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Sample records for m-2 a-1 increase

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

    Science.gov (United States)

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

    1996-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Christina Camell

    Full Text Available Several studies have implicated fatty-acids as inflammatory regulators, suggesting that there may be a direct role for common dietary fatty-acids in regulating innate immune cells. In humans, a single high-fat meal increases systemic cytokines and leukocytes. In mice, short term high-fat feeding increases adipose tissue (AT leukocytes and alters the inflammatory profile of AT macrophages. We have seen that short term high fat feeding to C57BL/6J male mice increases palmitic and oleic acid within AT depots, but oleic acid increase is highest in the mesenteric AT (MAT. In vitro, oleic acid increases M2 macrophage markers (CD206, MGL1, and ARG1 in a murine macrophage cell line, while addition of palmitic acid is able to inhibit that increase. Three day supplementation of a chow diet, with oleic acid, induced an increase in M2 macrophage markers in the MAT, but not in the epididymal AT. We tested whether increases in M2 macrophages occur during short term ad lib feeding of a high fat diet, containing oleic acid. Experiments revealed two distinct populations of macrophages were altered by a three day high milk-fat diet. One population, phenotypically intermediate for F4/80, showed diet-induced increases in CD206, an anti-inflammatory marker characteristic of M2 macrophages intrinsic to the AT. Evidence for a second population, phenotypically F4/80(HICD11b(HI macrophages, showed increased association with the MAT following short term feeding that is dependent on the adhesion molecule, ICAM-1. Collectively, we have shown that short term feeding of a high-fat diet changes two population of macrophages, and that dietary oleic acid is responsible for increases in M2 macrophage polarization.

  3. The flux distribution from a 1.25m2 target aligned heliostat: comparison of ray tracing and experimental results

    CSIR Research Space (South Africa)

    Maliage, M

    2012-05-01

    Full Text Available The purpose of this paper is to validate SolTrace for concentrating solar investigations at CSIR by means of a test case: the comparison of the flux distribution in the focal spot of a 1.25 m2 target aligned heliostat predicted by the ray tracing...

  4. 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.

  5. 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...

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    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...

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

    Science.gov (United States)

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

    2001-04-15

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

  8. 雌激素通过调节IRF4促进巨噬细胞向M2型极化%Estrogen promotes M2 macrophages polarization by increasing IRF4 expression

    Institute of Scientific and Technical Information of China (English)

    刘黎; 胡静平; 岳艳

    2013-01-01

    Differential macrophage polarization in male and female mice defines susceptibility to disease.It is reported that estrogen plays an important role in maerophage polarization,but its underlying molecular mechanism is still unknown.In this study we studied the effect of estrogen on polarization of the M-CSF-induced bone marrow macrophages and then explored its potential mechanisms.We found that estrogen did not affect macrophage differentiation but promoted M2 polarization.Further,we found that estrogen could increase expression of M2-associated transcription factor IRF4.More importantly,the level of IRF4 was correlated with the extent of estrogen-induced M2 polarization.This study may provide some explanation for difference in susceptibility to diseases between male and female mice,and may also provide new clues for macrophage polarization-based treatements.%病毒性心肌炎、系统性红斑狼疮及肝癌等多种疾病其发病及严重情况呈现明显的性别差异,其中巨噬细胞不同极化是引起上述差异的重要原因.目前发现,雌激素(estrogen)可显著影响巨噬细胞极化,然而其涉及的分子免疫学机制尚不明了.本研究我们探讨了雌激素对骨髓来源巨噬细胞(BMM)极化的影响极其分子机制.雌激素虽不影响巨噬细胞的分化,但可显著促进巨噬细胞向M2型极化.进一步研究发现雌激素可上调M2型巨噬细胞重要转录因子IRF4的表达,且上调水平与M2极化程度呈正相关.提示,雌激素通过上调转录因子IRF4进而促进了M2型巨噬细胞极化.本研究为雌雄小鼠对疾病发病敏感差异性作出了一定理论解释,同时为通过调控巨噬细胞极化治疗疾病提供了新的线索.

  9. Neuroinflammation increases GABAergic tone and impairs cognitive and motor function in hyperammonemia by increasing GAT-3 membrane expression. Reversal by sulforaphane by promoting M2 polarization of microglia.

    Science.gov (United States)

    Hernandez-Rabaza, Vicente; Cabrera-Pastor, Andrea; Taoro-Gonzalez, Lucas; Gonzalez-Usano, Alba; Agusti, Ana; Balzano, Tiziano; Llansola, Marta; Felipo, Vicente

    2016-04-18

    Hyperammonemia induces neuroinflammation and increases GABAergic tone in the cerebellum which contributes to cognitive and motor impairment in hepatic encephalopathy (HE). The link between neuroinflammation and GABAergic tone remains unknown. New treatments reducing neuroinflammation and GABAergic tone could improve neurological impairment. The aims were, in hyperammonemic rats, to assess whether: (a) Enhancing endogenous anti-inflammatory mechanisms by sulforaphane treatment reduces neuroinflammation and restores learning and motor coordination. (b) Reduction of neuroinflammation by sulforaphane normalizes extracellular GABA and glutamate-NO-cGMP pathway and identify underlying mechanisms. (c) Identify steps by which hyperammonemia-induced microglial activation impairs cognitive and motor function and how sulforaphane restores them. We analyzed in control and hyperammonemic rats, treated or not with sulforaphane, (a) learning in the Y maze; (b) motor coordination in the beam walking; (c) glutamate-NO-cGMP pathway and extracellular GABA by microdialysis; (d) microglial activation, by analyzing by immunohistochemistry or Western blot markers of pro-inflammatory (M1) (IL-1b, Iba-1) and anti-inflammatory (M2) microglia (Iba1, IL-4, IL-10, Arg1, YM-1); and (e) membrane expression of the GABA transporter GAT-3. Hyperammonemia induces activation of astrocytes and microglia in the cerebellum as assessed by immunohistochemistry. Hyperammonemia-induced neuroinflammation is associated with increased membrane expression of the GABA transporter GAT-3, mainly in activated astrocytes. This is also associated with increased extracellular GABA in the cerebellum and with motor in-coordination and impaired learning ability in the Y maze. Sulforaphane promotes polarization of microglia from the M1 to the M2 phenotype, reducing IL-1b and increasing IL-4, IL-10, Arg1, and YM-1 in the cerebellum. This is associated with astrocytes deactivation and normalization of GAT-3 membrane

  10. FTY720 Induces Apoptosis of M2 Subtype Acute Myeloid Leukemia Cells by Targeting Sphingolipid Metabolism and Increasing Endogenous Ceramide Levels

    Science.gov (United States)

    Li, Lianchun; Liu, Yuan-Fang; Wang, Jiang; Liu, Hong; Song, Heng; Jiang, Hualiang; Chen, Sai-Juan; Luo, Cheng; Li, Keqin Kathy

    2014-01-01

    The M2 subtype Acute Myeloid Leukemia (AML-M2) with t(8;21) represents an unmet challenge because of poor clinical outcomes in a sizable portion of patients. In this study,we report that FTY720 (Fingolimod), a sphingosine analogue and an FDA approved drug for treating of multiple sclerosis, shows antitumorigenic activity against the Kasumi-1 cell line, xenograft mouse models and leukemic blasts isolated from AML-M2 patients with t(8;21) translocation. Primary investigation indicated that FTY720 caused cell apoptosis through caspases and protein phosphatase 2A (PP2A) activation. Transcriptomic profiling further revealed that FTY720 treatment could upregulate AML1 target genes and interfere with genes involved in ceramide synthesis. Treatment with FTY720 led to the elimination of AML1-ETO oncoprotein and caused cell cycle arrest. More importantly, FTY720 treatment resulted in rapid and significant increase of pro-apoptotic ceramide levels, determined by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry based lipidomic approaches. Structural simulation model had also indicated that the direct binding of ceramide to inhibitor 2 of PP2A (I2PP2A) could reactivate PP2A and cause cell death. This study demonstrates, for the first time, that accumulation of ceramide plays a central role in FTY720 induced cell death of AML-M2 with t(8;21). Targeting sphingolipid metabolism by using FTY720 may provide novel insight for the drug development of treatment for AML-M2 leukemia. PMID:25050888

  11. FTY720 induces apoptosis of M2 subtype acute myeloid leukemia cells by targeting sphingolipid metabolism and increasing endogenous ceramide levels.

    Directory of Open Access Journals (Sweden)

    Limin Chen

    Full Text Available The M2 subtype Acute Myeloid Leukemia (AML-M2 with t(8;21 represents an unmet challenge because of poor clinical outcomes in a sizable portion of patients. In this study,we report that FTY720 (Fingolimod, a sphingosine analogue and an FDA approved drug for treating of multiple sclerosis, shows antitumorigenic activity against the Kasumi-1 cell line, xenograft mouse models and leukemic blasts isolated from AML-M2 patients with t(8;21 translocation. Primary investigation indicated that FTY720 caused cell apoptosis through caspases and protein phosphatase 2A (PP2A activation. Transcriptomic profiling further revealed that FTY720 treatment could upregulate AML1 target genes and interfere with genes involved in ceramide synthesis. Treatment with FTY720 led to the elimination of AML1-ETO oncoprotein and caused cell cycle arrest. More importantly, FTY720 treatment resulted in rapid and significant increase of pro-apoptotic ceramide levels, determined by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry based lipidomic approaches. Structural simulation model had also indicated that the direct binding of ceramide to inhibitor 2 of PP2A (I2PP2A could reactivate PP2A and cause cell death. This study demonstrates, for the first time, that accumulation of ceramide plays a central role in FTY720 induced cell death of AML-M2 with t(8;21. Targeting sphingolipid metabolism by using FTY720 may provide novel insight for the drug development of treatment for AML-M2 leukemia.

  12. 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

  13. N-Terminal Fatty Acid Substitution Increases the Leishmanicidal Activity of CA(1-7)M(2-9), a Cecropin-Melittin Hybrid Peptide

    Science.gov (United States)

    Chicharro, Cristina; Granata, Cesare; Lozano, Rosario; Andreu, David; Rivas, Luis

    2001-01-01

    In order to improve the leishmanicidal activity of the synthetic cecropin A-melittin hybrid peptide CA(1-7)M(2-9) (KWKLFKKIGAVLKVL-NH2), a systematic study of its acylation with saturated linear fatty acids was carried out. Acylation of the Nɛ-7 lysine residue led to a drastic decrease in leishmanicidal activity, whereas acylation at lysine 1, in either the α or the ɛ NH2 group, increased up to 3 times the activity of the peptide against promastigotes and increased up to 15 times the activity of the peptide against amastigotes. Leishmanicidal activity increased with the length of the fatty acid chain, reaching a maximum for the lauroyl analogue (12 carbons). According to the fast kinetics, dissipation of membrane potential, and parasite membrane permeability to the nucleic acid binding probe SYTOX green, the lethal mechanism was directly related to plasma membrane permeabilization. PMID:11502512

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

    Directory of Open Access Journals (Sweden)

    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

  15. 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

  16. 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....

  17. Increased adiposity in annexin A1-deficient mice.

    Directory of Open Access Journals (Sweden)

    Rand T Akasheh

    Full Text Available Production of Annexin A1 (ANXA1, a protein that mediates the anti-inflammatory action of glucocorticoids, is altered in obesity, but its role in modulation of adiposity has not yet been investigated. The objective of this study was to investigate modulation of ANXA1 in adipose tissue in murine models of obesity and to study the involvement of ANXA1 in diet-induced obesity in mice. Significant induction of ANXA1 mRNA was observed in adipose tissue of both C57BL6 and Balb/c mice with high fat diet (HFD-induced obesity versus mice on chow diet. Upregulation of ANXA1 mRNA was independent of leptin or IL-6, as demonstrated by use of leptin-deficient ob/ob mice and IL-6 KO mice. Compared to WT mice, female Balb/c ANXA1 KO mice on HFD had increased adiposity, as indicated by significantly elevated body weight, fat mass, leptin levels, and adipocyte size. Whereas Balb/c WT mice upregulated expression of enzymes involved in the lipolytic pathway in response to HFD, this response was absent in ANXA1 KO mice. A significant increase in fasting glucose and insulin levels as well as development of insulin resistance was observed in ANXA1 KO mice on HFD compared to WT mice. Elevated plasma corticosterone levels and blunted downregulation of 11-beta hydroxysteroid dehydrogenase type 1 in adipose tissue was observed in ANXA1 KO mice compared to diet-matched WT mice. However, no differences between WT and KO mice on either chow or HFD were observed in expression of markers of adipose tissue inflammation. These data indicate that ANXA1 is an important modulator of adiposity in mice, with female ANXA1 KO mice on Balb/c background being more susceptible to weight gain and diet-induced insulin resistance compared to WT mice, without significant changes in inflammation.

  18. 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.

  19. Acute calcineurin inhibition with tacrolimus increases phosphorylated UT-A1.

    Science.gov (United States)

    Ilori, Titilayo O; Wang, Yanhua; Blount, Mitsi A; Martin, Christopher F; Sands, Jeff M; Klein, Janet D

    2012-04-15

    UT-A1, the urea transporter present in the apical membrane of the inner medullary collecting duct, is crucial to the kidney's ability to concentrate urine. Phosphorylation of UT-A1 on serines 486 and 499 is important for plasma membrane trafficking. The effect of calcineurin on dephosphorylation of UT-A1 was investigated. Inner medullary collecting ducts from Sprague-Dawley rats were metabolically labeled and treated with tacrolimus to inhibit calcineurin or calyculin to inhibit protein phosphatases 1 and 2A. UT-A1 was immunoprecipitated, electrophoresed, blotted, and total UT-A1 phosphorylation was assessed by autoradiography. Total UT-A1 was determined by Western blotting. A phospho-specific antibody to pser486-UT-A1 was used to determine whether serine 486 can be hyperphosphorylated by inhibiting phosphatases. Inhibition of calcineurin showed an increase in phosphorylation per unit protein at serine 486. In contrast, inhibition of phosphatases 1 and 2A resulted in an increase in UT-A1 phosphorylation but no increase in pser486-UT-A1. In vitro perfusion of inner medullary collecting ducts showed tacrolimus-stimulated urea permeability consistent with stimulated urea transport. The location of phosphorylated UT-A1 in rats treated acutely and chronically with tacrolimus was determined using immunohistochemistry. Inner medullary collecting ducts of the acutely treated rats showed increased apical membrane association of phosphorylated UT-A1 while chronic treatment reduced membrane association of phosphorylated UT-A1. We conclude that UT-A1 may be dephosphorylated by multiple phosphatases and that the PKA-phosphorylated serine 486 is dephosphorylated by calcineurin. This is the first documentation of the role of phosphatases and the specific site of phosphorylation of UT-A1, in response to tacrolimus.

  20. Cold-induced alteration in the global structure of the male sex chromosome of In(1)B$^{M2}$(reinverted) of Drosophila melanogaster is associated with increased acetylation of histone 4 at lysine 16

    Indian Academy of Sciences (India)

    S. Kulkarni-Shukla; A. P. Barge; R. S. Vartak; Anita Kar

    2008-12-01

    In Drosophila melanogaster, dosage compensation occurs through hypertranscription of sex-linked genes in males. The hypertranscription involves acetylation of histone 4 at lysine 16 (H4K16) on amale X-chromosome, brought about by a histone acetyltransferase encoded by the dosage compensation gene, males absent on the first (mof). We report a phenomenon in the strain In(1)B$^{M2}$(reinverted) of D. melanogaster where the global structure of the male X-chromosome can be altered at the third instar larval stage through a 4-h cold shock at 12±1°C. We show that the cold shock results in a transient hyperacetylation of H4K16 and an increased expression of MOF. Control proteins H4 acetylated at lysine 5, and the dosage compensation gene msl-2, do not show any change in expression after cold shock. Cytology of the male X-chromosome at different time points during cold shock and recovery, suggests that the hyperacetylation of H4 at lysine 16 causes the X-chromosome to corkscrew into itself, thereby achieving the cold-induced change in the higher order structure of the male polytene X-chromosome. Our studies suggest a role for H4K16 in maintaining the structure of the male X-chromosome in Drosophila.

  1. Epac regulates UT-A1 to increase urea transport in inner medullary collecting ducts.

    Science.gov (United States)

    Wang, Yanhua; Klein, Janet D; Blount, Mitsi A; Martin, Christopher F; Kent, Kimilia J; Pech, Vladimir; Wall, Susan M; Sands, Jeff M

    2009-09-01

    Urea plays a critical role in the concentration of urine, thereby regulating water balance. Vasopressin, acting through cAMP, stimulates urea transport across rat terminal inner medullary collecting ducts (IMCD) by increasing the phosphorylation and accumulation at the apical plasma membrane of UT-A1. In addition to acting through protein kinase A (PKA), cAMP also activates Epac (exchange protein activated by cAMP). In this study, we tested whether the regulation of urea transport and UT-A1 transporter activity involve Epac in rat IMCD. Functional analysis showed that an Epac activator significantly increased urea permeability in isolated, perfused rat terminal IMCD. Similarly, stimulating Epac by adding forskolin and an inhibitor of PKA significantly increased urea permeability. Incubation of rat IMCD suspensions with the Epac activator significantly increased UT-A1 phosphorylation and its accumulation in the plasma membrane. Furthermore, forskolin-stimulated cAMP significantly increased ERK 1/2 phosphorylation, which was not prevented by inhibiting PKA, indicating that Epac mediated this phosphorylation of ERK 1/2. Inhibition of MEK 1/2 phosphorylation decreased the forskolin-stimulated UT-A1 phosphorylation. Taken together, activation of Epac increases urea transport, accumulation of UT-A1 at the plasma membrane, and UT-A1 phosphorylation, the latter of which is mediated by the MEK-ERK pathway.

  2. Selective ALDH3A1 inhibition by benzimidazole analogues increase mafosfamide sensitivity in cancer cells.

    Science.gov (United States)

    Parajuli, Bibek; Fishel, Melissa L; Hurley, Thomas D

    2014-01-23

    Aldehyde dehydrogenase enzymes irreversibly oxidize aldehydes generated from metabolism of amino acids, fatty acids, food, smoke, additives, and xenobiotic drugs. Cyclophosphamide is one such xenobiotic used in cancer therapies. Upon activation, cyclophosphamide forms an intermediate, aldophosphamide, which can be detoxified to carboxyphosphamide by aldehyde dehydrogenases (ALDH), especially ALDH1A1 and ALDH3A1. Consequently, selective inhibition of ALDH3A1 could increase chemosensitivity toward cyclophosphamide in ALDH3A1 expressing tumors. Here, we report detailed kinetics and structural characterization of a highly selective submicromolar inhibitor of ALDH3A1, 1-[(4-fluorophenyl)sulfonyl]-2-methyl-1H-benzimidazole (CB7, IC50 of 0.2 μM). CB7 does not inhibit ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, or ALDH2 activity. Structural, kinetics, and mutagenesis studies show that CB7 binds to the aldehyde binding pocket of ALDH3A1. ALDH3A1-expressing lung adenocarcinoma and glioblastoma cell lines are sensitized toward mafosfamide (MF) treatment in the presence analogues of CB7, whereas primary lung fibroblasts lacking ALDH3A1 expression, are not.

  3. Increased maternal and fetal cholesterol efflux capacity and placental CYP27A1 expression in preeclampsia.

    Science.gov (United States)

    Mistry, Hiten D; Kurlak, Lesia O; Mansour, Yosef T; Zurkinden, Line; Mohaupt, Markus G; Escher, Geneviève

    2017-06-01

    Preeclampsia is a pregnancy-specific condition that leads to increased cardiovascular risk in later life. A decrease in cholesterol efflux capacity is linked to CVD. We hypothesized that in preeclampsia there would be a disruption of maternal/fetal plasma to efflux cholesterol, as well as differences in the concentrations of both placental sterol 27-hydroxylase (CYP27A1) and apoA1 binding protein (AIBP). Total, HDL-, and ABCA1-mediated cholesterol effluxes were performed with maternal and fetal plasma from women with preeclampsia and normotensive controls (both n = 17). apoA1 and apoE were quantified by chemiluminescence, and 27-hydroxycholesterol (27-OHC) by GC-MS. Immunohistochemistry was used to determine placental expression/localization of CYP27A1, AIBP, apoA1, apoE, and SRB1. Maternal and fetal total and HDL-mediated cholesterol efflux capacities were increased in preeclampsia (by 10-20%), but ABCA1-mediated efflux was decreased (by 20-35%; P < 0.05). Maternal and fetal apoE concentrations were higher in preeclampsia. Fetal plasma 27-OHC levels were decreased in preeclamptic samples (P < 0.05). Placental protein expression of both CYP27A1 and AIBP were localized around fetal vessels and significantly increased in preeclampsia (P = 0.04). Placental 27-OHC concentrations were also raised in preeclampsia (P < 0.05). Increased HDL-mediated cholesterol efflux capacity and placental CYP27A1/27-OHC could be a rescue mechanism in preeclampsia, to remove cholesterol from cells to limit lipid peroxidation and increase placental angiogenesis. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  4. Development of the M2A1 Container Coatings ECP

    Science.gov (United States)

    2010-02-11

    735; 168 hour 2 hour recovery 70:30 isooctane /toluene 4 hrs immed/2 & 24 hr recovery JP-8 168 hours...2 hour recovery/24 hour recovery 70:30 isooctane /toluene 4 hrs immed/2 & 24 hr recovery DS2 30 min 1/2 ml

  5. 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 $\

  6. Prostaglandin A1 inhibits increases in intracellular calcium concentration, TXA2 production and platelet activation

    Institute of Scientific and Technical Information of China (English)

    Yi ZHU; Zhen-lun GU; Zhong-qin LIANG; Hui-lin ZHANG; Zheng-hong QIN

    2006-01-01

    Aim: In our previous studies we found that cyclopentenane prostaglandin A1 (PGA1) had neuroprotective effects in a rodent ischemic model. In the present study we aimed to investigate the inhibitory effect of PGA1 on platelet function. Method: The rate of aggregation of human platelets was measured by using turbidimetry. The rate of adhesion of platelets to cultured endothelial cells was determined by using [3H]-adenine labeled platelets. 5-Hydroxytryptamine release from platelets was measured with O-phthaldialdehyde fluorospectrophotometry. The levels of TXB2, a stable metabolite of TXA2, were determined by radioimmunoassay. Alternations in platelet morphology were observed using an electron microscope, and the intraplatelet free calcium concentrations were measured with Fluo-3/AM FCM assay. Results: PGA1 significantly inhibited thrombin-collagen-and ADP-induced aggregation and adhesion of platelets. The morphological changes of platelets induced by thrombin were blocked by PGA1. PGA1 inhibited the release of 5-hydroxytyptamine from dense granules and the synthesis of TXA2. Conclusion: PGA1 inhibits the activation of platelets probably through blocking increases in intracellular calcium concentration and TXA2 synthesis.

  7. Towards Horizontal Architecture for Autonomic M2M Service Networks

    Directory of Open Access Journals (Sweden)

    Juhani Latvakoski

    2014-05-01

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

  8. 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....

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

    Science.gov (United States)

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

    2016-11-01

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

  10. Assigning error to an M2 measurement

    Science.gov (United States)

    Ross, T. Sean

    2006-02-01

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

  11. M2 factor of four-petal Gaussian beam

    Institute of Scientific and Technical Information of China (English)

    Zhou Guo-Quan; Fan Yan

    2008-01-01

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

  12. 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.

  13. Carbon Monoxide Releasing Molecule-A1 (CORM-A1 Improves Neurogenesis: Increase of Neuronal Differentiation Yield by Preventing Cell Death.

    Directory of Open Access Journals (Sweden)

    Ana S Almeida

    Full Text Available Cerebral ischemia and neurodegenerative diseases lead to impairment or death of neurons in the central nervous system. Stem cell based therapies are promising strategies currently under investigation. Carbon monoxide (CO is an endogenous product of heme degradation by heme oxygenase (HO activity. Administration of CO at low concentrations produces several beneficial effects in distinct tissues, namely anti-apoptotic and anti-inflammatory. Herein the CO role on modulation of neuronal differentiation was assessed. Three different models with increasing complexity were used: human neuroblastoma SH-S5Y5 cell line, human teratocarcinoma NT2 cell line and organotypic hippocampal slice cultures (OHSC. Cell lines were differentiated into post-mitotic neurons by treatment with retinoic acid (RA supplemented with CO-releasing molecule A1 (CORM-A1. CORM-A1 positively modulated neuronal differentiation, since it increased final neuronal production and enhanced the expression of specific neuronal genes: Nestin, Tuj1 and MAP2. Furthermore, during neuronal differentiation process, there was an increase in proliferative cell number (ki67 mRNA expressing cells and a decrease in cell death (lower propidium iodide (PI uptake, limitation of caspase-3 activation and higher Bcl-2 expressing cells. CO supplementation did not increase the expression of RA receptors. In the case of SH-S5Y5 model, small amounts of reactive oxygen species (ROS generation emerges as important signaling molecules during CO-promoted neuronal differentiation. CO's improvement of neuronal differentiation yield was validated using OHSC as ex vivo model. CORM-A1 treatment of OHSC promoted higher levels of cells expressing the neuronal marker Tuj1. Still, CORM-A1 increased cell proliferation assessed by ki67 expression and also prevented cell death, which was followed by increased Bcl-2 expression, decreased levels of active caspase-3 and PI uptake. Likewise, ROS signaling emerged as key factors

  14. Carbon Monoxide Releasing Molecule-A1 (CORM-A1) Improves Neurogenesis: Increase of Neuronal Differentiation Yield by Preventing Cell Death.

    Science.gov (United States)

    Almeida, Ana S; Soares, Nuno L; Vieira, Melissa; Gramsbergen, Jan Bert; Vieira, Helena L A

    2016-01-01

    Cerebral ischemia and neurodegenerative diseases lead to impairment or death of neurons in the central nervous system. Stem cell based therapies are promising strategies currently under investigation. Carbon monoxide (CO) is an endogenous product of heme degradation by heme oxygenase (HO) activity. Administration of CO at low concentrations produces several beneficial effects in distinct tissues, namely anti-apoptotic and anti-inflammatory. Herein the CO role on modulation of neuronal differentiation was assessed. Three different models with increasing complexity were used: human neuroblastoma SH-S5Y5 cell line, human teratocarcinoma NT2 cell line and organotypic hippocampal slice cultures (OHSC). Cell lines were differentiated into post-mitotic neurons by treatment with retinoic acid (RA) supplemented with CO-releasing molecule A1 (CORM-A1). CORM-A1 positively modulated neuronal differentiation, since it increased final neuronal production and enhanced the expression of specific neuronal genes: Nestin, Tuj1 and MAP2. Furthermore, during neuronal differentiation process, there was an increase in proliferative cell number (ki67 mRNA expressing cells) and a decrease in cell death (lower propidium iodide (PI) uptake, limitation of caspase-3 activation and higher Bcl-2 expressing cells). CO supplementation did not increase the expression of RA receptors. In the case of SH-S5Y5 model, small amounts of reactive oxygen species (ROS) generation emerges as important signaling molecules during CO-promoted neuronal differentiation. CO's improvement of neuronal differentiation yield was validated using OHSC as ex vivo model. CORM-A1 treatment of OHSC promoted higher levels of cells expressing the neuronal marker Tuj1. Still, CORM-A1 increased cell proliferation assessed by ki67 expression and also prevented cell death, which was followed by increased Bcl-2 expression, decreased levels of active caspase-3 and PI uptake. Likewise, ROS signaling emerged as key factors in CO

  15. 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.

  16. 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

  17. CYP24A1 exacerbated activity during diabetes contributes to kidney tubular apoptosis via caspase-3 increased expression and activation.

    Directory of Open Access Journals (Sweden)

    Alexandre Tourigny

    Full Text Available Decreases in circulating 25,hydroxyl-vitamin D3 (25 OH D3 and 1,25,dihydroxyl-vitamin D3 (1,25 (OH2 D3 have been extensively documented in patients with type 2 diabetes. Nevertheless, the molecular reasons behind this drop, and whether it is a cause or an effect of disease progression is still poorly understood. With the skin and the liver, the kidney is one of the most important sites for vitamin D metabolism. Previous studies have also shown that CYP24A1 (an enzyme implicated in vitamin D metabolism, might play an important role in furthering the progression of kidney lesions during diabetic nephropathy. In this study we show a link between CYP24A1 increase and senescence followed by apoptosis induction in the renal proximal tubules of diabetic kidneys. We show that CYP24A1 expression was increased during diabetic nephropathy progression. This increase derived from protein kinase C activation and increased H(2O(2 cellular production. CYP24A1 increase had a major impact on cellular phenotype, by pushing cells into senescence, and later into apoptosis. Our data suggest that control of CYP24A1 increase during diabetes has a beneficial effect on senescence induction and caspase-3 increased expression. We concluded that diabetes induces an increase in CYP24A1 expression, destabilizing vitamin D metabolism in the renal proximal tubules, leading to cellular instability and apoptosis, and thereby accelerating tubular injury progression during diabetic nephropathy.

  18. 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...

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. Increased proportions of bacteria capable of cleaving IgA1 in the pharynx of infants with atopic disease

    DEFF Research Database (Denmark)

    Kilian, M; Husby, S; Høst, A

    1995-01-01

    Based on the observation that children with a history of atopic disease show significantly increased levels of cleaved secretory IgA in nasopharyngeal secretions, we have previously formulated the hypothesis that bacteria-induced local deficiencies of the immune barrier of the upper respiratory...... of atopic disease at the age of 18 mo, harbored significantly higher proportions of IgA1 protease-producing bacteria (median, 36%; range, 14-64%) than the 14 healthy infants (median, 5%; range, 0.4-14%). No statistically significant differences were observed at the two subsequent examinations, but healthy...... children showed a statistically significant increase in proportions of IgA1 protease-producing bacteria in the pharynx with increasing age. IgA1 protease-producing bacteria detected included Streptococcus mitis biovar 1, Haemophilus influenzae, Haemophilus parahaemolyticus, Streptococcus pneumoniae...

  4. Mutation of the Glucosinolate Biosynthesis Enzyme Cytochrome P450 83A1 Monooxygenase Increases Camalexin Accumulation and Powdery Mildew Resistance.

    Science.gov (United States)

    Liu, Simu; Bartnikas, Lisa M; Volko, Sigrid M; Ausubel, Frederick M; Tang, Dingzhong

    2016-01-01

    Small secondary metabolites, including glucosinolates and the major phytoalexin camalexin, play important roles in immunity in Arabidopsis thaliana. We isolated an Arabidopsis mutant with increased resistance to the powdery mildew fungus Golovinomyces cichoracearum and identified a mutation in the gene encoding cytochrome P450 83A1 monooxygenase (CYP83A1), which functions in glucosinolate biosynthesis. The cyp83a1-3 mutant exhibited enhanced defense responses to G. cichoracearum and double mutant analysis showed that this enhanced resistance requires NPR1, EDS1, and PAD4, but not SID2 or EDS5. In cyp83a1-3 mutants, the expression of genes related to camalexin synthesis increased upon G. cichoracearum infection. Significantly, the cyp83a1-3 mutant also accumulated higher levels of camalexin. Decreasing camalexin levels by mutation of the camalexin synthetase gene PAD3 or the camalexin synthesis regulator AtWRKY33 compromised the powdery mildew resistance in these mutants. Consistent with these observations, overexpression of PAD3 increased camalexin levels and enhanced resistance to G. cichoracearum. Taken together, our data indicate that accumulation of higher levels of camalexin contributes to increased resistance to powdery mildew.

  5. Mutation of the glucosinolate biosynthesis enzyme cytochrome P450 83A1 monooxygenase increases camalexin accumulation and powdery mildew resistance

    Directory of Open Access Journals (Sweden)

    Simu eLiu

    2016-03-01

    Full Text Available Small secondary metabolites, including glucosinolates and the major phytoalexin camalexin, play important roles in immunity in Arabidopsis thaliana. We isolated an Arabidopsis mutant with increased resistance to the powdery mildew fungus Golovinomyces cichoracearum and identified a mutation in the gene encoding cytochrome P450 83A1 monooxygenase (CYP83A1, which functions in glucosinolate biosynthesis. The cyp83a1-3 mutant exhibited enhanced defense responses to G. cichoracearum and double mutant analysis showed that this enhanced resistance requires NPR1, EDS1, and PAD4, but not SID2 or EDS5. In cyp83a1-3 mutants, the expression of genes related to camalexin synthesis increased upon G. cichoracearum infection. Significantly, the cyp83a1-3 mutant also accumulated higher levels of camalexin. Decreasing camalexin levels by mutation of the camalexin synthetase gene PAD3 or the camalexin synthesis regulator AtWRKY33 compromised the powdery mildew resistance in these mutants. Consistent with these observations, overexpression of PAD3 increased camalexin levels and enhanced resistance to G. cichoracearum. Taken together, our data indicate that accumulation of higher levels of camalexin contributes to increased resistance to powdery mildew.

  6. 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...

  7. The relationship between HbA(1c) and fasting plasma glucose in patients with increased plasma liver enzyme measurements

    DEFF Research Database (Denmark)

    Christiansen, R; Rasmussen, L Melholt; Nybo, H;

    2012-01-01

    levels of increased liver enzyme concentrations. Methods:  Data from 10 065 patients with simultaneous measurement of HbA(1c) , venous fasting plasma glucose, alanine aminotransferase and γ-glutamyl transferase were extracted from our laboratory database. Correlations were investigated in four patient...

  8. 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.

  9. 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.

  10. Mechanisms for increased expression of cholesterol 7α-hydroxylase (Cyp7a1) in lactating rats

    Science.gov (United States)

    Wooton-Kee, Clavia Ruth; Coy, Donna J; Athippozhy, Antony T; Zhao, Tianyong; Jones, Brett R; Vore, Mary

    2009-01-01

    Cholesterol 7α-hydroxylase (Cyp7a1) and the bile acid pool size are increased 2–3 fold in lactating postpartum rats. We investigated the interaction of nuclear receptors with the Cyp7a1 proximal promoter and the expression of regulatory signaling pathways in postpartum rats at day 10 (PPd10) vs female controls to identify the mechanisms of increased expression of Cyp7a1, which is maximal at 16 h. Liver X receptor (LXRα) and RNA Polymerase II (RNA Pol II) recruitment to Cyp7a1 chromatin were increased 1.5- and 2.5-fold, respectively, at 16 h on PPd10. Expression of nuclear receptors farnesoid X receptor (FXR), LXRα, liver receptor homologue (LRH-1), hepatocyte nuclear factor 4α (HNF4α), and short heterodimer partner (SHP) mRNA and co-activator peroxisome proliferators-activated receptor γ coactivator-1α (PGC-1α) mRNA was unchanged in PPd10 vs controls at 16 h, while chicken ovalbumin upstream transcription factor II (COUP-TFII) was decreased 40% at 16 h. Investigation of a repressive signaling pathway, the cJun-N-terminal kinase (JNK) signaling pathway in PPd10 vs controls, showed decreased mRNA expression of hepatocyte growth factor (HGF; decreased 60% at 16 h) and tyrosine kinase receptor cMet (decreased 44–50% at 16 h), but these were not accompanied by decreased expression of phosphorylated c-Jun. Importantly, expression of Fibroblast Growth Factor 15 (FGF15) mRNA in the ileum was decreased 70% in PPd10 vs controls, while phosphorylated mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 (Erk1/2) protein expression in liver was decreased 88% at 16 h. Conclusion The increased recruitment of LXRα, a Cyp7a1 stimulatory pathway, and decreased expression of FGF15 and phosphorylated Erk1/2, a Cyp7a1 repressive pathway, combined to increase Cyp7a1 expression during lactation. PMID:19957370

  11. 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...

  12. LOSA-M2 aerosol Raman lidar

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-10-31

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

  13. Periodic Arrays of M2-Branes

    CERN Document Server

    Jeon, Imtak; Richmond, Paul

    2012-01-01

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

  14. The (178m2)Hf Controversy

    Energy Technology Data Exchange (ETDEWEB)

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

    2003-07-24

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

  15. Evidence of paired M2 muscarinic receptors

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-02-01

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

  16. Bactericidal/Permeability-increasing protein fold-containing family member A1 in airway host protection and respiratory disease.

    Science.gov (United States)

    Britto, Clemente J; Cohn, Lauren

    2015-05-01

    Bactericidal/permeability-increasing protein fold-containing family member A1 (BPIFA1), formerly known as SPLUNC1, is one of the most abundant proteins in respiratory secretions and has been identified with increasing frequency in studies of pulmonary disease. Its expression is largely restricted to the respiratory tract, being highly concentrated in the upper airways and proximal trachea. BPIFA1 is highly responsive to airborne pathogens, allergens, and irritants. BPIFA1 actively participates in host protection through antimicrobial, surfactant, airway surface liquid regulation, and immunomodulatory properties. Its expression is modulated in multiple lung diseases, including cystic fibrosis, chronic obstructive pulmonary disease, respiratory malignancies, and idiopathic pulmonary fibrosis. However, the role of BPIFA1 in pulmonary pathogenesis remains to be elucidated. This review highlights the versatile properties of BPIFA1 in antimicrobial protection and its roles as a sensor of environmental exposure and regulator of immune cell function. A greater understanding of the contribution of BPIFA1 to disease pathogenesis and activity may clarify if BPIFA1 is a biomarker and potential drug target in pulmonary disease.

  17. 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 ...

  18. 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 ...

  19. 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 ...

  20. Urea transporters UT-A1 and UT-A3 accumulate in the plasma membrane in response to increased hypertonicity.

    Science.gov (United States)

    Blessing, Nathan W; Blount, Mitsi A; Sands, Jeff M; Martin, Christopher F; Klein, Janet D

    2008-11-01

    The UT-A1 and UT-A3 urea transporters are expressed in the terminal inner medullary collecting duct (IMCD) and play an important role in the production of concentrated urine. We showed that both hyperosmolarity and vasopressin increase urea permeability in perfused rat terminal IMCDs and that UT-A1 and UT-A3 accumulate in the plasma membrane in response to vasopressin. In this study, we investigated whether hyperosmolarity causes UT-A1 and/or UT-A3 to accumulate in the plasma membrane or represents a complimentary stimulatory pathway. Rat IMCD suspensions were incubated in 450 vs. 900 mosM solutions. We biotinylated the IMCD surface proteins, collected, and analyzed them. Membrane accumulation was assessed by Western blotting of the biotinylated protein pool probed with anti-UT-A1 or anti-UT-A3. We studied the effect of NaCl, urea, and sucrose as osmotic agents. Membrane-associated UT-A1 and UT-A3 increased relative to control levels when either NaCl (UT-A1 increased 37 +/- 6%; UT-A3 increased 46 +/- 13%) or sucrose (UT-A1 increased 81 +/- 13%; UT-A3 increased 60 +/- 8%) was used to increase osmolarity. There was no increase in membrane UT-A1 or UT-A3 when urea was added. Analogously, UT-A1 phosphorylation was increased in NaCl- and sucrose- but not in urea-based hyperosmolar solutions. Hypertonicity also increased UT-A3 phosphorylation. We conclude that the increase in the urea permeability in response to hyperosmolarity reflects both UT-A1 and UT-A3 movement to the plasma membrane and may be a direct response to tonicity. Furthermore, this movement is accompanied by, and may require, increased phosphorylation in response to hypertonicity.

  1. Coincubation of PON1, APO A1, and LCAT increases the time HDL is able to prevent LDL oxidation.

    Science.gov (United States)

    Hine, David; Mackness, Bharti; Mackness, Mike

    2012-02-01

    The inhibition of low-density lipoprotein (LDL) oxidation by high-density lipoprotein (HDL) is a major antiatherogenic property of this lipoprotein. This activity is due, in part, to HDL associated proteins. However, whether these proteins interact in the antioxidant activity of HDL is unknown. LDL was incubated with apolipoprotein A1 (apo A1), lecithin:cholesterol acyltransferase (LCAT), and paraoxonase-1 (PON1) alone or in combination, in the presence or absence of HDL under oxidizing conditions. LDL lipid peroxide concentrations were determined. Apo A1, LCAT, and PON1 all inhibit LDL oxidation in the absence of HDL and enhance the ability of HDL to inhibit LDL oxidation. Their effect was additive rather than synergistic; the combination of these proteins significantly enhanced the length of time LDL was protected from oxidation. This seemed to be due to the ability of PON1 to prevent the oxidative inactivation of LCAT. Apo A1, LCAT, and PON1 can all contribute to the antioxidant activity of HDL in vitro. The combination of apo A1, LCAT, and PON1 prolongs the time that HDL can prevent LDL oxidation, due, at least in part, to the prevention LCAT inactivation.

  2. Prediabetic increase in hemoglobin A1c compared with impaired fasting glucose in patients receiving antipsychotic drugs

    NARCIS (Netherlands)

    Manu, Peter; Correll, Christoph U.; Wampers, Martien; van Winkel, Ruud; Yu, Weiping; Mitchell, Alex J.; De Hert, Marc

    2013-01-01

    Background: In 2010, the American Diabetes Association recommended that individuals with hemoglobin A1c 5.7-6.4% be classified as prediabetic even in the absence of impaired fasting glucose (IFG). Aim of study: To compare the clinical and metabolic characteristics of patients receiving antipsychotic

  3. Relative effects of reduced weight and increased physical activity on hemoglobin A1c: Suggestions for behavioral treatments

    Directory of Open Access Journals (Sweden)

    James J. Annesi

    2013-01-01

    Full Text Available Los tratamientos conductuales para la diabetes a menudo han tenido éxito, y se pueden beneficiar de una mejor comprensión de los efectos relativos del tratamiento de dos focos comunes −pérdida de peso y aumento de actividad física− sobre la glucosa en sangre. Adultos con sobrepeso y obesos (N = 59; M = 60 años, con la hemoglobina A1c (HbA1c y con diabetes, participaron durante 6 meses en un tratamiento conductual basado en principios de la teoría de la auto-eficacia y la teoría cognitiva social. El tratamiento se asoció con el aumento de actividad física de forma significativa, la reducción del índice de masa corporal (IMC, y la reducción de los niveles de HbA1c (ps < 0,001. Los cambios en el IMC y la actividad física presentaban una parte significativa de la varianza en el cambio en la HbA1c, R2 = 0,13, p = 0,023. El cambio en la cantidad de actividad física β = −0,36, p = 0,007, pero sin cambiar el IMC, β = −0,03, p = 0,792, contribuyó significativamente a la varianza en el cambio de HbA1c encontrado. No hubo un efecto según el sexo de los participantes. La discusión se centró en cómo los resultados podrían afectar la eficacia, la eficiencia y la aplicación de tratamientos conductuales para el tratamiento de la diabetes.

  4. Increased CYP1A1 expression in human exfoliated urothelial cells of cigarette smokers compared to non-smokers

    Energy Technology Data Exchange (ETDEWEB)

    Doerrenhaus, Angelika; Roos, Peter H. [Institute for Occupational Physiology at the University Dortmund, Dortmund (Germany); Mueller, Tina [Institute for Occupational Physiology at the University Dortmund, Dortmund (Germany); University Dortmund, Department of Statistics, Mathematical Statistics with Applications in Biometrics, Dortmund (Germany)

    2007-01-15

    Polycyclic aromatic hydrocarbons, arylamines and nitrosamines, constituents of cigarette smoke, are known inducers of bladder cancer. The biochemical response of the target tissue, the bladder urothelium, following inhalation of cigarette smoke has not been studied so far. We used exfoliated transitional urothelial cells from human urine samples to analyze effects of smoking on induction of the cytochrome P450 enzyme CYP1A1. Samples of 40 subjects, including male and female smokers and non-smokers, were examined. A prerequisite for the immunofluorescence microscopic analysis of the cells was the enrichment of the urothelial cell population. This was achieved by a new method which is based on magnetic cell sorting exploiting specific binding of immobilized Griffonia simplicifolia lectin to the surface of urothelial cells. Immunostaining of the final cell preparation with a monoclonal antibody to CYP1A1 showed that about 6% of the urothelial cells of non-smokers stained positive for CYP1A1. However, this fraction of positive cells was more than 44% of the urothelial cells in samples from cigarette smokers. In spite of the individual variation, the difference was statistically significant. There were no gender-related differences in the portion of CYP1A1 expressing urothelial cells of smokers and non-smokers. In essence, we show for the first time that human urothelial cells respond to cigarette smoking by induction of CYP1A1. The approach opens new fields of mechanistic and biomarker research with respect to the pathogenetic processes of cancer development in the human bladder. (orig.)

  5. Deficient expression of aldehyde dehydrogenase 1A1 is consistent with increased sensitivity of Gorlin syndrome patients to radiation carcinogenesis.

    Science.gov (United States)

    Wright, Aaron T; Magnaldo, Thierry; Sontag, Ryan L; Anderson, Lindsey N; Sadler, Natalie C; Piehowski, Paul D; Gache, Yannick; Weber, Thomas J

    2015-06-01

    Human phenotypes that are highly susceptible to radiation carcinogenesis have been identified. Sensitive phenotypes often display robust regulation of molecular features that modify biological response, which can facilitate identification of the pathways/networks that contribute to pathophysiological outcomes. Here we interrogate primary dermal fibroblasts isolated from Gorlin syndrome patients (GDFs), who display a pronounced inducible tumorigenic response to radiation, in comparison to normal human dermal fibroblasts (NHDFs). Our approach exploits newly developed thiol reactive probes to define changes in protein thiol profiles in live cell studies, which minimizes artifacts associated with cell lysis. Redox probes revealed deficient expression of an apparent 55 kDa protein thiol in GDFs from independent Gorlin syndrome patients, compared with NHDFs. Proteomics tentatively identified this protein as aldehyde dehydrogenase 1A1 (ALDH1A1), a key enzyme regulating retinoic acid synthesis, and ALDH1A1 protein deficiency in GDFs was confirmed by Western blot. A number of additional protein thiol differences in GDFs were identified, including radiation responsive annexin family members and lamin A/C. Collectively, candidates identified in our study have plausible implications for radiation health effects and cancer susceptibility.

  6. 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.

  7. 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.

  8. Revisiting the Endocytosis of the M2 Muscarinic Acetylcholine Receptor

    OpenAIRE

    Wymke Ockenga; Ritva Tikkanen

    2015-01-01

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

  9. 2,3,7,8-Tetrachlorodibenzo-p-dioxin Increases Reactive Oxygen Species Production in Human Endothelial Cells Via Induction of Cytochrome P4501A1

    OpenAIRE

    2010-01-01

    Studies in our laboratory have demonstrated that subchronic 2,3,7,8,-tetrachlorodibenzo-p-dioxin (TCDD) exposure of adult mice results in hypertension, cardiac hypertrophy, and reduced nitric oxide (NO)-mediated vasodilation. Moreover, increased superoxide anion production was observed in cardiovascular organs of TCDD-exposed mice and this increase contributed to the reduced NO-mediated vasodilation. Since cytochrome P4501A1 (CYP1A1) can contribute to some TCDD-induced toxicity, we tested the...

  10. Mesangial cells from patients with IgA nephropathy have increased susceptibility to galactose-deficient IgA1.

    Science.gov (United States)

    Ebefors, Kerstin; Liu, Peidi; Lassén, Emelie; Elvin, Johannes; Candemark, Emma; Levan, Kristina; Haraldsson, Börje; Nyström, Jenny

    2016-04-05

    IgA nephropathy (IgAN) is the most common glomerulonephritis in the world, affecting close to a million people. Circulating galactose-deficient IgA (gd-IgA), present in patients with IgAN, form immune complex deposits in the glomerular mesangium causing local proliferation and matrix expansion. Intriguing though, individuals having gd-IgA deposits in the kidneys do not necessarily have signs of glomerular disease. Recurrence of IgAN only occurs in less than half of transplanted patients with IgAN, indicating that gd-IgA is not the only factor driving the disease. We hypothesize that, in addition to IgA complexes, patients with IgAN possess a subtype of mesangial cells highly susceptible to gd-IgA induced cell proliferation. To test the hypothesis, we designed a technique to culture primary mesangial cells from renal biopsies obtained from IgAN patients and controls. The cell response to gd-IgA treatment was then measured both on gene and protein level and the proliferation rate of the cells in response to PDGF was investigated. When treated with gd-IgA, mesangial cells from patients with IgAN express and release more PDGF compared to controls. In addition, the mesangial cells from patients with IgAN were more responsive to treatment with PDGF resulting in an increased proliferation rate of the cells compared to control. Mesangial cells cultured from patients with IgAN expressed and released more IL-6 than controls and had a higher expression of matrix genes. Both mesangial cells derived from patients with IgAN and controls increased their expressed TGFβ1 and CCL5 when treated with gd-IgA. We conclude that mesangial cells derived from IgAN patients have a mesangioproliferative phenotype with increased reactivity to IgA and that these cellular intrinsic properties may be important for the development of IgA nephropathy.

  11. A 1.82 m^2 ring laser gyroscope for nano-rotational motion sensing

    CERN Document Server

    Belfi, Jacopo; Bosi, Filippo; Carelli, Giorgio; Di Virgilio, Angela; Maccioni, Enrico; Ortolan, Antonello; Stefani, Fabio

    2011-01-01

    We present a fully active-controlled He-Ne ring laser gyroscope, operating in square cavity 1.35 m in side. The apparatus is designed to provide a very low mechanical and thermal drift of the ring cavity geometry and is conceived to be operative in two different orientations of the laser plane, in order to detect rotations around the vertical or the horizontal direction. Since June 2010 the system is active inside the Virgo interferometer central area with the aim of performing high sensitivity measurements of environmental rotational noise. So far, continuous not attempted operation of the gyroscope has been longer than 30 days. The main characteristics of the laser, the active remote-controlled stabilization systems and the data acquisition techniques are presented. An off-line data processing, supported by a simple model of the sensor, is shown to improve the effective long term stability. A rotational sensitivity at the level of ten nanoradiants per squareroot of Hz below 1 Hz, very close to the required ...

  12. 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.

  13. Retinoic acid prevents virus-induced airway hyperreactivity and M2 receptor dysfunction via anti-inflammatory and antiviral effects

    OpenAIRE

    Moreno-Vinasco, Liliana; Verbout, Norah G.; Fryer, Allison D.; Jacoby, David B.

    2009-01-01

    Inhibitory M2 muscarinic receptors on airway parasympathetic nerves normally limit acetylcholine release. Viral infections decrease M2 receptor function, increasing vagally mediated bronchoconstriction. Since retinoic acid deficiency causes M2 receptor dysfunction, we tested whether retinoic acid would prevent virus-induced airway hyperreactivity and prevent M2 receptor dysfunction. Guinea pigs infected with parainfluenza virus were hyperreactive to electrical stimulation of the vagus nerves,...

  14. Increased Signaling via Adenosine A1 Receptors, Sleep Deprivation, Imipramine, and Ketamine Inhibit Depressive-like Behavior via Induction of Homer1a.

    Science.gov (United States)

    Serchov, Tsvetan; Clement, Hans-Willi; Schwarz, Martin K; Iasevoli, Felice; Tosh, Dilip K; Idzko, Marco; Jacobson, Kenneth A; de Bartolomeis, Andrea; Normann, Claus; Biber, Knut; van Calker, Dietrich

    2015-08-05

    Major depressive disorder is among the most commonly diagnosed disabling mental diseases. Several non-pharmacological treatments of depression upregulate adenosine concentration and/or adenosine A1 receptors (A1R) in the brain. To test whether enhanced A1R signaling mediates antidepressant effects, we generated a transgenic mouse with enhanced doxycycline-regulated A1R expression, specifically in forebrain neurons. Upregulating A1R led to pronounced acute and chronic resilience toward depressive-like behavior in various tests. Conversely, A1R knockout mice displayed an increased depressive-like behavior and were resistant to the antidepressant effects of sleep deprivation (SD). Various antidepressant treatments increase homer1a expression in medial prefrontal cortex (mPFC). Specific siRNA knockdown of homer1a in mPFC enhanced depressive-like behavior and prevented the antidepressant effects of A1R upregulation, SD, imipramine, and ketamine treatment. In contrast, viral overexpression of homer1a in the mPFC had antidepressant effects. Thus, increased expression of homer1a is a final common pathway mediating the antidepressant effects of different antidepressant treatments.

  15. Hepatic bile acid metabolism in the neonatal hamster: expansion of the bile acid pool parallels increased Cyp7a1 expression levels.

    Science.gov (United States)

    Burke, Katie T; Horn, Paul S; Tso, Patrick; Heubi, James E; Woollett, Laura A

    2009-07-01

    Intraluminal concentrations of bile acids are low in newborn infants and increase rapidly after birth, at least partly owing to increased bile acid synthesis rates. The expansion of the bile acid pool is critical since bile acids are required to stimulate bile flow and absorb lipids, a major component of newborn diets. The purpose of the present studies was to determine the mechanism responsible for the increase in bile acid synthesis rates and the subsequent enlargement of bile acid pool sizes (BAPS) during the neonatal period, and how changes in circulating hormone levels might affect BAPS. In the hamster, pool size was low just after birth and increased modestly until 10.5 days postpartum (dpp). BAPS increased more significantly ( approximately 3-fold) between 10.5 and 15.5 dpp. An increase in mRNA and protein levels of cholesterol 7alpha-hydroxylase (Cyp7a1), the rate-limiting step in classical bile acid synthesis, immediately preceded an increase in BAPS. In contrast, levels of oxysterol 7alpha-hydroxylase (Cyp7b1), a key enzyme in bile acid synthesis by the alternative pathway, were relatively elevated by 1.5 dpp. farnesyl X receptor (FXR) and short heterodimeric partner (SHP) mRNA levels remained relatively constant at a time when Cyp7a1 levels increased. Finally, although simultaneous increases in circulating cortisol and Cyp7a1 levels occurred, precocious expression of Cyp7a1 could not be induced in neonatal hamsters with dexamethasone. Thus the significant increase in Cyp7a1 levels in neonatal hamsters is due to mechanisms independent of the FXR and SHP pathway and cortisol.

  16. TNF Counterbalances the Emergence of M2 Tumor Macrophages

    Directory of Open Access Journals (Sweden)

    Franz Kratochvill

    2015-09-01

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

  17. TNF counterbalances the emergence of M2 tumor macrophages

    Science.gov (United States)

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

    2015-01-01

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

  18. Multiple Access Technologies for Cellular M 2M Communications

    Institute of Scientific and Technical Information of China (English)

    Mahyar Shirvanimoghaddam; Sarah J. Johnson

    2016-01-01

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

  19. Theoretical Assessment of 178m2Hf De-Excitation

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-10-06

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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Elemene Increases Autophagic Apoptosis and Drug Sensitivity in Human Cisplatin (DDP)-Resistant Lung Cancer Cell Line SPC-A-1/DDP By Inducing Beclin-1 Expression.

    Science.gov (United States)

    Zhou, Kun; Wang, Liping; Cheng, Ruirui; Liu, Xia; Mao, Shengya; Yan, Yan

    2017-05-23

    Drug resistance is the major obstacle for the successful therapy of lung adenocarcinoma. It was suggested that ß-elemene, a major isoform of elemene, could reverse the drug resistance in lung cancer cells. However, the underlying mechanisms remains poorly known. Here, we aimed to investigate whether elemene is involved in the cisplatin (DDP)-resistance of lung adenocarcinoma cells and further explore the underlying mechanism. The results showed that human lung adenocarcinoma cell line SPC-A-1 and its DDP-resistant strain SPC-A-1/DDP had a similar sensitivity to elemene treatment. Low dose elemene increased the sensitivity of SPC-A-1/DDP cells to DDP, accompanied by a dramatically decrease in expression of multidrug-resistance proteins and cell proliferation, and an increase in cell autophagy and autophagic apoptosis. We found that the expression of Beclin-1, the key regulator of autophagy, was induced by elemene treatment in a dose-dependent manner. Furthermore, we found that Beclin-1 overexpression had a similar effect with elemene treatment on autophagy and autophagic apoptosis in SPC-A-1/DDP cells. In contrast, Beclin-1 knockdown could significantly rescue elemene-induced autophagic apoptosis and counteract elemene-induced sensitivity in SPC-A-1/DDP cells. Our findings demonstrate that elemene can reverses the drug resistance of SPC-A-1/DDP cells via promotion of Beclin-1-induced autophagy.

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

    OpenAIRE

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

    2013-01-01

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

  6. Is glycosylated hemoglobin A1 c associated with increased risk for severe early postoperative complications in nondiabetics after laparoscopic gastric bypass?

    Science.gov (United States)

    Stenberg, Erik; Szabo, Eva; Näslund, Ingmar

    2014-01-01

    Glycosylated hemoglobin A1 c (HbA1 c) has been described as a risk factor for adverse outcome after cardiovascular and colorectal surgery, but not for obese patients undergoing bariatric surgery. The objective of this study was to see if there is an association between HbA1 c and adverse outcome in laparoscopic gastric bypass surgery. From the Scandinavian Obesity Surgery Registry we identified 12,850 patients, without treatment for diabetes and operated with laparoscopic gastric bypass between January 1, 2010 and September 30, 2012, and where a baseline HbA1 c value was registered. Preoperative data were compared with data from a 30-day follow-up. Severe complications were defined according to the Clavien-Dindo-Scale as Grade 3 b or higher. HbA1 c levels below 5.7 % were associated with a lower incidence of severe complications (2.7 %) than higher levels (HbA1 c 5.7-6.49% incidence 3.5%, P = .015; HbA1 c>6.5%, incidence 4.5%, P = .012). After multivariate analysis with patient-specific confounders the difference remained significant (HbA1 c 5.7-6.49% adjusted P = .046; HbA1 c>6.5% adjusted P = .023) CONCLUSION: Elevated HbA1 c levels in patients without pharmacologic treatment for diabetes undergoing laparoscopic gastric bypass surgery is associated with an increased risk for severe complications during the first 30 postoperative days. This is the case, even at levels not regarded as diagnostic for diabetes. Copyright © 2014 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

  7. Combined UGT1A1 and UGT1A6 genotypes together with a stressful life event increase breast cancer risk

    OpenAIRE

    2010-01-01

    Combined UGT1A1 and UGT1A6 genotypes together with a stressful life event increase breast cancer risk phone: +49-711-81015765 (Justenhoven, Christina) (Justenhoven, Christina) Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University Tuebingen - Auerbachstrasse 112 - 70376 - Stuttgart - GERMANY (Justenhoven, Christina) Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University Tuebingen - Auerbachstrasse 11...

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

    Directory of Open Access Journals (Sweden)

    Denis Leclerc

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

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

    Directory of Open Access Journals (Sweden)

    Yi-Rang Na

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

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

    Science.gov (United States)

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

    2015-01-01

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

  11. Vasopressin increases expression of UT-A1, UT-A3, and ER chaperone GRP78 in the renal medulla of mice with a urinary concentrating defect.

    Science.gov (United States)

    Cai, Qi; Nelson, Sarah K; McReynolds, Matthew R; Diamond-Stanic, Maggie Keck; Elliott, David; Brooks, Heddwen L

    2010-10-01

    Activation of V2 receptors (V2R) during antidiuresis increases the permeability of the inner medullary collecting duct to urea and water. Extracellular osmolality is elevated as the concentrating capacity of the kidney increases. Osmolality is known to contribute to the regulation of collecting duct water (aquaporin-2; AQP2) and urea transporter (UT-A1, UT-A3) regulation. AQP1KO mice are a concentrating mechanism knockout, a defect attributed to the loss of high interstitial osmolality. A V2R-specific agonist, deamino-8-D-arginine vasopressin (dDAVP), was infused into wild-type and AQP1KO mice for 7 days. UT-A1 mRNA and protein abundance were significantly increased in the medullas of wild-type and AQP1KO mice following dDAVP infusion. The mRNA and protein abundance of UT-A3, the basolateral urea transporter, was significantly increased by dDAVP in both wild-type and AQP1KO mice. Semiquantitative immunoblots revealed that dDAVP infusion induced a significant increase in the medullary expression of the endoplasmic reticulum (ER) chaperone GRP78. Immunofluorescence studies demonstrated that GRP78 expression colocalized with AQP2 in principal cells of the papillary tip of the renal medulla. Using immunohistochemistry and immunogold electron microscopy, we demonstrate that vasopressin induced a marked apical targeting of GRP78 in medullary principal cells. Urea-sensitive genes, GADD153 and ATF4 (components of the ER stress pathway), were significantly increased in AQP1KO mice by dDAVP infusion. These findings strongly support an important role of vasopressin in the activation of an ER stress response in renal collecting duct cells, in addition to its role in activating an increase in UT-A1 and UT-A3 abundance.

  12. 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

  13. Adjuvant treatment with tumor-targeting Salmonella typhimurium A1-R reduces recurrence and increases survival after liver metastasis resection in an orthotopic nude mouse model.

    Science.gov (United States)

    Murakami, Takashi; Hiroshima, Yukihiko; Zhao, Ming; Zhang, Yong; Chishima, Takashi; Tanaka, Kuniya; Bouvet, Michael; Endo, Itaru; Hoffman, Robert M

    2015-12-01

    Colon cancer liver metastasis is often the lethal aspect of this disease. Well-isolated metastases are candidates for surgical resection, but recurrence is common. Better adjuvant treatment is therefore needed to reduce or prevent recurrence. In the present study, HT-29 human colon cancer cells expressing red fluorescent protein (RFP) were used to establish liver metastases in nude mice. Mice with a single liver metastasis were randomized into bright-light surgery (BLS) or the combination of BLS and adjuvant treatment with tumor-targeting S. typhimurium A1-R. Residual tumor fluorescence after BLS was clearly visualized at high magnification by fluorescence imaging. Adjuvant treatment with S. typhimurium A1-R was highly effective to increase survival and disease-free survival after BLS of liver metastasis. The results suggest the future clinical potential of adjuvant S. typhimurium A1-R treatment after liver metastasis resection.

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

    Directory of Open Access Journals (Sweden)

    Tanja Buchacher

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

  15. Utilizing a Diabetes Risk Test and A1c Point-of-Care Instrument to Identify Increased Risk for Diabetes In an Educational Dental Hygiene Setting.

    Science.gov (United States)

    Giblin, Lori J; Rainchuso, Lori; Rothman, Andrew

    2016-06-01

    The objective of this pilot study was to demonstrate the number of patients at increased risk for type 2 diabetes development using a validated survey; and to assess the rate of compliance for A1c screening in an educational dental hygiene setting. This was a descriptive study using a purposive sample of patients in an academic dental hygiene clinic, who were 18 years or older, not diagnosed with prediabetes or type 2 diabetes. Utilizing the American Diabetes Association adopted diabetes risk survey, patients determined to be at increased risk for type 2 diabetes were offered the opportunity for further assessment by having their A1c tested using a point of care instrument. Patients demonstrating an increased risk for prediabetes or type 2 diabetes, with either the survey or the point of care instrument, were referred to their primary physician for further evaluation. A total 179 of the 422 solicited patients agreed to participate in the American Diabetes Association adopted diabetes risk survey. According to the survey guidelines, 77 participants were considered increased risk for type 2 diabetes for an at-risk prevalence of 48% (95% Confidence Interval (CI): 40 to 56%). The at-risk participants were then asked to have an A1c test of which 45 agreed (compliance rate 58%, 95% CI: 47 to 70%). Using American Diabetes Association A1c parameters, 60.98% (n=25) indicated a prediabetes (5.7 to 6.4%) range, and 4.88% (n=2) indicated a diabetes (≥6.5%) range. Utilizing the American Diabetes Association adopted diabetes risk survey in any dental setting could provide patients with invaluable health information, and potentially improve overall health outcomes. Copyright © 2016 The American Dental Hygienists’ Association.

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

    Science.gov (United States)

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

    2016-04-01

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

  17. An orally active adenosine A1 receptor antagonist, FK838, increases renal excretion and maintains glomerular filtration rate in furosemide-resistant rats

    Science.gov (United States)

    Schnackenberg, Christine G; Merz, Emily; Brooks, David P

    2003-01-01

    Loop and thiazide diuretics are common therapeutic agents for the treatment of sodium retention and oedema. However, resistance to diuretics and decreases in renal function can develop during diuretic therapy. Adenosine causes renal vasoconstriction, sodium reabsorption, and participates in the tubuloglomerular feedback mechanism for the regulation of glomerular filtration rate.We tested the hypothesis that the selective adenosine A1 receptor antagonist FK838 is orally active and causes diuresis and natriuresis, but maintains glomerular filtration rate in normal rats or in rats with furosemide resistance.In normal male Sprague – Dawley rats, FK838 dose-dependently increased urine flow and sodium and chloride excretion while sparing potassium. In combination with furosemide, FK838 enhanced the diuretic and natriuretic actions of furosemide to the same extent as hydrochlorothiazide and did not increase the potassium loss in normal rats. In furosemide-resistant rats, FK838 increased urine flow and electrolyte excretion to a greater extent than hydrochlorothiazide. In addition, hydrochlorothiazide significantly decreased glomerular filtration rate, whereas FK838 maintained glomerular filtration rate in furosemide-resistant rats.This study shows that the adenosine A1 receptor antagonist FK838 is orally active and causes potent diuresis and natriuresis and maintains glomerular filtration rate in normal or furosemide-resistant rats. Adenosine A1 receptor antagonists may be novel therapeutics for the treatment of oedema in normal or otherwise diuretic-resistant patients. PMID:12922924

  18. 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、

  19. 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

  20. M2e-Based Universal Influenza A Vaccines

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    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.

  1. 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.

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

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    Veluchamy A. Barathi

    2013-09-01

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

  3. 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.

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

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    Becky J Proskocil

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

  5. M2 macrophages induce EMT through the TGF-β/Smad2 signaling pathway.

    Science.gov (United States)

    Zhu, Liangying; Fu, Xiao; Chen, Xiang; Han, Xiaodong; Dong, Ping

    2017-09-01

    IPF is characterized by fibroblast accumulation, collagen deposition, and ECM remodeling, with myofibroblasts believed to be the effector cell type. Myofibroblasts develop due to EMT of lung alveolar epithelial cells, which can be induced by TGF-β. M2 macrophages, a macrophage subpopulation, secrete large amounts of TGF-β. To clarify the relationship between IPF, EMT, TGF-β, and M2 macrophages, a bleomycin-induced pulmonary fibrosis mouse model was used. Seventeen days after mice were treated with bleomycin, the successful establishment of a pulmonary fibrosis model was confirmed by HE stain and Masson's trichrome stain. We found evidence in support of EMT, such as elevated protein levels of α-SMA in lung tissue and decreased levels of E-cadherin and CK-18. Additionally, increased TGF-β levels and TGF-β/Smad2 signaling activation was observed. Macrophages were recruited to pulmonary alveoli. Alveolar macrophages were phenotyped and identified as M2 macrophages, with up-regulated CD206 on the cell surfaces. For in vitro studies, we treated RAW 264.7 cells with IL-4 for 24 h, and the cells were then utilized as M2 macrophages. TGF-β levels increased significantly in the culture supernatant. Forty-eight hours after lung epithelial cells (MLE-12) were co-cultured with the M2 macrophages, the expression of α-SMA increased, and E-cadherin and CK-18 decreased. When a TGF-β receptor inhibitor, LY2109761 was used, the EMT induced by M2 macrophages was blocked. In conclusion, we demonstrated that M2 macrophages induce EMT through the TGF-β/Smad2 signaling pathway. © 2017 International Federation for Cell Biology.

  6. A splice acceptor site mutation in TaGW2-A1 increases thousand grain weight in tetraploid and hexaploid wheat through wider and longer grains.

    Science.gov (United States)

    Simmonds, James; Scott, Peter; Brinton, Jemima; Mestre, Teresa C; Bush, Max; Del Blanco, Alicia; Dubcovsky, Jorge; Uauy, Cristobal

    2016-06-01

    Across 13 experiments the gw2 - A1 mutant allele shifts grain size distribution consistently across all grains significantly increasing grain weight (6.6 %), width (2.8 %) and length (2.1 %) in tetraploid and hexaploid wheat. There is an urgent need to identify, understand and incorporate alleles that benefit yield in polyploid wheat. The rice OsGW2 gene functions as a negative regulator of grain weight and width and is homologous to the wheat TaGW2 gene. Previously it was shown that transcript levels of the A-genome homoeologue, TaGW2-A1, are negatively associated with grain width in hexaploid wheat. In this study we screened the tetraploid Kronos TILLING population to identify mutants in TaGW2-A1. We identified a G to A transition in the splice acceptor site of exon 5 which leads to mis-splicing in TaGW2-A1. We backcrossed the mutant allele into tetraploid and hexaploid wheat and generated a series of backcross derived isogenic lines which were evaluated in glasshouse and field conditions. Across 13 experiments the GW2-A1 mutant allele significantly increased thousand grain weight (6.6 %), grain width (2.8 %) and grain length (2.1 %) in tetraploid and hexaploid wheat compared to the wild type allele. In hexaploid wheat, this led to an increase in spike yield since no differences were detected for spikelet or grain number between isogenic lines. The increase in grain width and length was consistent across grains of different sizes, suggesting that the effect of the mutation is stable across the ear and within spikelets. Differences in carpel size and weight between alleles were identified as early as 5 days before anthesis, suggesting that TaGW2-A1 acts on maternal tissue before anthesis to restrict seed size. A single nucleotide polymorphism marker was developed to aid the deployment of the mutant allele into breeding programmes.

  7. Soluble ICAM-5, a product of activity dependent proteolysis, increases mEPSC frequency and dendritic expression of GluA1.

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    Irina Lonskaya

    Full Text Available Matrix metalloproteinases (MMPs are zinc dependent endopeptidases that can be released from neurons in an activity dependent manner to play a role in varied forms of learning and memory. MMP inhibitors impair hippocampal long term potentiation (LTP, spatial memory, and behavioral correlates of drug addiction. Since MMPs are thought to influence LTP through a β1 integrin dependent mechanism, it has been suggested that these enzymes cleave specific substrates to generate integrin binding ligands. In previously published work, we have shown that neuronal activity stimulates rapid MMP dependent shedding of intercellular adhesion molecule-5 (ICAM-5, a synaptic adhesion molecule expressed on dendrites of the telencephalon. We have also shown that the ICAM-5 ectodomain can interact with β1 integrins to stimulate integrin dependent phosphorylation of cofilin, an event that occurs with dendritic spine maturation and LTP. In the current study, we investigate the potential for the ICAM-5 ectodomain to stimulate changes in α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor (AMPAR dependent glutamatergic transmission. Single cell recordings show that the ICAM-5 ectodomain stimulates an increase in the frequency, but not the amplitude, of AMPA mini excitatory post synaptic currents (mEPSCs. With biotinylation and precipitation assays, we also show that the ICAM-5 ectodomain stimulates an increase in membrane levels of GluA1, but not GluA2, AMPAR subunits. In addition, we observe an ICAM-5 associated increase in GluA1 phosphorylation at serine 845. Concomitantly, ICAM-5 affects an increase in GluA1 surface staining along dendrites without affecting an increase in dendritic spine number. Together these data are consistent with the possibility that soluble ICAM-5 increases glutamatergic transmission and that post-synaptic changes, including increased phosphorylation and dendritic insertion of GluA1, could contribute. We suggest that future studies

  8. 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

  9. CYP1A1 gene polymorphisms increase lung cancer risk in a high-incidence region of Spain: a case control study

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    San Jose Carmen

    2010-08-01

    Full Text Available Abstract Background A rural region in south-west Spain has one of the highest lung cancer incidence rates of the country, as revealed by a previous epidemiological 10-year follow-up study. The present work was undertaken to ascertain the role of CYP1A1 gene polymorphisms and their interaction with tobacco smoking in the development of the disease in this location. Methods One-hundred-and-three cases of lung cancer and 265 controls participated in the study. The participants were screened for the presence of four CYP1A1 polymorphisms, namely MspI, Ile462Val, T3205C, and Thr461Asn. Lung cancer risk was estimated as odds ratios (OR and 95% confidence intervals (CI using unconditional logistic regression models adjusting for age, sex, and smoking. Results The distribution of the variant CYP1A1 alleles was different from that described for other Caucasian populations, with CYP1A1*2A showing an uncommonly high frequency (p CYP1A1*2B allele (carrying MspI and Ile462Val mutations was strongly associated with high lung cancer risk (OR = 4.59, CI:1.4-12.6, p p p = 0.04. Moreover, the Thr461Asn polymorphism was found to be associated with SCLC in a Caucasian population for the first time to our knowledge (OR = 8.33, CI: 1.3-15.2, p = 0.04. Conclusion The results suggest that CYP1A1 polymorphisms contribute to increase lung cancer susceptibility in an area with an uncommon high incidence rate.

  10. An Increased Ratio of Glycated Albumin to HbA1c Is Associated with the Degree of Liver Fibrosis in Hepatitis B Virus-Positive Patients

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    Hirayuki Enomoto

    2014-01-01

    Full Text Available Background. In hepatitis B virus- (HBV- positive patients, the relationship between the metabolic variables and histological degree of liver fibrosis has been poorly investigated. Methods. A total of 176 HBV-positive patients were assessed in whom the ratios of glycated albumin-to-glycated hemoglobin (GA/HbA1c were calculated in order to investigate the relationship with the degree of liver fibrosis. Results. The GA/HbA1c ratio increased in association with the severity of fibrosis (METAVIR scores: F0-1: 2.61 ± 0.24, F2: 2.65 ± 0.24, F3: 2.74 ± 0.38, and F4: 2.91 ± 0.63. The GA/HbA1c ratios were inversely correlated with four variables of liver function: the prothrombin time (PT percentage (P<0.0001, platelet count (P<0.0001, albumin value (P<0.0001, and cholinesterase value (P<0.0001. The GA/HbA1c ratio was positively correlated with two well-known markers of liver fibrosis, FIB-4 (P<0.0001 and the AST-to-platelet ratio index (APRI (P<0.0001. Furthermore, the GA/HbA1c showed better correlations with two variables of liver function (PT percentage and cholinesterase value than did FIB-4 and with all four variables than did the APRI. Conclusion. The GA/HbA1c ratio is associated with the degree of liver fibrosis in HBV-positive patients.

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

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    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.

  12. 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.

  13. Mice expressing the human CYP7A1 gene in the mouse CYP7A1 knock-out background lack induction of CYP7A1 expression by cholesterol feeding and have increased hypercholesterolemia when fed a high fat diet.

    Science.gov (United States)

    Chen, Jean Y; Levy-Wilson, Beatriz; Goodart, Sheryl; Cooper, Allen D

    2002-11-08

    Cholesterol 7alpha-hydroxylase (CYP7A1) catalyzes the rate-limiting step in the pathway responsible for the formation of the majority of bile acids. Transcription of the gene is regulated by the size of the bile acid pool and dietary and hormonal factors. The farnesoid X receptor and the liver X receptor (LXR) are responsible for regulation by bile acids and cholesterol, respectively. To study the effects of dietary cholesterol and fat upon expression of the human CYP7A1 gene, mice were generated by crossing transgenic mice carrying the human CYP7A1 gene with mice that were homozygous knock-outs (CYP7A1(-/-)). The mice (mCYP7A1(-/-)/hCYP7A1) expressed the human gene at much higher levels than did the transgenics bred in the wild-type background. A diet containing 1% cholic acid reduced the expression of the human gene in mCYP7A1(-/-)/hCYP7A1 mice to undetectable levels. Cholestyramine (5%) increased the level of expression of the human gene and the mouse gene. Thus, farnesoid X receptor-mediated regulation was preserved. A diet containing 2% cholesterol increased expression of the mouse gene in wild-type mice, but it did not affect expression of the human gene in mCYP7A1(-/-)/hCYP7A1 mice. None of the diets altered the serum cholesterol or triglyceride levels in these mice; 1% cholic acid caused a redistribution of cholesterol from the high density lipoprotein to the low density lipoprotein density in the humanized mice but not in wild-type mice. A diet containing 30% saturated fat and 2% cholesterol caused a decrease in CYP7A1 levels in mCYP7A1(-/-)/hCYP7A1 mice. The serum cholesterol levels rose in all mice fed this diet. The increase was greater in the mCYP7A1(-/-)/hCYP7A1 mice. Together, these data suggest that the lack of an LXR element in the region from -56 to -49 of the human CYP7A1 promoter may account for some of the differences in response to diets between humans and rodents.

  14. No association between variation in the NR4A1 gene locus and metabolic traits in white subjects at increased risk for type 2 diabetes

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    Fritsche Andreas

    2010-06-01

    Full Text Available Abstract Background The nuclear receptor NR4A1 is implicated in metabolic regulation in insulin-sensitive tissues, such as liver, adipose tissue, and skeletal muscle. Functional loss of NR4A1 results in insulin resistance and enhanced intramuscular and hepatic lipid content. Therefore, we investigated in a cohort of white European subjects at increased risk for type 2 diabetes whether genetic variation within the NR4A1 gene locus contributes to prediabetic phenotypes, such as insulin resistance, ectopic fat distribution, or β-cell dysfunction. Methods We genotyped 1495 subjects (989 women, 506 men for five single nucleotide polymorphisms (SNPs tagging 100% of common variants (MAF = 0.05 within the NR4A1 gene locus with an r2 = 0.8. All subjects underwent an oral glucose tolerance test (OGTT, a subset additionally had a hyperinsulinemic-euglycemic clamp (n = 506. Ectopic hepatic (n = 296 and intramyocellular (n = 264 lipids were determined by magnetic resonance spectroscopy. Peak aerobic capacity, a surrogate parameter for oxidative capacity of skeletal muscle, was measured by an incremental exercise test on a motorized treadmill (n = 270. Results After appropriate adjustment and Bonferroni correction for multiple comparisons, none of the five SNPs was reliably associated with insulin sensitivity, ectopic fat distribution, peak aerobic capacity, or indices of insulin secretion (all p ≥ 0.05. Conclusions Our data suggest that common genetic variation within the NR4A1 gene locus may not play a major role in the development of prediabetic phenotypes in our white European population.

  15. 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...

  16. 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.

  17. Increased blood glycohemoglobin A1c levels lead to overestimation of arterial oxygen saturation by pulse oximetry in patients with type 2 diabetes

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    Pu Li

    2012-09-01

    Full Text Available Abstract Background Non-enzymatic glycation increases hemoglobin-oxygen affinity and reduces oxygen delivery to tissues by altering the structure and function of hemoglobin. Objectives We investigated whether an elevated blood concentration of glycosylated hemoglobin (HbA1c could induce falsely high pulse oximeter oxygen saturation (SpO2 in type 2 diabetic patients during mechanical ventilation or oxygen therapy. Methods Arterial oxygen saturation (SaO2 and partial pressure of oxygen (PO2 were determined with simultaneous monitoring of SpO2 in 261 type 2 diabetic patients during ventilation or oxygen inhalation. Results Blood concentration of HbA1c was >7% in 114 patients and ≤ 7% in 147 patients. Both SaO2 (96.2 ± 2.9%, 95% confidence interval [CI] 95.7-96.7% vs. 95.1 ± 2.8%, 95% CI 94.7-95.6% and SpO2 (98.0 ± 2.6%, 95% CI 97.6-98.5% vs. 95.3 ± 2.8%, 95% CI 94.9-95.8% were significantly higher in patients with HbA1c >7% than in those with HbA1c ≤ 7% (Data are mean ± SD, all p 2 did not significantly differ between the two groups. Bland-Altman analysis demonstrated a significant bias between SpO2 and SaO2 (1.83 ±0.55%, 95% CI 1.73% -1.94% and limits of agreement (0.76% and 2.92% in patients with HbA1c >7%. The differences between SpO2 and SaO2 correlated closely with blood HbA1c levels (Pearson’s r = 0.307, p  Conclusions Elevated blood HbA1c levels lead to an overestimation of SaO2 by SpO2, suggesting that arterial blood gas analysis may be needed for type 2 diabetic patients with poor glycemic control during the treatment of hypoxemia.

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

    Science.gov (United States)

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

    2008-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Andrea M Siegel

    2008-04-01

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

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

    Science.gov (United States)

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

    1998-12-01

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

  1. Increased tumour extracellular pH induced by Bafilomycin A1 inhibits tumour growth and mitosis in vivo and alters 5-fluorouracil pharmacokinetics.

    Science.gov (United States)

    McSheehy, P M J; Troy, H; Kelland, L R; Judson, I R; Leach, M O; Griffiths, J R

    2003-03-01

    The aim was to determine if a specific inhibitor of vacuolar H(+)-ATPases (V-ATPases), Bafilomycin A1 (BFM), could increase the low extracellular pH (pHe) typical of solid tumours and thus inhibit their growth in vivo. BFM inhibited the proliferation of various human cells and rat pituitary GH3 tumour cells in vitro (IC50: 2.5-19.2 nM), and flow cytometry on GH3 cells showed a marked increase in S and G2M phases after 16-48 h, but no evidence of increased apoptosis. BFM caused significant inhibition of GH3 xenograft growth, and histomorphometry showed a 30% decrease in mitosis but no change in apoptosis. 31P-magnetic resonance spectroscopy (MRS) in vivo of GH3 xenografts showed that BFM increased pHe, but did not affect pHi, resulting in a decrease in the negative pH gradient (-delta pH). BFM decreased lactate formation suggesting a reduction in glycolysis. We suggest that BFM reduces extracellular H(+)-transport by inhibition of V-ATPases leading to an increase in pHe and decreased glycolysis, and thus reduced tumour cell proliferation. 19F-MRS in vivo showed that a smaller -delta pH was associated with decreased retention of 5-fluorouracil (5FU) which was consistent with our previous data in vivo implying the -delta pH controls tumour retention of 5 FU.

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

    Science.gov (United States)

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

    1998-01-01

    hippocampal formation. Only calretinin and somatostatin showed an appreciable degree of co-localization with m2 (20% and 15%, respectively). Using retrograde tracing, some of the m2-positive cells in stratum oriens were shown to project to the medial septum, accouting for 38% of all projection neurons. The present results demonstrate that there is a differential distribution of m2 receptor immunoreactivity on the axonal vs the somadendritic membranes of distinct interneuron types and suggest that acetylcholine via m2 receptors may reduce GABA release presynaptically from the terminals of perisomatic inhibitory cells, while it may act to increase the activity of another class of interneuron, which innervates the dendritic region of pyramidal cells.

  3. Rs964184 (APOA5-A4-C3-A1) is related to elevated plasma triglyceride levels, but not to an increased risk for vascular events in patients with clinically manifest vascular disease.

    Science.gov (United States)

    van de Woestijne, Anton P; van der Graaf, Yolanda; de Bakker, Paul I W; Asselbergs, Folkert W; Spiering, Wilko; Visseren, Frank L J

    2014-01-01

    Single nucleotide polymorphisms in the APOA5-A4-C3-A1 gene complex are associated with elevated plasma triglycerides and elevated vascular risk in healthy populations. In patients with clinically manifest vascular disease, hypertriglyceridemia and metabolic syndrome are frequently present, but the contribution of these single nucleotide polymorphisms to plasma triglycerides, effect modification by obesity and risk of recurrent vascular events is unknown in these patients. Prospective cohort study of 5547 patients with vascular disease. Rs964184 (APOA5-A4-C3-A1 gene complex) was genotyped, and we evaluated the relation with plasma lipid levels, presence of metabolic syndrome and the risk for new vascular events. The minor allele of rs964184 was strongly associated with log plasma triglycerides (β 0.12; 95%CI 0.10-0.15, p = 1.1*10(-19)), and was also associated with 0.03 mmol/L lower high-density lipoprotein-cholesterol (95%CI 0.01-0.04), and 0.14 mmol/L higher non-high-density lipoprotein-cholesterol (95%CI 0.09-0.20). The minor allele frequency increased from 10.9% in patients with plasma triglycerides triglycerides between 4 and 10 mmol/L. The relation between rs964184 and plasma triglycerides was modified by body mass index in patients with one minor allele (β 0.02; (95%CI -0.04-0.09) if body mass index 27 kg/m2, p for interaction = 0.02). The prevalence of the metabolic syndrome increased from 52% for patients with two copies of the major allele to 62% for patients with two copies of the minor allele (p = 0.01). Rs964184 was not related with recurrent vascular events (HR 0.99; 95%CI 0.86-1.13). The single nucleotide polymorphism rs964184 (APOA5-A4-C3-A1) is associated with elevated plasma triglycerides concentrations in patients with clinically manifest vascular disease. In carriers of one minor allele, the effect on plasma triglycerides was modified by body mass index. There is no relation between rs964184 and recurrent vascular events in these

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

    Science.gov (United States)

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

    2015-11-01

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

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

    Science.gov (United States)

    Tang, Yu; Le, Weidong

    2016-03-01

    One of the most striking hallmarks shared by various neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease (AD), and amyotrophic lateral sclerosis, is microglia-mediated neuroinflammation. Increasing evidence indicates that microglial activation in the central nervous system is heterogeneous, which can be categorized into two opposite types: M1 phenotype and M2 phenotype. Depending on the phenotypes activated, microglia can produce either cytotoxic or neuroprotective effects. In this review, we focus on the potential role of M1 and M2 microglia and the dynamic changes of M1/M2 phenotypes that are critically associated with the neurodegenerative diseases. Generally, M1 microglia predominate at the injury site at the end stage of disease, when the immunoresolution and repair process of M2 microglia are dampened. This phenotype transformation is very complicated in AD due to the phagocytosis of regionally distributed β-amyloid (Aβ) plaque and tangles that are released into the extracellular space. The endogenous stimuli including aggregated α-synuclein, mutated superoxide dismutase, Aβ, and tau oligomers exist in the milieu that may persistently activate M1 pro-inflammatory responses and finally lead to irreversible neuron loss. The changes of microglial phenotypes depend on the disease stages and severity; mastering the stage-specific switching of M1/M2 phenotypes within appropriate time windows may provide better therapeutic benefit.

  6. Three-dimensional numerical simulation of M2 internal tides in the Luzon Strait

    Institute of Scientific and Technical Information of China (English)

    LI Bingtian; CAO Anzhou; LV Xianqing

    2015-01-01

    A three-dimensional isopycnic-coordinate internal tidal model is employed to investigate the generation, propagation, vertical structure and energy conversion of M2 internal tides in the Luzon Strait (LS) with mooring observations. Simulated results, especially the tidal current amplitudes, agree well with observations, demonstrating the reasonability and accuracy of the model. Results indicate that M2 internal tides mainly propagate into three directions horizontally, i.e., eastward towards the western Pacific Ocean, westward towards the Dongsha Island and southwestward towards the South China Sea Basin. In the horizontal direction, tidal current amplitudes decrease as distance increases away from the LS; in the vertical direction, they show an obvious decreasing tendency with depth. Between the double ridges of the LS, a clockwise gyre of M2 baroclinic energy flux appears, which is caused by reflections of M2 internal tides at supercritical topographies, and resonance of M2 internal tides happens along 19.5° and 21.5°N due to the heights and separation distance of the double ridges. The total energy conversion in the LS is about 14.20 GW.

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

    Energy Technology Data Exchange (ETDEWEB)

    Sepehri, Alireza, E-mail: alireza.sepehri@uk.ac.ir [Faculty of Physics, Shahid Bahonar University, P.O. Box 76175, Kerman (Iran, Islamic Republic of); Research Institute for Astronomy and Astrophysics of Maragha (RIAAM), Maragha (Iran, Islamic Republic of); Faizal, Mir, E-mail: f2mir@uwaterloo.ca [Department of Physics and Astronomy, University of Waterloo, Waterloo, ON, N2L 3G1 (Canada); Setare, Mohammad Reza, E-mail: rezakord@ipm.ir [Department of Science, Campus of Bijar, University of Kurdistan, Bijar (Iran, Islamic Republic of); Ali, Ahmed Farag, E-mail: afali@fsu.edu [Department of Physics, Florida State University, Tallahassee, FL 32306 (United States); Department of Physics, Faculty of Science, Benha University, Benha 13518 (Egypt)

    2016-05-15

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

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

    Science.gov (United States)

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

    2016-05-01

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

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. Butyric acid increases transepithelial transport of ferulic acid through upregulation of the monocarboxylate transporters SLC16A1 (MCT1) and SLC16A3 (MCT4).

    Science.gov (United States)

    Ziegler, Kerstin; Kerimi, Asimina; Poquet, Laure; Williamson, Gary

    2016-06-01

    Ferulic acid is released by microbial hydrolysis in the colon, where butyric acid, a major by-product of fermentation, constitutes the main energy source for colonic enterocytes. We investigated how varying concentrations of this short chain fatty acid may influence the absorption of the phenolic acid. Chronic treatment of Caco-2 cells with butyric acid resulted in increased mRNA and protein abundance of the monocarboxylate transporters SLC16A1 (MCT1) and SLC16A3 (MCT4), previously proposed to facilitate ferulic acid absorption in addition to passive diffusion. Short term incubation with butyric acid only led to upregulation of MCT4 while both conditions increased transepithelial transport of ferulic acid in the apical to basolateral, but not basolateral to apical, direction. Chronic treatment also elevated intracellular concentrations of ferulic acid, which in turn gave rise to increased concentrations of ferulic acid metabolites. Immunofluorescence staining of cells revealed uniform distribution of MCT1 protein in the cell membrane, whereas MCT4 was only detected in the lateral plasma membrane sections of Caco-2 cells. We therefore propose that MCT1 may be acting as an uptake transporter and MCT4 as an efflux system across the basolateral membrane for ferulic acid, and that this process is stimulated by butyric acid.

  14. 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.

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

    Science.gov (United States)

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

    2017-01-01

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

  16. Multimeric recombinant M2e protein-based ELISA: a significant improvement in differentiating avian influenza infected chickens from vaccinated ones.

    Directory of Open Access Journals (Sweden)

    Farshid Hadifar

    Full Text Available Killed avian influenza virus (AIV vaccines have been used to control H5N1 infections in countries where the virus is endemic. Distinguishing vaccinated from naturally infected birds (DIVA in such situations however, has become a major challenge. Recently, we introduced the recombinant ectodomain of the M2 protein (M2e of H5N1 subtype as a novel tool for an ELISA based DIVA test. Despite being antigenic in natural infection the monomer form of the M2e used in ELISA had limited antigenicity and consequently poor diagnostic capability. To address this shortcoming, we evaluated the use of four tandem copies of M2e (tM2e for increased efficiency of M2e antibody detection. The tM2e gene of H5N1 strain from Indonesia (A/Indonesia/CDC540/2006 was cloned into a pMAL- p4x expression vector and expressed in E.coli as a recombinant tM2e-MBP or M2e-MBP proteins. Both of these, M2e and tM2e antigens reacted with sera obtained from chickens following live H5N1 infection but not with sera from vaccinated birds. A significantly stronger M2e antibody reaction was observed with the tM2e compared to M2e antigen. Western blotting also supported the superiority of tM2e over M2e in detection of specific M2e antibodies against live H5N1 infection. Results from this study demonstrate that M2e tetramer is a better antigen than single M2e and could be more suitable for an ELISA based DIVA test.

  17. 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.

  18. 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.)

  19. Kinetics of proton transport into influenza virions by the viral M2 channel.

    Directory of Open Access Journals (Sweden)

    Tijana Ivanovic

    Full Text Available M2 protein of influenza A viruses is a tetrameric transmembrane proton channel, which has essential functions both early and late in the virus infectious cycle. Previous studies of proton transport by M2 have been limited to measurements outside the context of the virus particle. We have developed an in vitro fluorescence-based assay to monitor internal acidification of individual virions triggered to undergo membrane fusion. We show that rimantadine, an inhibitor of M2 proton conductance, blocks the acidification-dependent dissipation of fluorescence from a pH-sensitive virus-content probe. Fusion-pore formation usually follows internal acidification but does not require it. The rate of internal virion acidification increases with external proton concentration and saturates with a pK(m of ∼4.7. The rate of proton transport through a single, fully protonated M2 channel is approximately 100 to 400 protons per second. The saturating proton-concentration dependence and the low rate of internal virion acidification derived from authentic virions support a transporter model for the mechanism of proton transfer.

  20. Raman spectroscopic analysis of the increase of the carotenoid antioxidant concentration in human skin after a 1-week diet with ecological eggs

    Science.gov (United States)

    Hesterberg, Karoline; Lademann, Jürgen; Patzelt, Alexa; Sterry, Wolfram; Darvin, Maxim E.

    2009-03-01

    Skin aging is mainly caused by the destructive action of free radicals, produced by the UV light of the sun. The human skin has developed a protection system against these highly reactive molecules in the form of the antioxidative potential. Carotenoids are one of the main components of the antioxidants of the human skin. From former studies, it is known that skin aging is reduced in individuals with high levels of carotenoids. Because most of the antioxidants cannot be produced by the human organism, they must be up taken by nutrition. Using noninvasive Raman spectroscopic measurements it is demonstrated that not only fruits and vegetables but also eggs contain high concentrations of antioxidants including carotenoids, which are even doubled in the case of ecological eggs. After a 1-week diet with ecological eggs performed by six volunteers, it is found that the concentration of the carotenoids in the skin of the volunteers increased by approx. 20%. Our study does not intend to recommend exorbitant egg consumption, as eggs also contain harmful cholesterol. But in the case of egg consumption, ecological eggs from hens kept on pasture should be preferred to also receive a benefit for the skin.

  1. 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...

  2. 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...

  3. 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.

  4. 25  W/m2 collection efficiency solar-pumped Nd:YAG laser by a heliostat-parabolic mirror system.

    Science.gov (United States)

    Liang, D; Almeida, J; Vistas, C R

    2016-09-20

    A large aspheric fused silica lens was used to couple efficiently the concentrated solar radiation from the focal zone of a 1.5-m-diameter primary concentrator into a 4-mm-diameter, 35-mm-long Nd:YAG single-crystal rod within a conical pump cavity. Continuous-wave laser power of 29.3 W was measured, attaining 25.0  W/m2 solar laser collection efficiency, corresponding to a 19% increase over the previous record. Its laser beam figure of merit-the ratio between laser power and the product of Mx2, My2 beam quality factors-of 0.01 W is 1.6 times higher than that of a direct tracking solar laser with 30  W/m2 collection efficiency. A strong dependency of solar laser power on laser resonator cavity length was found.

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

    Science.gov (United States)

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

    2012-03-01

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

  6. 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

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

    Science.gov (United States)

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

    2012-12-01

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

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

    Science.gov (United States)

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

    1998-02-27

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

  9. 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.

  10. 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.

  11. 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

  12. Conformational variability of the glycine receptor M2 domain in response to activation by different agonists.

    Science.gov (United States)

    Pless, Stephan A; Dibas, Mohammed I; Lester, Henry A; Lynch, Joseph W

    2007-12-07

    Models describing the structural changes mediating Cys loop receptor activation generally give little attention to the possibility that different agonists may promote activation via distinct M2 pore-lining domain structural rearrangements. We investigated this question by comparing the effects of different ligands on the conformation of the external portion of the homomeric alpha1 glycine receptor M2 domain. Conformational flexibility was assessed by tethering a rhodamine fluorophore to cysteines introduced at the 19' or 22' positions and monitoring fluorescence and current changes during channel activation. During glycine activation, fluorescence of the label attached to R19'C increased by approximately 20%, and the emission peak shifted to lower wavelengths, consistent with a more hydrophobic fluorophore environment. In contrast, ivermectin activated the receptors without producing a fluorescence change. Although taurine and beta-alanine were weak partial agonists at the alpha1R19'C glycine receptor, they induced large fluorescence changes. Propofol, which drastically enhanced these currents, did not induce a glycine-like blue shift in the spectral emission peak. The inhibitors strychnine and picrotoxin elicited fluorescence and current changes as expected for a competitive antagonist and an open channel blocker, respectively. Glycine and taurine (or beta-alanine) also produced an increase and a decrease, respectively, in the fluorescence of a label attached to the nearby L22'C residue. Thus, results from two separate labeled residues support the conclusion that the glycine receptor M2 domain responds with distinct conformational changes to activation by different agonists.

  13. Technological Transformation Practice of 105 m2 Sintering Machine%105 m2烧结机技术改造实践

    Institute of Scientific and Technical Information of China (English)

    白玮

    2015-01-01

    山钢股份莱芜分公司炼铁厂对3台105 m2烧结机进行了一系列技术改造,包括烧结熔剂破碎工艺优化,配料自动化控制系统改造,混合料温度提升,混合机筒体衬板及安装改造,烧结机漏风治理,单辊篦板保护帽改造等。改造后,烧结机作业率98.02%,烧结矿合格率98.19%,产量355.9万t。%A series of technological transformation for three 105 m2 sintering machines in Laiwu branch iron works has been made. That include to optimize sintering flux crushing process and transform automatic batching control, increase the temperature of mixture, reform of mixing machine barrel lining board and installation, control the air leakage of sinter, transform the single and grate plate protective cap. The sintering machine operating rate reached 98.02%, sinter and the qualified rate can reach 98.19%, sinter yield reached 355.9 million tons.

  14. Increased Expression of ALDH1A1 in Prostate Cancer is Correlated With Tumor Aggressiveness: A Tissue Microarray Study of Iranian Patients.

    Science.gov (United States)

    Kalantari, Elham; Saadi, Faezeh H; Asgari, Mojgan; Shariftabrizi, Ahmad; Roudi, Raheleh; Madjd, Zahra

    2017-09-01

    Subpopulations of prostate cancer (PCa) cells expressing putative stem cell markers possess the ability to promote tumor growth, maintenance, and progression. This study aimed to evaluate the expression patterns and clinical significance of putative stem cell marker aldehyde dehydrogenase 1 A1 (ALDH1A1) in prostate tumor tissues. ALDH1A1 expression was examined in a well-defined series of prostate tissues, including 105 (68%) samples of PCa, 21 (13%) samples of high-grade prostatic intraepithelial neoplasia, and 31 (19%) samples of benign prostate hyperplasia, which were embedded in tissue microarray blocks. The correlation of ALDH1A1 expression with clinicopathologic parameters was also assessed. There was a significant difference between the expression level of ALDH1A1 in PCa compared with the high-grade prostatic intraepithelial neoplasia and benign prostate hyperplasia samples (P<0.001). PCa cells expressing ALDH1A1 were more often seen in samples with advanced Gleason score (P=0.05) and high serum prostate specific antigen level (P=0.02). In addition, a positive correlation was found between ALDH1A1 expression and primary tumor stage and regional lymph node involvement (P=0.04 and 0.03, respectively). The significant association between ALDH1A1 expressions with Gleason score indicates the potential role of this protein in PCa tumorigenesis and aggressive behavior; therefore, this cancer stem cell marker can be used as a promising candidate for targeted therapy of PCa, especially those with high Gleason score.

  15. 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.

  16. Regional outbreak of CTX-M-2 β-lactamase-producing Proteus mirabilis in Japan.

    Science.gov (United States)

    Nakano, Ryuichi; Nakano, Akiyo; Abe, Michiko; Inoue, Matsuhisa; Okamoto, Ryoichi

    2012-12-01

    Proteus mirabilis is a common cause of urinary tract infection. Wild-type P. mirabilis strains are usually susceptible to penicillins and cephalosporins, but occurrences of P. mirabilis producing extended-spectrum β-lactamases (ESBLs) have been recently reported. Here, we surveyed the prevalence of cefotaxime resistance among P. mirabilis strains at seven different hospitals in Kanagawa Prefecture, Japan, and investigated their molecular epidemiology to explain the mechanism of their spread. The prevalence of cefotaxime resistance among P. mirabilis increased annually, from 10.1 % in 1998 to 23.1 % in 2003, and increased drastically in 2004, exceeding 40 %. We collected 105 consecutive and non-duplicate cefotaxime-resistant P. mirabilis isolates (MIC 16 to >256 µg ml(-1)) from these hospitals from June 2004 to May 2005 and characterized their profile. PCR and sequence analysis revealed that all resistant strains produced exclusively CTX-M-2 β-lactamase. PFGE analysis identified 47 banding patterns with 83 % or greater similarity. These results indicated that a regional outbreak of P. mirabilis producing CTX-M-2 β-lactamase has occurred in Japan and suggest that the epidemic spread occurred within and across hospitals and communities by extended clonal strains. Plasmid analysis revealed that 44.8 % of plasmids harboured by bla(CTX-M-2) isolates had common profiles, encoding ISEcp1, IS26 and Int1, and belonged to incompatibility group T. Spread of the resistant isolates in Japan resulted from dissemination of narrow-host-range plasmids of the IncT group encoding bla(CTX-M-2). These findings indicate the rapidly developing problem of treating the species to prevent dissemination of ESBL producers.

  17. Sent packing: protein engineering generates a new crystal form of Pseudomonas aeruginosa DsbA1 with increased catalytic surface accessibility

    Energy Technology Data Exchange (ETDEWEB)

    McMahon, Roisin M., E-mail: r.mcmahon1@uq.edu.au; Coinçon, Mathieu; Tay, Stephanie; Heras, Begoña [University of Queensland, 306 Carmody Road, Brisbane, Queensland 4072 (Australia); Morton, Craig J. [Biota Holdings Limited, Unit 10, 585 Blackburn Road, Notting Hill, Victoria 3168 (Australia); Scanlon, Martin J. [Monash University, 381 Royal Parade, Parkville, Victoria 3052 (Australia); Martin, Jennifer L. [University of Queensland, 306 Carmody Road, Brisbane, Queensland 4072 (Australia)

    2015-11-26

    The crystal structure of a P. aeruginosa DsbA1 variant is more suitable for fragment-based lead discovery efforts to identify inhibitors of this antimicrobial drug target. In the reported structures the active site of the protein can simultaneously bind multiple ligands introduced in the crystallization solution or via soaking. Pseudomonas aeruginosa is an opportunistic human pathogen for which new antimicrobial drug options are urgently sought. P. aeruginosa disulfide-bond protein A1 (PaDsbA1) plays a pivotal role in catalyzing the oxidative folding of multiple virulence proteins and as such holds great promise as a drug target. As part of a fragment-based lead discovery approach to PaDsbA1 inhibitor development, the identification of a crystal form of PaDsbA1 that was more suitable for fragment-soaking experiments was sought. A previously identified crystallization condition for this protein was unsuitable, as in this crystal form of PaDsbA1 the active-site surface loops are engaged in the crystal packing, occluding access to the target site. A single residue involved in crystal-packing interactions was substituted with an amino acid commonly found at this position in closely related enzymes, and this variant was successfully used to generate a new crystal form of PaDsbA1 in which the active-site surface is more accessible for soaking experiments. The PaDsbA1 variant displays identical redox character and in vitro activity to wild-type PaDsbA1 and is structurally highly similar. Two crystal structures of the PaDsbA1 variant were determined in complex with small molecules bound to the protein active site. These small molecules (MES, glycerol and ethylene glycol) were derived from the crystallization or cryoprotectant solutions and provide a proof of principle that the reported crystal form will be amenable to co-crystallization and soaking with small molecules designed to target the protein active-site surface.

  18. HbA1c variability is associated with increased mortality and earlier hospital admission in people with Type 1 diabetes.

    Science.gov (United States)

    Walker, G S; Cunningham, S G; Sainsbury, C A R; Jones, G C

    2017-08-19

    Despite evidence of morbidity, no evidence exists on the relationship between HbA1c variability and mortality in Type 1 diabetes. We performed an observational study to investigate whether the association between HbA1c variability and mortality exists in a population of people with Type 1 diabetes. As a secondary outcome, we compared onset of first hospital admission between groups. People with Type 1 diabetes were identified for inclusion from the Scottish Care Information - Diabetes data set. This database includes data of all people known to have diabetes who live within Scotland. A survival analysis was carried out over a 47-month period comparing two groups; group 1 with a HbA1c coefficient of variation (CV) above the median CV value, and group 2 with a CV below the median value. Time to death or first admission was also analysed. A Cox proportional hazard model was used to compare time to death, adjusting for appropriate covariables. Some 6048 individuals with Type 1 diabetes were included in the analysis. Median HbA1c CV was 7.9. The hazard ratio (HR) for mortality for those with an HbA1c CV above the median value is 1.5 over 47 months of follow-up (P < 0.001). HR for survival to either the first admission to hospital or death for those with an HbA1c CV above the median value was 1.35 (95% confidence interval 1.25-1.45) over 730 days of follow-up (P < 0.001). Our results show that people with greater HbA1c variability have a higher rate of mortality and earlier hospital admission in Type 1 diabetes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Mário Henrique M Barros

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

  20. From Genotype to Phenotype: Nonsense Variants in SLC13A1 Are Associated with Decreased Serum Sulfate and Increased Serum Aminotransferases

    Directory of Open Access Journals (Sweden)

    Christina G. Tise

    2016-09-01

    Full Text Available Using genomic applications to glean insights into human biology, we systematically searched for nonsense single nucleotide variants (SNVs that are rare in the general population but enriched in the Old Order Amish (Amish due to founder effect. We identified two nonlinked, nonsense SNVs (R12X and W48X in SLC13A1 (allele frequencies 0.29% and 0.74% in the Amish; enriched 1.2-fold and 3.7-fold, compared to the outbred Caucasian population, respectively. SLC13A1 encodes the apical sodium-sulfate cotransporter (NaS1 responsible for sulfate (reabsorption in the kidneys and intestine. SLC13A1 R12X and W48X were independently associated with a 27.6% (P = 2.7 × 10−8 and 27.3% (P = 6.9 × 10−14 decrease in serum sulfate, respectively (P = 8.8 × 10-20 for carriers of either SLC13A1 nonsense SNV. We further performed the first exome- and genome-wide association study (ExWAS/GWAS of serum sulfate and identified a missense variant (L348P in SLC26A1, which encodes the basolateral sulfate-anion transporter (Sat1, that was associated with decreased serum sulfate (P = 4.4 × 10−12. Consistent with sulfate’s role in xenobiotic detoxification and protection against acetaminophen-induced hepatotoxicity, SLC13A1 nonsense SNV carriers had higher aminotransferase levels compared to noncarriers. Furthermore, SLC26A1 L348P was associated with lower whole-body bone mineral density (BMD and higher serum calcium, consistent with the osteochondrodysplasia exhibited by dogs and sheep with naturally occurring, homozygous, loss-of-function mutations in Slc13a1. This study demonstrates the power and translational potential of systematic identification and characterization of rare, loss-of-function variants and warrants additional studies to better understand the importance of sulfate in human physiology, disease, and drug toxicity.

  1. 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.

  2. 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.

  3. RESTful M2M Gateway for Remote Wireless Monitoring for District Central Heating Networks

    Directory of Open Access Journals (Sweden)

    Bo Cheng

    2014-11-01

    Full Text Available In recent years, the increased interest in energy conservation and environmental protection, combined with the development of modern communication and computer technology, has resulted in the replacement of distributed heating by central heating in urban areas. This paper proposes a Representational State Transfer (REST Machine-to-Machine (M2M gateway for wireless remote monitoring for a district central heating network. In particular, we focus on the resource-oriented RESTful M2M gateway architecture, and present an uniform devices abstraction approach based on Open Service Gateway Initiative (OSGi technology, and implement the resource mapping mechanism between resource address mapping mechanism between RESTful resources and the physical sensor devices, and present the buffer queue combined with polling method to implement the data scheduling and Quality of Service (QoS guarantee, and also give the RESTful M2M gateway open service Application Programming Interface (API set. The performance has been measured and analyzed. Finally, the conclusions and future work are presented.

  4. 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.

  5. Foot pronation is not associated with increased injury risk in novice runners wearing a neutral shoe : a 1-year prospective cohort study

    NARCIS (Netherlands)

    Nielsen, Rasmus Oestergaard; Buist, Ida; Parner, Erik Thorlund; Nohr, Ellen Aagaard; Sorensen, Henrik; Lind, Martin; Rasmussen, Sten

    2014-01-01

    Objective To investigate if running distance to first running-related injury varies between foot postures in novice runners wearing neutral shoes. Design A 1-year epidemiological observational prospective cohort study. Setting Denmark. Participants A total of 927 novice runners equivalent to 1854 fe

  6. Genetic ablation of macrohistone H2A1 leads to increased leanness, glucose tolerance and energy expenditure in mice fed a high-fat diet.

    NARCIS (Netherlands)

    Sheedfar, F.; Vermeer, M.; Pazienza, V.; Villarroya, J.; Rappa, F.; Cappello, F.; Mazzoccoli, G.; Villarroya, F.; Molen, H. van der; Hofker, M.H.; Koonen, D.P.; Vinciguerra, M.

    2015-01-01

    BACKGROUND/OBJECTIVES: In the context of obesity, epigenetic mechanisms regulate cell-specific chromatin plasticity, perpetuating gene expression responses to nutrient excess. MacroH2A1, a variant of histone H2A, emerged as a key chromatin regulator sensing small nutrients during cell proliferation

  7. Genetic ablation of macrohistone H2A1 leads to increased leanness, glucose tolerance and energy expenditure in mice fed a high-fat diet.

    NARCIS (Netherlands)

    Sheedfar, F.; Vermeer, M.; Pazienza, V.; Villarroya, J.; Rappa, F.; Cappello, F.; Mazzoccoli, G.; Villarroya, F.; Molen, H. van der; Hofker, M.H.; Koonen, D.P.; Vinciguerra, M.

    2015-01-01

    BACKGROUND/OBJECTIVES: In the context of obesity, epigenetic mechanisms regulate cell-specific chromatin plasticity, perpetuating gene expression responses to nutrient excess. MacroH2A1, a variant of histone H2A, emerged as a key chromatin regulator sensing small nutrients during cell proliferation

  8. Genetic ablation of macrohistone H2A1 leads to increased leanness, glucose tolerance and energy expenditure in mice fed a high-fat diet

    NARCIS (Netherlands)

    Sheedfar, F.; Vermeer, M.; Pazienza, V.; Villarroya, J.; Rappa, F.; Cappello, F.; Mazzoccoli, G.; Villarroya, F.; van der Molen, H.; Hofker, M. H.; Koonen, D. P.; Vinciguerra, M.

    2015-01-01

    BACKGROUND/OBJECTIVES: In the context of obesity, epigenetic mechanisms regulate cell-specific chromatin plasticity, perpetuating gene expression responses to nutrient excess. MacroH2A1, a variant of histone H2A, emerged as a key chromatin regulator sensing small nutrients during cell proliferation

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

    Science.gov (United States)

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

    2014-07-01

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

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

    Science.gov (United States)

    Hawthorne, Rebecca; Lynch, Joseph W

    2005-10-28

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

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

    Institute of Scientific and Technical Information of China (English)

    符寒光; 杜建铭; 蒋志强; 邢建东

    2003-01-01

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

  12. Virus- and interferon-induced loss of inhibitory M2 muscarinic receptor function and gene expression in cultured airway parasympathetic neurons.

    OpenAIRE

    Jacoby, D B; Xiao, H Q; Lee, N. H.; Chan-Li, Y; Fryer, A. D.

    1998-01-01

    Viral infections increase vagally mediated reflex bronchoconstriction. Decreased function of inhibitory M2 muscarinic receptors on the parasympathetic nerve endings is likely to contribute to increased acetylcholine release. In this study, we used cultured airway parasympathetic neurons to determine the effects of parainfluenza virus and of interferon (IFN)-gamma on acetylcholine release, inhibitory M2 receptor function, and M2 receptor gene expression. In control cultures, electrically stimu...

  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. 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

  15. High enzyme activity UGT1A1 or low activity UGT1A8 and UGT2B4 genotypes increase esophageal cancer risk.

    NARCIS (Netherlands)

    Dura, P.; Salomon, J.; Morsche, R.H.M. te; Schaap-Roelofs, H.M.J.; Kristinsson, J.O.; Wobbes, T.; Witteman, B.J.; Tan, A.C.; Drenth, J.P.H.; Peters, W.H.M.

    2012-01-01

    Esophageal cancer (EC) has a globally increasing incidence with poor curative treatment options and survival rates. Environmental and dietary factors have crucial roles in esophageal carcinogenesis. Polymorphisms in the UGT genes, a superfamily of enzymes essential for the detoxification of

  16. Thermal testing results of an electroformed nickel secondary (M2) mirror

    Science.gov (United States)

    Smith, David R.; Gale, David M.; Cabrera Cuevas, Lizeth; Lucero Álvarez, Maribel; Castro Santos, David; Olmos Tapia, Arak

    2016-07-01

    To support higher-frequency operation, the Large Millimeter Telescope/Gran Telescopio Milimetrico (or LMT/GTM) is replacing its existing monolithic aluminum secondary mirror (M2). The new mirror is a segmented design based on the same electroformed nickel reflector panel technology that is already in use for the primary reflector segments. While the new M2 is lighter and has better surface accuracy than the original mirror, the electroformed panels are more sensitive to high temperatures. During the design phase, concerns were raised over the level of temperature increase that could occur at M2 during daytime observations. Although the panel surface is designed to scatter visible light, the LMT primary mirror is large enough to cause substantial solar heating, even at significant angular separation from the Sun. To address these concerns, the project conducted a series of field tests, within the constraint of having minimum impact on night time observations. The supplier sent two coupon samples of a reflector panel prepared identically to their proposed M2 surface. Temperature sensors were mounted on the samples and they were temporarily secured to the existing M2 mirror at different distances from the center. The goal was to obtain direct monitoring of the surface temperature under site thermal conditions and the concentration effects from the primary reflector. With the sensors installed, the telescope was then commanded to track the Sun with an elevation offset. Initially, elevation offsets from as far as 40 degrees to as close as 6 degrees were tested. The 6 degree separation test quickly passed the target maximum temperature and the telescope was returned to a safer separation. Based on these initial results, a second set of tests was performed using elevation separations from 30 degrees to 8 degrees. To account for the variability of site conditions, the temperature data were analyzed using multiple metrics. These metrics included maximum temperature, final

  17. Neuroprotection of Persea major extract against oxygen and glucose deprivation in hippocampal slices involves increased glutamate uptake and modulation of A1 and A2A adenosine receptors

    Directory of Open Access Journals (Sweden)

    Marielli Letícia Fedalto

    2013-10-01

    Full Text Available Ischemic stroke is characterised by a lack of oxygen and glucose in the brain, leading to excessive glutamate release and neuronal cell death. Adenosine is produced in response to ATP depletion and acts as an endogenous neuromodulator that reduces excitotoxicity. Persea major (Meins. L.E. Kopp (Lauraceae is a medical plant that is indigenous to South Brazil, and the rural population has used it medicinally due to its anti-inflammatory properties. The aim of this study was to evaluate the neuroprotective effect of Persea major methanolic extract against oxygen and glucose deprivation and re-oxygenation as well as to determine its underlying mechanism of action in hippocampal brain slices. Persea major methanolic extract (0.5 mg/ml has a neuroprotective effect on hippocampal slices when added before or during 15 min of oxygen and glucose deprivation or 2 h of re-oxygenation. Hippocampal slices subjected to oxygen and glucose deprivation and re-oxygenation showed significantly reduced glutamate uptake, and the addition of Persea major methanolic extract in the re-oxygenation period counteracted the reduction of glutamate uptake. The presence of A1 or A2A, but not A2B or A3 receptor antagonists, abolished the neuroprotective effect of Persea major methanolic extract. In conclusion, the neuroprotective effect of Persea majormethanolic extract involves augmentation of glutamate uptake and modulation of A1 and A2B adenosine receptors.

  18. Surgical Techniques to Increase the Apicocoronal Dimension of the Attached Gingiva: A 1-Year Comparison Between the Free Gingival Graft and the Modified Apically Repositioned Flap.

    Science.gov (United States)

    Carnio, João; Camargo, Paulo M; Pirih, Paulo Q

    2015-01-01

    The attached gingiva is a desirable anatomical element for the maintenance of gingival health. The free gingival graft (FGG) and the modified apically repositioned flap (MARF) are predictable surgical techniques often employed to increase the zone of attached gingiva. This randomized study compared the FGG and the MARF in increasing the zone of attached gingiva in contralateral sides of 15 patients 1 year posttreatment. There was an increase in keratinized tissue and attached gingiva in both groups. Gingival recession did not significantly change between pre- and posttreatment levels in either group. The MARF surgical time was approximately half as long as that of the FGG. The authors conclude that both techniques are viable; however, the main advantages of the MARF were decreased surgical time and less postoperative discomfort.

  19. 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.

  20. The microvascular volume of the achilles tendon is increased in patients with tendinopathy at rest and after a 1-hour treadmill run

    DEFF Research Database (Denmark)

    Pingel, Jessica; Harrison, Adrian; Simonsen, Lene

    2013-01-01

    BACKGROUND:Achilles tendinopathy (AT) is initiated asymptomatically and is therefore often discovered at a very late stage. PURPOSE:To elucidate whether the microvascular volume (MV) of the Achilles tendon is elevated in patients with AT compared with healthy controls during pre-exercise rest...... of tendinopathy. CLINICAL RELEVANCE:This study underlines that tendon flexibility is altered in patients with AT and that CEU is a promising tool to establish the early diagnosis of this condition......., after acute exercise, and 24 hours after exercise. Additionally, this study investigated the muscle activation pattern of the gastrocnemius muscle and the relative elasticity of the Achilles tendon during a 1-hour treadmill run in healthy patients and in patients with AT. STUDY DESIGN...

  1. 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.

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

    Science.gov (United States)

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

    2013-12-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2014-06-01

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

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

    Science.gov (United States)

    1967-01-01

    lifting body descended at an average rate of about 3,600 feet-per-minute. At 1,000 feet above the ground, the nose was lowered to increase speed to about 150 mph, flare was at 200 feet from a 20 degree dive. The landing was smooth, and the lifting body program was on its way. The M2-F1 was flown until August 16, 1966. It proved the lifting body concept and lead the way for subsequent, metal 'heavyweight' designs. Chuck Yeager, Bruce Peterson, Bill Dana, Jerry Gentry, James Wood, Don Sorlie, Fred Haise, Joe Engle, and Don Mallick also flew the M2-F1. More than 400 ground tows and 77 aircraft tow flights were carried out with the M2-F1. The success of Dryden's M2-F1 program led to NASA's development and construction of two heavyweight lifting bodies based on studies at NASA's Ames and Langley research centers--the M2-F2 and the HL-10, both built by the Northrop Corporation, and to the Air Force's X-24 program, for which the vehicles were built by Martin. The Lifting Body program also heavily influenced the Space Shuttle program.

  6. 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。

  7. 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 ...

  8. 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 ...

  9. 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 ...

  10. 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 ...

  11. 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 ...

  12. 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 ...

  13. 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 ...

  14. SMAD-PI3K-Akt-mTOR pathway mediates BMP-7 polarization of monocytes into M2 macrophages.

    Directory of Open Access Journals (Sweden)

    Crystal Rocher

    Full Text Available Previously we demonstrated that bone morphogenetic protein-7 (BMP-7 treatment polarizes monocytes into M2 macrophages and increases the expression of anti-inflammatory cytokines. Despite these findings, the mechanisms for the observed BMP-7 induced monocyte polarization into M2 macrophages are completely unknown. In this study, we demonstrate the mechanisms involved in the polarization of monocytes into M2 macrophages. Apoptotic conditioned media (ACM was generated to mimic the stressed conditions, inducing monocyte polarization. Monocytes were treated with ACM along with BMP-7 and/or its inhibitor, follistatin, for 48 hours. Furthermore, an inhibitor of the PI3K pathway, LY-294002, was also studied. Our data show that BMP-7 induces polarization of monocytes into M2 macrophages while significantly increasing the expression of anti-inflammatory markers, arginase-1 and IL-10, and significantly (p<0.05 decreasing the expression of pro-inflammatory markers iNOS, IL-6, TNF-α and MCP-1; (p<0.05. Moreover, addition of the PI3K inhibitor, LY-294002, significantly (p<0.05 decreases upregulation of IL-10 and arginase-1, suggesting involvement of the PI3K pathway in M2 macrophage polarization. Next, following BMP-7 treatment, a significant (p<0.05 increase in p-SMAD1/5/8 and p-PI3K expression resulting in downstream activation of p-Akt and p-mTOR was observed. Furthermore, expression of p-PTEN, an inhibitor of the PI3K pathway, was significantly (p<0.05 increased in the ACM group. However, BMP-7 treatment inhibited its expression, suggesting involvement of the PI3K-Akt-mTOR pathway. In conclusion, we demonstrate that BMP-7 polarizes monocytes into M2 macrophages and enhances anti-inflammatory cytokine expression which is mediated by the activated SMAD-PI3K-Akt-mTOR pathway.

  15. Extreme Levels of HbA1c Increase Incident ESRD Risk in Chinese Patients with Type 2 Diabetes: Competing Risk Analysis in National Cohort of Taiwan Diabetes Study.

    Directory of Open Access Journals (Sweden)

    Li-Na Liao

    Full Text Available Whether HbA1c is a predictor of end-stage renal disease (ESRD in type 2 diabetes patients remains unclear. This study evaluated relationship between HbA1c and ESRD in Chinese patients with type 2 diabetes.Patients aged ≥ 30 years who were free of ESRD (n = 51 681 were included from National Diabetes Care Management Program from 2002-2003. Extended Cox proportional hazard model with competing risk of death served to evaluate association between HbA1c level and ESRD.A total of 2613 (5.06% people developed ESRD during a follow-up period of 8.1 years. Overall incidence rate of ESRD was 6.26 per 1000 person-years. Patients with high levels of HbA1c had a high incidence rate of ESRD, from 4.29 for HbA1c of  6.0%-6.9% to 10.33 for HbA1c ≥ 10.0% per 1000 person-years. Patients with HbA1c < 6.0% particularly had a slightly higher ESRD incidence (4.34 per 1000 person-years than those with HbA1c  of 6.0%-6.9%. A J-shaped relationship between HbA1c level and ESRD risk was observed. After adjustment, patients with HbA1c < 6.0% and ≥ 10.0% exhibited an increased risk of ESRD (HR: 1.99, 95% CI: 1.62-2.44; HR: 4.42, 95% CI: 3.80-5.14, respectively compared with those with HbA1c of 6.0%-6.9%.Diabetes care has focused on preventing hyperglycemia, but not hypoglycemia. Our study revealed that HbA1c level ≥ 7.0% was linked with increased ESRD risk in type 2 diabetes patients, and that HbA1c < 6.0% also had the potential to increase ESRD risk. Our study provides epidemiological evidence that appropriate glycemic control is essential for diabetes care to meet HbA1c targets and improve outcomes without increasing the risk to this population. Clinicians need to pay attention to HbA1c results on diabetic nephropathy.

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

    Science.gov (United States)

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

    2016-01-29

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

  17. Apo A1 Mimetic Rescues the Diabetic Phenotype of HO-2 Knockout Mice via an Increase in HO-1 Adiponectin and LKBI Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Jian Cao

    2012-01-01

    Full Text Available Insulin resistance, with adipose tissue dysfunction, is one of the hallmarks of metabolic syndrome. We have reported a metabolic syndrome-like phenotype in heme oxygenase (HO-2 knockout mice, which presented with concurrent HO-1 deficiency and were amenable to rescue by an EET analog. Apo A-I mimetic peptides, such as L-4F, have been shown to induce HO-1 expression and decrease oxidative stress and adiposity. In this study we aimed to characterize alleviatory effects of HO-1 induction (if any on metabolic imbalance observed in HO-2 KO mice. In this regard, HO-2(−/− mice were injected with 2 mg/kg/day L-4F, or vehicle, i.p., for 6 weeks. As before, compared to WT animals, the HO-2 null mice were obese, displayed insulin resistance, and had elevated blood pressure. These changes were accompanied by enhanced tissue (hepatic oxidative stress along with attenuation of HO-1 expression and activity and reduced adiponectin, pAMPK, and LKB1 expression. Treatment with L-4F restored HO-1 expression and activity and increased adiponectin, LKB1, and pAMPK in the HO-2(−/− mice. These alterations resulted in a decrease in blood pressure, insulin resistance, blood glucose, and adiposity. Taken together, our results show that a deficient HO-1 response, in a state with reduced HO-2 basal levels, is accompanied by disruption of metabolic homeostasis which is successfully restored by an HO-1 inducer.

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

    Science.gov (United States)

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

    2006-01-01

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

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

    Science.gov (United States)

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

    2006-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  2. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2004-08-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-01-10

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

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

    CERN Document Server

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

    2013-01-01

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

  6. 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.

  7. 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.

  8. 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).

  9. Comparative scenario study of tropospheric ozone climate interactions using a global model. A 1% global increase rate, the IS92a IPCC scenario and a simplified aircraft traffic increase scenario

    Energy Technology Data Exchange (ETDEWEB)

    Chalita, S. [Centre National de la Recherche Scientifique (CNRS), 75 - Paris (France). Service d`Aeronomie; Le Treut, H. [Centre National de la Recherche Scientifique (CNRS), 75 - Paris (France). Lab. de Meteorologie Dynamique

    1997-12-31

    Sensitivity studies have been made to establish the relationship between different scenarios of tropospheric ozone increase and radiative forcing. Some aspects of the ozone-climate interactions for past and future scenarios are investigated. These calculations employ IMAGES tropospheric ozone concentrations for a pre-industrial, present and future atmospheres. The averaged last 10 years of the 25-year seasonal integrations were analyzed. The results of this study are preliminary. Ozone forcing is basically different from the CO{sub 2} forcing, for its regional and temporal structured nature and for its rather weak intensity. (R.P.) 14 refs.

  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. 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.

  12. 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.

  13. Wireless Device-to-Device (D2D) Links for Machine-to-Machine (M2M) Communication

    DEFF Research Database (Denmark)

    Pratas, Nuno; Popovski, Petar

    2017-01-01

    Device-to-Device (D2D) communications will play an important role in the fifth generation (5G) cellular networks, by increasing the spatial reuse of spectrum resources and enabling communication links with low latency. D2D is composed of two fundamental building blocks: proximity discovery...... and direct communication between nearby users. Another emerging trend in wireless cellular systems is Machine-to-Machine (M2M) communications, often characterized by fixed, low transmission rates. In this chapter we motivate the synergy between D2D and M2M, and present technologies that enable M2M-via-D2D...... communication to operate as an underlay to the ordinary cellular transmissions....

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

    Science.gov (United States)

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

    1999-11-01

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

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

    Directory of Open Access Journals (Sweden)

    S. F. Gnyusov

    2012-01-01

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

  16. 货币政策对M2的动态效应时滞分析及危机效应测算%Fluctuation Characteristics and Causes in M2 and Monetary Policy

    Institute of Scientific and Technical Information of China (English)

    柴建; 郭菊娥; 汪寿阳

    2012-01-01

    The rapid growth of economic development in China had begun exerting pressure on rising consumer price since 2008. Avoiding inflation and overheating economy have become major economic controlling issues for Chinese government. Maintaining stable economic development and controlling excessive rising of consumer price become the main focus of economic development. Financial crisis in the US has negative effect on China, including slow growth of investment, export, and economic development. In order to increase domestic demand and promote economic growth, Chinese government begins changing its monetary policy from tightness to moderate looseness. It is important to increase financial support for economic development with the goal of having an annual money supply target, which should be at least 3-4 percent higher than the sum of GDP growth rate. In another word, the M2 general money supply rises by about 17% . However, the impact of financial crisis is an uncertain factor. It is time to solve the pivotal issues as to how to access the exciting monetary policy in response to international financial crisis.In section 1, we divide the whole research period into different parts because the impact of explanatory variables on M2 varies with different analysis periods. In practice, we divide China's monetary policy timeline into expansion period and contraction period based the literature review. The paper uses Markov's state transition idea and HP filtering model to determine the turning point. The expansion period of monetary policy is from August 2002 to March 2004; the contraction period is from April 2004 to June 2005. Dividing the monetary policy into these two periods enables us to calculate a lag value for both periods.In section 2, we focus on factor filtering that affects M2 based on the elastic analysis. We use the path analysis to help us understand factor correlations and their potential effect on M2. The analysis result shows that foreign exchange reserve is a

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

    Science.gov (United States)

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

    1999-03-01

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

  18. 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.

  19. 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 ...

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    Teresa M. Evans

    2014-06-01

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

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    Science.gov (United States)

    1966-01-01

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

  8. 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.

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

    Science.gov (United States)

    Williams, Joshua; Newman, Sharlene

    2016-01-01

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

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

    Science.gov (United States)

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

    2007-08-02

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

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

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

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

  12. Almost optimal distributed M2M multicasting in wireless mesh networks

    DEFF Research Database (Denmark)

    Xin, Qin; Manne, Fredrik; Zhang, Yan

    2012-01-01

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

  13. 12 CFR Appendix M2 to Part 226 - Actual Repayment Disclosures

    Science.gov (United States)

    2010-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1990-12-01

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

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

    Institute of Scientific and Technical Information of China (English)

    田振军; 杜蕾

    2009-01-01

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

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

    Science.gov (United States)

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

    2006-01-01

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

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

    Science.gov (United States)

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

    2015-10-01

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

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

    Science.gov (United States)

    1963-01-01

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

  19. 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

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

    Science.gov (United States)

    Sankararamakrishnan, R; Samsom, M S

    1994-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Qi-Shi Du

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

  2. Augmented oxygen-mediated transcriptional activation of cytochrome P450 (CYP)1A expression and increased susceptibilities to hyperoxic lung injury in transgenic mice carrying the human CYP1A1 or mouse 1A2 promoter in vivo.

    Science.gov (United States)

    Jiang, Weiwu; Couroucli, Xanthi I; Wang, Lihua; Barrios, Roberto; Moorthy, Bhagavatula

    2011-04-01

    Supplemental oxygen administration is frequently administered to pre-term and term infants having pulmonary insufficiency. However, hyperoxia contributes to the development of bronchopulmonary dysplasia (BPD) in premature infants. Cytochrome P450 (CYP)A enzymes have been implicated in hyperoxic lung injury. In this study, we tested the hypothesis that hyperoxia induces CYP1A1 and 1A2 enzymes by transcriptional activation of the corresponding promoters in vivo, and transgenic mice expressing the human CYP1A1 or the mouse 1A2 promoter would be more susceptible to hyperoxic lung injury than wild type (WT) mice. Adult WT (CD-1) (12week-old) mice, transgenic mice carrying a 10kb human CYP1A1 promoter and the luciferase (luc) reporter gene (CYP1A1-luc), or mice expressing the mouse CYP1A2 promoter (CYP1A2-luc) were maintained in room air or exposed to hyperoxia for 24-72h. Hyperoxia exposure of CYP1A1-luc mice for 24 and 48h resulted in 2.5- and 1.25-fold increases, respectively, in signal intensities, compared to room air controls. By 72h, the induction had declined to control levels. CYP1A2-luc mice also showed enhanced luc expression after 24-48h, albeit to a lesser extent than those expressing the CYP1A1 promoter. Also, these mice showed decreased levels of endogenous CYP1A1 and 1A2 expression after prolonged hyperoxia, and were also more susceptible to lung injury than similarly exposed WT mice, with CYP1A2-luc mice showing the greatest injury. Our results support the hypothesis that hyperoxia induces CYP1A enzymes by transcriptional activation of its corresponding promoters, and that decreased endogenous expression of these enzymes contribute to the increased susceptibilities to hyperoxic lung injury in the transgenic animals. In summary, this is the first report providing direct evidence of hyperoxia-mediated induction of CYP1A1 and CYP1A2 expression in vivo by mechanisms entailing transcriptional activation of the corresponding promoters, a phenomenon that has

  3. Ethanol and 4-methylpyrazole increase DNA adduct formation of furfuryl alcohol in FVB/N wild-type mice and in mice expressing human sulfotransferases 1A1/1A2.

    Science.gov (United States)

    Sachse, Benjamin; Meinl, Walter; Glatt, Hansruedi; Monien, Bernhard H

    2016-03-01

    Furfuryl alcohol (FFA) is a carcinogenic food contaminant, which is formed by acid- and heat-catalyzed degradation of fructose and glucose. The activation by sulfotransferases (SULTs) yields a DNA reactive and mutagenic sulfate ester. The most prominent DNA adduct, N(2)-((furan-2-yl)methyl)-2'-deoxyguanosine (N(2)-MF-dG), was detected in FFA-treated mice and also in human tissue samples. The dominant pathway of FFA detoxification is the oxidation via alcohol dehydrogenases (ADHs) and aldehyde dehydrogenases (ALDHs). The activity of these enzymes may be greatly altered in the presence of inhibitors or competitive substrates. Here, we investigated the impact of ethanol and the ADH inhibitor 4-methylpyrazole (4MP) on the DNA adduct formation by FFA in wild-type and in humanized mice that were transgenic for human SULT1A1/1A2 and deficient in the mouse (m) Sult1a1 and Sult1d1 genes (h1A1/1A2/1a1(-)/1d1(-)). The administration of FFA alone led to hepatic adduct levels of 4.5 N(2)-MF-dG/10(8) nucleosides and 33.6 N(2)-MF-dG/10(8) nucleosides in male and female wild-type mice, respectively, and of 19.6 N(2)-MF-dG/10(8) nucleosides and 95.4 N(2)-MF-dG/10(8) nucleosides in male and female h1A1/1A2/1a1(-)/1d1(-) mice. The coadministration of 1.6g ethanol/kg body weight increased N(2)-MF-dG levels by 2.3-fold in male and by 1.7-fold in female wild-type mice and by 2.5-fold in male and by 1.5-fold in female h1A1/1A2/1a1(-)/1d1(-) mice. The coadministration of 100mg 4MP/kg body weight had a similar effect on the adduct levels. These findings indicate that modulators of the oxidative metabolism, e.g. the drug 4MP or consumption of alcoholic beverages, may increase the genotoxic effects of FFA also in humans.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-01-01

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

  6. Aggregation and Trunking of M2M Traffic via D2D Connections

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2012-10-01

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

  8. Structure and mechanism of proton transport through the transmembrane tetrameric M2 protein bundle of the influenza A virus.

    Science.gov (United States)

    Acharya, Rudresh; Carnevale, Vincenzo; Fiorin, Giacomo; Levine, Benjamin G; Polishchuk, Alexei L; Balannik, Victoria; Samish, Ilan; Lamb, Robert A; Pinto, Lawrence H; DeGrado, William F; Klein, Michael L

    2010-08-24

    The M2 proton channel from influenza A virus is an essential protein that mediates transport of protons across the viral envelope. This protein has a single transmembrane helix, which tetramerizes into the active channel. At the heart of the conduction mechanism is the exchange of protons between the His37 imidazole moieties of M2 and waters confined to the M2 bundle interior. Protons are conducted as the total charge of the four His37 side chains passes through 2(+) and 3(+) with a pK(a) near 6. A 1.65 A resolution X-ray structure of the transmembrane protein (residues 25-46), crystallized at pH 6.5, reveals a pore that is lined by alternating layers of sidechains and well-ordered water clusters, which offer a pathway for proton conduction. The His37 residues form a box-like structure, bounded on either side by water clusters with well-ordered oxygen atoms at close distance. The conformation of the protein, which is intermediate between structures previously solved at higher and lower pH, suggests a mechanism by which conformational changes might facilitate asymmetric diffusion through the channel in the presence of a proton gradient. Moreover, protons diffusing through the channel need not be localized to a single His37 imidazole, but instead may be delocalized over the entire His-box and associated water clusters. Thus, the new crystal structure provides a possible unification of the discrete site versus continuum conduction models.

  9. 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

  10. 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.

  11. HF183/BFDrev and HumM2 qPCR data

    Data.gov (United States)

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

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

    DEFF Research Database (Denmark)

    Madueño, Germán Corrales

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

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

    NARCIS (Netherlands)

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

    2011-01-01

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

  14. 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.

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

    NARCIS (Netherlands)

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

    2011-01-01

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

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

    National Research Council Canada - National Science Library

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Michio Kosugi

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-08-26

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

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

    Indian Academy of Sciences (India)

    E K Narayanan; Suparna Sen

    2010-04-01

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

  20. 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...

  1. 10D massive type IIA supergravities as the uplift of parabolic M2-brane torus bundles

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-04-15

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

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

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2003-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    Shuyin Li; Liming Zou; Carry Pope

    2008-01-01

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

  5. Essential role of the m2R-RGS6-IKACh pathway in controlling intrinsic heart rate variability.

    Directory of Open Access Journals (Sweden)

    Ekaterina Posokhova

    Full Text Available Normal heart function requires generation of a regular rhythm by sinoatrial pacemaker cells and the alteration of this spontaneous heart rate by the autonomic input to match physiological demand. However, the molecular mechanisms that ensure consistent periodicity of cardiac contractions and fine tuning of this process by autonomic system are not completely understood. Here we examined the contribution of the m2R-I(KACh intracellular signaling pathway, which mediates the negative chronotropic effect of parasympathetic stimulation, to the regulation of the cardiac pacemaking rhythm. Using isolated heart preparations and single-cell recordings we show that the m2R-I(KACh signaling pathway controls the excitability and firing pattern of the sinoatrial cardiomyocytes and determines variability of cardiac rhythm in a manner independent from the autonomic input. Ablation of the major regulator of this pathway, Rgs6, in mice results in irregular cardiac rhythmicity and increases susceptibility to atrial fibrillation. We further identify several human subjects with variants in the RGS6 gene and show that the loss of function in RGS6 correlates with increased heart rate variability. These findings identify the essential role of the m2R-I(KACh signaling pathway in the regulation of cardiac sinus rhythm and implicate RGS6 in arrhythmia pathogenesis.

  6. Essential Role of the m2R-RGS6-IKACh Pathway in Controlling Intrinsic Heart Rate Variability

    Science.gov (United States)

    Posokhova, Ekaterina; Ng, David; Opel, Aaisha; Masuho, Ikuo; Tinker, Andrew; Biesecker, Leslie G.; Wickman, Kevin; Martemyanov, Kirill A.

    2013-01-01

    Normal heart function requires generation of a regular rhythm by sinoatrial pacemaker cells and the alteration of this spontaneous heart rate by the autonomic input to match physiological demand. However, the molecular mechanisms that ensure consistent periodicity of cardiac contractions and fine tuning of this process by autonomic system are not completely understood. Here we examined the contribution of the m2R-IKACh intracellular signaling pathway, which mediates the negative chronotropic effect of parasympathetic stimulation, to the regulation of the cardiac pacemaking rhythm. Using isolated heart preparations and single-cell recordings we show that the m2R-IKACh signaling pathway controls the excitability and firing pattern of the sinoatrial cardiomyocytes and determines variability of cardiac rhythm in a manner independent from the autonomic input. Ablation of the major regulator of this pathway, Rgs6, in mice results in irregular cardiac rhythmicity and increases susceptibility to atrial fibrillation. We further identify several human subjects with variants in the RGS6 gene and show that the loss of function in RGS6 correlates with increased heart rate variability. These findings identify the essential role of the m2R-IKACh signaling pathway in the regulation of cardiac sinus rhythm and implicate RGS6 in arrhythmia pathogenesis. PMID:24204714

  7. Falsely increased HbA1c values by HPLC and falsely decreased values by immunoassay lead to identification of Hb Okayama and help in the management of a diabetic patient.

    Science.gov (United States)

    Frers, C R; Dorn, S; Schmidt, W; Kochhan, L; Simon-Schultz, J; Arndt, R

    2000-01-01

    A falsely increased HbA1c value of 47.1% was determined by cation exchange chromatography during a routine HbA1c measurement of the blood sample from a 63-year-old diabetic male patient living in Hamburg, Germany. In former determinations by immunological assays falsely decreased values in the range of 5.0 to 5.5% were obtained. The sample was inconspicuous in alkaline hemoglobin electrophoresis. But acid hemoglobin electrophoresis confirmed the falsely increased value. These facts let us consider the existence of a heterozygous "silent hemoglobin variant", such as hemoglobin Okayama, with an amino acid substitution in one of the first four amino acids of the beta chain, representing the epitope of common immunoassays. DNA analyses confirmed this presumption and we found the heterozygous mutation hemoglobin Okayama [beta 2 (NA 2) His (CAC)-->Gln (CAA)]. Knowing that an immunological assay only detects about half of the present HbA1c, the obtained values can be used for therapeutic management of this diabetic patient.

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

    Science.gov (United States)

    Hardt, Philip D; Ewald, Nils

    2008-09-01

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

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

    Directory of Open Access Journals (Sweden)

    G. Karina Chimal-Ramírez

    2016-01-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    徐伟康

    2010-01-01

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

  14. 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.

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

    Institute of Scientific and Technical Information of China (English)

    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 M1/M2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 M1/M2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

  16. Development of a universal influenza A vaccine based on the M2e peptide fused to the papaya mosaic virus (PapMV) vaccine platform.

    Science.gov (United States)

    Denis, Jérôme; Acosta-Ramirez, Elizabeth; Zhao, Yinghi; Hamelin, Marie-Eve; Koukavica, Irena; Baz, Mariana; Abed, Yacine; Savard, Christian; Pare, Christine; Lopez Macias, Constantino; Boivin, Guy; Leclerc, Denis

    2008-06-25

    With the emergence of highly virulent influenza viruses and the consequent risk of pandemics, new approaches to designing universal influenza vaccines are urgently needed. In this report, we demonstrate the potential of using a papaya mosaic virus (PapMV) platform carrying the universal M2e influenza epitope (PapMV-CP-M2e) as a candidate flu vaccine. We show that PapMV-CP-M2e virus-like particles (VLPs) can induce production in mice of anti-M2e antibodies that can recognize influenza-infected cells. PapMV-CP-M2e discs made of 20 coat protein (CP) subunits were shown to be poorly immunogenic compared to PapMV-CP-M2e VLPs composed of several hundred CP subunits. We also show that addition of either alum or PapMV-CP VLPs as adjuvant dramatically increased the immunogenicity of PapMV-CP-M2e-containing vaccine, and led to 100% protection against a challenge of 4LD(50) with the WSN/33 strain. These results show, for the first time, the potential of a recombinant plant virus protein to serve as both peptide delivery system and adjuvant in the crucial field of influenza vaccine development.

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

    Directory of Open Access Journals (Sweden)

    Angela M Liu

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

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

    Science.gov (United States)

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

    2014-01-01

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

  19. ProAlgaZyme and its subfractions increase plasma HDL cholesterol via upregulation of ApoA1, ABCA1, and SRB1, and inhibition of CETP in hypercholesterolemic hamsters

    Directory of Open Access Journals (Sweden)

    Geamanu A

    2012-06-01

    Full Text Available Andreea Geamanu, Nadia Saadat, Arvind Goja, Monika Wadehra, Xiangming Ji, Smiti V GuptaNutrition and Food Science, Wayne State University, Detroit, MI, USABackground: Plasma HDL cholesterol levels are inversely related to cardiovascular disease, which is the leading cause of death worldwide. This study investigated the effect of an algae infusion, ProAlgaZyme (PAZ, and its subfractions (P1, P2, P3, P4 on plasma HDL in a hamster model.Methods: Sixty male golden Syrian hamsters (8 weeks old were randomized into controls (W or PAZ (P, P1, P2, P3, and P4 (n = 10 per group. An infusion of either 5% (P1, P2, P3 or 20% (P, P4 concentration (v/v was administered via the drinking water for 4 weeks, while the hamsters were being fed a high-fat diet (30% of calories from fat. Serum lipids were assayed and liver samples subjected to reverse transcription polymerase chain reaction to determine the relative transcription levels of genes involved in HDL/reverse cholesterol transport metabolism, ie, ApoA1, ABCA1, CETP, and SRB1.Results: Non-HDL cholesterol was significantly reduced in the P (P < 0.05, P3 and P4 (P < 0.001 groups as compared with the W group, while HDL cholesterol showed a significant increase in the P, P3, and P4 groups (P < 0.001. Moreover, the total cholesterol/HDL ratio was significantly improved in the P, P1, and P2 (P < 0.05, and P3 and P4 (P < 0.001 groups. The shift in cholesterol towards the higher density fractions was validated by density gradient ultracentrifugation. Real-time quantitative polymerase chain reaction showed a significant increase in hepatic ApoA1 (P, P4 and ABCA1 (P3, P4 expression, consistent with an increase in HDL production, biogenesis, and maturation. A two-fold increase in SRB1 expression indicates that P4 further augments the reverse cholesterol transport mechanism. Reduction of CETP expression (P4 is consistent with a decrease in the transfer of cholesteryl ester to LDL, further increasing the amount of

  20. Genetic Variants in CYP2R1, CYP24A1, and VDR Modify the Efficacy of Vitamin D3 Supplementation for Increasing Serum 25-Hydroxyvitamin D Levels in a Randomized Controlled Trial

    Science.gov (United States)

    Rees, Judy R.; Peacock, Janet L.; Mott, Leila A.; Amos, Christopher I.; Bostick, Roberd M.; Figueiredo, Jane C.; Ahnen, Dennis J.; Bresalier, Robert S.; Burke, Carol A.; Baron, John A.

    2014-01-01

    Context: Adequate serum 25-hydroxyvitamin D concentrations, [25(OH)D], are required for optimal bone health, and low levels are associated with chronic diseases. Objective: We investigated whether 41 candidate single nucleotide polymorphisms (SNPs) in vitamin D and calcium pathway genes (GC, DHCR7, CYP2R1, CYP27B1, CYP24A1, VDR, and CASR) are associated with [25(OH)D] or modify the increase in [25(OH)D] from vitamin D3 supplementation. Design and Setting: Baseline and year 1 [25(OH)D] measurements from a randomized controlled trial conducted at 11 clinical centers in the United States. Participants: A total of 1787 healthy non-Hispanic white participants aged 45–75 years. Interventions: Vitamin D3 (1000 IU/d), calcium carbonate (1200 mg/d elemental), both, or placebo. Main Outcome Measures: Genotype main effects and interactions with vitamin D3 treatment estimated using multiple linear regression. Results: The baseline serum [25(OH)D] was 25.4 ± 8.7 ng/mL (mean ± SD). Associations with baseline levels were discovered for SNPs in CYP24A1 (rs2209314, rs2762939) and confirmed for SNPs in GC and CYP2R1. After 1 year, [25(OH)D] increased on average by 6.1 ± 8.9 ng/mL on vitamin D3 treatment and decreased by 1.1 ± 8.4 ng/mL on placebo. The increase in [25(OH)D] due to vitamin D3 supplementation was modified by genotypes at rs10766197 near CYP2R1, rs6013897 near CYP24A1, and rs7968585 near VDR. Conclusions: The increase in [25(OH)D] attributable to vitamin D3 supplementation may vary according to common genetic differences in vitamin D 25-hydroxylase (CYP2R1), 24-hydroxylase (CYP24A1), and the vitamin D receptor (VDR) genes. These findings have implications for achieving optimal vitamin D status and potentially for vitamin D-related health outcomes. PMID:25070320

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

    Science.gov (United States)

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

    2014-12-01

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

  2. The Analysis of Physiological Variations in M2 Generation of Solanum melongena L. Mutagenized by Ethyl Methane Sulfonate

    Science.gov (United States)

    Xi-ou, Xiao; Wenqiu, Lin; Wei, Li; Xiaoming, Gao; Lingling, Lv; Feiyue, Ma; Yuge, Liu

    2017-01-01

    The eggplant was mutagenized with ethyl methane sulfonate (EMS) to enhance its genetic variability in our previous paper. In this article, we further analyzed the phenotype of M2 generation of mutant eggplants. A total of 325 independent M2 families were investigated for phenotypic variation. In addition to the visible phenotypic variation, chlorogenic acid (CGA) concentrations were analyzed in 26 fruits of mutants with High Performance Liquid Chromatography assay. Seventeen fruits exhibited significantly higher concentrations of CGAs than those in wild-type. The anthocyanin concentration of S9-1, the purple black mutant, was higher than WT, meanwhile, the anthocyanin concentration of L6-4 and U36-1 was lower than WT. Furthermore, our RT-PCR result demonstrated that the expression levels of anthocyanin biosynthetic genes, except for SmPAL, were increased in S9-1, and the regulator SmMYB1 was decreased in L6-4 and U36-1 mutants. Together, our data indicated that, M2 generation showed abundant phenotypic variations and the strong potential usage for next step of breeding and molecular genetic mechanisms in eggplant.

  3. High glucose upregulates CYP24A1 expression which attenuates the ability of 1,25(OH)2D3 to increase NGF secretion in a rat Schwann cell line RSC96.

    Science.gov (United States)

    Zhou, Yi-Kun; Liang, Zhi; Guo, Yan; Zhang, Hua-Tang; Wang, Kun-Hua

    2015-03-15

    Vitamin D deficiency or insufficiency is an independent risk factor for diabetic peripheral neuropathy (DPN), but the relationship between 1,25(OH)2D3 and DPN remains unknown. We found that 1,25(OH)2D3 stimulated the secretion of nerve growth factor (NGF) in rat Schwann cell line RSC96, but ability of 1,25(OH)2D3 to increase NGF protein was impaired under high glucose conditions. High glucose upregulated the expression of CYP24A1 protein, which catalyzes the conversion of 1,25(OH)2D3 into inactive products, further impairing the ability of 1,25(OH)2D3 to upregulate NGF secretion in Schwann cells. Inhibition of CYP24A1 protein expression ameliorated the secretion of NGF in response to 1,25(OH)2D3. The findings of this study suggest that CYP24A1 protein plays an important role in the relationship between DPN and 1,25(OH)2D3.

  4. Tumor type M2 pyruvate kinase expression in gastric cancer,colorectal cancer and controls

    Institute of Scientific and Technical Information of China (English)

    Bo Zhang; Jian-Ying Chen; Dao-Da Chen; Guo-Bin Wang; Ping Shen

    2004-01-01

    AIM: Tumor formation is generally linked to an expansion of glycolytic phosphometabolite pools and aerobic glycolytic flux rates. To achieve this, tumor cells generally overexpress a special glycolytic isoenzyme, termed pyruvate kinase type M2. The present study was designed to evaluate the use of a new tumor marker, tumor M2-PK, in discriminating gastrointestinal cancer patients from healthy controls, and to compare with the reference tumor markers CEA and CA72-4.METHODS: The concentration of tumor M2-PK in body fluids could be quantitatively determined by a commercially available enzyme-linked immunosorbent assay (ELISA)-kit (ScheBo(R) Tech, Giessen, Germany). By using this kit, the tumor M2-PK concentration was measured in EDTA-plasma of 108 patients. For the healthy blood donors a cut-off value of 15 U/mL was evaluated, which corresponded to 90% specificity. Overall 108 patients were included in this study, 54 patients had a histological confirmed gastric cancer, 54 patients colorectal cancer, and 20 healthy volunteers served as controls.RESULTS: The cut-off value to discriminate patients from controls was established at 15 U/mL for tumor M2-PK. The mean tumor M2-PK concentration of gastric cancer was 26.937 U/mL. According to the TNM stage system, the mean tumor M2-PK concentration of stage Ⅰ was 16.324 U/mL, of stage Ⅱ 15.290 U/mL, of stage Ⅲ 30.289 U/mL, of stage Ⅳ127.31 U/mL, of non-metastasis 12.854 U/mL and of metastasis 35.711 U/mL. The mean Tumor M2-PK concentration of colorectal cancer was 30.588 U/mL. According to the Dukes stage system, the mean tumor M2-PK concentration of Dukes A was 16.638 U/mL, of Dukes B 22.070 U/mL, and of Dukes C 48.024 U/mL, of non-metastasis 19.501 U/mL, of metastasis 49.437 U/mL. The mean tumor M2-PK concentration allowed a significant discrimination of colorectal cancers (30.588 U/mL) from controls (10.965 U/mL) (P<0.01), and gastric cancer (26.937 U/mL) from controls (10.965 U/mL)(P<0.05). The overall

  5. 羊八井50m2 RPC地毯性能研究%Study on the Performance of YBJ 50m2 RPC Carpet

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    利用羊八井50m2 RPC地毯(YBJ-ARGO实验原型)的测试数据对其性能进行了分析研究,包括原初粒子方位角分布、天顶角分布、地毯的角分辨、探测时间系统误差对方位角分布的正弦调制、探测时间系统误差的离线修正、几何不对称的小型地毯探测器上原初粒子到达方向重建误差造成的方位角分布的不均匀性等.%The characteristics of a 50m2 RPC carpet(prototype of YBJ-ARGO experiment)was analyzed using its test run data.A correction method of the systematic time error is suggested,and non-uniform azimuthal angle distribution possibly due to direction reconstruction error on an asymmetric carpet is reported.

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

    Science.gov (United States)

    Du, Yongzhao; Fu, Yuqing; Zheng, Chaoying

    2017-02-01

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

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

    Science.gov (United States)

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

    2001-01-01

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

  8. Estimates of global M2 internal tide energy fluxes using TOPEX/POSEIDON altimeter data

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yanwei; LIANG Xinfeng; TIAN Jiwei; YANG Lifen

    2009-01-01

    TOPEX/POSEIDON altimeter data from October 1992 to June 2002 are used to calculate the global barotropic M2 tidal currents using long-term tidal harmonic analysis. The tides calculated agree well with ADCP data obtained from the South China Sea (SCS). The maximum tide velocities along the semi-major axis and semi-minor axis can be computed from the tidal ellipse. The global distribution of M2 internal tide vertical energy flux from the sea bottom is calculated based on a linear internal wave generation model. The global vertical energy flux of M2 internal tide is 0.96 TW, with 0.36 TW in the Pacific, 0.31 TW in the Atlantic and 0.29 TW in the Indian Ocean, obtained in this study. The total horizontal energy flux of M2 internal tide radiating into the open ocean from the lateral boundaries is 0.13 TW, with 0.06 TW in the Pacific, 0.04TW in the Atlantic, and 0.03 TW in the Indian Ocean. The result shows that the principal lunar semi-diurnal tide M2 provides enough energy to maintain the large-scale thermohaline circulation of the ocean.

  9. Dynamic Environmental/Economic Scheduling for Microgrid Using Improved MOEA/D-M2M

    Directory of Open Access Journals (Sweden)

    Xin Li

    2016-01-01

    Full Text Available The environmental/economic dynamic scheduling for microgrids (MGs is a complex multiobjective optimization problem, which usually has dynamic system parameters and constraints. In this paper, a biobjective optimization model of MG scheduling is established. And various types of microsources (like the conventional sources, various types of renewable sources, etc., electricity markets, and dynamic constraints are considered. A recently proposed MOEA/D-M2M framework is improved (I-MOEA/D-M2M to solve the real-world MG scheduling problems. In order to deal with the constraints, the processes of solutions sorting and selecting in the original MOEA/D-M2M are revised. In addition, a self-adaptive decomposition strategy and a modified allocation method of individuals are introduced to enhance the capability of dealing with uncertainties, as well as reduce unnecessary computational work in practice and meet the time requirements for the dynamic optimization tasks. Thereafter, the proposed I-MOEA/D-M2M is applied to the independent MG scheduling problems, taking into account the load demand variation and the electricity price changes. The simulation results by MATLAB show that the proposed method can achieve better distributed fronts in much less running time than the typical multiobjective evolutionary algorithms (MOEAs like the improved strength Pareto evolutionary algorithm (SPEA2 and the nondominated sorting genetic algorithm II (NSGAII. Finally, I-MOEA/D-M2M is used to solve a 24-hour MG dynamic operation scheduling problem and obtains satisfactory results.

  10. 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

  11. Wireless Access Control with Smart Antenna for M2M Communications

    Science.gov (United States)

    Sakamoto, Hiroshi; Bandai, Masaki; Watanabe, Takashi

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

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

    Science.gov (United States)

    Sankararamakrishnan, R; Sansom, M S

    1995-11-01

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

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

    Directory of Open Access Journals (Sweden)

    Andrea Biral

    2015-02-01

    Full Text Available The next generation of communication systems, which is commonly referred to as 5G, is expected to support, besides the traditional voice and data services, new communication paradigms, such as Internet of Things (IoT and Machine-to-Machine (M2M services, which involve communication between Machine-Type Devices (MTDs in a fully automated fashion, thus, without or with minimal human intervention. Although the general requirements of 5G systems are progressively taking shape, the technological issues raised by such a vision are still partially unclear. Nonetheless, general consensus has been reached upon some specific challenges, such as the need for 5G wireless access networks to support massive access by MTDs, as a consequence of the proliferation of M2M services. In this paper, we describe the main challenges raised by the M2M vision, focusing in particular on the problems related to the support of massive MTD access in current cellular communication systems. Then we analyze the most common approaches proposed in the literature to enable the coexistence of conventional and M2M services in the current and next generation of cellular wireless systems. We finally conclude by pointing out the research challenges that require further investigation in order to provide full support to the M2M paradigm.

  14. Prophylactic and therapeutic activity of fully human monoclonal antibodies directed against Influenza A M2 protein

    Directory of Open Access Journals (Sweden)

    Gwerder Myriam

    2009-12-01

    Full Text Available Abstract Influenza virus infection is a prevalent disease in humans. Antibodies against hemagglutinin have been shown to prevent infection and hence hemagglutinin is the major constituent of current vaccines. Antibodies directed against the highly conserved extracellular domain of M2 have also been shown to mediate protection against Influenza A infection in various animal models. Active vaccination is generally considered the best approach to combat viral diseases. However, passive immunization is an attractive alternative, particularly in acutely exposed or immune compromized individuals, young children and the elderly. We recently described a novel method for the rapid isolation of natural human antibodies by mammalian cell display. Here we used this approach to isolate human monoclonal antibodies directed against the highly conserved extracellular domain of the Influenza A M2 protein. The identified antibodies bound M2 peptide with high affinities, recognized native cell-surface expressed M2 and protected mice from a lethal influenza virus challenge. Moreover, therapeutic treatment up to 2 days after infection was effective, suggesting that M2-specific monoclonals have a great potential as immunotherapeutic agents against Influenza infection.

  15. Structure of anti-FLAG M2 Fab domain and its use in the stabilization of engineered membrane proteins

    Energy Technology Data Exchange (ETDEWEB)

    Roosild, Tarmo P.; Castronovo, Samantha; Choe, Senyon, E-mail: choe@salk.edu [Structural Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037 (United States)

    2006-09-01

    The X-ray crystallographic analysis of anti-FLAG M2 Fab is reported and the implications of the structure on FLAG epitope binding are described as a first step in the development of a tool for the structural and biophysical study of membrane proteins. The inherent difficulties of stabilizing detergent-solubilized integral membrane proteins for biophysical or structural analysis demand the development of new methodologies to improve success rates. One proven strategy is the use of antibody fragments to increase the ‘soluble’ portion of any membrane protein, but this approach is limited by the difficulties and expense associated with producing monoclonal antibodies to an appropriate exposed epitope on the target protein. Here, the stabilization of a detergent-solubilized K{sup +} channel protein, KvPae, by engineering a FLAG-binding epitope into a known loop region of the protein and creating a complex with Fab fragments from commercially available anti-FLAG M2 monoclonal antibodies is reported. Although well diffracting crystals of the complex have not yet been obtained, during the course of crystallization trials the structure of the anti-FLAG M2 Fab domain was solved to 1.86 Å resolution. This structure, which should aid future structure-determination efforts using this approach by facilitating molecular-replacement phasing, reveals that the binding pocket appears to be specific only for the first four amino acids of the traditional FLAG epitope, namely DYKD. Thus, the use of antibody fragments for improving the stability of target proteins can be rapidly applied to the study of membrane-protein structure by placing the short DKYD motif within a predicted peripheral loop of that protein and utilizing commercially available anti-FLAG M2 antibody fragments.

  16. Induction of CYP1A1, CYP1A2, CYP1B1, increased oxidative stress and inflammation in the lung and liver tissues of rats exposed to incense smoke.

    Science.gov (United States)

    Hussain, Tajamul; Al-Attas, Omar S; Al-Daghri, Nasser M; Mohammed, Arif A; De Rosas, Edgard; Ibrahim, Shebl; Vinodson, Benjamin; Ansari, Mohammed G; El-Din, Khaled I Alam

    2014-06-01

    Incense smoke is increasingly being recognized as a potential environmental contaminant and is linked to malignant and non-malignant respiratory diseases. The detoxification of environmental contaminants including polycyclic aromatic hydrocarbons (PAHs) involves the induction of cytochrome P-450 family enzymes (CYPs) by PAHs. However, the detoxification of PAHs also results in the generation of reactive and unstable intermediary metabolites which are implicated in the oxidative stress, DNA damage, and inflammation. It is unclear whether CYPs are similarly induced by incense smoke, which incidentally contains substantial amounts of PAHs. Here, we examined the impact of long-term incense smoke exposure on the induction of CYPs in male Wister Albino rats. Incense smoke exposure significantly induced the expression of CYP1A1, CYP1A2, and CYP1B1 mRNAs in both lung and liver tissues. The extent of CYP1A1 and CYP1B1 induction was significantly higher in the liver compared to that in the lung, while that of CYP1A2 was greater in the lung than in liver. Incense smoke exposure also increased malondialdehyde and reduced glutathione levels in lung and liver tissues, and the catalase activity in the liver tissues to significant levels. Furthermore incense smoke exposure led to a marked increase in TNF-α and IL-4 levels. The data demonstrate for the first time the capacity of incense smoke to induce CYP1 family enzymes in the target and non-target tissues. Induction of CYPs increased oxidative stress and inflammation appear to be intimately linked to promote the carcinogenesis and health complications in people chronically exposed to incense smoke.

  17. Does occupational exposure to solvents and pesticides in association with glutathione S-transferase A1, M1, P1, and T1 polymorphisms increase the risk of bladder cancer? The Belgrade case-control study.

    Directory of Open Access Journals (Sweden)

    Marija G Matic

    glutathione S-transferase A1, T1, and P1 did not contribute independently towards the risk of bladder cancer in males. However, in association with occupational exposure, low activity glutathione S-transferase A1 and glutathione S-transferase M1-null as well as glutathione S-transferase T1-active genotypes increase individual susceptibility to bladder cancer.

  18. 矢车菊素上调CYP7A1表达促进脂肪变性L02细胞内胆固醇降解%Cyanidin increased CYP7A1 expression and promoted cholesterol degradation in steatosis L02 cells

    Institute of Scientific and Technical Information of China (English)

    屠迪; 邬静; 袁莉芸; 文利新; 薛立群

    2012-01-01

    为了研究矢车菊素对肝细胞胆固醇代谢的影响,以人肝细胞系L02为研究对象,采用软脂酸建立肝细胞脂肪变性模型并通过不同浓度矢车菊素处理,采用ELISA检测细胞内胆固醇及胆汁酸浓度,RT—PCR和Westernblot检测胆固醇降解限速酶CYP7A11i3.RNA及蛋白表达水平。结果显示:与空白组相比,10g/L和30g/L软脂酸组L02细胞内胆固醇水平随软脂酸浓度增加而升高(P〈0.05),而胆汁酸水平没有明显变化,此过程伴随cYP7A1蛋白表达上调(P〈0.05)。舍有30g/L软脂酸的模型细胞组内添加5mg/L以上矢车菊素可显著降低细胞内胆固醇水平并同时增加胆汁酸浓度(P〈0.05),此过程伴随CYP7A1mRNA及蛋白的显著上调(P〈0.05);当矢车菊素添加剂量为20mg/L时,与模型组相比CYP7A1蛋白极显著上调(P〈0.01)。结果提示,矢车菊素能够通过促进L02细胞CYP7A1蛋白表达,实现促进脂肪变性肝细胞胆固醇代谢的调节作用。%The aim of this study was to explore the effect of cyanidin on cholesterol metabolism in liver cells. Human liver cell line L02 was treated with palmitic acid to establish the hepatic steato- sis model in vitro. Cholesterol and bile acid concentration were tested by ELISA,and RT-PCR and Western Blotting were used to detect cholesterol degradation rate-limiting enzyme CYP7A1 mRNA and its protein levels. The results showed that. compared with control group, 10 g/L and 30 g/L palmitic acid can increase L02 cells intracellar cholesterol concentration (P〉0. 05), but the bile acid levels did not change significantly. This process accompanied with actived CYP7A1 protein expression (P〉 0. 05 ). Model cell group were treated by 30 g/L palmitic acid. 5 mg/L above cyanidin can significantly reduce the model cell intracellular cholesterol levels and increasing bile acid concentrations (P〉 0.05). The levels of CYP7A1 mRNA and

  19. M2-KK6 System in ABJM Theory : Fuzzy $S^3$ and Wrapped KK6

    CERN Document Server

    Huang, Wung-Hong

    2011-01-01

    We study the properties of M2-KK6 solution in ABJM membrane theory. First, we find a new kind of BPS solution which has six coordinates, contrasts to our previous solutions which have four coordinates. Next, we argue that, after wrapping 2 sphere the new solution may correspond to the previous solution of four coordinates. We analyze the properties therein and conclude that M2-branes described in ABJM theory could expand into fuzzy three sphere plus a wrapped 2 sphere near the KK6 core. Especially, we show in detail how the fuzzy 3-sphere could arise in these solutions and discuss the property of wrapped KK6 and its relation to M5-brane. We also analyze the fluctuation of the M2-KK6 solution and see that it is U(1) field theory.

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

    Science.gov (United States)

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

    2016-10-04

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

  1. Aggregation and Trunking of M2M Traffic via D2D Connections

    DEFF Research Database (Denmark)

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

    2015-01-01

    , there is a need for new techniques to coordinate the access and allocate the resources. Although the majority of the proposed solutions are focused on the adaptation of the traditional cellular networks to the M2M traffic patterns, novel approaches based on the direct communication among nearby devices may......Machine-to-Machine (M2M) communications is one of the key enablers of the Internet of Things (IoT). Billions of devices are expected to be deployed in the near future for novel M2M applications demanding ubiquitous access and global connectivity. In order to cope with the massive number of machines...... generated packets is performed by a user device, which aggregates the machine-type data, supplements it with its own data and transmits all of them to the Base Station. We observe a fundamental trade-off between latency and the transmit power needed to deliver the aggregate traffic, in a sense that lower...

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

    Science.gov (United States)

    Grinter, Rhys; Josts, Inokentijs; Zeth, Kornelius; Roszak, Aleksander W; McCaughey, Laura C; Cogdell, Richard J; Milner, Joel J; Kelly, Sharon M; Byron, Olwyn; Walker, Daniel

    2014-07-01

    The colicin-like bacteriocins are potent protein antibiotics that have evolved to efficiently cross the outer membrane of Gram-negative bacteria by parasitizing nutrient uptake systems. We have structurally characterized the colicin M-like bacteriocin, pectocin M2, which is active against strains of Pectobacterium spp. This unusual bacteriocin lacks the intrinsically unstructured translocation domain that usually mediates translocation of these bacteriocins across the outer membrane, containing only a single globular ferredoxin domain connected to its cytotoxic domain by a flexible α-helix, which allows it to adopt two distinct conformations in solution. The ferredoxin domain of pectocin M2 is homologous to plant ferredoxins and allows pectocin M2 to parasitize a system utilized by Pectobacterium to obtain iron during infection of plants. Furthermore, we identify a novel ferredoxin-containing bacteriocin pectocin P, which possesses a cytotoxic domain homologous to lysozyme, illustrating that the ferredoxin domain acts as a generic delivery module for cytotoxic domains in Pectobacterium.

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

    Science.gov (United States)

    Sankararamakrishnan, R; Sansom, M S

    1995-12-27

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

  4. 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

  5. CEMS-investigations of AISI M2 steel after nitrogen plasma immersion ion implantation

    Energy Technology Data Exchange (ETDEWEB)

    Uglov, V.V. E-mail: info@research.bsu.unibel.by; Kholmetskii, A.L.; Kuleshov, A.K.; Fedotova, J.A.; Rusalsky, D.P.; Khodasevich, V.V.; Ruebenbauer, K.; Richter, E.; Guenzel, R.; Parascandola, S

    1999-01-02

    Plasma-immersion ion implantation (PIII) and high-current ion implantation (HCII) of nitrogen into M2 steel were carried out. The formation of a multilayer system consisting of a surface layer of austenite on top of {epsilon}-Fe{sub 3}N nitride precipitates was manifested in M2 steel after PIII. HCII forms a thick (more than 14 {mu}m) layer with {epsilon}-Fe{sub 3}N precipitates. Apparently, the formation of the austenite layer after PIII is connected with a local tempering of the steel surface by the pulsed nitrogen ion beam.

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

    Science.gov (United States)

    Bera, Amal K; Akabas, Myles H

    2005-10-21

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

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

    Science.gov (United States)

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

    2006-12-15

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

  8. 广雅SUNDAY三期7500元/m2起发售

    Institute of Scientific and Technical Information of China (English)

    张雷

    2008-01-01

    本报讯 6月22日,SUNDAY三期发售,此前已有近300名买家进行购买登记,而发展商把300多套货量一并推出,以最低价格7000元/m2,最高也不超过1万元/m2的诱人价格,且发售当天买家可享受95折优惠。

  9. M2M monitoring terminal based on Cortex-M3%基于Cortex-M3的M2M监控终端

    Institute of Scientific and Technical Information of China (English)

    张鑫; 丁志刚; 郑树泉

    2011-01-01

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

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

    Science.gov (United States)

    1963-01-01

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

  11. Structure and Mechanism of Proton Transport Through the Transmembrane Tetrameric M2 Protein Bundle of the Influenza A Virus

    Energy Technology Data Exchange (ETDEWEB)

    R Acharya; V Carnevale; G Fiorin; B Levine; A Polishchuk; V Balannick; I Samish; R Lamb; L Pinto; et al.

    2011-12-31

    The M2 proton channel from influenza A virus is an essential protein that mediates transport of protons across the viral envelope. This protein has a single transmembrane helix, which tetramerizes into the active channel. At the heart of the conduction mechanism is the exchange of protons between the His37 imidazole moieties of M2 and waters confined to the M2 bundle interior. Protons are conducted as the total charge of the four His37 side chains passes through 2{sup +} and 3{sup +} with a pK{sub a} near 6. A 1.65 {angstrom} resolution X-ray structure of the transmembrane protein (residues 25-46), crystallized at pH 6.5, reveals a pore that is lined by alternating layers of sidechains and well-ordered water clusters, which offer a pathway for proton conduction. The His37 residues form a box-like structure, bounded on either side by water clusters with well-ordered oxygen atoms at close distance. The conformation of the protein, which is intermediate between structures previously solved at higher and lower pH, suggests a mechanism by which conformational changes might facilitate asymmetric diffusion through the channel in the presence of a proton gradient. Moreover, protons diffusing through the channel need not be localized to a single His37 imidazole, but instead may be delocalized over the entire His-box and associated water clusters. Thus, the new crystal structure provides a possible unification of the discrete site versus continuum conduction models.

  12. M2-F1 on lakebed with pilots Milt Thompson, Chuck Yeager, Don Mallick, and Bruce Peterson

    Science.gov (United States)

    1963-01-01

    motoring. On April 5, 1963, Thompson lifted the M2-F1's nose off of the ground for the first time on tow. Speed was 86 miles per hour. The little craft seemed to bounce uncontrollably back and forth on the main landing gear, and stopped when he lowered the nose to the ground. He tried again, but each time with the same results. He felt it was a landing gear problem that could have caused the aircraft to roll on its back if he had lifting the main gear off of the ground. Looking at movies of the tests, engineers decided that the bouncing was probably caused by unwanted rudder movements. Flight control system number two was replaced in favor of number one, and it never bounced again. Speeds on tow inched up to 110 miles per hour, which allowed Thompson to climb to about 20 feet, then glide for about 20 seconds after releasing the line. That was the most that could be expected during an auto tow. In the spring of 1963 the M2-F1 was shipped to Ames Research Center, where it was mounted on twenty-foot poles inside the 40-foot by 80-foot wind tunnel. For two weeks, Thompson and engineers Ed Browne and Dick Eldredge took turns 'flying' it as air blasted by at a 135 miles per hour. They learned more about its flying qualities, and accumulated important data for the upcoming aero tows. A NASA C-47 was used for all of the aero tows. The first was on August 16, 1963. The M2-F1 had recently been equipped with an ejection seat, small rockets in the tail to extend the landing flare for about 5 seconds (if needed), and Thompson prepared for the flight with a few more tows behind the Pontiac. Forward visibility in the M2-F1 was very limited on tow, requiring Thompson to fly about 20 feet higher than the C-47 so he could see the plane through the nose window. Towing speed was about 100 miles per hour. Tow release was at 12,000 feet. The lifting body descended at an average rate of about 3,600 feet-per-minute. At 1,000 feet above the ground, the nose was lowered to increase speed to about

  13. Recent Development of QCD Factorization for B-> M1 M2

    CERN Document Server

    Yang, Deshan

    2010-01-01

    After briefly introducing the framework of QCD factorization for B-> M1 M2 in the language of the Soft-Collinear Effective Theory, we firstly address the recent efforts on higher-order radiative corrections in QCD factorization. Then we discuss some phenomenologies in B-> V V within the framework of QCD factorization.

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

    Science.gov (United States)

    Zhang, Jun; Chen, Liang; Sun, Yunyun; Li, Yuanhai

    2017-03-17

    Tramadol is an analgesic drug and relieves pain through activating μ-opioid receptors and inhibiting serotonin and noradrenaline reuptake. Emerging evidence shows that it also stimulates immune cells, including NK cells, splenocytes, and lymphocytes, and elevates IL-2 production. However, it remains unknown whether and how tramadol directly affects macrophages. To answer these questions, we collected human umbilical cord blood, isolated macrophages, and examined their responses to tramadol. Although tramadol did not alter resting macrophages and the antigen-presenting function in lipopolysaccharide-activated macrophages, it regulated M1 and M2 macrophages, which are, respectively, transformed by IFN-γ and IL-4. Interestingly, tramadol inhibits production and secretion of cytokines in M1 macrophages, but facilitates the production of inflammation-responding molecules, synthesized in M2 macrophages. We also found that STAT6 cascade pathway in M2 macrophages was significantly enhanced by tramadol. Therefore, this study reveals that tramadol regulates inflammation by inhibiting M1 macrophages (killing process), but promoting the function of M2 macrophages (healing process).

  15. 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.

  16. NO EVIDENCE FOR A ROLE OF MUSCARINIC M(2) RECEPTORS IN FUNCTIONAL ANTAGONISM IN BOVINE TRACHEA

    NARCIS (Netherlands)

    ROFFEL, AF; MEURS, H; ELZINGA, CRS; ZAAGSMA, J

    1 The functional antagonism between methacholine- or histamine-induced contraction and beta-adrenoceptor-mediated relaxation was evaluated in bovine tracheal smooth muscle in vitro. In addition, the putative contribution of muscarinic M(2) receptors mediating inhibition of beta-adrenoceptor-induced

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

    Directory of Open Access Journals (Sweden)

    Zhou Xuefeng

    2011-08-01

    Full Text Available The present work investigated the solidification microstructure of AISI M2 high speed steel manufactured by different casting technologies, namely iron mould casting and continuous casting. The results revealed that the as-cast structure of the steel was composed of the iron matrix and the M2C eutectic carbide networks, which were greatly refined in the ingot made by continuous casting process, compared with that by the iron mould casting process. M2C eutectic carbides presented variation in their morphologies and growth characteristics in the ingots by both casting methods. In the ingot by iron mould casting, they have a plate-like morphology and grow anisotropically. However, in the ingot made by continuous casting, the carbides evolved into the fiber-like shape that exhibited little characteristics of anisotropic growth. It was noticed that the fiber-like M2C was much easier to decompose and spheroidize after heated, as a result, the carbides refined remarkably, compared with the case of plate-like carbides in the iron mould casting ingot.

  18. Modifications to 25m2 target-aligned research Heliostat mirror panels

    CSIR Research Space (South Africa)

    Roos, TH

    2009-09-01

    Full Text Available Several heliostat mirror panels of the CSIR 25m2 target-aligned heliostat suffered corrosion-related failure, prompting a panel redesign. Two test samples of the new design were subjected to mechanical and thermal cycling tests in an attempt...

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

    Directory of Open Access Journals (Sweden)

    Nan eWang

    2014-11-01

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

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

    Science.gov (United States)

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

    2016-03-01

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

  1. Comparison of Plasma Tu-M2-PK and CA19-9 in Pancreatic Cancer

    DEFF Research Database (Denmark)

    Joergensen, Maiken Thyregod; Heegaard, Niels H H; Schaffalitzky de Muckadell, Ove B

    2009-01-01

    because of suspicion of pancreatic cancer. Of these, 51 patients had their conditions diagnosed as PDAC, whereas this diagnosis was ruled out in 52 after 12 months of follow-up. The performance of Tu-M2-PK was compared with that of CA19-9 using cutoff values 15 and 37 U/mL, respectively. RESULTS...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-03-15

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

  3. Experimental Conditions: SE37_S16_M2_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available opes SE37_S16 Blank (80% methanol) SE37_S16_M2 0mg [MassBase ID] MDLC1_43485 SE37_MS1 Metabolites extraction... with 80% methanol and analysis by LC-Orbitrap-MS SE37_DS1 Peak extraction for unlabeled data ...

  4. Serine is a natural ligand and allosteric activator of pyruvate kinase M2

    NARCIS (Netherlands)

    Chaneton, Barbara; Hillmann, Petra; Zheng, Liang; Martin, Agnes C. L.; Maddocks, Oliver D. K.; Chokkathukalam, Achuthanunni; Coyle, Joseph E.; Jankevics, Andris; Holding, Finn P.; Vousden, Karen H.; Frezza, Christian; O'Reilly, Marc; Gottlieb, Eyal

    2012-01-01

    Cancer cells exhibit several unique metabolic phenotypes that are critical for cell growth and proliferation(1). Specifically, they overexpress the M2 isoform of the tightly regulated enzyme pyruvate kinase (PKM2), which controls glycolytic flux, and are highly dependent on de novo biosynthesis of s

  5. Massive M2M Access with Reliability Guarantees in LTE Systems

    DEFF Research Database (Denmark)

    Madueño, Germán Corrales; Kiilerich Pratas, Nuno; Stefanovic, Cedomir

    2015-01-01

    Machine-to-Machine (M2M) communications are one of the major drivers of the cellular network evolution towards 5G systems. One of the key challenges is on how to provide reliability guarantees to each accessing device in a situation in which there is a massive number of almost-simultaneous arrivals...

  6. Changes in Autoantibodies against β1-Adrenoceptor and M2-Muscarinic Receptor during Development of Renovascular Hypertension in Rats

    Institute of Scientific and Technical Information of China (English)

    Jian-Ming ZHI; Rong-Fang CHEN; Heng WU; Hui-Rong LIU; Rong-Rui ZHAO

    2004-01-01

    In an experimental rat's renovascular hypertension model, we studied the genesis of anticardiac β1-adrenoceptor and M2-muscarinic receptor autoantibodies in relation to the changes in immunological function during the development of renal hypertension. The biological activities of these autoantibodies were also examined. It was shown that after two weeks of operation both the frequency of occurrence and the titre of autoantibodies to cardiac β1-adrenoceptor and M2-muscarinic receptor were significantly increased as compared with the control of pre-treatment. The increased autoantibodies lasted for several weeks and then automatically decreased gradually to the pre-clipping level at 10 weeks. Meanwhile the ratio of CD4+/CD8+was also undergone an initial increase followed by gradual recovery and correlated well with the changes in antibody titre. The biological effects of these autoantibodies displayed an "agonistic-like" activities on the beating frequency of cultured neonatal cardiomyocyte. It is suggested that autoimmune mechanisms are involved in the pathogenesis of renal hypertension and the cardiac receptor autoantibodies might be one of the mechanisms leading to cardiac dysfunction.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Improved sensitivity in the diagnosis of gastro-intestinal tumors by fuzzy logic-based tumor marker profiles including the tumor M2-PK.

    Science.gov (United States)

    Schneider, Joachim; Bitterlich, Norman; Schulze, Guntram

    2005-01-01

    The aim of this study was to improve diagnostic efficiency in the detection of gastro-intestinal cancers by using fuzzy logic modeling in combination with a tumor marker panel (CEA, CA72-4, CA19-9) including Tumor M2-PK. In this prospective study histologically confirmed colorectal (n=247), esophageal (n=86) and gastric cancer (n=122) patients were investigated and compared to control (n=53) persons without any malignant diseases. Tumor M2-PK was measured in plasma with an ELISA (ScheBoBiotech, Germany); all other markers were measured in sera (Roche, Germany). At 95% specificity, tumor detection was possible by the best single marker in colorectal cancer patients in 48% (Tumor M2-PK), in gastric cancers in 61% (CA72-4) and in esophageal cancers in 56% (Tumor M2-PK). A fuzzy logic rule-based system employing a tumor marker panel increased sensitivity significantly in colorectal cancers (pTumor M2-PK and CEA), in gastric cancers (pTumor M2-PK and CA 72-4) and in esophageal cancers (pTumor M2-PK and CA72-4). Adding a third marker further improved the sensitivity only marginally. Fuzzy logic analysis has proven to be more powerful than measurement of single markers alone or combinations using multiple logistic regression analysis of the markers. Therefore, with the fuzzy logic method and a tumor marker panel (including Tumor M2-PK), a new diagnostic tool for the detection of gastro-intestinal cancers is available.

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

    Science.gov (United States)

    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

  10. γδ T Cells Are Required for M2 Macrophage Polarization and Resolution of Ozone-Induced Pulmonary Inflammation in Mice.

    Directory of Open Access Journals (Sweden)

    Joel A Mathews

    Full Text Available We examined the role of γδ T cells in the induction of alternatively activated M2 macrophages and the resolution of inflammation after ozone exposure. Wildtype (WT mice and mice deficient in γδ T cells (TCRδ-/- mice were exposed to air or to ozone (0.3 ppm for up to 72h and euthanized immediately or 1, 3, or 5 days after cessation of exposure. In WT mice, M2 macrophages accumulated in the lungs over the course of ozone exposure. Pulmonary mRNA abundance of the M2 genes, Arg1, Retnla, and Clec10a, also increased after ozone. In contrast, no evidence of M2 polarization was observed in TCRδ-/- mice. WT but not TCRδ-/- mice expressed the M2c polarizing cytokine, IL-17A, after ozone exposure and WT mice treated with an IL-17A neutralizing antibody exhibited attenuated ozone-induced M2 gene expression. In WT mice, ozone-induced increases in bronchoalveolar lavage neutrophils and macrophages resolved quickly after cessation of ozone exposure returning to air exposed levels within 3 days. However, lack of M2 macrophages in TCRδ-/- mice was associated with delayed clearance of inflammatory cells after cessation of ozone and increased accumulation of apoptotic macrophages in the lungs. Delayed restoration of normal lung architecture was also observed in TCRδ-/- mice. In summary, our data indicate that γδ T cells are required for the resolution of ozone-induced inflammation, likely because γδ T cells, through their secretion of IL-17A, contribute to changes in macrophage polarization that promote clearance of apoptotic cells.

  11. Chemotherapy toxicity in gynecologic cancer patients with a body surface area (BSA)>2 m2.

    Science.gov (United States)

    Schwartz, Joanna; Toste, Beth; Dizon, Don S

    2009-07-01

    Although many clinicians practice empiric dose reduction to prevent toxicity, it is unknown whether obese patients given chemotherapy dosed according to actual body weight (ABW) experience excess toxicity. At our institution, cancer patients receive chemotherapy dosed by ABW unless on a protocol capping doses at a maximum body surface area (BSA). We compared toxicities and dose modifications between women with a BSA>2 m(2) on uncapped versus capped paclitaxel as part of adjuvant paclitaxel/carboplatin for gynecologic malignancy. In this retrospective study, women with a BSA>2 m(2) treated with paclitaxel (P) and carboplatin (C) for endometrial and ovarian cancer between January 1999 and July 2007 were identified using the chemotherapy database. Records were reviewed for patient age, BSA, diagnosis, stage, standardized and actual doses for each cycle, adverse drug reactions, and dosing modifications. Statistical comparisons were made using Fisher's exact test. We identified 59 women with BSA>2 m(2) on adjuvant P/C for endometrial and ovarian cancers. 50 received paclitaxel dosed by ABW and 9 received paclitaxel capped at a BSA of 2 m(2). There were no statistically significant differences in rates of toxicity or dose modification. Obese women with a BSA>2 m(2) on paclitaxel dosed by ABW do not experience excess toxicity in comparison to women on paclitaxel capped at a maximum BSA or women in published trials of adjuvant P/C. Empiric dose reduction is unnecessary and may result in suboptimal treatment of obese patients. However, as this was a retrospective review, more research is needed to make definitive recommendations on this topic.

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

    Science.gov (United States)

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

    2014-01-01

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

  13. Study on phylogenetic relationships, variability, and correlated mutations in M2 proteins of influenza virus A.

    Directory of Open Access Journals (Sweden)

    Ly Le

    Full Text Available M2 channel, an influenza virus transmembrane protein, serves as an important target for antiviral drug design. There are still discordances concerning the role of some residues involved in proton transfer as well as the mechanism of inhibition by commercial drugs. The viral M2 proteins show high conservativity; about 3/4 of the positions are occupied by one residue in over 95%. Nine M2 proteins from the H3N2 strain and possibly two proteins from H2N2 strains make a phylogenic cluster closely related to 2RLF. The variability range is limited to 4 residues/position with one exception. The 2RLF protein stands out by the presence of 2 serines at the positions 19 and 50, which are in most other M2 proteins occupied by cysteines. The study of correlated mutations shows that there are several positions with significant mutational correlation that have not been described so far as functionally important. That there are 5 more residues potentially involved in the M2 mechanism of action. The original software used in this work (Consensus Constructor, SSSSg, Corm, Talana is freely accessible as stand-alone offline applications upon request to the authors. The other software used in this work is freely available online for noncommercial purposes at public services on bioinformatics such as ExPASy or NCBI. The study on mutational variability, evolutionary relationship, and correlated mutation presented in this paper is a potential way to explain more completely the role of significant factors in proton channel action and to clarify the inhibition mechanism by specific drugs.

  14. An H5N1 M2e-based multiple antigenic peptide vaccine confers heterosubtypic protection from lethal infection with pandemic 2009 H1N1 virus

    Directory of Open Access Journals (Sweden)

    Yu Hong

    2010-07-01

    Full Text Available Abstract Background A 2009 global influenza pandemic caused by a novel swine-origin H1N1 influenza A virus has posted an increasing threat of a potential pandemic by the highly pathogenic avian influenza (HPAI H5N1 virus, driving us to develop an influenza vaccine which confers cross-protection against both H5N1 and H1N1 viruses. Previously, we have shown that a tetra-branched multiple antigenic peptide (MAP vaccine based on the extracellular domain of M2 protein (M2e from H5N1 virus (H5N1-M2e-MAP induced strong immune responses and cross-protection against different clades of HPAI H5N1 viruses. In this report, we investigated whether such M2e-MAP presenting the H5N1-M2e consensus sequence can afford heterosubtypic protection from lethal challenge with the pandemic 2009 H1N1 virus. Results Our results demonstrated that H5N1-M2e-MAP plus Freund's or aluminum adjuvant induced strong cross-reactive IgG antibody responses against M2e of the pandemic H1N1 virus which contains one amino acid variation with M2e of H5N1 at position 13. These cross-reactive antibodies may maintain for 6 months and bounced back quickly to the previous high level after the 2nd boost administered 2 weeks before virus challenge. H5N1-M2e-MAP could afford heterosubtypic protection against lethal challenge with pandemic H1N1 virus, showing significant decrease of viral replications and obvious alleviation of histopathological damages in the challenged mouse lungs. 100% and 80% of the H5N1-M2e-MAP-vaccinated mice with Freund's and aluminum adjuvant, respectively, survived the lethal challenge with pandemic H1N1 virus. Conclusions Our results suggest that H5N1-M2e-MAP has a great potential to prevent the threat from re-emergence of pandemic H1N1 influenza and possible novel influenza pandemic due to the reassortment of HPAI H5N1 virus with the 2009 swine-origin H1N1 influenza virus.

  15. Inflammatory Regulation by Driving Microglial M2 Polarization: Neuroprotective Effects of Cannabinoid Receptor-2 Activation in Intracerebral Hemorrhage

    Science.gov (United States)

    Lin, Li; Yihao, Tao; Zhou, Feng; Yin, Niu; Qiang, Tan; Haowen, Zheng; Qianwei, Chen; Jun, Tang; Yuan, Zhang; Gang, Zhu; Hua, Feng; Yunfeng, Yang; Zhi, Chen

    2017-01-01

    The cannabinoid receptor-2 (CB2R) was initially thought to be the “peripheral cannabinoid receptor.” Recent studies, however, have documented CB2R expression in the brain in both glial and neuronal cells, and increasing evidence suggests an important role for CB2R in the central nervous system inflammatory response. Intracerebral hemorrhage (ICH), which occurs when a diseased cerebral vessel ruptures, accounts for 10–15% of all strokes. Although surgical techniques have significantly advanced in the past two decades, ICH continues to have a high mortality rate. The aim of this study was to investigate the therapeutic effects of CB2R stimulation in acute phase after experimental ICH in rats and its related mechanisms. Data showed that stimulation of CB2R using a selective agonist, JWH133, ameliorated brain edema, brain damage, and neuron death and improved neurobehavioral outcomes in acute phase after ICH. The neuroprotective effects were prevented by SR144528, a selective CB2R inhibitor. Additionally, JWH133 suppressed neuroinflammation and upregulated the expression of microglial M2-associated marker in both gene and protein level. Furthermore, the expression of phosphorylated cAMP-dependent protein kinase (pPKA) and its downstream effector, cAMP-response element binding protein (CREB), were facilitated. Knockdown of CREB significantly inversed the increase of M2 polarization in microglia, indicating that the JWH133-mediated anti-inflammatory effects are closely associated with PKA/CREB signaling pathway. These findings demonstrated that CB2R stimulation significantly protected the brain damage and suppressed neuroinflammation by promoting the acquisition of microglial M2 phenotype in acute stage after ICH. Taken together, this study provided mechanism insight into neuroprotective effects by CB2R stimulation after ICH. PMID:28261199

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

    Science.gov (United States)

    1963-01-01

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

  17. Computer simulation of ion channel gating: the M(2) channel of influenza A virus in a lipid bilayer

    Science.gov (United States)

    Schweighofer, K. J.; Pohorille, A.

    2000-01-01

    The transmembrane fragment of the influenza virus M(2) protein forms a homotetrameric channel that transports protons. In this paper, we use molecular dynamics simulations to help elucidate the mechanism of channel gating by four histidines that occlude the channel lumen in the closed state. We test two competing hypotheses. In the "shuttle" mechanism, the delta nitrogen atom on the extracellular side of one histidine is protonated by the incoming proton, and, subsequently, the proton on the epsilon nitrogen atom is released on the opposite side. In the "water-wire" mechanism, the gate opens because of electrostatic repulsion between four simultaneously biprotonated histidines. This allows for proton transport along the water wire that penetrates the gate. For each system, composed of the channel embedded in a hydrated phospholipid bilayer, a 1.3-ns trajectory was obtained. It is found that the states involved in the shuttle mechanism, which contain either single-protonated histidines or a mixture of single-protonated histidines plus one biprotonated residue, are stable during the simulations. Furthermore, the orientations and dynamics of water molecules near the gate are conducive to proton transfer. In contrast, the fully biprotonated state is not stable. Additional simulations show that if only two histidines are biprotonated, the channel deforms but the gate remains closed. These results support the shuttle mechanism but not the gate-opening mechanism of proton gating in M(2).

  18. Conformational response of influenza A M2 transmembrane domain to amantadine drug binding at low pH (pH 5.5

    Directory of Open Access Journals (Sweden)

    Elka R. Georgieva

    2016-07-01

    Full Text Available The M2 protein from influenza A plays important roles in its viral cycle. It contains a single transmembrane helix, which oligomerizes into a homotetrameric proton channel that conducts in the low-pH environment of the host-cell endosome and Golgi apparatus, leading to virion uncoating at an early stage of infection. We studied conformational rearrangements that occur in the M2 core transmembrane domain residing on the lipid bilayer, flanked by juxtamembrane residues (M2TMD21-49 fragment, upon its interaction with amantadine drug at pH 5.5 when M2 is conductive. We also tested the role of specific mutation and lipid chain length. Electron spin resonance (ESR spectroscopy and electron microscopy were applied to M2TMD21-49, labeled at the residue L46C with either nitroxide spin-label or Nanogold® reagent, respectively. Electron microscopy confirmed that M2TMD21-49 reconstituted into DOPC/POPS at 1:10,000 peptide-to-lipid molar ratio (P/L either with or without amantadine, is an admixture of monomers, dimers, and tetramers, confirming our model based on a dimer intermediate in the assembly of M2TMD21-49. As reported by double electron-electron resonance (DEER, in DOPC/POPS membranes amantadine shifts oligomer equilibrium to favor tetramers, as evidenced by an increase in DEER modulation depth for P/L’s ranging from 1:18,000 to 1:160. Furthermore, amantadine binding shortens the inter-spin distances (for nitroxide labels by 5-8 Å, indicating drug induced channel closure on the C-terminal side. No such effect was observed for the thinner membrane of DLPC/DLPS, emphasizing the role of bilayer thickness. The analysis of continuous wave (cw ESR spectra of spin-labeled L46C residue provides additional support to a more compact helix bundle in amantadine-bound M2TMD21-49 through increased motional ordering. In contrast to wild-type M2TMD21-49, the amantadine-bound form does not exhibit noticeable conformational changes in the case of G34A mutation

  19. 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

  20. Potent neutralization of influenza A virus by a single-domain antibody blocking M2 ion channel protein.

    Directory of Open Access Journals (Sweden)

    Guowei Wei

    Full Text Available Influenza A virus poses serious health threat to humans. Neutralizing antibodies against the highly conserved M2 ion channel is thought to offer broad protection against influenza A viruses. Here, we screened synthetic Camel single-domain antibody (VHH libraries against native M2 ion channel protein. One of the isolated VHHs, M2-7A, specifically bound to M2-expressed cell membrane as well as influenza A virion, inhibited replication of both amantadine-sensitive and resistant influenza A viruses in vitro, and protected mice from a lethal influenza virus challenge. Moreover, M2-7A showed blocking activity for proton influx through M2 ion channel. These pieces of evidence collectively demonstrate for the first time that a neutralizing antibody against M2 with broad specificity is achievable, and M2-7A may have potential for cross protection against a number of variants and subtypes of influenza A viruses.

  1. M1, M2 Growth Scissors:Causes, Influence and Countermeasures%M1、M2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M1与M2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。

  2. A Novel MLC Scheme with M2-QAM Constellations over AWGN and Rayleigh Fading Channels

    Institute of Scientific and Technical Information of China (English)

    YUANDongfeng; ZHANGPeng; WayneE.Stark

    2003-01-01

    Optimal multilevel codes (MLC) with M2-QAM constellations are considered with focus on both AWGN and Rayleigh fading channels. With the proposition of three new set partitioning rules for M2-QAM constellations, a novel simplified MLC scheme with a very simple MSD (Multistage decoding) structure comes into being, which is operated on the capacity rule. Compared with traditional MLC/MSD scheme the new MLC/MSD structure greatly reduces the calculation of the individual capacities in MLC system because the new set partitioning rules ensure the independency of two dimensions symbols. Furthermore the new MLC/MSD system cannot enhance any performance loss and the time delay is just 1/2 of that with traditional partitioning rules. As an example 64-QAM constellation with three new set partitioning rules are provided. Their performance is simulated over AWGN and Rayleigh fading channels by choosing BCH codes as the component codes.

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

    Science.gov (United States)

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

    2017-03-01

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

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

    Science.gov (United States)

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

    2006-01-01

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

  5. The Mont Blanc mystery solved? A $m^2=-0.28 keV^2$ neutrino

    CERN Document Server

    Ehrlich, Robert

    2016-01-01

    Evidence is presented in support of a hypothesis made in 2013 predicting the existence of a tachyonic neutrino mass eigenstate doublet having $m^2\\approx -0.2 keV^2$ with $\\Delta m^2=1 eV^2.$ The evidence is based primarily on the puzzling LSD (Mont Blanc) neutrino burst observed on February 23, 1987, which the hypothesis thoroughly explains, with additional support from the Kamiokande-II events recorded on the same day. The probability of the null hypothesis, i.e., that background fluctuations can explain the noted features of the two data sets is estimated to be $4.2\\sigma$ (Mont Blanc), and $3.7\\sigma$ (K-II). Such a controversial hypothesis as a tachyonic neutrino requires absolutely definitive proof, and there may exist a test based on observing the neutrino spectrum from diffuse supernovae that could supply it.

  6. Unveiling the structure of the planetary nebula M 2-48 Kinematics and physical conditions

    CERN Document Server

    López-Martin, L; Esteban, C; Vázquez, R; Raga, A C; Torrelles, J M; Miranda, L F; Meaburn, J; Olguin, L

    2002-01-01

    The kinematics and physical conditions of the bipolar planetary nebula M 2-48 are analysed from high and low dispersion long-slit spectra. Previous CCD narrow-band optical observations have suggested that this nebula is mainly formed by a pair of symmetric bow-shocks, an off-center semi-circular shell, and an internal bipolar structure. The bipolar outflow has a complex structure, characterised by a series of shocked regions located between the bright core and the polar tips. There is an apparent kinematic discontinuity between the bright bipolar core and the outer regions. The fragmented ring around the bright bipolar region presents a low expansion velocity and could be associated to ejection in the AGB-PN transition phase, although its nature remains unclear. The chemical abundances of the central region are derived, showing that M 2-48 is a Type I planetary nebula (PN).

  7. Zebrafish M2 muscarinic acetylcholine receptor: cloning, pharmacological characterization, expression patterns and roles in embryonic bradycardia

    OpenAIRE

    Hsieh, Dennis Jine-Yuan; Liao, Ching-Fong

    2002-01-01

    A zebrafish M2 muscarinic acetylcholine receptor (mAChR) gene was cloned. It encodes 495 amino acids in a single exon. The derived amino acid sequence is 73.5% identical to its human homologue.Competitive binding studies of the zebrafish M2 receptor and [3H]-NMS gave negative log dissociation constants (pKi) for each antagonist as follows: atropine (9.16)>himbacine (8.05)⩾4-DAMP (7.83)>AF-DX 116 (7.26)⩾pirenzepine (7.18)⩾tropicamide (6.97)⩾methoctramine (6.82)⩾p-F-HHSiD (6.67)>carbachol (5.20...

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

    Energy Technology Data Exchange (ETDEWEB)

    Aali-Javanangrouh, M.; Rezaei-Aghdam, A. [Azarbaijan Shahid Madani University, Department of Physics, Faculty of Science, Tabriz (Iran, Islamic Republic of)

    2016-11-15

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

  9. Soft X-Ray Magneto-optical Faraday Effect around Ni M2,3 Edges

    Institute of Scientific and Technical Information of China (English)

    CHEN Kai; CUI Ming-Qi; YAN Fen; ZHAO Jia; SUN Li-Juan; ZHENG Lei; MA Chen-Yan; XI Shi-So; ZHAO Yi-Dong

    2008-01-01

    @@ We present magneto-optical (MO) Faraday spectra measured around the M2,3 edges (60-70eV) of Ni films at the Beijing Synchrotron Radiation Facility (BSRF).A polarization analysis of the final state of the transmitted radiation from the Ni film is employed to determine the Faraday rotation at the edges.The MO effect becomes resonantly enhanced at the M2,3 edges,and accordingly large values for the rotation angle β of 1.85 ± 0.19°for this ferromagnetic Ni film with thickness of 31 nm are measured. Without the magnetic field,the azimuthal angles do not shift; with parallel and antiparallel magnetic field the rotation angles shift in the opposite way and they are symmetrical.The uncertainty of Faraday rotation angles mainly comes from the data fitting and the state change of the beamline when the angles are measured.

  10. Anxiolytic activity of pyridoindole derivatives SMe1EC2 and SMe1M2: behavioral analysis using rat model.

    Science.gov (United States)

    Sedláčková, Natália; Ponechalová, Veronika; Ujházy, Eduard; Dubovický, Michal; Mach, Mojmír

    2011-12-01

    Anxiety and mood disorders have become very significant affections in the last decades. According to WHO at least one mental disease occurred per year in 27% of EU inhabitants (more than 82 mil. people). It is estimated that by 2020, depression will be the main cause of morbidity in the developed countries. These circumstances call for research for new prospective drugs with anxiolytic and antidepressive properties exhibiting no toxicity and withdrawal effect and possessing beneficial properties, like antioxidant and/or neuroprotective effects. The aim of this study was to obtain information about psychopharmacological properties of pyridoindole derivatives SMe1EC2 and SMe1M2, using non-invasive behavioral methods in rats.The battery of ethological tests (open field, elevated plus-maze, light/dark box exploration, forced swim test) was used to obtain information about anxiolytic and antidepressant activity of the pyridoindole derivatives. The substances were administered intraperitoneally 30 minutes before the tests at doses of 1, 10 and 25 mg/kg.In the behavioral tests, SMe1EC2 was found to exert anxiolytic activity in elevated plus maze with no affection of locomotor activity. The highest dose of SMe1M2 increased the time spent in the lit part of the Light/Dark box, however this result was influenced by inhibition of motor activity of the rats. Similar findings were observed also in elevated plus-maze, although these results were not statistically significant.In conclusion, from the results of our study it is evident that both pyridoindoles acted on the CNS. In the highest dose, SMe1M2 was found to possess rather sedative than anxiolytic or antidepressant activity.

  11. Epitope Mapping of Avian Influenza M2e Protein: Different Species Recognise Various Epitopes.

    Directory of Open Access Journals (Sweden)

    Noor Haliza Hasan

    Full Text Available A common approach for developing diagnostic tests for influenza virus detection is the use of mouse or rabbit monoclonal and/or polyclonal antibodies against a target antigen of the virus. However, comparative mapping of the target antigen using antibodies from different animal sources has not been evaluated before. This is important because identification of antigenic determinants of the target antigen in different species plays a central role to ensure the efficiency of a diagnostic test, such as competitive ELISA or immunohistochemistry-based tests. Interest in the matrix 2 ectodomain (M2e protein of avian influenza virus (AIV as a candidate for a universal vaccine and also as a marker for detection of virus infection in vaccinated animals (DIVA is the rationale for the selection of this protein for comparative mapping evaluation. This study aimed to map the epitopes of the M2e protein of avian influenza virus H5N1 using chicken, mouse and rabbit monoclonal or monospecific antibodies. Our findings revealed that rabbit antibodies (rAbs recognized epitope 6EVETPTRN13 of the M2e, located at the N-terminal of the protein, while mouse (mAb and chicken antibodies (cAbs recognized epitope 10PTRNEWECK18, located at the centre region of the protein. The findings highlighted the difference between the M2e antigenic determinants recognized by different species that emphasized the importance of comparative mapping of antibody reactivity from different animals to the same antigen, especially in the case of multi-host infectious agents such as influenza. The findings are of importance for antigenic mapping, as well as diagnostic test and vaccine development.

  12. Seamless communication in supply chains based on M2M technology

    OpenAIRE

    Walid Moneimne; Marcin Hajdul; Szymon Mikołajczak

    2016-01-01

    Background: Access to information is the key element in the successful and efficient organization of transport & logistic processes. The importance of real-time access to information is confirmed by a panel workshop carried out with support of design thinking methodology. There are two ways of gaining access to the right information - manual, where human agency is needed and fully automatic, where new M2M technology is implemented. Implementation of such technology improves seamless commu...

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

    Science.gov (United States)

    Dobrin, Carmen

    2014-11-01

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

  14. Power Aware Mobility Management of M2M for IoT Communications

    Directory of Open Access Journals (Sweden)

    Awais Ahmad

    2015-01-01

    Full Text Available Machine-to-Machine (M2M communications framework is evolving to sustain faster networks with the potential to connect millions of devices in the following years. M2M is one of the essential competences for implementing Internet of Things (IoT. Therefore, various organizations are now focusing on enhancing improvements into their standards to support M2M communications. Thus, Heterogeneous Mobile Ad Hoc Network (HetMANET can normally be considered appropriate for M2M challenges. These challenges incorporated when a mobile node (MN selects a target network in an energy efficient scanning for efficient handover. Therefore, to cope with these constraints, we proposed a vertical handover scheme for handover triggering and selection of an appropriate network. The proposed scheme is composed of two phases. Firstly, the MNs perform handover triggering based on the optimization of the Receive Signal Strength (RSS from an access point/base station (AP/BS. Secondly, the network selection process is performed by considering the cost and energy consumption of a particular application during handover. Moreover, if there are more networks available, then the MN selects the one provided with the highest quality of service (QoS. The decision regarding the selection of available networks is made on three metrics, that is, cost, energy, and data rate. Furthermore, the selection of an AP/BS of the selected network is made on five parameters: delay, jitter, Bit Error Rate (BER, communication cost, and response time. The numerical and experimental results are compared in the context of energy consumption by an MN, traffic management on an AP/BS, and QoS of the available networks. The proposed scheme efficiently optimizes the handoff related parameters, and it shows significant improvement in the existing models used for similar purpose.

  15. Description of $^{178}$Hf$^{m2}$ in the constrained relativistic mean field theory

    CERN Document Server

    Wei, Zhang; Shuang-Quan, Zhang

    2009-01-01

    The properties of the ground state of $^{178}$Hf and the isomeric state $^{178}$Hf$^{m2}$ are studied within the adiabatic and diabatic constrained relativistic mean field (RMF) approaches. The RMF calculations reproduce well the binding energy and the deformation for the ground state of $^{178}$Hf. Using the ground state single-particle eigenvalues obtained in the present calculation, the lowest excitation configuration with $K^\\pi=16^+$ is found to be $\

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

    Science.gov (United States)

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

    2009-12-01

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

  17. M2Align: parallel multiple sequence alignment with a multi-objective metaheuristic.

    Science.gov (United States)

    Zambrano-Vega, Cristian; Nebro, Antonio J; García-Nieto, José; Aldana Montes, José F

    2017-05-24

    Multiple Sequence Alignment (MSA) is an NP-complete optimization problem found in computational biology, where the time complexity of finding an optimal alignment raises exponentially along with the number of sequences and their lengths. Additionally, to assess the quality of a MSA, a number of objectives can be taken into account, such as maximizing the sum-of-pairs, maximizing the totally conserved columns, minimizing the number of gaps, or maximizing structural information based scores such as STRIKE. An approach to deal with MSA problems is to use multi-objective metaheuristics, which are non-exact stochastic optimization methods that can produce high quality solutions to complex problems having two or more objectives to be optimized at the same time. Our motivation is to provide a multi-objective metaheuristic for MSA that can run in parallel taking advantage of multi-core based computers. The software tool we propose, called M2Align (Multi-objective Multiple Sequence Alignment), is a parallel and more efficient version of the three-objective optimizer for sequence alignments MO-SAStrE, able of reducing the algorithm computing time by exploiting the computing capabilities of common multicore CPU clusters. Our performance evaluation over datasets of the benchmark BAliBASE (v3.0) shows that significant time reductions can be achieved by using up to 20 cores. Even in sequential executions, M2Align is faster than MO-SAStrE, thanks to the encoding method used for the alignments. M2Align is an open source project hosted in GitHub, where the source code and sample datasets can be freely obtained: https://github.com/KhaosResearch/M2Align. antonio@lcc.uma.es. Supplementary data are available at Bioinformatics online.

  18. Granulin exacerbates lupus nephritis via enhancing macrophage M2b polarization.

    Directory of Open Access Journals (Sweden)

    Xi Chen

    Full Text Available BACKGROUND AND AIMS: Lupus nephritis (LN, with considerable morbidity and mortality, is one of the most severe manifestations of systemic lupus erythematosus (SLE. Yet, the pathogenic mechanisms of LN have not been clearly elucidated, and efficient therapies are still in great need. Granulin (GRN, a multifunctional protein linked to inflammatory diseases, has recently been reported to correlate with the disease activity of autoimmune diseases. However, the role of GRN in the pathogenic process of LN still remains obscure. In this study, we explored its potential role and underlying mechanism in the pathogenesis of LN. METHODOLOGY/PRINCIPAL FINDINGS: We found that serum GRN levels were significantly up-regulated and were positively correlated with the severity of LN. Overexpression of GRN in vivo by transgenic injection remarkably exacerbated LN, whereas down-regulation of GRN with shRNA ameliorated LN, firmly demonstrating the critical role of GRN in the pathogenesis of LN. Notably, macrophage phenotype analysis revealed that overexpression of GRN could enhance macrophage polarization to M2b, a key mediator of the initiation and progression of LN. On the contrary, down-regulation of GRN resulted in impaired M2b differentiation, thus ameliorating LN. Moreover, we found that MAPK signals were necessary for the effect of GRN on macrophage M2b polarization. CONCLUSION/SIGNIFICANCE: We first demonstrated that GRN could aggravate lupus nephritis (LN via promoting macrophage M2b polarization, which might provide insights into the pathogenesis of LN as well as potential therapeutic strategies against LN.

  19. Performance Analysis of SNR-Based HDAF M2M Cooperative Networks

    Directory of Open Access Journals (Sweden)

    Lingwei Xu

    2015-01-01

    Full Text Available The lower bound on outage probability (OP of mobile-to-mobile (M2M cooperative networks over N-Nakagami fading channels is derived for SNR-based hybrid decode-amplify-forward (HDAF relaying. The OP performance under different conditions is evaluated through numerical simulation to verify the accuracy of the analysis. These results show that the fading coefficient, number of cascaded components, relative geometric gain, and power-allocation are important parameters that influence this performance.

  20. M2 Proton Channel: Toward a Model of a Primitive Proton Pump

    Science.gov (United States)

    Wei, Chenyu; Pohorille, Andrew

    2015-06-01

    Transmembrane proton transfer was essential to early cellular systems in order to transduce energy for metabolic functions. The reliable, efficient and controlled generation of proton gradients became possible only with the emergence of active proton pumps. On the basis of features shared by most modern proton pumps we identify the essential mechanistic steps in active proton transport. Further, we discuss the mechanism of action of a small, transmembrane M2 proton channel from influenza A virus as a model for proton transport in protocells. The M2 channel is a 94-residue long, α-helical tetramer that is activated at low pH and exhibits high selectivity and directionality. A shorter construct, built of transmembrane fragments that are only 24 amino acids in length, exhibits very similar proton transport properties. Molecular dynamics simulations on the microsecond time-scale carried out for the M2 channel provided atomic level details on the activation of the channel in response to protonation of the histidine residue, His37. The pathway of proton conduction is mediated by His37, which accepts and donates protons at different interconverting conformation states when pH is lower than 6.5. The Val27 and Trp41 gates and the salt bridge between Asp44 and Arg45 further enhance the directionality of proton transport. It is argued that the architecture and the mechanism of action similar to that found in the M2 channel might have been the perfect starting point for evolution towards the earliest proton pumps, indicating that active proton transport could have readily emerged from simple, passive proton channels.

  1. Study of the solidification of M2 high speed steel Laser Cladding coatings

    Directory of Open Access Journals (Sweden)

    Candel, J. J.

    2013-10-01

    Full Text Available High speed steel laser cladding coatings are complex because cracks appear and the hardness is lower than expected. In this paper AISI M2 tool steel coatings on medium carbon AISI 1045 steel substrate have been manufactured and after Laser Cladding (LC processing it has been applied a tempering heat treatment to reduce the amount of retained austenite and to precipitate secondary carbides. The study of metallurgical transformations by Scanning Electron Microscopy (SEM and Electron Back Scattered Diffraction (EBSD shows that the microstructure is extremely fine and complex, with eutectic transformations and MC, M2C and M6C precipitation. Therefore, after the laser coating is necessary to use post-weld heat treatments.Los recubrimientos de acero rápido por Laser Cladding (LC son complejos porque aparecen fisuras y la dureza es menor a la esperada. En este trabajo se han fabricado recubrimientos de acero AISI M2 sobre acero al carbono AISI 1045 y tras el procesado por láser, se han revenido para reducir la cantidad de austenita retenida y precipitar carburos secundarios. El estudio de las transformaciones metalúrgicas con Microscopía Electrónica de Barrido (MEB y Difracción de Electrones Retrodispersados (EBSD muestra que la microestructura es extremadamente fina y compleja, presenta transformaciones eutécticas y precipitación de carburos MC, M2C y M6C. Por tanto, tras el recubrimiento por láser es necesario recurrir a tratamientos térmicos post-soldeo.

  2. Study of the solidification of M2 high speed steel Laser Cladding coatings

    OpenAIRE

    Candel Bou, Juan Jose; Franconetti Rodríguez, Patricia; Amigó Borrás, Vicente

    2013-01-01

    [EN] High speed steel laser cladding coatings are complex because cracks appear and the hardness is lower than expected. In this paper AISI M2 tool steel coatings on medium carbon AISI 1045 steel substrate have been manufactured and after laser cladding (LC) processing it has been applied a tempering heat treatment to reduce the amount of retained austenite and to precipitate secondary carbides. The study of metallurgical transformations by scanning electron microscopy (SEM) and backscattered...

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

    Science.gov (United States)

    Entwistle, Lewis J.; Khoury, Hania; Papoutsopoulou, Stamatia; Mahmood, Radma; Mansour, Nuha R.; Ching-Cheng Huang, Stanley; Pearce, Edward J.; Pedro S. de Carvalho, Luiz; Ley, Steven C.

    2016-01-01

    Persistent TH2 cytokine responses following chronic helminth infections can often lead to the development of tissue pathology and fibrotic scarring. Despite a good understanding of the cellular mechanisms involved in fibrogenesis, there are very few therapeutic options available, highlighting a significant medical need and gap in our understanding of the molecular mechanisms of TH2-mediated immunopathology. In this study, we found that the Map3 kinase, TPL-2 (Map3k8; Cot) regulated TH2-mediated intestinal, hepatic and pulmonary immunopathology following Schistosoma mansoni infection or S. mansoni egg injection. Elevated inflammation, TH2 cell responses and exacerbated fibrosis in Map3k8–/–mice was observed in mice with myeloid cell-specific (LysM) deletion of Map3k8, but not CD4 cell-specific deletion of Map3k8, indicating that TPL-2 regulated myeloid cell function to limit TH2-mediated immunopathology. Transcriptional and metabolic assays of Map3k8–/–M2 macrophages identified that TPL-2 was required for lipolysis, M2 macrophage activation and the expression of a variety of genes involved in immuno-regulatory and pro-fibrotic pathways. Taken together this study identified that TPL-2 regulated TH2-mediated inflammation by supporting lipolysis and M2 macrophage activation, preventing TH2 cell expansion and downstream immunopathology and fibrosis. PMID:27487182

  4. Access Control in IoT/M2M - Cloud Platform

    DEFF Research Database (Denmark)

    Anggorojati, Bayu

    and quality of life. This paradigm, which is often called Internet of Things (IoT) or Machine-to-Machine (M2M), will provide an unprecedented opportunity to create applications and services that go far beyond the mere purpose of each participant. Many studies on the both technical and social aspects of IoT...... of a system can be accessed by other parties by means of a set of access policies. For an IoT system such as Radio Frequency Identification (RFID) that collects huge amounts of RFID events data and may store it in the cloud storage for tracking purpose, access control to such data becomes a critical point...... management in RFID system is of paramount importance. A distributed cloud platform approach for the IoT/M2M, which consists of a set of IoT/M2M gateways, is introduced to cope with some inherent issues of IoT network which is highly heterogeneous and distributed in nature. As aresult, access control becomes...

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

    Science.gov (United States)

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

    2009-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Yashaswini Kannan

    2016-08-01

    Full Text Available Persistent TH2 cytokine responses following chronic helminth infections can often lead to the development of tissue pathology and fibrotic scarring. Despite a good understanding of the cellular mechanisms involved in fibrogenesis, there are very few therapeutic options available, highlighting a significant medical need and gap in our understanding of the molecular mechanisms of TH2-mediated immunopathology. In this study, we found that the Map3 kinase, TPL-2 (Map3k8; Cot regulated TH2-mediated intestinal, hepatic and pulmonary immunopathology following Schistosoma mansoni infection or S. mansoni egg injection. Elevated inflammation, TH2 cell responses and exacerbated fibrosis in Map3k8-/-mice was observed in mice with myeloid cell-specific (LysM deletion of Map3k8, but not CD4 cell-specific deletion of Map3k8, indicating that TPL-2 regulated myeloid cell function to limit TH2-mediated immunopathology. Transcriptional and metabolic assays of Map3k8-/-M2 macrophages identified that TPL-2 was required for lipolysis, M2 macrophage activation and the expression of a variety of genes involved in immuno-regulatory and pro-fibrotic pathways. Taken together this study identified that TPL-2 regulated TH2-mediated inflammation by supporting lipolysis and M2 macrophage activation, preventing TH2 cell expansion and downstream immunopathology and fibrosis.

  7. Fasciola hepatica tegumental antigens indirectly induce an M2 macrophage-like phenotype in vivo.

    Science.gov (United States)

    Adams, P N; Aldridge, A; Vukman, K V; Donnelly, S; O'Neill, S M

    2014-10-01

    The M2 subset of macrophages has a critical role to play in host tissue repair, tissue fibrosis and modulation of adaptive immunity during helminth infection. Infection with the helminth, Fasciola hepatica, is associated with M2 macrophages in its mammalian host, and this response is mimicked by its excretory-secretory products (FhES). The tegumental coat of F. hepatica (FhTeg) is another major source of immune-modulatory molecules; we have previously shown that FhTeg can modulate the activity of both dendritic cells and mast cells inhibiting their ability to prime a Th1 immune response. Here, we report that FhTeg does not induce Th2 immune responses but can induce M2-like phenotype in vivo that modulates cytokine production from CD4(+) cells in response to anti-CD3 stimulation. FhTeg induces a RELMα expressing macrophage population in vitro, while in vivo, the expression of Arg1 and Ym-1/2 but not RELMα in FhTeg-stimulated macrophages was STAT6 dependent. To support this finding, FhTeg induces RELMα expression in vivo prior to the induction of IL-13. FhTeg can induce IL-13-producing peritoneal macrophages following intraperitoneal injection This study highlights the important role of FhTeg as an immune-modulatory source during F. hepatica infection and sheds further light on helminth-macrophage interactions.

  8. Characterization of the hrpZ gene from Pseudomonas syringae pv. maculicolaM2

    Science.gov (United States)

    Álvarez-Mejía, César; Rodríguez-Ríos, Dalia; Hernández-Guzmán, Gustavo; López-Ramírez, Varinia; Valenzuela-Soto, Humberto; Marsch, Rodolfo

    2015-01-01

    Pseudomonas syringae pv. maculicola is a natural pathogen of members of the Brassicaceae plant family. Using a transposon-based mutagenesis strategy in Pseudomonas syringaepv. maculicola M2 (PsmM2), we conducted a genetic screen to identify mutants that were capable of growing in M9 medium supplemented with a crude extract from the leaves of Arabidopsis thaliana. A mutant containing a transposon insertion in the hrpZ gene (PsmMut8) was unable to infect adult plants from Arabidopsis thaliana or Brassica oleracea, suggesting a loss of pathogenicity. The promotorless cat reporter present in the gene trap was expressed if PsmMut8 was grown in minimal medium (M9) supplemented with the leaf extract but not if grown in normal rich medium (KB). We conducted phylogenetic analysis using hrpAZB genes, showing the classical 5-clade distribution, and nucleotide diversity analysis, showing the putative position for selective pressure in this operon. Our results indicate that the hrpAZB operon from Pseudomonas syringaepv. maculicola M2 is necessary for its pathogenicity and that its diversity would be under host-mediated diversifying selection. PMID:26413080

  9. 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.

  10. Tumor-derived interleukin-1 promotes lymphangiogenesis and lymph node metastasis through M2-type macrophages.

    Directory of Open Access Journals (Sweden)

    Kosuke Watari

    Full Text Available Tumors formed by a highly metastatic human lung cancer cell line are characterized by activated signaling via vascular endothelial growth factor (VEGF-C through its receptor (VEGFR-3 and aggressive lymph node metastasis. In this study, we examined how these highly metastatic cancers acquired aggressive lymph node metastasis. Compared with their lower metastatic counterparts, the highly metastatic tumors formed by this cell line expressed higher amounts of interleukin (IL-1α, with similarly augmented expression of IL-1α and IL-1β by tumor stromal cells and of VEGF-A and VEGF-C by tumor-associated macrophages. These tumor-associated macrophages were mainly of the M2 type. Administration of a macrophage-targeting drug suppressed the production of these potent angiogenic and lymphangiogenic factors, resulting in decreased tumor growth, angiogenesis, lymphangiogenesis, and lymph node metastasis. In Matrigel plug assays, the highly metastatic cells formed tumors that were extensively infiltrated by M2-type macrophages and exhibited enhanced angiogenesis and lymphangiogenesis. All of these responses were suppressed by the IL-1 receptor (IL-1R antagonist anakinra. Thus, the IL-1α-driven inflammatory activation of angiogenesis and lymphangiogenesis seems to provide a highly metastatic tumor microenvironment favorable for lymph node metastasis through cross-talk with macrophages. Accordingly, the IL-1R/M2-type macrophage axis may be a good therapeutic target for patients with this form of lung cancer.

  11. Tumor-derived interleukin-1 promotes lymphangiogenesis and lymph node metastasis through M2-type macrophages.

    Science.gov (United States)

    Watari, Kosuke; Shibata, Tomohiro; Kawahara, Akihiko; Sata, Ken-ichi; Nabeshima, Hiroshi; Shinoda, Ai; Abe, Hideyuki; Azuma, Koichi; Murakami, Yuichi; Izumi, Hiroto; Takahashi, Takashi; Kage, Masayoshi; Kuwano, Michihiko; Ono, Mayumi

    2014-01-01

    Tumors formed by a highly metastatic human lung cancer cell line are characterized by activated signaling via vascular endothelial growth factor (VEGF)-C through its receptor (VEGFR-3) and aggressive lymph node metastasis. In this study, we examined how these highly metastatic cancers acquired aggressive lymph node metastasis. Compared with their lower metastatic counterparts, the highly metastatic tumors formed by this cell line expressed higher amounts of interleukin (IL)-1α, with similarly augmented expression of IL-1α and IL-1β by tumor stromal cells and of VEGF-A and VEGF-C by tumor-associated macrophages. These tumor-associated macrophages were mainly of the M2 type. Administration of a macrophage-targeting drug suppressed the production of these potent angiogenic and lymphangiogenic factors, resulting in decreased tumor growth, angiogenesis, lymphangiogenesis, and lymph node metastasis. In Matrigel plug assays, the highly metastatic cells formed tumors that were extensively infiltrated by M2-type macrophages and exhibited enhanced angiogenesis and lymphangiogenesis. All of these responses were suppressed by the IL-1 receptor (IL-1R) antagonist anakinra. Thus, the IL-1α-driven inflammatory activation of angiogenesis and lymphangiogenesis seems to provide a highly metastatic tumor microenvironment favorable for lymph node metastasis through cross-talk with macrophages. Accordingly, the IL-1R/M2-type macrophage axis may be a good therapeutic target for patients with this form of lung cancer.

  12. The outer envelopes of globular clusters - I. NGC 7089 (M2)

    Science.gov (United States)

    Kuzma, P. B.; Da Costa, G. S.; Mackey, A. D.; Roderick, T. A.

    2016-10-01

    We present the results of a wide-field imaging survey of the periphery of the Milky Way globular cluster NGC 7089 (M2). Data were obtained with MegaCam on the Magellan Clay Telescope and the Dark Energy Camera on the Blanco Telescope. We find that M2 is embedded in a diffuse stellar envelope extending to a radial distance of at least ˜60 arcmin (˜210 pc) - five times the nominal tidal radius of the cluster. The envelope appears nearly circular in shape, has a radial density decline well described by a power law of index γ = -2.2 ± 0.2, and contains approximately 1.6 per cent of the luminosity of the entire system. While the origin of the envelope cannot be robustly identified using the presently available data, the fact that M2 also hosts stellar populations exhibiting a broad dispersion in the abundances of both iron and a variety of neutron capture elements suggests that this object might plausibly constitute the stripped nucleus of a dwarf galaxy that was long ago accreted and destroyed by the Milky Way.

  13. The Outer Envelopes of Globular Clusters. I. NGC 7089 (M2)

    CERN Document Server

    Kuzma, P B; Mackey, A D; Roderick, T A

    2016-01-01

    We present the results of a wide-field imaging survey of the periphery of the Milky Way globular cluster NGC 7089 (M2). Data were obtained with MegaCam on the Magellan Clay Telescope, and the Dark Energy Camera on the Blanco Telescope. We find that M2 is embedded in a diffuse stellar envelope extending to a radial distance of at least $\\sim 60^{\\prime}$ ($\\sim 210$ pc) -- five times the nominal tidal radius of the cluster. The envelope appears nearly circular in shape, has a radial density decline well described by a power law of index $\\gamma = -2.2 \\pm 0.2$, and contains approximately $1.6\\%$ of the luminosity of the entire system. While the origin of the envelope cannot be robustly identified using the presently available data, the fact that M2 also hosts stellar populations exhibiting a broad dispersion in the abundances of both iron and a variety of neutron capture elements suggests that this object might plausibly constitute the stripped nucleus of a dwarf Galaxy that was long ago accreted and destroyed...

  14. Moldeo por inyección del acero rápido M2

    Directory of Open Access Journals (Sweden)

    Ruiz-Román, J. M.

    1996-12-01

    Full Text Available The purpose of this work is to study the feasibility of Powder Injection Molding in order to obtain M2 High Speed Steels with higher performances than those obtained by conventional P/M. With this object trials have been carried out in order to optimize all the process steps (mixing, injection, debinding and sintering, and to evaluate the mechanical properties (hardness and transverse tensile strengh of the manufactured M2 HSS sample.

    Se estudia la viabilidad de la tecnología de Moldeo por Inyección de Polvos (MIM en la fabricación con acero rápido M2 a fin de obtener componentes de este material de prestaciones superiores a las que se consiguen mediante métodos convencionales pulvimetalúrgicos. Los ensayos realizados se han dirigido a optimizar los parámetros de la eliminación del ligante y de la sinterización, con objeto de controlar el contenido de carbono y la densidad final de las piezas, así como evitar la aparición de los defectos típicos de esta tecnología.

  15. Measurement of M2-Curve for Asymmetric Beams by Self-Referencing Interferometer Wavefront Sensor

    Directory of Open Access Journals (Sweden)

    Yongzhao Du

    2016-11-01

    Full Text Available For asymmetric laser beams, the values of beam quality factor M x 2 and M y 2 are inconsistent if one selects a different coordinate system or measures beam quality with different experimental conditionals, even when analyzing the same beam. To overcome this non-uniqueness, a new beam quality characterization method named as M2-curve is developed. The M2-curve not only contains the beam quality factor M x 2 and M y 2 in the x-direction and y-direction, respectively; but also introduces a curve of M x α 2 versus rotation angle α of coordinate axis. Moreover, we also present a real-time measurement method to demonstrate beam propagation factor M2-curve with a modified self-referencing Mach-Zehnder interferometer based-wavefront sensor (henceforth SRI-WFS. The feasibility of the proposed method is demonstrated with the theoretical analysis and experiment in multimode beams. The experimental results showed that the proposed measurement method is simple, fast, and a single-shot measurement procedure without movable parts.

  16. Seamless communication in supply chains based on M2M technology

    Directory of Open Access Journals (Sweden)

    Walid Moneimne

    2016-12-01

    Full Text Available Background: Access to information is the key element in the successful and efficient organization of transport & logistic processes. The importance of real-time access to information is confirmed by a panel workshop carried out with support of design thinking methodology. There are two ways of gaining access to the right information - manual, where human agency is needed and fully automatic, where new M2M technology is implemented. Implementation of such technology improves seamless communication during transport execution and allows real-time access to needed information. The aim of the paper is to evaluate the influence of the effectiveness of using M2M technology and traditional way of communication as well as data gathering in order to ensure seamless communication in the supply chain. Methods: Survey, design thinking, desk research and real case study results were used in the paper. Results and conclusions: Seamless communication and implementation of M2M technology within the whole supply (including modes of transport and transport units chain is a backbone of the lean and reliable digital supply chain.

  17. Clinical significance of blood and fecal tumor M2-pyruvate kinase expression in patients with colorectal cancer%结直肠癌患者血清、粪便中M2-PK表达的临床意义

    Institute of Scientific and Technical Information of China (English)

    李勇; 王俊江

    2011-01-01

    目的 探讨结直肠癌患者血清和粪便中肿瘤M2型丙酮酸激酶(M2-PK)表达的临床意义.方法 收集44例结直肠癌患者和22名健康人血液和粪便标本,采用ELISA方法检测tumor M2-PK表达水平.结果 血清M2-PK和粪便M2-PK对结直肠癌的诊断的敏感性分别为59.1%、63.6%,特异性分别为86.4%、81.8%.血清M2 -PK和粪便M2-PK的吻合度有统计学意义.结论 血清和粪便tumor M2-PK的检测对结直肠癌的诊断有重要价值,值得进一步研究.%Objective To evaluate the clinical significance of blood and fecal expression of tumor M2-pyruvate kinase (Tumor M2-PK) in patients with colorectal cancer. Methods With 22 healthy subjects as controls, 44 patients with CRC were examined for tumor M2-PK in serum and fecal samples using a sandwich enzyme immunoassay. Results The sensitivity of serum and fecal tumor M2-PK for detecting CRC was 59.1% and 63.6% with a specificity of 86.4% and 81.8%, respectively. The serum and fecal levels of tumor M2-PK showed a significant correlation in CRC patients. Conclusions Tumor M2-PK has good sensitivity and specificity in the diagnosis of CRC.

  18. 铜绿假单胞菌M2联合小白菜对Pb污染土壤的生物修复%Bio-remediation of lead polluted soil by Pseudomonas aeruginosa strain M2 combined with pakchoi

    Institute of Scientific and Technical Information of China (English)

    陈宝; 徐晓萌; 曲娟娟; 董蕾; 闫立龙; 孙兴滨

    2012-01-01

    从Pb污染矿区筛选到1株铜绿假单胞菌(Pseudomonas aeruginosa) (M2),采用盆栽试验研究其对Pb污染土壤中小白菜生长、Pb吸收和根际微生物的影响.结果表明:接种M2菌后小白菜生物量提高20.9 %~31.3%,地上部Pb含量提高15.0 %~25.4%,根部Pb含量提高15.6 %~36.8%;对可培养微生物数量的测定表明,在同样的Pb污染浓度下,接种铜绿假单胞菌的土壤中细菌和真菌数量明显提高,细菌提高17.8 %~29.6%,真菌提高7.2 %~15.4%,而放线菌提高不明显;细菌16S rDNA的变性梯度凝胶电泳分析表明,接种铜绿假单胞菌的土壤细菌种类比对照土壤多50.0 %~60.0%.结果证明,接种铜绿假单胞菌能够促进小白菜生长,维持土壤细菌多样性,对土壤Pb污染的植物修复有明显的促进作用.%As one of the largest mollisol area in the world, the black soil in northeast of China is commonly thought to be fertile and productive. But recently, dozens of blood heavy metal exceeding events were caused by heavy metal polluted agricultural production through food chain. Soil quality of some farmland near a mining site is getting worse and the content of heavy metal has already exceeded the third level of environmental quality standard for soil in China (GB15618-1995). Crops harvested from these areas had high level of heavy metal and brought a further health problem to human. In order to decrease the adverse effect of heavy metal accumulation in soil, the phytoremediation technology, which is efficient, costless and non-secondary pollution compared with traditional method, has become a hot research point. In many researches, it is a promising way to enhance heavy metal absorption from soil through increasing plants biomass, improving plants resistant to heavy metal and raising the concentration of heavy metal in plants. As many studies proved, inoculation of plant growth-promoting microbes can not only increase plant

  19. Predictive value of pre-procedural autoantibodies against M2-muscarinic acetylcholine receptor for recurrence of atrial fibrillation one year after radiofrequency catheter ablation

    Directory of Open Access Journals (Sweden)

    Zou Changhong

    2013-01-01

    Full Text Available Abstract Background Increasing evidences have suggested that autoantibodies against muscarinic-2 acetylcholine receptor (anti-M2-R may play an important role in the development of atrial fibrillation (AF. Predictive value of pre-procedural anti-M2-R for the recurrence of AF after radiofrequency catheter ablation is still unclear. Methods Totally 76 AF patients with preserved left ventricular systolic function were prospectively enrolled and subjected to ablation after the detection of serum anti-M2-R by enzyme linked immunosorbent assay. These patients were given follow-up examination for one year after ablation. Risk estimation for the recurrence of AF was performed using the univariate and multivariate logistic regression. Results In AF group, serum anti-M2-R was significantly higher than that in the control group in terms of frequency (40.8% versus 11.7%; p p p = 0.009 and titer (1:132 versus 1:94; p = 0.012 for autoantibodies. During one-year follow-up examination after ablation, the recurrence of AF was observed in 25 (32.9% patients. Multivariate analysis showed that pre-procedural serum anti-M2-R was an independent predictor for the recurrence of AF at the time point of 12 months after ablation (odds ratio: 4.701; 95% confidence interval: 1.590-13.894; p = 0.005. Conclusions In AF patients, the frequency and titer of serum anti-M2-R were significantly higher than those in the control group with sinus rhythm. Pre-procedural serum anti-M2-R was an independent predictor for the recurrence of AF one year after radiofrequency catheter ablation.

  20. Murid Gammaherpesvirus Latency-Associated Protein M2 Promotes the Formation of Conjugates between Transformed B Lymphoma Cells and T Helper Cells.

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    Diana Fontinha

    Full Text Available Establishment of persistent infection in memory B cells by murid herpesvirus-4 (MuHV-4 depends on the proliferation of latently infected germinal center B cells, for which T cell help is essential. Whether the virus is capable of modulating B-T helper cell interaction for its own benefit is still unknown. Here, we investigate if the MuHV-4 latency associated M2 protein, which assembles multiprotein complexes with B cell signaling proteins, plays a role. We observed that M2 led to the upregulation of adhesion and co-stimulatory molecules in transduced B cell lines. In an MHC-II restricted OVA peptide-specific system, M2 polarized to the B-T helper contact zone. Furthermore, it promoted B cell polarization, as demonstrated by the increased proximity of the B cell microtubule organizing center to the interface. Consistent with these data, M2 promoted the formation of B-T helper cell conjugates. In an in vitro competition assay, this translated into a competitive advantage, as T cells preferentially conjugated with M2-expressing B cells. However, expression of M2 alone in B cells was not sufficient to lead to T cell activation, as it only occurred in the presence of specific peptide. Taken together, these findings support that M2 promotes the formation of B-T helper cell conjugates. In an in vivo context this may confer a competitive advantage to the infected B cell in acquisition of T cell help and initiation of a germinal center reaction, hence host colonization.

  1. Glucagon-like peptide-1 (GLP-1) induces M2 polarization of human macrophages via STAT3 activation.

    Science.gov (United States)

    Shiraishi, Daisuke; Fujiwara, Yukio; Komohara, Yoshihiro; Mizuta, Hiroshi; Takeya, Motohiro

    2012-08-24

    It is known that glucagon-like peptide-1 (GLP-1) is a hormone secreted postprandially from the L-cells of the small intestine and regulates glucose homeostasis. GLP-1 is now used for the treatment of diabetes because of its beneficial role against insulin resistance. The GLP-1 receptor (GLP-1R) is expressed on many cell types, including macrophages, and GLP-1 suppresses the development of atherosclerosis by inhibiting macrophage function. However, there have so far been few studies that have investigated the significance of GLP-1/GLP-1R signaling in macrophage activation. In the present study, we examined the effect of GLP-1 and exenatide, a GLP-1R agonist, on human monocyte-derived macrophage (HMDM) activation. We found that GLP-1 induced signal transducer and activator of transcription 3 (STAT3) activation. Silencing of GLP-1R suppressed the GLP-1-induced STAT3 activation. In addition, alternatively activated (M2) macrophage-related molecules, such as IL-10, CD163, and CD204 in HMDM, were significantly upregulated by GLP-1. Furthermore, the co-culture of 3T3-L1 adipocytes with GLP-1-treated RAW 264.7 macrophages increased the secretion of adiponectin compared to co-culture of the 3T3-L1 adipocytes with untreated RAW 264.7 macrophages. Our results demonstrate that GLP-1 induces macrophage polarization toward the M2 phenotype, which may contribute to the protective effects of GLP-1 against diabetes and cardiovascular diseases.

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

    Directory of Open Access Journals (Sweden)

    Juciane Maria de Andrade Castro

    2013-01-01

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

  3. 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.

  4. Modular to Monoblock: Difficulties of Detaching the M(2)a-Magnum(TM) Head Are Common in Metal-on-metal Revisions.

    Science.gov (United States)

    Mäntymäki, Heikki; Mäkelä, Keijo T; Vahlberg, Tero; Hirviniemi, Joni; Niinimäki, Tuukka

    2016-09-01

    Modern hip implants typically feature modular heads, which allow for easy exchange and removal from the femoral stem at the time of revision. However, owing to fretting, corrosion, or cold welding, the modular head may be difficult or impossible to separate from the underlying trunnion, especially if the implant has titanium interfaces between the head and the stem. We have repeatedly encountered difficulty removing the titanium sleeve adapter in the M(2)a-Magnum(TM) implant. Although the manufacturer warns about this complication and cases with these difficulties have been reported to the United States FDA, we believed this topic is important to study, because the frequency of difficulties in head removal is unknown and the complications related to this event have not been characterized. We asked: (1) Do revisions of M(2)a-Magnum(TM) implants differ from those of M(2)a-38(TM) implants in terms of ease of removal of the femoral head? (2) In cases where difficulty with M(2)a-Magnum(TM) head removal occurred, was the operative time, bleeding, risk of periprosthetic fracture, or joint infection increased compared with cases where the M(2)a-Magnum(TM) head was removed without difficulties? Between 2004 and 2014, we revised 296 THAs with metal-on-metal implants that involved M(2)a-Magnum(TM) (123) or M(2)a-38(TM) heads (88); of those, 84 were planned to include a femoral stem revision and insufficient data were available for three operations, so they were excluded from this analysis, leaving 124 THAs in the current retrospective study (70 THAs with M(2)a-Magnum(TM) and 54 THAs with M(2)a-38(TM) heads).The method of modular head removal, any difficulties removing the femoral head from the trunnion, operation time, and complications were recorded based on chart review. All the observed problems of detaching the head or taper adapter were among M(2)a-Magnum(TM) heads; there were no problems detaching the head in revisions of the M(2)a-38(TM) implant. In 29% (20 of 70) of

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

    Science.gov (United States)

    1971-01-01

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

  6. Photocatalytic removal of M(2+) (Ni(2+), Cu(2+), Zn(2+), Cd(2+), Hg(2+) and Ag(+)) over new catalyst CuCrO(2).

    Science.gov (United States)

    Ketir, W; Bouguelia, A; Trari, M

    2008-10-30

    The metal ions M(2+) (Ni(2+), Cu(2+), Zn(2+), Cd(2+), Hg(2+) and Ag(+)) are potentially toxic. Their electro deposition has been carried out in aqueous air-equilibrated CuCrO(2) suspension upon visible illumination. The delafossite CuCrO(2) is p-type semiconductor characterized by a low band gap (1.28 eV) and a long-term chemical stability. The corrosion rate is found to be 10(-2) micromol m(-2)month(-1) in aqua regia. The oxide has been elaborated through nitrate route where the specific surface area is increased via the surface/bulk ratio. A correlation exists between the dark M(2+) adsorption, the redox potential of M(2+/0) couple and the conduction band of CuCrO(2) positioned at -1.06 V(SCE). Ag(+) cannot be photoreduced because of its positive potential located far above the valence band. By contrast, Zn(2+) is efficiently deposited due to the large driving force at the interface. The improved photoactivity of copper with a deposition percentage (90%) is attributed to the strong dark adsorption onto the surface catalyst. The results indicate a competitive effect with the water reduction; it has been observed that the M(2+) deposition goes parallel with the hydrogen evolution. Such behavior is attributed to the low H(2) over voltage when ultra fine aggregate of M islands are photodeposited onto CuCrO(2) substrate.

  7. Evidence That Ly6C(hi) Monocytes are Protective in Acute Ischemic Stroke by Promoting M2 Macrophage Polarization.

    Science.gov (United States)

    Chu, Hannah X; Broughton, Brad R S; Kim, Hyun Ah; Lee, Seyoung; Drummond, Grant R; Sobey, Christopher G

    2015-07-01

    Ly6C(hi) monocytes are generally thought to exert a proinflammatory role in acute tissue injury, although their impact after injuries to the central nervous system is poorly defined. CC chemokine receptor 2 is expressed on Ly6C(hi) monocytes and plays an essential role in their extravasation and transmigration into the brain after cerebral ischemia. We used a selective CC chemokine receptor 2 antagonist, INCB3344, to assess the effect of Ly6C(hi) monocytes recruited into the brain early after ischemic stroke. Male C57Bl/6J mice underwent occlusion of the middle cerebral artery for 1 hour followed by 23 hours of reperfusion. Mice were administered either vehicle (dimethyl sulfoxide/carboxymethylcellulose) or INCB3344 (10, 30 or 100 mg/kg IP) 1 hour before ischemia and at 2 and 6 hours after ischemia. At 24 hours, we assessed functional outcomes, infarct volume, and quantified the immune cells in blood and brain by flow cytometry or immunofluorescence. Gene expression of selected inflammatory markers was assessed by quantitative polymerase chain reaction. Ly6C(hi) monocytes were increased 3-fold in the blood and 10-fold in the brain after stroke, and these increases were selectively prevented by INCB3344 in a dose-dependent manner. Mice treated with INCB3344 exhibited markedly worse functional outcomes and larger infarct volumes, in association with reduced M2 polarization and increased peroxynitrite production in macrophages, compared with vehicle-treated mice. Our data suggest that Ly6C(hi) monocytes exert an acute protective effect after ischemic stroke to limit brain injury and functional deficit that involves promotion of M2 macrophage polarization. © 2015 American Heart Association, Inc.

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    Siti H Sheikh Abdul Kadir

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

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

    Science.gov (United States)

    Pereira, Carlos; Aguiar, Ana

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Carlos Pereira

    2014-10-01

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

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

    Science.gov (United States)

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

    2005-07-12

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

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

    Science.gov (United States)

    Pereira, Carlos; Aguiar, Ana

    2014-10-20

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

  14. Application of Hot Air Ignition Technology in Jinan Steel’s 400 m2 Sintering Machine%热风点火技术在济钢400 m2烧结机的应用

    Institute of Scientific and Technical Information of China (English)

    夏世元; 申爱民; 潘玉斌; 凌子愚

    2013-01-01

    Combining with actual condition at the field, the reforming of hot air ignition project of Jinan Steel’s 400 m2 sintering machine was actualized. The seam was opened in the fume hood between No.2 and No.3 chimneys of annular cooler for installing the pipeline. A series of new equipment were increased, such as high-temperature precipitator, high performance high temperature combustion-supporting fan, regulating valves, steel structure support, electrical installation and instrumentation. After the commissioning of the system, the hot air temperature stabilized in 240-300℃, the ignition temperature increased to 1 100℃above, the unit consumption of mixed gas decreased by 20.09%and the annual benefits reached 3.703 3 million Yuan RBM.%  结合现场实际情况,对济钢400 m2烧结机实施了热风点火工程改造.在环冷机2#和3#烟囱之间的烟罩上开口,安装管道,新增高温除尘器、高效耐高温助燃风机、调节阀门、钢结构支架、电气及仪表设备等.热风点火系统投用后,热风温度稳定在240~300℃,点火温度提高到了1100℃以上,混合煤气单耗降低了20.09%,年效益达370.33万元.

  15. Sistemas de gestión de sensores mediante tecnologías M2M

    OpenAIRE

    Miguel Heredero, Miguel de

    2014-01-01

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

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

    Science.gov (United States)

    Igarashi, J.

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1990-05-01

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

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

    Science.gov (United States)

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

    2007-05-01

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

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

    OpenAIRE

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    A. Krishnamoorthy

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Lingwei Xu

    2016-01-01

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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    Qi Qingzhong

    2010-01-01

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

  4. M2型巨噬细胞的研究进展

    Institute of Scientific and Technical Information of China (English)

    罗冲; 杨锡强

    2010-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

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

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

    Science.gov (United States)

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

    2016-09-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-04-15

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

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

    Directory of Open Access Journals (Sweden)

    Cholhong Im

    2016-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    ZHAO ShengLi; ZHANG RunChu; LIU MinQian

    2008-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Etty Puji Lestari

    2008-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Hanumanthappa Vijay Raghavendra

    2012-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Marta Machado-Pereira

    2017-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-06-15

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

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

    CERN Document Server

    Honda, Masazumi

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-11-01

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

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

    Directory of Open Access Journals (Sweden)

    F. Beyrich

    2010-11-01

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

  17. Pyruvate Kinase M2 and Lactate Dehydrogenase A Are Overexpressed in Pancreatic Cancer and Correlate with Poor Outcome.

    Science.gov (United States)

    Mohammad, Goran Hamid; Olde Damink, S W M; Malago, Massimo; Dhar, Dipok Kumar; Pereira, Stephen P

    2016-01-01

    Pancreatic cancer has a 5-year survival rate of less than 4%. Despite advances in diagnostic technology, pancreatic cancer continues to be diagnosed at a late and incurable stage. Accurate biomarkers for early diagnosis and to predict treatment response are urgently needed. Since alteration of glucose metabolism is one of the hallmarks of cancer cells, we proposed that pyruvate kinase type M2 (M2PK) and lactate dehydrogenase A (LDHA) enzymes could represent novel diagnostic markers and potential therapeutic targets in pancreatic cancer. In 266 tissue sections from normal pancreas, pancreatic cystic neoplasms, pancreatic intraepithelial neoplasia (PanIN) and cancer, we evaluated the expression of PKM2, LDHA, Ki-67 and CD8+ by immunohistochemistry and correlated these markers with clinicopathological characteristics and patient survival. PKM2 and LDHA expression was also assessed by Western blot in 10 human pancreatic cancer cell lines. PKM2 expression increased progressively from cyst through PanIN to cancer, whereas LDHA was overexpressed throughout the carcinogenic process. All but one cell line showed high expression of both proteins. Patients with strong PKM2 and LDHA expression had significantly worse survival than those with weak PKM2 and/or LDHA expression (7.0 months vs. 27.9 months, respectively, p = 0.003, log rank test). The expression of both PKM2 and LDHA correlated directly with Ki-67 expression, and inversely with intratumoral CD8+ cell count. PKM2 was significantly overexpressed in poorly differentiated tumours and both PKM2 and LDHA were overexpressed in larger tumours. Multivariable analysis showed that combined expression of PKM2 and LDHA was an independent poor prognostic marker for survival. In conclusion, our results demonstrate a high expression pattern of two major glycolytic enzymes during pancreatic carcinogenesis, with increased expression in aggressive tumours and a significant adverse effect on survival.

  18. Pyruvate Kinase M2 and Lactate Dehydrogenase A Are Overexpressed in Pancreatic Cancer and Correlate with Poor Outcome.

    Directory of Open Access Journals (Sweden)

    Goran Hamid Mohammad

    Full Text Available Pancreatic cancer has a 5-year survival rate of less than 4%. Despite advances in diagnostic technology, pancreatic cancer continues to be diagnosed at a late and incurable stage. Accurate biomarkers for early diagnosis and to predict treatment response are urgently needed. Since alteration of glucose metabolism is one of the hallmarks of cancer cells, we proposed that pyruvate kinase type M2 (M2PK and lactate dehydrogenase A (LDHA enzymes could represent novel diagnostic markers and potential therapeutic targets in pancreatic cancer. In 266 tissue sections from normal pancreas, pancreatic cystic neoplasms, pancreatic intraepithelial neoplasia (PanIN and cancer, we evaluated the expression of PKM2, LDHA, Ki-67 and CD8+ by immunohistochemistry and correlated these markers with clinicopathological characteristics and patient survival. PKM2 and LDHA expression was also assessed by Western blot in 10 human pancreatic cancer cell lines. PKM2 expression increased progressively from cyst through PanIN to cancer, whereas LDHA was overexpressed throughout the carcinogenic process. All but one cell line showed high expression of both proteins. Patients with strong PKM2 and LDHA expression had significantly worse survival than those with weak PKM2 and/or LDHA expression (7.0 months vs. 27.9 months, respectively, p = 0.003, log rank test. The expression of both PKM2 and LDHA correlated directly with Ki-67 expression, and inversely with intratumoral CD8+ cell count. PKM2 was significantly overexpressed in poorly differentiated tumours and both PKM2 and LDHA were overexpressed in larger tumours. Multivariable analysis showed that combined expression of PKM2 and LDHA was an independent poor prognostic marker for survival. In conclusion, our results demonstrate a high expression pattern of two major glycolytic enzymes during pancreatic carcinogenesis, with increased expression in aggressive tumours and a significant adverse effect on survival.

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

    Directory of Open Access Journals (Sweden)

    Liqing He

    2015-11-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2000-01-01

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

  1. 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

    Directory of Open Access Journals (Sweden)

    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.

  2. 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

  3. Preserved Collateral Blood Flow in the Endovascular M2CAO Model Allows for Clinically Relevant Profiling of Injury Progression in Acute Ischemic Stroke

    Science.gov (United States)

    Little, Philip; Kvist, Ola; Grankvist, Rikard; Jonsson, Stefan; Damberg, Peter; Söderman, Michael; Arnberg, Fabian; Holmin, Staffan

    2017-01-01

    Interventional treatment regimens have increased the demand for accurate understanding of the progression of injury in acute ischemic stroke. However, conventional animal models severely inhibit collateral blood flow and mimic the malignant infarction profile not suitable for treatment. The aim of this study was to provide a clinically relevant profile of the emergence and course of ischemic injury in cases suitable for acute intervention, and was achieved by employing a M2 occlusion model (M2CAO) that more accurately simulates middle cerebral artery (MCA) occlusion in humans. Twenty-five Sprague-Dawley rats were subjected to Short (90 min), Intermediate (180 min) or Extended (600 min) transient M2CAO and examined longitudinally with interleaved diffusion-, T2- and arterial spin labeling perfusion-weighted magnetic resonance imaging before and after reperfusion. We identified a rapid emergence of cytotoxic edema within tissue regions undergoing infarction, progressing in several distinct phases in the form of subsequent moderation and then reversal at 230 min (p < 0.0001). We identified also the early emergence of vasogenic edema, which increased consistently before and after reperfusion (p < 0.0001). The perfusion of the penumbra correlated more strongly to the perfusion of adjacent tissue regions than did the perfusion of regions undergoing infarction (p = 0.0088). This was interpreted as an effect of preserved collateral blood flow during M2CAO. Accordingly, we observed only limited recruitment of penumbra regions to the infarction core. However, a gradual increase in infarction size was still occurring as late as 10 hours after M2CAO. Our results indicate that patients suffering MCA branch occlusion stand to benefit from interventional therapy for an extended time period after the emergence of ischemic injury. PMID:28068417

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-03-06

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

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

    Science.gov (United States)

    Pálfalvi, J K; Szabó, J; Dudás, B

    2007-01-01

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

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

    CERN Document Server

    Hu, Feng; Mei, Maofei; Yang, Jiamin

    2016-01-01

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

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

    Indian Academy of Sciences (India)

    ESRA ÖZTÜRK; ERKUL KARACAOGLU

    2017-02-01

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

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

    KAUST Repository

    Gandi, Appala

    2016-02-21

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

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

    Directory of Open Access Journals (Sweden)

    Hua-Ching Chen

    2016-01-01

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

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

    CERN Document Server

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

    2015-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    Zhimin Lu

    2012-01-01

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

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

    Science.gov (United States)

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

    2013-05-01

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

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

    CERN Document Server

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

    2016-01-01

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

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

    CERN Document Server

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2017-02-01

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

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

    Institute of Scientific and Technical Information of China (English)

    王群; 钱焕延

    2012-01-01

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

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

    Science.gov (United States)

    Belokonov, Igor V.; Semkin, Nikolay D.

    2009-06-01

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

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

    Science.gov (United States)

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

    2017-02-01

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

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

    Science.gov (United States)

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

    2015-02-01

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

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

    Institute of Scientific and Technical Information of China (English)

    彭捷剑; 王振营

    2013-01-01

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

  1. Murine gammaherpesvirus M2 protein induction of IRF4 via the NFAT pathway leads to IL-10 expression in B cells.

    Science.gov (United States)

    Rangaswamy, Udaya S; Speck, Samuel H

    2014-01-01

    Reactivation of the gammaherpesviruses Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV) and murine gammaherpesvirus 68 (MHV68) from latently infected B cells has been linked to plasma cell differentiation. We have previously shown that the MHV68 M2 protein is important for virus reactivation from B cells and, when expressed alone in primary murine B cells, can drive B cell differentiation towards a pre-plasma cell phenotype. In addition, expression of M2 in primary murine B cells leads to secretion of high levels of IL-10 along with enhanced proliferation and survival. Furthermore, the absence of M2 in vivo leads to a defect in the appearance of MHV68 infected plasma cells in the spleen at the peak of MHV68 latency. Here, employing an inducible B cell expression system, we have determined that M2 activates the NFAT pathway in a Src kinase-dependent manner--leading to induction of the plasma cell-associated transcription factor, Interferon Regulatory Factor-4 (IRF4). Furthermore, we show that expression of IRF4 alone in a B cell line up-regulates IL-10 expression in culture supernatants, revealing a novel role for IRF4 in B cell induced IL-10. Consistent with the latter observation, we show that IRF4 can regulate the IL-10 promoter in B cells. In primary murine B cells, addition of cyclosporine (CsA) resulted in a significant decrease in M2-induced IL-10 levels as well as IRF4 expression, emphasizing the importance of the NFAT pathway in M2- -mediated induction of IL-10. Together, these studies argue in favor of a model wherein M2 activation of the NFAT pathway initiates events leading to increased levels of IRF4--a key player in plasma cell differentiation--which in turn triggers IL-10 expression. In the context of previous findings, the data presented here provides insights into how M2 facilitates plasma cell differentiation and subsequent virus reactivation.

  2. Murine gammaherpesvirus M2 protein induction of IRF4 via the NFAT pathway leads to IL-10 expression in B cells.

    Directory of Open Access Journals (Sweden)

    Udaya S Rangaswamy

    2014-01-01

    Full Text Available Reactivation of the gammaherpesviruses Epstein-Barr virus (EBV, Kaposi's sarcoma-associated herpesvirus (KSHV and murine gammaherpesvirus 68 (MHV68 from latently infected B cells has been linked to plasma cell differentiation. We have previously shown that the MHV68 M2 protein is important for virus reactivation from B cells and, when expressed alone in primary murine B cells, can drive B cell differentiation towards a pre-plasma cell phenotype. In addition, expression of M2 in primary murine B cells leads to secretion of high levels of IL-10 along with enhanced proliferation and survival. Furthermore, the absence of M2 in vivo leads to a defect in the appearance of MHV68 infected plasma cells in the spleen at the peak of MHV68 latency. Here, employing an inducible B cell expression system, we have determined that M2 activates the NFAT pathway in a Src kinase-dependent manner--leading to induction of the plasma cell-associated transcription factor, Interferon Regulatory Factor-4 (IRF4. Furthermore, we show that expression of IRF4 alone in a B cell line up-regulates IL-10 expression in culture supernatants, revealing a novel role for IRF4 in B cell induced IL-10. Consistent with the latter observation, we show that IRF4 can regulate the IL-10 promoter in B cells. In primary murine B cells, addition of cyclosporine (CsA resulted in a significant decrease in M2-induced IL-10 levels as well as IRF4 expression, emphasizing the importance of the NFAT pathway in M2- -mediated induction of IL-10. Together, these studies argue in favor of a model wherein M2 activation of the NFAT pathway initiates events leading to increased levels of IRF4--a key player in plasma cell differentiation--which in turn triggers IL-10 expression. In the context of previous findings, the data presented here provides insights into how M2 facilitates plasma cell differentiation and subsequent virus reactivation.

  3. Rhinovirus infection induces interleukin-13 production from CD11b-positive, M2-polarized exudative macrophages.

    Science.gov (United States)

    Chung, Yutein; Hong, Jun Young; Lei, Jing; Chen, Qiang; Bentley, J Kelley; Hershenson, Marc B

    2015-02-01

    Rhinovirus (RV) causes asthma exacerbations. Previously, we showed that adherent bronchoalveolar cells from allergen-treated mice produce IL-13 when stimulated with RV ex vivo, implicating cells of the monocyte/macrophage lineage in viral-induced airway inflammation. In this study, we hypothesized that RV infection of allergen-treated mice results in IL-13 production by CD11b+ exudative macrophages in vivo. We sensitized and challenged BALB/c mice with ovalbumin (OVA), after which mice were inoculated with RV or sham HeLa cell lysate. After 1 day, lungs were harvested, and cell suspensions were analyzed by flow cytometry. We repeated this process in IL-13 reporter mice, CD11b-DTR mice in which diphtheria toxin selectively depletes CD11b+ cells, and chemokine receptor 2 (CCR2) null mice. We found that lungs of mice infected with RV alone showed increases in CD45+, CD68+, F4/80+, Ly6C+, and CD11b(high) cells, indicating an influx of inflammatory monocytes and exudative macrophages. The combination of OVA and RV had synergistic effects on the exudative macrophage number. However, CD11b+ cells from OVA-treated, RV-infected mice showed M2 polarization, including expression of CD206 and CD301 and production of IL-13. Similar results were obtained in IL-13 reporter mice. Diphtheria toxin depleted CD11b+, IL-13-producing cells in OVA-treated, RV-infected, CD11b-DTR mice, decreasing airway inflammation and responsiveness. CD11b+, Ly6C+ cells were reduced in CCR2 knockout mice. We conclude that, in contrast to naive mice, RV infection of mice with allergic airways disease induces an influx of IL-13-producing CD11b+ exudative macrophages bearing M2 macrophage markers. This finding further implicates alternatively activated macrophages in RV-induced asthma exacerbations.

  4. Adamantane-Resistant Influenza A Viruses in the World (1902–2013): Frequency and Distribution of M2 Gene Mutations

    Science.gov (United States)

    Dong, Guoying; Peng, Chao; Luo, Jing; Wang, Chengmin; Han, Le; Wu, Bin; Ji, Guangju; He, Hongxuan

    2015-01-01

    Adamantanes (amantadine and rimantadine) have been used to prevent and treat influenza A virus infections for many years; however, resistance to these drugs has been widely reported in the world. To investigate the frequency and distribution of M2 gene mutations in adamantane-resistant influenza variants circulated in the world between 1902 and 2013, 31251 available M2 protein sequences from different HA-subtype influenza A viruses (H1–H17) were analyzed and adamantane resistance-associated mutations were compared (L26F, V27A, A30T, A30V, S31N, G34E, and L38F). We find that 45.2% (n = 14132) of influenza A (H1–H17) viruses circulating globally were resistant to adamantanes, and the vast majority of resistant viruses (95%) bear S31N mutations. Whereas, only about 1% have V27A mutations and other mutations (L26F, A30T, G34E, and L38F) were extremely rare (their prevalence appeared to be resistance to adamantanes. In contrast, the appearance of adamantane-resistant mutants in H2, H4, H6, H10, and H11 subtypes was rare. However, no adamantane resistance viruses were identified among other HA subtypes (H8, H12–H16). Our findings indicate that the frequency and distribution of adamantane-resistant influenza variants varied among different HA subtypes, host species, years of isolation, and geographical areas. This comprehensive study raises concerns about the increasing prevalence of adamantane-resistant influenza A viruses and highlights the importance of monitoring the emergence and worldwide spread of adamantane-resistant variants. PMID:25768797

  5. Roux-en-Y gastric bypass for Chinese type 2 diabetes mellitus patients with a BMI < 28 kg/m2: a multi-institutional study

    Institute of Scientific and Technical Information of China (English)

    Hui Liang; Wei Guan; Yanling Yang; Zhongqi Mao; Yijun Mei; Huan Liu; Yi Miao

    2015-01-01

    Roux-en-Y gastric bypass surgery (RYGB) has been demonstrated to be successful for treating type-Ⅱ diabetes mellitus (T2DM) patients with a body mass index (BMI) <30 kg/m2,but reports of RYGB for T2DM patients with a BMI <28 kg/m2 are lacking.T2DM patients with a BMI <28 kg/m2 were prospectively recruited to participate in this study in four hospitals.The endpoint was T2DM remission (defined by fasting blood glucose (FBG) level <110 mg/dL and hemoglobin (Hb)A1c level <6.0% at 12 months postoperatively).Predictors of remission were investigated by univariate and multivariate analyses.Eighty-six patients were assessed.Eighty-five patients underwent RYGB,with one conversion to open surgery.We compared the values of various variables before and after surgery.The mean BMI decreased from 24.68 ± 2.12 to 21.72 ± 2.43 kg/m2 (P<0.001).Fifty-eight (67.4%) patients were not treated by drugs or insulin after surgery,and 20 patients (23.3%) had complete remission of T2DM at 12 months after surgery with an acceptable number of complications.The mean HbA1c level in the remission group was significantly lower than that in the non-remission group.Patients with a higher weight,lower HbA1c level,higher C-peptide level,and higher FBG level were more likely to have T2DM remission in multivariate analyses.In conclusion,RYGB was effective and safe for treating T2DM patients with a BMI <28 kg/m2.Complete remission can be predicted by cases having a higher weight,lower HbA1c level,higher C-peptide level,and higher FBG level.

  6. [Responses of ecosystem carbon budget to increasing nitrogen deposition in differently degraded Leymus chinensis steppes in Inner Mongolia, China].

    Science.gov (United States)

    Qi, Yu-Chun; Peng, Qin; Dong, Yun-She; Xiao, Sheng-Sheng; Jia, Jun-Qiang; Quo, Shu-Fang; He, Yun-Long; Yan, Zhong-Qing; Wang, Li-Qin

    2015-02-01

    Based on a field manipulative nitrogen (N) addition experiment, the effects of atmospheric N deposition level change on the plant biomass and net primary productivity (NPP), soil respiration (Rs) and net ecosystem exchange (NEE) were investigated respectively in 2009 and 2010 in two differently degraded Leymus chinensis steppes in Inner Mongolia of China, and the difference in the response of NEE to equal amount of N addition [10 g x (M2 x a)(-1), MN] between the two steppes was also discussed. The results indicated that for the light degraded Leymus chinensis steppe (site A) , the average plant aboveground biomass (AGB) in MN treatment were 21.5% and 46.8% higher than those of CK in these two years. But for the moderate degraded Leymus chinensis steppe (site B), the N addition decreased the plant AGB and ANPP in 2009, while showed positive effects in 2010. N addition increased the belowground biomass (BGB) of the both sites and belowground NPP (BNPP) of site B in both years, but decreased the BNPP of site A in 2010. The increase of N input in the two steppes did not change the seasonal variation of Rs. The cumulative annual soil C emissions in MN treatment in site A showed an increase of about 14.6% and 25.7% of those in the CK respectively for these two years, while were decreased by about 10.4% and 11.3%, respectively in site B. The NEE of MN treatments, expressed by C, for the two steppes were 59.22 g x (m2 x a)(1) and 166.68 g x (m2 x a)(-1), as well as 83.27 g x (m2 x a)(-1) and 117.47 g x (m2 x a)(-1), respectively in these two years. The increments in NEE originated from N addition for these two years were 15.79 g x (M2 x a)(-1) and 82.94 g x (M2 x a)(-1) in site A and 74.54 g x (M2 x a)(-1) and 101.23 g x (M2 x a)(-1) in site B. The N input per unit could obtain greater C sink effect in the steppe with lower initial N level.

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

    NARCIS (Netherlands)

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

    1996-01-01

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

  9. A possible mechanism in the recruitment of eosinophils and Th2 cells through CD163(+) M2 macrophages in the lesional skin of eosinophilic cellulitis.

    Science.gov (United States)

    Fujimura, Taku; Kambayashi, Yumi; Furudate, Sadanori; Kakizaki, Aya; Aiba, Setsuya

    2014-01-01

    M2 macrophages play a critical role in the recruitment of T helper 2 (Th2) regulatory T cells (Treg). To study the role of M2 macrophages and Treg cells in eosinophilic celulitis. We employed immunohistochemical staining for CD163( )and CD206 (macrophages) as well as FoxP3 (Treg), in lesional skin of four cases of eosinophilic cellulitis. CD163(+) CD206(+) M2 macrophages, which were previously reported to produce CCL17 to induce Th2 cells and Treg cells, were predominantly infiltrating the subcutaneous tissues and interstitial area of the dermis. M2 macrophages derived from PBMC showed significantly increased expression of CCL11, CCL17, CCL24 and CCL26 mRNA and production of CCL17 and CCL24, when stimulated by IL-4 or IL- 13. In addition, CCL17-producing cells and CCL24-producing cells were prominent in the lesional skin of EC. Our study sheds light on one of the possible immunological mechanisms of eosinophilic cellulitis.

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

    Directory of Open Access Journals (Sweden)

    Zhang Li

    2010-05-01

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

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

    Science.gov (United States)

    Martin, S.; Bange, J.

    2009-09-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-02-15

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

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

    Science.gov (United States)

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

    2006-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Carmen Chak-Lui Wong

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-07-01

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

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

    CERN Document Server

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

    2012-01-01

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

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

    CERN Document Server

    Lashkevich, Michael

    2014-01-01

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

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

    Science.gov (United States)

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

    2016-06-01

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

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

    Science.gov (United States)

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

    2003-01-01

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

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

    CERN Document Server

    Danehkar, A; Steffen, W

    2016-01-01

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

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

    CERN Document Server

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2016-06-01

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