of α7 nAChR in BV-2 microglia incubated with lipopolysaccharides (LPS, 0.1 μg/mL) and measured the acetylcholine (Ach, 1 μg/mL)-mediated release of cytokines, such as IL-1β, IL-4, IL-6, and IL-10, in the culture supernatant via radioimmunoassay. After stimulation with Ach, the expression of typical biomarkers for different microglia phenotypes, Iba-1 and Arg-1, was determined by cellular immunofluorescence. Furthermore, the expression of signaling molecules, including p38, JAK2/STAT3, PI3K/Akt and miR-124, was analyzed via western blotting and real-time PCR. We found that Ach inhibited LPS-induced IL-1β and IL-6 elevation and promoted IL-4 and IL-10 production and that knockdown of the α7 nAChR abolished these effects of Ach. In addition, Ach decreased LPS-induced Iba-1 expression and increased Arg-1 levels in an α7 nAChR-dependent manner. The LPS-inhibited activation of JAK2/STAT3 and PI3K/Akt was also rescued by Ach, an effect that was blocked by knockdown of the α7 nAChR. In contrast, Ach triggered the phosphorylation of JAK2 and STAT3 that was otherwise inactivated by LPS in BV-2 cells. Finally, the levels of miR-124 and downstream targets C/EBPα and PU.1 were significantly enhanced in LPS-treated BV-2 microglia, and the effect of Ach on this signaling pathway was blocked by α7 nAChR knockdown as expected. Overall, our data demonstrate that activation ofα7 nAChRs inhibits the transformation of M1 microglia and promotes the M2

  13. Unilateral supraorbital keyhole approach in patients with middle cerebral artery (M1-M2 segment) symmetrical aneurysms.

    Science.gov (United States)

    Martellotta, N; Gigante, N; Toscano, S; Maddalena, G F; Tripodi, M; Settembrini, G; Stroscio, C; Distefano, G; Citro, E

    2003-08-01

    A left middle cerebral artery aneurysm at the bifurcation (M1-M2 segment) and a right smaller aneurysm, symmetrical to the previous one were diagnosed in a 69-year-old female after angiographic examination for subarachnoid hemorrhage. The preoperative radiological study did not enable us to identify the bleeding aneurysm so a left supraorbital keyhole approach was performed to operate on the bigger aneurysm. In the same surgical session, using the same way of approach, we decided to attack also the right aneurysm which then revealed itself as being responsible for bleeding. The postoperative angiograms confirmed the complete exclusion of both aneurysms and the patient was discharged after good recovery. Although there are remarkable controversies about the surgical strategies for multiple aneurysms, our experience gives us the opportunity to emphasize the supraorbital keyhole approach and to reconsider the "timing" of multiple/bilateral aneurysms.

  14. M1-M2 balancing act in white adipose tissue browning - a new role for RIP140.

    Science.gov (United States)

    Liu, Pu-Ste; Lin, Yi-Wei; Burton, Frank H; Wei, Li-Na

    2015-01-01

    A "Holy Grail" sought in medical treatment of obesity is to be able to biologically reprogram their adipose tissues to burn fat rather than store it. White adipose tissue (WAT) stores fuel and its expansion underlines insulin resistance (IR) whereas brown adipose tissue (BAT) burns fuel and stimulates insulin sensitivity. These two types of fats seesaw within our bodies via a regulatory mechanism that involves intricate communication between adipocytes and blood cells, particularly macrophages that migrate into adipose deposits. The coregulator, Receptor Interacting Protein 140 (RIP140), plays a key role in regulating this communication. In mice on a high-fat diet, the level of RIP140 in macrophages is dramatically elevated to activate their inflammatory M1 polarization and enhance their recruitment into WAT, facilitating IR. Conversely, lowering the level of RIP140 in macrophages not only reduces M1 macrophages but also expands alternatively polarized, anti-inflammatory M2 macrophages, triggering white adipose tissue browning, fat burning, and restoration of insulin sensitivity. This suggests a potential therapeutic strategy for reversing IR, obesity, and atherosclerotic or even cosmetic fat deposits: therapeutic browning of white adipose deposits by diminishing RIP140 levels in macrophages.

  15. Production of the $^{178m2}$Hf Isomer Using a 4.5-GeV Electron Accelerator

    CERN Document Server

    Karamian, S A; Adam, J; Demekhina, N A

    2004-01-01

    High-productivity methods are required for the accumulation of long-lived isomers in amounts that are sufficient for the creation of experimental targets. A tantalum sample was activated with the Yerevan synchrotron using 4.5-GeV bremsstrahlung and the presence of ^{178m2}Hf was detected with good statistical accuracy by gamma-activity measurements. The integrated and mean cross-section values were deduced from the experiment. The isomer-to-ground-state ratio was then estimated and compared with that known for the p+Ta reaction studied at 660 MeV. In the present experiment, both the converter and the target were relatively thin for better definition of the experimental conditions. However, an assembly designed for high-productivity irradiations should be thick and the converter can also serve as a target sample when irradiated with a high-energy electron beam. The optimization of the isomer production was solved analytically and the largest estimated yield was determined as calibrated to the experimental yiel...

  16. Bone marrow-derived and peritoneal macrophages have different inflammatory response to oxLDL and M1/M2 marker expression - implications for atherosclerosis research

    DEFF Research Database (Denmark)

    Bisgaard, Line S; Mogensen, Christina K; Rosendahl, Alexander;

    2016-01-01

    Macrophages are heterogeneous and can polarize into specific subsets, e.g. pro-inflammatory M1-like and re-modelling M2-like macrophages. To determine if peritoneal macrophages (PEMs) or bone marrow derived macrophages (BMDMs) resembled aortic macrophages from ApoE-/- mice, their M1/M2 phenotype,...

  17. The Role of M1 and M2 Macrophages in Prostate Cancer in relation to Extracapsular Tumor Extension and Biochemical Recurrence after Radical Prostatectomy

    Directory of Open Access Journals (Sweden)

    M. Lanciotti

    2014-01-01

    Full Text Available Introduction. The aim of our work was to investigate the causal connection between M1 and M2 macrophage phenotypes occurrence and prostate cancer, their correlation with tumor extension (ECE, and biochemical recurrence (BR. Patient and Methods. Clinical and pathological data were prospectively gathered from 93 patients treated with radical prostatectomy. Correlations of commonly used variables were evaluated with uni- and multivariate analysis. The relationship between M1 and M2 occurrence and BR was also assessed with Kaplan-Meier survival analysis. Results. Above all in 63.4% there was a M2 prevalence. M1 occurred more frequently in OC disease, while M2 was more represented in ECE. At univariate analysis biopsy and pathologic GS and M2 were statistically correlated with ECE. Only pathologic GS and M2 confirmed to be correlated with ECE. According to macrophage density BCR free survival curves presented a statistically significant difference. When we stratified our population for M1 and M2,we did not find any statistical difference among curves. At univariate analysis GS, pTNM, and positive margins resulted to be significant predictors of BCR, while M1 and M2 did not achieve the statistical significance. At multivariate analysis, only GS and pathologic stage were independent predictors of BR. Conclusion. In our study patients with higher density of M count were associated with poor prognosis; M2 phenotype was significantly associated with ECE.

  18. IL-35 Decelerates the Inflammatory Process by Regulating Inflammatory Cytokine Secretion and M1/M2 Macrophage Ratio in Psoriasis.

    Science.gov (United States)

    Zhang, Junfeng; Lin, Yi; Li, Chunlei; Zhang, Xiaomei; Cheng, Lin; Dai, Lei; Wang, Youcui; Wang, Fangfang; Shi, Gang; Li, Yiming; Yang, Qianmei; Cui, Xueliang; Liu, Yi; Wang, Huiling; Zhang, Shuang; Yang, Yang; Xiang, Rong; Li, Jiong; Yu, Dechao; Wei, Yuquan; Deng, Hongxin

    2016-09-15

    IL-35 downregulates Th17 cell development and suppresses certain types of autoimmune inflammation such as collagen-induced arthritis and experimental autoimmune uveitis. Psoriasis is thought to be initiated by abnormal interactions between cutaneous keratinocytes and systemic immune cells. However, the role of IL-35 in psoriasis remains unclear. In this study, we assessed IL-35 in three well-known psoriasis models: a human keratinocyte cell line (HaCaT), a keratin 14 (K14)-vascular endothelial growth factor A (VEGF-A)-transgenic (Tg) mouse model, and an imiquimod-induced psoriasis mouse model. First, we found that IL-35 suppressed the expression of IL-6, CXCL8, and S100A7, which are highly upregulated by a mixture of five proinflammatory cytokines in HaCaT. Second, a plasmid coding for the human IL-35 sequence coated with cationic liposomes showed potent immunosuppressive effects on K14-VEGF-A-Tg and imiquimod-induced psoriasis mouse models. In the K14-VEGF-A-Tg model, our results showed that several types of proinflammatory cytokines were significantly reduced, whereas IL-10 was remarkably induced by IL-35. Compared with pcDNA3.1, there was a small number of CD4(+)IL-17(+) T cells and a large number of CD4(+)IL-10(+) and CD4(+)CD25(+)Foxp3(+) T cells in the IL-35 group. Most importantly, we found that IL-35 decreased the total number of macrophages and ratio of M1/M2 macrophages, which has not been reported previously. In addition, compared with dexamethasone, IL-35 showed long-term therapeutic efficacy. In summary, our results strongly indicate that IL-35 plays a potent immunosuppressive role in psoriasis. Thus, IL-35 has potential for development as a new therapeutic strategy for patients with chronic psoriasis and other cutaneous inflammatory diseases.

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

    Science.gov (United States)

    2016-04-05

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

  20. Diversification of the vacAs1m1 and vacAs2m2 Strains of Helicobacter pylori in Meriones unguiculatus

    Science.gov (United States)

    Mendoza-Elizalde, Sandra; Arteaga-Resendiz, Nancy K.; Valencia-Mayoral, Pedro; Luna, Raúl C.; Moreno-Espinosa, Sarbelio; Arenas-Huertero, Francisco; Zúñiga, Gerardo; Velázquez-Guadarrama, Norma

    2016-01-01

    The bacterium Helicobacter pylori exhibits great genetic diversity, and the pathogenic roles of its virulence factors have been widely studied. However, the evolutionary dynamics of H. pylori strains during stomach colonization are not well-characterized. Here, we analyzed the microevolutionary dynamics of the toxigenic strain vacAs1m1, the non-toxigenic strain vacAs2m2, and a combination of both strains in an animal model over time. Meriones unguiculatus were inoculated with the following bacteria: group 1-toxigenic strain vacAs1m1/cagA+/cagE+/babA2+; ST181, group 2-non-toxigenic strain vacAs2m2/cagA+/cagE+/babA2+; ST2901, and group 3-both strains. The gerbils were euthanized at different time points (3, 6, 12, and 18 months). In group 1, genetic alterations were observed at 6 and 12 months. With the combination of both strains, group 3 also exhibited genetic alterations at 3 and 18 months; moreover, a chimera, vacA m1-m2, was detected. Additionally, four new sequence types (STs) were reported in the PubMLST database for H. pylori. Synonymous and non-synonymous mutations were analyzed and associated with alterations in amino acids. Microevolutionary analysis of the STs (PHYLOViZ) identified in each group revealed many mutational changes in the toxigenic (vacAs1m1) and non-toxigenic (vacAs2m2) strains. Phylogenetic assessments (eBURST) did not reveal clonal complexes. Our findings indicate that the toxigenic strain, vacAs1m1, and a combination of toxigenic and non-toxigenic strains acquired genetic material by recombination. The allelic combination, vacAs2m1, displayed the best adaptation in the animal model over time, and a chimera, m1-m2, was also identified, which confirmed previous reports. PMID:27877163

  1. Diversification of the vacAs1m1 and vacAs2m2 strains of Helicobacter pylori in Meriones unguiculatus

    Directory of Open Access Journals (Sweden)

    Sandra Mendoza Elizalde

    2016-11-01

    Full Text Available The bacterium Helicobacter pylori exhibits great genetic diversity, and the pathogenic roles of its virulence factors have been widely studied. However, the evolutionary dynamics of H. pylori strains during stomach colonization are not well characterized. Here, we analyzed the microevolutionary dynamics of the toxigenic strain vacAs1m1, the non-toxigenic strain vacAs2m2, and a combination of both strains in an animal model over time. Meriones unguiculatus were inoculated with the following bacteria: group 1–toxigenic strain vacAs1m1/cagA+/cagE+/babA2+; ST181, group 2–non-toxigenic strain vacAs2m2/ cagA+/ cagE+/ babA2+; ST2901, and group 3–both strains. The gerbils were euthanized at different time points (3, 6, 12 and 18 months. In group 1, genetic alterations were observed at 6 and 12 months. With the combination of both strains, group 3 also exhibited genetic alterations at 3 and 18 months; moreover, a chimera, vacA m1-m2, was detected. Additionally, four new sequence types (STs were reported in the PubMLST database for H. pylori. Synonymous and non-synonymous mutations were analyzed and associated with alterations in amino acids. Microevolutionary analysis of the STs (PHYLOViZ identified in each group revealed many mutational changes in the toxigenic (vacAs1m1 and non-toxigenic (vacAs2m2 strains. Phylogenetic assessments (eBURST did not reveal clonal complexes. Our findings indicate that the toxigenic strain, vacAs1m1, and a combination of toxigenic and non-toxigenic strains acquired genetic material by recombination. The allelic combination, vacAs2m1, displayed the best adaptation in the animal model over time, and a chimera, m1-m2, was also identified, which confirmed previous reports.

  2. EPA protects against muscle damage in the mdx mouse model of Duchenne muscular dystrophy by promoting a shift from the M1 to M2 macrophage phenotype.

    Science.gov (United States)

    Carvalho, Samara Camaçari de; Apolinário, Leticia Montanholi; Matheus, Selma Maria Michelin; Santo Neto, Humberto; Marques, Maria Julia

    2013-11-15

    In dystrophic mdx mice and in Duchenne muscular dystrophy, inflammation contributes to myonecrosis. Previously, we demonstrated that eicosapentaenoic acid (EPA) decreased inflammation and necrosis in dystrophic muscle. In the present study, we examined the effects of EPA and the corticoid deflazacort (DFZ) as modulators of M1 (iNOS-expressing cells) and M2 (CD206-expressing cells) macrophages. Mdx mice (14 days old) received EPA or DFZ for 16 days. The diaphragm, biceps brachii and quadriceps muscles were studied. Immunofluorescence, immunoblotting and ELISA assays showed that EPA increased interleucin-10, reduced interferon-γ and was more effective than DFZ in promoting a shift from M1 to M2.

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

    OpenAIRE

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

    1992-01-01

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

  4. Determination of elemental compositions from mass peak profiles of the molecular ion (m) and the m + 1 and m + 2 ions.

    Science.gov (United States)

    Grange, A H; Donnelly, J R; Sovocool, G W; Brumley, W C

    1996-02-01

    The relative abundances of M + 1 and M + 2 ions help to identify the elemental composition of the molecular ion (M). But scan speed, sensitivity, and resolution limitations of mass spectrometers have impeded determination of these abundances. Mass peak profiling from selected ion recording data (MPPSIRD) provided faster sampling and enhanced sensitivity, which permitted use of higher resolution. M + 2 profiles having only a few percent of the ion abundance of M were monitored at 20 000 resolution. The relative abundances, exact masses, and shapes of M, M + 1, and M + 2 mass peak profiles were determined. By applying five criteria based on these quantities, elemental compositions were determined even for ions too large (up to 766 Da) to be uniquely assigned from their exact mass and accuracy limits alone. A profile generation model (PGM) was written to predict these resolution-dependent quantities by considering all M + 1 and M + 2 ions for each candidate composition. The model also provided assurance that no other compositions were possible. Characterization of the M + 1 and M + 2 profiles by MPPSIRD and the PGM greatly expanded the practical ability of high-resolution mass spectrometry to determine elemental compositions.

  5. Temperature-dependent Raman and ultraviolet photoelectron spectroscopy studies on phase transition behavior of VO{sub 2} films with M1 and M2 phases

    Energy Technology Data Exchange (ETDEWEB)

    Okimura, Kunio, E-mail: okifn@keyaki.cc.u-tokai.ac.jp; Hanis Azhan, Nurul [Graduate School of Engineering, Tokai University, Hiratsuka 259-1292 (Japan); Hajiri, Tetsuya [UVSOR Facility, Institute for Molecular Science, Okazaki 444-8585 (Japan); Graduate School of Engineering, Nagoya University, Nagoya 464-8603 (Japan); Kimura, Shin-ichi [UVSOR Facility, Institute for Molecular Science, Okazaki 444-8585 (Japan); Graduate School of Frontier Biosciences, Osaka University, Suita 565-0871 (Japan); Zaghrioui, Mustapha; Sakai, Joe [GREMAN, UMR 7347 CNRS, Université François Rabelais de Tours, Parc de Grandmont, 37200 Tours (France)

    2014-04-21

    Structural and electronic phase transitions behavior of two polycrystalline VO{sub 2} films, one with pure M1 phase and the other with pure M2 phase at room temperature, were investigated by temperature-controlled Raman spectroscopy and ultraviolet photoelectron spectroscopy (UPS). We observed characteristic transient dynamics in which the Raman modes at 195 cm{sup −1} (V-V vibration) and 616 cm{sup −1} (V-O vibration) showed remarkable hardening along the temperature in M1 phase film, indicating the rearrangements of V-V pairs and VO{sub 6} octahedra. It was also shown that the M1 Raman mode frequency approached those of invariant M2 peaks before entering rutile phase. In UPS spectra with high energy resolution of 0.03 eV for the M2 phase film, narrower V{sub 3d} band was observed together with smaller gap compared to those of M1 phase film, supporting the nature of Mott insulator of M2 phase even in the polycrystalline film. Cooperative behavior of lattice rearrangements and electronic phase transition was suggested for M1 phase film.

  6. 微小RNA-155在小鼠骨髓来源M1M2巨噬细胞中表达的差异%Diverse expression patterns of microRNA-155 between bone marrow-derived M1 and M2 macrophages

    Institute of Scientific and Technical Information of China (English)

    梁艳冰; 王中华; 唐皓; 马中富

    2012-01-01

    BACKGROUND: Previous studies of microRNA-155 expression and function in macrophage predominantly focus on total mononuclear macrophage. OBJCTIVE: To evaluate the expression difference of microRNA-155 in M1 and M2 macrophages. METHODS: Bone marrow-derived macrophages were induced to differentiate t owards M1 and M2 macrophages using interferon-γ(100 U/mL) + lipopolysaccharide (5 ng/mL) and interleukin-4 (10 ng/mL), respectively. RESULTS AND CONCLUSION: The differentiation proportion of M1 and M2 macrophages detected by flow cytometry was 91% and 95%, respectively. Reverse transcription PCR method showed that inducible nitric oxide synthase (iNOS) mRNA was highly expressed in M1 macrophages, but it was hardly expressed in M2 macrophages. Arginase-1 and found in inflammatory zone 1 mRNA expression was highly expressed in M2 macrophages, but the expression was low in M1 macrophages. Tumor necrosis factor α mRNA expression was significantly higher in M1 macrophages than in M2 macrophages, on the contrary, interleukin 10 mRNA expression was significantly higher in M2 macrophages than in M1 macrophages (P < 0.05). Real-time fluorescence quantitative PCR showed that microRNA-155 expression in M1 macrophages was significantly higher compared with that in M2 macrophages (P < 0.05). These findings suggest that MiRNA-155 can serve as a useful maker for differential diagnosis of M1 and M2 macrophages.%背景:目前对微小RNA-155 在巨噬细胞中的表达和功能的研究还集中在总体单核巨噬细胞水平.目的:了解小鼠骨髓来源M1M2 巨噬细胞中微小RNA-15 表达的差异.方法:用100 U/mL 干扰素γ和5 μg/L 脂多糖诱导骨髓细胞来源的巨噬细胞向M1 分化,用10 μg/L 白细胞介素4 诱导出M2 巨噬细胞.结果与结论:流式细胞检测显示实验诱导的M1M2 巨噬细胞纯度分别达91%和95%.RT-PCR 检测显示诱导型一氧化氮合酶mRNA 在M1 巨噬细胞中高表达,在M2 中则基本不表达;而Ⅰ型精氨

  7. Effect of modulation of PPAR-γ activity on Kupffer cells M1/M2 polarization in the development of non-alcoholic fatty liver disease

    Science.gov (United States)

    Luo, Wenjing; Xu, Qinyu; Wang, Qi; Wu, Huimin; Hua, Jing

    2017-01-01

    Abnormal lipid-mediated hepatic inflammatory-immune dysfunction and chronic low grade inflammation play an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Macrophage polarization is an important mechanism for the regulation of inflammatory response. Since PPAR-γ has emerged as a master regulator of macrophage polarization, we aimed to investigate the lipid-induced macrophage/Kupffer cell polarization in vivo and in vitro, and explore the association between PPAR-γ activity and macrophages M1/M2 polarization shifting. Here we showed that long-term high-fat diet increased Kupffer cells content with M1-predominant phenotype and increasing production of pro-inflammatory cytokines. Saturated fatty acids polarized Kupffer cells/macrophages to an M1-predominant phenotype while n-3 PUFA polarized Kupffer cells/macrophages to an M2 phenotype, which was associated with activation of NF-κB signal pathway and PPAR-γ respectively. Furthermore, up-regulation of PPAR-γ shifted lipid-induced macrophages polarization from M1-predominant phenotype to M2 phenotype. Macrophages polarization switch was associated with the interaction between PPAR-γ and NF-κBp65 signal pathway. Rosiglitazone restored high-fat diet-induced imblance of Kupffer cells M1/M2 polarization and alleviated hepatic steatosis as well as local pro-inflammatory response. These findings suggest that manipulation of PPAR-γ activity has the potential to balance lipid-induced M1/M2 macrophage/Kupffer cell polarization, and leading to prevent the development of NAFLD. PMID:28300213

  8. Liposomal targeting of prednisolone phosphate to synovial lining macrophages during experimental arthritis inhibits M1 activation but does not favor M2 differentiation.

    Directory of Open Access Journals (Sweden)

    Wouter Hofkens

    Full Text Available BACKGROUND: To determine the effects of liposomal targeting of prednisolone phosphate (Lip-PLP to synovial lining macrophages on M1 and M2 polarization in vitro and during experimental arthritis. MATERIAL AND METHODS: Experimental arthritis (antigen and immune complex induced was elicited in mice and prednisolone containing liposomes were given systemically. Synovium was investigated using microarray analysis, RT-PCR and histology. Bone-marrow macrophages were stimulated towards M1 using LPS and IFNγ before treatment by PLP-liposomes. M1 and M2 markers were determined using RT-PCR. RESULTS: Microarray analysis of biopsies of inflamed synovium during antigen induced arthritis (AIA showed an increased M1 signature characterized by upregulation of IL-1β, IL-6 and FcγRI starting from day 1 and lasting up until day 7 after arthritis induction. The M2 signature remained low throughout the 7 day course of arthritis. Treatment of AIA with intravenously delivered Lip-PLP strongly suppressed joint swelling and synovial infiltration whereas colloidal gold containing liposomes exclusively targeted the macrophages within the inflamed synovial intima layer. In vitro studies showed that Lip-PLP phagocytosed by M1 macrophages resulted in a suppression of the M1 phenotype and induction of M2 markers (IL-10, TGF-β, IL-1RII, CD163, CD206 and Ym1. In vivo, Lip-PLP treatment strongly suppressed M1 markers (TNF-α, IL-1β, IL-6, IL-12p40, iNOS, FcγRI, Ciita and CD86 after local M1 activation of lining macrophages with LPS and IFN-γ and during experimental AIA and immune complex arthritis (ICA. In contrast, M2 markers were not significantly upregulated in antigen-induced arthritis and down regulated in immune complex arthritis. CONCLUSION: This study clearly shows that systemic treatment with PLP-liposomes selectively targets synovial lining macrophages and inhibits M1 activation. In contrast to in vitro findings, PLP-liposomes do not cause a shift of synovial

  9. Liposomal Targeting of Prednisolone Phosphate to Synovial Lining Macrophages during Experimental Arthritis Inhibits M1 Activation but Does Not Favor M2 Differentiation

    Science.gov (United States)

    Hofkens, Wouter; Schelbergen, Rik; Storm, Gert; van den Berg, Wim B.; van Lent, Peter L.

    2013-01-01

    Background To determine the effects of liposomal targeting of prednisolone phosphate (Lip-PLP) to synovial lining macrophages on M1 and M2 polarization in vitro and during experimental arthritis. Material and Methods Experimental arthritis (antigen and immune complex induced) was elicited in mice and prednisolone containing liposomes were given systemically. Synovium was investigated using microarray analysis, RT-PCR and histology. Bone–marrow macrophages were stimulated towards M1 using LPS and IFNγ before treatment by PLP-liposomes. M1 and M2 markers were determined using RT-PCR. Results Microarray analysis of biopsies of inflamed synovium during antigen induced arthritis (AIA) showed an increased M1 signature characterized by upregulation of IL-1β, IL-6 and FcγRI starting from day 1 and lasting up until day 7 after arthritis induction. The M2 signature remained low throughout the 7 day course of arthritis. Treatment of AIA with intravenously delivered Lip-PLP strongly suppressed joint swelling and synovial infiltration whereas colloidal gold containing liposomes exclusively targeted the macrophages within the inflamed synovial intima layer. In vitro studies showed that Lip-PLP phagocytosed by M1 macrophages resulted in a suppression of the M1 phenotype and induction of M2 markers (IL-10, TGF-β, IL-1RII, CD163, CD206 and Ym1). In vivo, Lip-PLP treatment strongly suppressed M1 markers (TNF-α, IL-1β, IL-6, IL-12p40, iNOS, FcγRI, Ciita and CD86) after local M1 activation of lining macrophages with LPS and IFN-γ and during experimental AIA and immune complex arthritis (ICA). In contrast, M2 markers were not significantly upregulated in antigen-induced arthritis and down regulated in immune complex arthritis. Conclusion This study clearly shows that systemic treatment with PLP-liposomes selectively targets synovial lining macrophages and inhibits M1 activation. In contrast to in vitro findings, PLP-liposomes do not cause a shift of synovial lining

  10. Role of microstructures on the M1-M2 phase transition in epitaxial VO2 thin films

    Science.gov (United States)

    Ji, Yanda; Zhang, Yin; Gao, Min; Yuan, Zhen; Xia, Yudong; Jin, Changqing; Tao, Bowan; Chen, Chonglin; Jia, Quanxi; Lin, Yuan

    2014-05-01

    Vanadium dioxide (VO2) with its unique sharp resistivity change at the metal-insulator transition (MIT) has been extensively considered for the near-future terahertz/infrared devices and energy harvesting systems. Controlling the epitaxial quality and microstructures of vanadium dioxide thin films and understanding the metal-insulator transition behaviors are therefore critical to novel device development. The metal-insulator transition behaviors of the epitaxial vanadium dioxide thin films deposited on Al2O3 (0001) substrates were systematically studied by characterizing the temperature dependency of both Raman spectrum and Fourier transform infrared spectroscopy. Our findings on the correlation between the nucleation dynamics of intermediate monoclinic (M2) phase with microstructures will open a new avenue for the design and integration of advanced heterostructures with controllable multifunctionalities for sensing and imaging system applications.

  11. Bone marrow-derived and peritoneal macrophages have different inflammatory response to oxLDL and M1/M2 marker expression – implications for atherosclerosis research

    Science.gov (United States)

    Bisgaard, Line S.; Mogensen, Christina K.; Rosendahl, Alexander; Cucak, Helena; Nielsen, Lars Bo; Rasmussen, Salka E.; Pedersen, Tanja X.

    2016-01-01

    Macrophages are heterogeneous and can polarize into specific subsets, e.g. pro-inflammatory M1-like and re-modelling M2-like macrophages. To determine if peritoneal macrophages (PEMs) or bone marrow derived macrophages (BMDMs) resembled aortic macrophages from ApoE−/− mice, their M1/M2 phenotype, inflammatory status, and lipid metabolism signatures were compared. oxLDL accumulation was similar in PEMs and BMDMs. On protein expression level, BMDMs showed an M2-like CD206highCD11clow profile, while cholesterol loading led to enhanced CD11c expression and reduced MCP-1 secretion. In contrast, PEMs expressed low levels of CD206 and CD11c, and responded to cholesterol loading by increasing CD11c expression and MCP-1 secretion. mRNA expression of M1/M2 markers was higher in PEMS than BMDMs, while lipid metabolism genes were similarly expressed. Whole aorta flow cytometry showed an accumulation of M2-like CD206highCD11clow macrophages in advanced versus early atherosclerotic disease in ApoE−/− mice. In isolated lesions, mRNA levels of the M2 markers Socs2, CD206, Retnla, and IL4 were downregulated with increasing disease severity. Likewise, mRNA expression of lipid metabolism genes (SREBP2, ACSL1, SRB1, DGAT1, and cpt1a) was decreased in advanced versus early lesions. In conclusion, PEMs and BMDMs are phenotypically distinct and differ from macrophages in lesions with respect to expression of M1/M2 markers and lipid metabolism genes. PMID:27734926

  12. On the crystal chemistry of olivine-type germanate compounds, Ca1 + xM1 - xGeO4 (M2+ = Ca, Mg, Co, Mn).

    Science.gov (United States)

    Redhammer, Günther J; Roth, Georg; Amthauer, Georg; Lottermoser, Werner

    2008-06-01

    Germanate compounds, CaMGeO(4) with M(2+) = Ca, Mg, Co and Mn, were synthesized as single crystals by slow cooling from the melt or by flux growth techniques. All the compositions investigated exhibit Pnma symmetry at 298 K and adopt the olivine structure. The M2 site is exclusively occupied by Ca(2+), while on M1 both Ca(2+) and M(2+) cations are found. The amount of Ca(2+) on M1 increases with the size of the M1 cation, with the smallest amount in the Mg compound (0.1 atoms per formula unit) and the largest in the Mn compound (0.20 atoms per formula unit), while in Ca(2)GeO(4), also with olivine structure, both sites are completely filled with Ca(2+). When compared with those of Ca silicate olivine, the lattice parameters a and c are distinctly larger in the analogous germanate compounds, while b has essentially the same values, regardless of the tetrahedral cation, meaning that b is independent of the tetrahedral cation. Structural variations on the octahedrally coordinated M1 site are largely determined by the size of the M1 cation, the average M1-O bond lengths being identical in Ca silicate and Ca germanate olivine. Increasing the size of the M1 cation induces an increasing polyhedral distortion, expressed by the parameters bond-length distortion, octahedral angle variance and octahedral quadratic elongation. However, the Ca germanate olivine compounds generally have more regular octahedra than the analogous silicates. The octahedrally coordinated M2 site does not exhibit large variations in structural parameters as a consequence of the constant chemical composition; the same is valid for the tetrahedral site.

  13. Dendrosomal curcumin suppresses metastatic breast cancer in mice by changing m1/m2 macrophage balance in the tumor microenvironment.

    Science.gov (United States)

    Shiri, Sadaf; Alizadeh, Ali Mohammad; Baradaran, Behzad; Farhanghi, Baharak; Shanehbandi, Dariush; Khodayari, Saeed; Khodayari, Hamid; Tavassoli, Abbas

    2015-01-01

    Curcumin, a lipid-soluble compound extracted from the plant Curcuma Longa, has been found to exert immunomodulatory effects via macrophages. However, most studies focus on the low bioavailability issue of curcumin by nano and microparticles, and thus the role of macrophages in the anticancer mechanism of curcumin has received little attention so far. We have previously shown the potential biocompatibility, biodegradability and anti-cancer effects of dendrosomal curcumin (DNC). In this study, twenty-seven BALB/c mice were equally divided into control as well as 40 and 80 mg/kg groups of DNC to investigate the involvement of macrophages in the antitumor effects of curcumin in a typical animal model of metastatic breast cancer. At the end of intervention, the tumor volume and weight were significantly reduced in DNC groups compared to control (PDNC increased the expression of STAT4 and IL-12 genes in tumor and spleen tissues in comparison with control (PDNC decreased STAT3, IL-10 and arginase I gene expression (P<0.05), indicating low levels of M2 macrophage. The results confirm the role of macrophages in the protective effects of dendrosomal curcumin against metastatic breast cancer in mice.

  14. Role of Macrophage (M1 and M2) in Titanium-Dioxide Nanoparticle-Induced Oxidative Stress and Inflammatory Response in Rat.

    Science.gov (United States)

    Kumar, Sumit; Meena, Ramovatar; Paulraj, R

    2016-12-01

    Titanium-dioxide nanoparticles (TNP) are used in various consumable goods. Evidence has demonstrated the cytotoxicity of TNPs, but exact mechanism is yet to be elucidated. The present study has been aimed at finding out the mechanism of TNP-induced toxicity in biological system. Different doses of anatase-TNPs administrated intravenously to Wistar rats for once a week for 1 month and properties of TH cells, macrophages, cytokines secretion, oxidative damage, apoptotic pathway, and hematological and pathological changes were investigated as downstream events of TNP-mediated cytotoxicity. Result suggests that TNPs induce TH1 and TH2 response as measured by immunophenotyping (interferon gamma (IFN-γ) and interleukin (IL)-4) of TH cells, causing induction of M1 (nitric oxide (NO), nitric oxide synthase (iNOS), NF-kappaB (NF-κB), cyclooxygenase-2 (COX-2), IL-1, IL-6, and TNF-α) and M2 (Arg-1, Ym1) macrophages response. At lower dose, TH1 or M1 response counteracted by TH2 or M2 response, resulting in insignificant oxidative damage. However, with increasing dose of TNPs, the M1 response was increased over M2 response resulting in significant tissue damage. The M1-induced inflammatory response was found to cause DNA and chromosomal damage resulting apoptosis induction via upregulation of Bax/Bcl-2 ratio and subsequent loss of mitochondrial membrane potential and cyto c release in splenocytes. The TNP-led inflammatory response also causes damage at different tissue levels.

  15. Symmetry Relationship and Strain-Induced Transitions between Semiconducting (M1 and M2) and Metallic (R) Phases of Vanadium Dioxide

    Energy Technology Data Exchange (ETDEWEB)

    Budai, John D [ORNL; Ivanov, Ilia N [ORNL; Kalinin, Sergei V [ORNL; Kolmakov, Andrei [ORNL; Luk' yanchuk, Prof. Igor A. [University of Picardie Jules Verne, Amiens, France; Strelcov, Evgheni [Southern Illinois University; Tischler, Jonathan Zachary [ORNL; Tselev, Alexander [ORNL

    2010-01-01

    The ability to synthesize VO{sub 2} in the form of single-crystalline nanobeams and nano- and microcrystals uncovered a number of previously unknown aspects of the metal-insulator transition (MIT) in this oxide. In particular, several reports demonstrated that the MIT can proceed through competition between two monoclinic (insulating) phases M1 and M2 and the tetragonal (metallic) R phase under influence of strain. The nature of such phase behavior has been not identified. Here we show that the competition between M1 and M2 phases is purely lattice-symmetry-driven. Within the framework of the Ginzburg-Landau formalism, both M phases correspond to different directions of the same four-component structural order parameter, and as a consequence, the M2 phase can appear under a small perturbation of the M1 structure such as doping or stress. We analyze the strain-controlled phase diagram of VO{sub 2} in the vicinity of the R-M2-M1 triple point using the Ginzburg-Landau formalism and identify and experimentally verify the pathways for strain-control of the transition. These insights open the door toward more systematic approaches to synthesis of VO{sub 2} nanostructures in desired phase states and to use of external fields in the control of the VO{sub 2} phase states. Additionally, we report observation of the triclinic T phase at the heterophase domain boundaries in strained quasi-two-dimensional VO{sub 2} nanoplatelets, and theoretically predict phases that have not been previously observed.

  16. Increased expression of M1 and M2 phenotypic markers in isolated microglia after four-day binge alcohol exposure in male rats.

    Science.gov (United States)

    Peng, Hui; Geil Nickell, Chelsea R; Chen, Kevin Y; McClain, Justin A; Nixon, Kimberly

    2017-08-01

    Microglia activation and neuroinflammation are common features of neurodegenerative conditions, including alcohol use disorders (AUDs). When activated, microglia span a continuum of diverse phenotypes ranging from classically activated, pro-inflammatory (M1) microglia/macrophages to alternatively activated, growth-promoting (M2) microglia/macrophages. Identifying microglia phenotypes is critical for understanding the role of microglia in the pathogenesis of AUDs. Therefore, male rats were gavaged with 25% (w/v) ethanol or isocaloric control diet every 8 h for 4 days and sacrificed at 0, 2, 4, and 7 days after alcohol exposure (e.g., T0, T2, etc.). Microglia were isolated from hippocampus and entorhinal cortices by Percoll density gradient centrifugation. Cells were labeled with microglia surface antigens and analyzed by flow cytometry. Consistent with prior studies, isolated cells yielded a highly enriched population of brain macrophages/microglia (>95% pure), evidenced by staining for the macrophage/microglia antigen CD11b. Polarization states of CD11b(+)CD45(low) microglia were evaluated by expression of M1 surface markers, major histocompatibility complex (MHC) II, CD32, CD86, and M2 surface marker, CD206 (mannose receptor). Ethanol-treated animals begin to show increased expression of M1 and M2 markers at T0 (p = n.s.), with significant changes at the T2 time point. At T2, expression of M1 markers, MHC-II, CD86, and CD32 were increased (p < 0.05) in hippocampus and entorhinal cortices, while M2 marker, CD206, was increased significantly only in entorhinal cortices (p < 0.05). All effects resolved to control levels by T4. In summary, four-day binge alcohol exposure produces a transient increase in both M1 (MHC-II, CD32, and CD86) and M2 (CD206) populations of microglia isolated from the entorhinal cortex and hippocampus. Thus, these findings that both pro-inflammatory and potentially beneficial, recovery-promoting microglia phenotypes can be observed

  17. Glioma-associated microglia/macrophages display an expression profile different from M1 and M2 polarization and highly express Gpnmb and Spp1.

    Directory of Open Access Journals (Sweden)

    Frank Szulzewsky

    Full Text Available Malignant glioma belong to the most aggressive neoplasms in humans with no successful treatment available. Patients suffering from glioblastoma multiforme (GBM, the highest-grade glioma, have an average survival time of only around one year after diagnosis. Both microglia and peripheral macrophages/monocytes accumulate within and around glioma, but fail to exert effective anti-tumor activity and even support tumor growth. Here we use microarray analysis to compare the expression profiles of glioma-associated microglia/macrophages and naive control cells. Samples were generated from CD11b+ MACS-isolated cells from naïve and GL261-implanted C57BL/6 mouse brains. Around 1000 genes were more than 2-fold up- or downregulated in glioma-associated microglia/macrophages when compared to control cells. A comparison with published data sets of M1, M2a,b,c-polarized macrophages revealed a gene expression pattern that has only partial overlap with any of the M1 or M2 gene expression patterns. Samples for the qRT-PCR validation of selected M1 and M2a,b,c-specific genes were generated from two different glioma mouse models and isolated by flow cytometry to distinguish between resident microglia and invading macrophages. We confirmed in both models the unique glioma-associated microglia/macrophage phenotype including a mixture of M1 and M2a,b,c-specific genes. To validate the expression of these genes in human we MACS-isolated CD11b+ microglia/macrophages from GBM, lower grade brain tumors and control specimens. Apart from the M1/M2 gene analysis, we demonstrate that the expression of Gpnmb and Spp1 is highly upregulated in both murine and human glioma-associated microglia/macrophages. High expression of these genes has been associated with poor prognosis in human GBM, as indicated by patient survival data linked to gene expression data. We also show that microglia/macrophages are the predominant source of these transcripts in murine and human GBM. Our

  18. Regulation of Human Macrophage M1M2 Polarization Balance by Hypoxia and the Triggering Receptor Expressed on Myeloid Cells-1

    Directory of Open Access Journals (Sweden)

    Federica Raggi

    2017-09-01

    Full Text Available Macrophages (Mf are a heterogeneous population of tissue-resident professional phagocytes and a major component of the leukocyte infiltrate at sites of inflammation, infection, and tumor growth. They can undergo diverse forms of activation in response to environmental factors, polarizing into specialized functional subsets. A common hallmark of the pathologic environment is represented by hypoxia. The impact of hypoxia on human Mf polarization has not been fully established. The objective of this study was to elucidate the effects of a hypoxic environment reflecting that occurring in vivo in diseased tissues on the ability of human Mf to polarize into classically activated (proinflammatory M1 and alternatively activated (anti-inflammatory M2 subsets. We present data showing that hypoxia hinders Mf polarization toward the M1 phenotype by decreasing the expression of T cell costimulatory molecules and chemokine homing receptors and the production of proinflammatory, Th1-priming cytokines typical of classical activation, while promoting their acquisition of phenotypic and secretory features of alternative activation. Furthermore, we identify the triggering receptor expressed on myeloid cells (TREM-1, a member of the Ig-like immunoregulatory receptor family, as a hypoxia-inducible gene in Mf and demonstrate that its engagement by an agonist Ab reverses the M2-polarizing effect of hypoxia imparting a M1-skewed phenotype to Mf. Finally, we provide evidence that Mf infiltrating the inflamed hypoxic joints of children affected by oligoarticular juvenile idiopatic arthritis express high surface levels of TREM-1 associated with predominant M1 polarization and suggest the potential of this molecule in driving M1 proinflammatory reprogramming in the hypoxic synovial environment.

  19. 姜黄素促进 RAW264.7源性 M1巨噬细胞向替代激活 M2表型极化%Curcumin induces M1 phenotype derived from murine RAW264.7 macrophages polarization to alternatively activated M2 phenotype

    Institute of Scientific and Technical Information of China (English)

    陈方圆; 袁祖贻; 周娟; 王欢; 薛丽; 郭宁

    2015-01-01

    目的:观察姜黄素对 LPS 和 IFNγ诱导的 RAW264.7巨噬细胞(M1)极化的影响及机制。方法不同浓度姜黄素(6.25、12.5、25μmol/L)干预 LPS 和 IFNγ诱导的 RAW264.7巨 噬 细 胞 (M1)12 h,同时再加入20μmol/L GW9662与25μmol/L 姜黄素共同干预 LPS 和 IFNγ诱导的 RAW264.7巨 噬 细 胞(M1)12 h,采用 Real-time PCR、ELISA 及 Western blot 方法检测 IL-1β、IL-6和 M2表型标志分子 KLF4、FIZZ1、MGL1、PPARγ的表达,及阻断PPARγ后 KLF4和 FIZZ1的表达。结果不同浓度姜黄素均能上调 LPS 和 IFNγ诱导的 RAW264.7巨噬细胞(M1)的 M2标志分子的表达,并且抑制炎症因子 IL-1β和 IL-6的分泌;阻断 PPARγ后,RAW264.7巨噬细胞源性 M1表型巨噬细胞表达 M2标志分子下调。结论姜黄素通过活化 PPARγ促进 LPS 和 IFNγ诱导的 RAW264.7巨噬细胞(M1)向 M2表型极化。%ABSTRACT:Objective To observe the effect of curcumin on RAW264.7 macrophages induced with LPS and IFNγ(M1)and the mechanisms involved.Methods Curcumin of different concentrations (6.25 μmol/L,12.5μmol/L and 25 μmol/L)was used to treat RAW264.7 macrophages induced with LPS and IFNγ(M1)for 12 h,and RAW264.7 macrophages induced with LPS and IFNγ(M1)were incubated with 20μmol/L GW9662 and 25 μmol/L curcumin for 12 h.Using Real-time PCR,ELISA and Western blotting analysis,we examined the expressions of IL-1β,IL-6,PPARγand phenotype markers M2 (KLF4,FIZZ1,and MGL1 )and the expressions of KLF4 and FIZZ1 when PPARγwas inhibited.Results Curcumin of different concentrations all could inhibit the expressions of IL-1βand IL-6 in RAW264.7 macrophages induced with LPS and IFNγ(M1).Curcumin of different concentra-tions could upregulate the expression of M2 markers (KLF4,FIZZ1 and MGL1)and PPARγin RAW264.7 macro-phages induced with LPS and IFNγ(M1).When M1 macrophages were incubated with curcumin and GW9662,the expression of the M2 phenotype markers was reduced.Conclusion Curcumin polarized the M

  20. LPS converts Gr-1(+)CD115(+) myeloid-derived suppressor cells from M2 to M1 via P38 MAPK.

    Science.gov (United States)

    Yang, Yi; Zhang, Ruihua; Xia, Fei; Zou, Ting; Huang, Anfei; Xiong, Sidong; Zhang, Jinping

    2013-07-15

    Myeloid-derived suppressor cells (MDSCs) are heterogeneous populations of immature myeloid cells with strong immunosuppressive function, and play a critical role in the immune evasion of cancer. A subset of MDSCs share many similar characteristics with tumor-associated macrophages (TAMs), but it is largely unclear whether MDSCs also have M1/M2 type polarization in tumor microenvironments. In the present study, we found that Gr-1(+)CD115(+) monocytes in tumor-bearing mice exhibited M2 characteristics with significantly lower expression of iNOS and higher expression of Arginase I. Immunofluorescence staining showed that Gr-1(+)CD115(+) monocytes in tumor sites from LPS-injected mice had a higher expression of iNOS. Similarly, in vitro experiments displayed that LPS-treated Gr-1(+)CD115(+) cells expressed higher levels of iNOS, IL-6, TNF, IL-12, and IL-10 compared with those in non-treated Gr-1(+)CD115(+) monocytes. Extensive study showed that LPS-treated Gr-1(+)CD115(+) monocytes had less ability to convert the CD4(+)CD25(-)cells into CD4(+)CD25(+) Tregs, and also had less suppressive function on CD4(+)CD25(-) conventional T cells. LLC tumors in LPS-injected mice grew significantly slower than those in non-LPS-injected mice. Further experiments suggested that LPS may function through the P38 MAPK signaling pathway to increase the expression of iNOS, and of MyD88 independently. Thus, we can get conclusion that Gr-1(+)CD115(+) monocytes in tumor-bearing mice show M2 type characteristics and LPS can skew this M2 type cells into M1 type through the P38 MAPK pathway and lead to inhibition of the suppressive function of Gr-1(+)CD115(+) monocytes. It suggests that LPS or its analogs may be potential drugs for tumor treatment, inflammation induced by LPS or other components of bacterium or virus may be benefit to the inhibition of tumor cell growth in vivo.

  1. ECHELLE SPECTROSCOPY OF THE NUCLEI OF THE HIGHLY COLLIMATED BIPOLAR PLANETARY NEBULAE M 2-9 AND M 1-91

    Directory of Open Access Journals (Sweden)

    S. Torres-Peimbert

    2010-01-01

    Full Text Available Presentamos espectroscopía echelle del núcleo sin resolver de las nebulosas bipolares M 2-9 and M 1-91. Los espectros están dominados por líneas de emisión emitidas en un amplio intervalo de condiciones físicas. De las observaciones identificamos las líneas de emisión, las condiciones físicas y los movimientos relativos de las diferentes especies ionizadas en la región circunestelar de ambos objetos. Proponemos que las líneas prohibidas observadas se originan en la parte interior del toro extendido que rodea a cada objeto.

  2. M1 and M2 Functional Imprinting of Primary Microglia: Role of P2X7 Activation and miR-125b

    Directory of Open Access Journals (Sweden)

    Chiara Parisi

    2016-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a most frequently occurring and severe form of motor neuron disease, causing death within 3–5 years from diagnosis and with a worldwide incidence of about 2 per 100,000 person-years. Mutations in over twenty genes associated with familial forms of ALS have provided insights into the mechanisms leading to motor neuron death. Moreover, mutations in two RNA binding proteins, TAR DNA binding protein 43 and fused in sarcoma, have raised the intriguing possibility that perturbations of RNA metabolism, including that of the small endogenous RNA molecules that repress target genes at the posttranscriptional level, that is, microRNAs, may contribute to disease pathogenesis. At present, the mechanisms by which microglia actively participate to both toxic and neuroprotective actions in ALS constitute an important matter of research. Among the pathways involved in ALS-altered microglia responses, in previous works we have uncovered the hyperactivation of P2X7 receptor by extracellular ATP and the overexpression of miR-125b, both leading to uncontrolled toxic M1 reactions. In order to shed further light on the complexity of these processes, in this short review we will describe the M1/M2 functional imprinting of primary microglia and a role played by P2X7 and miR-125b in ALS microglia activation.

  3. Study of Nonleptonic $B^{\\ast}_{(s)}\\to M_1 M_2$ $(M=D$, $D_s$, $\\pi$, $K)$ Weak Decays with Factorization Approach

    CERN Document Server

    Chang, Qin; Hu, Xiao-Hui; Han, Lin

    2016-01-01

    Motivated by the experiments of heavy flavor physics at running LHC and upgrading SuperKEKB/Belle-II in the future, the nonleptonic $B^{\\ast}_{(s)}\\to M_1 M_2$ $(M=D$, $D_s$, $\\pi$, $K)$ weak decays are studied in this paper. The amplitudes are calculated with factorization approach, and the transition form factors $A_0^{B^{\\ast}_{(s)}\\to M_1}(0)$ are evaluated within BSW model. With the reasonable approximation $\\Gamma_{tot}(B^*_{(s)})\\simeq \\Gamma(B^*_{(s)}\\to B_{(s)}\\gamma)$, our predictions of branching fractions are presented. Numerically, the CKM-favored tree-dominated $\\bar{B}^{*0} \\to D^+D^-_s$ and $\\bar{B}^{*0}_s \\to D^+_sD^-_s$ decays have the largest branching fractions of the order $\\sim{\\cal O}(10^{-8})$, and hence will be firstly observed by forthcoming Belle-II experiment. However, most of the other decay modes have the branching fractions~$<{\\cal O}(10^{-9})$ and thus are hardly to be observed soon. Besides, for the possible detectable $B^{\\ast}_{(s)}$ decays with branching fractions $\\gtrs...

  4. Ethyl methane sulfonate induced mutations in M2 generation and physiological variations in M1 generation of peppers (Capsicum annuum L.

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    Mohamed Hamed Arisha

    2015-06-01

    Full Text Available This study was conducted to enhance genetic variability in peppers (Capsicum annuum, cv B12 using ethyl methansulphonate (EMS. Exposure to an EMS concentration of 0.6%, v/v for 12 hours was used to mutagenize 2000 seeds for the first generation (M1. It was observed that the growth behaviors including plant height, flowering date and number of seeds per first fruit were different in the M1 generation than in wild type plants. In addition one phenotypic mutation (leaf shape and plant architecture was observed during the M1 generation. During the seedling stage in the M2 generation, the observed changes were in the form of slow growth or chlorophyll defect (e.g., albino, pale green and yellow seedlings. At maturity, there were three kinds of phenotypic mutations observed in three different families of the mutant population. The first observed change was a plant with yellow leaf color, and the leaves of this mutant plant contained 62.19% less chlorophyll a and 64.06% less chlorophyll b as compared to the wild-type. The second mutation resulted in one dwarf plant with a very short stature (6 cm, compact internodes and the leaves and stem were rough and thick. The third type of mutation occurred in four plants and resulted in the leaves of these plants being very thick and longer than those of wild type plants. Furthermore, anatomical observations of the leaf blade section of this mutant plant type contained more xylem and collenchyma tissue in the leaf midrib of the mutant plant than wild type. In addition, its leaf blade contained thicker palisade and spongy tissue than the wild type.

  5. Proinflammatory-activated glioma cells induce a switch in microglial polarization and activation status, from a predominant M2b phenotype to a mixture of M1 and M2a/B polarized cells

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    Lucia Lisi

    2014-05-01

    Full Text Available Malignant gliomas are primary brain tumors characterized by morphological and genetic complexities, as well as diffuse infiltration into normal brain parenchyma. Within gliomas, microglia/macrophages represent the largest tumor-infiltrating cell population, contributing by at least one-third to the total tumor mass. Bi-directional interactions between glioma cells and microglia may therefore play an important role on tumor growth and biology. In the present study, we have characterized the influence of glioma-soluble factors on microglial function, comparing the effects of media harvested under basal conditions with those of media obtained after inducing a pro-inflammatory activation state in glioma cells. We found that microglial cells undergo a different pattern of activation depending on the stimulus; in the presence of activated glioma-derived factors, i.e. a condition mimicking the late stage of pathology, microglia presents as a mixture of polarization phenotypes (M1 and M2a/b, with up-regulation of iNOS (inducible nitric oxide synthase, ARG (arginase and IL (interleukine-10. At variance, microglia exposed to basal glioma-derived factors, i.e. a condition resembling the early stage of pathology, shows a more specific pattern of activation, with increased M2b polarization status and up-regulation of IL-10 only. As far as viability and cell proliferation are concerned, both LI-CM [LPS (lipopolysaccharide–IFNγ (interferon γ conditioned media] and C-CM (control-conditioned media induce similar effects on microglial morphology. Finally, in human glioma tissue obtained from surgical resection of patients with IV grade glioblastoma, we detected a significant amount of CD68 positive cells, which is a marker of macrophage/microglial phagocytic activity, suggesting that in vitro findings presented here might have a relevance in the human pathology as well.

  6. Adipose-derived stem cells promote the polarization from M1 macrophages to M2 macrophages%脂肪间充质干细胞促进M1型巨噬细胞向M2型巨噬细胞转化

    Institute of Scientific and Technical Information of China (English)

    尹学红; 庞春燕; 白力; 张颖; 耿立霞

    2016-01-01

    目的 探索脂肪间充质干细胞(ADSC)对M1/M2型巨噬细胞的影响以及ADSC能否促使M1型巨噬细胞向M2型巨噬细胞转化.方法 利用脂多糖(LPS)、γ干扰素(IFN-γ)刺激J774.1巨噬细胞24h诱导为M1型巨噬细胞,利用白细胞介素4(IL-4)刺激J774.1巨噬细胞24h诱导为M2型巨噬细胞;将M1/M2型巨噬细胞分别与ADSC共培养24h后,收集巨噬细胞和上清液,用实时定量PCR和ELISA检测巨噬细胞IL-6、肿瘤坏死因子α(TNF-α)、诱导型一氧化氮合酶(iNOS)、CC趋化因子配体2 (CCL2)、CD86、精氨酸酶1(Arg1)、甘露糖受体/CD206 (MR/CD206)、IL-10、炎症区分子1(found in inflammatory zone 1,FIZZ1)、几丁质酶3样分子3(chitinase 3-like 3,即Ym-1)的变化.结果 ADSC使M1型巨噬细胞分泌的IL-6、TNF-α、iNOS、CCL2、CD86明显减少,Arg1、CD206、IL-10明显增加,且上清液中IL-6和TNF-α含量明显减少,CD206明显增加;使M2型巨噬细胞分泌的IL-6、TNF-α、iNOS、CD86明显减少,Arg1、CD206、FIZZ-1、Ym-1、IL-10明显增加,且上清液中IL-6和TNF-α含量明显减少,CD206明显增加.结论 ADSC抑制M1型巨噬细胞的特异性基因的表达,促进M2型巨噬细胞特异性基因的表达,并使M1型巨噬细胞向M2型巨噬细胞转化.

  7. Trichoderma asperelloides Spores Downregulate dectin1/2 and TLR2 Receptors of Mice Macrophages and Decrease Candida parapsilosis Phagocytosis Independent of the M1/M2 Polarization

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    Andréa G. dos Santos

    2017-09-01

    Full Text Available The intensive use of pesticides to control pests in agriculture has promoted several issues relating to environment. As chemical pesticides remain controversial, biocontrol agents originating from fungi could be an alternative. Among them, we highlight biocontrol agents derived from the fungi genus Trichoderma, which have been documented in limiting the growth of other phytopathogenic fungus in the roots and leaves of several plant species. An important member of this genus is Trichoderma asperelloides, whose biocontrol agents have been used to promote plant growth while also treating soil diseases caused by microorganisms in both greenhouses and outdoor crops. To evaluate the safety of fungal biological agents for human health, tests to detect potentially adverse effects, such as allergenicity, toxicity, infectivity and pathogenicity, are crucial. In addition, identifying possible immunomodulating properties of fungal biocontrol agents merits further investigation. Thus, the aim of this study was to evaluate the effects of T. asperelloides spores in the internalization of Candida parapsilosis yeast by mice phagocytes, in order to elucidate the cellular and molecular mechanism of this interaction, as a model to understand possible in vivo effects of this fungus. For this, mice were exposed to a fungal spore suspension through-intraperitoneal injection, euthanized and cells from the peripheral blood and peritoneal cavity were collected for functional, quantitative and phenotypic analysis, throughout analysis of membrane receptors gene expression, phagocytosis ability and cells immunophenotyping M1 (CCR7 and CD86 and M2 (CCR2 and CD206. Our analyses showed that phagocytes exposed to fungal spores had reduced phagocytic capacity, as well as a decrease in the quantity of neutrophils and monocytes in the peripheral blood and peritoneal cavity. Moreover, macrophages exposed to T. asperelloides spores did not display the phenotypic profile M1/M2, and

  8. Effect of insulin analogues on insulin/IGF1 hybrid receptors: increased activation by glargine but not by its metabolites M1 and M2.

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    Cécile Pierre-Eugene

    Full Text Available BACKGROUND: In diabetic patients, the pharmacokinetics of injected human insulin does not permit optimal control of glycemia. Fast and slow acting insulin analogues have been developed, but they may have adverse properties, such as increased mitogenic or anti-apoptotic signaling. Insulin/IGF1 hybrid receptors (IR/IGF1R, present in most tissues, have been proposed to transmit biological effects close to those of IGF1R. However, the study of hybrid receptors is difficult because of the presence of IR and IGF1R homodimers. Our objective was to perform the first study on the pharmacological properties of the five marketed insulin analogues towards IR/IGF1R hybrids. METHODOLOGY: To study the effect of insulin analogues on IR/IGF1R hybrids, we used our previously developed Bioluminescence Resonance Energy Transfer (BRET assay that permits specific analysis of the pharmacological properties of hybrid receptors. Moreover, we have developed a new, highly sensitive BRET-based assay to monitor phophatidylinositol-3 phosphate (PIP(3 production in living cells. Using this assay, we performed a detailed pharmacological analysis of PIP(3 production induced by IGF1, insulin and insulin analogues in living breast cancer-derived MCF-7 and MDA-MB231 cells. RESULTS: Among the five insulin analogues tested, only glargine stimulated IR/IGF1R hybrids with an EC50 that was significantly lower than insulin and close to that of IGF1. Glargine more efficiently stimulated PIP(3 production in MCF-7 cells but not in MDA-MB231 cells as compared to insulin. In contrast, glargine metabolites M1 and M2 showed lower potency for hybrid receptors stimulation, PIP(3 production, Akt and Erk1/2 phosphorylation and DNA synthesis in MCF-7 cells, compared to insulin. CONCLUSION: Glargine, possibly acting through IR/IGF1R hybrids, displays higher potency, whereas its metabolites M1 and M2 display lower potency than insulin for the stimulation of proliferative/anti-apoptotic pathways in

  9. Radiative rates for E1, E2, M1, and M2 transitions in Br-like ions with 43 $\\le$ Z $\\le$ 50

    CERN Document Server

    Aggarwal, K M

    2015-01-01

    Energies and lifetimes are reported for the eight Br-like ions with 43 $\\le$ Z $\\le$ 50, namely Tc ~IX, Ru~X, Rh~XI, Pd~XII, Ag~XIII, Cd~XIV, In~XV, and Sn~XVI. Results are listed for the lowest 375 levels, which mostly belong to the 4s$^2$4p$^5$, 4s$^2$4p$^4$4$\\ell$, 4s4p$^6$, 4s$^2$4p$^4$5$\\ell$, 4s$^2$4p$^3$4d$^2$, 4s4p$^5$4$\\ell$, and 4s4p$^5$5$\\ell$ configurations. Extensive configuration interaction among 39 configurations (generating 3990 levels) has been considered and the general-purpose relativistic atomic structure package ({\\sc grasp}) has been adopted for the calculations. Radiative rates are listed for all E1, E2, M1, and M2 transitions involving the lowest 375 levels. Previous experimental and theoretical energies are available for only a few levels of three, namely Ru~X, Rh~XI and Pd~XII. Differences with the measured energies are up to 4\\% but the present results are an improvement (by up to 0.3 Ryd) in comparison to other recently reported theoretical data. Similarly for radiative rates and ...

  10. Arctigenin ameliorates inflammation in vitro and in vivo by inhibiting the PI3K/AKT pathway and polarizing M1 macrophages to M2-like macrophages.

    Science.gov (United States)

    Hyam, Supriya R; Lee, In-Ah; Gu, Wan; Kim, Kyung-Ah; Jeong, Jin-Ju; Jang, Se-Eun; Han, Myung Joo; Kim, Dong-Hyun

    2013-05-15

    Seeds of Arctium lappa, containing arctigenin and its glycoside arctiin as main constituents, have been used as a diuretic, anti-inflammatory and detoxifying agent in Chinese traditional medicine. In our preliminary study, arctigenin inhibited IKKβ and NF-κB activation in peptidoglycan (PGN)- or lipopolysaccharide (LPS)-induced peritoneal macrophages. To understand the anti-inflammatory effect of arctigenin, we investigated its anti-inflammatory effect in LPS-stimulated peritoneal macrophages and on LPS-induced systemic inflammation as well as 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. Arctigenin inhibited LPS-increased IL-1β, IL-6 and TNF-α expression in LPS-stimulated peritoneal macrophages, but increased LPS-reduced IL-10 and CD204 expression. Arctigenin inhibited LPS-induced PI3K, AKT and IKKβ phosphorylation, but did not suppress LPS-induced IRAK-1 phosphorylation. However, arctigenin did not inhibit NF-κB activation in LPS-stimulated PI3K siRNA-treated peritoneal macrophages. Arctigenin suppressed the binding of p-PI3K antibody and the nucleus translocation of NF-κB p65 in LPS-stimulated peritoneal macrophages. Arctigenin suppressed blood IL-1β and TNF-α level in mice systemically inflamed by intraperitoneal injection of LPS. Arctigenin also inhibited colon shortening, macroscopic scores and myeloperoxidase activity in TNBS-induced colitic mice. Arctigenin inhibited TNBS-induced IL-1β, TNF-α and IL-6 expression, as well as PI3K, AKT and IKKβ phosphorylation and NF-κB activation in mice, but increased IL-10 and CD204 expression. However, it did not affect IRAK-1 phosphorylation. Based on these findings, arctigenin may ameliorate inflammatory diseases, such as colitis, by inhibiting PI3K and polarizing M1 macrophages to M2-like macrophages.

  11. 1,25(OH)2D3 promotes M1 macrophage switching to M2 via VDR-PPARγ pathway induced by high glucose%1,25(OH)2D3通过VDR-PPARγ通路促使高糖诱导的M1型巨噬细胞向M2型转换

    Institute of Scientific and Technical Information of China (English)

    周敏; 郭银凤; 宋志霞; 张晓良

    2015-01-01

    Objective To investigate the effect of 1,25(OH)2D3 on high glucose induced macrophage activation and its underlying signal transduction mechanism.Methods RAW 264.7 cells were used to perform cell culture,the activity of intracellular iNOS was measured.VDR siRNA and PPARγ antagonist pre-treatment with macrophages were done before using 10-8 mol/L1,25(OH)2D3 to intervene high glucose pre-incubated macrophages.M1 markers including iNOS,TNF-α,IL-12,M2 markers including MR,Arg-1,IL-10 and nuclear receptors VDR and PPARγ were separately examined.Results The iNOS activity was increased in a glucose-dose and time dependent manner.Particularly,25 mmol/L glucose at 24 h gave the maximum response.After being treated with 25 mmol/L glucose for 24 h,not only inflammatory cytokines of TNF-α,IL-12 in the supernatant were increased,but quantitative real-time PCR and Western blotting analysis showed iNOS was also up-regulated (P < 0.05).However,M2 markers,i.e.MR and Arg-l were significantly decreased (P < 0.05).When in the presence of 1,25(OH),D3,the trends were reversed:the markers of M1,including TNF-α,IL-12 and iNOS were obviously reduced (P < 0.05),while M2 markers,IL-10,Arg-1 and MR were increased (P < 0.05).In addition,VDR and PPARγ were also increased (P < 0.05).However,the above effects of 1,25 (OH)2D3 were abolished when further inhibited the expression of VDR and PPARγby VDR siRNA and PPARγ antagonist.Besides,accompanied by VDR,PPARγwas also decreased upon the treatment with VDR siRNA (P < 0.05).Conclusion 1,25(OH)2D3 can promote high glucose induced classically activated macrophages (M1) converting to alternatively activated macrophages (M2) and this is achieved through VDR-PPARγ pathway.%目的 探讨1,25(OH)2D3对高糖环境下巨噬细胞活化状态的调节作用及其信号转导机制.方法 体外培养小鼠巨噬细胞系(RAW264.7),检测细胞内诱导型一氧化氮合酶(iNOS)活力.10-8 mol/L 1,25 (OH)2D3干预高糖预处理的巨

  12. Cervical Cancer Cell Supernatants Induce a Phenotypic Switch from U937-Derived Macrophage-Activated M1 State into M2-Like Suppressor Phenotype with Change in Toll-Like Receptor Profile

    Science.gov (United States)

    Sánchez-Reyes, Karina; Bravo-Cuellar, Alejandro; Hernández-Flores, Georgina; Lerma-Díaz, José Manuel; Jave-Suárez, Luis Felipe; Gómez-Lomelí, Paulina; de Celis, Ruth; Aguilar-Lemarroy, Adriana; Domínguez-Rodríguez, Jorge Ramiro; Ortiz-Lazareno, Pablo Cesar

    2014-01-01

    Cervical cancer (CC) is the second most common cancer among women worldwide. Infection with human papillomavirus (HPV) is the main risk factor for developing CC. Macrophages are important immune effector cells; they can be differentiated into two phenotypes, identified as M1 (classically activated) and M2 (alternatively activated). Macrophage polarization exerts profound effects on the Toll-like receptor (TLR) profile. In this study, we evaluated whether the supernatant of human CC cells HeLa, SiHa, and C-33A induces a shift of M1 macrophage toward M2 macrophage in U937-derived macrophages. Results. The results showed that soluble factors secreted by CC cells induce a change in the immunophenotype of macrophages from macrophage M1 into macrophage M2. U937-derived macrophages M1 released proinflammatory cytokines and nitric oxide; however, when these cells were treated with the supernatant of CC cell lines, we observed a turnover of M1 toward M2. These cells increased CD163 and IL-10 expression. The expression of TLR-3, -7, and -9 is increased when the macrophages were treated with the supernatant of CC cells. Conclusions. Our result strongly suggests that CC cells may, through the secretion of soluble factors, induce a change of immunophenotype M1 into M2 macrophages. PMID:25309919

  13. Cervical Cancer Cell Supernatants Induce a Phenotypic Switch from U937-Derived Macrophage-Activated M1 State into M2-Like Suppressor Phenotype with Change in Toll-Like Receptor Profile

    Directory of Open Access Journals (Sweden)

    Karina Sánchez-Reyes

    2014-01-01

    Full Text Available Cervical cancer (CC is the second most common cancer among women worldwide. Infection with human papillomavirus (HPV is the main risk factor for developing CC. Macrophages are important immune effector cells; they can be differentiated into two phenotypes, identified as M1 (classically activated and M2 (alternatively activated. Macrophage polarization exerts profound effects on the Toll-like receptor (TLR profile. In this study, we evaluated whether the supernatant of human CC cells HeLa, SiHa, and C-33A induces a shift of M1 macrophage toward M2 macrophage in U937-derived macrophages. Results. The results showed that soluble factors secreted by CC cells induce a change in the immunophenotype of macrophages from macrophage M1 into macrophage M2. U937-derived macrophages M1 released proinflammatory cytokines and nitric oxide; however, when these cells were treated with the supernatant of CC cell lines, we observed a turnover of M1 toward M2. These cells increased CD163 and IL-10 expression. The expression of TLR-3, -7, and -9 is increased when the macrophages were treated with the supernatant of CC cells. Conclusions. Our result strongly suggests that CC cells may, through the secretion of soluble factors, induce a change of immunophenotype M1 into M2 macrophages.

  14. Theoretical study of forbidden M1, M2, E2 transitions for highly charged Ni-like ions%类镍等电子系列离子M1,M2,E2禁戒跃迁特性的理论研究

    Institute of Scientific and Technical Information of China (English)

    万建杰; 颉录有; 董晨钟; 蒋军; 颜君

    2007-01-01

    利用基于全相对论框架下的多组态Dirac-Fock理论方法发展起来的程序包GRASP92和新发展的处理辐射跃迁过程的程序REOS99,计算了类镍等电子系列离子(Z=45-95)的基组态3s23p63d10 1S0以及低激发组态3s23p63d94l,3s23p53d104l和3s3p63d104 l(l=s,p,d,f)的能级及其向基态的M1,M2,E2禁戒跃迁概率.通过分析高离化类镍离子在特定的原子序数范围内由于存在能级交叉而产生的强组态相互作用,解释了高离化类镍离子禁戒跃迁概率的反常变化现象,探讨了禁戒跃迁概率受强组态相互作用影响而变化的一般规律.

  15. Effects of beta-amyloid protein on M1 and M2 subtypes of muscarinic acetylcholine receptors in the medial septum-diagonal band complex of the rat: relationship with cholinergic, GABAergic, and calcium-binding protein perikarya.

    Science.gov (United States)

    González, Iván; Arévalo-Serrano, Juan; Sanz-Anquela, José Miguel; Gonzalo-Ruiz, Alicia

    2007-06-01

    Cortical cholinergic dysfunction has been correlated with the expression and processing of beta-amyloid precursor protein. However, it remains unclear as to how cholinergic dysfunction and beta-amyloid (Abeta) formation and deposition might be related to one another. Since the M1- and M2 subtypes of muscarinic acetylcholine receptors (mAChRs) are considered key molecules that transduce the cholinergic message, the purpose of the present study was to assess the effects of the injected Abeta peptide on the number of M1mAchR- and M2mAChR-immunoreactive cells in the medial septum-diagonal band (MS-nDBB) complex of the rat. Injections of Abeta protein into the retrosplenial cortex resulted in a decrease in M1mAChR and M2mAChR immunoreactivity in the MS-nDBB complex. Quantitative analysis revealed a significant reduction in the number of M1mAChR- and M2mAChR-immunoreactive cells in the medial septum nucleus (MS) and in the horizontal nucleus of the diagonal band of Broca (HDB) as compared to the corresponding hemisphere in control animals and with that seen in the contralateral hemisphere, which corresponds to the PBS-injected side. Co-localization studies showed that the M1mAChR protein is localized in GABA-immunoreactive cells of the MS-nDBB complex, in particular those of the MS nucleus, while M2mAChR protein is localized in both the cholinergic and GABAergic cells. Moreover, GABAergic cells containing M2mAChR are mainly localized in the MS nucleus, while cholinergic cells containing M2mAChR are localized in the MS and the HDB nuclei. Our findings suggest that Abeta induces a reduction in M1mAChR- and M2mAChR-containing cells, which may contribute to impairments of cholinergic and GABAergic transmission in the MS-nDBB complex.

  16. Gas-phase chemistry of diphosphate anions as a tool to investigate the intrinsic requirements of phosphate ester enzymatic reactions: the [M1M2HP2O7]- ions.

    Science.gov (United States)

    Pepi, Federico; Barone, Vincenzo; Cimino, Paola; Ricci, Andreina

    2007-01-01

    Experimental studies on gaseous inorganic phosphate ions are practically nonexistent, yet they can prove helpful for a better understanding of the mechanisms of phosphate ester enzymatic processes. The present contribution extends our previous investigations on the gas-phase ion chemistry of diphosphate species to the [M(1)M(2)HP(2)O(7)](-) ions where M(1) and M(2) are the same or different and correspond to the Li, Na, K, Cs, and Rb cations. The diphosphate ions are formed by electrospray ionization of 10(-4) M solutions of Na(5)P(3)O(10) in CH(3)CN/H(2)O (1/1) and MOH bases or M salts as a source of M(+) cations. The joint application of mass spectrometric techniques and quantum-mechanical calculations makes it possible to characterize the gaseous [M(1)M(2)HP(2)O(7)](-) ions as a mixed ionic population formed by two isomeric species: linear diphosphate anion coordinated to two M(+) cations (group I) and [PO(3)M(1)M(2)HPO(4)](-) clusters (group II). The relative gas-phase stabilities and activation barriers for the isomerization I-->II, which depend on the nature of the M(+) cations, highlight the electronic susceptibility of P-O-P bond breaking in the active site of enzymes. The previously unexplored gas-phase reactivity of [M(1)M(2)HP(2)O(7)](-) ions towards alcohols of different acidity was investigated by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR/MS). The reaction proceeds by addition of the alcohol molecule followed by elimination of a water molecule.

  17. Inhibition of AGEs/RAGE/Rho/ROCK pathway suppresses non-specific neuroinflammation by regulating BV2 microglial M1/M2 polarization through the NF-κB pathway.

    Science.gov (United States)

    Chen, Jingkao; Sun, Zhaowei; Jin, Minghua; Tu, Yalin; Wang, Shengnan; Yang, Xiaohong; Chen, Qiuhe; Zhang, Xiao; Han, Yifan; Pi, Rongbiao

    2017-04-15

    The microglia-mediated neuroinflammation plays an important role in the pathogenesis of Alzheimer's disease (AD). Advanced glycation end products (AGEs)/receptor for advanced glycation end products (RAGE) or Rho/Rho kinase (ROCK) are both involved in the development of non-specific inflammation. However, there are few reports about their effects on neuroinflammation. Here, we explored the mechanism of AGEs/RAGE/Rho/ROCK pathway underlying the non-specific inflammation and microglial polarization in BV2 cells. AGEs could activate ROCK pathway in a concentration-dependent manner. ROCK inhibitor fasudil and RAGE-specific blocker FPS-ZM1 significantly inhibited AGEs-mediated activation of BV2 cells and induction of reactive oxygen species (ROS). FPS-ZM1 and fasudil exerted their anti-inflammatory effects by downregulating inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), NLRP3 and nuclear translocation of nuclear factor kappa B (NF-κB) p65. In addition, AGEs induced both M1 (CD16/32, M1 marker) and M2 (CD206, M2 marker) phenotype in BV2 cells. Fasudil and FPS-ZM1 led to a decreased M1 and increased M2 phenotype. Together, these results indicate that the AGEs/RAGE/Rho/ROCK pathway in BV2 cells could intensify the non-specific inflammation of AD, which will provide novel strategies for the development of anti-AD drugs.

  18. M1/M2 muscarinic receptor selectivity using potassium (K/sup +/)-stimulated release of (/sup 3/H)-dopamine (DA) and (/sup 14/C)-acetyl-choline (ACH) in striatum

    Energy Technology Data Exchange (ETDEWEB)

    DeHaven, D.L.; Steranka, L.R.

    1986-03-05

    Raiteri et al have suggested that muscarinic receptor subtypes can be differentiated in striatal synaptosomes by the release of DA (M1) or ACh (M2). The authors attempted to replicate this finding and to characterize responses of selective and non-selective cholinergic agonists and antagonists using K+-stimulated release of transmitters from rat striatal slices. The non-selective agonists ACh, carbachol and oxotremorine stimulated release of (/sup 3/H)-DA and inhibited release of (/sup 14/C)-ACh with EC50 values of 10.6, 9.2 and 4.2 ..mu..M (DA) and 1.2, 0.77 and 0.43 ..mu..M (ACh), respectively. The M1 agonist McN-A-343-11 selectively inhibited release of DA with an EC50 value of 4.8 ..mu..M. Pilocarpine was ineffective in this system. The M1 antagonist pirenzepine reversed the effects of 10/sup -4/ M carbachol on release with an eight-fold selectivity for release of (/sup 3/H)-DA (IC50 = 0.77 ..mu..M) vs (/sup 14/C)-ACh (IC50 = 6.3 ..mu..M). These results suggest that although this system can determine relative subtype selectivities, the results obtained in this assay do not always correlate with those obtained from phosphatidyl inositol turnover or adenylate cyclase activity.

  19. On the decrease in charge radii of multi-quasi particle isomers

    Energy Technology Data Exchange (ETDEWEB)

    Bissell, M.L. [School of Physics and Astronomy, University of Birmingham, Edgbaston, Birmingham B15 2TT (United Kingdom); Flanagan, K.T. [Schuster Laboratory, University of Manchester, Manchester M13 9PL (United Kingdom); Gardner, M.D. [School of Physics and Astronomy, University of Birmingham, Edgbaston, Birmingham B15 2TT (United Kingdom); Avgoulea, M. [Schuster Laboratory, University of Manchester, Manchester M13 9PL (United Kingdom); Billowes, J. [Schuster Laboratory, University of Manchester, Manchester M13 9PL (United Kingdom); Campbell, P. [Schuster Laboratory, University of Manchester, Manchester M13 9PL (United Kingdom); Cheal, B. [Schuster Laboratory, University of Manchester, Manchester M13 9PL (United Kingdom)]. E-mail: bc@mags.ph.man.ac.uk; Eronen, T. [Department of Physics, University of Jyvaeskylae, PB 35 (YFL) FIN-40351 Jyvaeskylae (Finland); Forest, D.H. [School of Physics and Astronomy, University of Birmingham, Edgbaston, Birmingham B15 2TT (United Kingdom); Huikari, J. [Department of Physics, University of Jyvaeskylae, PB 35 (YFL) FIN-40351 Jyvaeskylae (Finland); Jokinen, A. [Department of Physics, University of Jyvaeskylae, PB 35 (YFL) FIN-40351 Jyvaeskylae (Finland); Moore, I.D. [Department of Physics, University of Jyvaeskylae, PB 35 (YFL) FIN-40351 Jyvaeskylae (Finland); Nieminen, A. [Schuster Laboratory, University of Manchester, Manchester M13 9PL (United Kingdom); Penttilae, H. [Department of Physics, University of Jyvaeskylae, PB 35 (YFL) FIN-40351 Jyvaeskylae (Finland); Rinta-Antila, S. [Department of Physics, University of Jyvaeskylae, PB 35 (YFL) FIN-40351 Jyvaeskylae (Finland); Tordoff, B. [Schuster Laboratory, University of Manchester, Manchester M13 9PL (United Kingdom); Tungate, G. [School of Physics and Astronomy, University of Birmingham, Edgbaston, Birmingham B15 2TT (United Kingdom); Aystoe, J. [Department of Physics, University of Jyvaeskylae, PB 35 (YFL) FIN-40351 Jyvaeskylae (Finland)

    2007-02-15

    We report changes in mean-square charge radii, {delta}, magnetic moments and quadrupole moments for three multi-quasi particle isomers; {sup 97m2}Y, {sup 176m}Yb and {sup 178m1}Hf. All the isomers are observed to display a decrease in compared to the lower-lying nuclear state on which the isomer is built. The decreases in occur despite the isomers showing increases in quadrupole moment. Possible mechanisms for the effect, which is now seen for six multi-quasi particle isomers, are discussed.

  20. 辛伐他汀对小鼠炎症型巨噬细胞极性的影响%Anti-inflammation of simvastatin by polarization of murine macrophages from M1 phenotype to M2 phenotype

    Institute of Scientific and Technical Information of China (English)

    李全忠; 孙婧; 韩金杰; 钱宗杰

    2013-01-01

    Objective To explore the effects of statin on pro-inflammatory macrophage phenotype in a murine M1 macrophage model.Methods Macrophages isolated from murine bone barrow were stimulated with interferon-gamma (IFN-γ) and lipopolysaccharide (LPS) to establish a M1 macrophage model.And 1.0,2.5,5.0 μmol/L of simvastatin were added to M1 macrophages for a 9-hour culture.Cell surface markers CD16/23 and CD206 were detected by fluorescence activated cell sorter (FACS) and interleukin-10 (IL-10) and IL-12 by ELISA.Results The CD16/32 expression was 86.39% ± 2.24% and IL-12secretion (1562 ± 217) pg/ml in IFN-γ and LPS-stimulated macrophages.After a 9-hour incubation with 1.0,2.5,5.0 μmol/L simvastatin,the CD206 expression levels were 68.10% ± 2.48%,75.28% ± 1.66%,86.32% ±2.19% and the secretion of IL-10 (500 ±5),(675 ±28) and (916 ± 15) pg/ml respectively.By analysis of variance and q test of mean,the difference was statistically significant (all P <0.01) between the groups of M1 model(9.67% ±5.48%,(298 ± 11) pg/ml).And the phenotypic features were similar to those of the groups of M2 model.Conclusion Simvastatin may inhibit inflammation by enhancing the switching of M1 macrophage to M2 macrophage phenotype.%目的 观察辛伐他汀对炎症型M1型巨噬细胞极性的影响,探讨他汀类药物在细胞水平的抗炎作用.方法 以γ-干扰素及脂多糖刺激小鼠骨髓来源巨噬细胞诱导成M1型炎症性巨噬细胞模型,给予辛伐他汀1.0、2.5、5.0 μmol/L分别干预9h,以流式细胞仪检测巨噬细胞膜CD16/23、CD206标志分子的表达,用ELISA检测白细胞介素(IL)-10和IL-12的分泌.结果 γ-干扰素及脂多糖刺激的巨噬细胞CD16/32表达阳性率为86.39%±2.24%,IL-12分泌量为(1562±217) pg/ml,符合M1型巨噬细胞表型特点;与辛伐他汀1.0、2.5、5.0 μmol/L孵育9h后测定的CD206表达阳性率分别为68.10%±2.48%、75.28%±1.66%、86.32%±2.19%,IL-10

  1. Expression of iNOS, CD163 and ARG-1 taken as M1 and M2 markers of microglial polarization in human glioblastoma and the surrounding normal parenchyma.

    Science.gov (United States)

    Lisi, L; Ciotti, G M P; Braun, D; Kalinin, S; Currò, D; Dello Russo, C; Coli, A; Mangiola, A; Anile, C; Feinstein, D L; Navarra, P

    2017-04-03

    Microglia and macrophages appear to be the most common cells in the GBM microenvironment. In the present study we investigated the status of macrophages/microglia activation in surgical specimens from 41 patients diagnosed with grade IV GBM. For each patient we analyzed both the center of tumor and the parenchyma surrounding the tumor. The specimens were stained for: i) IBA1, a 17-kDa EF hand protein specifically expressed in microglia/macrophages ii) CD163, a cell surface antigen associated with M2 phenotype; iii) iNOS, taken as a functional marker of M1 phenotype, and iv) ARG-I, taken as a functional marker of M2 phenotype. Staining was scored in a double-blinded score on a scale from 0 to 5. Our results suggest that CD163 expression is higher within the tumor than in surrounding periphery in both male and female patients; while iNOS is higher within the tumor in males, no significant difference was found for ARG-1. In addition, analyzing the data in TGCA database, we found that CD163 expression was significantly and inversely correlated with mean survival times, with average survival times ranging from 448days in patients having low expression, to 319 in mid, and 353 in patients with high CD163 expressing tumors. In contrast, no significant association was found between survival time and ARG-1 or iNOS expression. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Study on polarization of macrophage in peripheral blood of patients with asthma%哮喘患儿外周血巨噬细胞M1M2极化状态研究

    Institute of Scientific and Technical Information of China (English)

    陈娜; 庞保东

    2016-01-01

    Objective:To investigate the different function of macrophage between patients with asthma and healthy control , and discuss the pathogenesis of the disease .Methods:Choose 50 healthy controls ,50 patients with asthma , and isolation of blood mac-rophage.Then samples were induced with GM-CSF, and cells were collected on day 7.Macrophage function was evaluated using the following methods:fluorescence-activated cell sorting analysis for cell surface markers and phagocytosis ;enzyme-linked immunosorbent assay for cytokine production and the induction of T cell .Results: Compared with the control group , asthma group had decreased CD64, CD11c, CD40 expression, and increased CD206, CD14, CD23 expression(P<0.05);displayed the decreased IL-10 level(P<0.05 );displayed a decreased phagocytosis ability ( P<0.05 );when co-cultured with T cells , the supernatantdisplayed the increased IL-4 expression , and decreased IFN-γlevel ( P<0.05 ) .Conclusion: Compared with the control group , macrophage in asthma group displayed M2 phenotype, which inditates macrophage play the important role in the pathogenesis of asthma .%目的:体外培养哮喘患儿外周血巨噬细胞,并从细胞的表型和功能方面观察巨噬细胞M1M2 极化状态的变化,从而探讨巨噬细胞在哮喘发病中的作用。方法:选取50 例健康对照者与50 例哮喘患儿,收集哮喘患儿及健康对照组的血液,分离纯化得到巨噬细胞,体外给予10 ng/ml GM-CSF 的血清培养液培养,并在第7 天,收集细胞及上清,运用流式细胞技术检测巨噬细胞表型表达,ELISA 方法检测细胞上清IL-10、IL-12 含量变化,检测巨噬细胞吞噬外来性抗原及刺激淋巴细胞分化的能力。结果:与健康对照组相比,哮喘患儿外周血巨噬细胞表面表达的共刺激分子CD64、CD11c、CD40 明显降低,CD206、CD14 及CD23 明显升高(P 均<0.05);患儿巨噬细胞分泌的IL-10

  3. Polysaccharide Agaricus blazei Murill stimulates myeloid derived suppressor cell differentiation from M2 to M1 type, which mediates inhibition of tumour immune-evasion via the Toll-like receptor 2 pathway.

    Science.gov (United States)

    Liu, Yi; Zhang, Lingyun; Zhu, Xiangxiang; Wang, Yuehua; Liu, WenWei; Gong, Wei

    2015-11-01

    Gr-1(+) CD11b(+) myeloid-derived suppressor cells (MDSCs) accumulate in tumor-bearing animals and play a critical negative role during tumor immunotherapy. Strategies for inhibition of MDSCs are expected to improve cancer immunotherapy. Polysaccharide Agaricus blazei Murill (pAbM) has been found to have anti-cancer activity, but the underlying mechanism of this is poorly understood. Here, pAbM directly activated the purified MDSCs through inducing the expression of interleukin-6 (IL-6), IL-12, tumour necrosis factor and inducible nitric oxide synthase (iNOS), CD86, MHC II, and pSTAT1 of it, and only affected natural killer and T cells in the presence of Gr-1(+) CD11b(+) monocytic MDSCs. On further analysis, we demonstrated that pAbM could selectively block the Toll-like receptor 2 (TLR2) signal of Gr-1(+) CD11b(+) MDSCs and increased their M1-type macrophage characteristics, such as producing IL-12, lowering expression of Arginase 1 and increasing expression of iNOS. Extensive study showed that Gr-1(+) CD11b(+) MDSCs by pAbM treatment had less ability to convert the CD4(+) CD25(-) cells into CD4(+) CD25(+) phenotype. Moreover, result from selective depletion of specific cell populations in xenograft mice model suggested that the anti-tumour effect of pAbM was dependent on Gr-1(+ ) CD11b(+) monocytes, nether CD8(+) T cells nor CD4(+) T cells. In addition to, pAbM did not inhibit tumour growth in TLR2(-/-) mice. All together, these results suggested that pAbM, a natural product commonly used for cancer treatment, was a specific TLR2 agonist and had potent anti-tumour effects through the opposite of the suppressive function of Gr-1(+) CD11b(+) MDSCs.

  4. The high-spin {sup 178m2}Hf isomer: production, chemical and isotopic separations, gamma spectrometry and internal conversion electrons spectrometry; L`isomere de haut spin {sup 178m2}Hf: production, separations chimiques et isotopiques, spectrometrie gamma et spectrometrie d`electrons de conversion interne

    Energy Technology Data Exchange (ETDEWEB)

    Kim, J.B.

    1993-10-13

    The high-spin isometric state of the nucleus 178Hf is a challenge for new and exotic nuclear physics studies. With its long half-life of 31 years, the production of a reasonable micro-weight quantity, with an isometric to ground state ratio as high as 5 per cent, is now regularly performed by intensive irradiations of ytterbium targets with helium ions of 36 MeV. Using sur-enriched, at 99,998 per cent, ytterbium 176 that we have prepared at the PARIS mass separator, the isomer purity has been improved. Targets of such material but also of enriched stable isotopes of hafnium have been prepared by electro-spraying of methanolic and acetic solutions. By inelastic diffusion of protons and deuton on these targets, the energy of the first state of the rotation band built on the isomer has been measured. Isotopic separations of the isomer have been performed, with a yield greater than 20 per cent, by the use of isotopically pure hafnium 176 as carrier. The separated beam of the mass 178 allowed to record the complete hyperfine spectrum of the isomer and to measure, for the first time, the magnetic dipole moment and the electric quadrupole moment. Isomer targets, implanted in various materials like copper, iron and hafnium monocrystal, provide the opportunity to accurately measure gamma and internal conversion decay of this nuclei and so to precise the multipolarity mixing of all transitions from K=16{sup +} to K=8{sup -}. (author). 49 refs., 47 figs., 11 tabs.

  5. Determination of aflatoxins M1, M2, B1, B2, G1 and G2 in peanut by modified QuEChERS method and ultra-high performance liquid chromatography-tandem mass spectrometry | Determinação de aflatoxinas M1, M2, B1, B2, G1 e G2 em amendoim utilizando um método QuEChERS modificado e cromatografia líquida de ultraeficiência com detecção por espectrometria de massas sequencial

    Directory of Open Access Journals (Sweden)

    Juliana Swensson de Mattos

    2015-08-01

    Full Text Available A suitable method for routine analysis of aflatoxins M1, M2, B1, B2, G1, G2 in peanut by ultra-high performance liquid chromatography-tandem mass spectrometry was developed and validated. The sample preparation was performed using a triple partitioning (water/acetonitrile/hexane modified Quick Easy Cheap Effective Rugged and Safe (QuEChERS method. For the first time, this method is reportedly used for aflatoxins analysis in peanut. Satisfactory recoveries ranged from 71 to 101%, with relative standard deviation lower than 15% were obtained for the target aflatoxins. The determination coefficients were ≥ 0.99 which showed good linearity. The LOD and LOQ varied from 0.03 to 0.26 ng g-1 and 0.1 to 0.88 ng g-1, respectively. The validated method was successfully applied to for the determination of aflatoxins in ten peanut samples. Total aflatoxin concentration exceeded the maximum level permitted by the Brazilian regulation in one sample of roasted peanut, while aflatoxins M1 and M2 were detected respectively in three and in one of the samples. The results strongly suggest that peanuts and peanut products should be continuously monitored for the aflatoxins investigated in this work. ---------------------------------------------------------------------------------------------- Um método adequado para a análise de rotina de aflatoxinas M1, M2, B1, B2, G1, G2 em amendoim por cromatografia líquida de ultraeficiência com espectrometria de massas foi desenvolvido e validado. A preparação da amostra foi realizada utilizando um método QuEChERS (Quick Easy Cheap Effective Rugged and Safe modificado, empregando partição tripla (água/acetonitrila/hexano. Pela primeira vez este método foi utilizado para análise de aflatoxinas em amendoim. Recuperações satisfatórias, entre 71 e 101%, com coeficientes de variação inferiores a 15%, foram obtidas para as aflatoxinas estudadas. Os coeficientes de determinação foram ≥ 0,99, demostrando boa

  6. Energies and E1, M1, E2, and M2 transition rates for states of the 2s22p3, 2s2p4, and 2p5 configurations in nitrogen-like ions between F III and Kr XXX

    Science.gov (United States)

    Rynkun, P.; Jönsson, P.; Gaigalas, G.; Froese Fischer, C.

    2014-03-01

    Based on relativistic wavefunctions from multiconfiguration Dirac-Hartree-Fock and configuration interaction calculations, E1, M1, E2, and M2 transition rates, weighted oscillator strengths, and lifetimes are evaluated for the states of the (1s2)2s22p3,2s2p4, and 2p5 configurations in all nitrogen-like ions between F III and Kr XXX. The wavefunction expansions include valence, core-valence, and core-core correlation effects through single-double multireference expansions to increasing sets of active orbitals. The computed energies agree very well with experimental values, with differences of only 300-600 cm-1 for the majority of the levels and ions in the sequence. Computed transitions rates are in close agreement with available data from MCHF-BP calculations by Tachiev and Froese Fischer [G.I. Tachiev, C. Froese Fischer, A&A 385 (2002) 716].

  7. An Assessment of Nuclear Isomers as an Energy Storage Medium

    Energy Technology Data Exchange (ETDEWEB)

    Hartouni, E P

    2008-12-08

    Nuclear Isomers have been suggested as a potential high energy density medium that might be used to store energy. This talk assesses the state of the science supporting key elements of using nuclear isomers in energy storage applications. The focus is on the nuclear isomer {sup 178m2}Hf which has been most widely suggested for energy storage applications. However, the science issues apply to all nuclear isomer. The assessment addresses the production of the nuclear isomer, and inducing the release of the isomer. Also discussed are novel speculations on photon and/or neutron chain reactions, both as a 'pure' material as well as mixed with other materials.

  8. High spin isomer beam line at RIKEN

    Energy Technology Data Exchange (ETDEWEB)

    Kishida, T.; Ideguchi, E.; Wu, H.Y. [Institute of Physical and Chemical Research, Saitama (Japan)] [and others

    1996-12-31

    Nuclear high spin states have been the subject of extensive experimental and theoretical studies. For the production of high spin states, fusion reactions are usually used. The orbital angular momentum brought in the reaction is changed into the nuclear spin of the compound nucleus. However, the maximum induced angular momentum is limited in this mechanism by the maximum impact parameter of the fusion reaction and by the competition with fission reactions. It is, therefore, difficult to populate very high spin states, and as a result, large {gamma}-detector arrays have been developed in order to detect subtle signals from such very high spin states. The use of high spin isomers in the fusion reactions can break this limitation because the high spin isomers have their intrinsic angular momentum, which can bring the additional angular momentum without increasing the excitation energy. There are two methods to use the high spin isomers for secondary reactions: the use of the high spin isomers as a target and that as a beam. A high spin isomer target has already been developed and used for several experiments. But this method has an inevitable shortcoming that only {open_quotes}long-lived{close_quotes} isomers can be used for a target: {sup 178}Hf{sup m2} (16{sup +}) with a half-life of 31 years in the present case. By developing a high spin isomer beam, the authors can utilize various short-lived isomers with a short half-life around 1 {mu}s. The high spin isomer beam line of RIKEN Accelerator Facility is a unique apparatus in the world which provides a high spin isomer as a secondary beam. The combination of fusion-evaporation reaction and inverse kinematics are used to produce high spin isomer beams; in particular, the adoption of `inverse kinematics` is essential to use short-lived isomers as a beam.

  9. 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....

  10. 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.

  11. Studies of high-K isomers at TRIUMF-ISAC

    Energy Technology Data Exchange (ETDEWEB)

    Smith, M.B. [TRIUMF, 4004 Wesbrook Mall, Vancouver, BC (Canada); Walker, P.M. [TRIUMF, 4004 Wesbrook Mall, Vancouver, BC (Canada); Department of Physics, University of Surrey, Guildford, Surrey (United Kingdom); Chakrawarthy, R.S. [TRIUMF, 4004 Wesbrook Mall, Vancouver, BC (Canada); Austin, R.A.E. [Department of Physics and Astronomy, McMaster University, Hamilton, ON (Canada); Ball, G.C. [TRIUMF, 4004 Wesbrook Mall, Vancouver, BC (Canada); Carroll, J.J. [Department of Physics and Astronomy, Youngstown State University, Ohio (United States); Cunningham, E. [TRIUMF, 4004 Wesbrook Mall, Vancouver, BC (Canada); Finlay, P. [Department of Physics, University of Guelph, Guelph, ON (Canada); Garrett, P.E. [Lawrence Livermore National Laboratory, Livermore, California (United States); Grinyer, G.F. [Department of Physics, University of Guelph, Guelph, ON (Canada); Hackman, G. [TRIUMF, 4004 Wesbrook Mall, Vancouver, BC (Canada); Hyland, B. [Department of Physics, University of Guelph, Guelph, ON (Canada); Koopmans, K. [TRIUMF, 4004 Wesbrook Mall, Vancouver, BC (Canada); Department of Physics and Astronomy, McMaster University, Hamilton, ON (Canada); Kulp, W.D. [School of Physics, Georgia Institute of Technology, Atlanta, Georgia (United States); Leslie, J.R. [Physics Department, Queen' s University, Kingston, ON (Canada); Phillips, A.A. [Department of Physics, University of Guelph, Guelph, ON (Canada); Propri, R. [Department of Physics and Astronomy, Youngstown State University, Ohio (United States); Regan, P.H. [Department of Physics, University of Surrey, Guildford, Surrey (United Kingdom); Sarazin, F. [TRIUMF, 4004 Wesbrook Mall, Vancouver, BC (Canada); Schumaker, M.A. [Department of Physics, University of Guelph, Guelph, ON (Canada); Scraggs, H.C. [TRIUMF, 4004 Wesbrook Mall, Vancouver, BC (Canada)] [and others

    2004-12-27

    The properties of high-K isomers have been investigated by measuring {gamma} rays from a source of the 31-year {sup 178}Hf{sup m2} isomer and from the decay of implanted {sup 178,179}Lu beams. Low-intensity transitions have been identified in the decay of {sup 178}Hf{sup m2}, demonstrating a consistent extension of K-hindrance systematics to higher multipolarities, and elucidating the spin-dependence of the mixing between the two K{sup {pi}} = 8{sup -} bands. A search is underway for new isomers in {sup 178,179}Lu and the preliminary results of the analysis are reported.

  12. Ultrasonic Investigations of Molecular Interaction in Binary Mixtures of Cyclohexanone with Isomers of Butanol

    Directory of Open Access Journals (Sweden)

    Sk. Md Nayeem

    2014-01-01

    Full Text Available Ultrasonic speed, u, and density, ρ, have been measured in binary liquid mixtures of cyclohexanone with the isomers of butanol (n-butanol, sec-butanol, and tert-butanol at 308.15 K over the entire range of composition. Molar volume (Vm, adiabatic compressibility (ks, intermolecular free length (Lf, acoustic impedance (z, and their excess/deviation along with Δu have been calculated from the experimental data. These values have been fitted to Redlich-Kister type polynomial equation. Positive values of VmE, Δks, LfE and negative values of zE, Δu have been observed for all the liquid mixtures indicating the existence of weak interactions between components. Rupture of H-bond or reduction in H-bond strength of isomers of butanol or breaking of the structure of one or both of the components in a solution causes the existence of dispersions in the present investigated binary mixtures. The data obtained from V-m,1, V-m,2, and excess partial molar volumes V-m, 1E, V-m, 2E, reflects the inferences drawn from VmE. Furthermore, FTIR spectra support the conclusions drawn from excess/deviation properties. The measured values of ultrasonic speed for all the investigated mixtures have been compared with the theoretically estimated values using empirical relations such as, Nomoto, Van Dael and Vangeels, Impedance and Rao specific sound speed.

  13. 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.

  14. Three-Parton Contributions to B --> M_1 M_2 Annihilation at Leading Order

    CERN Document Server

    Arnesen, C M; Stewart, I W; Arnesen, Christian M.; Rothstein, Ira Z.; Stewart, Iain W.

    2006-01-01

    We compute annihilation amplitudes for charmless B decays that are proportional to the three-parton twist-3 light meson distribution amplitude phi_{3M}(x1,x2) with an active gluon. Due to an enhancement from a quark propagator at the scale p^2 ~ mb\\Lambda_QCD these terms occur at the same parametric order in alpha_s(mb) and 1/mb as the known leading order annihilation involving fB and twist-2 meson distributions. With our calculation the leading order annihilation amplitude is now complete. At lowest order in alpha_s the amplitudes are real and only O_{5-8} contribute. Using simple models we find that the three-parton and two-parton terms are of comparable size.

  15. M1- and M2-type macrophage responses are predictive of adverse outcomes in human atherosclerosis

    Directory of Open Access Journals (Sweden)

    Monica De Gaetano

    2016-07-01

    Full Text Available Atherosclerosis is an inflammatory disease caused by endothelial injury, lipid deposition and oxidative stress. This progressive disease can be converted into an acute clinical event by plaque rupture and thrombosis. In the context of atherosclerosis, the underlying cause of myocardial infarction and stroke, macrophages uniquely possess a dual functionality, regulating lipid accumulation and metabolism and sustaining the chronic inflammatory response, two of the most well documented pathways associated with the pathogenesis of the disease. Macrophages are heterogeneous cell populations and it is hypothesized that, during the pathogenesis of atherosclerosis, macrophages in the developing plaque can switch from a pro-inflammatory (MΦ1 to an anti-inflammatory (MΦ2 phenotype and vice versa, depending on the microenvironment. The aim of this study was to identify changes in macrophage subpopulations in the progression of human atherosclerotic disease. Established atherosclerotic plaques from symptomatic and asymptomatic patients with existing coronary artery disease undergoing carotid endarterectomy were recruited to the study. Comprehensive histological and immunohistochemical analyses were performed to quantify the cellular content and macrophage subsets of atherosclerotic lesion. In parallel, expression of MΦ1 and MΦ2 macrophage markers were analysed by real time-PCR and Western blot analysis.Gross analysis and histological staining demonstrated that symptomatic plaques presented greater haemorrhagic activity and the internal carotid was the most diseased segment, based on the predominant prevalence of fibrotic and necrotic tissue, calcifications and haemorrhagic events. Immunohistochemical analysis showed that both MΦ1 and MΦ2 macrophages are present in human plaques. However, MΦ2 macrophages are localised to more stable locations within the lesion. Importantly, gene and protein expression analysis of MΦ1/ MΦ2 markers evidenced that MΦ1 markers and Th1 associated cytokines are highly expressed in symptomatic plaques, whereas, expression of the MΦ2 markers, MR and CD163 and Th2 cytokines are inversely related with disease progression.This data increases the understanding of atherosclerosis development, identifying the cellular content of lesions during disease progression and characterising macrophage subpopulation within human atherosclerotic plaques.

  16. Population and decay of a Kπ=8- two-quasineutron isomer in 244Pu

    Science.gov (United States)

    Hota, S. S.; Tandel, S. K.; Chowdhury, P.; Ahmad, I.; Carpenter, M. P.; Chiara, C. J.; Greene, J. P.; Hoffman, C. R.; Jackson, E. G.; Janssens, R. V. F.; Kay, B. P.; Khoo, T. L.; Kondev, F. G.; Lakshmi, S.; Lalkovski, S.; Lauritsen, T.; Lister, C. J.; McCutchan, E. A.; Moran, K.; Peterson, D.; Shirwadkar, U.; Seweryniak, D.; Stefanescu, I.; Toh, Y.; Zhu, S.

    2016-08-01

    The decay of a Kπ=8- isomer in 244Pu and the collective band structures populating the isomer were studied using deep inelastic excitations with 47Ti and 208Pb beams, respectively. Precise measurements of M 1 /E 2 branching ratios in the band confirm a 9 /2-[734] ν⊗7 /2+[624] ν configuration assignment for the isomer, validating the systematics of Kπ=8- , two-quasineutron isomers observed in even-Z , N =150 isotones. These isomers around the deformed shell gap at N =152 provide critical benchmarks for theoretical predictions of single-particle energies in this gateway region to superheavy nuclei.

  17. 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

  18. On (2m + 1)-variable symmetric Boolean functions with submaximum algebraic immunity 2m-1

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    All (2m +1)-variable symmetric Boolean functions with submaximal algebraic immunity 2m-1 are described and constructed. The total number of such Boolean functions is 32 ·22m-3 +3m-2 · 24 - 2 for m≥2.

  19. Isolation and Characterization of a Novel Rebaudioside M Isomer from a Bioconversion Reaction of Rebaudioside A and NMR Comparison Studies of Rebaudioside M Isolated from Stevia rebaudiana Bertoni and Stevia rebaudiana Morita

    OpenAIRE

    Indra Prakash; Cynthia Bunders; Krishna P. Devkota; Romila D. Charan; Catherine Ramirez; Christopher Priedemann; Avetik Markosyan

    2014-01-01

    A minor product, rebaudioside M2 (2), from the bioconversion reaction of rebaudioside A (4) to rebaudioside D (3), was isolated and the complete structure of the novel steviol glycoside was determined. Rebaudioside M2 (2) is considered an isomer of rebaudioside M (1) and contains a relatively rare 1→6 sugar linkage. It was isolated and characterized with NMR (1H, 13C, COSY, HSQC-DEPT, HMBC, 1D-TOCSY, and NOESY) and mass spectral data. Additionally, we emphasize the importance of 1D and 2D NMR...

  20. Isolation and characterization of a novel rebaudioside M isomer from a bioconversion reaction of rebaudioside A and NMR comparison studies of rebaudioside M isolated from Stevia rebaudiana Bertoni and Stevia rebaudiana Morita.

    Science.gov (United States)

    Prakash, Indra; Bunders, Cynthia; Devkota, Krishna P; Charan, Romila D; Ramirez, Catherine; Priedemann, Christopher; Markosyan, Avetik

    2014-03-31

    A minor product, rebaudioside M2 (2), from the bioconversion reaction of rebaudioside A (4) to rebaudioside D (3), was isolated and the complete structure of the novel steviol glycoside was determined. Rebaudioside M2 (2) is considered an isomer of rebaudioside M (1) and contains a relatively rare 1→6 sugar linkage. It was isolated and characterized with NMR (1H, 13C, COSY, HSQC-DEPT, HMBC, 1D-TOCSY, and NOESY) and mass spectral data. Additionally, we emphasize the importance of 1D and 2D NMR techniques when identifying complex steviol glycosides. Numerous NMR spectroscopy studies of rebaudioside M (1), rebaudioside D (3), and mixture of 1 and 3 led to the discovery that SG17 which was previously reported in literature, is a mixture of rebaudioside D (3), rebaudioside M (1), and possibly other related steviol glycosides.

  1. Isolation and Characterization of a Novel Rebaudioside M Isomer from a Bioconversion Reaction of Rebaudioside A and NMR Comparison Studies of Rebaudioside M Isolated from Stevia rebaudiana Bertoni and Stevia rebaudiana Morita

    Directory of Open Access Journals (Sweden)

    Indra Prakash

    2014-03-01

    Full Text Available A minor product, rebaudioside M2 (2, from the bioconversion reaction of rebaudioside A (4 to rebaudioside D (3, was isolated and the complete structure of the novel steviol glycoside was determined. Rebaudioside M2 (2 is considered an isomer of rebaudioside M (1 and contains a relatively rare 1→6 sugar linkage. It was isolated and characterized with NMR (1H, 13C, COSY, HSQC-DEPT, HMBC, 1D-TOCSY, and NOESY and mass spectral data. Additionally, we emphasize the importance of 1D and 2D NMR techniques when identifying complex steviol glycosides. Numerous NMR spectroscopy studies of rebaudioside M (1, rebaudioside D (3, and mixture of 1 and 3 led to the discovery that SG17 which was previously reported in literature, is a mixture of rebaudioside D (3, rebaudioside M (1, and possibly other related steviol glycosides.

  2. Isolation and Characterization of a Novel Rebaudioside M Isomer from a Bioconversion Reaction of Rebaudioside A and NMR Comparison Studies of Rebaudioside M Isolated from Stevia rebaudiana Bertoni and Stevia rebaudiana Morita

    Science.gov (United States)

    Prakash, Indra; Bunders, Cynthia; Devkota, Krishna P.; Charan, Romila D.; Ramirez, Catherine; Priedemann, Christopher; Markosyan, Avetik

    2014-01-01

    A minor product, rebaudioside M2 (2), from the bioconversion reaction of rebaudioside A (4) to rebaudioside D (3), was isolated and the complete structure of the novel steviol glycoside was determined. Rebaudioside M2 (2) is considered an isomer of rebaudioside M (1) and contains a relatively rare 1→6 sugar linkage. It was isolated and characterized with NMR (1H, 13C, COSY, HSQC-DEPT, HMBC, 1D-TOCSY, and NOESY) and mass spectral data. Additionally, we emphasize the importance of 1D and 2D NMR techniques when identifying complex steviol glycosides. Numerous NMR spectroscopy studies of rebaudioside M (1), rebaudioside D (3), and mixture of 1 and 3 led to the discovery that SG17 which was previously reported in literature, is a mixture of rebaudioside D (3), rebaudioside M (1), and possibly other related steviol glycosides. PMID:24970220

  3. GSM(m,1)(m=1,2)模型的数值解%Numeriacl Solution of GSM (m, 1)(m= 1,2)Model

    Institute of Scientific and Technical Information of China (English)

    吴强; 刘炳琪

    2001-01-01

    The prediction accuracy can be improved by using the spline function to correct the residue of GM (m,1)(m=1,2). Numerical Solution of GSM (m,1)(m=1,2)Modle is given.%本文用样条函数对GM(m,1)(m=1,2)模型的残差序列进行插值拟合,得到GSM(m,1)(m=1,2)模型的数值解.

  4. Isomer Energy System Design Concepts

    Energy Technology Data Exchange (ETDEWEB)

    Vogt, D

    2003-09-01

    Isomer energy supplies offer the potential to increase the output power over time to accommodate varying power needs. Other materials with similar energy density (for example isotopic energy sources such as {sup 238}Pu) do not offer the potential to increase power with time. Often the design life of an energy source is significant when compared to the half-life of the isotope. As a result, the conventional isotopic energy supplies operate with significant excess power at start of life to meet the power needs at end-of-life. For example a {sup 238}Pu radioisotope energy supply with a 35-year design life must account for radioactive decay losses of about 25% of the plutonium present at the start of life. This decay loss is significant if the required output power from the device is constant with time. If the required power output from the device increases with time (such as some space applications), significant increases in power supply weight are required to meet design power requirements. Isomer energy supplies offer the potential to increase the output power over time to meet varying power needs, thereby offering a significant advantage over conventional systems. Isomer energy supplies also offer the possibility of being ''turned on'' based on need at a specific time. These characteristics offer distinct advantages to isomer energy supplies. This report examines the basic engineering characteristics of a hypothetical isomer energy supply in order to gain insight into properties of isomers that will make them potentially useful as energy sources in engineered systems. These isomer properties provide a basis for identification of candidate isomers and provide a basis for an isomer search.

  5. 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.

  6. 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

  7. Isomer Spectrum of Small Carbon Clusters

    Institute of Scientific and Technical Information of China (English)

    SHENG Yang; LI Peng; NING Xi-Jing

    2004-01-01

    A theoretical method is developed to find isomers of cluster particles, and the isomer spectrum of carbon clusters Cn (n = 3-44) is obtained. It is found that the isomers of 3-11 atoms are in either mono-ring or line shapes,while the isomers of 12-18 atoms show flat sheet shapes. As cluster size increases, bowl isomers become more (n > 19) until cage isomers dominate the structures (n > 27). Based on the isomer spectrum, results of a previous experiment are interpreted.

  8. Lipid and Glycolipid Isomer Analyses Using Ultra-High Resolution Ion Mobility Spectrometry Separations

    Energy Technology Data Exchange (ETDEWEB)

    Wojcik, Roza; Webb, Ian; Deng, Liulin; Garimella, Sandilya; Prost, Spencer; Ibrahim, Yehia; Baker, Erin; Smith, Richard

    2017-01-01

    Understanding the biological mechanisms related to lipids and glycolipids is challenging due to the vast number of possible isomers. Mass spectrometry (MS) measurements are currently the dominant approach for studying and providing detailed information on lipid and glycolipid structures. However, difficulties in distinguishing many structural isomers (e.g. distinct acyl chain positions, double bond locations, as well as glycan isomers) inhibit the understanding of their biological roles. Here we utilized ultra-high resolution ion mobility spectrometry (IMS) separations based upon the use of traveling waves in a serpentine long path length multi-pass Structures for Lossless Manipulations (SLIM) to enhance isomer resolution. The multi-pass arrangement allowed separations ranging from ~16 m (1 pass) to ~470 m (32 passes) to be investigated for the distinction of lipids and glycolipids with extremely small structural differences. These ultra-high resolution SLIM IMS-MS analyses provide a foundation for exploring and better understanding isomer specific biological and disease processes.

  9. Adsorption equilibria of dimethylnaphthalene isomers

    Energy Technology Data Exchange (ETDEWEB)

    Rota, R.; Morbidelli, M. [Politecnico di Milano (Italy). Dipt. di Chimica Fisica Applicata; Rombi, E.; Monaci, R.; Ferino, I.; Solinas, V. [Univ. di Cagliari (Italy). Dipt. di Scienze Chimiche

    1996-01-01

    Commercial sources of DMNs are the aromatic petroleum fraction of the appropriate boiling range and the coal liquefaction products. Adsorption processes for separating mixtures of dimethylnaphthalene (DMN) isomers are of potential interest for the production of 2,6-DMN. In this work, the adsorption equilibria of liquid mixtures of DMN isomers on zeolites have been investigated experimentally. The separation factors between the various isomers have been found to depend strongly on the composition of the fluid phase. A suitable equilibrium model, based on the adsorbed solution theory, has been developed to describe the multicomponent adsorption equilibria in the entire range of interest. Its performance has been tested using binary and ternary equilibrium data.

  10. M1-M2 balancing act in white adipose tissue browning – a new role for RIP140

    OpenAIRE

    Liu, Pu-Ste; LIN, YI-WEI; Burton, Frank H; Wei, Li-Na

    2015-01-01

    A “Holy Grail” sought in medical treatment of obesity is to be able to biologically reprogram their adipose tissues to burn fat rather than store it. White adipose tissue (WAT) stores fuel and its expansion underlines insulin resistance (IR) whereas brown adipose tissue (BAT) burns fuel and stimulates insulin sensitivity. These two types of fats seesaw within our bodies via a regulatory mechanism that involves intricate communication between adipocytes and blood cells, particularly macrophage...

  11. Isoform switch of pyruvate kinase M1 indeed occurs but not to pyruvate kinase M2 in human tumorigenesis.

    Directory of Open Access Journals (Sweden)

    Cheng Zhan

    Full Text Available Muscle type of pyruvate kinase (PKM is one of the key mediators of the Warburg effect and tumor metabolism. Due to alternative splicing, there are at least 12 known isoforms of the PKM gene, of which PKM1 and PKM2 are two major isoforms with only a 23 amino acid sequenced difference but quite different characteristics and functions. It was previously thought the isoform switch from PKM1 to PKM2 resulted in high PKM2 expression in tumors, providing a great advantage to tumor cells. However, this traditional view was challenged by two recent studies; one study claimed that this isoform switch does not occur during the Warburg effect; the other study asserted that the isoform switch is tissue-specific. Here, we re-analyzed the RNA sequencing data of 25 types of human tumors from The Cancer Genome Atlas Data Portal, and confirmed that PKM2 was the major isoform in the tumors and was highly elevated in addition to the entire PKM gene. We further demonstrated that the expression level of PKM1 significantly declined even though there was substantially increased expression of the entire PKM gene. The proportion of PKM1 in total transcript variants also significantly declined in tumors but the proportion of PKM2 did not change accordingly. Therefore, we conclude that the isoform switch of PKM1 does indeed occur, but it switches to other isoforms rather than PKM2. Considering the change in the expression levels of PKM1, PKM2 and the entire PKM gene, we propose that the upregulation of PKM2 is primarily due to elevated transcriptional levels of the entire PKM gene, instead of the isoform switch.

  12. Modulation of macrophage activity by aflatoxins B1 and B2 and their metabolites aflatoxins M1 and M2.

    Science.gov (United States)

    Bianco, G; Russo, R; Marzocco, S; Velotto, S; Autore, G; Severino, L

    2012-05-01

    Aflatoxins are natural contaminants frequently found both in food and feed. Many of them exert immunomodulatory properties in mammals; therefore, the aim of the current study was to investigate immune-effects of AFB1, AFB2, AFM1 and AFM2, alone and differently combined, in J774A.1 murine macrophages. MTT assay showed that AFB1, alone and combined with AFB2, possess antiproliferative activity only at the highest concentration; such effect was not shown by their hydroxylated metabolites, AFM1 and AFM2, respectively. However, the immunotoxic effects of the aflatoxins evaluated in the current study may be due to the inhibition of production of active oxygen metabolites such as NO. Cytofluorimetric assay in macrophages exposed to aflatoxins (10-100 μM) revealed that their cytoxicity is not related to apoptotic pathways. Nevertheless, a significant increase of the S phase cell population accompanied by a decrease in G0/G1 phase cell population was observed after AFB1 treatment. In conclusion, the results of the current study suggest that aflatoxins could compromise the macrophages functions; in particular, co-exposure to AFB1, AFB2, AFM1 and AFM2 may exert interactions which can significantly affect immunoreactivity.

  13. Biological actions of formoterol isomers.

    Science.gov (United States)

    Handley, Dean A; Senanayake, Chris H; Dutczak, William; Benovic, Jeffrey L; Walle, Thomas; Penn, Raymond B; Wilkinson, H Scott; Tanoury, Gerald J; Andersson, Rolf G G; Johansson, Fredrik; Morley, John

    2002-01-01

    Racemic beta(2) agonists, composed of equal amounts of (R)- and (S)-isomers, can display anomalous actions that compromise their effectiveness as asthma therapies. Loss of efficacy during regular use is characteristic of isoprenaline, albuterol and terbutaline and has in part been attributed to the biological effects of the (S)-isomer. This hypothesis was applied to the (R,R)- and (S,S)-isomers of formoterol. (R,R)-formoterol had 1000-times greater affinity (2.9 nm) to the human beta(2) adrenoceptor than (S,S)-formoterol (3100 nm), with receptor binding modulating intracellular cAMP levels. The minimum lethal intravenous (IV) dose was determined to be 100 mg/kg for (R,R)- and 50 mg/kg for (S,S)-formoterol, suggesting that the toxicity of (S,S)-formoterol may not be related to the binding of beta(2) adrenoceptors. In tissues pretreated with (S,S)-formoterol but not with (R,R)- or racemic formoterol contractions to high concentrations of carbachol were exaggerated. In vivo experiments with sensitized guinea pigs demonstrated that (R,R)-formoterol inhibited both histamine and antigen-induced bronchoconstriction with greater potency than (R,R/S,S)-formoterol while (S,S)-formoterol was ineffective. Metabolic radiolabeling experiments of (R,R)-, (S,S)- or (R,R/S,S)-formoterol with crude human liver phenolsulfotransferase (PST) determined the V(max)/K(m) values to be (0.151), (0.74) and (0.143), respectively. The reciprocal plot illustrates a 2-fold reduction in sulfation rate when (R,R)-formoterol is present as a single isomer. The data presented here suggest that (R,R)-formoterol binds to the beta(2) adrenoceptor and inhibits the contraction of bronchial tissues by spasmogens. However, (S,S)-formoterol exhibits properties inconsistent as an asthma therapeutic and may antagonize the actions of (R,R)-formoterol. Copyright 2002 Elsevier Science Ltd.

  14. Isomers chart; Table des isomeres

    Energy Technology Data Exchange (ETDEWEB)

    Dupont-Gautier, P.; Chantelot, S.; Moisson, N. [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1967-07-01

    The nuclear isomers are nuclides offering the same mass number and the same atomic number, but different energy levels. In the following chart the zero energy ground states are omitted and the metastable isomers, i.e. of non-zero energy, known and of measurable lifetime, are listed. The lower limit of this lifetime was set here to 0.1 x 10{sup -6} s. The various isomers were classified in increasing lifetimes. (authors) [French] Les isomeres nucleaires sont des nucleides presentant le meme nombre de masse et le meme numero atomique, mais des niveaux energetiques differents. Dans la table suivante, on a neglige les etats fondamentaux d'energie nulle et on a recense les isomeres metastables, c'est-a-dire d'energie non nulle, connus et de periode mesurable. La limite inferieure de cette periode a ete fixee ici a 0,1 x 10{sup -6} s. Les differents isomeres ont ete classes par periodes croissantes. (auteurs)

  15. Isomers chart; Table des isomeres

    Energy Technology Data Exchange (ETDEWEB)

    Dupont-Gautier, P.; Chantelot, S.; Moisson, N. [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1967-07-01

    The nuclear isomers are nuclides offering the same mass number and the same atomic number, but different energy levels. In the following chart the zero energy ground states are omitted and the metastable isomers, i.e. of non-zero energy, known and of measurable lifetime, are listed. The lower limit of this lifetime was set here to 0.1 x 10{sup -6} s. The various isomers were classified in increasing lifetimes. (authors) [French] Les isomeres nucleaires sont des nucleides presentant le meme nombre de masse et le meme numero atomique, mais des niveaux energetiques differents. Dans la table suivante, on a neglige les etats fondamentaux d'energie nulle et on a recense les isomeres metastables, c'est-a-dire d'energie non nulle, connus et de periode mesurable. La limite inferieure de cette periode a ete fixee ici a 0,1 x 10{sup -6} s. Les differents isomeres ont ete classes par periodes croissantes. (auteurs)

  16. 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

  17. 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 $\

  18. The (178m2) Hf Controversy

    CERN Document Server

    Becker, J A; Schiffer, J P; Wilhelmy, J

    2003-01-01

    Since its discovery in the 1960's the sup 1 sup 7 sup 8 sup m sup 2 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 fo...

  19. M$_1$ - M* correlation in galaxy clusters

    CERN Document Server

    Trevese, D; Appodia, B

    1994-01-01

    Photographic F band photometry of a sample of 36 Abell clusters has been used to study the relation between the magnitude M_1 of the brightest cluster member and the Schechter function parameter M^*. Clusters appear segregated in the M_1-M^* plane according to their Rood \\& Sastry class. We prove on a statistical basis that on average, going from early to late RS classes, M_1 becomes brighter while M^* becomes fainter. The result agrees with the predictions of galactic cannibalism models, never confirmed by previous analyses.

  20. Selectivity of oxomemazine for the M1 muscarinic receptors.

    Science.gov (United States)

    Lee, S W; Woo, C W; Kim, J G

    1994-12-01

    The binding characteristics of pirenzepine and oxomemazine to muscarinic receptor were studied to evaluate the selectivity of oxomemazine for the muscarinic receptor subtypes in rat cerebral microsomes. Equilibrium dissociation constant (KD) of (-)-[3H]quinuclidinyl benzilate([3H]QNB) determined from saturation isotherms was 64 pM. Analysis of the pirenzepine inhibition curve of [3H]QNB binding to cerebral microsome indicated the presence of two receptor subtypes with high (Ki = 16 nM, M1 receptor) and low (Ki = 400 nM, M3 receptor) affinity for pirenzepine. Oxomemazine also identified two receptor subtypes with about 20-fold difference in the affinity for high (Ki = 84 nM, OH receptor) and low (Ki = 1.65 microM, OL receptor) affinity sites. The percentage populations of M1 and M3 receptors to the total receptors were 61:39, and those of OH and OL receptors 39:61, respectively. Both pirenzepine and oxomemazine increased the KD value for [3H]QNB without affecting the binding site concentrations and Hill coefficient for the [3H]QNB binding. Oxomemazine had a 10-fold higher affinity at M1 receptors than at M3 receptors, and pirenzepine a 8-fold higher affinity at OH receptors than at OL receptors. Analysis of the shallow competition binding curves of oxomemazine for M1 receptors and pirenzepine for OL receptors yielded that 69% of M1 receptors were of OH receptors and the remaining 31% of OL receptors, and that 29% of OL receptors were of M1 receptors and 71% of M3 receptors. However, M3 for oxomemazine and OH for pirenzepine were composed of a uniform population. These results suggest that oxomemazine could be classified as a selective drug for M1 receptors and also demonstrate that rat cerebral microsomes contain three different subtypes of M1, M3 and the other site which is different from M1, M2 and M3 receptors.

  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. Isomer Energy Source for Space Propulsion Systems

    Science.gov (United States)

    2004-03-01

    Nuclear Thermal Rocket PBR Particle-Bed Reactor SNTP Space Nuclear Thermal Propulsion TIC Triggered Isomer Core TIHE Triggered Isomer Heat...energy in a nuclear thermal rocket (NTR) configuration. This includes study of the current state of triggered isomer research, an investigation of 4... thermal rocket this means that heat from the reactive core must be prevented from raising the temperature of the propellant prior to its release from

  3. Optical absorption spectra of Ag-11 isomers

    DEFF Research Database (Denmark)

    Martinez, Jose Ignacio; Fernandez, E. M.

    2009-01-01

    The optical absorption spectra of the three most; stable structural isomers of the Ag-11 cluster were calculated using the time-dependent, density functional theory within the Casida formalism. The slightly different, spectra, of the isomers may permit the identification of the ground-stale confi......The optical absorption spectra of the three most; stable structural isomers of the Ag-11 cluster were calculated using the time-dependent, density functional theory within the Casida formalism. The slightly different, spectra, of the isomers may permit the identification of the ground...

  4. 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.

  5. 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.

  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. On the calculation of Mossbauer isomer shift

    NARCIS (Netherlands)

    Filatov, Michael

    2007-01-01

    A quantum chemical computational scheme for the calculation of isomer shift in Mossbauer spectroscopy is suggested. Within the described scheme, the isomer shift is treated as a derivative of the total electronic energy with respect to the radius of a finite nucleus. The explicit use of a finite nuc

  8. Characterization of Compass M-1 signals

    NARCIS (Netherlands)

    Hauschild, A.; Montenbruck, O.; Sleewaegen, J.-M.; Huisman, L.; Teunissen, P.J.G.

    2011-01-01

    An analysis of observations from China’s first medium earth orbit satellite Compass M-1 is presented, with main focus on the first orbit and clock solution for this satellite. The orbit is computed from laser ranging measurements. Based on this orbit solution, the apparent clock offset is estimated

  9. Analytic closures for M1 neutrino transport

    Science.gov (United States)

    Murchikova, E. M.; Abdikamalov, E.; Urbatsch, T.

    2017-08-01

    Carefully accounting for neutrino transport is an essential component of many astrophysical studies. Solving the full transport equation is too expensive for most realistic applications, especially those involving multiple spatial dimensions. For such cases, resorting to approximations is often the only viable option for obtaining solutions. One such approximation, which recently became popular, is the M1 method. It utilizes the system of the lowest two moments of the transport equation and closes the system with an ad hoc closure relation. The accuracy of the M1 solution depends on the quality of the closure. Several closures have been proposed in the literature and have been used in various studies. We carry out an extensive study of these closures by comparing the results of M1 calculations with precise Monte Carlo calculations of the radiation field around spherically symmetric protoneutron star models. We find that no closure performs consistently better or worse than others in all cases. The level of accuracy that a given closure yields depends on the matter configuration, neutrino type and neutrino energy. Given this limitation, the maximum entropy closure by Minerbo on average yields relatively accurate results in the broadest set of cases considered in this work.

  10. SAR studies on carboxylic acid series M(1) selective positive allosteric modulators (PAMs).

    Science.gov (United States)

    Kuduk, Scott D; Beshore, Douglas C

    2014-01-01

    There is mounting evidence from preclinical and early proof-of-concept studies suggesting that selective modulation of the M1 muscarinic receptor is efficacious in cognitive models of Alzheimer's disease (AD). A number of nonselective M1 muscarinic agonists have previously shown positive effects on cognitive function in AD patients, but were limited due to cholinergic adverse events thought to be mediated by pan activation of the M2 to M5 sub-types. Thus, there is a need to identify selective activators of the M1 receptor to evaluate their potential in cognitive disorders. One strategy to confer selectivity for M1 is the identification of allosteric agonists or positive allosteric modulators, which would target an allosteric site on the M1 receptor rather than the highly conserved orthosteric acetylcholine binding site. BQCA has been identified as a highly selective carboxylic acid M1 PAM and this review focuses on an extensive lead optimization campaign undertaken on this compound.

  11. M1 muscarinic receptor activation mediates cell death in M1-HEK293 cells.

    Science.gov (United States)

    Graham, E Scott; Woo, Kerhan K; Aalderink, Miranda; Fry, Sandie; Greenwood, Jeffrey M; Glass, Michelle; Dragunow, Mike

    2013-01-01

    HEK293 cells have been used extensively to generate stable cell lines to study G protein-coupled receptors, such as muscarinic acetylcholine receptors (mAChRs). The activation of M1 mAChRs in various cell types in vitro has been shown to be protective. To further investigate M1 mAChR-mediated cell survival, we generated stable HEK293 cell-lines expressing the human M1 mAChR. M1 mAChRs were efficiently expressed at the cell surface and efficiently internalised within 1 h by carbachol. Carbachol also induced early signalling cascades similar to previous reports. Thus, ectopically expressed M1 receptors behaved in a similar fashion to the native receptor over short time periods of analysis. However, substantial cell death was observed in HEK293-M1 cells within 24 h after carbachol application. Death was only observed in HEK cells expressing M1 receptors and fully blocked by M1 antagonists. M1 mAChR-stimulation mediated prolonged activation of the MEK-ERK pathway and resulted in prolonged induction of the transcription factor EGR-1 (>24 h). Blockade of ERK signalling with U0126 did not reduce M1 mAChR-mediated cell-death significantly but inhibited the acute induction of EGR-1. We investigated the time-course of cell death using time-lapse microscopy and xCELLigence technology. Both revealed the M1 mAChR cytotoxicity occurs within several hours of M1 activation. The xCELLigence assay also confirmed that the ERK pathway was not involved in cell-death. Interestingly, the MEK blocker did reduce carbachol-mediated cleaved caspase 3 expression in HEK293-M1 cells. The HEK293 cell line is a widely used pharmacological tool for studying G-protein coupled receptors, including mAChRs. Our results highlight the importance of investigating the longer term fate of these cells in short term signalling studies. Identifying how and why activation of the M1 mAChR signals apoptosis in these cells may lead to a better understanding of how mAChRs regulate cell-fate decisions.

  12. 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...

  13. [The BION-M1 project: overview and first results].

    Science.gov (United States)

    Sychev, V N; Ilyin, E A; Yarmanova, E N; Rakov, D V; Ushakov, I B; Kirilin, A N; Orlov, O I; Grigoriev, A I

    2014-01-01

    Biosatellite BION-M1 was launched on April 19 and landed on May 19, 2013. The mission program was largely a continuation of the earlier flown 11 BION projects, FOTON-M2 and FOTON-M3. The biosatellite was inhabited by a great variety of living organisms used for experiments and studies in gravitational physiology, gravitational biology, biotechnology, astrobiology and radiation biology, dosimetry and spectrometry. This was the first time in the history of national biology and physiology when male mice C57bl/6 were chosen for a long-term space experiment focused upon molecular biology investigations. Unfortunately, because of technical failures during the flight a part of the animals were lost. However, the major objectives were attained through reconsideration of biomaterial division among investigators and completion of virtually the total scope of investigations.

  14. "m=1" coatings for neutron guides

    OpenAIRE

    Cooper-Jensen, C.P.; Vorobiev, A.; Klinkby, Esben Bryndt; Kapaklis, V.; Wilkens, H.; Rats, D.; Hjörvarsson, B.; Kirstein, O.; Bentley, Philip

    2014-01-01

    A substantial part of the price for a neutron guide is the shielding needed because of the gamma ray produced when neutrons are absorbed. This absorption occurs in the coating and the substrate of the neutron guides. Traditional m=1 coatings have been made of Ni and if reflectivity over the critical angle of Ni is needed one has used Ni58 or Ni/Ti multilayer coatings. Ni has one of the highest neutron scattering density but it also has a fairly high absorption cross section for cold and therm...

  15. 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.

  16. 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.

  17. 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.

  18. Spectral identification of fullerene C82 isomers

    Science.gov (United States)

    Gao, Bin; Liu, Lei; Wang, ChunRu; Wu, ZiYu; Luo, Yi

    2007-10-01

    Ultraviolet photoelectron spectra (UPS) of C82 isomers have been calculated using hybrid density functional theory in combination with the Gelius model [Proceedings of the International Conference on Electron spectroscopy, edited by D. A. Shirley (North-Holland, Amsterdam, 1972), p. 311; J. Electron Spectrosc. Relat. Phenom. 5, 985 (1974)]. The calculated UPS spectra are found to be isomer dependent and in good agreement with the experimental counterparts. Near-edge x-ray absorption fine structure (NEXAFS), x-ray photoelectron spectroscopy (XPS), x-ray emission spectroscopy, and the resonant inelastic x-ray scattering (RIXS) spectra of three important isomers [3(C2), 6(Cs), and 9(C2v)] have also been simulated. Strong isomer dependence has also been found for NEXAFS, XPS, and RIXS spectra.

  19. Conjugated linoleic acid isomers and cancer.

    Science.gov (United States)

    Kelley, Nirvair S; Hubbard, Neil E; Erickson, Kent L

    2007-12-01

    We reviewed the literature regarding the effects of conjugated linoleic acid (CLA) preparations enriched in specific isomers, cis9, trans11-CLA (c9, t11-CLA) or trans10, cis12-CLA (t10, c12-CLA), on tumorigenesis in vivo and growth of tumor cell lines in vitro. We also examined the potential mechanisms by which CLA isomers may alter the incidence of cancer. We found no published reports that examined the effects of purified CLA isomers on human cancer in vivo. Incidence of rat mammary tumors induced by methylnitrosourea was decreased by c9, t11-CLA in all studies and by t10, c12-CLA in just a few that included it. Those 2 isomers decreased the incidence of forestomach tumors induced by benzo (a) pyrene in mice. Both isomers reduced breast and forestomach tumorigenesis. The c9, t11-CLA isomer did not affect the development of spontaneous tumors of the intestine or mammary gland, whereas t10, c12-CLA increased development of genetically induced mammary and intestinal tumors. In vitro, t10, c12-CLA inhibited the growth of mammary, colon, colorectal, gastric, prostate, and hepatoma cell lines. These 2 CLA isomers may regulate tumor growth through different mechanisms, because they have markedly different effects on lipid metabolism and regulation of oncogenes. In addition, c9, t11-CLA inhibited the cyclooxygenase-2 pathway and t10, c12-CLA inhibited the lipooxygenase pathway. The t10, c12-CLA isomer induced the expression of apoptotic genes, whereas c9, t11-CLA did not increase apoptosis in most of the studies that assessed it. Several minor isomers including t9, t11-CLA; c11, t13-CLA; c9, c11-CLA; and t7, c11-CLA were more effective than c9, t11-CLA or t10, c12-CLA in inhibiting cell growth in vitro. Additional studies with purified isomers are needed to establish the health benefit and risk ratios of each isomer in humans.

  20. "m=1" coatings for neutron guides

    DEFF Research Database (Denmark)

    Cooper-Jensen, C.P.; Vorobiev, A.; Klinkby, Esben Bryndt

    2014-01-01

    A substantial part of the price for a neutron guide is the shielding needed because of the gamma ray produced when neutrons are absorbed. This absorption occurs in the coating and the substrate of the neutron guides. Traditional m=1 coatings have been made of Ni and if reflectivity over...... the critical angle of Ni is needed one has used Ni58 or Ni/Ti multilayer coatings. Ni has one of the highest neutron scattering density but it also has a fairly high absorption cross section for cold and thermal neutrons and when a neutron is absorbed it emits a lot of gamma rays, some with energies above 9 Me......V. Materials like diamond and Be have higher neutron scattering density than Ni, have smaller absorption cross section and when a neutron is absorbed they emit much less gamma ray and at lower energies. We present results, both theoretically and experimentally, comparing Ni with Be and preliminary results...

  1. 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.

  2. 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.

  3. 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.

  4. Accumulation of the $^{178m2}Hf$ Isomeric Nuclei Through Spallation with Intermediate-Energy Protons of Tantalum and Rhenium Targets

    CERN Document Server

    Karamian, S A; Adam, J; Filossofov, D V; Henzlova, D; Henzl, V; Kalinnikov, V G; Lebedev, N A; Novgorodov, A F; Collins, C B; Popescu, I I; Ur, C A

    2001-01-01

    The productivity of the spallation reactions at proton energies of 100-660 MeV for accumulation of the radioactive isotopes and isomers has been studied experimentally. Spectra of Ta and Re targets activated at Dubna synchrocyclotron were measured using the methods of radiochemistry and gamma-spectroscopy. Many radioactive products of the spallation and fission reactions are identified, and their yields are compared with the LAHET code simulations. Cross sections, \\sigma_m and isomer-to-ground state ratios, \\sigma_m/\\sigma_g are deduced for nuclear isomers, in particular, for high-spin isomers, as ^{179m2}Hf, ^{179m2}Hf and ^{177m2}Lu. Spin distributions for the spallation-residue nuclei are estimated to understand the \\sigma_m/\\sigma_g ratios. Possibilities to optimize the methods for the long-lived isomers production are discussed, and it would be a necessary step on the way to accumulate such exotic radionuclides in milligram amount under reasonable cost and radiation safety conditions.

  5. 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...

  6. Excitation functions of the nat-Ta(p,x)178m2Hf and nat-W(p,x)178m2Hf reactions at energies up to 2600 MeV

    CERN Document Server

    Titarenko, Yu E; Pavlov, K V; Titarenko, A Yu; Zhivun, V M; Chauzova, M V; Ignatyuk, A V; Mashnik, S G; Leray, S; Boudard, A; David, J -C; Mancusi, D; Cugnon, J; Yariv, Y; Nishihara, K; Matsuda, N; Kumawat, H; Stankovsky, A Yu

    2015-01-01

    Due to potential level of energy intensity 178m2Hf is an extremely interesting isomer. One possible way to produce this isomer is irradiation of nat-Ta or nat-W samples with high energy protons. Irradiation of nat-Ta and nat-W samples performed for other purposes provides an opportunity to study the corresponding reactions. This paper pre-sents the 178m2Hf independent production cross sections for both targets measured by the gamma-ray spectrometry method. The reaction excitation functions have been obtained for the proton energies from 40 up to 2600 MeV. The experimental results were compared with calculations by various versions of the intranuclear cascade model in the well-known codes: ISABEL, Bertini, INCL4.5+ABLA07, PHITS, CASCADE07 and CEM03.02. The isomer ratio for the nat-Ta(p,x)178m2Hf reaction is evaluated on the basis of the available data.

  7. Isolation and Metabolic Characterization of a Pseudomonas stutzeri Mutant Able To Grow on the Three Isomers of Xylene

    Science.gov (United States)

    Di, Le; Accarino, M.; Bolognese, F.; Galli, E.; Barbieri, P.

    1997-01-01

    From an o-xylene-degrading Pseudomonas stutzeri strain (OX1), we previously isolated mutant M1, which had acquired the ability to grow on m-xylene and p-xylene but lost the ability to utilize the ortho isomer. From M1 cultures we have now isolated a revertant strain (R1) which grows on o-xylene and retains the ability to grow with the meta and para isomers regardless of the selective pressure applied. In P. stutzeri R1, o-xylene is degraded through two successive monooxygenations of the aromatic ring, while m-xylene and p-xylene catabolism proceeds through the progressive oxidation of a methyl substituent, although unquantifiable amounts of these two substrates are transformed into the corresponding dimethylphenols, which are not utilized for further growth. The two catabolic pathways are inducible by all three xylene isomers. PMID:16535677

  8. High-harmonic spectroscopy of molecular isomers

    Energy Technology Data Exchange (ETDEWEB)

    Wong, M. C. H.; Brichta, J.-P.; Bhardwaj, V. R. [Department of Physics, University of Ottawa, 150 Louis-Pasteur, Ottawa, Ontario, K1N 6N5 (Canada); Spanner, M.; Patchkovskii, S. [National Research Council of Canada, 100 Sussex Drive, Ottawa, Ontario, K1A 0R6 (Canada)

    2011-11-15

    We demonstrate that high-order-harmonic generation (HHG) spectroscopy can be used to probe stereoisomers of randomly oriented 1,2-dichloroethylene (C{sub 2}H{sub 2}Cl{sub 2}) and 2-butene (C{sub 4}H{sub 8}). The high-harmonic spectra of these isomers are distinguishable over a range of laser intensities and wavelengths. Time-dependent numerical calculations of angle-dependent ionization yields for 1,2-dichloroethylene suggest that the harmonic spectra of molecular isomers reflect differences in their strong-field ionization. The subcycle ionization yields for the cis isomer are an order of magnitude higher than those for the trans isomer. The sensitivity in discrimination of the harmonic spectra of cis- and trans- isomers is greater than 8 and 5 for 1,2-dichloroethylene and 2-butene, respectively. We show that HHG spectroscopy cannot differentiate the harmonic spectra of the two enantiomers of the chiral molecule propylene oxide (C{sub 3}H{sub 6}O).

  9. Cancer risks posed by aflatoxin M1.

    Science.gov (United States)

    Hsieh, D P; Cullen, J M; Hsieh, L S; Shao, Y; Ruebner, B H

    1985-01-01

    The suspect milk-borne carcinogen, aflatoxin M1 (AFM), was produced and isolated from the rice culture of the fungus Aspergillus flavus NRRL3251 for confirmation and determination of the potency of its carcinogenicity in the male adult Fischer rat. The carcinogen was mixed into an agar-based, semisynthetic diet at 0, 0.5, 5, and 50 ppb (microgram/kg) and was fed to groups of animals continuously for 19-21 months. Aflatoxin B1 (AFB), of which AFM is a metabolite, at 50 ppb was used as a positive control. Hepatocarcinogenicity of AFM was detected at 50 ppb, but not at 5 or 0.5 ppb, with a potency of 2-10% that of AFB. A low incidence of intestinal adenocarcinomas was found in the AFM 50 ppb group, but not in any other groups. At 0.5 ppb, the action level enforced by the U.S.A. Food and Drug Administration, AFM induced no liver lesions in the rats but stimulated the animals' growth. On the average, the rats in the 0.5 ppb group weighed 11% (p less than 0.001) more than those in the control group. This increased growth was associated with increased feed intake. Based on the biological activity of AFM at the relevant low doses and the estimated level of human exposure to AFM through consumption of milk, the cancer risk posed by this contaminant for human adults is assessed to be very low. For infants, further studies are warranted because milk constitutes the major ingredient of the infant diet and because infant animals have been shown to be more sensitive to the carcinogenicity of AFB than adult animals.

  10. Cis and Trans Isomers of Cycloalkenes

    Science.gov (United States)

    Barrows, Susan E.; Eberlein, Thomas H.

    2005-09-01

    As a rule, a trans disubstituted alkene is more stable than the corresponding cis isomer. For cycloalkenes of fewer than eleven members, cis isomers are more stable than their trans counterparts. Although this exception to the normal rule is occasionally noted in beginning organic chemistry textbooks, it is often done without a careful analysis of the reasons behind it. The purpose of this article is to provide that analysis. In order for a cycloalkene to accommodate a trans double bond one or more of the following nonideal geometries must occur: a twisted π bond; pyramidal sp 2 -carbon atoms; nonideal sp 3 bond angles; or longer than normal C C single and double bonds. This article provides a list of experimentally determined relative energies of the cis and trans isomers within the series cycloheptene cycloundecene, along with computationally derived energies at several levels of theory. It also examines the geometric distortions through which cycloalkenes relieve the strain introduced by a trans double bond.

  11. Analysis of Heme oxygenase isomers in rat

    Institute of Scientific and Technical Information of China (English)

    Yun-ZhuLi; Wen-JunCui; Xue-HongZhang; Qing-XiangShen; JianWang; She

    2002-01-01

    AIM:To purify and identify heme oxygenase(HO) isomers which exist in rat liver,spleen and brain treated with hematin and phenylhydrazine and in untrated rat liver and to investigate the characteristics of HO isomers,to isolate and confirm the rat HO-1 cDNA that actually encodes HO-1 by expressing cDNA in monkey Kidney cells(COS-1 cells),to prepare the rat heme oxygenase-1(HO-1)mutant and to detect inhibition of HO-1 mutated enzyme.

  12. Two Novel Isomers of HPS3 System

    Institute of Scientific and Technical Information of China (English)

    Hai Tao YU; Ming Xia LI; Yu Juan CHI; Fu Long YUANG; Hong Gang FU; Jia Zhong SUN

    2003-01-01

    Two new isomers of HPS3 system, HP(S)S2 and HSSPS, are predicted by means of B3LYP method with 6-311++G(3df,3pd) basis set. The two isomers can isomerize into thermodynamically the most stable species HSPS2, which have been experimentally identified, with relatively higher reaction barriers. In view of their higher thermodynamical and kinetic stability and the experimental observation for HP(O)O2 and HOOPO in previous study, we can reasonably believe that the two species can be spectrosymmetrically characterized in future experiments.

  13. 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.

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

  15. 'Melatonin isomer' in wine is not an isomer of the melatonin but tryptophan-ethylester.

    Science.gov (United States)

    Gardana, Claudio; Iriti, Marcello; Stuknytė, Milda; De Noni, Ivano; Simonetti, Paolo

    2014-11-01

    Melatonin is a neurohormone, chronobiotic, and antioxidant compound found in wine and deriving directly from grapes and/or synthesized by yeast during alcoholic fermentation. In addition, a melatonin isomer has been detected in different foods, wine among them. The special interest for melatonin isomer related to the fact that it was found in greater quantities than melatonin and probably shares some of its biological properties. Despite this, its chemical structure has not yet been defined; although some researchers hypothesize, it could be melatonin with the ethylacetamide group shifted into position N1. Thus, the aim of our study was to identify the structures of the melatonin isomer. For this purpose, melatonin and melatonin isomer in Syrah wine were separated chromatographically by a sub-2 μm particle column and detected by tandem mass spectrometry. The sample was then purified and concentrated by solid-phase extraction, hydrolyzed with alkali or esterase, and substrates and products quantified by UPLC-MS/MS. Moreover, melatonin, melatonin isomer, and their product ions were evaluated by high-resolution mass spectrometry. The amount of melatonin isomer and melatonin in the wine was 84 ± 4 and 3 ± 0 ng/mL, respectively. In the solutions, containing diluted alkali or esterase, melatonin isomer was hydrolyzed in about 8 min. Correspondingly, tryptophan was detected, and its amount increased and reached the maximum concentration in about 8 min. Melatonin concentration was not affected by diluted alkali or esterase. The fragmentation pattern of melatonin isomer was different from that of melatonin but comparable to that of tryptophan-ethylester. Finally, the so-called melatonin isomer identity was verified by cochromatography with authentic standard of tryptophan-ethylester. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. 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

  17. A new isomer in {sup 125}La

    Energy Technology Data Exchange (ETDEWEB)

    Canchel, G. [Lyon-1 Univ., 69 - Villeurbanne (France). Inst. de Physique Nucleaire]|[Department of Physics, Accelerator Laboratory, University of Jyvaeskylae, P.O. Box 35, FIN-40351 Jyvaeskylae (Finland); Beraud, R.; Chabanat, E.; Emsallem, A.; Redon, N. [Lyon-1 Univ., 69 - Villeurbanne (France). Inst. de Physique Nucleaire; Dendooven, P.; Huikari, J.; Jokinen, A.; Kolhinen, V.; Lhersonneau, G.; Oinonen, M.; Nieminen, A.; Penttilae, H.; Peraejaervi, K.; Wang, J.C.; Aeystoe, J. [Department of Physics, Accelerator Laboratory, University of Jyvaeskylae, P.O. Box 35, FIN-40351 Jyvaeskylae (Finland)

    1999-05-01

    Levels in {sup 125}La have been studied via {beta}{sup +}/EC decay of on-line mass-separated {sup 125}Ce using the HIGISOL technique. A new (390{+-}40) ms isomer is definitely attributed to {sup 125}La by conversion electron measurements of the 107 keV E3 isomeric transition. (orig.) With 2 figs., 1 tab., 11 refs.

  18. Organometallic chemistry: Heavyweight isomer brings stability

    Science.gov (United States)

    Scheschkewitz, David

    2016-11-01

    Due to its high reactivity, vinylidene -- the sole 'electron-precise' isomer of acetylene -- is only known to exist in the gas phase. Now, a stable base-free digermanium version of a vinylidene has been isolated by the clever use of suitable substituents.

  19. 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.

  20. 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.

  1. Intravirion cohesion of matrix protein M1 with ribonucleocapsid is a prerequisite of influenza virus infectivity.

    Science.gov (United States)

    Zhirnov, O P; Manykin, A A; Rossman, J S; Klenk, H D

    2016-05-01

    Influenza virus has two major structural modules, an external lipid envelope and an internal ribonucleocapsid containing the genomic RNA in the form of the ribonucleoprotein (RNP) complex, both of which are interlinked by the matrix protein M1. Here we studied M1-RNP cohesion within virus exposed to acidic pH in vitro. The effect of acidification was dependent on the cleavage of the surface glycoprotein HA. Acidic pH caused a loss of intravirion RNP-M1 cohesion and activated RNP polymerase activity in virus with cleaved HA (HA1/2) but not in the uncleaved (HA0) virus. The in vitro acidified HA1/2 virus rapidly lost infectivity whereas the HA0 one retained infectivity, following activation by trypsin, suggesting that premature activation and release of the RNP is detrimental to viral infectivity. Rimantadine, an inhibitor of the M2 ion channel, was found to protect the HA1/2 virus interior against acidic disintegration, confirming that M2-dependent proton translocation is essential for the intravirion RNP release and suggesting that the M2 ion channel is only active in virions with cleaved HA. Acidic treatment of both HA0 and HA1/2 influenza viruses induces formation of spikeless bleb-like protrusion of ~ 25 nm in diameter on the surface of the virion, though only the HA1/2 virus was permeable to protons and permitted RNP release. It is likely that this bleb corresponds to the M2-enriched and M1-depleted focus arising from pinching off of the virus during the completion of budding. Cooperatively, the data suggest that the influenza virus has an asymmetric structure where the M1-mediated organization of the RNP inside the virion is a prerequisite for infectious entry into target cell. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Reverse phase liquid chromatographic determination and confirmation of aflatoxin M1 in cheese.

    Science.gov (United States)

    Hisada, K; Terada, H; Yamamoto, K; Tsubouchi, H; Sakabe, Y

    1984-01-01

    A systematic method is proposed for determination and confirmation of aflatoxin M1 in cheese by liquid chromatography (LC). A sample of cheese is extracted with chloroform, cleaned up on 2 silica gel columns followed by a Sep-Pak C18 cartridge, and chromatographed on a 5 microns octadecyl silica column with fluorometric detection. The sample extract or standard is treated with n-hexane-trifluoroacetic acid (TFA) (4 + 1) for 30 min at 40 degrees C. Analysis by LC with TFA-treatment of the extract provides quantitative data. Multiple assays of 5 samples of Gouda cheese spiked with aflatoxin M1 at levels of 0.5, 0.1, and 0.05 ng/g showed average recoveries of 93.2, 91.6, and 92.4%, with coefficients of variation of 2.63, 3.97, and 4.52%, respectively. Assay of 5 naturally contaminated cheeses resulted in 0.051-0.448 ng/g of aflatoxin M1. Limit of quantitation is about 0.01 ng/g. The identity of aflatoxin M1 is confirmed by treating aflatoxin M1 or the M2a derivative with TFA-methanol (or ethanol) (3 + 1). The TFA-methanol reaction products of M2a could be detected quantitatively.

  3. 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.

  4. 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.

  5. On the nonexistence of $[\\binom{2m}{m-1}, 2m, \\binom{2m-1}{m-1}]$, $m$ odd, complex orthogonal design

    CERN Document Server

    Li, Yuan

    2011-01-01

    Complex orthogonal designs (CODs) are used to construct space-time block codes. COD $\\mathcal{O}_z$ with parameter $[p, n, k]$ is a $p\\times n$ matrix, where nonzero entries are filled by $\\pm z_i$ or $\\pm z^*_i$, $i = 1, 2,..., k$, such that $\\mathcal{O}^H_z \\mathcal{O}_z = (|z_1|^2+|z_2|^2+...+|z_k|^2)I_{n \\times n}$. Adams et al. in "The final case of the decoding delay problem for maximum rate complex orthogonal designs," IEEE Trans. Inf. Theory, vol. 56, no. 1, pp. 103-122, Jan. 2010, first proved the nonexistence of $[\\binom{2m}{m-1}, 2m, \\binom{2m-1}{m-1}]$, $m$ odd, COD. Combining with the previous result that decoding delay should be an integer multiple of $\\binom{2m}{m-1}$, they solved the final case $n \\equiv 2 \\pmod 4$ of the decoding delay problem for maximum rate complex orthogonal designs. In this paper, we give another proof of the nonexistence of COD with parameter $[\\binom{2m}{m-1}, 2m, \\binom{2m-1}{m-1}]$, $m$ odd. Our new proof is based on the uniqueness of $[\\binom{2m}{m-1}, 2m-1, \\binom{...

  6. 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.

  7. 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.

  8. Modelling Study of Interstellar Ethanimine Isomers

    Science.gov (United States)

    Quan, Donghui; Herbst, Eric; Corby, Joanna F.; Durr, Allison; Hassel, George

    2016-06-01

    Ethanimine (CH3CHNH) , including both the E- and Z- isomers, were detected towards the star-forming region Sgr B2(N) using the GBT PRIMOS data (Loomis et al 2013), and were recently imaged by the ACTA (Corby et al. 2015). These aldimines can serve as precursors of biological molecules such as amino acids thus are considered prebiotic molecules in interstellar medium. In this study, we present chemical simulations of ethanimine with various physical conditions. From models for Sgr B2(N) and environs, calculated ethanimine abundances show reasonable agreement with observed values, while the translucent cloud models yield much lower abundances. These results agree with locations suggested by observations that ethanimine isomers were detected in the foreground of the shells of the hot core.

  9. Radiationless transitions to atomic M 1,2,3 shells - Results of relativistic theory

    Science.gov (United States)

    Chen, M. H.; Crasemann, B.; Mark, H.

    1983-01-01

    Radiationless transitions filling vacancies in atomic M1, M2, and M3 subshells have been calculated relativistically with Dirac-Hartree-Slater wave functions for ten elements with atomic numbers 67-95. Results are compared with those of nonrelativistic calculations and experiment. Relativistic effects are found to be significant. Limitations of an independent-particle model for the calculation of Coster-Kronig rates are noted.

  10. Phase transition equilibrium of terthiophene isomers

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Jose C.S.; Lima, Carlos F.R.A.C.; Rocha, Marisa A.A. [Centro de Investigacao em Quimica, Departamento de Quimica e Bioquimica, Faculdade de Ciencias da Universidade do Porto, Rua do Campo Alegre, 687, P-4169-007 Porto (Portugal); Gomes, Ligia R. [CIAGEB, Faculdade de Ciencias de Saude Escola Superior de Saude da UFP, Universidade Fernando Pessoa, Rua Carlos da Maia, 296, P-4200-150 Porto (Portugal); REQUIMTE, Departamento de Quimica e Bioquimica, Faculdade de Ciencias, Universidade do Porto, Rua do Campo Alegre, 687, P-4169-007 Porto (Portugal); Santos, Luis M.N.B.F., E-mail: lbsantos@fc.up.p [Centro de Investigacao em Quimica, Departamento de Quimica e Bioquimica, Faculdade de Ciencias da Universidade do Porto, Rua do Campo Alegre, 687, P-4169-007 Porto (Portugal)

    2011-02-15

    The thermodynamic study of the phase transition (fusion and sublimation) of 2,2':5',2''-terthiophene and 3,2':5',3''-terthiophene is presented. The obtained data is used to evaluate the (solid + liquid) and (solid + gas) phase equilibrium, and draw the phase diagrams of the pure compounds near the triple point coordinates. For each compound the vapour pressures at different temperatures were measured by a combined Knudsen effusion method with a vacuum quartz crystal microbalance. Based on the previous results, the standard molar enthalpies, entropies and Gibbs energies of sublimation were derived at T = 298.15 K. For the two terthiophenes and for 3,3'-bithiophene, the temperature, and the molar enthalpies of fusion were measured in a power compensated differential scanning calorimetry. The relationship between structure and energetics is discussed based on the experimental results, ab initio calculations and previous literature data for 2,2'-bithiophene and 3,3'-bithiophene. The 3,2':5',3''-terthiophene shows a higher solid phase stability than the 2,2':5',2''-terthiophene isomer arising from the higher cohesive energy due to positioning of the sulphur atom in the thiophene ring. The higher phase stability of 3,3'-bithiophene relative to 2,2'-bithiophene isomer is also related to its higher absolute entropy in the solid phase associated with the ring positional degeneracy observed in the crystal structure of this isomer. A significant differentiation in the crystal phase stability between isomers was found.

  11. A thirty second isomer in Hf-171

    NARCIS (Netherlands)

    Campbell, P; Billowes, J; Cochrane, ECA; Cooke, JL; Cooper, TG; Dendooven, P; Evans, DE; Grant, IS; Griffith, JAR; Honkanen, A; Huhta, M; Oinonen, M; Pearson, MR; Penttila, H; Persson, B.L.; Richardson, DS; Tungate, G; Wheeler, PD; Zybert, L; Aysto, J

    1997-01-01

    An isomer has been detected in Hf-171 with a half-life of T-1/2 = 29.5(9) s. The state was populated in the Yb-170(alpha,3n)Hf-171m reaction at a beam energy of E-alpha = 50 MeV in an on-line ion guide isotope separator. The isomeric Hf-17lm(+) beam was extracted from the ion guide, mass-analysed an

  12. Large-scale shell model study of the newly found isomer in 136La

    Science.gov (United States)

    Teruya, E.; Yoshinaga, N.; Higashiyama, K.; Nishibata, H.; Odahara, A.; Shimoda, T.

    2016-07-01

    The doubly-odd nucleus 136La is theoretically studied in terms of a large-scale shell model. The energy spectrum and transition rates are calculated and compared with the most updated experimental data. The isomerism is investigated for the first 14+ state, which was found to be an isomer in the previous study [Phys. Rev. C 91, 054305 (2015), 10.1103/PhysRevC.91.054305]. It is found that the 14+ state becomes an isomer due to a band crossing of two bands with completely different configurations. The yrast band with the (ν h11/2 -1⊗π h11 /2 ) configuration is investigated, revealing a staggering nature in M 1 transition rates.

  13. 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

  14. Conjugated linoleic acid isomers: differences in metabolism and biological effects.

    Science.gov (United States)

    Churruca, Itziar; Fernández-Quintela, Alfredo; Portillo, Maria Puy

    2009-01-01

    The term conjugated linoleic acid (CLA) refers to a mixture of linoleic acid positional and geometric isomers, characterized by having conjugated double bonds, not separated by a methylene group as in linoleic acid. CLA isomers appear as a minor component of the lipid fraction, found mainly in meat and dairy products from cows and sheep. The most abundant isomer is cis-9,trans-11, which represents up to 80% of total CLA in food. These isomers are metabolized in the body through different metabolic pathways, but important differences, that can have physiological consequences, are observed between the two main isomers. The trans-10,cis-12 isomer is more efficiently oxidized than the cis-9,trans-11 isomer, due to the position of its double bounds. Interest in CLA arose in its anticarcinogenic action but there is an increasing amount of specific scientific literature concerning the biological effects and properties of CLA. Numerous biological effects of CLA are due to the separate action of the most studied isomers, cis-9,trans-11 and trans-10,cis-12. It is also likely that some effects are induced and/or enhanced by these isomers acting synergistically. Although the cis-9,trans-11 isomer is mainly responsible for the anticarcinogenic effect, the trans-10,cis-12 isomer reduces body fat and it is referred as the most effective isomer affecting blood lipids. As far as insulin function is concerned, both isomers seem to be responsible for insulin resistance in humans. Finally, with regard to the immune system it is not clear whether individual isomers of CLA could act similarly or differently.

  15. 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M1M2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].

  16. Polarisation of Tumor-Associated Macrophages toward M2 Phenotype Correlates with Poor Response to Chemoradiation and Reduced Survival in Patients with Locally Advanced Cervical Cancer.

    Directory of Open Access Journals (Sweden)

    Marco Petrillo

    Full Text Available We investigate the prognostic role of pre-treatment ratio between Type 1 (M1 and Type 2 (M2 tumor-associated macrophages (TAMs in locally advanced cervical cancer (LACC patients treated with chemoradiation (CT/RT.84 consecutive LACC patients treated with cisplatin-based CT/RT for a total dose of 50.0 Gy, followed by radical surgery were analysed. Double-staining immunohistochemistry of CD163/p-STAT, CD68/pSTAT1, CD163/c-MAF, and CD68/c-MAF was performed on tumor samples taken at the time of diagnosis. TAMs with CD163+pSTAT1+, or CD68+pSTAT1+ were defined M1; CD163+c-MAF+ or CD68+c-MAF+ defined the M2 phenotype. The number of M1 and M2 cells was counted at low magnification by evaluating for each case the same tumour area. The ratio between M1 and M2 (M1/M2 was finally calculated.At diagnosis, we observed a direct correlation between the number of circulating monocytes and of TAMs (p-value = 0.001. Patients with high M1/M2 experienced more frequently complete pathologic response (no residual tumor to CT/RT, compared to cases with low M1/M2 (55.0% Vs 29.5%; p-value = 0.029. At multivariate analysis M1/M2 (OR = 2.067; p-value = 0.037 emerged as independent predictor of pathologic response to CT/RT. Women with high M1/M2 showed a longer 5-yrs Disease-free (67.2% Vs. 44.3%; p-value = 0.019, and 5-yrs Overall (69.3% Vs. 46.9%; p-value = 0.037 survival, compared to cases with low M1/M2. The presence of a high M1/M2 ratio was independently associated with an unfavourable survival outcome in multivariate analysis.Polarisation of TAMs toward a M2 phenotype, as reflected by a lower M1/M2 ratio, is an independent predictor of poor response to CT/RT, and shorter survival in LACC.

  17. Bioaccumulation of perfluoroalkyl acids including the isomers of perfluorooctane sulfonate in carp (Cyprinus carpio) in a sediment/water microcosm.

    Science.gov (United States)

    Fang, Shuhong; Zhang, Yifeng; Zhao, Shuyan; Qiang, Liwen; Chen, Meng; Zhu, Lingyan

    2016-12-01

    Carp (Cyprinus carpio) were exposed to perfluoroalkyl acids (PFAAs) including perfluorooctane sulfonate (PFOS) isomers in an artificially contaminated sediment/water microcosm. The uptake constant of PFAAs increased with increasing carbon chain length, whereas the elimination coefficient displayed the opposite trend, suggesting that carbon chain length plays an important role in the bioaccumulation of PFAAs. When the contribution of suspended particulate matter was taken into account, the bioaccumulation factors (BAFs) became lower (3.61-600 L/kg) compared with BAFs derived from only considering the absorption from free PFAAs in water (3.85-97000 L/kg). The results indicate that suspended particulate matter in water constitutes an important source of exposure for aquatic organisms to long-chain PFAAs. Linear (n-)PFOS was preferentially accumulated compared with branched isomers in carp. Among the branched isomers, 1m-PFOS displayed the greatest bioaccumulation, whereas m2 -PFOS had the lowest. Linear PFOS displayed greater partitioning ability from blood to other tissues over branched PFOS (br-PFOS) isomers, leading to a relatively lower n-PFOS proportion in blood. In summary, suspended particulate matter made a contribution to the accumulation of long-chain PFAAs in aquatic organisms, and n-PFOS was preferentially accumulated compared with br-PFOS isomers. Environ Toxicol Chem 2016;35:3005-3013. © 2016 SETAC.

  18. Maternal low protein diet leads to placental angiogenic compensation via dysregulated M1/M2 macrophages and TNFa expression in Sprague-Dawley rats

    Science.gov (United States)

    A maternal low-protein (LP) diet results in low birth weight, increased offspring rapid adipose tissue catch-up growth, adult obesity, and insulin resistance in Sprague-Dawley rats. The placenta plays key roles in nutrient transport and fetal growth. Placental function is dependent on regulation of ...

  19. Cell plasticity in wound healing : paracrine factors of M1/M2 polarized macrophages influence the phenotypical state of dermal fibroblasts

    NARCIS (Netherlands)

    Ploeger, Diana T. A.; Hosper, Nynke A.; Schipper, Martin; Koerts, Jasper A.; de Rond, Saskia; Bank, Ruud A.

    2013-01-01

    Background: Macrophages and fibroblasts are two major players in tissue repair and fibrosis. Despite the relevance of macrophages and fibroblasts in tissue homeostasis, remarkably little is known whether macrophages are able to influence the properties of fibroblasts. Here we investigated the role o

  20. Discrimination of putative M1 and M2 muscarinic receptor subtypes in rat brain by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ)

    Energy Technology Data Exchange (ETDEWEB)

    Norman, A.B.; Creese, I.

    1986-03-01

    The EC/sub 50/ of EEDQ for the inhibition of (/sup 3/H)(-)QNB binding in vitro was approximately 3 fold lower for homogenates of hippocampus than brainstem (containing predominantly putative M/sub 1/ and M/sub 2/ muscarinic receptor subtypes respectively). Furthermore, the time-dependent loss of (/sup 3/H)(-)QNB binding produced by 100 ..mu..M EEDQ was faster in homogenates of hippocampus than brainstem. Administration of EEDQ (20 mg/kg i.p.) irreversibly reduced the Bmax of (/sup 3/H)(-)QNB binding by 56% and 34% in hippocampus and brainstem respectively. Pirenzepine competition for the remaining (/sup 3/H)(-)QNB binding sites following in vitro and in vivo treatment with EEDQ revealed a significant increase in the proportion of (/sup 3/H)(-)QNB binding sites having low affinity for pirenzepine (M/sub 2/ receptors), indicating that the high affinity pirenzepine binding sites (M/sub 1/ receptors) were selectively and irreversibly lost. Thus, EEDQ discriminates the same putative M/sub 1/ and M/sub 2/ muscarinic receptor subtypes that are discriminated by pirenzepine. The reduction of (/sup 3/H)(-)QNB binding could be prevented both in vitro and in vivo by atropine or scopolamine. These data may indicate differences in the accessibility of these putative receptor subtypes to EEDQ or, alternatively, differences in the availability of carboxyl groups able to interact with EEDQ at the ligand recognition site of M/sub 1/ and M/sub 2/ muscarinic receptors.

  1. Cartilage inflammation and degeneration is enhanced by pro-inflammatory (M1) macrophages in vitro, but not inhibited directly by anti-inflammatory (M2) macrophages

    NARCIS (Netherlands)

    L. Utomo (Lizette); Y.M. Bastiaansen-Jenniskens (Yvonne); J.A.N. Verhaar (Jan); G.J.V.M. van Osch (Gerjo)

    2016-01-01

    textabstractObjective Macrophages play a crucial role in the progression of osteoarthritis (OA). Their phenotype may range from pro-inflammatory to anti-inflammatory. The aim of this study was to evaluate the direct effects of macrophage subtypes on cartilage by culturing macrophage conditioned

  2. Cell plasticity in wound healing : paracrine factors of M1/M2 polarized macrophages influence the phenotypical state of dermal fibroblasts

    NARCIS (Netherlands)

    Ploeger, Diana T. A.; Hosper, Nynke A.; Schipper, Martin; Koerts, Jasper A.; de Rond, Saskia; Bank, Ruud A.

    2013-01-01

    Background: Macrophages and fibroblasts are two major players in tissue repair and fibrosis. Despite the relevance of macrophages and fibroblasts in tissue homeostasis, remarkably little is known whether macrophages are able to influence the properties of fibroblasts. Here we investigated the role

  3. Intravirion cohesion of matrix protein M1 with ribonucleocapsid is a prerequisite of influenza virus infectivity

    Energy Technology Data Exchange (ETDEWEB)

    Zhirnov, O.P., E-mail: zhirnov@inbox.ru [D.I. Ivanovsky Institute of Virology, Moscow 123098 (Russian Federation); Manykin, A.A. [D.I. Ivanovsky Institute of Virology, Moscow 123098 (Russian Federation); Rossman, J.S. [School of Biosciences, University of Kent, Canterbury CT27NJ (United Kingdom); Klenk, H.D. [Institute of Virology, Philipps University, Marburg 35037 (Germany)

    2016-05-15

    Influenza virus has two major structural modules, an external lipid envelope and an internal ribonucleocapsid containing the genomic RNA in the form of the ribonucleoprotein (RNP) complex, both of which are interlinked by the matrix protein M1. Here we studied M1-RNP cohesion within virus exposed to acidic pH in vitro. The effect of acidification was dependent on the cleavage of the surface glycoprotein HA. Acidic pH caused a loss of intravirion RNP-M1 cohesion and activated RNP polymerase activity in virus with cleaved HA (HA1/2) but not in the uncleaved (HA0) virus. The in vitro acidified HA1/2 virus rapidly lost infectivity whereas the HA0 one retained infectivity, following activation by trypsin, suggesting that premature activation and release of the RNP is detrimental to viral infectivity. Rimantadine, an inhibitor of the M2 ion channel, was found to protect the HA1/2 virus interior against acidic disintegration, confirming that M2-dependent proton translocation is essential for the intravirion RNP release and suggesting that the M2 ion channel is only active in virions with cleaved HA. Acidic treatment of both HA0 and HA1/2 influenza viruses induces formation of spikeless bleb-like protrusion of ~25 nm in diameter on the surface of the virion, though only the HA1/2 virus was permeable to protons and permitted RNP release. It is likely that this bleb corresponds to the M2-enriched and M1-depleted focus arising from pinching off of the virus during the completion of budding. Cooperatively, the data suggest that the influenza virus has an asymmetric structure where the M1-mediated organization of the RNP inside the virion is a prerequisite for infectious entry into target cell. - Highlights: • The influenza A virus has a novel asymmetric internal structure. • The structure is largely maintained by M1-RNP cohesion within the virion. • This asymmetry plays an important role during viral entry, facilitating virus uncoating and the initiation of a productive

  4. The conformation of acetylated virginiamycin M1 and virginiamycin M1 in explicit solvents.

    Science.gov (United States)

    Ng, Chai Ann; Zhao, Wen; Dang, Jason; Bergdahl, Mikael; Separovic, Frances; Brownlee, Robert T C; Metzger, Robert P

    2007-05-01

    The three-dimensional structure of acetylated virginiamycin M(1) (acetylated VM1) in chloroform and in a water/acetonitrile mixture (83:17 v/v) have been established through 2D high resolution NMR experiments and molecular dynamics modeling and the results compared with the conformation of the antibiotic VM1 in the same and other solvents. The results indicated that acetylation of the C-14 OH group of VM1 caused it to rotate about 90 degrees from the position it assumed in non-acetylated VM1. The conformation of both VM1 and acetylated VM1 appear to flatten in moving from a nonpolar to polar solvent. However, the acetylated form has a more hydrophobic nature. The acetylated VM1 in chloroform and in water/acetonitrile solution had a similar configuration to that of VM1 bound to 50S ribosomes and to the Vat(D) active sites as previously determined by X-ray crystallography. Docking studies of VM1 to the 50S ribosomal binding site and the Vat(D) gave conformations very similar to those derived from X-ray crystallographic studies. The docking studies with acetylated VM1 suggested the possibility of a hydrogen bond from the acetyl carbonyl group oxygen of acetylated VM1 to the 2' hydroxyl group of ribose of adenosine 2538 at the ribosomal VM1 binding site. No hydrogen bonds between acetylated VM1 and the Vat(D) active sites were found; the loss of this binding interaction partly accounts for the release of the product from the active site.

  5. 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 ...

  6. 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 ...

  7. 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 ...

  8. Qualification Lab Testing on M1 Abrams Engine Oil Filters

    Science.gov (United States)

    2016-11-01

    UNCLASSIFIED QUALIFICATION LAB TESTING ON M1 ABRAMS ENGINE OIL FILTERS FINAL REPORT TFLRF No. 483 by Kristi K. Rutta U.S...the originator. UNCLASSIFIED QUALIFICATION LAB TESTING ON M1 ABRAMS ENGINE OIL FILTERS FINAL REPORT TFLRF No. 483 by Kristi K...TITLE AND SUBTITLE Qualification Lab Testing on M1 Abrams Engine Oil Filter 5a. CONTRACT NUMBER W56HZV-15-C-0030 5b. GRANT NUMBER 5c. PROGRAM

  9. Develop Efficient Leak Proof M1 Abrams Plenum Seal

    Science.gov (United States)

    2014-05-07

    UNCLASSIFIED UNCLASSIFIED ER-GLSV11389-001.docx Develop Efficient Leak Proof M1 Abrams Plenum Seal SBIR Phase I: Topic A13-061...Leak Proof M1 Abrams Plenum Seal Christian Muehfeld Steve Pennala Great Lakes Sound & Vibration, Inc. 47140 North Main Street Houghton, MI 49931 ER...061. The purpose of this report is to show the feasibility of developing an efficient, leak proof plenum seal for the M1 Abrams . It also shows the

  10. Conformation analysis of isomers of imidoyl halides

    Energy Technology Data Exchange (ETDEWEB)

    Gershikov, A.G.; Vul' fov, A.L.; Savelova, V.A.; Drizhd, L.P.

    1985-09-01

    The possible mechanisms of the intramolecular syn-anti isomerization of imidoyl halides have been analyzed with the aid of nonempirical quantum-chemical calculations. In the liquid phase isomerization can occur after a preliminary step of ionization with the formation of nitrilium cations. The conformational features have been studied by the methods of molecular mechanics, the differences between the energies of the syn and anti isomers of a number of imidoyl halides and closely related azomethines have been calculated, and the relative equilibrium concentrations of the isomeric forms at 298/sup 0/K have been evaluated.

  11. Involvement of an Arginine Triplet in M1 Matrix Protein Interaction with Membranes and in M1 Recruitment into Virus-Like Particles of the Influenza A(H1N1)pdm09 Virus

    Science.gov (United States)

    Moncorgé, Olivier; Panthu, Baptiste; Prchal, Jan; Décimo, Didier; Ohlmann, Théophile; Lina, Bruno; Favard, Cyril; Decroly, Etienne; Ottmann, Michèle; Roingeard, Philippe; Muriaux, Delphine

    2016-01-01

    The influenza A(H1N1)pdm09 virus caused the first influenza pandemic of the 21st century. In this study, we wanted to decipher the role of conserved basic residues of the viral M1 matrix protein in virus assembly and release. M1 plays many roles in the influenza virus replication cycle. Specifically, it participates in viral particle assembly, can associate with the viral ribonucleoprotein complexes and can bind to the cell plasma membrane and/or the cytoplasmic tail of viral transmembrane proteins. M1 contains an N-terminal domain of 164 amino acids with two basic domains: the nuclear localization signal on helix 6 and an arginine triplet (R76/77/78) on helix 5. To investigate the role of these two M1 basic domains in influenza A(H1N1)pdm09 virus molecular assembly, we analyzed M1 attachment to membranes, virus-like particle (VLP) production and virus infectivity. In vitro, M1 binding to large unilamellar vesicles (LUVs), which contain negatively charged lipids, decreased significantly when the M1 R76/77/78 motif was mutated. In cells, M1 alone was mainly observed in the nucleus (47%) and in the cytosol (42%). Conversely, when co-expressed with the viral proteins NS1/NEP and M2, M1 was relocated to the cell membranes (55%), as shown by subcellular fractionation experiments. This minimal system allowed the production of M1 containing-VLPs. However, M1 with mutations in the arginine triplet accumulated in intracellular clusters and its incorporation in VLPs was strongly diminished. M2 over-expression was essential for M1 membrane localization and VLP production, whereas the viral trans-membrane proteins HA and NA seemed dispensable. These results suggest that the M1 arginine triplet participates in M1 interaction with membranes. This R76/77/78 motif is essential for M1 incorporation in virus particles and the importance of this motif was confirmed by reverse genetic demonstrating that its mutation is lethal for the virus. These results highlight the molecular

  12. The interstellar chemistry of H2C3O isomers

    Science.gov (United States)

    Loison, Jean-Christophe; Agúndez, Marcelino; Marcelino, Núria; Wakelam, Valentine; Hickson, Kevin M.; Cernicharo, José; Gerin, Maryvonne; Roueff, Evelyne; Guélin, Michel

    2016-01-01

    We present the detection of two H2C3O isomers, propynal and cyclopropenone, toward various starless cores and molecular clouds, together with upper limits for the third isomer propadienone. We review the processes controlling the abundances of H2C3O isomers in interstellar media showing that the reactions involved are gas-phase ones. We show that the abundances of these species are controlled by kinetic rather than thermodynamic effects. PMID:27013768

  13. Nuclear isomers as ultra-high-energy-density materials

    Science.gov (United States)

    Poppe, C. H.; Weiss, M. S.; Anderson, J. D.

    1992-09-01

    A major energy advance could result if the enormous potential of nuclear energy storage could be tapped without the penalty of radioactive by-products. Recent research has uncovered a new method for nuclear energy storage with high energy density and no residual radioactivity. Nuclear isomers are metastable states of atomic nuclei which release their energy in a prompt burst of electromagnetic radiation; in many cases the product remaining after decay of isomer is stable and no activity is produced by the electromagnetic decay. Two kinds of nuclear isomers are known: spin isomers and shape isomers. The former lacks a release mechanism. Theory has predicted the existence of shape isomers in the mass range around mercury and gold where decay by fission is prohibited. Experiments on the existence of fissionless shape isomers have resulted in evidence for 27 different shape isomers in isotopes of mercury, lead, and thallium. Three potential candidates for release mechanisms have been identified to date: neutron catalysis (Hf- 178), laser-electron-nuclear coupling (Th-229), and Stark-shift-induced mixing (speculative). Ways of producing nonfissioning shape isomers are discussed.

  14. Paraoxonase 2 Induces a Phenotypic Switch in Macrophage Polarization Favoring an M2 Anti-Inflammatory State

    Science.gov (United States)

    Koren-Gluzer, Marie; Rosenblat, Mira; Hayek, Tony

    2015-01-01

    Inflammatory processes are involved in atherosclerosis development. Macrophages play a major role in the early atherogenesis, and they are present in the atherosclerotic lesion in two phenotypes: proinflammatory (M1) or anti-inflammatory (M2). Paraoxonase 2 (PON2) is expressed in macrophages, and it was shown to protect against atherosclerosis. Thus, the aim of our study was to analyze the direct effect of PON2 on macrophage inflammatory phenotypes. Ex vivo studies were performed with murine peritoneal macrophages (MPM) harvested from control C57BL/6 and PON2-deficient (PON2KO) mice. PON2KO MPM showed an enhanced proinflammatory phenotype compared to the control, both in the basal state and following M1 activation by IFNγ and lipopolysaccharide (LPS). In parallel, PON2KO MPM also showed reduced anti-inflammatory responses in the basal state and also following M2 activation by IL-4. Moreover, the PON2-null MPM demonstrated enhanced phagocytosis and reactive oxygen species (ROS) production in the basal state and following M1 activation. The direct effect of PON2 was shown by transfecting human PON2 (hPON2) into PON2KO MPM. PON2 transfection attenuated the macrophages' response to M1 activation and enhanced M2 response. These PON2 effects were associated with attenuation of macrophages' abilities to phagocyte and to generate ROS. We conclude that PON2 promotes an M1 to M2 switch in macrophage phenotypes. PMID:26779262

  15. Paraoxonase 2 Induces a Phenotypic Switch in Macrophage Polarization Favoring an M2 Anti-Inflammatory State

    Directory of Open Access Journals (Sweden)

    Marie Koren-Gluzer

    2015-01-01

    Full Text Available Inflammatory processes are involved in atherosclerosis development. Macrophages play a major role in the early atherogenesis, and they are present in the atherosclerotic lesion in two phenotypes: proinflammatory (M1 or anti-inflammatory (M2. Paraoxonase 2 (PON2 is expressed in macrophages, and it was shown to protect against atherosclerosis. Thus, the aim of our study was to analyze the direct effect of PON2 on macrophage inflammatory phenotypes. Ex vivo studies were performed with murine peritoneal macrophages (MPM harvested from control C57BL/6 and PON2-deficient (PON2KO mice. PON2KO MPM showed an enhanced proinflammatory phenotype compared to the control, both in the basal state and following M1 activation by IFNγ and lipopolysaccharide (LPS. In parallel, PON2KO MPM also showed reduced anti-inflammatory responses in the basal state and also following M2 activation by IL-4. Moreover, the PON2-null MPM demonstrated enhanced phagocytosis and reactive oxygen species (ROS production in the basal state and following M1 activation. The direct effect of PON2 was shown by transfecting human PON2 (hPON2 into PON2KO MPM. PON2 transfection attenuated the macrophages’ response to M1 activation and enhanced M2 response. These PON2 effects were associated with attenuation of macrophages’ abilities to phagocyte and to generate ROS. We conclude that PON2 promotes an M1 to M2 switch in macrophage phenotypes.

  16. Structures and Stability of HNS2 Isomers

    Institute of Scientific and Technical Information of China (English)

    CHI,Yu-Juan(池玉娟); YU,Hai-Tao(于海涛); Fu,Hong-Gang(傅宏刚); HUANG,Xu-Ri(黄旭日); LI,Ze-Sheng(李泽生); SUN,Jia-Zhong(孙家钟)

    2002-01-01

    Potential energy surface of HNS2 is investigated by means of second-order Moller-Plesset perturbation theory (MP2) and QCISD(T) (single-point) methods. At final QCISD (T)/6-311++ G(3df,2p)//MP2/6-311++ G(d,p) level with zero-point vibrational energies included, cis-HNSS is found to be global minimum on the potential energy surface, followed by low-lying trans-HNSS, HN(S)S(C2v), cis-HSNS, cis-HSSN,rans-HSNS, trans-HSSN, and HN(S)S(Cs) by 13.46,66.92, 78.25, 80.38, 81.22, 81.38 and 86.40 kJ/mol, respectively. A new high-lying HS(N)S isomer with Cs symmetry is located on the potential energy surface. The kinetic stabilities of all isomers are predicted. Comparisons are made for HNS2 with its analogues, HNO2, HPS2 and HPO2. The causes that lead to the differences between HNS2 and its analogues are hypervalent capacity of phosphorus and distinct electronegativities of hydrogen, nitrogen and phosphorus.

  17. Patchouli alkohol isomers pogostemon herba predicted virtually

    Directory of Open Access Journals (Sweden)

    Sentot Joko Raharjo

    2014-02-01

    Full Text Available The aim of our research is predicting the alpha-patchouli alcohol isomer Pogostemon Herba as inhibitors cyclooxygenase (COX-1 and COX-2 isoenzymes. The data for the alpha-patchouli alcohol isomer (CD521903, CD442384, and/or CD6432585 Pogostemon Herba were explored from the pubchem database. Molecular interaction studies with COX-1 and COX-2 from mouse were done using the molecular docking tools Hex 6.12 and LeadIT2 Bisolve. The analysis of the alpha-patchouli alcohol compounds of patchouli oil showed that alpha-Patchouli alcohol (CD521903 binds to COX-1 at active sites including: LEU223B, ASP228B, LEU237B, ARG 332B, TRP 138A, GLU 139A, SER 142A, ASN 143A, and the interaction to COX-2 at active site including: GLN 289B, GLU 290B, ARG 222B, LYS 211B, THR 212B, HIS 214B, ASN 382B, HEM682B, GLN 454B, HIS 386B, TRP 387B, HIS 388B, VAL 274B, GLN 203B, VAL 291B, VAL 295B. The interaction hydrogen bond energy between alpha-patchouli alcohol: (CD521903-COX-1 complexes (-4 kJ/mol and CD521903-COX-2 complexes (-8 kJ/ mol by LeadIT2 Biosolve. This suggests alpha-patchouli alcohol CD521903 as candidate for a selective COX-2 inhibitor. These in silico data need further analyses of biological function activity

  18. Structures and Stability of NHS2 Isomers

    Institute of Scientific and Technical Information of China (English)

    池玉娟; 于海涛; 等

    2002-01-01

    Potential energy surface of HNS2 is investigated by means of second-order Moller-Plesset Perturbation theory(MP2) and QCISD(T) (single-point)methods,At final QCISD (T)/6-311++G(3df,2p)//MP2/6-311+G(d,p),level with zero-point vibrational energies included,cis-NHSS is found to be global minimum on the potential energy sufrace,followed by low-lying trans-HNSS ,HN(S)S(C2v).cis-HSNS,cis-NSSN,trans-HSNS,trans-NSSN,and HN(S)S(Cs) by 13.46,66.92,78.25,80.38,81.22,81.38 and 86.40 kJ/mol,respectively.A new high-lying HS(N)S isomer with Cs symmetry is located on the potential energy surface ,The kinetic stabilities of all isomers are predicted.Comprisons are made for HNS2 with its analogues,NHO2,HPS2 and HPO2,The causes that lead to the differences between HNS2 and its analogues are hypervalent capacity of phosphorus and distinct electronegativities of hydrogen,nitrogen and phosphorus.

  19. Genomic Characterization of Campylobacter jejuni strain M1

    DEFF Research Database (Denmark)

    Friis, Carsten; Wassenaar, Gertrude Maria; Javed, Muhammad A.

    2010-01-01

    publicly available. Compared to these, M1 is closest to strain 81116. Based on the 13 genome sequences, we have identified the C. jejuni pan-genome, as well as the core genome, the auxiliary genes, and genes unique between strains M1 and 81116. The pan-genome contains 2,427 gene families, whilst the core...

  20. FoxM1 Regulates Mammary Luminal Cell Fate

    Directory of Open Access Journals (Sweden)

    Janai R. Carr

    2012-06-01

    Full Text Available Elevated expression of FoxM1 in breast cancer correlates with an undifferentiated tumor phenotype and a negative clinical outcome. However, a role for FoxM1 in regulating mammary differentiation was not known. Here, we identify another function of FoxM1, the ability to act as a transcriptional repressor, which plays an important role in regulating the differentiation of luminal epithelial progenitors. Regeneration of mammary glands with elevated levels of FoxM1 leads to aberrant ductal morphology and expansion of the luminal progenitor pool. Conversely, knockdown of FoxM1 results in a shift toward the differentiated state. FoxM1 mediates these effects by repressing the key regulator of luminal differentiation, GATA-3. Through association with DNMT3b, FoxM1 promotes methylation of the GATA-3 promoter in an Rb-dependent manner. This study identifies FoxM1 as a critical regulator of mammary differentiation with significant implications for the development of aggressive breast cancers.

  1. The geometrical structure, electronic structure and magnetism of bimetallic AunM2 (n=1, 2; M=Y, Zr, Nb, Mo, Tc, Ru, Rh, Pd) clusters

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    The geometrical structure, stability, magnetism, and electronic structure of bimetallic clusters AuM2 and Au2M2, where M are 4d transition metal elements, are investigated systematically by using the first-principles method based on density functional theory. The calculation results show that there is a large amount of low-energy isomers with the very similar structure. AuM2 and Au2M2 clusters display dramatic magnetism. The magnetic moment of the 4d element is either enhanced or weakened with respect to the bulk value, which is largely dependent on the orbital exchange-splitting.

  2. Pomegranate juice polyphenols induce a phenotypic switch in macrophage polarization favoring a M2 anti-inflammatory state.

    Science.gov (United States)

    Aharoni, Saar; Lati, Yoni; Aviram, Michael; Fuhrman, Bianca

    2015-01-01

    It was documented that pomegranate has anti-inflammatory effects. In this study, we investigated a direct effect of pomegranate juice (PJ) and its polyphenols on macrophage inflammatory phenotype. In vitro, PJ and its major polyphenols dose-dependently attenuated macrophage response to M1 proinflammatory activation in J774.A1 macrophage-like cell line. This was evidenced by a significant decrease in TNFα and IL-6 secretion in response to stimulation by IFNγ and Lipopolysaccharide. In addition, PJ and punicalagin dose-dependently promoted the macrophages toward a M2 anti-inflammatory phenotype, as determined by a significant increase in the spontaneous secretion of IL-10. In mice, supplementation with dietary PJ substantially inhibited the M2 to M1 macrophage phenotypic shift associated with age, toward a favorable anti-inflammatory M2 phenotype. This effect was also reflected in the mice atherosclerotic plaques, as evaluated by the distinct expression of arginase isoforms. PJ consumption inhibited the increment of arginase II (Arg II, M1) mRNA expression during aging, and maintained the levels of Arg I (M2) expression similar to those in young mice aorta. This study demonstrates, for the first time, that pomegranate polyphenols directly suppress macrophage inflammatory responses and promote M1 to M2 switch in macrophage phenotype. Furthermore, this study indicates that PJ consumption may inhibit the progressive proinflammatory state in the aorta along atherosclerosis development with aging, due to a switch in macrophage phenotype from proinflammatory M1 to anti-inflammatory M2.

  3. 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

  4. Stereospecific Synthesis of the Geometrical Isomers of a Natural Product

    Science.gov (United States)

    Grove, T.; DiLella, D.; Volker, E.

    2006-01-01

    Stereospecific synthesis of a geometrical isomer is not a common topic for the introductory organic chemistry laboratory. We have developed and tested an experiment for the synthesis of (Z) and (E) isomers that has been performed successfully by undergraduate students. The experiment is presented to the students as a puzzle in which they must…

  5. M2 Phenotype Microglia-derived Cytokine Stimulates Proliferation and Neuronal Differentiation of Endogenous Stem Cells in Ischemic Brain

    Science.gov (United States)

    Choi, Ja Yong; Kim, Jong Youl; Kim, Jae Young; Park, Joohyun; Lee, Won Taek

    2017-01-01

    Microglia play a key role in the immune response and inflammatory reaction that occurs in response to ischemic stroke. Activated microglia promote neuronal damage or protection in injured brain tissue. Extracellular signals polarize the microglia towards the M1/M2 phenotype. The M1/M2 phenotype microglia released pro- and anti-inflammatory cytokines which induce the activation of neural stem/progenitor cells (NSPCs). In this study, we investigated how the cytokines released by microglia affect the activation of NSPCs. First, we treated BV2 cells with a lipopolysaccharide (LPS; 20 ng/ml) for M1 phenotype microglia and interleukin-4 (IL-4; 20 ng/ml) for M2 phenotype microglia in BV2 cells. Mice were subjected to transient middle cerebral artery occlusion (tMCAO) for 1 h. In ex vivo, brain sections containing the subventricular zone (SVZ) were cultured in conditioned media of M1 and M2 phenotype-conditioned media for 3 d. We measured the expression of cytokines in the conditioned media by RT-PCR and ELISA. The M2 phenotype microglia-conditioned media led to the proliferation and neural differentiation of NSPCs in the ipsilateral SVZ after ischemic stroke. The RT-PCR and ELISA results showed that the expression of TGF-α mRNA was significantly higher in the M2 phenotype microglia-conditioned media. These data support that M2 phenotype microglia-derived TGF-α is one of the key factors to enhance proliferation and neural differntiation of NSPCs after ischemic stroke.

  6. The Structures and Stability of HNOS Isomers

    Institute of Scientific and Technical Information of China (English)

    CHI,Yu-Juan; YU,Hai-Tao; FU,Hong-Gang; XIN,Bai-Fu; LI,Ze-Sheng; SUN,Jia-Zhong

    2003-01-01

    Potential energy surface of HNOS system is investigated by means ofMP2 method with 6-311 ++ G(d, p)basis set. The energyfor each minimum and saddle point on the potential energy surface is corrected at the QCISD(T)/6-311 ++ G(3df, 2p) level of theory with zero-point vibrational energy included. As a result, eighteen isoners are theoretically predicted and cis-HNSO is found to be global minimum on the potential energy surface. Wherein, fourteen isoners are considered as kinetically stable species, and should be experimentally observed. Comparisons are made for HNOS system with its analogues, HNO2 and HNS2. The nature of bonding and isomers' stability of HNOS system are similar to HNS2. The obvious similarities and discrepancies among HNOS, HNO2 and HNS2are attributed to the hypervalent capacity of sulfur, oxygen and nitrogen atoms.

  7. Analysis of Heme oxygenase isomers in rat

    Institute of Scientific and Technical Information of China (English)

    Zhen-Wei Xia; Wen-Jun Cui; Xue-Hong Zhang; Qing-Xiang Shen; Jian Wang; Yun-Zhu Li; Shen-Nian Chen; Shan-Chang Yu

    2002-01-01

    AIM: To purify and identify heme oxygenase (HO) isomers which exist in rat liver, spleen and brain treated with hematin and phenylhydrazine and in untreated rat liver and to investigate the characteristics of HO isomers, to isolate and confirm the rat HO-1 cDNA that actually encodes HO-1 by expressing cDNA in monkey kidney cells (COS-1 cells), to prepare the rat heme oxygenase-1 (HO-1) mutant and to detect inhibition of HO-1 mutated enzyme.METHODS: First, rat liver, spleen and brain microsomal fi-actions were purified by DEAE-Sephacel and hydroxylapatite. The characteristics including activity, immunity and inducibility of two isomers (HO-1 and HO-2), and their apparent molecular weight were measured by detecting enzymatic activities, SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting analysis, respectively. Second, plasmid pcDNA3HO1 containing native rat HO-1 cDNA and pcDNA3HO1D25 carrying mutated rat HO-1 cDNA (His25Ala) were constructed by site-directed mutagenesis. COS-1 cells transfected with pcDNA3HO1 and pcDNA3HO1D25 were collected and disrupted by sonication, the microsomes were prepared by ultracentrifugation. Third, the inhibition of rat HO-1 mutant was analyzed.RESULTS: Two isomers were purified and identified in treated rat liver, spleen, brain and untreated rat liver. HO-1 was the predominant form with a ratio of 2.0:1 and 3.2:1 of HO-1 and HO-2 in liver and spleen, respectively, but only the activity of HO-2 in the brain and untreated liver could be detected. The apparent molecular weights of HO-1 and HO-2 were about Mr 30 000 and Mr 36 000 under reducing conditions, respectively. The antiserum against liver HO-2 was employed in Western blotting analysis, the reactivity of HO-1 in the liver was not observed. The plasmid pcDNA3HO1 was highly expressed in endoplasmic reticulum of transfected COS-1 cells. The specific activity was ≈5-fold higher than that of the control. However, the enzyme activity of mutated HO-1 declined. While

  8. 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.

  9. 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...

  10. Diverse Effects on M1 Signaling and Adverse Effect Liability within a Series of M1 Ago-PAMs.

    Science.gov (United States)

    Rook, Jerri M; Abe, Masahito; Cho, Hyekyung P; Nance, Kellie D; Luscombe, Vincent B; Adams, Jeffrey J; Dickerson, Jonathan W; Remke, Daniel H; Garcia-Barrantes, Pedro M; Engers, Darren W; Engers, Julie L; Chang, Sichen; Foster, Jarrett J; Blobaum, Anna L; Niswender, Colleen M; Jones, Carrie K; Conn, P Jeffrey; Lindsley, Craig W

    2017-01-10

    Both historical clinical and recent preclinical data suggest that the M1 muscarinic acetylcholine receptor is an exciting target for the treatment of Alzheimer's disease and the cognitive and negative symptom clusters in schizophrenia; however, early drug discovery efforts targeting the orthosteric binding site have failed to afford selective M1 activation. Efforts then shifted to focus on selective activation of M1 via either allosteric agonists or positive allosteric modulators (PAMs). While M1 PAMs have robust efficacy in rodent models, some chemotypes can induce cholinergic adverse effects (AEs) that could limit their clinical utility. Here, we report studies aimed at understanding the subtle structural and pharmacological nuances that differentiate efficacy from adverse effect liability within an indole-based series of M1 ago-PAMs. Our data demonstrate that closely related M1 PAMs can display striking differences in their in vivo activities, especially their propensities to induce adverse effects. We report the discovery of a novel PAM in this series that is devoid of observable adverse effect liability. Interestingly, the molecular pharmacology profile of this novel PAM is similar to that of a representative M1 PAM that induces severe AEs. For instance, both compounds are potent ago-PAMs that demonstrate significant interaction with the orthosteric site (either bitopic or negative cooperativity). However, there are subtle differences in efficacies of the compounds at potentiating M1 responses, agonist potencies, and abilities to induce receptor internalization. While these differences may contribute to the differential in vivo profiles of these compounds, the in vitro differences are relatively subtle and highlight the complexities of allosteric modulators and the need to focus on in vivo phenotypic screening to identify safe and effective M1 PAMs.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. Broad analgesic activity of a novel, selective M1 agonist.

    Science.gov (United States)

    Wood, Michael W; Martino, Giovanni; Coupal, Martin; Lindberg, Mattias; Schroeder, Patricia; Santhakumar, Vijayaratnam; Valiquette, Manon; Sandin, Johan; Widzowski, Daniel; Laird, Jennifer

    2017-09-01

    Although the muscarinic receptor family has long been a source of potentially compelling targets for small molecule drug discovery, it was difficult to achieve agonist selectivity within the family. A new class of M1 muscarinic agonists has emerged, and these compounds have been characterized as agonists that activate the receptor at an allosteric site. Members of this class of M1 agonists have been shown to be selective across the muscarinic receptors. However, upon introduction of a novel pharmacologic mechanism, it is prudent to ensure that no new off-target activities have arisen, particularly within the context of in vivo experiments. Reported here, is the in vitro and in vivo characterization of a novel M1 agonist tool compound, PPBI, and demonstrations that the primary biological effects of PPBI are mediated through M1. PPBI reverses d-amphetamine locomotor activity, but fails to do so in transgenic mice that do not express M1. PPBI also reverses a natural deficit in a rat cognition model at a level of exposure which also activates cortical circuitry. Most notably, PPBI is analgesic in a variety of rat and mouse models and the analgesic effect of PPBI is reversed by an M1-preferring antagonist and an M1-selective toxin. Finally, the pharmacokinetic/pharmacodynamic measures of PPBI are compared across multiple endpoints which highlights that activity in models of psychosis and pain require higher exposures than that required in the cognition model. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. Comparison of the repeated dose toxicity of isomers of dinitrotoluene.

    Science.gov (United States)

    Lent, Emily May; Crouse, Lee C B; Quinn, Michael J; Wallace, Shannon M

    2012-03-01

    Dinitrotoluene (DNT) is a nitroaromatic explosive used in propellant mixtures and in the production of plastics. Isomers of DNT were administered daily via oral gavage to male Sprague-Dawley rats for 14 days to determine the subacute toxicity of individual isomers of DNT. The 3,5-DNT isomer was the most toxic isomer, inducing weight loss and mortality within 3 days. Cyanosis and anemia were observed for all isomers. Exposure to 2,4-, 2,6-, and 3,5-DNT resulted in decreased testes mass and degenerative histopathological changes. Increased splenic mass was observed for 2,4-, 2,6-, and 2,5-DNT. Extramedullary hematopoiesis of the spleen was noted for all isomers, while lymphoid hyperplasia of the spleen was noted for all isomers except 2,5-DNT. Increased liver mass was observed for 2,3-DNT and 3,4-DNT. Hepatocellular lesions were observed for 2,6-DNT and 2,4-DNT. Neurotoxic effects were noted for 3,4-DNT, 2,4-DNT, and 3,5-DNT.

  20. M1.3--a small scaffold for DNA origami .

    Science.gov (United States)

    Said, Hassan; Schüller, Verena J; Eber, Fabian J; Wege, Christina; Liedl, Tim; Richert, Clemens

    2013-01-07

    The DNA origami method produces programmable nanoscale objects that form when one long scaffold strand hybridizes to numerous oligonucleotide staple strands. One scaffold strand is dominating the field: M13mp18, a bacteriophage-derived vector 7249 nucleotides in length. The full-length M13 is typically folded by using over 200 staple oligonucleotides. Here we report the convenient preparation of a 704 nt fragment dubbed "M1.3" as a linear or cyclic scaffold and the assembly of small origami structures with just 15-24 staple strands. A typical M1.3 origami is large enough to be visualized by TEM, but small enough to show a cooperativity in its assembly and thermal denaturation that is reminiscent of oligonucleotide duplexes. Due to its medium size, M1.3 origami with globally modified staples is affordable. As a proof of principle, two origami structures with globally 5'-capped staples were prepared and were shown to give higher UV-melting points than the corresponding assembly with unmodified DNA. M1.3 has the size of a gene, not a genome, and may function as a model for gene-based nanostructures. Small origami with M1.3 as a scaffold may serve as a workbench for chemical, physical, and biological experiments.

  1. Surface properties of new virginiamycin M(1) derivatives.

    Science.gov (United States)

    Nott, Katherine; Paquot, Michel; Dufour, Samuel; Eeman, Marc; Deleu, Magali

    2009-03-01

    Three kinds of derivatives of the M(1) factor of virginiamycin have been synthesised: esters with long chain fatty acids, oximes with modified polar amino acids and bis-derivatives with both the ester and oxime function. The study of the surface tension time dependence of M(1) and its derivatives has shown that it is necessary to enhance simultaneously the hydrophobicity and the hydrophilicity of M(1) to render M(1) surface-active. A structure/function relationship study of the surface-active bis-derivatives has shown that enhancing the hydrophobicity of the molecule led to slower adsorption kinetics, higher stability of the monolayers formed and a better capacity to penetrate a membrane model. The repulsive electrostatic forces due to the presence of charges on the amino acids linked to M(1) lead to higher surface tensions, a greater molecular area at the interface and lower penetration into a membrane model. This study has demonstrated that modifying systematically the hydrophobicity and hydrophilicity of a non surface-active molecule allows the production of surface-active derivatives.

  2. Genomic characterization of Campylobacter jejuni strain M1.

    Directory of Open Access Journals (Sweden)

    Carsten Friis

    Full Text Available Campylobacter jejuni strain M1 (laboratory designation 99/308 is a rarely documented case of direct transmission of C. jejuni from chicken to a person, resulting in enteritis. We have sequenced the genome of C. jejuni strain M1, and compared this to 12 other C. jejuni sequenced genomes currently publicly available. Compared to these, M1 is closest to strain 81116. Based on the 13 genome sequences, we have identified the C. jejuni pan-genome, as well as the core genome, the auxiliary genes, and genes unique between strains M1 and 81116. The pan-genome contains 2,427 gene families, whilst the core genome comprised 1,295 gene families, or about two-thirds of the gene content of the average of the sequenced C. jejuni genomes. Various comparison and visualization tools were applied to the 13 C. jejuni genome sequences, including a species pan- and core genome plot, a BLAST Matrix and a BLAST Atlas. Trees based on 16S rRNA sequences and on the total gene families in each genome are presented. The findings are discussed in the background of the proven virulence potential of M1.

  3. Investigation of aflatoxin M1 degradation in milk

    Directory of Open Access Journals (Sweden)

    Smajlović Ahmed

    2012-01-01

    Full Text Available Aflatoxin M1 is a highly toxic 4-hydroxylated metabolite of aflatoxins B1 and B2. It is one of the most potent hepatocarcinogens, mutagens, teratogens and immunosuppressors. Feed is often contaminated with aflatoxigenic moulds and aflatoxins with a high possibility of contaminating milk and dairy products with aflatoxin M1. Samples of artificially contaminated milk were exposed to the effects of physical conditions (temperature of -18oC and for microwaves in a microwave oven, time (during the period from 1 to 12 months and a combination of the above mentioned conditions. Following this, levels of aflatoxin M1 degradation were established by using the ELISA method. An insignificant decrease in concentration of toxin was observed which indicates that a temperature of -18°C does not significantly influence the concentration of aflatoxin M1 in the artificially contaminated milk. At the same time, treatment of milk with microwaves in a microwave oven showed an insignificant influence on the percentage of aflatoxin M1 absorbance.

  4. 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

  5. Adsorption and Diffusion of Xylene Isomers on Mesoporous Beta Zeolite

    Directory of Open Access Journals (Sweden)

    Aixia Song

    2015-12-01

    Full Text Available A systematic and detailed analysis of adsorption and diffusion properties of xylene isomers over Beta zeolites with different mesoporosity was conducted. Adsorption isotherms of xylene isomers over microporous and mesoporous Beta zeolites through gravimetric methods were applied to investigate the impact of mesopores inside Beta zeolites on the adsorption properties of xylene isomers in the pressure range of lower 20 mbar. It is seen that the adsorption isotherms of three xylene isomers over microporous and mesoporous Beta zeolites could be successfully described by the single-site Toth model and the dual-site Toth model, respectively. The enhanced adsorption capacities and decreased Henry’s constants (KH and the initial heats of adsorption (Qst for the all xylene isomers are observed after the introduction of mesopores in the zeolites. For three xylene isomers, the order of Henry’s constant is o-xylene > m-xylene > p-xylene, whereas the adsorption capacities of Beta zeolite samples for xylene isomers execute the following order of o-xylene > p-xylene > m-xylene, due to the comprehensive effects from the molecular configuration and electrostatic interaction. At the same time, the diffusion properties of xylene isomers in the mesoporous Beta zeolites were also studied through the desorption curves measured by the zero length column (ZLC method at 333–373 K. It turned out that the effective diffusion time constant (Deff/R2 is a growing trend with the increasing mesoporosity, whereas the tendency of the activation energy is just the reverse, indicating the contribution of mesopores to facilitate molecule diffusion by shortening diffusion paths and reducing diffusion resistances. Moreover, the diffusivities of three xylene isomers in all Beta zeolites follow an order of p-xylene > m-xylene > o-xylene as opposed to KH, conforming the significant effects of adsorbate-adsorbent interaction on the diffusion.

  6. Separation and identification of indene–C70 bisadduct isomers

    Science.gov (United States)

    Zhang, Bolong; Subbiah, Jegadesan; Jones, David J

    2016-01-01

    Summary Following an initial work on the isolation of a single geometric isomer from an indene–C70 bisadduct (IC70BA) mixture, we report the full fractionation and identification of the bisadduct species in the material. Eleven fractions of IC70BA isomers were separated by high-performance liquid chromatography. A number of fractions contained relatively pure isomer species and their configuration were deduced using a variety of analytical techniques including 1H and 13C NMR and UV–vis spectroscopy. The electrochemical properties and the organic solar cell device performance were investigated for fractions where a reasonable quantity of sample could be isolated. PMID:27340480

  7. Properties of neutron-rich hafnium high-spin isomers

    CERN Document Server

    Tungate, G; Walker, P M; Neyens, G; Billowes, J; Flanagan, K; Koester, U H; Litvinov, Y

    It is proposed to study highly-excited multi-quasiparticle isomers in neutron-rich hafnium (Z=72) isotopes. Long half-lives have already been measured for such isomers in the storage ring at GSI, ensuring their accessibility with ISOL production. The present proposal focuses on:\\\\ (i) an on-line experiment to measure isomer properties in $^{183}$Hf and $^{184}$Hf, and\\\\ (ii) an off-line molecular breakup test using REXTRAP, to provide Hf$^{+}$ beams for future laser spectroscopy and greater sensitivity for the future study of more neutron-rich isotopes.

  8. Detection of Actinides via Nuclear Isomer De-Excitation

    Energy Technology Data Exchange (ETDEWEB)

    Francy, Christopher J. [Oregon State Univ., Corvallis, OR (United States)

    2009-07-01

    This dissertation discusses a data collection experiment within the Actinide Isomer Identification project (AID). The AID project is the investigation of an active interrogation technique that utilizes nuclear isomer production, with the goal of assisting in the interdiction of illicit nuclear materials. In an attempt to find and characterize isomers belonging to 235U and its fission fragments, a 232Th target was bombarded with a monoenergetic 6Li ion beam, operating at 45 MeV.

  9. 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.

  10. Telmisartan prevention of LPS-induced microglia activation involves M2 microglia polarization via CaMKKβ-dependent AMPK activation.

    Science.gov (United States)

    Xu, Yuan; Xu, Yazhou; Wang, Yurong; Wang, Yunjie; He, Ling; Jiang, Zhenzhou; Huang, Zhangjian; Liao, Hong; Li, Jia; Saavedra, Juan M; Zhang, Luyong; Pang, Tao

    2015-11-01

    Brain inflammation plays an important role in the pathophysiology of many psychiatric and neurological diseases. During brain inflammation, microglia cells are activated, producing neurotoxic molecules and neurotrophic factors depending on their pro-inflammatory M1 and anti-inflammatory M2 phenotypes. It has been demonstrated that Angiotensin II type 1 receptor blockers (ARBs) ameliorate brain inflammation and reduce M1 microglia activation. The ARB telmisartan suppresses glutamate-induced upregulation of inflammatory genes in cultured primary neurons. We wished to clarify whether telmisartan, in addition, prevents microglia activation through polarization to an anti-inflammatory M2 phenotype. We found that telmisartan promoted M2 polarization and reduced M1 polarization in LPS-stimulated BV2 and primary microglia cells, effects partially dependent on PPARγ activation. The promoting effects of telmisartan on M2 polarization, were attenuated by an AMP-activated protein kinase (AMPK) inhibitor or AMPK knockdown, indicating that AMPK activation participates on telmisartan effects. Moreover, in LPS-stimulated BV2 cells, telmisartan enhancement of M2 gene expression was prevented by the inhibitor STO-609 and siRNA of calmodulin-dependent protein kinase kinase β (CaMKKβ), an upstream kinase of AMPK. Furthermore, telmisartan enhanced brain AMPK activation and M2 gene expression in a mouse model of LPS-induced neuroinflammation. In addition, telmisartan reduced the LPS-induced sickness behavior in this in vivo model, and this effect was prevented by prior administration of an AMPK inhibitor. Our results indicate that telmisartan can be considered as a novel AMPK activator, suppressing microglia activation by promoting M2 polarization. Telmisartan may provide a novel, safe therapeutic approach to treat brain disorders associated with enhanced inflammation.

  11. Improvement of ISOM by using filter

    Directory of Open Access Journals (Sweden)

    Imen Chaabouni

    2012-05-01

    Full Text Available Image compression helps in storing the transmitted data in proficient way by decreasing its redundancy. This technique helps in transferring more digital or multimedia data over internet as it increases the storage space. It is important to maintain the image quality even if it is compressed to certain extent. Depend upon this the image compression is classified into two categories : lossy and lossless image compression. There are many lossy digital image compression techniques exists. Among this Incremental Self Organizing Map is a familiar one. The good pictures quality can be retrieved if image denoising technique is used for compression and also provides better compression ratio. Image denoising is an important pre-processing step for many image analysis and computer vision system. It refers to the task of recovering a good estimate of the true image from a degraded observation without altering and changing useful structure in the image such as discontinuities and edges. Many approaches have been proposed to remove the noise effectively while preserving the original image details and features as much as possible. This paper proposes a technique for image compression using Incremental Self Organizing Map (ISOM with Discret Wavelet Transform (DWT by applying filtering techniques which play a crucial role in enhancing the quality of a reconstructed image. The experimental result shows that the proposed technique obtained better compression ratio value.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Fast-timing study of the l -forbidden 1 /2+→3 /2+ M 1 transition in 129Sn

    Science.gov (United States)

    Licǎ, R.; Mach, H.; Fraile, L. M.; Gargano, A.; Borge, M. J. G.; Mǎrginean, N.; Sotty, C. O.; Vedia, V.; Andreyev, A. N.; Benzoni, G.; Bomans, P.; Borcea, R.; Coraggio, L.; Costache, C.; De Witte, H.; Flavigny, F.; Fynbo, H.; Gaffney, L. P.; Greenlees, P. T.; Harkness-Brennan, L. J.; Huyse, M.; Ibáñez, P.; Judson, D. S.; Konki, J.; Korgul, A.; Kröll, T.; Kurcewicz, J.; Lalkovski, S.; Lazarus, I.; Lund, M. V.; Madurga, M.; Mǎrginean, R.; Marroquín, I.; Mihai, C.; Mihai, R. E.; Morales, A. I.; Nácher, E.; Negret, A.; Page, R. D.; Pakarinen, J.; Pascu, S.; Paziy, V.; Perea, A.; Pérez-Liva, M.; Picado, E.; Pucknell, V.; Rapisarda, E.; Rahkila, P.; Rotaru, F.; Swartz, J. A.; Tengblad, O.; Van Duppen, P.; Vidal, M.; Wadsworth, R.; Walters, W. B.; Warr, N.; IDS Collaboration

    2016-04-01

    The levels in 129Sn populated from the β- decay of 129In isomers were investigated at the ISOLDE facility of CERN using the newly commissioned ISOLDE Decay Station (IDS). The lowest 1 /2+ state and the 3 /2+ ground state in 129Sn are expected to have configurations dominated by the neutron s1 /2 (l =0 ) and d3 /2 (l =2 ) single-particle states, respectively. Consequently, these states should be connected by a somewhat slow l -forbidden M 1 transition. Using fast-timing spectroscopy we have measured the half-life of the 1 /2+ 315.3-keV state, T1 /2= 19(10) ps, which corresponds to a moderately fast M 1 transition. Shell-model calculations using the CD-Bonn effective interaction, with standard effective charges and g factors, predict a 4-ns half-life for this level. We can reconcile the shell-model calculations to the measured T1 /2 value by the renormalization of the M 1 effective operator for neutron holes.

  17. Concerning the Integral dx/x[superscript m] (1+x)

    Science.gov (United States)

    Walters, William; Huber, Michael

    2010-01-01

    Consider the integral dx/x[superscript m] (1+x). In the "CRC Standard Mathematical Tables," this integral can require repeated integral evaluations. Enter this integral into your favourite computer algebra system, and the results may be unrecognizable. In this article, we seek to provide a simpler evaluation for integrals of this form. We state up…

  18. Theory of the M = 1 Kink Mode in Toroidal Plasma

    NARCIS (Netherlands)

    de Blank, H. J.; Schep, T. J.

    1991-01-01

    The energy principle of ideal magnetohydrodynamics (MHD) is used to study the ideal MHD stability of the m = 1 internal kink mode in a toroidal plasma. The equilibrium configurations that are considered allow for a broad region where the safety factor q is close to unity. This region may extend to t

  19. Concerning the Integral dx/x[superscript m] (1+x)

    Science.gov (United States)

    Walters, William; Huber, Michael

    2010-01-01

    Consider the integral dx/x[superscript m] (1+x). In the "CRC Standard Mathematical Tables," this integral can require repeated integral evaluations. Enter this integral into your favourite computer algebra system, and the results may be unrecognizable. In this article, we seek to provide a simpler evaluation for integrals of this form. We state up…

  20. 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.

  1. 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.

  2. 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.

  3. A novel strain of Bacteroides fragilis enhances phagocytosis and polarises M1 macrophages

    Science.gov (United States)

    Deng, Huimin; Li, Zhengchao; Tan, Yafang; Guo, Zhaobiao; Liu, Yangyang; Wang, Ye; Yuan, Yuan; Yang, Ruifu; Bi, Yujing; Bai, Yang; Zhi, Fachao

    2016-01-01

    Commensal Bacteroides fragilis possesses immune-regulatory characteristics. Consequently, it has been proposed as a potential novel probiotic because of its therapeutic effects on immune imbalance, mental disorders and inflammatory diseases. Macrophages play a central role in the immune response, developing either a classical-M1 or an alternative-M2 phenotype after stimulation with various signals. The interactions between macrophages and B. fragilis, however, remain to be defined. Here, a new isolate of B. fragilis, ZY-312, was shown to possess admirable properties, including tolerance to simulated gastric fluid, intestinal fluid and ox bile, and good safety (MOI = 100, 200) and adherent ability (MOI = 100) to LoVo cells. Isolate ZY-312 cell lysate promoted phagocytosis of fluorescent microspheres and pathogenic bacteria in bone marrow-derived macrophage (BMDM) cells. Gene expression of IL-12, iNOS and IL-1β in BMDM cells was increased after treatment with ZY-312, indicating the induction of M1 macrophages, consistent with enhanced secretion of NO. Cell surface expression of CD80 and CD86 was also increased. This study is the first to demonstrate that B. fragilis enhances the phagocytic functions of macrophages, polarising them to an M1 phenotype. Our findings provide insight into the close relationship between B. fragilis and the innate immune system. PMID:27381366

  4. Surface Termination of M1 Phase and Rational Design of Propane Ammoxidation Catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Guliants, Vadim

    2015-02-16

    This final report describes major accomplishments in this research project which has demonstrated that the M1 phase is the only crystalline phase required for propane ammoxidation to acrylonitrile and that a surface monolayer terminating the ab planes of the M1 phase is responsible for their activity and selectivity in this reaction. Fundamental studies of the topmost surface chemistry and mechanism of propane ammoxidation over the Mo-V-(Te,Sb)-(Nb,Ta)-O M1 and M2 phases resulted in the development of quantitative understanding of the surface molecular structure – reactivity relationships for this unique catalytic system. These oxides possess unique catalytic properties among mixed metal oxides, because they selectively catalyze three alkane transformation reactions, namely propane ammoxidation to acrylonitrile, propane oxidation to acrylic acid and ethane oxidative dehydrogenation, all of considerable economic significance. Therefore, the larger goal of this research was to expand this catalysis to other alkanes of commercial interest, and more broadly, demonstrate successful approaches to rational design of improved catalysts that can be applied to other selective (amm)oxidation processes.

  5. Enhanced Macrophage M1 Polarization and Resistance to Apoptosis Enable Resistance to Plague.

    Science.gov (United States)

    Pachulec, Emilia; Abdelwahed Bagga, Rym Ben; Chevallier, Lucie; O'Donnell, Hope; Guillas, Chloé; Jaubert, Jean; Montagutelli, Xavier; Carniel, Elisabeth; Demeure, Christian E

    2017-09-15

    Susceptibility to infection is in part genetically driven, and C57BL/6 mice resist various pathogens through the proinflammatory response of their M1 macrophages (MPs). However, they are susceptible to plague. It has been reported elsewhere that Mus spretus SEG mice resist plague and develop an immune response characterized by a strong recruitment of MPs. The responses of C57BL/6 and SEG MPs exposed to Yersinia pestis in vitro were examined. SEG MPs exhibit a stronger bactericidal activity with higher nitric oxide production, a more proinflammatory polarized cytokine response, and a higher resistance to Y. pestis-induced apoptosis. This response was not specific to Y. pestis and involved a reduced sensitivity to M2 polarization/signal transducer and activator of transcription 6 activation and inhibition of caspase 8. The enhanced M1 profile was inducible in C57BL/6 MPs in vitro, and when transferred to susceptible C57BL/6 mice, these MPs significantly increased survival of bubonic plague. MPs can develop an enhanced functional profile beyond the prototypic M1, characterized by an even more potent proinflammatory response coordinated with resistance to killing. This programming plays a key role in the plague-resistance phenotype and may be similarly significant in other highly lethal infections, suggesting that orienting the MP response may represent a new therapeutic approach.

  6. Carotenoids and their isomers: color pigments in fruits and vegetables.

    Science.gov (United States)

    Khoo, Hock-Eng; Prasad, K Nagendra; Kong, Kin-Weng; Jiang, Yueming; Ismail, Amin

    2011-02-18

    Fruits and vegetables are colorful pigment-containing food sources. Owing to their nutritional benefits and phytochemicals, they are considered as 'functional food ingredients'. Carotenoids are some of the most vital colored phytochemicals, occurring as all-trans and cis-isomers, and accounting for the brilliant colors of a variety of fruits and vegetables. Carotenoids extensively studied in this regard include β-carotene, lycopene, lutein and zeaxanthin. Coloration of fruits and vegetables depends on their growth maturity, concentration of carotenoid isomers, and food processing methods. This article focuses more on several carotenoids and their isomers present in different fruits and vegetables along with their concentrations. Carotenoids and their geometric isomers also play an important role in protecting cells from oxidation and cellular damages.

  7. Reelfoot and Lake Isom National Wildlife Refuges : Wildlife Inventory Plan

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This wildlife inventory plan for Reelfoot and Lake Isom National Wildlife Refuges includes survey procedure forms that represent cost effective inventory of the...

  8. Carotenoids and Their Isomers: Color Pigments in Fruits and Vegetables

    Directory of Open Access Journals (Sweden)

    Yueming Jiang

    2011-02-01

    Full Text Available Fruits and vegetables are colorful pigment-containing food sources. Owing to their nutritional benefits and phytochemicals, they are considered as ‘functional food ingredients’. Carotenoids are some of the most vital colored phytochemicals, occurring as all-trans and cis-isomers, and accounting for the brilliant colors of a variety of fruits and vegetables. Carotenoids extensively studied in this regard include β-carotene, lycopene, lutein and zeaxanthin. Coloration of fruits and vegetables depends on their growth maturity, concentration of carotenoid isomers, and food processing methods. This article focuses more on several carotenoids and their isomers present in different fruits and vegetables along with their concentrations. Carotenoids and their geometric isomers also play an important role in protecting cells from oxidation and cellular damages.

  9. Aromaticity of All Possible C26N2 Isomers

    Institute of Scientific and Technical Information of China (English)

    TANG,Ming-Hui; ABLIKIM,Kerim

    2008-01-01

    The aromaticity of all possible heterofullerenes C26N2 and C28 based on Td symmetry has been studied by means of the topological resonance energy and percentage topological resonance energy methods. The relationship between the aromaticity of the C26N2 isomers and the sites where nitrogen atoms dope at the C28 cage has been discussed. The calculation results show that the most stable isomer of C26N2 derivatives is formed by nitrogen atoms doping at the two tetrahedral vertices. C26N2 isomers are more stable than C28, but the C26N2-2 isomers are less stable than C4-28. The effect of nitrogen substitution on C28 stability was investigated by the topological charge stabilization rule.

  10. Separation of amyl alcohol isomers in ZIF-77

    NARCIS (Netherlands)

    Bueno-Perez, R.; Gutiérrez-Sevillano, J.J.; Dubbeldam, D.; Merkling, P.J.; Calero, S.

    2015-01-01

    The separation of pentanol isomer mixtures is shown to be very efficient using the nanoporous adsorbent zeolitic imidazolate framework ZIF-77. Through molecular simulations, we demonstrate that this material achieves a complete separation of linear from monobranchedand these from dibranchedisomers.

  11. Reelfoot/Lake Isom National Wildlife Refuge: Comprehensive Conservation Plan

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This Comprehensive Conservation Plan (CCP) was written to guide management on Reelfoot and Lake Isom NWRs for the next 15 years. This plan outlines the refuges'...

  12. Tolerance and M2 (alternative) macrophage polarization are related processes orchestrated by p50 nuclear factor κB

    Science.gov (United States)

    Porta, Chiara; Rimoldi, Monica; Raes, Geert; Brys, Lea; Ghezzi, Pietro; Di Liberto, Diana; Dieli, Francesco; Ghisletti, Serena; Natoli, Gioacchino; De Baetselier, Patrick; Mantovani, Alberto; Sica, Antonio

    2009-01-01

    Cells of the monocyte–macrophage lineage play a central role in the orchestration and resolution of inflammation. Plasticity is a hallmark of mononuclear phagocytes, and in response to environmental signals these cells undergo different forms of polarized activation, the extremes of which are called classic or M1 and alternative or M2. NF-κB is a key regulator of inflammation and resolution, and its activation is subject to multiple levels of regulation, including inhibitory, which finely tune macrophage functions. Here we identify the p50 subunit of NF-κB as a key regulator of M2-driven inflammatory reactions in vitro and in vivo. p50 NF-κB inhibits NF-κB–driven, M1-polarizing, IFN-β production. Accordingly, p50-deficient mice show exacerbated M1-driven inflammation and defective capacity to mount allergy and helminth-driven M2-polarized inflammatory reactions. Thus, NF-κB p50 is a key component in the orchestration of M2-driven inflammatory reactions. PMID:19706447

  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. 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 of Scientific and Technical Information of China (English)

    胡修明; 蒋纪恺

    2009-01-01

    Human pyruvate kinase (hPK) has four isozymes-M1, M2, R and L, among which M2 gene is mainly expressed in early embryonic tissues and its expression is progressively replaced by the other three isozymes after birth. But expression of hPKM2 gene remains in adult stem cells. In addition, it is specifically present in most tumor cells, hPKM2 seems to interact with different kinds of endogenous, exogenous oncopro-reins and factors that regulate cell growth to enhance proliferation of tumor cells. Thus,hPKM2 has been named as tumor specific PK.%人丙酮酸激酶(PK)有M1M2、R和L等4种同工酶.其中M2型主要在早期胚胎组织中表达,胎儿出生后逐渐被其他3种同工酶取代,但在成体干细胞中人丙酮酸激酶也有表达.几乎所有的肿瘤细胞都存在M2型表达,并同各种内源性、外源性癌蛋白及增殖调节因子相互作用以增强肿瘤细胞的增殖,因此被称为肿瘤特异性丙酮酸激酶.

  15. 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...

  16. The E2/M1 ratio in {Delta} photoproduction

    Energy Technology Data Exchange (ETDEWEB)

    Hoblit, S. [Brookhaven National Lab., Upton, NY (United States). Physics Dept.]|[Univ. of Virginia, Charlottesville, VA (United States). Dept. of Physics; Blanpied, G. [Univ. of South Carolina, Columbia, SC (United States). Dept. of Physics; Blecher, M. [Virginia Polytechnic Inst. and State Univ., Blacksburg, VA (United States). Physics Dept.] [and others; LEGS Collaboration

    1997-10-01

    New high-precision measurements of p({rvec {gamma}}, {pi}) and p({rvec {gamma}}, {gamma}) cross sections and beam asymmetries have been combined with other polarization ratios in a simultaneous analysis of both reactions. The E2/M1 mixing ratio for the n {r_arrow} {Delta} transition extracted from this analysis is EMR = {minus}3.0% {+-} 0.3 (stat+sys) {+-} 0.2 (model).

  17. Yield of Radionuclides and Isomers Measured in Fragmentation of the ^{nat}W and ^{186}W (97%) Targets with Protons at 630, 420 and 270 MeV

    CERN Document Server

    Karamian, S A; Chaloun, P; Filossofov, D V; Henzl, V; Henzlova, D; Kalinnikov, V G; Korolev, N A; Lebedev, N A; Novgorodov, A F; Collins, C B; Popescu, I I; Ur, C A

    2004-01-01

    Yields and cross sections of the radioactive nuclide formation have been measured via induced activity gamma-spectra after irradiation of the natural composition W and enriched ^{186)W targets at Dubna synchrocyclotron. Spallation and fission products have been represented among the detected nuclides. The high-spin isomers of Hf and Lu were produced and the isomer-to-ground state ratios could be estimated. The nuclide yields have also been calculated using the LAHET code at 6 values of proton energy in the range from 100 to 800 MeV both for ^{nat)W and for enriched ^{186)W targets. Measured isotope yields are generally in agreement with the calculations, however, the code is incapable to predict the isomer-to-ground state ratios. In experiment, it has been shown that the ^{177m}Lu, ^{178m2}Hf and ^{179m2}Hf high-spin isomers are produced with 2.5 times higher yield in the 97% enriched ^{186)W target as compared to the ^{nat)W target at identical irradiations. This makes significance for the creation of high-a...

  18. The E2/M1 ratio in {Delta} photoproduction

    Energy Technology Data Exchange (ETDEWEB)

    Sandorfi, A.M. [Brookhaven National Lab., Upton, NY (United States). Physics Dept.; Blanpied, G. [Univ. of South Carolina, Columbia, SC (United States). Dept. of Physics; Blecher, M. [Virginia Polytechnic Inst. and State Univ., Blacksburg, VA (United States). Physics Dept.] [and others; LEGS Collaboration

    1997-08-01

    The properties of the transition from the nucleon to the {Delta}(1232) serve as a benchmark for models of nucleon structure. To first order, N {r_arrow} {Delta} photo-excitation is dominated by a simple M1 quark spin-flip transition. At higher order, small L = 2 components in the N and {Delta} wavefunctions allow this excitation to proceed via an electric quadrupole transition. Since Nucleon models differ greatly on the mechanisms used to generate these L = 2 components,, the ratio of E2/M1 transitions (EMR) provides a sensitive test for structure models. Here, new high-precision measurements of p({rvec {gamma}}, {pi}) and p({rvec {gamma}}, {gamma}) cross sections and beam asymmetries have been combined with other polarization ratios in a simultaneous analysis of both reactions. Compton scattering has provided two important new constraints on the photo-pion amplitude. The E2/M1 mixing ratio for the N {r_arrow} {Delta} transition extracted from this analysis is EMR = {minus}3.0% {+-} 0.3 (stat+sys) {+-} 0.2 (model).

  19. Role of the tumor suppressor ARF in macrophage polarization: Enhancement of the M2 phenotype in ARF-deficient mice.

    Science.gov (United States)

    Herranz, Sandra; Través, Paqui G; Luque, Alfonso; Hortelano, Sonsoles

    2012-11-01

    The ARF locus is frequently inactivated in human cancer. The oncosuppressor ARF has indeed been described as a general sensor for different situation of cellular stress. We have previously demonstrated that ARF deficiency severely impairs inflammatory responses in vitro and in vivo, establishing a role for ARF in the regulation of innate immunity. The aim of the present work was to get further insights into the immune functions of ARF and to evaluate its possible contribution to the polarization of macrophages toward the M1 or M2 phenotype. Our results demonstrate that resting Arf(-/-) macrophages express high levels of Ym1 and Fizz-1, two typical markers of alternatively-activated macrophages (M2). Additionally, Arf(-/-) peritoneal macrophages showed an impaired response to lipopolysaccharide (a classical inducer of M1 polaryzation) and a reduced production of pro-inflammatory cytokines/chemokines. Moreover, upon stimulation with interleukin-4 (IL-4), an inducer of the M2 phenotype, well established M2 markers such as Fizz-1, Ym1 and arginase-1 were upregulated in Arf(-/-) as compared with wild type macrophages. Accordingly, the cytokine and chemokine profile associated with the M2 phenotype was significantly overexpressed in Arf(-/-) macrophages responding to IL-4. In addition, multiple pro-angiogenic factors such as VEGF and MMP-9 were also increased. In summary, these results indicate that ARF contributes to the polarization and functional plasticity of macrophages.

  20. Deficiency in the voltage-gated proton channel Hv1 increases M2 polarization of microglia and attenuates brain damage from photothrombotic ischemic stroke.

    Science.gov (United States)

    Tian, Dai-Shi; Li, Chun-Yu; Qin, Chuan; Murugan, Madhuvika; Wu, Long-Jun; Liu, Jun-Li

    2016-10-01

    Microglia become activated during cerebral ischemia and exert pro-inflammatory or anti-inflammatory role dependent of microglial polarization. NADPH oxidase (NOX)-dependent reactive oxygen species (ROS) production in microglia plays an important role in neuronal damage after ischemic stroke. Recently, NOX and ROS are consistently reported to participate in the microglial activation and polarization; NOX2 inhibition or suppression of ROS production are shown to shift the microglial polarization from M1 toward M2 state after stroke. The voltage-gated proton channel, Hv1, is selectively expressed in microglia and is required for NOX-dependent ROS generation in the brain. However, the effect of Hv1 proton channel on microglial M1/M2 polarization state after cerebral ischemia remains unknown. In this study, we investigated the role of microglial Hv1 proton channel in modulating microglial M1/M2 polarization during the pathogenesis of ischemic cerebral injury using a mouse model of photothrombosis. Following photothrombotic ischemic stroke, wild-type mice presented obvious brain infarct, neuronal damage, and impaired motor coordination. However, mice lacking Hv1 (Hv1(-/-)) were partially protected from brain damage and motor deficits compared to wild-type mice. These rescued phenotypes in Hv1(-/-) mice in ischemic stroke is accompanied by reduced ROS production, shifted the microglial polarization from M1 to M2 state. Hv1 deficiency was also found to shift the M1/M2 polarization in primary cultured microglia. Our study suggests that the microglial Hv1 proton channel is a unique target for modulation of microglial M1/M2 polarization in the pathogenesis of ischemic stroke. The voltage-gated proton channel, Hv1, is selectively expressed in microglia and is required for NOX-dependent generation of reactive oxygen species (ROS) in the brain. ROS participate in microglial activation and polarization. However, the effect of Hv1 on microglial M1/M2 polarization state after

  1. 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...

  2. 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

  3. 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.

  4. 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.

  5. Anaerobic biodegradability of phthalic acid isomers and related compounds.

    Science.gov (United States)

    Kleerebezem, R; Pol, L W; Lettinga, G

    1999-02-01

    All three phthalic acid isomers (ortho, meta and para benzene dicarboxylic acid) are produced in massive amounts, and used in the chemical industry as plasticizers or for the production of polyester. Wastestreams generated during the production of phthalate isomers generally contain high concentrations of aromatic acids. To study the potential biodegradability of these primarily anthropogenic compounds in anaerobic bioreactors, biodegradability studies were performed. Compounds tested were benzoate, ortho-phthalate, isophthalate, terephthalate, dimethyl phthalate, dimethyl terephthalate, para-toluate and para-xylene. Seed materials tested were two types of granular sludge and digested sewage sludge. It was found that all phthalate isomers and their corresponding dimethyl-esters, could be completely mineralized by all seed materials studied. Lag phases required for 50% degradation of these compounds, ranged from 17 to 156 days. The observed degradation curves could be explained by growth of an initially small amount of organisms in the inoculum with the specific ability to degrade one phthalate isomer. The observed order in the length of the lag phases for the phthalate isomers is: phthalate terephthalate terephthalate was found to be fermentation of the phthalate isomer. Para-toluate was degraded only by digested sewage sludge after a lag phase of 425 days. The observed degradation rates of this compound were very low. No mineralization of para-xylene was observed. In general, the differences in the lag phases between different seed materials were relatively small. These results indicate that the time needed for the start-up of anaerobic bioreactors treating wastewaters containing phthalic acid isomers, depends little on the microbial composition of the seed material applied, but may take several months.

  6. 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.

  7. Effect of the radial plasma nonuniformity on the propagation of guided m = + 1 and m = - 1 modes in helicon discharges

    Science.gov (United States)

    Aliev, Yu. M.; Krämer, M.

    2016-10-01

    Theoretical as well as numerical analyses of the full set of Maxwell's equations is carried out to study non-axisymmetric ( m ≠ 0 ) guided modes in radially nonuniform helicon (HE) discharges. Unlike the axisymmetric (m = 0) modes, these modes reveal a non-reciprocal behavior with respect to the azimuthal direction. We develop the conditions for propagation and non-propagation of the various modes in the helicon parameter range, thereby focussing on the important role of the radial density gradient. Three types of modes occurring in different parameter ranges are described, i.e., the helicon (HE) mode, the electrostatic (ES) or Trivelpiece-Gould mode, and the locally coupled (LC) mode that is characterized by mode coupling (MC) in a certain region of the plasma density profile. In contrast to m = + 1 modes, the parameter range of m = - 1 modes is much more restricted as rather high densities are needed for the propagation of the helicon and LC modes. An important issue of the investigations is the rf power coupling and absorption via the various modes. Computations based on a simple antenna-plasma model show that the axial wavenumber of the antenna determines decisively which type of mode is excited. In case of LC mode excitation, the dominant role of the MC layer for the absorption is demonstrated. Finally, the rf power coupling to helicon modes is studied. The density limit for m = - 1 helicon mode propagation and the narrow magnetic field profiles of these modes are the main reasons why the rf power absorption in helicon discharges occurs via m = + 1 helicon modes.

  8. 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、

  9. 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

  10. 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.

  11. 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.

  12. Electrochemical immunochip sensor for aflatoxin M1 detection.

    Science.gov (United States)

    Parker, Charlie O; Lanyon, Yvonne H; Manning, Mary; Arrigan, Damien W M; Tothill, Ibtisam E

    2009-07-01

    An investigation into the fabrication, electrochemical characterization, and development of a microelectrode array (MEA) immunosensor for aflatoxin M(1) is presented in this paper. Gold MEAs (consisting of 35 microsquare electrodes with 20 microm x 20 microm dimensions and edge-to-edge spacing of 200 microm) together with on-chip reference and counter electrodes were fabricated using standard photolithographic methods. The MEAs were then characterized by cyclic voltammetry, and the behavior of the on-chip electrodes were evaluated. The microarray sensors were assessed for their applicability to the development of an immunosensor for the analysis of aflatoxin M(1) directly in milk samples. Following the sensor surface silanization, antibodies were immobilized by cross-linking with 1,4-phenylene diisothiocyanate (PDITC). Surface characterization was conducted by electrochemistry, fluorescence microscopy, scanning electron microscopy (SEM), and atomic force microscopy (AFM). A competitive enzyme linked immunosorbent assay (ELISA) assay format was developed on the microarray electrode surface using the 3,3,5',5'-tetramethylbenzidine dihyrochloride (TMB)/H(2)O(2) electrochemical detection scheme with horseradish peroxidase (HRP) as the enzyme label. The performance of the assay and the microarray sensor were characterized in pure buffer conditions before applying to the milk samples. With the use of this approach, the detection limit for aflatoxin M(1) in milk was estimated to be 8 ng L(-1), with a dynamic detection range of 10-100 ng L(-1), which meets present legislative limits of 50 ng L(-1). The milk interference with the sensor surface was also found to be minimal. These devices show high potential for development of a range of new applications which have previously only been detected using elaborate instrumentation.

  13. A review of aflatoxin M1 in liquid milk

    OpenAIRE

    2015-01-01

    Mycotoxins continue to pose a health concern via human exposure to contaminated food. Aflatoxin M1 (AFM1), the hydroxylated metabolite of aflatoxin B1 (AFB1), may be found in the milk of dairy cattle and other mammals. In humans, AFM1 is excreted through the feces, urine, and in the case of lactating mothers, also in breast milk after consumption of aflatoxin contaminated food. Concentration of AFM1 in milk is a function of several factors, namely: animal type, milking day, milk yield, season...

  14. PEMBUATAN PROGRAM INTERFACE UNTUK PENGONTROLAN RV-M1

    Directory of Open Access Journals (Sweden)

    Endra Endra

    2007-10-01

    Full Text Available Article explores the making of interface of RV-M1 hand robot control that replaced the cosiprog program,a program that is able to help student in Mecatronica-1 Practice, and able to control the hand robot by localnetwork by two user or more. The used methods were literature study, and field study, that is design method. Theresearch result are control of hand robot on X,Y,Z axis and point to point, the use of local network to control thehand robot, save certain position, and use several user to control the robot.Keywords: interface program, robot, local network

  15. 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

  16. A new high-spin isomer in {sup 195}Bi

    Energy Technology Data Exchange (ETDEWEB)

    Roy, T.; Mukherjee, G.; Rana, T.K.; Bhattacharya, Soumik; Asgar, Md.A.; Bhattacharya, C.; Bhattacharya, S.; Bhattacharyya, S.; Pai, H. [Variable Energy Cyclotron Centre, Kolkata (India); Madhavan, N.; Bala, I.; Gehlot, J.; Gurjar, R.K.; Jhingan, A.; Kumar, R.; Muralithar, S.; Nath, S.; Singh, R.P.; Varughese, T. [Inter University Acclerator Centre, New Delhi (India); Basu, K.; Bhattacharjee, S.S.; Ghugre, S.S.; Raut, R.; Sinha, A.K. [UGC-DAE-CSR Kolkata Centre, Kolkata (India); Palit, R. [Tata Institute of Fundamental Research, Department of Nuclear and Atomic Physics, Mumbai (India)

    2015-11-15

    A new high-spin isomer has been identified in {sup 195}Bi at the focal plane of the HYbrid Recoil mass Analyser (HYRA) used in the gas-filled mode. The fusion evaporation reactions {sup 169}Tm ({sup 30}Si, x n) {sup 193,} {sup 195}Bi were used with the beam energies on targets of 168 and 146MeV for 6n and 4n channels, respectively. The evaporation residues, separated from the fission fragments, and their decays were detected at the focal plane of HYRA using MWPC, Si-Pad and clover HPGe detectors. The half-life of the new isomer in {sup 195}Bi has been measured to be 1.6(1) μs. The configuration of the new isomer has been proposed and compared with the other isomers in this region. The Total Routhian Surface (TRS) calculations for the three-quasiparticle configurations corresponding to the new isomer suggest an oblate deformation for this isomeric state. The same calculations for different configurations in {sup 195}Bi and for the even-even {sup 194}Pb core indicate that the proton i{sub 13/2} orbital has a large shape driving effect towards oblate shape in these nuclei. (orig.)

  17. Direct observation of long-lived isomers in $^{212}$Bi

    CERN Document Server

    Chen, L; Geissel, H; Litvinov, Yu A; Beckert, K; Beller, P; Bosch, F; Boutin, D; Caceres, L; Carroll, J J; Cullen, D M; Cullen, I J; Franzke, B; Gerl, J; Górska, M; Jones, G A; Kishada, A; Knöbel, R; Kozhuharov, C; Kurcewicz, J; Litvinov, S A; Liu, Z; Mandal, S; Montes, F; Münzenberg, G; Nolden, F; Ohtsubo, T; Patyk, Z; Plaß, W R; Podolyák, Zs; Rigby, S; Saito, N; Saito, T; Scheidenberger, C; Simpson, E C; Shindo, M; Steck, M; Sun, B; Williams, S J; Weick, H; Winkler, M; Wollersheim, H -J; Yamaguchi, T

    2013-01-01

    Long-lived isomers in 212Bi have been studied following 238U projectile fragmentation at 670 MeV per nucleon. The fragmentation products were injected as highly charged ions into the GSI storage ring, giving access to masses and half-lives. While the excitation energy of the first isomer of 212Bi was confirmed, the second isomer was observed at 1478(30) keV, in contrast to the previously accepted value of >1910 keV. It was also found to have an extended Lorentz-corrected in-ring halflife >30 min, compared to 7.0(3) min for the neutral atom. Both the energy and half-life differences can be understood as being due a substantial, though previously unrecognised, internal decay branch for neutral atoms. Earlier shell-model calculations are now found to give good agreement with the isomer excitation energy. Furthermore, these and new calculations predict the existence of states at slightly higher energy that could facilitate isomer de-excitation studies.

  18. Identification of M(1) muscarinic receptor subtype in rat stomach using a tissue segment binding method, and the effects of immobilization stress on the muscarinic receptors.

    Science.gov (United States)

    Anisuzzaman, Abu Syed Md; Morishima, Shigeru; Suzuki, Fumiko; Tanaka, Takashi; Muramatsu, Ikunobu

    2008-12-03

    Distinct muscarinic acetylcholine receptor subtypes widely distribute in stomach tissues and are involved in many physiological functions. Although mRNA of M(1) subtype was found in gastric mucosa, the M(1) subtype has not been detected by conventional membrane binding assays. In the present study, muscarinic receptor subtypes in the rat stomach were reevaluated by using the tissue segment binding technique recently developed to recognize the inherent/native profiles of receptors without receptor environment perturbation. [(3)H]-N-methylscopolamine (NMS) bound to muscarinic receptors in the intact segments of rat gastric mucosa and muscle layers. The muscarinic receptors in the mucosal segments were composed of M(1), M(2) and M(3) subtypes, among which the M(1) subtype selectively showed high affinity for pirenzepine. However, in the membrane preparations, binding sites with high affinity for pirenzepine could not be detected. In the muscle layer, M(2) and M(3) subtypes, but not M(1), were identified in tissue segment and conventional membrane binding assays. Western blotting analysis recognized the M(1) subtype in the membrane preparations of mucosal but not muscle layers. Chronic immobilization stress increased the M(3) subtype in mucosal and muscle layers and decreased the M(2) subtype in the muscle layer, whereas M(1) and M(2) subtypes in mucosal layer did not change after the stress. The current study shows that M(1) subtype occurs as a pirenzepine-high affinity entity in intact segments of rat gastric mucosa, but that it loses the affinity for pirenzepine upon homogenization. Careful identification of native in vivo muscarinic receptors may further elucidate their functions in stomach.

  19. E1 and M1 strength functions at low energy

    Directory of Open Access Journals (Sweden)

    Schwengner Ronald

    2017-01-01

    Full Text Available We report photon-scattering experiments using bremsstrahlung at the γELBE facility of Helmholtz-Zentrum Dresden-Rossendorf and using quasi-monoenergetic, polarized γ beams at the HIγS facility of the Triangle Universities Nuclear Laboratory in Durham. To deduce the photoabsorption cross sections at high excitation energy and high level density, unresolved strength in the quasicontinuum of nuclear states has been taken into account. In the analysis of the spectra measured by using bremsstrahlung at γELBE, we perform simulations of statistical γ-ray cascades using the code γDEX to estimate intensities of inelastic transitions to low-lying excited states. Simulated average branching ratios are compared with model-independent branching ratios obtained from spectra measured by using monoenergetic γ beams at HIγS. E1 strength in the energy region of the pygmy dipole resonance is discussed in nuclei around mass 90 and in xenon isotopes. M1 strength in the region of the spin-flip resonance is also considered for xenon isotopes. The dipole strength function of 74Ge deduced from γELBE experiments is compared with the one obtained from experiments at the Oslo Cyclotron Laboratory. The low-energy upbend seen in the Oslo data is interpreted as M1 strength on the basis of shell-model calculations.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Panot Tangsucharit

    2016-01-01

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

  2. 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.

  3. 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.

  4. Molecular Probes for Muscarinic Receptors: Derivatives of the M1-Antagonist Telenzepine

    Science.gov (United States)

    Karton, Yishai; Baumgold, Jesse; Handen, Jeffrey S.; Jacobson, Kenneth A.

    2012-01-01

    Functionalized congeners of the M1-selective muscarinic antagonist telenzepine (4,9-dihydro-3-methyl-4-[(4-methyl-1-piperazinyl)acetyl]-10H-thieno[3,4–b][1,5]benzodiazepin-10-one) were developed and found to bind to the receptor with affinities (Ki values) in approximately the nanomolar range. The derivatives contain a 10-aminodecyl group, which provides a nucleophilic functionality for further derivatization. The attachment of a spacer chain to the distal piperazinyl nitrogen was based on previous findings of enhanced affinity at muscarinic receptors in an analogous series of alkylamino derivatives of pirenzepine [J. Med. Chem. (1991) 34, 2133–2145]. The telenzepine derivatives contain prosthetic groups for radioiodination, protein cross-linking, photoaffinity labeling, and fluorescent labeling and biotin for avidin complexation. The affinity for muscarinic receptors in rat forebrain (mainly m1 subtype) was determined in competitive binding assays vs [3H]-N-methylscopolamine. A (p-aminophenyl)-acetyl derivative for photoaffinity labeling had a Ki value of 0.29 nM at forebrain muscarinic receptors (16-fold higher affinity than telenzepine). A biotin conjugate displayed a Ki value of 0.60 nM at m2-receptors and a 5-fold selectivity versus forebrain. The high affinity of these derivatives makes them suitable for the characterization of muscarinic receptors in pharmacological and spectroscopic studies, for peptide mapping, and for histochemical studies. PMID:1520727

  5. Effects of butanol isomers on dipalmitoylphosphatidylcholine bilayer membranes.

    Science.gov (United States)

    Reeves, Megan D; Schawel, Adam K; Wang, Weidong; Dea, Phoebe

    2007-06-01

    Differential scanning calorimetry and (31)P-NMR were used to study the effects of butanol isomers on the thermotropic phase behavior of dipalmitoylphosphatidylcholine (DPPC) bilayers. The threshold concentration for the onset of interdigitation for each isomer was determined by the disappearance of the pretransition and the onset of a large hysteresis between the heating and cooling scans of the gel-to-liquid main transition. The threshold concentration was found to correlate with increased solubility of the isomers in the aqueous phase, led by tert-butanol. However, as the solution concentration of tert-butanol increased, there was an abrupt shrinking of the hysteresis, initially with well-resolved shoulder peaks indicating mixed phases. The eventual disappearance of the shoulder peaks was correlated with a breakdown of the multilamellar structure identified using (31)P-NMR.

  6. 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...

  7. 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.

  8. Downregulation of cystathionine β-synthase/hydrogen sulfide contributes to rotenone-induced microglia polarization toward M1 type.

    Science.gov (United States)

    Du, Chenchen; Jin, Mengmeng; Hong, Yu; Li, Qian; Wang, Xian-Hui; Xu, Jin-Min; Wang, Fen; Zhang, Ye; Jia, Jia; Liu, Chun-Feng; Hu, Li-Fang

    2014-08-22

    Microglia-mediated neuroinflammation is implicated in the pathogenesis of several neurodegenerative disorders. Microglia can be activated and polarized to exert pro- or anti-inflammatory roles in response to specific stimulus. Rotenone is an environmental toxin that has been shown to activate microglia and neuroinflammation. However, the effects and mechanisms of rotenone on microglia polarization are poorly studied. In the present study, we demonstrated that rotenone enhanced the levels of M1 phenotypic genes including TNF-α, iNOS and COX-2/PGE2 but reduced that of M2 markers such as Ym1/2 and IL-10 in mouse primary and immortalized microglia. Moreover, the transcription and protein expression of cystathionine-β-synthase (CBS), as well as hydrogen sulfide (H2S) production were decreased in rotenone-treated primary microglia. Elevating endogenous H2S via CBS over-expression in immortalized microglia not only reduced the expression of pro-inflammatory M1 genes, but also enhanced the anti-inflammatory M2 marker IL-10 production in response to rotenone stimulation as compared to vector-transfected cells. Similarly, pretreatment with H2S donor NaHS (50, 100 and 500μmol/L) attenuated the increases of M1 gene expression triggered by rotenone treatment, and enhanced the M2 gene Ym1/2 expression in mouse primary microglia. In addition, we observed reactive oxygen species (ROS) scavenger N-acetyl-l-cysteine reversed the down-regulation of CBS and H2S generation caused by rotenone in microglia. NaHS pretreatment also decreased the ROS formation in rotenone-stimulated microglia. Taken together, these results reveal that probably via triggering ROS formation, rotenone suppressed the CBS-H2S pathway and thus promoted microglia polarization toward M1 pro-inflammatory phenotype.

  9. Presence of moulds and aflatoxin M1 in milk

    Directory of Open Access Journals (Sweden)

    Janković Vesna V.

    2009-01-01

    Full Text Available Aflatoxin M1 (AFM1 appears in milk or dairy products as a direct result of the cattle's ingestion of feed contaminated with aflatoxin B1 (AFB1. This study comprises mycological and mycotoxicological investigations of 23 milk samples (raw, infant food, pasteurized, whey and yoghurt. The mycological testing showed dominant presence of genus Geotrichum. G. candidum was found in 9 samples, with the highest contamination in the raw milk samples. The contamination level of AM1 is defined by using direct competitive enzyme- -linked immunosorbent assay (ELISA. AFM1 was found in 9 samples. AFM1 levels were lower than the recommended limits. However, as AFM1 is considered a probable human carcinogen (2B type, it is necessary to achieve a low level of AFM1 in milk. Therefore, cows' feed samples from various cowsheds are supposed to be evaluated routinely for aflatoxin, and kept away from fungal contamination as much as possible.

  10. Aflatoxin M1 Contamination in Ice-Cream

    Directory of Open Access Journals (Sweden)

    R. Kazemi Darsanaki

    2013-06-01

    Full Text Available Aflatoxin M1 (AFM1 is the hydroxylated metabolite of aflatoxin B1 (AFB1 that it can be found in milk and dairy products. In this study, ELISA (Enzyme Linked Immunosorbent Assay technique was used for detection of AFM1 in ice-cream in Guilan province (Northern Iran. A total of 90 ice-cream samples was randomly obtained from different supermarkets. In 62 of the 90 ice-cream samples examined (68.88%, the presence of AFM1 was detected in concentrations between 8.4 -147.7 ng/l. The mean level of AFM1 in positive samples was 40.36 ng/l. AFM1 levels in 11 samples (12.22% were higher than the maximum tolerance limit (50 ng/l accepted by ISIRI, European Community and Codex Alimentarius.

  11. Theoretical Study of the Diastereofacial Isomers of Aldrin and Dieldrin

    Directory of Open Access Journals (Sweden)

    Zoran Zdravkovski

    2006-02-01

    Full Text Available The Diels-Alder reaction of hexachlorocyclopentadiene with norbornadiene givesaldrin but theoretically three other diastereofacial isomers are possible. On oxidation theseisomers can generate eight adducts one of which is known as dieldrin. All these, as well asthe corresponding reactions with hexafluorocyclopenadiene were studied by semiempirical(AM1 and PM3 and hybrid density functional (B3LYP methods. Besides the energy levels,the transition states were calculated for the reactions leading to the diastereofacial isomers ofaldrin, which indicate that aldrin is the favored product of the reaction both fromthermodynamic and kinetic point of view.

  12. Enhanced M1 macrophage polarization in human helicobacter pylori-associated atrophic gastritis and in vaccinated mice.

    Directory of Open Access Journals (Sweden)

    Marianne Quiding-Järbrink

    Full Text Available BACKGROUND: Infection with Helicobacter pylori triggers a chronic gastric inflammation that can progress to atrophy and gastric adenocarcinoma. Polarization of macrophages is a characteristic of both cancer and infection, and may promote progression or resolution of disease. However, the role of macrophages and their polarization during H. pylori infection has not been well defined. METHODOLOGY/PRINCIPAL FINDINGS: By using a mouse model of infection and gastric biopsies from 29 individuals, we have analyzed macrophage recruitment and polarization during H. pylori infection by flow cytometry and real-time PCR. We found a sequential recruitment of neutrophils, eosinophils and macrophages to the gastric mucosa of infected mice. Gene expression analysis of stomach tissue and sorted macrophages revealed that gastric macrophages were polarized to M1 after H. pylori infection, and this process was substantially accelerated by prior vaccination. Human H. pylori infection was characterized by a mixed M1/M2 polarization of macrophages. However, in H. pylori-associated atrophic gastritis, the expression of inducible nitric oxide synthase was markedly increased compared to uncomplicated gastritis, indicative of an enhanced M1 macrophage polarization in this pre-malignant lesion. CONCLUSIONS/SIGNIFICANCE: These results show that vaccination of mice against H. pylori amplifies M1 polarization of gastric macrophages, and that a similar enhanced M1 polarization is present in human H. pylori-induced atrophic gastritis.

  13. 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.

  14. 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.

  15. 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.

  16. Isomer and decay studies for the rp process at IGISOL

    Energy Technology Data Exchange (ETDEWEB)

    Kankainen, A.; Elomaa, V.V.; Eronen, T.; Hakala, J.; Jokinen, A.; Karvonen, P.; Reponen, M.; Rissanen, J.; Saastamoinen, A.; Weber, C.; Aeystoe, J. [University of Jyvaeskylae, Department of Physics, Jyvaeskylae (Finland); Novikov, Yu.N.; Batist, L. [Petersburg Nuclear Physics Institute, Gatchina (Russian Federation); Oinonen, M. [University of Helsinki, Dating Laboratory, Helsinki (Finland); Vorobjev, G. [Gesellschaft fuer Schwerionenforschung mbH, Darmstadt (Germany)

    2012-04-15

    This article reviews the decay studies of neutron-deficient nuclei within the mass region A=56-100 performed at the Ion-Guide Isotope Separator On-Line (IGISOL) facility in the University of Jyvaeskylae over last 25 years. Development from He-jet measurements to on-line mass spectrometry, and eventually to atomic mass measurements and post-trap spectroscopy at IGISOL, has yielded studies of around 100 neutron-deficient nuclei over the years. The studies form a solid foundation to astrophysical rp -process path modelling. The focus is on isomers studied either via spectroscopy or via Penning-trap mass measurements. The review is complemented with recent results on the ground and isomeric states of {sup 90}Tc. The excitation energy of the low-spin isomer in {sup 90}Tc has been measured as E{sub x}=144.1(17) keV with JYFLTRAP double Penning trap and the ground state of {sup 90}Tc has been confirmed to be the (8{sup +}) state with a half-life of T{sub 1/2}=49.2(4) s. Finally, the mass-excess results for the spin-gap isomers {sup 53}Co{sup m} and {sup 95}Pd{sup m} and implications from the JYFLTRAP mass measurements for the (21{sup +}) isomer in {sup 94}Ag are discussed. (orig.)

  17. ISOMER-SELECTED DECAY OF THE GDR IN DY-156

    NARCIS (Netherlands)

    VANSCHAGEN, JPS; HARAKEH, MN; HESSELINK, WHA; NOORMAN, RF

    1995-01-01

    The strength distribution of high-energy gamma-rays emitted in the statistical decay of the 156Dy compound nucleus, with E* = 92.5 MeV, has been measured inclusively and for selected decay pathways in which isomers in 149Dy, 151Dy and 152Dy were populated. For both spectra a deformation \\beta\\ = 0.3

  18. The molecular properties of nitrobenzanthrone isomers and their mutagenic activities.

    Science.gov (United States)

    Ostojić, Bojana D; Stanković, Branislav; Ðorđević, Dragana S

    2014-06-01

    The mutagenic activity of five mono-substituted nitrobenzanthrones (NBA) has been determined in the Ames assay (Takamura-Enya et al., 2006). In the present study, a theoretical investigation of the electronic properties of all mono-substituted NBA isomers and their relation to mutagenic activity are presented. Equilibrium geometries, vertical ionization potentials (VIP), vertical electron affinities (VEA), relative energies, dipole moments and electronic dipole polarizabilities, and the IR and Raman spectra of NBA isomers calculated by Density Functional Theory (DFT) methods are presented. The position of the nitro group affects the spectral features of the IR and Raman spectra of the NBA isomers. The results show that a good linear relationship exists between the summation of Raman activities (∑ARaman) over all the 3N-6 vibrational modes and the mutagenic activity of the NBA isomers in Salmonella typhimurium strains. The spectroscopic results suggest that the unknown mutagenic activities of 4-NBA, 5-NBA, 6-NBA, 8-NBA and 10-NBA are predicted to follow the order 4-NBA>10-NBA>5-NBA>8-NBA>6-NBA. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. High Spin Isomers and Super Heavy Elements (SHE) Synthesis

    Science.gov (United States)

    Popescu, Domitian G.

    2010-04-01

    To get closer to the SHE-Island the new radioactive beams are proposed for future fusion reaction. We suggest something different : to use the advantage of High Spin Isomer States, by tacking into account the importance of the G (spin-isospin cupling) suggested by Ripka 1.

  20. Identification of position isomers by energy-resolved mass spectrometry.

    Science.gov (United States)

    Menachery, Sunil Paul M; Laprévote, Olivier; Nguyen, Thao P; Aravind, Usha K; Gopinathan, Pramod; Aravindakumar, Charuvila T

    2015-07-01

    This study reports an energy-resolved mass spectrometric (ERMS) strategy for the characterization of position isomers derived from the reaction of hydroxyl radicals ((●)OH) with diphenhydramine (DPH) that are usually hard to differentiate by other methods. The isomer analogues formed by (●)OH attack on the side chain of DPH are identified with the help of a specific fragment ion peak (m/z 88) in the collision-induced dissociation (CID) spectrum of the protonated molecule. In the negative ion mode, the breakdown curves of the deprotonated molecules show an order of stability (supported by density functional theory (DFT) calculations) ortho > meta > para of the positional isomers formed by the hydroxylation of the aromatic ring. The gas phase stability of the deprotonated molecules [M - H](-) towards the benzylic cleavage depends mainly on the formation of intramolecular hydrogen bonds and of the mesomeric effect of the phenol hydroxyl. The [M - H](-) molecules of ortho and meta isomers result a peak at m/z 183 with notably different intensities because of the presence/absence of an intramolecular hydrogen bonding between the OH group and C9 protons. The ERMS approach discussed in this report might be an effective replacement for the conventional methods that requires very costly and time-consuming separation/purification methods along with the use of multi-spectroscopic methods.

  1. Generalized seniority states and isomers in tin isotopes

    Science.gov (United States)

    Jain, Ashok Kumar; Maheshwari, Bhoomika

    2017-07-01

    Isomeric studies in neutron-rich nuclei are a powerful tool for exploring structure at the nuclear extremes. In this paper we discuss the systematic features of the excitation energies and transition probabilities of Sn isotopes in the region N = 50-82 and present their basic understanding in terms of generalized seniority. We further use generalized seniority as a probe to explore the neutron-rich {6}+ seniority isomers in 134-138Sn, and to validate the neutron single-particle energies beyond N = 82. We show that these isomers behave as generalized seniority isomers, where the so-called anomalous {{B}}(E2) behavior of the {6}+ isomer in 136Sn may be naturally explained. We support these results by shell model calculations, where the latest neutron single-particle energies of the N = 82-126 region have been used, and the i13/2 neutron single-particle energy has been suitably modified in the renormalized charge-dependent Bonn interaction. This entails a possible new subshell closure at N = 112 due to the suggested higher location of the i13/2 neutron orbital, also consistent with the choice of orbitals in the generalized seniority scheme. However, a small reduction in the f7/2 two-body matrix elements is still required in the shell model calculations to consistently reproduce the experimental level energies as well as the transition probabilities in 134-138Sn isotopes.

  2. Shape Isomer in 236U Populated by Thermal Neutron Capture

    DEFF Research Database (Denmark)

    Andersen, Verner; Christensen, Carl Jørgen; Borggreen, J.

    1976-01-01

    The 116 ns shape isomer in 236U was populated by thermal neutron capture. Conversion electrons and X-rays were detected simultaneously in delayed coincidence with fission. The ratio of delayed to prompt fission was measured with the result, σIIf/σf = (1.0±0.2) × 10−5. A branching of the isomeric...

  3. Thorium isomer for radiative emission of neutrino pair

    CERN Document Server

    Sasao, N; Yoshimi, A; Yoshimura, K; Yoshimura, M

    2013-01-01

    It is proposed to use the isomer ionic ground state $^{229m}$Th$^{4+}$ embedded in transparent crystals for precision determination of unknown neutrino parameters. Isolation from solid environment of the proposed nuclear process, along with available experimental techniques of atomic physics, has a great potentiality for further study.

  4. Unstable $m=1$ modes of counter-rotating Keplerian discs

    CERN Document Server

    Gulati, Mamta; Sridhar, S

    2012-01-01

    We study the linear $m=1$ counter-rotating instability in a two-component, nearly Keplerian disc. Our goal is to understand these \\emph{slow} modes in discs orbiting massive black holes in galactic nuclei. They are of interest not only because they are of large spatial scale--and can hence dominate observations--but also because they can be growing modes that are readily excited by accretion events. Self-gravity being nonlocal, the eigenvalue problem results in a pair of coupled integral equations, which we derive for a two-component softened gravity disc. We solve this integral eigenvalue problem numerically for various values of mass fraction in the counter-rotating component. The eigenvalues are in general complex, being real only in the absence of the counter-rotating component, or imaginary when both components have identical surface density profiles. Our main results are as follows: (i) the pattern speed appears to be non negative, with the growth (or damping) rate being larger for larger values of the ...

  5. The conformational flexibility of the antibiotic virginiamycin M(1).

    Science.gov (United States)

    Dang, Jason; Metzger, Robert P; Brownlee, Robert T C; Ng, Chai Ann; Bergdahl, Mikael; Separovic, Frances

    2005-07-01

    The antibiotic virginiamycin is a combination of two molecules, virginiamycin M(1) (VM1) and virginiamycin S(1) (VS1) or analogues, which function synergistically by binding to bacterial ribosomes and inhibiting bacterial protein synthesis. Both VM1 and VS1 dissolve poorly in water and are soluble in more hydrophobic solvents. We have recently reported that the 3D conformation of VM1 in CDCl(3) solution differs markedly from the conformation bound to a VM1 binding enzyme and to 50S ribosomes as found by X-ray crystallographic studies. We now report the results of further NMR studies and subsequent molecular modeling of VM1 dissolved in CD(3)CN/H(2)O and compare the structure with that in CD(3)OD and CDCl(3). The conformations of VM1 in CD(3)CN/H(2)O, CD(3)OD and CDCl(3) differ substantially from one another and from the bound form, with the aqueous form most like the bound structure. We propose that the flexibility of the VM1 molecule in response to environmental conditions contributes to its effectiveness as an antibiotic.

  6. The m=1 amplituhedron and cyclic hyperplane arrangements

    CERN Document Server

    Karp, Steven N

    2016-01-01

    The (tree) amplituhedron A(n,k,m) is the image in the Grassmannian Gr(k,k+m) of the totally nonnegative part of Gr(k,n), under a (map induced by a) linear map which is totally positive. It was introduced by Arkani-Hamed and Trnka in 2013 in order to give a geometric basis for the computation of scattering amplitudes in N=4 supersymmetric Yang-Mills theory. When k+m=n, the amplituhedron is isomorphic to the totally nonnegative Grassmannian, and when k=1, the amplituhedron is a cyclic polytope. While the case m=4 is most relevant to physics, the amplituhedron is an interesting mathematical object for any m. In this paper we study it in the case m=1. We start by taking an orthogonal point of view and define a related "B-amplituhedron" B(n,k,m), which we show is isomorphic to A(n,k,m). We use this reformulation to describe the amplituhedron in terms of sign variation. We then give a cell decomposition of the amplituhedron A(n,k,1) using the images of a collection of distinguished cells of the totally nonnegative ...

  7. Abundances of Planetary Nebula M1-42

    CERN Document Server

    Pottasch, S R; Roellig, T L

    2007-01-01

    The spectra of the planetary nebula M1-42 is reanalysed using spectral measurements made in the mid-infrared with the Spitzer Space Telescope. The aim is to determine the chemical composition of this object. We also make use of ISO, IUE and ground based spectra. Abundances determined from the mid- and far-infrared lines, which are insensitive to electron temperature, are used as the basis for the determination of the composition, which are found to substantially differ from earlier results. High values of neon, argon and sulfur are found. They are higher than in other PN, with the exception of NGC6153, a nebula of very similar abundances. The high values of helium and nitrogen found indicate that the second dredge-up and hot bottom burning has occurred in the course of evolution and that the central star was originally more massive than 4Msun. The present temperature and luminosity of the central star is determined and at first sight may be inconsistent with such a high mass.

  8. Thermoelectric waste heat recovery from an M1 Abrams tank

    Science.gov (United States)

    Stokes, C. David; Thomas, Peter M.; Baldasaro, Nicholas G.; Mantini, Michael J.; Venkatasubramanian, Rama; Barton, Michael D.; Cardine, Christopher V.; Walker, Grayson W.

    2012-06-01

    The addition of advanced sensors, targeting systems and electronic countermeasures to military vehicles has created a strategic need for additional electric power. By incorporating a thermoelectric (TE) waste heat recovery system to convert available exhaust heat to electricity, increased electric power needs can be met without reducing the energy efficiency of the vehicle. This approach allows existing vehicles to be upgraded without requiring a complete re-design of the engine and powertrain to support the integration of advanced electronic sensors and systems that keep the performance at the state of the art level. RTI has partnered with General Dynamics Land Systems and Creare, Inc. under an Army Research Lab program to develop a thermoelectric exhaust waste heat recovery system for the M1 Abrams tank. We have designed a reduced-scale system that was retrofitted to the tank and generated 80W of electric power on the vehicle operating on a test track by capturing a portion of the exhaust heat from the Honeywell/Lycoming AGT-1500 gas turbine engine.

  9. FY2011 Annual Report for the Actinide Isomer Detection Project

    Energy Technology Data Exchange (ETDEWEB)

    Warren, Glen A.; Francy, Christopher J.; Ressler, Jennifer J.; Erikson, Luke E.; Tatishvili, Gocha; Hatarik, R.

    2011-10-01

    This project seeks to identify a new signature for actinide element detection in active interrogation. This technique works by exciting and identifying long-lived nuclear excited states (isomers) in the actinide isotopes and/or primary fission products. Observation of isomers in the fission products will provide a signature for fissile material. For the actinide isomers, the decay time and energy of the isomeric state is unique to a particular isotope, providing an unambiguous signature for SNM. This project entails isomer identification and characterization and neutron population studies. This document summarizes activities from its third year - completion of the isomer identification characterization experiments and initialization of the neutron population experiments. The population and decay of the isomeric state in 235U remain elusive, although a number of candidate gamma rays have been identified. In the course of the experiments, a number of fission fragment isomers were populated and measured [Ressler 2010]. The decays from these isomers may also provide a suitable signature for the presence of fissile material. Several measurements were conducted throughout this project. This report focuses on the results of an experiment conducted collaboratively by PNNL, LLNL and LBNL in December 2010 at LBNL. The measurement involved measuring the gamma-rays emitted from an HEU target when bombarded with 11 MeV neutrons. This report discussed the analysis and resulting conclusions from those measurements. There was one strong candidate, at 1204 keV, of an isomeric signature of 235U. The half-life of the state is estimated to be 9.3 {mu}s. The measured time dependence fits the decay time structure very well. Other possible explanations for the 1204-keV state were investigated, but they could not explain the gamma ray. Unfortunately, the relatively limited statistics of the measurement limit, and the lack of understanding of some of the systematic of the experiment, limit

  10. 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.

  11. 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.

  12. Dopamine induces growth inhibition and vascular normalization through reprogramming M2-polarized macrophages in rat C6 glioma

    Energy Technology Data Exchange (ETDEWEB)

    Qin, Tian; Wang, Chenlong; Chen, Xuewei; Duan, Chenfan; Zhang, Xiaoyan [Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Zhang, Jing [Animal Experimental Center of Wuhan University, Wuhan 430071 (China); Chai, Hongyan [Center for Gene Diagnosis, Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Tang, Tian [Department of Oncology, Renmin Hospital of Wuhan University, Wuhan 430060 (China); Chen, Honglei [Department of Pathology and Pathophysiology, School of Medicine, Wuhan University, Wuhan 430071 (China); Yue, Jiang [Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Li, Ying, E-mail: lyying0@163.com [Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China); Yang, Jing, E-mail: yangjingliu2013@163.com [Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071 (China)

    2015-07-15

    Dopamine (DA), a monoamine catecholamine neurotransmitter with antiangiogenic activity, stabilizes tumor vessels in colon, prostate and ovarian cancers, thus increases chemotherapeutic efficacy. Here, in the rat C6 glioma models, we investigated the vascular normalization effects of DA and its mechanisms of action. DA (25, 50 mg/kg) inhibited tumor growth, while a precursor of DA (levodopa) prolonged the survival time of rats bearing orthotopic C6 glioma. DA improved tumor perfusion, with significant effects from day 3, and a higher level at days 5 to 7. In addition, DA decreased microvessel density and hypoxia-inducible factor-1α expression in tumor tissues, while increasing the coverage of pericyte. Conversely, an antagonist of dopamine receptor 2 (DR2) (eticlopride) but not DR1 (butaclamol) abrogated DA-induced tumor regression and vascular normalization. Furthermore, DA improved the delivery and efficacy of temozolomide therapy. Importantly, DA increased representative M1 markers (iNOS, CXCL9, etc.), while decreasing M2 markers (CD206, arginase-1, etc.). Depletion of macrophages by clodronate or zoledronic acid attenuated the effects of DA. Notably, DA treatment induced M2-to-M1 polarization in RAW264.7 cells and mouse peritoneal macrophages, and enhanced the migration of pericyte-like cells (10T1/2), which was reversed by eticlopride or DR2-siRNA. Such changes were accompanied by the downregulation of VEGF/VEGFR2 signaling. In summary, DA induces growth inhibition and vascular normalization through reprogramming M2-polarized macrophages. Thus, targeting the tumor microvasculature by DA represents a promising strategy for human glioma therapy. - Highlights: • Dopamine induces tumor growth inhibition and vascular normalization in rat C6 glioma. • Dopamine switches macrophage phenotype from M2 to M1. • Dopamine-induced vascular normalization is mediated by macrophage polarization. • Dopamine is a promising agent targeting the microvasculature in tumor

  13. 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.

  14. The M1 form of tumor-associated macrophages in non-small cell lung cancer is positively associated with survival time

    Directory of Open Access Journals (Sweden)

    Dai Fuqiang

    2010-03-01

    Full Text Available Abstract Background Tumor-associated macrophages (TAMs play an important role in growth, progression and metastasis of tumors. In non-small cell lung cancer (NSCLC, TAMs' anti-tumor or pro-tumor role is not determined. Macrophages are polarized into M1 (with anti-tumor function and M2 (with pro-tumor function forms. This study was conducted to determine whether the M1 and M2 macrophage densities in NSCLC are associated with patient's survival time. Methods Fifty patients with an average of 1-year survival (short survival group and 50 patients with an average of 5-year survival (long survival group were included in this retrospective study. Paraffin-embedded NSCLC specimens and their clinicopathological data including up to 8-year follow-up information were used. Immunohistochemical double-staining of CD68/HLA-DR (markers for M1 macrophages and CD68/CD163 (markers for M2 macrophages was performed and evaluated in a blinded fashion. The M1 and M2 macrophage densities in the tumor islets, stroma, or islets and stroma were determined using computer-aided microscopy. Correlation of the macrophage densities and patient's survival time was analyzed using the Statistical Package for the Social Sciences. Results Approximately 70% of TAMs were M2 macrophages and the remaining 30% were M1 macrophages in NSCLC. The M2 macrophage densities (approximately 78 to 113 per mm2 in the tumor islets, stroma, or islets and stroma were not significantly different between the long survival and short survival groups. The M1 macrophage densities in the tumor islets (approximately 70/mm2 and stroma (approximately 34/mm2 of the long survival group were significantly higher than the M1 macrophage densities in the tumor islets (approximately 7/mm2 and stroma (13/mm2 of the short survival group (P Conclusions The M1 macrophage density in the tumor islets is an independent predictor of survival time in NSCLC patients.

  15. Isomer-specific regulation of metabolism and PPARγ signaling by CLA in human preadipocytes

    OpenAIRE

    Brown, J. Mark; Boysen, Maria Sandberg; Jensen, Søren Skov; Morrison, Ron F.; Storkson, Jayne; Lea-Currie, Renee; Pariza, Michael; Mandrup, Susanne; McIntosh, Michael K.

    2003-01-01

    Trans-10,cis-12 conjugated linoleic acid (CLA) has previously been shown to be the CLA isomer responsible for CLA-induced reductions in body fat in animal models, and we have shown that this isomer, but not the cis-9,trans-11 CLA isomer, specifically decreased triglyceride (TG) accumulation in primary human adiopcytes in vitro. Here we investigated the mechanism behind the isomer-specific, CLA-mediated reduction in TG accumulation in differentiating human preadipocytes. Trans-10,cis-12 CLA de...

  16. 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.

  17. Stress-induced VO{sub 2} films with M2 monoclinic phase stable at room temperature grown by inductively coupled plasma-assisted reactive sputtering

    Energy Technology Data Exchange (ETDEWEB)

    Okimura, Kunio; Watanabe, Tomo [School of Engineering, Tokai University, 4-1-1 Kitakaname, Hiratsuka, Kanagawa 259-1292 (Japan); Sakai, Joe [GREMAN, UMR 7347 CNRS, Universite Francois Rabelais de Tours, Parc de Grandmont 37200 Tours (France)

    2012-04-01

    We report on growth of VO{sub 2} films with M2 monoclinic phase stable at room temperature under atmospheric pressure. The films were grown on quartz glass and Si substrates by using an inductively coupled plasma-assisted reactive sputtering method. XRD-sin{sup 2}{Psi} measurements revealed that the films with M2 phase are under compressive stress in contrast to tensile stress of films with M1 phase. Scanning electron microscopy observations revealed characteristic crystal grain aspects with formation of periodical twin structure of M2 phase. Structural phase transition from M2 to tetragonal phases, accompanied by a resistance change, was confirmed to occur as the temperature rises. Growth of VO{sub 2} films composed of M2 phase crystalline is of strong interest for clarifying nature of Mott transition of strongly correlated materials.

  18. Substance P Induces HO-1 Expression in RAW 264.7 Cells Promoting Switch towards M2-Like Macrophages

    Science.gov (United States)

    Montana, Giovanna

    2016-01-01

    Substance P (SP) is a neuropeptide that mediates many physiological as well as inflammatory responses. Recently, SP has been implicated in the resolution of inflammation through induction of M2 macrophages phenotype. The shift between M1-like and M2-like, allowing the resolution of inflammatory processes, also takes place by means of hemeoxygenase-1 (HO-1). HO-1 is induced in response to oxidative stress and inflammatory stimuli and modulates the immune response through macrophages polarisation. SP induces HO-1 expression in human periodontal ligament (PDL), the latter potentially plays a role in cytoprotection. We demonstrated that SP promotes M2-like phenotype from resting as well as from M1 macrophages. Indeed, SP triggers the production of interleukine-10 (IL-10), interleukine-4 (IL-4) and arginase-1 (Arg1) without nitric oxide (NO) generation. In addition, SP increases HO-1 expression in a dose- and time-dependent manner. Here we report that SP, without affecting cell viability, significantly reduces the production of pro-inflammatory cytokines and enzymes, such as tumor necrosis factor-alpha (TNF-α), interleukine-6 (IL-6), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and ameliorates migration and phagocytic properties in LPS-stimulated RAW 264.7 cells. M2-like conversion required retention of NF-κB p65 into the cytoplasm and HO-1 induced expression. Silencing of the HO-1 mRNA expression reversed the induction of pro-inflammatory cytokines in RAW 264.7 stimulated by LPS and down-regulated anti-inflammatory hallmarks of M2 phenotype. In conclusion, our data show that SP treatment might be associated with anti-inflammatory effects in LPS-stimulated RAW 264.7 cells by suppressing NF-κB activation and inducing HO-1 expression. PMID:27907187

  19. 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.

  20. 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.)

  1. Enhancement of CD147 on M1 macrophages induces differentiation of Th17 cells in the lung interstitial fibrosis.

    Science.gov (United States)

    Geng, Jie-jie; Zhang, Kui; Chen, Li-na; Miao, Jin-lin; Yao, Meng; Ren, Ying; Fu, Zhi-guang; Chen, Zhi-nan; Zhu, Ping

    2014-09-01

    Lung interstitial fibrosis is a chronic lung disease, and few effective therapies are available to halt or reverse the progression of the disease. In murine and human lung fibrosis, the expression of CD147 is increased. However, the role of CD147 in lung fibrosis has not been identified, and it remains to be determined whether lung fibrosis would be improved by decreasing the expression of CD147. A murine bleomycin-induced lung interstitial fibrosis model was used in the experiments, and HAb18 mAbs and CsA were administered during the induction of lung fibrosis. In our study, we found that the HAb18 mAbs markedly reduced the collagen score and down-regulated M1 macrophages and Th17 cells. In vitro, flow cytometry analysis showed that M1 macrophages induced higher Th17 differentiation than M2 macrophages. After treatment with HAb18 mAbs or after reducing the expression of CD147 by lentivirus interference in M1 macrophages, the level of Th17 cells were significantly inhibited. In conclusion, HAb18 mAbs or CsA treatment ameliorates lung interstitial fibrosis. CD147 promoted M1 macrophage and induced the differentiation of Th17 cells in lung interstitial fibrosis, perhaps by regulating some cytokines such as IL-6, IL-1β, IL-12 and IL-23. These results indicated that CD147 may play an important role in the development of lung interstitial fibrosis.

  2. Paracoccin Induces M1 Polarization of Macrophages via Interaction with TLR4

    Science.gov (United States)

    Freitas, Mateus S.; Oliveira, Aline F.; da Silva, Thiago A.; Fernandes, Fabrício F.; Gonçales, Relber A.; Almeida, Fausto; Roque-Barreira, Maria C.

    2016-01-01

    The fungal human pathogen Paracoccidioides brasiliensis contains paracoccin (PCN), a multi-domain protein that has lectin and N-acetyl-glucosaminidase activities, which account for its effects on the growth and morphogenesis of the fungus and on the activation of host macrophages through its interaction with TLR N-glycans. With the purpose of detailing the knowledge on the effects of PCN on macrophages, we used recombinant PCN expressed in Pichia pastoris (p-rPCN) to stimulate isolated murine peritoneal macrophages. The activation of these cells manifested through the release of high levels of inflammatory mediators, such as nitric oxide, TNF-α, IL-12p40, and IL-6. Furthermore, peritoneal macrophages stimulated with p-rPCN increased the relative expression of STAT1, SOCS3, and iNOS2 mRNA (M1 polarization markers). However, the expression of Arginase-1, Ym-1, and FIZZ1 (M2 polarization markers) remained at basal levels. Interestingly, the observed M1 macrophages’ polarization triggered by p-rPCN was abolished in cells obtained from knockout Toll-like receptor-4 mice. In this case, the p-rPCN-induced production of pro-inflammatory mediators was blocked too. These results demonstrate that the classical activation of macrophages induced by paracoccin depends on TLR4. Taken together, the results of our study indicate that paracoccin acts as a TLR agonist able to modulate immunity and exerts biological activities that favor its applicability as an immunotherapeutic agent to combat systemic fungal infections. PMID:27458431

  3. Recruitment of beneficial M2 macrophages to injured spinal cord is orchestrated by remote brain choroid plexus.

    Science.gov (United States)

    Shechter, Ravid; Miller, Omer; Yovel, Gili; Rosenzweig, Neta; London, Anat; Ruckh, Julia; Kim, Ki-Wook; Klein, Eugenia; Kalchenko, Vyacheslav; Bendel, Peter; Lira, Sergio A; Jung, Steffen; Schwartz, Michal

    2013-03-21

    Monocyte-derived macrophages are essential for recovery after spinal cord injury, but their homing mechanism is poorly understood. Here, we show that although of common origin, the homing of proinflammatory (M1) and the "alternatively activated" anti-inflammatory (M2) macrophages to traumatized spinal cord (SC) was distinctly regulated, neither being through breached blood-brain barrier. The M1 macrophages (Ly6c(hi)CX3CR1(lo)) derived from monocytes homed in a CCL2 chemokine-dependent manner through the adjacent SC leptomeninges. The resolving M2 macrophages (Ly6c(lo)CX3CR1(hi)) derived from monocytes trafficked through a remote blood-cerebrospinal-fluid (CSF) barrier, the brain-ventricular choroid plexus (CP), via VCAM-1-VLA-4 adhesion molecules and epithelial CD73 enzyme for extravasation and epithelial transmigration. Blockage of these determinants, or mechanical CSF flow obstruction, inhibited M2 macrophage recruitment and impaired motor-function recovery. The CP, along with the CSF and the central canal, provided an anti-inflammatory supporting milieu, potentially priming the trafficking monocytes. Overall, our finding demonstrates that the route of monocyte entry to central nervous system provides an instructional environment to shape their function.

  4. Theoretical Prediction on [5]Radialene Sandwich Complexes (CpM)2(C10H10) (Cp = η(5)-C5H5; M = Fe, Co, Ni): Geometry, Spin States, and Bonding.

    Science.gov (United States)

    Liu, Nan-Nan; Xue, Ying-Ying; Ding, Yi-Hong

    2017-02-09

    [5]Radialene, the missing link for synthesis of radialene family, has been finally obtained via the preparation and decomplexation of the [5]radialene-bis-Fe(CO)3 complex. The stability of [5]radialene complex benefits from the coordination with Fe(CO)3 by losing free 1,3-butadiene structures to avoid polymerization. In light of the similar coordination ability of half-sandwiches CpM(Cp = η(5)-C5H5; M = Fe, Co, Ni), there is a great possibility that the sandwiched complexes of [5]radialene with CpM are available. Herein, we present the first theoretical prediction on the geometry, spin states and bonding of (CpM)(C10H10) and (CpM)2(C10H10). For M = Fe, Co, Ni, the ground states of (CpM)(C10H10) and (CpM)2(C10H10) are doublet and triplet, singlet and singlet, and doublet and triplet states, where each Fe, Co, and Ni adopts 17, 18, and 19 electron-configuration, respectively. In particular, (CpFe)2(C10H10) and (CpNi)2(C10H10) have considerable open-shell singlet features. Generally the trans isomers of (CpM)2(C10H10) with two CpM fragments on the opposite sides of the [5]radialene plane are apparently more stable than the cis ones with CpM fragments on the same side. However, for the singlet and triplet isomers of (CpNi)2(C10H10) (both cis and trans isomers), the energy differences are relatively small, indicating that these isomers all have the opportunity to exist. Besides, the easy Diels-Alder (DA) dimerization between the [3]dendralene-like fragments of (CpM)(C10H10) suggests the great difficulty in isolating the (CpM)(C10H10) monomer.

  5. 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.

  6. Modulation of Effects of Intermittent Theta Burst Stimulation Applied Over Primary Motor Cortex (M1) by Conditioning Stimulation of the Opposite M1

    Science.gov (United States)

    Ragert, Patrick; Camus, Mickael; Vandermeeren, Yves; Dimyan, Michael A.; Cohen, Leonardo G.

    2009-01-01

    The excitability of the human primary motor cortex (M1) as tested with transcranial magnetic stimulation (TMS) depends on its previous history of neural activity. Homeostatic plasticity might be one important physiological mechanism for the regulation of corticospinal excitability and synaptic plasticity. Although homeostatic plasticity has been demonstrated locally within M1, it is not known whether priming M1 could result in similar homeostatic effects in the homologous M1 of the opposite hemisphere. Here, we sought to determine whether down-regulating excitability (priming) in the right (R) M1 with 1-Hz repetitive transcranial magnetic stimulation (rTMS) changes the excitability-enhancing effect of intermittent theta burst stimulation (iTBS) applied over the homologous left (L) M1. Subjects were randomly allocated to one of four experimental groups in a sham-controlled parallel design with real or sham R M1 1-Hz TMS stimulation always preceding L M1 iTBS or sham by about 10 min. The primary outcome measure was corticospinal excitability in the L M1, as measured by recruitment curves (RCs). Secondary outcome measures included pinch force, simple reaction time, and tapping speed assessed in the right hand. The main finding of this study was that preconditioning R M1 with 1-Hz rTMS significantly decreased the excitability-enhancing effects of subsequent L M1 iTBS on RCs. Application of 1-Hz rTMS over R M1 alone and iTBS over L M1 alone resulted in increased RC in L M1 relative to sham interventions. The present findings are consistent with the hypothesis that homeostatic mechanisms operating across hemispheric boundaries contribute to regulate motor cortical function in the primary motor cortex. PMID:19474173

  7. A thirty second isomer in {sup 171}Hf

    Energy Technology Data Exchange (ETDEWEB)

    Campbell, P.; Billowes, J.; Cooper, T.G.; Grant, I.S.; Pearson, M.R.; Wheeler, P.D. [Schuster Laboratory, University of Manchester, M13 9PL (United Kingdom); Cochrane, E.C.A.; Cooke, J.L.; Evans, D.E.; Griffith, J.A.R.; Persson, J.R.; Richardson, D.S.; Tungate, G.; Zybert, L. [School of Physics and Space Research, University of Birmingham, Edgbaston, Birmingham B15 2TT (United Kingdom); Dendooven, P.; Honkanen, A.; Huhta, M.; Oinonen, M.; Penttilae, H.; Aeystoe, J. [Accelerator Laboratory, University of Jyvaeskylae, PL 35 Jyvaeskylae SF-403 51 (Finland)

    1997-09-01

    An isomer has been detected in {sup 171}Hf with a half-life of T{sub 1/2} 29.5(9) s. The state was populated in the {sup 170}Yb({alpha},3n){sup 171m}Hf reaction at a beam energy of E{sub {alpha}} = 50 MeV in an on-line ion guide isotope separator. The isomeric {sup 171m}Hf{sup +} beam was extracted from the ion guide, mass-analysed and implanted in the surface of a microchannel-plate. The half-life of the collected activity was measured from the decay of the microchannel-plate count rate. We associate the isomer with the first excited state in {sup 171}Hf with spin 1/2{sup -} at an excitation energy of 22(2) keV. (author)

  8. Fluorescence characteristics of polychlorinated biphenyl isomers in cyclodextrin media

    Energy Technology Data Exchange (ETDEWEB)

    Femia, R.A.; Scypinski, S.; Love, L.J.C.

    1985-01-01

    The fluorescence characteristics of several polychlorinated biphenyl (PCB) isomers in ..cap alpha..- and ..beta..-cyclodextrin (CD) are discussed and contrasted. The steric hindrance of PCBs imposed by the positions of the chlorine atoms on the rings determines the overall stability of the resulting inclusion complexes with cyclodextrin which is reflected in the fluorescence intensities. Less substituted homologues include into the CD cavity equally well in both cyclodextrins, but very heavily substituted molecules show drastic differences between their fluorescence intensities in the ..cap alpha..- and ..beta..-cyclodextrin solutions. This behavior can be employed as a method for spectral fractionation of PCB isomers. Spectral separation is demonstrated here for two variably substituted molecules, and the photophysical limitations of this approach are discussed.

  9. Spectroscopic Studies of the Several Isomers of UO3

    Energy Technology Data Exchange (ETDEWEB)

    Sweet, Lucas E.; Reilly, Dallas D.; Abrecht, David G.; Buck, Edgar C.; Meier, David E.; Su, Yin-Fong; Brauer, Carolyn S.; Schwantes, Jon M.; Tonkyn, Russell G.; Szecsody, James E.; Blake, Thomas A.; Johnson, Timothy J.

    2013-09-26

    Uranium trioxide is known to adopt seven different structural forms. While these structural forms have been well characterized using x-ray or neutron diffraction techniques, little work has been done to characterize their spectroscopic properties, particularly of the pure phases. Since the structural isomers of UO3 all have similar thermodynamic stabilities and most tend to hydrolyze under open atmospheric conditions, mixtures of UO3 phases and the hydrolysis products are common. Much effort went into isolating pure phases of UO3. Utilizing x-ray diffraction as a sample identification check, UV/Vis/NIR spectroscopic signatures of α-UO3, β-UO3, γ-UO3 and UO2(OH)2 products were obtained. The spectra of the pure phases can now be used to characterize typical samples of UO3, which are often mixtures of isomers.

  10. Observation of the 2$^+$ isomer in $^{52}$Co

    CERN Document Server

    Orrigo, S E A; Gelletly, W; Fujita, Y; Blank, B; Giovinazzo, J; Agramunt, J; Algora, A; Ascher, P; Bilgier, B; Cáceres, L; Cakirli, R B; de France, G; Ganioğlu, E; Gerbaux, M; Grévy, S; Kamalou, O; Kozer, H C; Kucuk, L; Kurtukian-Nieto, T; Molina, F; Popescu, L; Rogers, A M; Susoy, G; Stodel, C; Suzuki, T; Tamii, A; Thomas, J C

    2016-01-01

    We report the first observation of the 2$^+$ isomer in $^{52}$Co, produced in the $\\beta$ decay of the 0$^+$, $^{52}$Ni ground state. We have observed three $\\gamma$-rays at 849, 1910, and 5185 keV characterizing the de-excitation of the isomer. We have measured a half-life of 102(6) ms for the isomeric state. The Fermi and Gamow-Teller transition strengths for the $\\beta$ decay of $^{52m}$Co to $^{52}$Fe have been determined. We also add new information on the $\\beta$ decay of the 6$^+$, $^{52}$Co ground state, for which we have measured a half-life of 112(3) ms.

  11. The structural and dynamical variables of pentane isomers

    Science.gov (United States)

    Patel, Tarika K.; Vaghela, M. V.; Gajjar, P. N.

    2016-05-01

    We derived structural and dynamical properties of pentane isomers: normal pentane, iso-pentane and neo pentane for liquid and gaseous state. We use molecular dynamics simulation to calculate the dynamical properties of pentane isomers for number of particles 729 using the intermolecular potential and force due to Lenard Jones potential. The computations also include mean square displacement and self diffusion co-efficient using Einstein relation. In structural properties, structure factor and phonon frequency are obtaining from P Y Method and Hubbard and Beeby Approach respectively. The Intermolecular potential and self diffusion co-efficient depend on the branching in the structure. The pair correlation function and phonon dispersion curves revels the complex structure of neo-pentane with respect to iso-pentane and n-pentane.

  12. Theoretical characterisation of the SSO, cyclic SOS and SOS isomers

    Science.gov (United States)

    Denis, Pablo A.

    2010-01-01

    The SSO, cyclic SOS and open SOS isomers have been investigated, employing the CCSD(T) methodology and the cc-pV(X + d)Z X = 3, 4, 5, 6 basis sets. The anharmonic force fields have been calculated to predict the fundamental vibrational frequencies, rotational constants, vibration-rotation corrections, anharmonic corrections to zero-point energies, and structural parameters. At the CCSD(T)/CBS limit and including corrections for scalar relativistic effects, complete quadruple excitations, spin-orbit and core-valence correlation effects, the estimated enthalpies of formation are -13.9 ± 1, 32.1 ± 1, and -51.2 ± 1 kcal/mol, for SSO, cyclic-SOS and open-SOS, respectively. Finally, it was found that the asymmetric SO stretch of the open and cyclic SOS isomers are located in a nearly identical position and it is likely that SOS also maybe present in the surface of Io.

  13. Mobilities of Li(+)-attached butanol isomers in He gas.

    Science.gov (United States)

    Takahashi, K; Saito, K; Koizumi, T; Matoba, S; Kojima, T M; Tanuma, H; Shiromaru, H

    2013-08-28

    Mobilities of Li(+)-attached butanol isomers, (n-BuOH)Li(+), (s-BuOH)Li(+), (i-BuOH)Li(+), and (t-BuOH)Li(+), in helium gas were measured over a range of reduced electric fields (E/N = 25-96 Td) at room temperature. Arrival time measurements accurately identified small differences in the measured mobilities of the isomer ions. At low E/N (≤30 Td, corresponding to a mean collision energy ε≤0.05 eV), (n-BuOH)Li(+) showed a mobility about 1.5% greater than that of the other ions, but at high E/N (≥75 Td, ε≥0.1 eV) its mobility was about 1.1% less.

  14. Preparation of Conjugated Linoleic Acid and Identification of Its Isomers

    Institute of Scientific and Technical Information of China (English)

    郭诤; 张根旺; 孙彦

    2003-01-01

    Conjugated linoleic acid(CLA)is a kind of fatty acid with physiological activities and potential appli-cation prospect ,A synthesis method of conjugated linoleic acid and a purification technology were studied .CLA was prepared and purified by urea-complexation and conjugation using safflower oil as raw material,The purity of CLA and total recovery of the product was more than 95% and 48%,respectively,The main isomers produced in alkali-catalyzed conjugation were identified by gas chromatography (GC)linked to mass spectrometry(MS) and Fourier transform infrared spectroscopy(FTIR),The total amount of the two main isomers (9cis,11trans-and 10trans,12cis-CLA) determined by GC was more than 90% of the product.

  15. A simple, rapid method for HPLC analysis of lycopene isomers.

    Science.gov (United States)

    Ishida, B K; Ma, J; Chan, B

    2001-01-01

    A rapid method for the extraction, separation and quantification of the geometric isomers of lycopene and beta-carotene from tomato fruit is described. Carotenoids in tomato were separated and eluted using a reversed-phase HPLC with a C30 column and a mobile phase consisting of methyl-t-butyl ether, methanol and ethyl acetate. The system provided sharp resolution of cis- and trans-isomers of lycopene within approximately 23 min in contrast to the longer and more complex gradient procedures required by previously described methods. Experiments indicate that the stability of extracts of fresh tomato may be improved if stored at -20 degrees C, and that the presence of the antioxidant BHA has no apparent effect on stability.

  16. Condensations of single DNA molecules induced by heptaplatin and its chiral isomer

    Science.gov (United States)

    Zhang, Hong-Yan; Liu, Yu-Ru; Li, Wei; Li, Hui; Dou, Shuo-Xing; Xie, Ping; Wang, Wei-Chi; Wang, Peng-Ye

    2014-08-01

    Heptaplatin is a third-generation platinum antitumor drug. It has a chiral isomer. We studied the interactions between the two isomers and DNA by using magnetic tweezers and atomic force microscopy (AFM) to investigate the effect of chiralities of the isomers on the interactions. We found that the extension curves and average condensation rates of DNA molecules incubated with heptaplatin were nearly the same as those incubated with its chiral isomer. In addition, the structures of DNA molecules incubated with heptaplatin were also similar to those incubated with its chiral isomer. These results indicate the difference in chirality of the two isomers does not induce different interactions of the isomers with DNA. Our study may facilitate the understanding of interactions of platinum complexes with DNA and the design of new antitumor platinum complexes.

  17. Focal point analysis of torsional isomers of acrylic acid

    Science.gov (United States)

    Alev Çiftçioğlu, Gökçen; Trindle, Carl; Yavuz, Ilhan

    2010-10-01

    The thermochemistry of acrylic acid has presented challenges owing to its high reactivity, tendency to dimerize in the gas phase, and the existence of two very nearly equal energy conformational isomers. Well-tested thermochemical schemes including G2, G3, G4, and CBS-QB3 agree in the prediction that the s-cis syn structure is the most stable of the torsional isomers, with the s-cis anti form lying 3 kJ mol-1 or less higher in energy. Microwave spectra suggest a value of 0.63 kJ mol-1. The energy barrier between these forms is in the neighbourhood of 25 kJ mol-1 according to a MP2/cc-pVDZ calculation. We present estimates of the relative energies of all four torsional isomers and the rotational barrier based on a variant of the Focal Point Analysis developed by Császár and co-workers. These calculations, extending to the CCSD(T)/cc-pV5Z level, predict that the s-cis anti torsional isomer is the most stable form, in contrast to prior estimates. The s-cis syn form lies about 2.9 kJ mol-1 higher, while the s-trans syn and anti forms lie at about 21.7 and 23.3 kJ mol-1, respectively. We estimate the rotational barrier between the s-cis trans and s-cis anti structures to be about 23.9 kJ mol-1. Error ranges derived from the fit to extrapolation forms suggest that our estimates have an uncertainty of about 0.1 kJ mol-1.

  18. Island of high-spin isomers near N = 82

    Energy Technology Data Exchange (ETDEWEB)

    Pedersen, J.; Back, B.B.; Bernthal, F.M.; Bjornholm, S.; Borggreen, J.; Christensen, O.; Folkmann, F.; Herskind, B.; Khoo, T.L.; Neiman, M.; Puehlhofer, F.; Sletten, G.

    1977-10-17

    Experiments aimed at testing for the existence of yrast traps are reported. A search for delayed ..gamma.. radiation of lifetimes longer than approx. 10 ns and of high multiplicity has been performed by producing more than 100 compound nuclei between Ba and Pb in bombardments with /sup 40/Ar, /sup 50/Ti, and /sup 65/Cu projectiles. An island of high-spin isomers is found to exist in the region 64 < or approx. = Z > or approx. = 71 and N < or approx. = 82.

  19. Characteristics of Butanol Isomers Oxidation in a Micro Flow Reactor

    KAUST Repository

    Bin Hamzah, Muhamad Firdaus

    2017-05-01

    Ignition and combustion characteristics of n-butanol/air, 2-butanol.air and isobutanol/air mixtures at stoichiometric (ϕ = 1) and lean (ϕ = 0.5) conditions were investigated in a micro flow reactor with a controlled temperature profile from 323 K to 1313 K, under atmospheric pressure. Sole distinctive weak flame was observed for each mixture, with inlet fuel/air mixture velocity set low at 2 cm/s. One-dimensional computation with comprehensive chemistry and transport was conducted. At low mixture velocities, one-stage oxidation was confirmed from heat release rate profiles, which was broadly in agreement with the experimental results. The weak flame positions were congruent with literature describing reactivity of the butanol isomers. These weak flame responses were also found to mirror the trend in Anti-Knock Indexes of the butanol isomers. Flux and sensitivity analyses were performed to investigate the fuel oxidation pathways at low and high temperatures. Further computational investigations on oxidation of butanol isomers at higher pressure of 5 atm indicated two-stage oxidation through the heat release rate profiles. Low temperature chemistry is accentuated in the region near the first weak cool flame for oxidation under higher pressure, and its impact on key species – such as hydroxyl radical, hydrogen peroxide and carbon monoxide – were considered. Both experimental and computational findings demonstrate the advantage of employing the micro flow reactor in investigating oxidation processes in the temperature region of interest along the reactor channel. By varying physical conditions such as pressure, the micro flow reactor system is proven to be highly beneficial in elucidating oxidation behavior of butanol isomers in conditions in engines such as those that mirror HCCI operations.

  20. Determination of aminocresol isomers by high-speed liquid chromatography.

    Science.gov (United States)

    Sakurai, H; Kito, M

    Aminocresol isomers (4-hydroxy-m-toluidine [II], 3-hydroxy-p-toluidine [II], 2-hydroxy-p-toluidine [III]) and p-aminophenol have been separated and determined by a high-speed liquid Chromatographie method. Since this method is applicable in aqueous media, it was used to investigate the suitability of a haemin-cysteine system as a model for the cytochrome P-450 mono-oxygenase system, by determination of the [I], [II], [III] and p-aminophenol formed.

  1. Flame Propagation of Butanol Isomers/Air Mixtures

    Energy Technology Data Exchange (ETDEWEB)

    Veloo, Peter S.; Egolfopoulos, Fokion N.

    2011-01-01

    An experimental and computational study was conducted on the propagation of flames of saturated butanol isomers. The experiments were performed in the counterflow configuration under atmospheric pressure, unburned mixture temperature of 343 K, and for a wide range of equivalence ratios. The experiments were simulated using a recent kinetic model for the four isomers of butanol. Results indicate that n-butanol/air flames propagate somewhat faster than both sec-butanol/air and iso-butanol/air flames, and that tert-butanol/air flames propagate notably slower compared to the other three isomers. Reaction path analysis of tert-butanol/air flames revealed that iso-butene is a major intermediate, which subsequently reacts to form the resonantly stable iso-butenyl radical retarding thus the overall reactivity of tert-butanol/air flames relatively to the other three isomers. Through sensitivity analysis, it was determined that the mass burning rates of sec-butanol/air and iso-butanol/air flames are sensitive largely to hydrogen, carbon monoxide, and C{sub 1}–C{sub 2} hydrocarbon kinetics and not to fuel-specific reactions similarly to n-butanol/air flames. However, for tert-butanol/air flames notable sensitivity to fuel-specific reactions exists. While the numerical results predicted closely the experimental data for n-butanol/air and sec-butanol/air flames, they overpredicted and underpredicted the laminar flame speeds for iso-butanol/air and tert-butanol/air flames respectively. It was demonstrated further that the underprediction of the laminar flame speeds of tert-butanol/air flames by the model was most likely due to deficiencies of the C{sub 4}-alkene kinetics.

  2. Spectroscopic and computational study of a new isomer of salinomycin

    Science.gov (United States)

    Pankiewicz, Radosław

    2013-09-01

    A new derivative of polyether ionophore salinomycin was obtained as a result of a rearrangement catalysed by sulphuric acid in two-phase medium of water/methylene chloride solution. The new isomer was fully characterized by multinuclear 2D NMR, NOESY and MALDI-TOF. The properties of the new compound were additionally study by semiempirical (PM5) and DFT (B3LYP) methods. A potential mechanism of the rearrangement was also proposed.

  3. Characterization and performance of short cationic antimicrobial peptide isomers.

    Science.gov (United States)

    Juba, Melanie; Porter, Devin; Dean, Scott; Gillmor, Susan; Bishop, Barney

    2013-07-01

    Cationic antimicrobial peptides (CAMPs) represent an ancient defense mechanism against invading bacteria, with peptides such as the cathelicidins being essential elements of vertebrate innate immunity. CAMPs are typically associated with broad-spectrum antimicrobial potency and limited bacterial resistance. The cathelicidin identified from the elapid snake Naja atra (NA-CATH) contains a semi-conserved repeated 11-residue motif (ATRA motif) with a sequence pattern consistent with formation of an amphipathic helical conformation. Short peptide amides (ATRA-1, -1A, -1P, and -2) generated based on the pair of ATRA motifs in NA-CATH exhibited varied antimicrobial potencies. The small size of the ATRA peptides, coupled with their varied antimicrobial performances, make them interesting models to study the impact various physico-chemical properties have on antimicrobial performance in helical CAMPs. Accordingly, the D- and L-enantiomers of the peptide ATRA-1A, which in earlier studies had shown both good antimicrobial performance and strong helical character, were investigated in order to assess the impact peptide stereochemistry has on antimicrobial performance and interaction with chiral membranes. The ATRA-1A isomers exhibit varied potencies against four bacterial strains, and their conformational properties in the presence of mixed zwitterionic/anionic liposomes are influenced by anionic lipid content. These studies reveal subtle differences in the properties of the peptide isomers. Differences are also seen in the abilities of the ATRA-1A isomers to induce liposome fusion/aggregation, bilayer rearrangement and lysing through turbidity studies and fluorescence microscopy. The similarities and differences in the properties of the ATRA-1A isomers could aid in efforts to develop D-peptide-based therapeutics using high-performing L-peptides as templates.

  4. Photoelectron spectroscopy and density functional calculations of C(n)S(m)(-) (n = 2-7; m = 1, 2) clusters.

    Science.gov (United States)

    Xu, Xi-Ling; Deng, Xiao-Jiao; Xu, Hong-Guang; Zheng, Wei-Jun

    2015-12-14

    CnSm(-) (n = 2-7; m = 1, 2) clusters were investigated by using photoelectron spectroscopy combined with density functional theory calculations. We found that the vertical detachment energies of both CnS(-) and CnS2(-) (n = 2-7) clusters exhibit a strong odd-even alternation with an increasing number of carbon atoms: the VDEs of even-n clusters are higher than those of adjacent odd-n clusters. The most stable structures of the anionic and neutral CnS (n = 2-7) clusters are linear with the S atom locating at one end of the carbon chain except that the structure of C3S(-) is slightly bent. The ground state isomers of the anionic and neutral CnS2 (n = 2-7) clusters are all linear structures with two S atoms locating at two ends of the carbon chain. The electron affinities of the neutral CnS (n = 2, 4-7) and CnS2 (n = 2-7) clusters are determined based on the experimental adiabatic detachment energies of the corresponding anion species, because the most stable structures of the neutral clusters are similar to those of the corresponding anions.

  5. 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...

  6. 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...

  7. 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.

  8. The TNM 8 M1b and M1c classification for non-small cell lung cancer in a cohort of patients with brain metastases.

    Science.gov (United States)

    Nieder, C; Hintz, M; Oehlke, O; Bilger, A; Grosu, A L

    2017-09-01

    According to the recent TNM 8 classification, patients with metastatic non-small cell lung cancer (NSCLC) and single extrathoracic metastasis should be classified as stage M1b, while those with 2 or more metastases comprise stage M1c. The purpose of this study was to analyze the impact of this classification in patients with brain metastases. This retrospective study included 172 patients treated with individualized approaches. Actuarial survival was calculated. Uni- and multivariate analyses were performed. Thirty patients (17%) were staged as M1b. Those with squamous cell cancer were more likely to harbor M1b disease (29%, adenocarcinoma 14%, other histology 17%, p = 0.16). Median survival was 5.4 months (8.0 months in case of M1b disease and 4.5 months in case of M1c disease, p = 0.001). Multivariate analysis confirmed the role of M1b stage. M1b patients managed with upfront surgery or radiosurgery had significantly longer median survival than those who received whole-brain irradiation (21.0 vs. 3.5 months, p = 0.0001) and the potential to survive beyond 5 years. We found the M1b classification to provide clinically relevant information. The multivariate analysis suggested that patients with M1b disease, better performance status and younger age have better survival.

  9. Isomer probes of nuclear structure following deep inelastic collisions

    CERN Document Server

    Al-Garni, S A; Walker, P

    2002-01-01

    Deep-inelastic collisions of sup 1 sup 3 sup 6 Xe ions with tantalum, tungsten and rhenium targets have been used to study beta-decays and high-spin isomers in neutron-rich A approx 180 nuclei at the GSI on-line mass separator. In particular, gamma rays -associated with the decay of the previously identified K suppi = 37/2 sup - , T sub 1 sub / sub 2 = 51 min isomer in sup 1 sup 7 sup 7 Hf have been observed, but with an unexpectedly high yield considering the release efficiency for short-lived hafnium isotopes from a thermal ion source. These results may be interpreted as possible evidence for a hitherto unrecognised, high-spin beta-decaying isomer in sup 1 sup 7 sup 7 Lu. A two-component half-life analysis of the sup 1 sup 7 sup 7 Hf gamma-ray intensities gives an upper-lying component of 6 + 3 - 2 min, when the lower-lying component half-life is fixed at 51 min. Nilsson multi-quasiparticle calculations with BCS pairing predict a favoured K suppi = 39/2 sup - state in sup 1 sup 7 sup 7 Lu, which is a candid...

  10. Isomer-specific biodegradation of methylphenanthrenes by soil bacteria.

    Science.gov (United States)

    Lamberts, Rasmus F; Christensen, Jan H; Mayer, Philipp; Andersen, Ole; Johnsen, Anders R

    2008-07-01

    It is assumed that bacteria generally degrade 2-methylphenanthrene (2MPhe) in preference to 1-methylphenanthrene (1MPhe), and that environmental biodegradation of methylated PAHs therefore can be described qualitatively by changes in relative concentrations of these isomers. Our objective was to investigate whether microbial phenanthrene degraders (Sphingomonas and Mycobacterium) show such isomer-specific PAH degradation. Eleven out of twenty-nine phenanthrene degraders could grow on methylphenanthrene. The mycobacteria grew only on 2MPhe, the sphingomonads grew mostly on 1MPhe, and one sphingomonad could utilize both substrates. Seven strains were tested in a two-phase system where 1MPhe and 2MPhe were supplied in heptamethylnonane. For these strains, a consistent description of biodegradation based on the 2MPhe/1MPhe diagnostic ratio would not be possible because three Mycobacterium and one Sphingomonas degraded 2MPhe faster than 1MPhe, another Sphingomonas degraded 1MPhe and 2MPhe at almost equal rates, and two Sphingomonas degraded 1MPhe faster than 2MPhe. Thus, environmental biodegradation of phenanthrenes may theoretically proceed with only minor changes in 2MPhe/1MPhe ratios if individual members of the degrader community have different isomer preferences. However, two soil microcosms polluted with bunker oil confirmed the general decline in 2MPhe/1MPhe ratio during oil biodegradation.

  11. Diffusion studies of dihydroxybenzene isomers in water-alcohol systems.

    Science.gov (United States)

    Codling, Dale J; Zheng, Gang; Stait-Gardner, Tim; Yang, Shu; Nilsson, Mathias; Price, William S

    2013-03-01

    Nuclear magnetic resonance diffusion studies can be used to identify different compounds in a mixture. However, because the diffusion coefficient is primarily dependent on the effective hydrodynamic radius, it is particularly difficult to resolve compounds with similar size and structure, such as isomers, on the basis of diffusion. Differential solution interactions between species in certain solutions can afford possibilities for separation. In the present study, the self-diffusion of the three isomers of dihydroxybenzene (i.e., (1,2-) catechol, (1,3-) resorcinol, and (1,4-) hydroquinone) was studied in water, aqueous monohydric alcohols (i.e., ethanol, 1-propanol, tert-butanol), and aqueous ethylene glycol. These systems allowed the effects of isomerism and differential solvent interactions on diffusion to be examined. It was found that, while in aqueous solution these isomers had the same diffusion coefficient, in water-monohydric alcohol systems the diffusion coefficient of catechol differed from those of resorcinol and hydroquinone. The separation was found to increase at higher concentrations of monohydric alcohols. The underlying chemical reasons for these differences were investigated.

  12. Borromean halo, Tango halo, and halo isomers in atomic nuclei

    Science.gov (United States)

    Izosimov, Igor

    2016-01-01

    Structure of the ground and excited states in halo-like nuclei is discussed. Both the Borromean and tango halo types can be observed for n-p configurations of atomic nuclei.Structure of the halo may be different for the different levels and resonances in atomic nuclei. Isobar analog, double isobar analog, configuration, and double configuration states can simultaneously have n-n, n-p, and p-p halo components in their wave functions. When the halo structure of the excited state differs from that of the ground state, or the ground state has non-halo structure, the γ-transition from the excited state to the ground state can be essentially hindered, i.e. the formation of a specific type of isomers (halo isomers) becomes possible. B(Mγ) and B(Eγ) values for γ-transitions in 6,7,8Li, 8,9,10Be, 8,10,11B, 10,11,12,13,14C, 13,14,15,16,17N, 15,16,17,19O, and 17F are analyzed. Special attention is given to nuclei which ground state does not exhibit halo structure but the excited state (halo isomer) may have one.

  13. Solvent and temperature induced switching between structural isomers of Rh(I) phosphinoalkyl thioether (PS) complexes.

    Science.gov (United States)

    Wiester, Michael J; Braunschweig, Adam B; Yoo, Hyojong; Mirkin, Chad A

    2010-08-02

    To develop functional systems based on the weak-link approach (WLA), it is important to understand how solvent and ligand binding strength alter the coordination geometry of complexes formed from this method. A series of phosphinoalkyl thioether (PS) hemilabile ligands with varying electron donating abilities were synthesized and incorporated into homoligated Rh(I)(PS)2Cl complexes to help understand the effects of solvent and ligand binding strength on the preferred coordination modes. The switching between closed and semiopen structural isomers of these Rh(I)(PS)2Cl complexes was studied by variable temperature 31P NMR spectroscopy in different solvent mixtures of CH2Cl2 and tetrahydrofuran (THF) to obtain thermodynamic parameters (DeltaG(o), DeltaH(o), TDeltaS(o), and K(eq)). The isomers differ in the position of the chloride counterion. In the closed isomer, the Cl- anion occupies the outer coordination sphere, while in the semiopen isomer, the Cl- has moved inner sphere and displaced one of the Rh-S bonds. The closed isomer is favored in CH2Cl2 and the semiopen isomer is favored in THF. The preference for either isomer at equilibrium depends on the solvent polarity, based upon the E(T)(N) solvent polarity scale, as was determined from 15 different solvents, with more polar solvents favoring the closed isomer. The isomer preference also depends on the electron donating ability of the group attached to the sulfur of the PS ligand, with electron donating groups favoring the closed isomers and electron withdrawing groups favoring the semiopen isomers. The formation of the semiopen isomer from the closed isomer is entropically favored but enthalpically disfavored under all conditions studied. Elucidation of the principles and environments that determine the equilibrium between the two isomers will aid in the design of functional complexes prepared by the WLA.

  14. In vitro and in vivo models of cerebral ischemia show discrepancy in therapeutic effects of M2 macrophages.

    Directory of Open Access Journals (Sweden)

    Virginie Desestret

    Full Text Available THE INFLAMMATORY RESPONSE FOLLOWING ISCHEMIC STROKE IS DOMINATED BY INNATE IMMUNE CELLS: resident microglia and blood-derived macrophages. The ambivalent role of these cells in stroke outcome might be explained in part by the acquisition of distinct functional phenotypes: classically (M1 and alternatively activated (M2 macrophages. To shed light on the crosstalk between hypoxic neurons and macrophages, an in vitro model was set up in which bone marrow-derived macrophages were co-cultured with hippocampal slices subjected to oxygen and glucose deprivation. The results showed that macrophages provided potent protection against neuron cell loss through a paracrine mechanism, and that they expressed M2-type alternative polarization. These findings raised the possibility of using bone marrow-derived M2 macrophages in cellular therapy for stroke. Therefore, 2 million M2 macrophages (or vehicle were intravenously administered during the subacute stage of ischemia (D4 in a model of transient middle cerebral artery occlusion. Functional neuroscores and magnetic resonance imaging endpoints (infarct volumes, blood-brain barrier integrity, phagocytic activity assessed by iron oxide uptake were longitudinally monitored for 2 weeks. This cell-based treatment did not significantly improve any outcome measure compared with vehicle, suggesting that this strategy is not relevant to stroke therapy.

  15. Infiltration of M2 Tumor-Associated Macrophages in Oral Squamous Cell Carcinoma Correlates with Tumor Malignancy

    Directory of Open Access Journals (Sweden)

    Jun Shimada

    2011-09-01

    Full Text Available Tumor-associated macrophages (TAMs are a major cellular component in the tumor microenvironment of many solid tumors. The functional competence of TAMs varies depending on the type of tumors and their respective microenvironments. The classically activated M1 macrophages exhibit antitumor functions, whereas the alternatively activated M2 macrophages exhibit protumor functions that contribute to tumor development and progression. Although TAMs have been detected in oral squamous cell carcinoma (OSCC, little is known about their phenotype. In the present study, we performed an immunohistochemical analysis to identify TAMs in surgically resected specimens from 50 patients with OSCC and evaluated the relationship between infiltrated TAMs and the pathological grade of OSCC. Positive staining for CD163, which has been used as a marker for M2 macrophages, was observed in OSCC specimens, and the percentages of CD163+ cells were significantly increased based on the pathological grade. CD163+ cells were detected in the tumor stroma in grade I tumors, whereas an increase in the CD163+ cells in the tumor nest was observed in higher grades of tumors. Although infiltrated CD4+ and CD8+ T cells were detected in all pathological grades of OSCC, no correlation between the infiltrated T cells and the CD163+ TAMs was observed. These results indicate that the infiltrated TAMs in OSCC have an M2 phenotype and that the M2 macrophages may participate in the development of OSCC.

  16. Infiltration of M2 Tumor-Associated Macrophages in Oral Squamous Cell Carcinoma Correlates with Tumor Malignancy

    Energy Technology Data Exchange (ETDEWEB)

    Mori, Kazumasa [Division of Oral and Maxillofacial Surgery, Department of Diagnosis and Therapeutics, Meikai University of School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283 (Japan); Hiroi, Miki [Division of Microbiology and Immunology, Department of Oral Biology and Tissue Engineering, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283 (Japan); Shimada, Jun [Division of Oral and Maxillofacial Surgery, Department of Diagnosis and Therapeutics, Meikai University of School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283 (Japan); Ohmori, Yoshihiro, E-mail: ohmori@dent.meikai.ac.jp [Division of Microbiology and Immunology, Department of Oral Biology and Tissue Engineering, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283 (Japan)

    2011-09-28

    Tumor-associated macrophages (TAMs) are a major cellular component in the tumor microenvironment of many solid tumors. The functional competence of TAMs varies depending on the type of tumors and their respective microenvironments. The classically activated M1 macrophages exhibit antitumor functions, whereas the alternatively activated M2 macrophages exhibit protumor functions that contribute to tumor development and progression. Although TAMs have been detected in oral squamous cell carcinoma (OSCC), little is known about their phenotype. In the present study, we performed an immunohistochemical analysis to identify TAMs in surgically resected specimens from 50 patients with OSCC and evaluated the relationship between infiltrated TAMs and the pathological grade of OSCC. Positive staining for CD163, which has been used as a marker for M2 macrophages, was observed in OSCC specimens, and the percentages of CD163{sup +} cells were significantly increased based on the pathological grade. CD163{sup +} cells were detected in the tumor stroma in grade I tumors, whereas an increase in the CD163{sup +} cells in the tumor nest was observed in higher grades of tumors. Although infiltrated CD4{sup +} and CD8{sup +} T cells were detected in all pathological grades of OSCC, no correlation between the infiltrated T cells and the CD163{sup +} TAMs was observed. These results indicate that the infiltrated TAMs in OSCC have an M2 phenotype and that the M2 macrophages may participate in the development of OSCC.

  17. M1 Site Splitting Due to Next Nearest Neighbor Effects and Ferric Iron in Tetrahedral Site in Clinopyroxene Megacrysts

    Institute of Scientific and Technical Information of China (English)

    李一良; 李玉芝; 等

    1998-01-01

    It is well known that in pyroxene structure,there are two metal sites,M1 and M2.Generally speaking,Ferrous iron in each of these sites would normally be expected to give rise to a doublet,However,anomalies have been found in the relative areas of the peaks in the room temperature spectra of some clinopyroxene(CPX)when the above assignment is followed.According to the calculation of Next Nearest Neighbor configurations of divalent cations in M1,we found that the four configurations of M1 can be divided into two groups.One group is 3Ca configuration that increases with the content of Ca(p.f.u);the other group is made up of three No-3Ca configurations that decrease with the content of Ca.The two groups contribute to the spectrum structure of M1.so in this study we fit two doublets for ferrous iron in M1.Though there were several reports on Fe3+ in tetrahedral site previously,it was not sure that Fe3+ occupies the T site is a universal fact in CPX,despite of the content of Al.We found that the Fe3+ in the T site fitted by Moessbauer spectroscopy is negatively correlated to the Si content in the T site and positively correlated to the Fe3+ in the T site estimated on the supposition that Fe3+ and Al occupy the T site randomly.If it is true.it is important in the modeling of ion exchange geobarometries and geothermomeries.

  18. Experimental Conditions: SE37_S18_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available opes SE37_S18 PSEUDO: Unlabeled and labeled Medicago samples for metabolite annotation using ShiftedIonsFind...17_M1), and for Medicago samples labeled by 13C (S05_M1), 15N (S07_M1), 28O (S10_M1), and 34S (S13_M1) are used. SE37_DS4 Labeled peak search by ShiftedIonsFinder ...

  19. PICK1 confers anti-inflammatory effects in acute liver injury via suppressing M1 macrophage polarization.

    Science.gov (United States)

    Xie, Juan; Wu, Xiaoqin; Zhou, Qun; Yang, Yang; Tian, Yuanyao; Huang, Cheng; Meng, Xiaoming; Li, Jun

    2016-08-01

    Protein interacting with C kinase 1 (PICK1) is a scaffolding protein mainly implicated in neurological diseases, however, the function of PICK1 in acute liver injury (ALI) remains unknown. Our study found a dramatical decrease in mRNA and protein levels of PICK1 in liver tissues and isolated Kupffer cells (KCs) from the liver in mice with ALI. Furthermore, pretreatment the mice with ALI with FSC-231, a pharmacological inhibitor of PICK1, could significantly augment inflammatory response. Furthermore, in vitro studies showed that both lipopolysaccharide (LPS) and interferon gamma (IFN-γ) significantly reduced the expression of PICK1, while IL-4 elevated its expression in RAW 264.7 cells. Additionally, over-expression of PICK1 inhibited the expression of M1 biomarkers by suppressing NF-κB activity, and enhanced the expression of M2 biomarkers by promoting STAT6 activity. In contrast, knockdown of PICK1 or FSC-231 pretreatment promoted M1 polarization and suppressed M2 polarization. Besides, caveolin-1 was identified as a potential target gene controlled by PICK1 in RAW 264.7 cells. Mechanistic investigation revealed a dual role of PICK1 in regulating macrophage polarization and implied PICK1 as a potential therapeutic target in ALI.

  20. EFFECT OF GAMMA RADIATION OF MACRO MUTATIONS, EFFECTIVENESS AND EFFICIENCY UNDER M2 GENERATION IN PEA (Pisum sativum L.

    Directory of Open Access Journals (Sweden)

    Arvind KUMAR

    2016-06-01

    Full Text Available The present investigation was undertaken to study the spectrum of macro mutants, effectiveness and efficiency of different doses of gamma rays in pea variety (Arkel. The seeds were treated with gamma rays viz., 00kR (dry control, 05kR, 10kR, 15kR, 20kR, 25kR, 30kR, 35kR, 40kR (dry seeds and presoaked seeds of the same was exposed to 00kR (wet control, 05kR, 10kR, 15kR, 20kR (kilo Roentgen biological damage was calculated in M1 and M2 generation based on lethality (L and pollen sterility. The irradiated seeds were sown in the M1 field their respective controls and harvested in bulk to raise the M2 generation in Randomized Block Design (RBD with three replications. The spectrum of macro mutants i.e., plant stature (tall, dwarf, small dwarf, maturity (early, late, pod shape (bold, long, short, seed colour (brown, light white, light green and seed shape (small, bold, wrinkled were observed in M2 generation. The usefulness of any mutagen in plant breeding depends not only on its effectiveness but also upon if efficiency. Mutagenic effectiveness is a measure of the frequency of mutations induced by unit mutagen dose, whereas mutagenic efficiency is measure of proportion of mutations in relation of undesirable changes like lethality and sterility are used for gamma rays. A result of the indicated positive relationship in M2 generation with macro mutation, effectiveness and efficiency was found to be highest at lowest doses.

  1. Graft-Infiltrating Macrophages Adopt an M2 Phenotype and Are Inhibited by Purinergic Receptor P2X7 Antagonist in Chronic Rejection.

    Science.gov (United States)

    Wu, C; Zhao, Y; Xiao, X; Fan, Y; Kloc, M; Liu, W; Ghobrial, R M; Lan, P; He, X; Li, X C

    2016-09-01

    Macrophages exhibit diverse phenotypes and functions; they are also a major cell type infiltrating chronically rejected allografts. The exact phenotypes and roles of macrophages in chronic graft loss remain poorly defined. In the present study, we used a mouse heart transplant model to examine macrophages in chronic allograft rejection. We found that treatment of C57BL/6 mice with CTLA4 immunoglobulin fusion protein (CTLA4-Ig) prevented acute rejection of a Balb/c heart allograft but allowed chronic rejection to develop over time, characterized by prominent neointima formation in the graft. There was extensive macrophage infiltration in the chronically rejected allografts, and the graft-infiltrating macrophages expressed markers associated with M2 cells but not M1 cells. In an in vitro system in which macrophages were polarized into either M1 or M2 cells, we screened phenotypic differences between M1 and M2 cells and identified purinergic receptor P2X7 (P2x7r), an adenosine triphosphate (ATP)-gated ion channel protein that was preferentially expressed by M2 cells. We further showed that blocking the P2x7r using oxidized ATP (oATP) inhibited M2 induction in a dose-dependent fashion in vitro. Moreover, treatment of C57BL/6 recipients with the P2x7r antagonist oATP, in addition to CTLA4-Ig treatment, inhibited graft-infiltrating M2 cells, prevented transplant vasculopathy, and induced long-term heart allografts survival. These findings highlight the importance of the P2x7r-M2 axis in chronic rejection and establish P2x7r as a potential therapeutic target in suppression of chronic rejection.

  2. Distribution of perfluorooctane sulfonate isomers and predicted risk of thyroid hormonal perturbation in drinking water.

    Science.gov (United States)

    Yu, Nanyang; Wang, Xiaoxiang; Zhang, Beibei; Yang, Jingping; Li, Meiying; Li, Jun; Shi, Wei; Wei, Si; Yu, Hongxia

    2015-06-01

    We documented the distribution of seven perfluorooctane sulfonate (PFOS) isomers in drinking water in Jiangsu Province, China. Compared to the 30% proportion of branched PFOS in technical PFOS, the levels of branched PFOS in drinking water increased to 31.8%-44.6% of total PFOS. Because of previous risk assessment without considering the PFOS isomer profile and the toxicity of individual PFOS isomers, here we performed a new health risk assessment of PFOS for thyroid hormonal perturbation in drinking water with the contribution from individual PFOS isomers. The risk quotients (RQs) of individual PFOS isomers indicated that linear PFOS contributed most to the risk among all the target PFOS isomers (83.0%-90.2% of the total PFOS RQ), and that risk from 6m-PFOS (5.2%-11.9% of the total PFOS RQ) was higher than that from other branched PFOS isomers. We found that the risks associated with PFOS in drinking water would be overestimated by 10.0%-91.7% if contributions from individual PFOS isomers were not considered. The results revealed that the PFOS isomer profile and the toxicity of individual PFOS isomers were important factors in health risk assessment of PFOS and should be considered in the future risk assessments. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. 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.

  4. Identification of hyperhalogens in Ag(n)(BO2)(m) (n = 1-3, m = 1-2) clusters: anion photoelectron spectroscopy and density functional calculations.

    Science.gov (United States)

    Kong, Xiang-Yu; Xu, Hong-Guang; Koirala, Pratik; Zheng, Wei-Jun; Kandalam, Anil K; Jena, Puru

    2014-12-21

    The electronic and structural properties of neutral and anionic Agn(BO2)m (n = 1-3, m = 1-2) clusters are investigated by using mass-selected anion photoelectron spectroscopy and density functional theory calculations. Agreement between the measured and calculated vertical detachment energies (VDEs) allows us to validate the equilibrium geometries of [Agn(BO2)m](-) clusters obtained from theory. The ground state structures of anionic Ag2(BO2) and Agn(BO2)2 (n = 1-3) clusters are found to be very different from those of their neutral counterparts. The structures of anionic clusters are chain-like while those of the neutral clusters are closed-rings. The presence of multiple isomers for [Ag2(BO2)2](-) and [Ag3(BO2)2](-) in the cluster beam has also been confirmed. Several of these clusters are found to be hyperhalogens.

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

    Institute of Scientific and Technical Information of China (English)

    胡雅儿; 施菊; 夏宗勤

    1999-01-01

    转染m1m2和m4 Cdna的CHO细胞膜受体与3H-QNB结合,能给出典型的饱和曲线,Hill系数接近1.单位点竞争结合表明,对PZP抑制能力为CHOm1>CHOm4>CHOm2,对METH抑制强度为CHOm2>CHOm4>CHOm1.与药理学PZP对M1受体的亲和力最高和METH对M2的亲和力最高是一致的.CHOm2对Forskolin和Carbachol影响Camp的结果,证明该M受体亚型信号传导系统的完整性,因此是研究M受体亚型与其信号传导的较好模型,也可用于筛选M受体亚型的药物

  6. Nuclear magnetic resonance for differentiating two inequivalent M sites in double anhydrous M2CuCl4 (M = K, Cs, and NH4) single crystals

    Science.gov (United States)

    Lim, Ae Ran; Yoon, Ma Byong

    2016-05-01

    Nuclear magnetic resonance (NMR) spectra and the spin-lattice relaxation times (T1) for the M nuclei (M = K, Cs, and NH4) in M2CuCl4 crystals were studied as functions of temperature. The K2CuCl4, Cs2CuCl4, and (NH4)2CuCl4 single crystals all have the same M2BX4 structure, and their two inequivalent sites M(1) and M(2) were differentiated using the NMR results. Because M(2) is surrounded by fewer but closer Cl ligands than M(1), it has a shorter T1 value than M(1). However, the three crystals have different T1 temperature dependences and dynamic properties. The rotational tumbling motion defined by the Bloembergen-Purcell-Pound theory was found to occur in (NH4)2CuCl4, but not in K2CuCl4 or Cs2CuCl4. The differences observed in the spin-lattice relaxation times of the M nuclei may be related to their ionic masses.

  7. 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.

  8. 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.

  9. 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.

  10. Differential adsorption of CHON isomers at interstellar grain surfaces

    Science.gov (United States)

    Lattelais, M.; Pauzat, F.; Ellinger, Y.; Ceccarelli, C.

    2015-06-01

    Context. The CHON generic chemical formula covers different isomers such as isocyanic acid (HNCO), cyanic acid (HOCN), fulminic acid (HCNO), and isofulminic acid (HONC); the first three have been identified in a large variety of environments in the interstellar medium (ISM). Several phenomena could be at the origin of the observed abundances, such as different pathways of formation and destruction involving gas phase reactions with different possible activation barriers and/or surface processes depending on the local temperature and the nature of the support. Aims: The scope of this article is to shed some light on the interaction of the CHON isomers with interstellar grains as a function of the nature of the surface and to determine the corresponding adsorption energies in order to find whether this phenomenon could play a role in the abundances observed in the ISM. Methods: The question was addressed by means of numerical simulations using first principle periodic density functional theory (DFT) to represent the grain support as a solid of infinite dimension. Results: Regardless of the nature of the model surface (water ice, graphene, silica), two different classes of isomers were identified: weakly bound (HNCO and HCNO) and strongly bound (HOCN and HONC), with the adsorption energies of the latter group being about twice those of the former. The range of the adsorption energies is (from highest to lowest) HOCN > HONC > HNCO > HCNO. They are totally disconnected from the relative stabilities, which range from HNCO > HOCN > HCNO > HONC. Conclusions: The possibility of hydrogen bonding is the discriminating factor in the trapping of CHON species on grain surfaces. Whatever the environment, differential adsorption is effective and its contribution to the molecular abundances should not be ignored. The theoretical adsorption energies provided here could be profitably used for a more realistic modeling of molecule-surfaces interactions.

  11. M2(m-dobdc) (M = Mn, Fe, Co, Ni) Metal-Organic Frameworks as Highly-Selective, High-Capacity Adsorbents for Olefin/Paraffin Separations.

    Science.gov (United States)

    Bachman, Jonathan E; Kapelewski, Matthew T; Reed, Douglas A; Gonzalez, Miguel I; Long, Jeffrey R

    2017-10-05

    The metal-organic frameworks M2(m-dobdc) (M = Mn, Fe, Co, Ni; m-dobdc4- = 4,6-dioxido-1,3-benzenedicarboxylate) were evaluated as adsorbents for separating olefins from paraffins. Using single-component and multicomponent equilibrium gas adsorption measurements, we show that the coordinatively-unsaturated M2+ sites in these materials lead to superior performance for the physisorptive separation of ethylene from ethane and propylene from propane relative to any known adsorbent, including para-functionalized structural isomers of the type M2(p-dobdc) (p-dobdc4- = 2,5-dioxido-1,4-benzenedicarboxylate). Notably, the M2(m-dobdc) frameworks all exhibit an increased affinity for olefins over paraffins relative to their corresponding structural isomers, with the Fe, Co, and Ni variants showing more than double the selectivity. Among these frameworks, Fe2(m-dobdc) displays the highest ethylene/ethane (> 25) and propylene/propane (> 55) selectivity under relevant conditions, together with olefin capacities exceeding 7 mmol/g. Differential enthalpy calculations in conjunction with structural characterization of ethylene binding in Co2(m-dobdc) and Co2(p-dobdc) via in-situ single-crystal X-ray diffraction reveal that the vast improvement in selectivity arises from enhanced metal-olefin interactions induced by increased charge density at the metal site. Moderate olefin binding enthalpies, below 55 kJ/mol and 70 kJ/mol for ethylene and propylene, respectively, indicate that these adsorbents maintain sufficient reversibility under mild regeneration conditions. Additionally, transient adsorption experiments show fast kinetics, with more than 90% of ethylene adsorption occurring within 30 s after dosing. Breakthrough measurements further indicate that Co2(m-dobdc) can produce high purity olefins without a temperature swing, an important test of process applicability. The excellent olefin/paraffin selectivity, high olefin capacity, rapid adsorption kinetics, and low raw materials

  12. Theoretical Study on Two C16H12O4 Isomers of Derivatives of Pagodane

    Institute of Scientific and Technical Information of China (English)

    LIU Feng-Ling; DU Ai-Ming; WANG Su-Jing

    2006-01-01

    Two C16H12O4 isomers of derivatives of pagodane were firstly reported and studied by using DFT method. Geometries, energies, and vibrational frequencies have been calculated for the two C16H12O4 isomers with pagodane-like structures at the B3LYP/6-31G** level of theory. Symmetries of isomer 1 and 2 are D2h and D2d, respectively. Heats of formation for the two C16H12O4 isomers have been estimated in this paper. According to the heats of formation, the two C16H12O4 isomers are more stable than pagodane. Heats of formation as well as the vibrational analysis indicate that the two C16H12O4 isomers enjoy sufficient stability to allow for the experi- mental preparation.

  13. An Isomer-Specific Approach to Endocrine-Disrupting Nonylphenol in Infant Food.

    Science.gov (United States)

    Günther, Klaus; Räcker, Torsten; Böhme, Roswitha

    2017-02-15

    Nonylphenols (NPs) are persistent endocrine disruptors that are priority hazardous substances of the European Union Water Framework Directive. Their presence in the environment has caused growing concern regarding their impact on human health. Recent studies have shown that nonylphenol is ubiquitous in commercially available foodstuffs and is also present in human blood. The isomer distribution of 4-nonylphenol was analyzed by gas chromatography - mass spectrometry in 44 samples of infant food. Our study shows that the distribution of nonylphenol isomers is dependent on the foodstuff analyzed. Although some isomer groups prevail, different distributions are frequent. Variations are even found in the same food group. Nonylphenol is a complex mixture of isomers, and the estrogenic potentials of each of these isomers are very different. Consequently, to determine the potential toxicological impact of NP in food, an isomer-specific approach is necessary.

  14. Formation of melatonin and its isomer during bread dough fermentation and effect of baking.

    Science.gov (United States)

    Yılmaz, Cemile; Kocadağlı, Tolgahan; Gökmen, Vural

    2014-04-02

    Melatonin is produced mainly by the pineal gland in vertebrates. Also, melatonin and its isomer are found in foods. Investigating the formation of melatonin and its isomer is of importance during bread dough fermentation and its degradation during baking since bread is widely consumed in high amounts. Formation of melatonin was not significant during dough fermentation. The melatonin isomer content of nonfermented dough was found to be 4.02 ng/g and increased up to 16.71 ng/g during fermentation. Lower amounts of isomer in crumb and crust than dough showed that the thermal process caused a remarkable degree of degradation in melatonin isomer. At the end of the 180 min fermentation Trp decreased by 58%. The results revealed for the first time the formation of a melatonin isomer in bread dough during yeast fermentation.

  15. Aromatic Character of All Possible C36H2 Isomers

    Institute of Scientific and Technical Information of China (English)

    Ablikim Kerim

    2006-01-01

    The stability of C36H2 isomers and selection rules for choosing position in addition reactions based on symmetrical C36(D6h and D2d) fullerene have been studied by means of Aihara's topological resonance energy (TRE) and bond resonance energy (BRE) methods. The relation between the addition pattern and BREs is established, showing high antiaromatic bonds are preferred for addition. These results show that TRE and BRE methods can be used to predict and interpret addition sites for these systems.

  16. Stability and electronic spectra of C76N2 isomers

    Institute of Scientific and Technical Information of China (English)

    TENG Qi-wen; WU Shi

    2005-01-01

    Study of geometries of 16 possible isomers for C76N2 based on C78(C2v) by intermediate neglect of differential overlap (INDO) series of methods indicated that the most stable geometry 25,78-C76N2 where two nitrogen atoms substitute two apexes C(25) and C(78) near the shortest X axis and Y axis formed by two hexagons and a pentagon. Electronic structures and spectra of C76N2 were investigated. The reason for the red-shift for absorptions of C76N2 compared with that of C78(C2v) is discussed.

  17. Nuclear states with anomalously large radius (size isomers)

    Energy Technology Data Exchange (ETDEWEB)

    Ogloblin, A. A.; Demyanova, A. S., E-mail: a.s.demyanova@bk.ru; Danilov, A. N. [National Research Center Kurchatov Institute (Russian Federation); Belyaeva, T. L. [Ciudad Universitaria, Universidad Nacional Autónoma de Meéxico (Mexico); Goncharov, S. A. [Moscow State University, Faculty of Physics (Russian Federation); Trzaska, W. [University of Jyvaäskylaä (Finland)

    2016-07-15

    Methods of determination of the nuclear excited state radii are discussed together with the recently obtained data on the states of some light nuclei having abnormally large radii (size isomers). It is shown that such states include excited neutron-halo states in {sup 9}Be, {sup 11}Be, and {sup 13}C and some alpha-cluster states in {sup 12}C, {sup 11}B, and {sup 13}C. Among the latter ones, there is the well-known Hoyle state in {sup 12}C—the structure of this state exhibit rudimentary features of alpha-particle states.

  18. Isomers of broparoestrol and antiestrogen action: comparison with tamoxifen.

    Science.gov (United States)

    Edery, M; Barnova, A; Drosdowsky, M; Guggiari, M; Vives, C; Rudali, G

    1985-01-01

    This study compares the relative biological potencies of a known antiestrogen tamoxifen to two triarylethylene compounds which have been shown previously to be potent inhibitors of rodent mammary tumorigenesis. Based on a) uterotrophic and anti-uterotrophic tests, b) indexes of cellularity, and c) protein content, these studies indicate that the trans, as well as the cis, isomers of bromotriphenylethylene are partial estrogen antagonists with no estrogenic effects in rat uteri and partial agonists in mouse uteri, whereas tamoxifen shows partial antiestrogenic/estrogenic effects in rats and is fully estrogenic in mice.

  19. Mutagenic activities of a chlorination by-product of butamifos, its structural isomer, and their related compounds.

    Science.gov (United States)

    Kamoshita, Masahiro; Kosaka, Koji; Endo, Osamu; Asami, Mari; Aizawa, Takako

    2010-01-01

    The mutagenic activities of 5-methyl-2-nitrophenol (5M2NP), a chlorination by-product of butamifos, its structural isomer 2-methyl-5-nitrophenol (2M5NP), and related compounds were evaluated by the Ames assay. The mutagenic activities of 5M2NP and 2M5NP were negative or not particularly high. However, those of their chlorinated derivatives were increased in Salmonella typhimurium strain TA100 and the overproducer strains YG1026, and YG1029 in the absence and/or presence of a rat liver metabolic activation system (S9 mix), particularly for YG1029. The mutagenic activities of 6-chloro-2-methyl-5-nitrophenol (6C2M5NP) in YG1029 in the absence and presence of S9 mix were 70000 and 110000 revertants mg(-1), respectively. When nitro functions of 6C2M5NP and 4-chloro-5-methyl-2-nitrophenol (4C5M2NP) were reduced to amino functions, their mutagenic activities were markedly decreased. The mutagenic activities of 5M2NP and 4C5M2NP were lower than those of 2M5NP and 6C2M5NP, respectively. Thus, it was shown that substituent position is a key factor for the mutagenic activities of methylnitrophenols (MNPs) and related compounds. The mutagenic activities of the extracts of 2M5NP in chlorination increased early during the reaction time and then decreased. The main chlorination by-product contributing to the mutagenic activities of the extracts of 2M5NP in chlorination was 6C2M5NP. The results of chlorination of 2M5NP suggested that MNPs were present as their dichlorinated derivatives or further chlorination by-products in drinking water.

  20. Correlation of Fe2+ isomer shifts with bond lengths and bond strengths in neso- and sorosilicates

    Institute of Scientific and Technical Information of China (English)

    李哲; E.DeGrave

    1995-01-01

    An evaluation of Mbssbauer isomer shift and quadrupole splitting data of Fe2+ in a number of structurally well characterized neso- and sorosilicates is presented. It is found that the nearly linear correlations exist both between the isomer shift and the bond length and between the isomer shift and the bond strength. These correlations are discussed on the basis of the variation of the s-electron density at the Fe2+ nuclei with the chemical bond characteristics.

  1. Dynamic Regulation of Quaternary Organization of the M1 Muscarinic Receptor by Subtype-selective Antagonist Drugs.

    Science.gov (United States)

    Pediani, John D; Ward, Richard J; Godin, Antoine G; Marsango, Sara; Milligan, Graeme

    2016-06-17

    Although rhodopsin-like G protein-coupled receptors can exist as both monomers and non-covalently associated dimers/oligomers, the steady-state proportion of each form and whether this is regulated by receptor ligands are unknown. Herein we address these topics for the M1 muscarinic acetylcholine receptor, a key molecular target for novel cognition enhancers, by using spatial intensity distribution analysis. This method can measure fluorescent particle concentration and assess oligomerization states of proteins within defined regions of living cells. Imaging and analysis of the basolateral surface of cells expressing some 50 molecules·μm(-2) human muscarinic M1 receptor identified a ∼75:25 mixture of receptor monomers and dimers/oligomers. Both sustained and shorter term treatment with the selective M1 antagonist pirenzepine resulted in a large shift in the distribution of receptor species to favor the dimeric/oligomeric state. Although sustained treatment with pirenzepine also resulted in marked up-regulation of the receptor, simple mass action effects were not the basis for ligand-induced stabilization of receptor dimers/oligomers. The related antagonist telenzepine also produced stabilization and enrichment of the M1 receptor dimer population, but the receptor subtype non-selective antagonists atropine and N-methylscopolamine did not. In contrast, neither pirenzepine nor telenzepine altered the quaternary organization of the related M3 muscarinic receptor. These data provide unique insights into the selective capacity of receptor ligands to promote and/or stabilize receptor dimers/oligomers and demonstrate that the dynamics of ligand regulation of the quaternary organization of G protein-coupled receptors is markedly more complex than previously appreciated. This may have major implications for receptor function and behavior. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Identifying isomers of C-78 by means of x-ray spectroscopy

    DEFF Research Database (Denmark)

    Bassan, Arianna; Nyberg, Mats; Luo, Yi

    2002-01-01

    X-ray photoelectron and absorption spectra of C-78 isomers have been generated using density functional theory with inclusion of the full core-hole potentials. Strong isomer dependence has been found in absorption, but not in the photoelectron spectra. C-78 isomers can be thought to be formed...... by inserting 18 carbon atoms into an opened C-60. We have shown how the different local arrangements of these 18 carbon atoms are responsible for the significant isomer dependence observed. Our calculated spectra are in excellent agreement with the experimental counterparts....

  3. Plaque Size Is Decreased but M1 Macrophage Polarization and Rupture Related Metalloproteinase Expression Are Maintained after Deleting T-Bet in ApoE Null Mice.

    Directory of Open Access Journals (Sweden)

    Aikaterini Tsaousi

    Full Text Available Thelper1 (Th1 lymphocytes have been previously implicated in atherosclerotic plaque growth but their role in plaque vulnerability to rupture is less clear. We investigated whether T-bet knockout that prevents Th1 lymphocyte differentiation modulates classical (M1 macrophage activation or production of matrix degrading metalloproteinases (MMPs and their tissue inhibitors, TIMPs.We studied the effect of T-bet deletion in apolipoproteinE (ApoE knockout mice fed a high fat diet (HFD or normal chow diet (ND. Transcript levels of M1/M2 macrophage polarization markers, selected MMPs and TIMPs were measured by RT-qPCR in macrophages isolated from subcutaneous granulomas or in whole aortae. Immunohistochemistry of aortic sinus (AS and brachiocephalic artery (BCA plaques was conducted to quantify protein expression of the same factors. Deletion of T-bet decreased mRNA for the M1 marker NOS-2 in granuloma macrophages but levels of M2 markers (CD206, arginase-1 and Ym-1, MMPs-2, -9, -12, -13, -14 and -19 or TIMPs-1 to -3 were unchanged. No mRNA differences were observed in aortic extracts from mice fed a HFD for 12 weeks. Moreover, AS and BCA plaques were similarly sized between genotypes, and had similar areas stained for NOS-2, COX-2, MMP-12 and MMP-14 proteins. T-bet deletion increased MMP-13, MMP-14 and arginase-1 in AS plaques. After 35 weeks of ND, T-bet deletion reduced the size of AS and BCA plaques but there were no differences in the percentage areas stained for M1 or M2 markers, MMPs-12, -13, -14, or TIMP-3.Absence of Th1 lymphocytes is associated with reduced plaque size in ApoE knockout mice fed a normal but not high fat diet. In either case, M1 macrophage polarization and expression of several MMPs related to plaque instability are either maintained or increased.

  4. Chemical Simulations of Prebiotic Molecules: Interstellar Ethanimine Isomers

    Science.gov (United States)

    Quan, Donghui; Herbst, Eric; Corby, Joanna F.; Durr, Allison; Hassel, George

    2016-06-01

    The E- and Z-isomers of ethanimine (CH3CHNH) were recently detected toward the star-forming region Sagittarius (Sgr) B2(N) using the Green Bank Telescope PRIMOS cm-wave spectral data, and imaged by the Australia Telescope Compact Array. Ethanimine is not reported in the hot cores of Sgr B2, but only in gas that absorbs at +64 and +82 km s-1 in the foreground of continuum emission generated by H ii regions. The ethanimine isomers can serve as precursors of the amino acid alanine and may play important roles in forming biological molecules in the interstellar medium. Here we present a study of the chemistry of ethanimine using a gas-grain simulation based on rate equations, with both isothermal and warm-up conditions. In addition, the density, kinetic temperature, and cosmic ray ionization rate have been varied. For a variety of physical conditions in the warm-up models for Sgr B2(N) and environs, the simulations show reasonable agreement with observationally obtained abundances. Isothermal models of translucent clouds along the same line of sight yield much lower abundances, so that ethanimine would be much more difficult to detect in these sources despite the fact that other complex molecules have been detected there.

  5. The prenucleosome, a stable conformational isomer of the nucleosome.

    Science.gov (United States)

    Fei, Jia; Torigoe, Sharon E; Brown, Christopher R; Khuong, Mai T; Kassavetis, George A; Boeger, Hinrich; Kadonaga, James T

    2015-12-15

    Chromatin comprises nucleosomes as well as nonnucleosomal histone-DNA particles. Prenucleosomes are rapidly formed histone-DNA particles that can be converted into canonical nucleosomes by a motor protein such as ACF. Here we show that the prenucleosome is a stable conformational isomer of the nucleosome. It consists of a histone octamer associated with ∼ 80 base pair (bp) of DNA, which is located at a position that corresponds to the central 80 bp of a nucleosome core particle. Monomeric prenucleosomes with free flanking DNA do not spontaneously fold into nucleosomes but can be converted into canonical nucleosomes by an ATP-driven motor protein such as ACF or Chd1. In addition, histone H3K56, which is located at the DNA entry and exit points of a canonical nucleosome, is specifically acetylated by p300 in prenucleosomes relative to nucleosomes. Prenucleosomes assembled in vitro exhibit properties that are strikingly similar to those of nonnucleosomal histone-DNA particles in the upstream region of active promoters in vivo. These findings suggest that the prenucleosome, the only known stable conformational isomer of the nucleosome, is related to nonnucleosomal histone-DNA species in the cell.

  6. Reduced Necrosis and Content of Apoptotic M1 Macrophages in Advanced Atherosclerotic Plaques of Mice With Macrophage-Specific Loss of Trpc3

    Science.gov (United States)

    Solanki, Sumeet; Dube, Prabhatchandra R.; Birnbaumer, Lutz; Vazquez, Guillermo

    2017-01-01

    In previous work we reported that ApoeKO mice transplanted with bone marrow cells deficient in the Transient Receptor Potential Canonical 3 (TRPC3) channel have reduced necrosis and number of apoptotic macrophages in advanced atherosclerotic plaques. Also, in vitro studies with polarized macrophages derived from mice with macrophage-specific loss of TRPC3 showed that M1, but not M2 macrophages, deficient in Trpc3 are less susceptible to ER stress-induced apoptosis than Trpc3 expressing cells. The questions remained (a) whether the plaque phenotype in transplanted mice resulted from a genuine effect of Trpc3 on macrophages, and (b) whether the reduced necrosis and macrophage apoptosis in plaques of these mice was a manifestation of the selective effect of TRPC3 on apoptosis of M1 macrophages previously observed in vitro. Here, we addressed these questions using Ldlr knockout (Ldlr−/−) mice with macrophage-specific loss of Trpc3 (MacTrpc3−/−/Ldlr−/− → Ldlr−/−). Compared to controls, we observed decreased plaque necrosis and number of apoptotic macrophages in MacTrpc3−/−/Ldlr−/− → Ldlr−/− mice. Immunohistochemical analysis revealed a reduction in apoptotic M1, but not apoptotic M2 macrophages. These findings confirm an effect of TRPC3 on plaque necrosis and support the notion that this is likely a reflection of the reduced susceptibility of Trpc3-deficient M1 macrophages to apoptosis. PMID:28186192

  7. Hyperoxia Exacerbates Postnatal Inflammation-Induced Lung Injury in Neonatal BRP-39 Null Mutant Mice Promoting the M1 Macrophage Phenotype

    Directory of Open Access Journals (Sweden)

    Mansoor A. Syed

    2013-01-01

    Full Text Available Rationale. Hyperoxia exposure to developing lungs—critical in the pathogenesis of bronchopulmonary dysplasia—may augment lung inflammation by inhibiting anti-inflammatory mediators in alveolar macrophages. Objective. We sought to determine the O2-induced effects on the polarization of macrophages and the role of anti-inflammatory BRP-39 in macrophage phenotype and neonatal lung injury. Methods. We used RAW264.7, peritoneal, and bone marrow derived macrophages for polarization (M1/M2 studies. For in vivo studies, wild-type (WT and BRP-39−/− mice received continuous exposure to 21% O2 (control mice or 100% O2 from postnatal (PN 1 to PN7 days, along with intranasal lipopolysaccharide (LPS administered on alternate days (PN2, -4, and -6. Lung histology, bronchoalveolar lavage (BAL cell counts, BAL protein, and cytokines measurements were performed. Measurements and Main Results. Hyperoxia differentially contributed to macrophage polarization by enhancing LPS induced M1 and inhibiting interleukin-4 induced M2 phenotype. BRP-39 absence led to further enhancement of the hyperoxia and LPS induced M1 phenotype. In addition, BRP-39−/− mice were significantly more sensitive to LPS plus hyperoxia induced lung injury and mortality compared to WT mice. Conclusions. These findings collectively indicate that BRP-39 is involved in repressing the M1 proinflammatory phenotype in hyperoxia, thereby deactivating inflammatory responses in macrophages and preventing neonatal lung injury.

  8. 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.

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

    Science.gov (United States)

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

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

  10. Identification of M1 muscarinic receptors in pulmonary sympathetic nerves in the guinea-pig by use of pirenzepine.

    Science.gov (United States)

    Maclagan, J.; Fryer, A. D.; Faulkner, D.

    1989-01-01

    1. The effect of pirenzepine, a muscarinic antagonist considered to be selective for M1 receptors, was studied on bronchoconstriction and bradycardia elicited by preganglionic stimulation of the parasympathetic vagal nerves and by i.v. injections of acetylcholine (ACh) in anaesthetized guinea-pigs. 2. Pirenzepine was equipotent in the heart and lung as an antagonist of the effects of i.v. ACh at postjunctional muscarinic receptors. Doses of pirenzepine in excess of 1 mumol kg-1 abolished all muscarinic responses consistent with non-selective blockade of M3 receptors on airway smooth muscle and M2 receptors on atrial cells. 3. In the lung, low doses of pirenzepine (1-100 nmol kg-1) increased vagally-induced bronchoconstriction despite concurrent partial blockade of the postjunctional receptors. This suggests blockade of neuronal muscarinic receptors. 4. Propranolol (1 mg kg-1) increased control bronchoconstrictor responses elicited by ACh and vagal stimulation but did not alter the potency of pirenzepine for postjunctional receptors in heart or lung. However, pirenzepine-induced enhancement of vagally-induced bronchoconstriction was abolished by propranolol, suggesting that pirenzepine may be an antagonist for muscarinic receptors located in the sympathetic nerves innervating airway smooth muscle. 5. These results confirm that bronchoconstrictor stimuli indirectly initiate activation of an opposing sympathetic reflex in the guinea-pig lung. This response is facilitated by muscarinic receptors located in the sympathetic nervous pathway. 6. The high potency of pirenzepine for the neuronal receptors in the sympathetic nerves suggests that these are M1 receptors. In contrast, the parasympathetic nerves innervating airway smooth muscle in this species contain M2 receptors which inhibit neurotransmission. PMID:2758228

  11. Induction of murine macrophage M2 polarization by cigarette smoke extract via the JAK2/STAT3 pathway.

    Directory of Open Access Journals (Sweden)

    Fengjiao Yuan

    Full Text Available Cigarette smoking is a major pathogenic factor in lung cancer. Macrophages play an important role in host defense and adaptive immunity. These cells display diverse phenotypes for performing different functions. M2 type macrophages usually exhibit immunosuppressive and tumor-promoting characteristics. Although macrophage polarization toward the M2 phenotype has been observed in the lungs of cigarette smokers, the molecular basis of the process remains unclear. In this study, we evaluated the possible mechanisms for the polarization of mouse macrophages that are induced by cigarette smoking (CS or cigarette smoke extract (CSE. The results showed that exposure to CSE suppressed the production of reactive oxygen species (ROS and nitric oxide (NO and down-regulated the phagocytic ability of Ana-1 cells. The CD163 expressions on the surface of macrophages from different sources were significantly increased in in vivo and in vitro studies. The M1 macrophage cytokines TNF-α, IL-12p40 and enzyme iNOS decreased in the culture supernatant, and their mRNA levels decreased depending on the time and concentration of CSE. In contrast, the M2 phenotype macrophage cytokines IL-10, IL-6, TGF-β1 and TGF-β2 were up-regulated. Moreover, phosphorylation of JAK2 and STAT3 was observed after the Ana-1 cells were treated with CSE. In addition, pretreating the Ana-1 cells with the STAT3 phosphorylation inhibitor WP1066 inhibited the CSE-induced CD163 expression, increased the mRNA level of IL-10 and significantly decreased the mRNA level of IL-12. In conclusion, we demonstrated that the M2 polarization of macrophages induced by CS could be mediated through JAK2/STAT3 pathway activation.

  12. Association between CYP1A1m1 gene polymorphism and primary open-angle glaucoma.

    Science.gov (United States)

    Costa, N B; Silva, C T X; Frare, A B; Silva, R E; Moura, K K V O

    2014-12-04

    The CYP1A1 gene is related to the generation of secondary metabolites that are capable of inducing DNA damage. The CYP1A1m1 polymorphism has been examined in many studies, and is located in a region near loci that have been linked to glaucoma, including the locus GLC1I. As a result, this polymorphism has been related to several diseases that are influenced by exposure to xenobiotic as well as primary open-angle glaucoma. We compared the prevalence of the CYP1A1m1 polymorphism in 152 Brazilian patients, 100 patients with primary open-angle glaucoma, and 52 normal controls using restriction fragment length polymorphism analysis. The frequency of the homozygous wild-type (w1/w1) CYP1A1 gene among patients with primary open-angle glaucoma (N = 100) was 16%, for genotype w1/m1, the frequency was 77%, and for m1/m1 it was 7%. Among the control group (N = 52), the frequency of the homozygous wild-type (w1/w1) CYP1A1 gene was 54%, the frequency of w1/m1 was 46%, and the frequency of m1/m1 was 0%. The presence of the CYP1A1m1 polymorphism may interfere with xenobiotic metabolism and exacerbate direct or indirect damage to the optic nerve. These CYP1A1m1 polymorphisms may be risk factors for primary open-angle glaucoma.

  13. The behaviour of EDDHA isomers in soils as influenced by soil properties.

    NARCIS (Netherlands)

    Schenkeveld, W.D.C.; Reichwein, A.M.; Temminghoff, E.J.M.; Riemsdijk, van W.H.

    2007-01-01

    FeEDDHA products are applied to correct iron chlorosis in plants and consist of a mixture of EDDHA isomers chelated to iron. In this study such mixtures have been divided into four (groups of) isomers: racemic o,o-EDDHA, meso o,o-EDDHA, o,p-EDDHA and rest-EDDHA. The physical and chemical properties

  14. Structures and stability of isomers of [Si,N,N,P] system

    Institute of Scientific and Technical Information of China (English)

    KAN Wei; YU Haitao; LI Mingxia; FU Honggang; SUN Jiazhong

    2004-01-01

    Some stationary points on the potential energy surface of [Si, N, N, P] system were located at the B3LYP/6-311G(d) and QCISD(t)/6-311+G(2df)(single-point) levels of theory, while the isomerization, structures, and stability of these obtained isomers were suggested. The computed results indicate that only four-membered ring isomer SiNPN(E1, 2A"), which possesses butterfly-like structure and Si-P cross bonding, is kinetically stable in all optimized isomers. Other isomers may be considered as kinetically unstable towards isomerization or dissociation because of the corresponding smaller reaction barriers. Furthermore, the present paper also proposes electronic and geometric structures, vibrational frequencies and the corresponding vibrational modes, dipole moments, and rotational constants of isomer E1. To make use of the computed results, we can clearly know that the reaction pathway via an intermediate E3 (SiNPN) is the most favorable channel producing isomer E1 from fragments SiN (2∏) and PN (1∑), which have been well characterized in space, and thus, isomer E1 can be considered as a candidate for interstellar observation. The reaction enthalpy of SiN (2∏) + pN(1∑)→E1 and the standard enthalpy of formation of isomer E1 are 215.25 and 457.99 k J/mol, respectively, at 298.15 K.

  15. Influenza A Virus NS1 Protein Promotes Efficient Nuclear Export of Unspliced Viral M1 mRNA.

    Science.gov (United States)

    Pereira, Carina F; Read, Eliot K C; Wise, Helen M; Amorim, Maria J; Digard, Paul

    2017-08-01

    Influenza A virus mRNAs are transcribed by the viral RNA-dependent RNA polymerase in the cell nucleus before being exported to the cytoplasm for translation. Segment 7 produces two major transcripts: an unspliced mRNA that encodes the M1 matrix protein and a spliced transcript that encodes the M2 ion channel. Export of both mRNAs is dependent on the cellular NXF1/TAP pathway, but it is unclear how they are recruited to the export machinery or how the intron-containing but unspliced M1 mRNA bypasses the normal quality-control checkpoints. Using fluorescent in situ hybridization to monitor segment 7 mRNA localization, we found that cytoplasmic accumulation of unspliced M1 mRNA was inefficient in the absence of NS1, both in the context of segment 7 RNPs reconstituted by plasmid transfection and in mutant virus-infected cells. This effect was independent of any major effect on steady-state levels of segment 7 mRNA or splicing but corresponded to a ∼5-fold reduction in the accumulation of M1. A similar defect in intronless hemagglutinin (HA) mRNA nuclear export was seen with an NS1 mutant virus. Efficient export of M1 mRNA required both an intact NS1 RNA-binding domain and effector domain. Furthermore, while wild-type NS1 interacted with cellular NXF1 and also increased the interaction of segment 7 mRNA with NXF1, mutant NS1 polypeptides unable to promote mRNA export did neither. Thus, we propose that NS1 facilitates late viral gene expression by acting as an adaptor between viral mRNAs and the cellular nuclear export machinery to promote their nuclear export.IMPORTANCE Influenza A virus is a major pathogen of a wide variety of mammalian and avian species that threatens public health and food security. A fuller understanding of the virus life cycle is important to aid control strategies. The virus has a small genome that encodes relatively few proteins that are often multifunctional. Here, we characterize a new function for the NS1 protein, showing that, as well as

  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. Quantification of minerals and tocopherols isomers in chestnuts approach chemometrics

    Directory of Open Access Journals (Sweden)

    Nilson Evelazio de Souza

    2014-10-01

    Full Text Available The levels of the ?, ?, and (?+?-tocopherol isomers and the amounts of the minerals Se, Zn, Ca, Fe, K, Mn, Mg, and Cu were analyzed in chestnuts. High contents of Zn (>65% relative to the recommended dietary intake (RDI were found in all chestnuts except macadamia nuts (25% of the RDI. All samples had Se contents higher than the RDI: Brazil nuts > macadamia nuts, cashew nuts > pecans > almonds > pistachio nuts > hazelnuts > European nuts. A greater concentration of ?-tocopherol was found in almonds (30% of RDI. All samples, except for hazelnuts, almonds, and macadamia nuts, had (?+?- tocopherols, with the largest amount found in pistachios. Only pecan nuts and European nuts had ?-tocopherol and only in low amounts. Multivariate analysis allowed for better characterization and distinction of the chestnuts

  5. Synthesis and Applications of Hajos-Parrish Ketone Isomers.

    Science.gov (United States)

    Eagan, James M; Hori, Masahiro; Wu, Jianbin; Kanyiva, Kyalo Stephen; Snyder, Scott A

    2015-06-26

    Numerous natural products possess ring systems and functionality for which Hajos-Parrish ketone isomers with a transposed methyl group (termed "iso-Hajos-Parrish ketones") would be of value. However, such building blocks have not been exploited to the same degree as the more typical Hajos-Parrish hydrindane. An efficient three-step synthesis of such materials was fueled by a simple method for the rapid preparation of highly functionalized cyclopentenones, several of which are new chemical entities that would be challenging to access through other approaches. Furthermore, one iso-Hajos-Parrish ketone was converted into two distinct natural product analogues and one natural product. As one indication of the value of these new building blocks, that latter target was obtained in 10 steps, having previously been accessed in 18 steps using the Hajos-Parrish ketone. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Electronic Single Molecule Identification of Carbohydrate Isomers by Recognition Tunneling

    CERN Document Server

    Im, JongOne; Liu, Hao; Zhao, Yanan; Sen, Suman; Biswas, Sudipta; Ashcroft, Brian; Borges, Chad; Wang, Xu; Lindsay, Stuart; Zhang, Peiming

    2016-01-01

    Glycans play a central role as mediators in most biological processes, but their structures are complicated by isomerism. Epimers and anomers, regioisomers, and branched sequences contribute to a structural variability that dwarfs those of nucleic acids and proteins, challenging even the most sophisticated analytical tools, such as NMR and mass spectrometry. Here, we introduce an electron tunneling technique that is label-free and can identify carbohydrates at the single-molecule level, offering significant benefits over existing technology. It is capable of analyzing sub-picomole quantities of sample, counting the number of individual molecules in each subset in a population of coexisting isomers, and is quantitative over more than four orders of magnitude of concentration. It resolves epimers not well separated by ion-mobility and can be implemented on a silicon chip. It also provides a readout mechanism for direct single-molecule sequencing of linear oligosaccharides.

  7. Separation of C6-Olefin Isomers in Reactive Extractants

    Institute of Scientific and Technical Information of China (English)

    SONG Fengxia; YU Yanmei; CHEN Jian

    2008-01-01

    Chemical complexation,in which certain metal ions (especially Ag+ and Cu+) reversibly and selectively complex olefin isomers,was used to separate 1-hexene from a mixture of intemal hexenes as an attractive alternative to traditional distillation.Several potential reactive extractants were investigated for their selectivity of both 1-hexene to 2-hexene and 1-hexene to 3-hexene.With 3 mol/L AgNO3-N-methyl-pyrrolidone (NMP) solution as extractant,the selectivity of 1-hexene to 3-hexane was increased to about 2.0 and the selectivity of 1-hexene to 2-hexene reached 1.5.Both the raffinate phase and the extracted phase were analyzed using a gas chromatograph equipped with a flame ionization detector and a 50-m capillary column.The experimental results show that the silver nitrate NMP solution has the better selectivity than other reactive extractions.

  8. Energetics of cyclohexane isomers: a density-functional study

    CERN Document Server

    Lee, C Y

    1999-01-01

    The binding energies and the geometric structures of conformational isomers of cyclohexane (C sub 6 H sub 1 sub 2) are determined from the density-functional theory combined with ultrasoft pseudopotentials and gradient-corrected nonlocal exchange-correlation functionals. The ground-state chair conformation is found to have a binding energy of 99.457 eV, and the metastable twist-boat conformation has 99.161 eV. The chair conformation converts to another conformation via a half-chair conformation with an energy barrier of 0.507 eV whereas the twist-boat conformation converts to another twist-boat conformation via a boat conformation with a much smaller energy barrier of 0.015 eV.

  9. Electronic Structure and Stability of C20 Isomers

    Institute of Scientific and Technical Information of China (English)

    曹则贤

    2001-01-01

    The electronic structure of the C20 cluster in monocyclic ring, bowl and fullerene isomers has been calculated using the tight-binding scheme developed by Harrison, starting in particular from the sp2.803-hybrids for the fullerene structure. The study of energetics predicts the fullerene to be the ground state with the bowl and ring lying over 1.32 and 3.35 eV higher in energy. The total energies will be lowered by Peierls or Jahn-Teller distortion, but the energetic ordering remains unchanged. It is also shown that the range of valence electron, the level difference between the highest occupied molecular orbital and the lowest unoccupied molecular orbital as well as the σ - π gap, which are less sensitive to the exact geometry, vary in the ring, bowl and fullerene sequence.

  10. Communication: "Position" does matter: The photofragmentation of the nitroimidazole isomers

    Science.gov (United States)

    Bolognesi, P.; Casavola, A. R.; Cartoni, A.; Richter, R.; Markus, P.; Borocci, S.; Chiarinelli, J.; Tošić, S.; Sa'adeh, H.; Masič, M.; Marinković, B. P.; Prince, K. C.; Avaldi, L.

    2016-11-01

    A combined experimental and theoretical approach has been used to disentangle the fundamental mechanisms of the fragmentation of the three isomers of nitroimidazole induced by vacuum ultra-violet (VUV) radiation, namely, 4-, 5-, and 2-nitroimidazole. The results of mass spectrometry as well as photoelectron-photoion coincidence spectroscopy display striking differences in the radiation-induced decomposition of the different nitroimidazole radical cations. Based on density functional theory (DFT) calculations, a model is proposed which fully explains such differences, and reveals the subtle fragmentation mechanisms leading to the release of neutral species like NO, CO, and HCN. Such species have a profound impact in biological media and may play a fundamental role in radiosensitising mechanisms during radiotherapy.

  11. Metabolic engineering of Saccharomyces cerevisiae for production of butanol isomers.

    Science.gov (United States)

    Generoso, Wesley Cardoso; Schadeweg, Virginia; Oreb, Mislav; Boles, Eckhard

    2015-06-01

    Saccharomyces cerevisiae has decisive advantages in industrial processes due to its tolerance to alcohols and fermentation conditions. Butanol isomers are considered as suitable fuel substitutes and valuable biomass-derived chemical building blocks. Whereas high production was achieved with bacterial systems, metabolic engineering of yeast for butanol production is in the beginning. For isobutanol synthesis, combination of valine biosynthesis and degradation, and complete pathway re-localisation into cytosol or mitochondria gave promising results. However, competing pathways, co-factor imbalances and FeS cluster assembly are still major issues. 1-Butanol production via the Clostridium pathway seems to be limited by cytosolic acetyl-CoA, its central precursor. Endogenous 1-butanol pathways have been discovered via threonine or glycine catabolism. 2-Butanol production was established but was limited by B12-dependence.

  12. Submolecular imaging of chloronitrobenzene isomers on Cu(111)

    Science.gov (United States)

    Niemi, Eeva; Simic-Milosevic, Violeta; Morgenstern, Karina; Korventausta, Antti; Paavilainen, Sami; Nieminen, Jouko

    2006-11-01

    We compare computer simulations to experimental scanning tunneling microscopy (STM) images of chloronitrobenzene molecules on a Cu(111) surface. The experiments show that adsorption induced isomerization of the molecules takes place on the surface. Furthermore, not only the submolecular features can be seen in the STM images, but different isomers can also be recognized. The Todorov-Pendry approach to tunneling produces simulated STM images which are in good accordance with the experiments. Alongside with STM simulations in a tight-binding basis, ab initio calculations are performed in order to analyze the symmetry of relevant molecular orbitals and to consider the nature of tunneling channels. Our calculations show that while the orbitals delocalized to the phenyl ring create a relatively transparent tunneling channel, they also almost isolate the orbitals of the substitute groups at energies which are relevant in STM experiments. These features of the electronic structure are the key ingredients of the accurate submolecular observations.

  13. Enantiomers of a nonylphenol isomer: absolute configurations and estrogenic potencies.

    Science.gov (United States)

    Zhang, Haifeng; Oppel, Iris M; Spiteller, Michael; Guenther, Klaus; Boehmler, Gabriele; Zuehlke, Sebastian

    2009-02-01

    Enantiomers of 4-(1,1,2-trimethylhexyl)phenol, a chiral isomer of the endocrine disrupting chemical nonylphenol, have been resolved and isolated by preparative chiral HPLC. The absolute configurations of the enantiomers were then determined by an X-ray crystallographic study of the (-)-camphanoyl derivative of the first eluted enantiomer NP(35)E1. The first enantiomer (NP(35)E1) and the second enantiomer (NP(35)E2) eluted were found to have the S and R absolute configurations, respectively. The estrogenic potencies of the S and R enantiomers were tested by the E-screen assay. A slight difference was observed in the relative proliferative effect between the S enantiomer and R enantiomer in the E-screen assay.

  14. Pharmacologic or Genetic Targeting of Glutamine Synthetase Skews Macrophages toward an M1-like Phenotype and Inhibits Tumor Metastasis

    Directory of Open Access Journals (Sweden)

    Erika M. Palmieri

    2017-08-01

    Full Text Available Glutamine-synthetase (GS, the glutamine-synthesizing enzyme from glutamate, controls important events, including the release of inflammatory mediators, mammalian target of rapamycin (mTOR activation, and autophagy. However, its role in macrophages remains elusive. We report that pharmacologic inhibition of GS skews M2-polarized macrophages toward the M1-like phenotype, characterized by reduced intracellular glutamine and increased succinate with enhanced glucose flux through glycolysis, which could be partly related to HIF1α activation. As a result of these metabolic changes and HIF1α accumulation, GS-inhibited macrophages display an increased capacity to induce T cell recruitment, reduced T cell suppressive potential, and an impaired ability to foster endothelial cell branching or cancer cell motility. Genetic deletion of macrophagic GS in tumor-bearing mice promotes tumor vessel pruning, vascular normalization, accumulation of cytotoxic T cells, and metastasis inhibition. These data identify GS activity as mediator of the proangiogenic, immunosuppressive, and pro-metastatic function of M2-like macrophages and highlight the possibility of targeting this enzyme in the treatment of cancer metastasis.

  15. Structures and stability of isomers of [C,N,N,P] system

    Institute of Scientific and Technical Information of China (English)

    KAN Wei; ZHONG Hua; YU Haitao; FU Honggang; SUN Jiazhong

    2005-01-01

    Nine isomers, twenty transition states, and some relative dissociation fragments of [C,N,N,P] system were located at the B3LYP/6-311G(d) and QCISD(t)/6-311+G(2df) (single-point) levels of theory, and the isomerization, structures, and stability of these obtained isomers were suggested. The results indicate that four nonlinear chainlike isomers NCNP, NCPN, CNPN, and CNNP with 2A′ electronic state are kinetically stable. Other isomers are kinetically unstable towards isomerization or dissociation because of the corresponding smaller reaction barriers. Furthermore, calculated vibrational frequencies, rotational constants, dipole moments, the first adiabatic ionization energies, and adiabatic electron affinities of the four isomers may provide some theoretical information that is helpful for identifying their existence in future laboratory and interstellar investigations. The results are also compared with [Si,N,N,P] system.

  16. Aqueous phase partitioning of hexachlorocyclohexane (HCH) isomers by biosurfactant produced by Pseudomonas aeruginosa WH-2

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Suman; Singh, Partapbir [Department of Microbiology, Guru Nanak Dev University, Amritsar 143005, Punjab (India); Raj, Mayil [MTCC, IMTECH, Sector 39-A, Chandigarh 160036 (India); Chadha, Bhupinder Singh [Department of Microbiology, Guru Nanak Dev University, Amritsar 143005, Punjab (India); Saini, Harvinder Singh, E-mail: sainihs@yahoo.com [Department of Microbiology, Guru Nanak Dev University, Amritsar 143005, Punjab (India)

    2009-11-15

    The different isomers of technical-grade hexachlorocyclohexane (t-HCH) including the insecticidal {gamma}-isomer, commonly known as lindane, have been reported to be toxic, carcinogenic and endocrine disrupters. The spatial arrangements of the chlorine atoms on different isomers and low aqueous phase solubility contribute to their persistence in environment, {beta}-HCH being the most resistance to transformation. The biosurfactant preparation of Pseudomonas aeruginosa isolate WH-2 was evaluated for its ability to improve the aqueous phase partitioning of different isomers of HCH-muck. Further, the ability of biosurfactant preparation to emulsify HCH and n-hexadecane was checked under different conditions, usually characteristic of sites contaminated with pollutants viz. wide range of pH, temperature, and salinity. The data obtained from this study will be helpful in designing suitable bioremediation strategies for huge stock piles of HCH-muck and sites polluted by reckless use/disposal of HCH-isomers.

  17. Comparative Autoignition Trends in Butanol Isomers at Elevated Pressure

    KAUST Repository

    Weber, Bryan W.

    2013-03-21

    Autoignition experiments of stoichiometric mixtures of s-, t-, and i-butanol in air have been performed using a heated rapid compression machine (RCM). At compressed pressures of 15 and 30 bar and for compressed temperatures in the range 715-910 K, no evidence of a negative temperature coefficient region in terms of ignition delay response is found. The present experimental results are also compared with previously reported RCM data of n-butanol in air. The order of reactivity of the butanols is n-butanol > s-butanol ≈ i-butanol > t-butanol at the lower pressure but changes to n-butanol > t-butanol > s-butanol > i-butanol at higher pressure. In addition, t-butanol shows preignition heat release behavior, which is especially evident at higher pressures. To help identify the controlling chemistry leading to this preignition heat release, off-stoichiometric experiments are further performed at 30 bar compressed pressure, for t-butanol at φ = 0.5 and φ = 2.0 in air. For these experiments, higher fuel loading (i.e., φ = 2.0) causes greater preignition heat release (as indicated by greater pressure rise) than the stoichiometric or φ = 0.5 cases. Comparison of the experimental ignition delays with the simulated results using two literature kinetic mechanisms shows generally good agreement, and one mechanism is further used to explore and compare the fuel decomposition pathways of butanol isomers. Using this mechanism, the importance of peroxy chemistry in the autoignition of the butanol isomers is highlighted and discussed. © 2013 American Chemical Society.

  18. Temperature Effects on the Dissociative Electron Attachment to Dichlorobenzene Isomers

    Science.gov (United States)

    Mahmoodi-Darian, M.; Mauracher, A.; Aleem, A.; Denifl, S.; Rittenschober, B.; Bacher, A.; Probst, M.; Märk, T. D.; Scheier, P.

    2009-10-01

    Dissociative electron attachment to all three isomers of dichlorobenzene has been investigated in the electron energy range from 0 to 2 eV and in the gas temperature range from 391 to 696 K using a crossed electron-molecular beam apparatus with a new temperature-regulated effusive molecular beam source. In the case of the dissociative electron attachment channel Cl-/1,2-dichlorobenzene and Cl-/1,4-dichlorobenzene, strong enhancement of the negative ion production with the gas temperature at low electron energies has been observed. The low-energy peak increases dramatically when the gas temperature is raised from 391 to 696 K. Activation energies for dissociative electron attachment of (482 ± 20) meV for 1,2-dichlorobenzene and (59 ± 20) meV for 1,4-dichlorobenzene have been determined. For the resonance at (0.49 ± 0.03) eV in 1,2-dichlorobenzene and (0.32 ± 0.03) eV in 1,4-dichlorobenzene, no dependence of the cross sections on the gas temperature has been observed. In the case of the dissociative electron attachment to Cl-/1,3-dichlorobenzene, the cross section does not depend on the temperature in the electron energy range from 0 to 2 eV. Quantum chemical calculations of the reaction energies and of the potential energy curves involved in the dissociation of Cl- have been performed, together with an analysis of the thermo dynamical accessibility of the relevant vibrational modes. Possible reasons for the different temperature dependences of the isomers are discussed.

  19. Table of superdeformed nuclear bands and fission isomers

    Energy Technology Data Exchange (ETDEWEB)

    Firestone, R.B. [Lawrence Berkeley Lab., CA (United States); Singh, B. [McMaster Univ., Hamilton, ON (Canada)

    1994-06-01

    A minimum in the second potential well of deformed nuclei was predicted and the associated shell gaps are illustrated in the harmonic oscillator potential shell energy surface calculations shown in this report. A strong superdeformed minimum in {sup 152}Dy was predicted for {beta}{sub 2}-0.65. Subsequently, a discrete set of {gamma}-ray transitions in {sup 152}DY was observed and, assigned to the predicted superdeformed band. Extensive research at several laboratories has since focused on searching for other mass regions of large deformation. A new generation of {gamma}-ray detector arrays is already producing a wealth of information about the mechanisms for feeding and deexciting superdeformed bands. These bands have been found in three distinct regions near A=l30, 150, and 190. This research extends upon previous work in the actinide region near A=240 where fission isomers were identified and also associated with the second potential well. Quadrupole moment measurements for selected cases in each mass region are consistent with assigning the bands to excitations in the second local minimum. As part of our committment to maintain nuclear structure data as current as possible in the Evaluated Nuclear Structure Reference File (ENSDF) and the Table of Isotopes, we have updated the information on superdeformed nuclear bands. As of April 1994, we have complied data from 86 superdeformed bands and 46 fission isomers identified in 73 nuclides for this report. For each nuclide there is a complete level table listing both normal and superdeformed band assignments; level energy, spin, parity, half-life, magneto moments, decay branchings; and the energies, final levels, relative intensities, multipolarities, and mixing ratios for transitions deexciting each level. Mass excess, decay energies, and proton and neutron separation energies are also provided from the evaluation of Audi and Wapstra.

  20. Identification of m =2 competent mode of complex magneto-hydro-dynamics activities during internal soft disruption based on singular value decomposition and tomography of soft-X-ray emission on the HT-7 tokamak

    Institute of Scientific and Technical Information of China (English)

    Xu Li-Qing; Mao Song-Tao; Duan Yan-Min; Hu Li-Qun; Li Er-Zhong; Chen Kai-Yun; Liu Zhi-Yuan; Chen Ye-Bin; Zhang Ji-Zong; Zhou Rui-Jie; Yang Mao

    2012-01-01

    In this paper,the singular value decomposition(SVD)method as a filter is applied before the tomographic inversion of soft-X-ray emission.Series of ‘filtered' signals including specific chronos and topos are obtained.(Here,chronos and topos are the decomposed spatial vectors and the decomposed temporal vectors,respectively).Given specific magnetic flux function with coupling m=1 and m=2 modes,the line-integrated soft-X-ray signals at all chords have been obtained.Then m=1 and m=2 modes have been identified by tomography of simulated ‘filtered' signals extracted by the SVD method.Finaly,using the experimental line-integrated soft-X-ray signals,m=2 competent mode of complex magnetohydrodynamics(MHD)activities during internal soft disruption is observed.This result demonstrates that m=2 mode plays an important role in internal disruption(Here,m is the poloidal mode number).

  1. Identification of m = 2 competent mode of complex magneto-hydro-dynamics activities during internal soft disruption based on singular value decomposition and tomography of soft-X-ray emission on the HT-7 tokamak

    Science.gov (United States)

    Xu, Li-Qing; Hu, Li-Qun; Li, Er-Zhong; Chen, Kai-Yun; Liu, Zhi-Yuan; Chen, Ye-Bin; Zhang, Ji-Zong; Zhou, Rui-Jie; Yang, Mao; Mao, Song-Tao; Duan, Yan-Min

    2012-05-01

    In this paper, the singular value decomposition (SVD) method as a filter is applied before the tomographic inversion of soft-X-ray emission. Series of ‘filtered’ signals including specific chronos and topos are obtained. (Here, chronos and topos are the decomposed spatial vectors and the decomposed temporal vectors, respectively). Given specific magnetic flux function with coupling m = 1 and m = 2 modes, the line-integrated soft-X-ray signals at all chords have been obtained. Then m = 1 and m = 2 modes have been identified by tomography of simulated ‘filtered’ signals extracted by the SVD method. Finaly, using the experimental line-integrated soft-X-ray signals, m = 2 competent mode of complex magnetohydrodynamics(MHD) activities during internal soft disruption is observed. This result demonstrates that m = 2 mode plays an important role in internal disruption (Here, m is the poloidal mode number).

  2. [Estimation of efficiency of seed irradiation by thermal neutrons for inducing chromosomal aberration in M2 of cotton Gossipium hirsutum L].

    Science.gov (United States)

    Rakhmatullina, E M; Sanam'ian, M F

    2007-05-01

    Cytogenetic analysis of M2 plants after irradiation of cotton by thermal neutrons was performed in 56 families. In 40 plants of 27 M2 families, different abnormalities of chromosome pairing were found. These abnormalities were caused by primary monosomy, chromosomal interchange, and desynapsis. The presence of chromosome aberrations in some cases decreased meiotic index and pollen fertility. Comparison of the results of cytogenetics analysis, performed in M1 and M2 after irradiation, showed a nearly two-fold decrease in the number of plants with chromosomal aberrations in M2, as well as narrowing of the spectrum of these aberrations. The latter result is explained by the fact that some mutations are impossible to detect in subsequent generations because of complete or partial sterility of aberrant M1 plants. It was established that the most efficient radiation doses for inducing chromosomal aberrations in the present study were 15 and 25 Gy, since they affected survival and fertility of altered plant to a lesser extent.

  3. Astrocyte-Derived CCL2 is Associated with M1 Activation and Recruitment of Cultured Microglial Cells

    Directory of Open Access Journals (Sweden)

    Mingfeng He

    2016-02-01

    Full Text Available Background/Aims: Microglia are an essential player in central nervous system inflammation. Recent studies have demonstrated that the astrocytic chemokine, CCL2, is associated with microglial activation in vivo. However, CCL2-induced microglial activation has not yet been studied in vitro. The purpose of the current study was to understand the role of astrocyte-derived CCL2 in microglial activation and to elucidate the underlying mechanism(s. Methods: Primary astrocytes were pre-treated with CCL2 siRNA and stimulated with TNF-α. The culture medium (CM was collected and added to cultures of microglia, which were incubated with and without CCR2 inhibitor. Microglial cells were analyzed by quantitative RT-PCR to determine whether they polarized to the M1 or M2 state. Microglial migratory ability was assessed by transwell migration assay. Results: TNF-α stimulated the release of CCL2 from astrocytes, even if the culture media containing TNF-α was replaced with fresh media after 3 h. CM from TNF-α-stimulated astrocytes successfully induced microglial activation, which was ascertained by increased activation of M1 and enhanced migration ability. In contrast, CM from astrocytes pretreated with CCL2 siRNA showed no effect on microglial activation, compared to controls. Additionally, microglia pre-treated with RS102895, a CCR2 inhibitor, were resistant to activation by CM from TNF-α-stimulated astrocytes. Conclusion: This study demonstrates that the CCL2/CCR2 pathway of astrocyte-induced microglial activation is associated with M1 polarization and enhanced migration ability, indicating that this pathway could be a useful target to ameliorate inflammation in the central nervous system.

  4. M1 Protein Allows Group A Streptococcal Survival in Phagocyte Extracellular Traps through Cathelicidin Inhibition

    OpenAIRE

    Lauth, Xavier; von Köckritz-Blickwede, Maren; McNamara, Case W; Myskowski, Sandra; Zinkernagel, Annelies S.; Beall, Bernard; Ghosh, Partho; Richard L Gallo; Nizet, Victor

    2009-01-01

    M1 protein contributes to Group A Streptococcus (GAS) systemic virulence by interfering with phagocytosis and through proinflammatory activities when released from the cell surface. Here we identify a novel role of M1 protein in the stimulation of neutrophil and mast cell extracellular trap formation, yet also subsequent survival of the pathogen within these DNA-based innate defense structures. Targeted mutagenesis and heterologous expression studies demonstrate M1 protein promotes resistance...

  5. Non-viral FoxM1 gene delivery to hepatocytes enhances liver repopulation.

    Science.gov (United States)

    Xiang, D; Liu, C-C; Wang, M-J; Li, J-X; Chen, F; Yao, H; Yu, B; Lu, L; Borjigin, U; Chen, Y-X; Zhong, L; Wangensteen, K J; He, Z-Y; Wang, X; Hu, Y-P

    2014-05-22

    Hepatocyte transplantation as a substitute strategy of orthotopic liver transplantation is being studied for treating end-stage liver diseases. Several technical hurdles must be overcome in order to achieve the therapeutic liver repopulation, such as the problem of insufficient expansion of the transplanted hepatocytes in recipient livers. In this study, we analyzed the application of FoxM1, a cell-cycle regulator, to enhance the proliferation capacity of hepatocytes. The non-viral sleeping beauty (SB) transposon vector carrying FoxM1 gene was constructed for delivering FoxM1 into the hepatocytes. The proliferation capacities of hepatocytes with FoxM1 expression were examined both in vivo and in vitro. Results indicated that the hepatocytes with FoxM1 expression had a higher proliferation rate than wild-type (WT) hepatocytes in vitro. In comparison with WT hepatocytes, the hepatocytes with FoxM1 expression had an enhanced level of liver repopulation in the recipient livers at both sub-acute injury (fumaryl acetoacetate hydrolase (Fah)(-/-) mice model) and acute injury (2/3 partial hepatectomy mice model). Importantly, there was no increased risk of tumorigenicity with FoxM1 expression in recipients even after serial transplantation. In conclusion, expression of FoxM1 in hepatocytes enhanced the capacity of liver repopulation without inducing tumorigenesis. FoxM1 gene delivered by non-viral SB vector into hepatocytes may be a viable approach to promote therapeutic repopulation after hepatocyte transplantation.

  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. A population-based incidence of M2 strokes indicates potential expansion of large vessel occlusions amenable to endovascular therapy.

    Science.gov (United States)

    Rai, Ansaar T; Domico, Jennifer R; Buseman, Chelsea; Tarabishy, Abdul R; Fulks, Daniel; Lucke-Wold, Noelle; Boo, SoHyun; Carpenter, Jeffrey S

    2017-09-28

    M2 occlusions may result in poor outcomes and potentially benefit from endovascular therapy. Data on the rate of M2 strokes is lacking. Patients with acute ischemic stroke discharged over a period of 3 years from a tertiary level hospital in the 'stroke belt' were evaluated for M2 occlusions on baseline vascular imaging. Regional and national incidence was calculated from discharge and multicounty data. There were 2739 ICD-9 based AIS discharges. M2 occlusions in 116 (4%, 95% CI 3.5% to 5%) patients constituted the second most common occlusion site. The median National Institute of Health Stroke Scale (NIHSS) score was 12 (IQR 5-18). Good outcomes were observed in 43% (95% CI 34% to 53%), poor outcomes in 57% (95% CI 47% to 66%), and death occurred in 27% (95% CI 19% to 37%) of patients. Receiver operating characteristics curves showed the NIHSS to be predictive of outcomes (area under the curve 0.829, 95% CI 0.745 to 0.913, p<0.0001). An NIHSS score ≥9 was the optimal cut-off point for predicting poor outcomes (sensitivity 85.7%, specificity 67.4%). 71 (61%) patients had an NIHSS score ≥9 and 45 (39%) an NIHSS score <9. The rate of good-outcome was 22.6% for NIHSS score ≥9 versus 78.4% for NIHSSscore <9 (OR=0.08, 95% CI 0.03 to 0.21, p<0.0001). Mortality was 42% for NIHSS score ≥9versus 2.7% for NIHSS score <9 (OR=26, 95% CI 3.3 to 202, p<0.0001). Infarct volume was 57 (±55.7) cm(3) for NIHSS score ≥9 versus 30 (±34)cm(3) for NIHSS score <9 (p=0.003). IV recombinant tissue plasminogen activator (rtPA) administered in 28 (24%) patients did not affect outcomes. The rate of M2 occlusions was 7 (95% CI 5 to 9)/100 000 people/year (3%, 95% CI 2% to 4%), giving an incidence of 21 176 (95% CI 15 282 to 29 247)/year. Combined with M1, internal carotid artery terminus and basilar artery, this yields a 'large vessel occlusion (LVO)+M2' rate of 31 (95% CI 26 to 35)/100 000 people/year and a national incidence of 99 227 (95% CI 84 004 to 112

  9. Identification of a novel splice variant form of the influenza A virus M2 ion channel with an antigenically distinct ectodomain.

    Directory of Open Access Journals (Sweden)

    Helen M Wise

    Full Text Available Segment 7 of influenza A virus produces up to four mRNAs. Unspliced transcripts encode M1, spliced mRNA2 encodes the M2 ion channel, while protein products from spliced mRNAs 3 and 4 have not previously been identified. The M2 protein plays important roles in virus entry and assembly, and is a target for antiviral drugs and vaccination. Surprisingly, M2 is not essential for virus replication in a laboratory setting, although its loss attenuates the virus. To better understand how IAV might replicate without M2, we studied the reversion mechanism of an M2-null virus. Serial passage of a virus lacking the mRNA2 splice donor site identified a single nucleotide pseudoreverting mutation, which restored growth in cell culture and virulence in mice by upregulating mRNA4 synthesis rather than by reinstating mRNA2 production. We show that mRNA4 encodes a novel M2-related protein (designated M42 with an antigenically distinct ectodomain that can functionally replace M2 despite showing clear differences in intracellular localisation, being largely retained in the Golgi compartment. We also show that the expression of two distinct ion channel proteins is not unique to laboratory-adapted viruses but, most notably, was also a feature of the 1983 North American outbreak of H5N2 highly pathogenic avian influenza virus. In identifying a 14th influenza A polypeptide, our data reinforce the unexpectedly high coding capacity of the viral genome and have implications for virus evolution, as well as for understanding the role of M2 in the virus life cycle.

  10. 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.

  11. Experimental Conditions: SE37_S19_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available opes SE37_S19 PSEUDO: Unlabeled and labeled Medicago samples for flavonoid annotation using ShiftedIonsFinde...03_M1) and for a blank sample (S16_M1 to S16_M3) are used. Import file name is unlabeling SE37_DS5 Flavonoid like peak search by ShiftedIonsFinder ...

  12. Radioiodinated ganglioside G/sub M1/: A potential tracer for neurological studies

    Energy Technology Data Exchange (ETDEWEB)

    Zalutsky, M.R.; Gallagher, P.; Magistretti, P.L.; Ghidoni, R.

    1985-05-01

    Ganglioside G/sub M1/ is a glycosphingolipid which appears to be involved in the regeneration of damaged neuronal tissue. In addition, it is being investigated clinically in the treatment of various neuropathies. If labeled with the appropriate isotope, G/sub M1/ might be useful as a probe of these processes, particularly if it accumulates preferentially in cerebral infarcts. The G/sub M1/ -tyr derivative was labeled with I-125 in 75% yield using the Iodogen method and at micellar concentration was isolated using gel chromatography. Binding of I-125 (G/sub M1/ -tyr) to rat neuronal membranes was measured at concentrations of 5,50, and 500 nM. The amount bound (8,26, and 158 pmol/gm membrane) was similar to that reported for H-3(G/sub M1/). The biodistribution of I-125(G/sub M1/ -tyr) in mice at both micellar and monomeric concentrations was also similar to that of H-3(G/sub M1/). However, at monomeric concentrations, thyroid uptake of I-125 was about 10 times higher than at micellar concentrations, suggesting differential dehalogenation of the two forms. Initial studies in the gerbil stroke model suggest that the uptake of I-125(G/sub M1/ -tyr) in damaged brain is twice that in normal tissue.

  13. CONDITIONAL INVOLVEMENT OF MUSCARINIC M(1) RECEPTORS IN VAGALLY MEDIATED CONTRACTION OF GUINEA-PIG BRONCHI

    NARCIS (Netherlands)

    TENBERGE, REJ; ROFFEL, AF; ZAAGSMA, J

    The involvement of ganglionic muscarinic M(1) receptors in vagally induced bronchoconstriction in guinea-pig airways is controversial. Therefore, we studied the effects of the M(1)-selective muscarinic receptor antagonist pirenzepine on vagus nerve (VNS, preganglionic) and electrical field

  14. A note on predicting recessions in the euro area using real M1

    OpenAIRE

    Jens Boysen-Hogrefe

    2012-01-01

    Real M1 is a renowned leading indicator used to forecast real economic activity. This note provides evidence that real M1 is also a suitable recession indicator that gave a clear and early signal for the Great Recession as long as changes in money demand are controlled for.

  15. Analytical Method (M): SE37_S18_M1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available SE37_S18_M1 This is a pseudo metadata prepared for integrated analyses of multiple ...datasets. The raw data obtained from LC-Orbitarp MS analyses for Medicago samples and a blank sample (S17_M1

  16. 12 CFR Appendix M1 to Part 226 - Generic Repayment Estimates

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Generic Repayment Estimates M1 Appendix M1 to Part 226 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE... rounded down to the nearest whole year if the estimate contains a fractional year less than 0.5,...

  17. Experimental Conditions: SE19_S2_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available SE19_S2_M1_D1 SE19 Grobal triacylglycerol analysis in mouse liver and white adipose... tissue (WAT) by high resolution LC/ESI-QTOF MS/MS SE19_S2 Mouse white adipose tissue (WAT) SE19_S2_M1 20 ug

  18. FoxM1 is required for execution of the mitotic programme and chromosome stability

    NARCIS (Netherlands)

    Laoukili, J.; Kooistra, M.R.H.; Brás, A.; Kauw, J.; Kerkhoven, R.M.; Morrison, A.; Clevers, H.C.; Medema, R.H.

    2005-01-01

    Transcriptional induction of cell-cycle regulatory proteins ensures proper timing of subsequent cell-cycle events. Here we show that the Forkhead transcription factor FoxM1 regulates expression of many G2-specific genes and is essential for chromosome stability. Loss of FoxM1 leads to pleiotropic ce

  19. FoxM1 is required for execution of the mitotic programme and chromosome stability.

    NARCIS (Netherlands)

    Laoukili, J.; Kooistra, M.R.H.; Bras, A.; Kauw, J.; Kerkhoven, R.M.; Morrison, A.; Clevers, J.C.; Medema, R.H.

    2005-01-01

    Transcriptional induction of cell-cycle regulatory proteins ensures proper timing of subsequent cell-cycle events. Here we show that the Forkhead transcription factor FoxM1 regulates expression of many G2-specific genes and is essential for chromosome stability. Loss of FoxM1 leads to pleiotropic ce

  20. Nanometre-accurate form measurement machine for E-ELT M1 segments

    NARCIS (Netherlands)

    Bos, A.; Henselmans, R.; Rosielle, P.C.J.N.; Steinbuch, M.

    2015-01-01

    To enable important scientific discoveries, ESO has defined a new ground-based telescope: the European Extremely Large Telescope (E-ELT). The baseline design features a telescope with a 39-m-class primary mirror (M1), making it the largest and most powerful telescope in the world. The M1 consists of

  1. Analysis and deconvolution of dimethylnaphthalene isomers using gas chromatography vacuum ultraviolet spectroscopy and theoretical computations.

    Science.gov (United States)

    Schenk, Jamie; Mao, James X; Smuts, Jonathan; Walsh, Phillip; Kroll, Peter; Schug, Kevin A

    2016-11-16

    An issue with most gas chromatographic detectors is their inability to deconvolve coeluting isomers. Dimethylnaphthalenes are a class of compounds that can be particularly difficult to speciate by gas chromatography - mass spectrometry analysis, because of their significant coelution and similar mass spectra. As an alternative, a vacuum ultraviolet spectroscopic detector paired with gas chromatography was used to study the systematic deconvolution of mixtures of coeluting isomers of dimethylnaphthalenes. Various ratio combinations of 75:25; 50:50; 25:75; 20:80; 10:90; 5:95; and 1:99 were prepared to test the accuracy, precision, and sensitivity of the detector for distinguishing overlapping isomers that had distinct, but very similar absorption spectra. It was found that, under reasonable injection conditions, all of the pairwise overlapping isomers tested could be deconvoluted up to nearly two orders of magnitude (up to 99:1) in relative abundance. These experimental deconvolution values were in agreement with theoretical covariance calculations performed for two of the dimethylnaphthalene isomers. Covariance calculations estimated high picogram detection limits for a minor isomer coeluting with low to mid-nanogram quantity of a more abundant isomer. Further characterization of the analytes was performed using density functional theory computations to compare theory with experimental measurements. Additionally, gas chromatography - vacuum ultraviolet spectroscopy was shown to be able to speciate dimethylnaphthalenes in jet and diesel fuel samples. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. The luminosity function of cluster galaxies relations among M$_{1}$, M* and the morphological type

    CERN Document Server

    Trevese, D; Appodia, B

    1996-01-01

    A study of the luminosity function of 36 Abell clusters of galaxies has been carried out using photographic plates obtained with the Palomar 1.2 m Schmidt telescope. The relation between the magnitude M_1 of the brightest cluster member and the Schechter function parameter M* has been analyzed. A positive correlation between M* and M_1 is found. However clusters appear segregated in the M_1-M* plane according to their Rood & Sastry class in such a way that on average M_1 becomes brighter while M* becomes fainter going from late to early Rood & Sastry and also Bautz & Morgan classes. Also a partial correlation analysis involving the magnitude M_10 of the 10th brightest galaxy, shows a negative intrinsic correlation between M_1 and M*. These results agree with the cannibalism model for the formation of brightest cluster members, and provide new constraints for theories of cluster formation and evolution.

  3. 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.

  4. Effects of Lactobacillus kefiranofaciens M1 isolated from kefir grains on germ-free mice.

    Directory of Open Access Journals (Sweden)

    Yen-Po Chen

    Full Text Available Lactobacillus kefiranofaciens M1 is a novel probiotic strain that was isolated from kefir grains. Previously, we have demonstrated the immunoregulatory, anti-allergic, anti-asthmatic and anti-colitis abilities of L. kefiranofaciens M1 in a number of in-vitro and in-vivo experiments. However, whether the effects of L. kefiranofaciens M1 are elicited directly on the host or act by regulating the host's microbiota remains unknown. A number of studies have used germ-free or gnotobiotic animals to investigate the relationship between probiotics and colitis; therefore the aim of this study was to investigate the effects of L. kefiranofaciens M1 on germ-free mice. Such an approach should help in determining the direct effects of L. kefiranofaciens M1 on the host itself. Four-week-old female germ-free mice were inoculated intragastrically with 2×10(8 CFU/mouse L. kefiranofaciens M1 once or at 2-day intervals for 14 days. Bacterial colonization, the Th1/Th2 cytokine profile of the mice's splenocytes and the anti-colitis effect of L. kefiranofaciens M1 were investigated. The strongest response in terms of splenic Th1 cytokine IFN-γ and IL-12 production upon TLR activation was detected in the continuous treatment group when comparing to the single inoculation group and the germ-free control. In addition, continuous inoculation with L. kefiranofaciens M1 was found to ameliorate the symptoms of DSS-induced colitis in germ-free mice. However, L. kefiranofaciens M1 failed to colonize the host. Thus it would seem that L. kefiranofaciens M1 is likely to act directly on the host and not be involved in microbiota regulation.

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

    Science.gov (United States)

    Cousens, Graham A; Beckley, Jacob T

    2007-07-19

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

  6. IFN-γ promotes muscle damage in the mdx mouse model of Duchenne muscular dystrophy by suppressing M2 macrophage activation and inhibiting muscle cell proliferation.

    Science.gov (United States)

    Villalta, S Armando; Deng, Bo; Rinaldi, Chiara; Wehling-Henricks, Michelle; Tidball, James G

    2011-11-15

    Duchenne muscular dystrophy is a degenerative disorder that leads to death by the third decade of life. Previous investigations have shown that macrophages that invade dystrophic muscle are a heterogeneous population consisting of M1 and M2 macrophages that promote injury and repair, respectively. In the present investigation, we tested whether IFN-γ worsens the severity of mdx dystrophy by activating macrophages to a cytolytic M1 phenotype and by suppressing the activation of proregenerative macrophages to an M2 phenotype. IFN-γ is a strong inducer of the M1 phenotype and is elevated in mdx dystrophy. Contrary to our expectations, null mutation of IFN-γ caused no reduction of cytotoxicity of macrophages isolated from mdx muscle and did not reduce muscle fiber damage in vivo or improve gross motor function of mdx mice at the early, acute peak of pathology. In contrast, ablation of IFN-γ reduced muscle damage in vivo during the regenerative stage of the disease and increased activation of the M2 phenotype and improved motor function of mdx mice at that later stage of the disease. IFN-γ also inhibited muscle cell proliferation and differentiation in vitro, and IFN-γ mutation increased MyoD expression in mdx muscle in vivo, showing that IFN-γ can have direct effects on muscle cells that could impair repair. Taken together, the findings show that suppression of IFN-γ signaling in muscular dystrophy reduces muscle damage and improves motor performance by promoting the M2 macrophage phenotype and by direct actions on muscle cells.

  7. Systematic Investigation of Benzodithiophene-Benzothiadiazole Isomers for Organic Photovoltaics.

    Science.gov (United States)

    Du, Jia; Fortney, Andria; Washington, Katherine E; Bulumulla, Chandima; Huang, Peishen; Dissanayake, Dushanthi; Biewer, Michael C; Kowalewski, Tomasz; Stefan, Mihaela C

    2016-12-07

    Two new donor-acceptor small molecules based on benzo[1,2-b:4,5-b']dithiophene (BDT) and benzo[c][1,2,5]thiadiazole (BT) were designed and synthesized. Small molecules 4,4'-[(4,8-bis(5-(2-ethylhexyl)thiophen-2-yl)benzo[1,2-b:4,5-b']dithiophene-2,6-diyl)bis(2,2'-bithiophene)-5,5'-diyl]bis(benzo[c][1,2,5]thiadiazole) (BDT-TT-BT) and 4,4'-(4,8-bis(5-(2-ethylhexyl)thiophen-2-yl)benzo[1,2-b:4,5-b']dithiophene-2,6-diyl)bis[7-(2,2'-bithiophene-5-yl)benzo[c][1,2,5]thiadiazole] (BDT-BT-TT) are structural isomers with the 2,2-bithiophene unit placed either between the BDT and BT units or at the end of the BT units. This work is targeted toward finding the effect of structural variation on optoelectronic properties, morphology, and photovoltaic performance. On the basis of theoretical calculations, the molecular geometry and energy levels are different for these two molecules when the position of the 2,2-bithiophene unit is changed. Optical and electrochemical properties of these two small molecules were characterized using UV-vis and cyclic voltammetry. The results showed that BDT-BT-TT has broader absorption and an elevated HOMO energy level when compared with those of BDT-TT-BT. The performance of these two isomers in solar cell devices was tested by blending with [6,6]-phenyl-C71-butyric acid methyl ester (PC71BM). Power conversion efficiencies as high as 3.22 and 3.71% were obtained in conventional solar cell structures for BDT-TT-BT and BDT-BT-TT, respectively. The morphology was studied using grazing incident wide-angle X-ray scattering and transmission electron microscopy, which revealed different phase separations of these two molecules when blended with PC71BM.

  8. Physical chemistry and membrane properties of two phosphatidylinositol bisphosphate isomers.

    Science.gov (United States)

    Slochower, David R; Wang, Yu-Hsiu; Radhakrishnan, Ravi; Janmey, Paul A

    2015-05-21

    The most highly charged phospholipids, polyphosphoinositides, are often involved in signaling pathways that originate at cell-cell and cell-matrix contacts, and different isomers of polyphosphoinositides have distinct biological functions that cannot be explained by separate highly specific protein ligand binding sites [Lemmon, Nat. Rev. Mol. Cell Biol., 2008, 9, 99-111]. PtdIns(3,5)P2 is a low abundance phosphoinositide localized to cytoplasmic-facing membrane surfaces, with relatively few known ligands, yet PtdIns(3,5)P2 plays a key role in controlling membrane trafficking events and cellular stress responses that cannot be duplicated by other phosphoinositides [Dove et al., Nature, 1997, 390, 187-192; Michell, FEBS J., 2013, 280, 6281-6294]. Here we show that PtdIns(3,5)P2 is structurally distinct from PtdIns(4,5)P2 and other more common phospholipids, with unique physical chemistry. Using multiscale molecular dynamics techniques on the quantum level, single molecule, and in bilayer settings, we found that the negative charge of PtdIns(3,5)P2 is spread over a larger area, compared to PtdIns(4,5)P2, leading to a decreased ability to bind divalent ions. Additionally, our results match well with experimental data characterizing the cluster forming potential of these isomers in the presence of Ca(2+) [Wang et al., J. Am. Chem. Soc., 2012, 134, 3387-3395; van den Bogaart et al., Nature, 2011, 479, 552-555]. Our results demonstrate that the different cellular roles of PtdIns(4,5)P2 and PtdIns(3,5)P2in vivo are not simply determined by their localization by enzymes that produce or degrade them, but also by their molecular size, ability to chelate ions, and the partial dehydration of those ions, which might affect the ability of PtdIns(3,5)P2 and PtdIns(4,5)P2 to form phosphoinositide-rich clusters in vitro and in vivo.

  9. Isolation and spectral characterization of thermally generated multi-Z-isomers of lycopene and the theoretically preferred pathway to di-Z-isomers.

    Science.gov (United States)

    Honda, Masaki; Kudo, Tatsuya; Kuwa, Takahiro; Higashiura, Takuma; Fukaya, Tetsuya; Inoue, Yoshinori; Kitamura, Chitoshi; Takehara, Munenori

    2017-02-01

    Lycopene has a large number of geometric isomers caused by E/Z isomerization at arbitrary sites within the 11 conjugated double bonds, offering varying characteristics related to features such as antioxidant capacity and bioavailability. However, the geometric structures of only a few lycopene Z-isomers have been thoroughly identified from natural sources. In this study, seven multi-Z-isomers of lycopene, (9Z,13'Z)-, (5Z,13Z,9'Z)-, (9Z,9'Z)-, (5Z,13'Z)-, (5Z,9'Z)-, (5Z,9Z,5'Z)-, and (5Z,9Z)-lycopene, were obtained from tomato samples by thermal isomerization, and then isolated by elaborate chromatography, and fully assigned using proton nuclear magnetic resonance. Moreover, the theoretically preferred pathway from (all-E)-lycopene to di-Z-isomers was examined with a computational approach using a Gaussian program. Fine-tuning of the HPLC separation conditions led to the discovery of novel multi-Z-isomers, and whose formation was supported by advanced theoretical calculations.

  10. Isomer Shift and Magnetic Moment of the Long-Lived 1/2^{+} Isomer in _{30}^{79}Zn_{49}: Signature of Shape Coexistence near ^{78}Ni.

    Science.gov (United States)

    Yang, X F; Wraith, C; Xie, L; Babcock, C; Billowes, J; Bissell, M L; Blaum, K; Cheal, B; Flanagan, K T; Garcia Ruiz, R F; Gins, W; Gorges, C; Grob, L K; Heylen, H; Kaufmann, S; Kowalska, M; Kraemer, J; Malbrunot-Ettenauer, S; Neugart, R; Neyens, G; Nörtershäuser, W; Papuga, J; Sánchez, R; Yordanov, D T

    2016-05-01

    Collinear laser spectroscopy is performed on the _{30}^{79}Zn_{49} isotope at ISOLDE-CERN. The existence of a long-lived isomer with a few hundred milliseconds half-life is confirmed, and the nuclear spins and moments of the ground and isomeric states in ^{79}Zn as well as the isomer shift are measured. From the observed hyperfine structures, spins I=9/2 and I=1/2 are firmly assigned to the ground and isomeric states. The magnetic moment μ (^{79}Zn)=-1.1866(10)μ_{N}, confirms the spin-parity 9/2^{+} with a νg_{9/2}^{-1} shell-model configuration, in excellent agreement with the prediction from large scale shell-model theories. The magnetic moment μ (^{79m}Zn)=-1.0180(12)μ_{N} supports a positive parity for the isomer, with a wave function dominated by a 2h-1p neutron excitation across the N=50 shell gap. The large isomer shift reveals an increase of the intruder isomer mean square charge radius with respect to that of the ground state, δ⟨r_{c}^{2}⟩^{79,79m}=+0.204(6)  fm^{2}, providing first evidence of shape coexistence.

  11. Theoretical studies of possible toroidal high-spin isomers in the light-mass region

    CERN Document Server

    Staszczak, Andrzej

    2015-01-01

    We review our theoretical knowledge of possible toroidal high-spin isomers in the light mass region in 28$\\le$$A$$\\le$52 obtained previously in cranked Skyrme-Hartree-Fock calculations. We report additional toroidal high-spin isomers in $^{56}$Ni with $I$=114$\\hbar$ and 140$\\hbar$, which follow the same (multi-particle)--(multi-hole) systematics as other toroidal high-spin isomers. We examine the production of these exotic nuclei by fusion of various projectiles on $^{20}$Ne or $^{28}$Si as an active target in time-projection-chamber (TCP) experiments.

  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. Exploration of FoxM1 and downstream related target molecule expression in cervical cancer tissue

    Institute of Scientific and Technical Information of China (English)

    Yi-Chong Yuan; QiongYang

    2016-01-01

    Objective:To study the expression of FoxM1 and downstream related target molecules in cervical cancer tissue.Methods:Cervical cancer tissue and normal cervical tissue were collected to detect the expression of FoxM1, proliferation-related genes (CDK6 and CDK8) and angiogenesis-related genes (VEGFA, VEGFB and VEGFC); Hela cells were cultured and transfected with FoxM1 siRNA, and then expression of CDK6, CDK8, VEGFA, VEGFB and VEGFC were detected.Results:mRNA contents of FoxM1, CDK6, CDK8, VEGFA, VEGFB and VEGFC in cervical cancer tissue were significantly higher than those in normal cervical tissue; mRNA content of FoxM1 was positively correlated with mRNA contents of CDK6, CDK8, VEGFA, VEGFB and VEGFC; mRNA contents of CDK6, CDK8, VEGFA, VEGFB and VEGFC of FoxM1-siRNA group were significantly lower than those of negative control-siRNA group.Conclusion:FoxM1 expression abnormally increases in cervical cancer tissue, and its downstream target genes include CDK6, CDK8, VEGFA, VEGFB and VEGFC.

  17. Emergence and oscillation of cosmic space by joining M1-branes

    CERN Document Server

    Sepehri, Alireza; Capozziello, Salvatore; Ali, Ahmed Farag; Pradhan, Anirudh

    2016-01-01

    Recently, it has been proposed by Padmanabhan that the difference between the number of degrees of freedom on the boundary surface and the number of degrees of freedom in a bulk region leads to the expansion of the universe. Now, a natural question arises, how this model could explain the oscillation of universe between contraction and expansion branches? We try to address this issue in the framework of BIonic system. In this model, $M0$-branes join to each other and give rise to a pair of $M1$-anti-$M1$-branes. The fields which live on these branes play the roles of massive gravitons that cause the emergence of a wormhole between them and formation of a BIon system. This wormhole dissolves into M1-branes and causes a divergence between the number of degrees of freedom on the boundary surface of $M1$ and the bulk leading to an expansion of $M1$-branes. When $M1$-branes become close to each other, the square energy of their system becomes negative and some tachyonic states emerge. To removes these states, $M1$...

  18. 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...

  19. Enzyme-linked immunosorbent assay for determination of aflatoxin M1 based on magnetic nanoparticles

    Science.gov (United States)

    Atanasova, M. K.; Ivanova, N. V.; Godjevargova, T. I.

    2017-02-01

    A sensitive enzyme immunoassay with magnetic nanoparticles (Method A) for the quantitative determination of aflatoxin M1 in milk was developed. This immunoassay was based on the immobilization of monoclonal antibody (mAb) on the modified magnetic nanoparticles (MNPs-NH2). It was observed that for each mg of the MNPs, 25 µg of antibody was immobilized. Both aflatoxin M1 in the sample and aflatoxin M1-BSA-peroxidase conjugate competed for the immobilized antibody. The proposed Method A was compared with other method (B). The Method B was based on the immobilization of aflatoxin M1-BSA conjugate on the MNPs-NH2, which competed with the aflatoxin M1 in the sample for binding to the added mAb. The binding of mAb to the aflatoxin M1-BSA-MNPs-NH2 was detected using a target secondary IgG-peroxidase antibody. The analytical characteristics of the two methods were compared. Real milk samples were investigated for present of aflatoxin M1. Two methods were based on the use of MNPs as a solid support for covalently immunoreagents immobilization. A comfortable separation of bound and free fraction of the tracer can be performed only through a simple collection of the MNPs by a permanent magnet. The application of MNPs helps to eliminate non-specific binding and to retain higher activity of bound biomolecules. The development of a MNPs-based ELISA for determination of aflatoxin M1 has a great potential to supersede the traditional ELISA for aflatoxin M1 diagnosis.

  20. Quantification of Triacylglycerol Positional Isomers in Rat Milk.

    Science.gov (United States)

    Watanabe, Natsuko; Nagai, Toshiharu; Mizobe, Hoyo; Yoshinaga, Kazuaki; Yoshida, Akihiko; Kitamura, Yohei; Shimizu, Takashi; Beppu, Fumiaki; Gotoh, Naohiro

    2016-12-01

    The absolute amount of triacylglycerol (TAG) positional isomers was analyzed in rat milk fat, a representative of non-ruminant milk fat, using a HPLC-UV-atmospheric pressure chemical ionization-MS/MS system equipped with an octacosyl silylation column or polymeric ODS column. TAGs consisting of two oleic acids (O) and one palmitic acid (P) were the most abundant. In particular, β-OPO, a TAG binding P at the β-position (sn-2) and two Os at the α-positions (sn-1/3), was prominent. The β-OPO content decreased over time, while a TAG consisting of two Ps and one capric acid, a medium-chain fatty acid, increased. TAGs consisting of two Ps and one docosahexaenoic acid were present in small amounts and decreased with time. These results indicated that the recombination of fatty acids in TAGs in milk fat occurs in the mother, and is thought to depend on the infant's stage of growth, in response to their nutritional needs. It was also demonstrated that medium-chain fatty acids were mainly located at the α-position (sn-3), while Ps were mainly located at the β-position (sn-2). Therefore, the combination and binding positions of fatty acids of TAG are considered very important in infant nutrition.

  1. Interstellar Isomers: The Importance of Bonding Energy Differences

    CERN Document Server

    Remijan, A J; Lovas, F J; Plusquellic, D F; Jewell, P R; Remijan, Anthony J.

    2005-01-01

    We present strong detections of methyl cyanide, vinyl cyanide, ethyl cyanide and cyanodiacetylene molecules with the Green Bank Telescope (GBT) toward the Sgr B2(N) molecular cloud. Attempts to detect the corresponding isocyanide isomers were only successful in the case of methyl isocyanide for its J(K)=1(0)-0(0) transition, which is the first interstellar report of this line. To determine the spatial distribution of methyl isocyanide, we used archival Berkeley-Illinois-Maryland Association (BIMA) array data for the J(K)=4(K)-3(K) (K=0-3) transitions but no emission was detected. From ab initio calculations, the bonding energy difference between the cyanide and isocyanide molecules is >8500 cm^-1 (>12,000 K). That we detect methyl isocyanide emission with a single antenna (Gaussian beamsize(Omega_B)=1723 arcsec^2) but not with an interferometer (Omega_B=192 arcsec^2), strongly suggests that methyl isocyanide has a widespread spatial distribution toward the Sgr B2(N) region. Thus, large-scale, non-thermal proc...

  2. Isomer spectroscopy of {sup 125,127}Cd

    Energy Technology Data Exchange (ETDEWEB)

    Naqvi, F. [Institut fuer Kernphysik, Universitaet Koeln (Germany); GSI, Helmholtzzentrum fuer Schwerionenforschung, Darmstadt (Germany); Gorska, M.; Grawe, H.; Pietri, S. [GSI, Helmholtzzentrum fuer Schwerionenforschung, Darmstadt (Germany); Caceres, L. [GSI, Helmholtzzentrum fuer Schwerionenforschung, Darmstadt (Germany); Departmento de Fisicia Teorica, Universidad Autonoma de Madrid (Spain); Jungclaus, A. [Departmento de Fisicia Teorica, Universidad Autonoma de Madrid (Spain); Pfuetzner, M. [IEP, Warsaw University, Warsaw (Poland); Regan, P.H; Podolyak, Z. [Department of Physics, University of Surrey, Guildford (United Kingdom); Rudolf, D. [Department of Physics, Lund University (Sweden)

    2010-07-01

    The results of investigations of isomeric decay in odd mass heavy Cd isotopes namely {sup 125,127}Cd are reported. To date information has been obtained on even mass heavy Cd isotopes and the systematics show evolution of single particle energies for them. The experiment was performed at GSI, Darmstadt to investigate the single particle level structure of odd mass heavy Cd isotopes. Nuclei of interest were produced in fragmentation reaction of {sup 136}Xe beam at energy 750MeV/u on a {sup 9}Be target of 4g/cm{sup 2} thickness. Selection of ions from unwanted reaction products and event by event identification was facilitated by FRagment Separator (FRS). Isomers populated in the reaction were implanted in a plastic catcher surrounded by 15 Ge cluster detectors from RISING array to detect gamma radiations. Level schemes based on the intensity balance and life time information were constructed for the first time for these nuclei. Comparison of the experimental results with shell model calculation are discussed.

  3. Isomers of fluoroamphetamines detected in forensic cases in Denmark

    DEFF Research Database (Denmark)

    Johansen, Sys Stybe; Hansen, Tina Maria

    2012-01-01

    A study was performed on the detection, separation and quantification of isomers from the new designer drugs named fluoroamphetamines (FAs) in forensic cases in eastern Denmark. The drugs were detected in whole blood extracts by ultraperformance liquid chromatography with time of flight mass...... by the retention time, multiple reaction monitoring (MRM) traces [154¿>¿109 (quantifier); 154¿>¿137], and ion ratio of the two transitions. For all FAs, LOQ was 0.002 mg/kg with linear ranges from 0.002 to 1.0 mg/kg whole blood. Since 2008, a total of 15 forensic investigations, mainly driving under the influence...... of drugs (DUID) cases, involving 4-fluoroamphetamine (4-FA) have been observed with whole blood concentrations ranging from 0.006 to 0.58 mg/kg. One autopsy case involved 4-FA; however, it was determined to be a combined intoxication. In 2010, ortho-fluoroamphetamine (2-FA) was discovered in forensic...

  4. Search for superradiant emission states in nuclear isomer crystals

    Energy Technology Data Exchange (ETDEWEB)

    Rundberg, R.S.; Wilhelmy, J.B.; Taylor, R.D.; Solem, J.C.; Fowler, M.M.; Miller, G.G.; Baldwin, G.

    1998-01-01

    This is the final report of a one-year, Laboratory Directed Research and Development (LDRD) project at Los Alamos National Laboratory (LANL). The objective was to verify the stimulated emission of gamma rays from {sup 125m}Te, as claimed by Russian scientists. The reported cross section for stimulated emission was sufficiently large to allow gain in a single-pass gamma-ray laser. The stimulated emission of gamma rays from a nuclear isomer is expected to result in collinear photons and, therefore, should be observable as a sum peak in the gamma-ray spectrum. Skorobogatov and Dzevitskii reported an increase of an order of magnitude in the sum peak (218.56 keV) when a sample of beryllium telluride containing {sup 125m}Te was cooled from room temperature to near-liquid-helium temperatures. The authors have repeated their experiment and have observed no increase in the sum peak above accidental summing. The upper limit for the stimulated-emission cross section based on the three-standard-deviation statistical error is 6.8 x 10 {sup {minus}21} cm{sup 2}. This result is one order of magnitude lower than the cross section reported by Skorobogatov and Dzevitskii. The cross section would not allow gain in a single-pass gamma-ray laser. Their results support the position of Baldwin and Solem rather than that of Kamenov.

  5. Bounds on Subspace Codes Based on Subspaces of Type (m,1 in Singular Linear Space

    Directory of Open Access Journals (Sweden)

    You Gao

    2014-01-01

    Full Text Available The Sphere-packing bound, Singleton bound, Wang-Xing-Safavi-Naini bound, Johnson bound, and Gilbert-Varshamov bound on the subspace codes n+l,M,d,(m,1q based on subspaces of type (m,1 in singular linear space Fq(n+l over finite fields Fq are presented. Then, we prove that codes based on subspaces of type (m,1 in singular linear space attain the Wang-Xing-Safavi-Naini bound if and only if they are certain Steiner structures in Fq(n+l.

  6. 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.

  7. Differential Effect of Amphetamine Optical Isomers on Bender Gestalt Performance of the Minimally Brain Dysfunctioned

    Science.gov (United States)

    Arnold, L. Eugene; And Others

    1978-01-01

    The differential effect of amphetamine optical isomers on Bender Gestalt performance was examined in 31 hyperkinetic minimally brain dysfunctioned children between the ages of 4 and 12 years, using a double-blind Latin-square crossover comparison. (Author)

  8. Theoretical Studies on Structures and Stabilities of C4H2+ Isomers

    Institute of Scientific and Technical Information of China (English)

    ZHAO Ying; WAN Su-qin; LIU Hui-ling; HUANG Xu-ri; SUN Chia-chung

    2013-01-01

    The structures,energies,stabilities and spectroscopies of doublet C4H2+ cations were explored at the DFT/B3LYP/6-311G(d,p),CCSD(T)/6-311+G(2df,2pd)(single-point),and G3B3 levels.Ten minimum isomers including the chainlike,three-member-ring,and four-member-ring structures are interconverted by means of 15 interconversion transition states.The potential energy surface was investigated.At the CCSD(T)/6-311+G(2df,2pd) and G3B3 levels,the global minimum isomer was found to be a linear HCCCCH.The structures of the stable isomer and its relevant transition state are further optimized at the QCISD/6-311G(d,p) level.The bonding nature and structure of isomer HCCCCH were analyzed.

  9. Study on Separation of Structural Isomer with Magneto-Archimedes method

    Science.gov (United States)

    Kobayashi, T.; Mori, T.; Akiyama, Y.; Mishima, F.; Nishijima, S.

    2017-09-01

    Organic compounds are refined by separating their structural isomers, however each separation method has some problems. For example, distillation consumes large energy. In order to solve these problems, new separation method is needed. Considering organic compounds are diamagnetic, we focused on magneto-Archimedes method. With this method, particle mixture dispersed in a paramagnetic medium can be separated in a magnetic field due to the difference of the density and magnetic susceptibility of the particles. In this study, we succeeded in separating isomers of phthalic acid as an example of structural isomer using MnCl2 solution as the paramagnetic medium. In order to use magneto-Archimedes method for separating materials for food or medicine, we proposed harmless medium using oxygen and fluorocarbon instead of MnCl2 aqueous solution. As a result, the possibility of separating every structural isomer was shown.

  10. Toroidal high-spin isomers in light nuclei with N not equal to Z

    CERN Document Server

    Staszczak, Andrzej

    2014-01-01

    The combined considerations of both the bulk liquid-drop-type behavior and the quantized aligned rotation with cranked Skyrme-Hartree-Fock approach revealed previously that even-even, N=Z, toroidal high-spin isomeric states have general occurrences for light nuclei with A between 28 and 52. We find that in this mass region there are in addition N not equal to Z toroidal high-spin isomers when the single-particle shells for neutrons and protons occur at the same cranked frequency $\\hbar \\omega$. Examples of N not equal to Z toroidal high-spin isomers, $^{36}_{16}$S$_{20}$($I$=74$\\hbar$) and $^{40}_{18}$Ar$_{22}$($I$=80,102$\\hbar$), are located and examined. The systematic properties of these N not equal to Z toroidal high-spin isomers fall into the same regular (muti-particle)-(muti-hole) patterns as other N=Z toroidal high-spin isomers.

  11. Synthesis of an isomer of dihydrocolensenone; Sintesis parcial de un isomero de la dihidrocolensenona

    Energy Technology Data Exchange (ETDEWEB)

    Fraga, B.M.; Hernandez, M.G.; Luis, J.G. [Instituto de Productos naturales y Agrobiologia CSIC, Universidad de La Laguna, Tenerife (Spain)

    1994-12-31

    Starting from the diterpene ribenone, a isomer of dihydrocolensenone has been prepared. Its structure was different of dihydrotiganone, showing that the structure previously assigned to tiganone was erroneous. 13 refs.

  12. Isomer shift and magnetic moment of the long-lived 1/2$^{+}$ isomer in $^{79}_{30}$Zn$_{49}$: signature of shape coexistence near $^{78}$Ni

    CERN Document Server

    Yang, X.F.; Xie, L.; Babcock, C.; Billowes, J.; Bissell, M.L.; Blaum, K.; Cheal, B.; Flanagan, K.T.; Garcia Ruiz, R. F.; Gins, W.; Gorges, C.; Grob, L.K.; Heylen, H.; Kaufmann, S.; Kowalska, M.; Kraemer, J.; Malbrunot-Ettenauer, S.; Neugart, R.; Neyens, G.; Nörtershäuser, W.; Papuga, J.; Sánchez, R.; Yordanov, D.T.

    2016-01-01

    Collinear laser spectroscopy has been performed on the $^{79}_{30}$Zn$_{49}$ isotope at ISOLDE-CERN. The existence of a long-lived isomer with a few hundred milliseconds half-life was confirmed, and the nuclear spins and moments of the ground and isomeric states in $^{79}$Zn as well as the isomer shift were measured. From the observed hyperfine structures, spins $I = 9/2$ and $I = 1/2$ are firmly assigned to the ground and isomeric states. The magnetic moment $\\mu$ ($^{79}$Zn) = $-$1.1866(10) $\\mu_{\\rm{N}}$, confirms the spin-parity $9/2^{+}$ with a $\

  13. Locations of All Shotpoints, USGS Cruise M1-98-GM (GOM98SHTALLG.SHP)

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — All shotpoint locations from multichannel seismics survey, USGS cruise M1-98-GM. During June 1998 and April 1999, the U.S. Geological Survey (USGS) conducted two...

  14. Aflatoxin M1 levels in raw milk, pasteurized milk and infant formula

    National Research Council Canada - National Science Library

    Omar, Sharaf Shareef

    2016-01-01

    The incidence of contamination of aflatoxin M1 (AFM1) in milk samples collected from the Jordanian market was investigated by using the competitive enzyme linked immunosorbent assay (ELISA) technique...

  15. Experimental Conditions: SE24_S1_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available rometry with 13C‑Labeling for Chemical Assignment of Sulfur-Containing Metabolites ...SE24_S1_M1_D1 SE24 Combination of Liquid Chromatography-Fourier Transform Ion Cyclotron Resonance-Mass Spect

  16. Towards Revised Step IV MICE Optics in the Absence of M1 SSD

    Energy Technology Data Exchange (ETDEWEB)

    Bayes, R. [Univ. of Glasgow, Scotland (United Kingdom); Berg, J. S. [Brookhaven National Lab. (BNL), Upton, NY (United States); Blackmore, V. [Imperial College, London (United Kingdom); Hunt, C. [Imperial College, London (United Kingdom); Liu, A. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Pasternak, J. [Imperial College, London (United Kingdom); Rogers, C. T. [Science and Technology Facilities Council (STFC), Oxford (United Kingdom). Rutherford Appleton Lab. (RAL)

    2015-10-01

    During magnet commissioning in September 2015, the leads on coil M1 of the downstream spectrometer solenoid failed. The coil will not be operational for MICE Step IV. Revised optics settings for the Step IV data taking are reviewed.

  17. Coiled-Coil Irregularities and Instabilities in Group A Streptococcus M1 Are Required for Virulence

    Energy Technology Data Exchange (ETDEWEB)

    McNamara, Case; Zinkernagel, Annelies S.; Macheboeuf, Pauline; Cunningham, Madeleine W.; Nizet, Victor; Ghosh, Partho (UO-HSC); (UCSD)

    2008-07-21

    Antigenically variable M proteins are major virulence factors and immunogens of the human pathogen group A Streptococcus (GAS). Here, we report the -3 angstrom resolution structure of a GAS M1 fragment containing the regions responsible for eliciting type-specific, protective immunity and for binding fibrinogen, which promotes M1 proinflammatory and antiphagocytic functions. The structure revealed substantial irregularities and instabilities throughout the coiled coil of the M1 fragment. Similar structural irregularities occur in myosin and tropomyosin, explaining the patterns of cross-reactivity seen in autoimmune sequelae of GAS infection. Sequence idealization of a large segment of the M1 coiled coil enhanced stability but diminished fibrinogen binding, proinflammatory effects, and antibody cross-reactivity, whereas it left protective immunogenicity undiminished. Idealized M proteins appear to have promise as vaccine immunogens.

  18. Presence of Aflatoxin M1 in Raw Milk for Human Consumption in Palestinian

    Directory of Open Access Journals (Sweden)

    Ibrahim Mahmoud AL ZUHEIR

    2012-09-01

    Full Text Available The absences or insufficient food control program result in the occurrence of mycotoxin in milk and milk products, which poses a serious risk for humans and can be a public health concern. This study was conducted to highlight the occurrence of aflatoxin M1 in Palestine raw milk collected at farms from Tulkarm, Nablus and Jenin. Aflatoxin M1 was determined by direct competitive ELISA technique. 85 % (34 of 40 of the total examined raw milk samples tested were positive. The aflatoxin M1 contamination levels were between 3 - 80 ppt with a mean of 29.57 ppt. There was a high incidence rate with 92 % (11 of 12 and the highest means of contaminated with aflatoxin M1 in the samples tested in Tulkarm city (P ≤ 0.05. 20 % of the analyzed samples (8 of 40 exceeded the maximum permissible limit (50 ppt in European Codex, with a range of 2 - 80 ppt.

  19. FoxM1 mediated resistance to gefitinib in non-small-cell lung cancer cells

    Institute of Scientific and Technical Information of China (English)

    Nuo XU; Xin ZHANG; Xun WANG; Hai-yan GE; Xiao-ying WANG; David GARFIELD; Ping YANG; Yuan-lin SONG; Chun-xue BAI

    2012-01-01

    Gefitinib is effective in only approximately 20% of patients with non-small-cell lung cancer (NSCLC),and the underlying mechanism remains unclear.FoxM1 is upregulated in NSCLC and associated with a poor prognosis in NSCLC patients.In this study,we examined the possible role of FoxM1 in gefitinib resistance and the related mechanisms.Methods:Gefitinib resistant human lung adenocarcinoma cell line SPC-A-1 and gefitinib-sensitive human lung mucoepidermoid carcinoma cell line NCI-H292 were used.mRNA and protein expression of FoxM1 and other factors were tested with quantitative RT PCR and Western blot analysis.RNA interference was performed to suppress FoxM1 expression in SPC-A-1 cells,and lentiviral infection was used to overexpress FoxM1 in H292 cells.MTT assay and flow cytometry were used to examine the proliferation and apoptosis of the cells.Results:Treatment of SPC-A-1 cells with gefitinib (1 and 10 μmol/L) upregulated the expression of FoxM1 in time- and concentrationdependent manners,while gefrtinib (1 μmol/L) downregulated in H292 cells.In SPC-A-1 cells treated with gefitinib (1 μmol/L),the expression of several downstream targets of FoxM1,including survivin,cyclin B1,SKP2,PLK1,Aurora B kinase and CDC25B,were significantly upregulated.Overexpression of FoxM1 increased the resistance in H292 cells,while attenuated FoxM1 expression restored the sensitivity to gefitinib in SPC-A-1 cells by inhibiting proliferation and inducing apoptosis.Conclusion:The results suggest that FoxM1 plays an important role in the resistance of NSCLC cells to gefitinib in vitro.FoxM1 could be used as a therapeutic target to overcome the resistance to gefitinib.

  20. q-differential operator representation of the quantum superalgebra Uq(sl(M+1|N+1))

    CERN Document Server

    Kimura, K

    1996-01-01

    A representation of the quantum superalgebra Uq(sl(M+1|N+1)) is constructed based on the q-differential operators acting on the coherent states parameterized by coordinates. These coordinates correspond to the local ones of the flag manifold. This realization provides us with a guide to construct the free field realization for the quantum affine superalgebra Uq^(sl(M+1|N+1)) at arbitrary level.

  1. Aflatoxin M1 Contamination in Milk and Milk Products in Iran: A Review

    Directory of Open Access Journals (Sweden)

    R. Kazemi Darsanaki

    2013-11-01

    Full Text Available Mycotoxins are secondary metabolites of molds and have adverse effects on humans, animals, and crops. Those can cause illnesses and economic losses. Aflatoxin M1 (AFM1 is one of the mycotoxins produced from the hydroxylated metabolite of aflatoxin B1 (AFB1. It can be found in milk or milk products obtained from livestock that have ingested contaminated feed. In this paper, recent studies were reviewed in aflatoxin M1 contamination in milk and milk products in Iran.

  2. Aflatoxin M1 Contamination in Milk and Milk Products in Iran: A Review

    Directory of Open Access Journals (Sweden)

    R. Kazemi Darsanaki

    2014-05-01

    Full Text Available Mycotoxins are secondary metabolites of molds and have adverse effects on humans, animals, and crops. Those can cause illnesses and economic losses. Aflatoxin M1 (AFM1 is one of the mycotoxins produced from the hydroxylated metabolite of aflatoxin B1 (AFB1. It can be found in milk or milk products obtained from livestock that have ingested contaminated feed. In this paper, recent studies were reviewed in aflatoxin M1 contamination in milk and milk products in Iran.

  3. The Evaluation of Aflatoxin M1 Level in Collected Raw Milk for Pasteurized Dairy

    Directory of Open Access Journals (Sweden)

    Ehsan Sadeghi

    2013-03-01

    Full Text Available Background: Aflatoxins are fungal toxins that have carcinogenic, cellular mutations and malformation effects. Aflatoxin M1 resists pasteurization, autoclave and the other methods that make foodstuff healthy. This study aims to determine the contents of aflatoxin M1 in raw milk of milk factories in Kermanshah province.Materials and Methods: This research is carried out through the descriptive-cross sectional method. Among the raw milk received by four pasteurized milk factories in Kermanshah, coded by (A, B, C, D labels, six samples, totally 320 samples (80 samples from each factory, were taken within four seasons. The concentration of aflatoxin M1 was examined by Enzyme-Linked Immunosorbent Assay (ELISA. The mean difference was analyzed statistically through t-test using SPSS software. Results: The content of aflatoxin was higher than Codex standard (0.5 µg/l in 295 samples. The total mean was 1.21, which exceeds two times the Codex standard. The highest and lowest contents of aflatoxin M1 were observed in “Factory D” in spring and in “Factory A” in autumn, respectively. There was a significant difference between contamination of aflatoxin M1 and different seasons (p< 0.05.Conclusion: High content of aflatoxin M1 in raw milk is worrying. Measuring the content of aflatoxin M1 is essential to reduce the toxin entering the daily food of animals and the other related factors. The considerable difference of aflatoxin M1 content between Factory D and Factory A can be attributed to the amount of the local milk and the industrial milk received by the factories.

  4. Emergence and oscillation of cosmic space by joining M1-branes

    Energy Technology Data Exchange (ETDEWEB)

    Sepehri, Alireza [Shahid Bahonar University, Faculty of Physics, Kerman (Iran, Islamic Republic of); Research Institute for Astronomy and Astrophysics of Maragha (RIAAM), Maragha (Iran, Islamic Republic of); Rahaman, Farook [Jadavpur University, Department of Mathematics, Kolkata, West Bengal (India); Capozziello, Salvatore [Universita di Napoli Federico II, Dipartimento di Fisica ' ' E. Pancini' ' , Naples (Italy); Gran Sasso Science Institute (INFN), L' Aquila (Italy); Tomsk State Pedagogical University, Tomsk (Russian Federation); INFN Sezione di Napoli, Naples (Italy); Ali, Ahmed Farag [Benha University, Department of Physics, Faculty of Science, Benha (Egypt); Pradhan, Anirudh [G L A University, Department of Mathematics, Institute of Applied Sciences and Humanities, Mathura, Uttar Pradesh (India)

    2016-05-15

    Recently, it has been proposed by Padmanabhan that the difference between the number of degrees of freedom on the boundary surface and the number of degrees of freedom in a bulk region leads to the expansion of the universe. Now, a natural question arises; how could this model explain the oscillation of the universe between contraction and expansion branches? We try to address this issue in the framework of a BIonic system. In this model, M0-branes join to each other and give rise to a pair of M1-anti-M1-branes. The fields which live on these branes play the roles of massive gravitons that cause the emergence of a wormhole between them and formation of a BIon system. This wormhole dissolves into M1-branes and causes a diverg